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25 December 2024, Volume 40 Issue 24
Basic Research
Inositol⁃trisphosphate 3⁃kinase B causes impaired testosterone synthesis in senescent leydig cells by inhibiting mitophagy
Ziguang LI,Cun WEI,Lei ZHAO,Qizhao. ZHOU
2024, 40(24):  3427-3437.  doi:10.3969/j.issn.1006-5725.2024.24.001
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Objective To explore the effect and mechanism of ITPKB on testosterone synthesis disorder of senescent Leydig cells. Methods A comprehensive analysis of public datasets was performed using GO, GSEA enrichment analysis and protein interaction network to determine the expression of related pathways and genes in testicular tissue in aging-related diseases. D-galactose intraperitoneal injection to construct an aging mouse model; Mouse Leydig cells (TM3) were cultured, and the cells were divided into four groups, control group (NC group), senescence group (D-gal group), inhibitor group (GNF362 group) and D-gal+GNF362 group. The serum levels of testosterone, follicle-stimulating hormone and luteinizing hormone in mice were detected by ELISA. q-PCR was used to detect the mRNA levels of IL-1α, IL-6, TNF-α and ITPKB. Immunofluorescence was used to detect the protein expressions of StAR, 3β-HSD, ITPKB and LC3. Western blot was used to detect the protein expressions of P53, P21, StAR and ITPKB. Transmission electron microscopy to observe intracellular structures. Results Bioinformatics analysis showed that ITPKB was highly expressed in the testes of aging mice. The serum testosterone level of aging mice was lower than that of young mice. Compared with the younger group, the mRNA levels of IL-1α, IL-6, TNF-α and ITPKB in the testes of mice in the aging group were increased, and the protein levels of P53, P21 and ITPKB were increased. The levels of StAR, 3β-HSD, LC3 protein and mitophagy decreased. Compared with the cells in the D-gal group, the testosterone level in the supernatant of the D-gal+GNF362 group was increased, and the level of mitophagy was significantly increased. Conclusion ITPKB causes impaired testosterone synthesis in senescent Leydig cells by inhibiting mitophagy.

Clinical Research
Exploratory study on the relationship between brain structural network changes and gut microbiota in patients with mild cognitive impairment associated with Parkinson′s disease
Zihui TIE,Peikun HE,Yanyi LI,Qingrui DUAN,Kun NIE,Lijuan. WANG
2024, 40(24):  3438-3445.  doi:10.3969/j.issn.1006-5725.2024.24.002
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Objective To investigate the relationship between brain structural networks and gut microbiota in patients with mild cognitive impairment associated with Parkinson's disease (PD-MCI), and the impact on cognitive function by neuroimaging and intestinal microbiology techniques. Methods 29 cases of patients with PD-MCI and 17 cases of PD patients with normal cognitive function (PD-NC) were enrolled. MRI T1-weighted and diffusion tensor imaging were collected for graph theory analysis, and fecal samples were analyzed using 16s DNA sequencing. Partial correlation analysis assessed relationships among differential bacteria, structural network properties, and cognitive scale scores, finally followed by mediation effect analysis. Results In PD patients, the abundance of Prevotellaceae, Alloprevotella, and UCG-10 bacteria was positively correlated with language and memory cognitive domains, while the abundance of UCG-010 showed a negative correlation with executive function. Additionally, the gut microbiota also was associated with several distinct brain structural network node characteristics. Mediation analysis indicated that Prevotellaceae's effect on logical memory was mediated by the node degree in the right opercular inferior frontal gyrus (IE = 0.074,95%CI:0.21 ~ 0.001,P = 0.046). Conclusions PD-MCI patients showed distinct gut microbiota and brain network features compared to PD-NC patients. The association and the mediation analysis of gut microbiota with brain networks and cognitive impairment suggests a role for Prevotellaceae in brain network alterations related to MCI, highlighting the gut-brain axis's potential influence on cognition.

Analysis of the application and prognostic factors of extracorporeal cardiopulmonary resuscitation (ECPR) in patients with refractory cardiac arrest in the emergency department
Gengzhou WEI,Guoge HUANG,Chuangzhi ZHU,Wenqiang JIANG,Bei. HU
2024, 40(24):  3446-3451.  doi:10.3969/j.issn.1006-5725.2024.24.003
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Objective To analyze the clinical application of Extracorporeal Cardiopulmonary Resuscitation (ECPR) in patients with refractory cardiac arrest in the emergency department and to investigate the factors affecting survival and neurological outcomes. Methods A retrospective analysis was conducted on the clinical data of 61 patients who underwent Extracorporeal Membrane Oxygenation (ECMO) for cardiopulmonary resuscitation at the emergency department from January 2021 to March 2024. The hospital discharge survival rate, favorable neurological outcome rate, and incidence of complications were summarized. Factors affecting survival and neurological outcomes were also analyzed. Results In a study of 61 patients, the ECMO weaning success rate was 55.7%, the hospital discharge survival rate was 29.5%, the favorable neurological prognosis rate was 21.3%, and the incidence of complications was 47.5%. The proportion of initial cardiac rhythm being shockable was significantly higher in the survival group compared to the mortality group. The ECMO establishment time, low-flow time, and pre-ECMO blood lactate levels were all significantly lower in the survival group than in the mortality group. The pre-ECMO blood pH level was higher in the survival group. The ECMO maintenance time and ICU stay were significantly longer in the survival group than in the mortality group, with all P-values being less than 0.05, indicating statistically significant differences. Patients with an initial shockable cardiac rhythm and low-flow time ≤ 60 minutes had a better favorable neurological prognosis rate. Conclusions Extracorporeal cardiopulmonary resuscitation can provide effective life support for patients with refractory cardiac arrest. Patients with an initial shockable rhythm, lower blood lactate levels and higher pH levels before ECMO support, and shorter low-flow time have a better prognosis.

Association of serum MMP⁃9, CYRFA21⁃1, and VEGF levels on cisplatin treatment efficacy in patients with non⁃small cell lung cancer
Haiying WANG,Kai WU,Yinchun. TIAN
2024, 40(24):  3452-3457.  doi:10.3969/j.issn.1006-5725.2024.24.004
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Objective To investigate the relationship between serum matrix metalloproteinase-9 (MMP-9), cytokeratin 19 fragment (CYRFA21-1) and vascular endothelial growth factor (VEGF) levels and cisplatin treatment in patients with non-small cell lung cancer. Methods 130 advanced B-stage non-small cell lung cancer treated with cisplatin in Affiliated Hospital of Nantong University from December 2020 to December 2022 were selected as the study subjects; 100 patients with physical examination in our hospital were selected as the control group. By comparing the serum levels of MMP-9, CYRFA21-1 and VE GF in each group, the cisplatin treatment effect was divided into 15 patients and 37 patients in the treatment-effective group, and 78 patients in the treatment-effective group to clarify the relationship between the treatment effect of patients with non-small-cell lung cancer. Results Serum levels of MMP-9, CYRFA21-1 and VEGF were decreased in NSCLC patients after cisplatin treatment (P < 0.05). Compared with the ineffective group, serum MMP-9, CYRFA21-1 and VEGF levels in the significantly effective group and the effective group were decreased (P < 0.05). Logistic regression analysis showed that MMP-9, CYRFA21-1 and VEGF were also risk factors affecting cisplatin treatment effect in NSCLC patients (P < 0.05). ROC analysis showed that serum MMP-9, CYRFA21-1 and VEGF had high predictive value for cisplatin treatment in NSCLC patients (P < 0.05). Conclusions MMP-9, CYRFA21-1 and VEGF are highly expressed in the serum of patients with severe pneumonia, and the expression levels of MMP-9, CYRFA21-1 and VEGF are decreased after cisplatin treatment in patients with non-small cell lung cancer, which is related to the cisplatin treatment effect in patients with non-small cell lung cancer. Clinical monitoring of serum levels of MMP-9, CYRFA21-1 and VEGF can predict the therapeutic effect early to improve the prognosis of patients.

To evaluate the benefits and limitations of enteral nutrition supplementation with probiotics in the treatment of severe pancreatitis based on intestinal biomarkers
Lele XU,Yanjun CHEN,Jian LU,Ya′ou. CHEN
2024, 40(24):  3458-3467.  doi:10.3969/j.issn.1006-5725.2024.24.005
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Objective To assess the efficacy and limitations of enteral nutrition supplemented with probiotics in managing severe pancreatitis, we investigated the dynamic alterations of enteric fatty acid-binding protein (I-FABP), D-lactic acid (D-Lac), and citrulline. Methods Between June 2021 and June 2024, a total of 153 cases of severe pancreatitis were enrolled from the Department of Gastroenterology at the First Affiliated Hospital of Soochow University and the Department of Critical Care Medicine at Suzhou Hospital Affiliated with Nanjing Medical University. These cases were divided into two groups: A treatment group receiving probiotics in addition to enteral nutrition (EN), and a control group without probiotic supplementation. The treatment group received a daily dosage of four capsules containing bifidobacterium triple live bacteria. Intestinal biomarkers were assessed at three time points following EN initiation: before initiation (D0), on day 3 (D3), and on day 10 (D10) after initiation. Repeated measures ANOVA was employed to analyze the efficacy of the three intestinal biomarkers, with D10 as the endpoint for evaluation. Subgroup analysis was conducted to explore any potential influence of antibiotic usage on probiotic effects. Various conventional evaluation indicators for pancreatitis, including amylase levels, inflammation markers, relevant scores, post-EN intestinal tolerance, 90-day mortality rates, discharge times, and other related outcomes were compared between the two groups. Results The results of a repeated measurement ANOVA showed that: (1) the main effect of I-FABP did not reach statistical significance (P = 0.076), whereas the interaction effect was statistically significant (F = 10.691, P = 0.001, partial η2 = 0.066); (2) Neither the main effect of D-Lac nor its interaction effect reached statistical significance (P = 0.761 and P = 0.995, respectively; F < 0.004 for both effects, partial η2 < 0.001); (3) Although the main effect of citrulline did not reach statistical significance (P = 0.161), its interaction effect was found to be statistically significant with a large effect size (F = 32.437, P < 0.001, partial η2 = 0.177). Endpoint efficacy analysis demonstrated that: (1) The I-FABP treatment group exhibited significantly higher pre-reduction levels compared to the control group (Difference in LS Mean (95% CI) -0.43 (-0.47 ~ -0.40) μg/L, P < 0.001); (2) There was no statistically significant difference observed in the D-Lac treatment group compared to the control group [Difference in LS Mean (95%CI) = 0.01 (0.00 ~ 0.02) mmol/L, P = 0.229]. However, subgroup analysis revealed that the decline in D-Lac levels was comparatively lower in the treatment group than in the control group (P = 0.043), and there was an interaction between antibiotic use and the level of D-Lac decline within both groups (P for interaction = 0.012); (3) The citrulline level was found to be significantly higher in the treatment group compared to the control group (P < 0.001). There were no significant differences observed between the two groups regarding routine evaluation indexes, intestinal tolerance after enteral nutrition, and 90-day mortality rates (P > 0.05). After a follow-up period of 90 days, it was noted that patients from the treatment group had a higher rate of early discharge when compared to those from the control group. (Breslow P = 0.012). Conclusions Based on conventional evaluation criteria such as symptom remission, 90-day mortality, inflammatory markers, and amylase changes, probiotics do not demonstrate efficacy for severe pancreatitis. The dynamic changes of I-FABP and citrulline provide evidence supporting the potential of probiotics to reverse intestinal epithelial cell necrosis and promote recovery of their absorption/synthesis function in patients with severe pancreatitis. D-lactic acid has the potential to serve as an indicator for assessing the effectiveness of supplemental probiotics in the gut, thereby highlighting how the use of broad-spectrum antibiotics may limit their efficacy.

Analysis on clinicopathologic features and prognosis of proliferative glomerulonephritis with monoclonal IgG deposits
Rui LU,Ye CHEN,Di WANG,Lijuan ZHAO,Meilan ZHOU,Ming BAI,Lijie HE,Shiren. SUN
2024, 40(24):  3468-3475.  doi:10.3969/j.issn.1006-5725.2024.24.006
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Objective To analyze the clinicopathological features, treatment and prognosis of patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposition. Methods The clinical data, renal pathology, treatment and prognosis of patients with PGNMID diagnosed by renal biopsy in Xijing Hospital from January 2018 to January 2024 were retrospectively analyzed and summarized. Results A total of 28 patients were enrolled in this study, with a male to female ratio of 4:3. The clinical manifestations were proteinuria (100%), hematuria (82.1%), renal insufficiency (28.6%), and low complement C3 or C4 emia (32.1%). One patient (3.6%) had serum monoclonal immunoglobulin, and 5 patients (17.9%) had abnormal serum free light chain ratio. The deposition of immunoglobulin in the kidney was IgG3 in 24 cases, IgG1 in 4 cases, and IgG3κwas the most common type (17 cases). Then there are 24 cases (85.7%) of MPGN, 3 cases (10.7%) characterized by EPGN, 1 case (3.6%) of MGN. Under electron microscope, most of the electron-dense deposits were found in the mesangial area and subendothelium, and a few were accompanied by subepithelial deposits.The follow-up time ranged from 3 to 56 months. Until the last follow-up, a total of 5 patients entered ESRD, of which 2 patients died, 1 patient underwent peritoneal dialysis, 1 patient underwent hemodialysis, and 1 patient underwent preparation for renal replacement therapy. Follow-up of 1 year, 2 years, 3 years renal total response rate of 32.1%, 57.1% and 64.2% respectively. According to the situation of kidney ease into remission group (n = 16) and non-remission group (n = 12). The average age of the remission group was 44 ± 17.35 years,including 8 males (50%); The average age of the non-remission group was 59.83 ± 18.09 years, including 8 males (66.7%). The age, nT-proBNP, troponin I and urea nitrogen of the non-remission group were higher than those of the remission group, and the differences were statistically significant (P < 0.05). Among the 5 patients with renal complete remission, 2 were treated with BD (bortezomib combined with dexamethasone), 1 was treated with Dara, and the remaining 2 were treated with steroids combined with immunosuppressants. Conclusions The clinical manifestations of PGNMID are proteinuria, hematuria and renal insufficiency. Under light microscope, MPGN was the main manifestation, and IgG3κwas the most common subtype. Based on bortezomib treatment can obtain good hematology and kidney remission rate.Dara may be a safe and effective drug for the treatment of PGNMID, the best treatment needs further exploration.

Application of general anesthesia under nociception index combined with BIS monitoring in laparoscopic radical resection of colorectal cancer
Wei DENG,Dan PENG,Haijun HU,Jing ZHANG,Shuchun YU,Song. HUANG
2024, 40(24):  3476-3481.  doi:10.3969/j.issn.1006-5725.2024.24.007
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Objective To evaluate the Nociception Index (NOX) combined with Bispectral Index (BIS) monitoring of anesthesia management during laparoscopic radical resection of colorectal cancer. Methods A total of 80 patients, regardless of gender, aged 50 to 80 years old, and ASA grade Ⅰ or Ⅱ, chose to undergo elective laparoscopic colorectal surgery under total intravenous anesthesia. They were randomly divided into two groups: NOX combined with BIS group (Group N) and BIS alone group (Group C), with 40 cases in each group. Group N maintains an appropriate analgesia depth (NOX value is 30 ~ 50) and sedation depth (BIS value is 40 ~ 60), and group C maintains an appropriate sedation depth (BIS 40 ~ 60) and is covered with opaque cards Hide NOX and adjust the appropriate analgesia depth based on the experience of the anesthesiologist. The main observational indicator is the intraoperative remifentanil dosage, and the secondary observational indicators include the intraoperative propofol and cisatracurium dosage, vasoactive drug use, anesthesia recovery and extubation time, postoperative NRS pain score and sufen. The dosage of Titanyl, adverse reactions such as agitation in the postoperative recovery period, postoperative nausea and vomiting, dizziness, and intraoperative awareness. Results The amount of remifentanil used during the operation in group N was significantly less than that in group C (P < 0.05). The time of postoperative recovery and extubation in group N was significantly earlier than that in group C (P < 0.05). The number of cases of intraoperative use of vasoactive drugs, the incidence of postoperative agitation during recovery, postoperative nausea and vomiting, and dizziness in group N were significantly lower than those in group C (P < 0.05). There were no significant differences in the amount of propofol and cis-atracurium used during surgery and the incidence of awareness between the two groups (P > 0.05). The NRS scores of patients in group N were significantly lower than those in group C at 2, 4, 6, and 24 hours after surgery (P < 0.05), while there was no significant difference in the NRS scores between the two groups at 48 hours after surgery (P > 0.05). The consumption of sufentanil in group N was significantly lower than that in group C during the first 12 hours and 12 to 24 hours after surgery (P < 0.05). There was no significant difference in the consumption of sufentanil between the two groups during the second 24 to 48 hours after surgery (P > 0.05). Conclusion Compared with BIS monitoring alone, the use of NOX combined with BIS monitoring can maintain relatively stable intraoperative hemodynamics, reduce the amount of general anesthesia drugs, accelerate postoperative anesthesia recovery, improve the quality of anesthesia recovery, and reduce acute postoperative pain, which is beneficial to patients postoperative recovery.

Comparative study on the clinical effect of different spinal traction therapy on degenerative lumbar spondylolisthesis based on the change of lumbosacral and pelvic sagittal position parameters
Junbiao GUO,Siyuan RAO,Zhenhong XIAO,Siyi FENG,Huimin. WANG
2024, 40(24):  3482-3488.  doi:10.3969/j.issn.1006-5725.2024.24.008
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Objective To investigate the comparative effect of different spinal traction therapy on the treatment of degenerative lumbar spondylolisthesis based on the change of lumbosacral and pelvic sagittal position parameters. Methods The clinical data of 108 patients with degenerative lumbar spondylolisthesis admitted to Guangdong Provincial Hospital of Traditional Chinese Medicine from March 2022 to January 2024 were selected for retrospective analysis, and they were divided into the three-dimensional group (n = 55) and the four-dimensional group (n = 53) according to the difference in treatment methods. The four dimensional group received four dimensional traction combined with basic treatment, and the three dimensional group received three dimensional traction combined with basic treatment. Lumbosacral pelvis sagittal position parameters, vertebral glide reduction degree, lumbar curvature value, coronal Cobb Angle of lumbar spine, lumbar function, pain degree and clinical efficacy were compared between the two groups. Results At the end of treatment and 3 months after treatment, the levels of sacral inclination Angle (SS) and lumbar lordosis Angle (LL) in 3D and 4D groups were lower than before treatment, and at 3 months after treatment were lower than at the end of treatment (P < 0.05). At the end of treatment, SS and LL levels in 3D group were lower than those in 4D group (P < 0.05), while there was no difference in SS and LL levels between the two groups at 3 months after treatment (P > 0.05). The lumbar lordotic index and coronal Cobb Angle of both groups were lower than before treatment (P < 0.05), and at 3 months after treatment, the lumbar lordotic index and coronal Cobb Angle of both groups were lower than at the end of treatment (P < 0.05). At the end of treatment, the lumbar protrusion index and coronal Cobb Angle in the three-dimensional group were lower than those in the four-dimensional group (P < 0.05). At the end of treatment and 3 months after treatment, the distance of lumbar arch top in both groups was higher than before treatment (P < 0.05), and at 3 months after treatment, the distance of lumbar arch top in both groups was higher than at the end of treatment (P < 0.05). At the end of treatment, the distance of lumbar arch in the three-dimensional group was higher than that in the four-dimensional group (P < 0.05). At 3 months after treatment, there were no significant differences in lumbar lordosis index, coronal Cobb Angle of lumbar spine and distance between the two groups (P > 0.05). At the end of treatment and 3 months after treatment, visual analogue pain scale (VAS) scores in both groups were lower than before treatment (P < 0.05), and at 3 months after treatment, VAS scores in both groups were lower than at the end of treatment (P < 0.05). At the end of treatment and 3 months after treatment, the Japanese Orthopaedic Association evaluated treatment score (JOA) in both groups was higher than that before treatment (P < 0.05), and at 3 months after treatment, the JOA score in both groups was higher than that at the end of treatment (P < 0.05). At the end of treatment and 3 months after treatment, there was no significant difference in JOA score and VAS score between the two groups (P > 0.05). At the end of treatment and 3 months after treatment, there was no difference in the reduction rate of vertebral slippage between the two groups (P > 0.05). There was no difference in total effective rate between the two groups (P > 0.05). Conclusion Four dimensional traction and three dimensional traction combined with basic treatment of degenerative lumbar spondylolisthesis have the same efficacy, both can effectively reduce pain and improve lumbar function, but three dimensional traction is better in improving lumbar function and lumbosacral pelvic sagittal position parameters, and correcting lumbar curvature abnormalities.

Retrospective follow⁃up and analysis of repairing upper trunk with nerve root stump as power source
Liang LI,Jiajun HUANG,Liqiang. GU
2024, 40(24):  3489-3496.  doi:10.3969/j.issn.1006-5725.2024.24.009
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Objective To analyze and compare the clinical effects of upper brachial plexus repair with nerve root stumps and each type of power source nerves, determine the availability of nerve root stumps and the effectiveness and rationality of clinical use. Methods Retrospective analysis was performed for the patients admitted to our department from January 2007 to December 2015. The patients were diagnosed with partial or total brachial plexus injury. Case data were collected including gender, age,diagnosis, cause of injury, interval between injury and operation, follow-up time, injury type, operation method, gap length between donor and recipient nerve, graft type and length, and complications. In addition, we also examine the adverse events in the donor site. The British Medical Research Council (BMRC) muscle strength evaluation criteria were used to evaluate the patients' deltoid muscle and biceps muscle strength and we also performed disabilities of arm, shoulder and hand (DASH) score. Results A total of 136 patients received brachial plexus repair, 112 cases included in the study after 24 cases were excluded. The patients were divided into four groups: 22 cases in modified Oberlin surgery group, 45 cases in CC7 transfer comebined with huamn acellular nerve allograft group, 27 cases in CC7 transfer and direct suture group. There were 14 cases of nerve root stumps repair upper trunk directly or combined with huamn acellular nerve allografting, which including 10 cases of BPAI and 4 cases of stab wound. The effective rate of deltoid muscle strength was 68.2%, 71.2%, 88.9% and 78.6%, respectively. The muscle strength and effective rate of biceps were 81.8%, 60.0%, 85.2% and 64.3%, respectively. Subgroup analysis: (1) operative methods for upper brachial plexus injuries: 4 cases with stab wounds in the nerve root stump repair group; in the modified Oberlin surgery group, 22 cases were avulsion injury. The results showed that there were no statistically significant differences between the two groups in the ROM, deltoid muscle strength, biceps muscle strength and DASH score. For the comparison of C5-C8 or TBAI: there is no statistical difference in ROM of shoulder abduction between the nerve root stump repair group and CC7 transfer and direct suture group; the evaluation indexes include angle of elbow flexion, biceps muscle strength and DASH score in CC7 transfer and direct suture group were better than the other two groups, followed by CC7 transfer combined with shenqiao group and nerve root stump repair group. Conclusions This part evaluated and analyzed the clinical effects of various kinds of power sources nerve on the recovery of elbow flexion and shoulder abduction after upper brachial plexus repairing, and determined the availability of nerve root stump and the validity and rationality of its clinical use. Protecting the nerve stump roots may improve the clinical effect of nerve stump utilization and increase the power source nerve in the future.

Expression levels of HIF⁃3α methylation and DDIT4 in gestational diabetes mellitus and its relationship with pregnancy outcomes
Wenqing XU,Yishan LI,Qiuyu HAN,Fangjing SONG,Lin. MENG
2024, 40(24):  3497-3502.  doi:10.3969/j.issn.1006-5725.2024.24.010
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Objective To investigate the methylation levels of the HIF?3α gene, as well as the expression of HIF?3α mRNA and DDIT4 mRNA in peripheral blood samples from pregnant women with gestational diabetes mellitus (GDM), and their association with pregnancy outcomes, aiming to provide insights for pregnancy monitoring and clinical diagnosis and treatment of GDM patients, thereby mitigating the risk of adverse pregnancy outcomes. Methods From March 2023 to March 2024, a total of 80 pregnant women with GDM were randomly selected at the Affiliated Hospital of Xuzhou Medical University. They were divided into two groups based on glycemic control: GDM1 (n = 40) representing good glycemic control and GDM2 (n = 40) representing poor glycemic control. Additionally, a control group consisting of 40 pregnant women without any pregnancy complications or comorbidities was included. Methylation-specific PCR was employed to determine the rate of HIF- methylation, while quantitative real-time PCR was used to assess the expressions of HIF- mRNA and DDIT4 mRNA. Adverse pregnancy outcomes were recorded across all three groups, and correlations between HIF- mRNA, DDIT4 mRNA, and various adverse pregnancy outcomes were analyzed using logistic regression analysis. Results Prior to pregnancy, GDM1 and GDM2 groups exhibited higher levels of FPG, HbA1c, TC, TG, LDL-C, FINS and HOMA-IR (P < 0.05), as well as lower levels of HOMA-β compared to the control group (P < 0.05). The incidence of adverse pregnancy outcomes was also higher in both GDM groups than in the control group; this difference was significant for GDM2 (P < 0.05) but not for GDM1 (P > 0.05). Furthermore, methylation rates of the HIF- gene were higher in both GDM groups compared to controls while expression levels of HIF- and DDIT4 mRNA were lower; these differences were significant for the GDM2 group versus controls (P < 0.05) but not for the GDM1 group versus controls (P > 0.05). Finally, all adverse pregnancy outcomes among women with gestational diabetes mellitus showed a negative correlation with expression levels of both HIF- and DDIT4 mRNA (r < 0,P < 0.05); moreover, these two mRNAs served as protective factors against such outcomes occurring(OR < 1,P < 0.05). Conclusion The higher methylation rate of HIF- and the decreased expression of HIF- and DDIT4 genes are associated with the development of GDM and may serve as significant factors contributing to adverse pregnancy outcomes.

Expression level of neutrophil/lymphocyte ratio and monocyte/high density lipoprotein cholesterol ratio in patients with sudden deafness and their correlation with prognosis
Hongmei ZHU,Yongjiu HUANG,Jiusheng CHU,Xiuhong. PANG
2024, 40(24):  3503-3508.  doi:10.3969/j.issn.1006-5725.2024.24.011
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Objective To explore the correlation between neutrophil/lymphocyte ratio (NLR) and monocyte/high density lipoprotein cholesterol ratio (MHR) and the onset and prognosis of sudden deafness (SSNHL). Methods 138 patients with sudden deafness who were treated in the hospital from January 2022 to May 2024 were selected as the study group, and 116 normal healthy people were selected as the control group. The changes of NLR and MHR in two groups and different types of SSNHL patients were compared. Logistic regression was used to explore the prognostic factors of patients with SSNHL. Results NLR and MHR in the study group were significantly higher than those in the control group (P < 0.05). There were statistical differences in the average hearing threshold, total cholesterol (TC), fibrinogen (FIB), platelet count (PLT), cortisol (COR), NLR and MHR in patients with different types of SSNHL (P < 0.05). NLR, MHR and SSNHL were significantly correlated (P < 0.05). The increase of NLR and MHR is a risk factor for poor prognosis in patients with SSNHL. Conclusion NLR and MHR are closely related to the pathogenesis of SSNHL and are important factors leading to poor prognosis of patients with SSNHL.

Drugs and Clinic Practice
Effects of sevoflurane or propofol anesthesia maintenance on renal function and postoperative cognition in patients undergoing liver transplantation
Jinhui XU,Mailong YUAN,Tao ZHOU,Mingsheng ZHANG,Yaqi. LI
2024, 40(24):  3509-3514.  doi:10.3969/j.issn.1006-5725.2024.24.012
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Objective To compare the application of sevoflurane or propofol anesthesia maintenance in liver transplantation patients and explore its effects on renal function and postoperative cognition and possible mechanisms. Methods A total of 60 patients aged 18 ~ 60 years old and ASA grade Ⅱ-Ⅲ who were scheduled to undergo orthotopic liver transplantation in our hospital were selected. They were randomly divided into two groups (n = 30) according to the different maintenance schemes: group P (propofol group) and group S (sevoflurane group). Anesthesia maintenance: group P received continuous target-controlled infusion of propofol combined with remifentanil hydrochloride injection during surgery; group S received sevoflurane inhalation combined with infusion of remifentanil hydrochloride injection during surgery. The mean arterial pressure (MAP), heart rate (HR) and central venous pressure (CVP) of the two groups of patients were recorded at seven time points, including before anesthesia induction (T0), immediately after skin incision (T1), 30 minutes in the anhepatic phase (T2), 3 hours in the neohepatic phase (T3), 12 hours after surgery (T4), 24 hours after surgery (T5) and 72 hours after surgery (T6). 3 mL of central venous blood was drawn from each group. The serum neutrophil gelatinase-associated lipocalin (NGAL), serum cystatin C (Cys C), kidney injury molecule 1 (KIM-1), syndecan 1 (SDC-1), heparin sulfate (HS), hyaluronic acid (HA) and serum concentrations of inflammatory markers (TNF-α, IL-6) were detected by ELISA at the above time points. The cognitive function was evaluated by the Mini-Mental State Examination (MMSE) at T0, T5 and T6, and the occurrence of cognitive dysfunction (MMSE < 23 points) was counted. Results There were no significant differences in MAP, HR, and CVP between the two groups at each time point (P > 0.05). At T4, the serum levels of NGAL and Cys in the two groups were significantly higher than those in the other groups. C and KIM-1 increased, and the P group was significantly higher than the S group, the difference was statistically significant (P < 0.05), and there was no significant difference between the two groups at other times (P > 0.05); SDC-1, HS, and HA increased significantly in both groups at T3 and T4, and the P group was significantly higher than the S group at T4, the difference was statistically significant (P < 0.05), and there was no significant difference between the two groups at other times (P > 0.05); TNF-α and IL-6 increased significantly in both groups at T3 and T4, decreased at T5 and T6, but still higher than T0, and the P group was significantly higher than the S group at T4 and T5, the difference was statistically significant (P < 0.05); MMSE scores decreased at T5 and T6, and the P score was significantly lower than the S group at T5, the difference was statistically significant (P < 0.05), and there was no significant difference at T6 (P > 0.05); there was no significant difference in the incidence of postoperative cognitive dysfunction between the two groups (P > 0.05). Conclusion Compared with propofol, sevoflurane anesthesia maintenance has less effect on the degree of short-term renal injury and cognitive function changes in patients undergoing liver transplantation, which may be related to its more obvious effect of inhibiting inflammatory response and reducing glycocalyx degradation.

Effects of semaglutide on prognosis in patients with diabetes mellitus complicated with unstable angina after percutaneous coronary intervention
Ziming ZHAO,Qi MA,Jian CHEN,Yuan CHEN,Liuyi CUI,Yujie. ZHAO
2024, 40(24):  3515-3520.  doi:10.3969/j.issn.1006-5725.2024.24.013
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Objective To investigate the effect of semaglutide on the prognosis in patients with unstable angina complicated with diabetes after percutaneous coronary intervention. Methods A total of 178 patients with unstable angina complicated with diabetes diagnosed in Zhengzhou Cardiovascular Hospital from September 1, 2022 to March 31, 2023 were included. The patients were divided into a study group (43 patients) and a control group (135 patients) according to whether they received semiglutide or not. Changes in HbA1c, fasting blood glucose, body weight, blood pressure and blood lipid were observed before and after treatment. Baseline data and differences in postoperative adverse cardiovascular events including cardiovascular death, all-cause death, acute myocardial infarction, acute ischemic stroke, re-hospitalization due to unstable angina, and coronary revascularization were compared between the two groups. Results After 12 weeks of treatment, fasting blood-glucose levels in the study group and the control group were (6.0 ± 0.9), (8.5 ± 1.3) mmol/L, HbA1c levels were (6.5 ± 0.7)%, (7.9 ± 0.5)%, BMI was (22. 8 ± 3.0), (25.0 ± 2.4) kg/m2, systolic blood pressure was (135.3 ± 9.7) (141.5 ± 8.3) mmHg, respectively, with significant differences (P < 0.05 for all comparisons). Diastolic blood pressure showed a trend of improvement (84.7 ± 7.7), (86.6 ± 7.7)mmHg, but there was no statistical difference. Conclusions For patients with unstable angina complicated with diabetes after percutaneous coronary intervention, the application of semaglutide can effectively control blood glucose, body weight, systolic blood pressure, and reduce the risk of cardiovascular events.

The effects of different extracorporeal circulation temperature combined with dexmedetomidine on oxidative stress in patients undergoing cardiac surgery under cardiopulmonary bypass
Peng SUN,Zhaojin JIA,Xiuhua LI,Xiaowei CHEN,Runsheng WEI,Yantao JIN,Jiantao. JIN
2024, 40(24):  3521-3526.  doi:10.3969/j.issn.1006-5725.2024.24.014
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Objective To study the effects of different extracorporeal circulation temperature combined with dexmedetomidine on oxidative stress in patients undergoing cardiac surgery under cardiopulmonary bypass. Methods 240 patients who underwent cardiac surgery under cardiopulmonary bypass were selected from June 2021 to June 2024. The patients were 50 to 75 years old and did not have severe hepatic or renal insufficiency. The Mini-Mental State Examination was completed 1 day before the operation. Patients were routinely established for cardiopulmonary bypass. Patients were randomly divided into four groups (n = 55): hypothermia + normal saline group (L0), hypothermia + dexmedetomidine group (L1), hyperthermia + normal saline group (H0) and hyperthermia + dexmedetomidine group (H1). The nasopharyngeal temperature was maintained at (30 ± 1)℃ in the hypothermia group and (33 ± 1)℃ in the high-temperature group during the reflux period. Dexmedetomidine injection was intravenously injected at 1 μg/kg 10 minutes before anesthesia in L1 and H1 groups, and pumped continuously at a rate of 0.5 μg/(kg·h) until the end of surgery. L0 and H0 groups were given equal volume of normal saline until the end of operation. 5 mL of central venous blood was collected before the beginning of anesthesia (T1), at the end of surgery (T2), 24 h (T3) and 48 h(T4) after surgery, and serum neuron specific enolase (NSE), interleukin-6 (IL-6) and tumor necrosis factor -α(TNF-α) levels were detected by ELISA. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in serum were determined by xanthine oxidase method and thiobarbituric acid method. The Confusion Assessment Method-ICU was used to evaluate the occurrence of POD. Results 220 patients were finally enrolled, including 81 patients in POD group, with an incidence of 36.8%. Compared with NPOD group, the concentrations of NSE, IL-6, TNF-ɑ and MDA in POD group were increased, while the concentration of SOD was decreased.Compared with L0 group, the concentrations of NSE, IL-6, TNF-ɑ and MDA were decreased and the concentration of SOD increased in L1 group.Compared with H0 group, NSE, IL-6, TNF-ɑ and MDA concentrations in H1 group were decreased, while SOD concentration was increased.Compared with L0 group, concentration of NSE, IL-6, TNF-ɑ and MDA increased, while the concentration of SOD decreased in H0 group. Compared with L1 group, concentration of NSE, IL-6, TNF-ɑ and MDA increased, while the concentration of SOD decreased in H1 group. Conclusion Hypothermia combined with dexmedetomidine during cardiopulmonary bypass can reduce oxidative stress response and POD in patients.

Effects of different doses of dexmedetomidine combined with ropivacaine TPVB under ultrasound guidance on vital signs and stress response of patients undergoing thoracoscopic surgery under general anesthesia
Jianqiang ZENG,Zhaoying ZHONG,Lei YUAN,Donglan. PENG
2024, 40(24):  3527-3533.  doi:10.3969/j.issn.1006-5725.2024.24.015
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Objective To investigate the effects of dexmedetomidine (0.5, 1.0, 2.0 μg/kg) combined with ropivacaine ultrasound guided thoracic paravertebral nerve block (TPVB) in patients undergoing thoracoscopic surgery under general anesthesia on the vital signs, stress response and other indexes, and to provide reference for the optimization of anesthesia regimen in the clinic. Methods A total of 99 cases of patients undergoing thoracoscopic surgery under general anesthesia were selected, and the patients were divided into the low, medium, and high-dose groups of 33 cases each according to the method of randomized numerical table. At the end of anesthesia induction, dexmedetomidine 0.5, 1.0, and 2.0 μg/kg compounded with 0.375% ropivacaine ultrasound-guided TPVB was administered to the low, medium, and high-dose groups, respectively, and all three groups were observed until 3 d postoperatively. Perioperative indicators, quality of awakening, degree of pain at 2, 6, 12, and 24 h postoperatively, vital signs before anesthesia (T1), at tracheal extubation (T2), and at 5 min of tracheal extubation (T3), and immune function, stress response, and adverse reactions during the observation time were compared between the groups. Results Compared with the low-dose group, remifentanil and propofol dosages were lower in the medium- and high-dose groups, and the number of postoperative self-controlled analgesia was lower (P < 0.05). Awakening, tracheal extubation, and recovery room stay were prolonged between the low, medium, and high dose groups (P < 0.05). Scores of visual analog scale (VAS) were progressively lower in the three groups at 2, 6, 12, and 24 h postoperatively (P < 0.05), and compared with the low-dose group, scores of VAS were lower in the medium and high-dose groups at 2, 6, and 12 h postoperatively (P < 0.05). Compared with T1, heart rate (HR), mean arterial pressure (MAP) were higher in all three groups at T2, T3, and HR, MAP at T2, T3 were higher between the low, medium, and high dose groups (P < 0.05); compared with T2, HR, MAP were lower in all three groups at T3 (P < 0.05). Compared with the preoperative period, levels of whole blood CD8+, serum cortisol (Cor), C-reactive protein (CRP), norepinephrine (NE), and epinephrine (E) were increased in the three groups at 3 d postoperatively, and the above indexes were elevated between the low, medium, and high dosage groups at 3 d postoperatively (P < 0.05); levels of whole blood CD3+, CD4+, CD4+/CD8+ were decreased in the three groups at 3 d postoperatively, and the above indexes were elevated between the low, medium, and high dosage groups at 3 d postoperatively (P < 0.05). There was no statistically significant difference in the safety comparison among the three groups (P > 0.05). Conclusions 1.0 μg/kg dexmedetomidine combined with ropivacaine ultrasound guided TPVB had certain advantages in reducing the degree of pain of general anesthesia thoracoscopic surgery patients, reducing the dosage of remifentanil and propofol and the number of postoperative self-controlled analgesia, while 0.5 μg/kg dexmedetomidine combined with ropivacaine ultrasound guided TPVB had certain advantages in improving patients' vital signs, reducing immunosuppression, stress reaction and promoting post-anesthesia awakening. Clinical anesthesia protocols could be rationally selected according to the actual situation of patients.

Efficacy and safety analysis of pabolizumab plus low⁃dose apatinib combined chemotherapy in elderly patients with esophageal cancer
Tingting ZHANG,Ke LIU,Dan CHEN,Bingwen YAN,Peijuan ZHAO,Ning. WANG
2024, 40(24):  3534-3538.  doi:10.3969/j.issn.1006-5725.2024.24.016
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Objective To evaluate the efficacy and safety of pabolizumab plus low-dose apatinib combined chemotherapy in elderly patients with esophageal cancer. Methods A total of 188 elderly patients with esophageal cancer admitted to Shengli Oilfield Central Hospital from May 2020 to July 2022 were selected and divided into study group (n = 94) and control group (n = 94) by random number table method. The control group received pabolizumab combined with FP chemotherapy regimen, and the study group received low-dose Apatinib combined with Pabolizumab and FP chemotherapy regimen. Clinical efficacy, tumor markers, phosphatidylinositol 3 kinase (PI3K)/threonine protein kinase (Akt) signaling protein pathway, immune function, adverse reactions and survival were compared between the two groups. Results The objective remission rate of the study group was higher than control group (P < 0.05). After treatment, squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), PI3K, Akt and CD8+ were all decreased in the two groups (P < 0.05), and those in study group were lower (P < 0.05). After treatment, CD3+ and CD4+ were increased in both groups (P < 0.05), and higher in study group (P < 0.05). There was no difference in the total incidence of adverse reactions between the two groups (P > 0.05). The survival rate of the study group was higher than control group (P < 0.05). Conclusion Pabolizumab plus low-dose apatinib combined with chemotherapy is effective in the treatment of elderly esophageal cancer, which may inhibit tumor progression by reducing the activity of PI3K/Akt signaling protein pathway and improve the short-term survival rate.

Medical Examination and Clinical Diagnosis
Relationship between multi⁃omics combined detection and clinicopathological characteristics, neoadjuvant chemotherapy effect of breast cancer
Fen LIU,Hui ZHAO,Limin. GUO
2024, 40(24):  3539-3546.  doi:10.3969/j.issn.1006-5725.2024.24.017
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Objective To assess the levels of peripheral blood markers including carbohydrate antigen 15-3 (CA15-3), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), cytokeratin-18 (CK18), and neutrophil-to-lymphocyte count ratio (NLR) in breast cancer patients, investigate their correlation with clinicopathological characteristics, and evaluate the impact of neoadjuvant chemotherapy. Methods The clinical data of 187 patients with breast cancer who underwent neoadjuvant chemotherapy at our hospital between January 2020 and December 2023 were retrospectively analyzed. Based on the evaluation criteria for solid tumor response after 8 cycles of chemotherapy, the patients were divided into two groups: an effective group (n = 84) and an ineffective group (n = 103). The levels of CA15-3, CA125, CEA, CK18, and NLR in the peripheral blood of breast cancer patients before neoadjuvant chemotherapy were measured. Furthermore, a comparison was made between the levels of CA15-3, CA125, CEA, CK18, and NLR in the peripheral blood among breast cancer patients with different clinicopathological characteristics. Additionally, a comparison was conducted between the levels of CA15-3, CA125, CEA, CK18,and NLR in the peripheral blood as well as clinical data between the effective group and ineffective group. Univariate and multivariate logistic regression analyses were employed to examine the factors influencing the ineffectiveness of neoadjuvant chemotherapy in breast cancer patients. Additionally, a receiver operating characteristic (ROC) curve was constructed to assess the predictive efficacy of peripheral blood markers including CA15-3, CA125, CEA, CK18, and NLR on the response to neoadjuvant chemotherapy in breast cancer patients. Results The levels of CA15-3, CA125, CEA, CK18, and NLR in the peripheral blood of breast cancer patients with T3~T4 stage, N1~N3 stage, and human epidermal growth factor receptor-2 (HER-2) positivity were significantly elevated compared to those in breast cancer patients with T2 stage, N0 stage, and HER-2 negativity (P < 0.05). The levels of CA15-3, CA125, CEA, CK18, and NLR in the peripheral blood were found to be higher in the ineffective group than in the effective group (P < 0.05). Moreover, a higher proportion of patients in the ineffective group exhibited T3~T4 stage tumors along with N1~N3 lymph node involvement. Additionally observed were histological grade of low differentiation as well as positive progesterone receptor and estrogen receptor expression. Furthermore high expression of tumor proliferation antigen was more prevalent among patients classified under the ineffective group. (P < 0.05). Elevated peripheral blood CA15-3, CA125, CEA, CK18 and NLR levels, T3~T4 stage, N1~N3 stage, low differentiation, and ER positive were identified as significant risk factors for neoadjuvant chemotherapy in breast cancer patients (P < 0.05). The predictive performance of peripheral blood CA15-3, CA125, CEA, CK18 and NLR in assessing the efficacy of neoadjuvant chemotherapy yielded a sensitivity of 96.43%, specificity of 82.52%, and an area under the curve (AUC) value of 0.956. Furthermore, combined prediction demonstrated higher sensitivity and AUC compared to individual predictors (P < 0.05), while maintaining similar specificity levels. Conclusions The levels of CA15-3, CA125, CEA, CK18 and NLR in peripheral blood are closely associated with the clinicopathological characteristics of breast cancer patients and can impact the efficacy of neoadjuvant chemotherapy. These biomarkers have potential for predicting response to neoadjuvant chemotherapy in breast cancer patients, with improved accuracy when used in combination.

Investigations
Analysis of fatigue status and influencing factors of adult patients at home after cardiac surgery
Yuan LIU,Jing LAI,Danying MA,Lingzi WU,Wei. WANG
2024, 40(24):  3547-3553.  doi:10.3969/j.issn.1006-5725.2024.24.018
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Objective This study aimed to explore the current status of home-based fatigue among patients after cardiac surgery and analyze its influencing factors. Methods From January 2023 to December 2023, we retrospectively collected data from 200 patients who underwent cardiac surgery and were discharged for more than 3 months from Guangdong Provincial People's Hospital. The Multidimensional Fatigue Inventory-20, Overall Pain Assessment Scale, Cardiac Rehabilitation Inventory and Self-efficacy for Managing Chronic Disease 6-Item Scale were used to assess the patients. Results Overall fatigue of patients at home after cardiac surgery was at a moderate level. A stepwise multiple linear regression analysis revealed that anxiety during cardiac rehabilitation (β = 7.476, P = 0.001), severe pain (β = 11.939, P = 0.001), and frequency of discomfort symptoms (P < 0.001) significantly positively predicted post-cardiac surgery fatigue, whereas self-efficacy in chronic disease management (β = -6.974, P < 0.001) significantly negatively predicted it. Conclusions Fatigue among home-based patients after cardiac surgery requires further improvement and is associated with cardiac rehabilitation anxiety, pain severity, self-efficacy, and frequency of discomfort symptoms. Healthcare providers could develop targeted continuity interventions based on these influencing factors to reduce fatigue levels and promote recovery among home-based patients after cardiac surgery.

Reviews
Effects of VEGF inhibitors for treating cholangiocarcinoma: A review of literature
Jianfang ZHANG,Xueqin SUN,Yeqian CUI,Yang CHEN,Shaobo. WANG
2024, 40(24):  3554-3560.  doi:10.3969/j.issn.1006-5725.2024.24.019
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Cholangiocarcinoma (CCA) is an aggressive malignant tumor originating from bile duct epithelial cells, characterized by a poor prognosis. Surgery is the primary treatment, but late diagnosis often leads to poor surgical outcomes. Consequently, patients typically rely on comprehensive treatment such as chemotherapy. However, the median survival remains short, highlighting the urgent need for new strategies. Vascular endothelial growth factor (VEGF), a crucial factor in angiogenesis, is frequently overexpressed in tumor cells of CCA patients. Recent studies have shown that VEGF not only promotes angiogenesis but also exacerbates the invasion and metastasis of CCA. Therefore, targeting VEGF-mediated angiogenesis provides a new strategy for treating CCA. VEGF inhibitors represent a new frontier in CCA treatment, offering opportunities for precision therapy. By integrating VEGF inhibitors with immunotherapy and chemotherapy, it is possible to not only effectively prolong the survival of CCA patients but also to offer new hope for improving their quality of life. This review examines the expression of VEGF in CCA, its role in tumorigenesis, and the clinical application of VEGF inhibitors in treating CCA.

Clinical application of hepatocellular carcinoma prediction models: current challenges and future directions
Hang DENG,Hao. ZHANG
2024, 40(24):  3561-3567.  doi:10.3969/j.issn.1006-5725.2024.24.020
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Hepatocellular carcinoma (HCC) is a prevalent global malignancy characterized by inconspicuous early clinical manifestations; the majority of patients have already progressed to an advanced stage by the time symptoms and signs become apparent, thereby missing the opportunity for surgical intervention. Despite surgical interventions, early recurrence and unfavorable prognoses are common, while subsequent treatment options remain limited, contributing to an elevated HCC-associated mortality rate. The increasing awareness and emphasis on HCC prevention and treatment have stimulated the development of numerous predictive models in recent years. This review aims to discuss the current state of research on HCC predictive models, comparing the strengths and limitations of widely recognized models, and evaluating their applicability in clinical settings with an ultimate goal of promoting their integration into clinical practice for improved outcomes in managing HCC.

Recent advances in the study of biofeedback therapy for outlet dysfunction constipation
Zefeng YUAN,Minjing CHENG,Qiang CHEN,Bo WANG,Bin. KONG
2024, 40(24):  3568-3574.  doi:10.3969/j.issn.1006-5725.2024.24.021
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The main symptoms of dyssynergic defecation are difficult defecation and incomplete emptying, and may also be accompanied by anal swelling, pain, manual assisted defecation, urination and sexual dysfunction, etc. Patients often have poor effects on conventional treatment such as laxatives. Biofeedback therapy is an emerging therapy for dyssynergic defecation in recent years. The researches of dyssynergic defecation in recent years show that patients' symptoms can be effectively improved by monitoring pelvic floor muscle activity and providing real-time feedback. With the continuous progress of technology, the accuracy and portability of biofeedback therapeutic equipment has gradually improve, making it more convenient and effective in clinical application. However, the single biofeedback effect is slow, which easily affects the patient's treatment confidence. At the same time, the study has found that biofeedback therapy can be combined with other treatment methods to achieve better efficacy. This paper reviews the efficacy status of biofeedback combination therapy at home and abroad, and discusses the biological mechanism and their respective effects, in order to provide more effective treatment options for patients with dyssynergic defecation.

Difficult Case Discussions
Study on the clinical characteristics and genetic mechanisms of mucolipidosis Ⅲα/β caused by a novel mutation in the GNPTAB gene
Li WANG,Congcong SHI,Xueqin YAN,Jiayan TANG,Sitao LI,Hu HAO,Xin. XIAO
2024, 40(24):  3575-3581.  doi:10.3969/j.issn.1006-5725.2024.24.022
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Objective To explore the clinical characteristics and genetic mechanisms of patients with Mucolipidosis Ⅲα/β caused by GNPTAB gene mutations. Methods A retrospective analysis was conducted on the clinical data and genetic tests of a confirmed case of Mucolipidosis Ⅲα/β. Various protein prediction tools were used to generate protein models of the wild type and mutant GNPTAB proteins, and computational biology tools were employed to elucidate the differences in protein structure and function between the wild type and mutant variants. Results The patient in this case mainly presented with joint deformities and short stature. Genetic sequencing revealed compound heterozygous mutations in the GNPTAB gene, c.2715 + 1G > A and c.1582T > C; the missense mutation c.1582T > C has not been reported in the literature. By constructing and analyzing three-dimensional models of the mutants, it was found that the c.2715 + 1G > A mutation alters the overall structure of the protein, leading to the loss of protein function, while the c.1582T > C mutation affects the interaction between the subunit of N-acetylglucosamine-1-phosphate transferase and its ligand. Conclusions This case of MLⅢα/β results from a mutation in the GNPTAB gene, including a missense mutation c.1582T > C that has not been previously reported, which expands the spectrum of pathogenic mutations of this gene. Through computational analysis of the protein variants resulting from the GNPTAB gene mutation, the understanding of their structure-function relationship has been elaborated, revealing the molecular mechanisms behind the onset of ML Ⅲα/β disease.