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25 September 2023, Volume 39 Issue 18
Feature Reports:lumbar spine disease
Analysis of the relationship between FGF⁃1 and VEGF expression in the ligamentum flavum of patients with lumbar spinal stenosis and restenosis after decompression
Yaoxin CHEN,Songbo LI,Guanjun FANG,Guobiao YE,Xianyin. LIU
2023, 39(18):  2289-2293.  doi:10.3969/j.issn.1006-5725.2023.18.001
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Objective To investigate the relationship between the expressions of fibroblast growth factor 1 (FGF?1) and vascular endothelial growth factor (VEGF) in the ligamentum luteum in patients with lumbar spinal stenosis (LSS) and restenosis after decompression. Methods 138 LSS patients underwent lumbar decompression were selected, including mild group [absolute claudication distance (ACD) ≤ 200 m, 41 cases], moderate group (ACD 201 ~ 400 m, 67 cases) and severe group (ACD > 400 m, 30 cases), and 138 non?LSS patients were selected as control group. The expressions of FGF?1 and VEGF in ligamentum flavum were detected, and the restenosis was measured after the operation. Results The expression of FGF?1 in LSS group was lower than that in control group (P < 0.001), and the expression of VEGF was higher than that in control group (P < 0.001). The expression of FGF?1 in severe group was lower than that in moderate and low degree groups (P < 0.05), and the expression of VEGF was higher than that in moderate and low degree groups (P < 0.05). Severe spinal stenosis, incomplete decompression and high expression of VEGF were risk factors for restenosis after lumbar decompression in patients with LSS (P < 0.05,P < 0.001), and FGF?1 was protective factor (P < 0.05). Conclusion FGF?1 expression decreased and VEGF expression increased in ligamentum flavum of LSS patients, which was related to the degree of spinal canal stenosis and postoperative restenosis.

Construction and validation of risk warning model of postoperative re⁃fracture in patients with osteoporosis vertebral compressibility fracture
Ye TIAN,Qiuwen YUAN,Liangshen. HU
2023, 39(18):  2294-2299.  doi:10.3969/j.issn.1006-5725.2023.18.002
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Objective To explore the risk factors of postoperative re-fracture in patients with osteoporotic vertebral compressibility fracture (OVCF), and toestablish a risk early warning model and verify it. Methods One hundred and eighty OVCF patients who underwent surgical treatment in nanchang hongdu traditional chinese medicine hospital from January 2020 to June 2021 were selected and divided into a re-fracture group and a nonre-fracture group. Logistic regression analysis was performed, and a line chart risk model was constructed and validated. Results Among 180 OVCF patients who underwent surgical treatment, the incidence of postoperative fractures was 22.78%. Factor analysis showed that age ≥ 60 years old, bone cement leakage, postoperative low bone mineral density, high bone cement injection rate and postoperative kyphosis Coob angle were independent risk factors for re-fracture after OVCF (P < 0.05). Long-term anti-osteoporosis treatment and high BMI were independent protective factors (P < 0.05).Hosmer-Lemeshow Test showed that the area under the ROC curve of 0.979 (95% CI: 0.957 ~ 1.000, P < 0.001), the sensitivity of 92.70%, the specificity of 96.40%, and the maximum Jordan index of 0.891, the overall trend of the model correction curve was close to the ideal curve. The decision curve analysis showed a positive net benefit. Conclusion The occurrence of postoperative re-fracture in OVCF patients is influenced by multiple factors, and the risk warning model established based on risk factors has good predictive performance.

Establishment of Nomogram prediction model for latent blood loss in patients with lumbar disc herniation after operation
Xiuquan QI,Wei WANG,Xiaokang QIU,Ye. XU
2023, 39(18):  2300-2305.  doi:10.3969/j.issn.1006-5725.2023.18.003
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Objective To analyze the risk factors of recessive blood loss in patients with lumbar disc herniation after surgery and establish a nomogram prediction model. Methods Two hundred patients with lumbar disc herniation who came to our hospital from February 2019 to August 2022 were selected as the research objects. According to the recessive blood loss after surgery, the patients were divided into positive group (n = 85) and negative group (n = 115). ROC experiment was used to analyze the predictive value of continuous variables. Logistic regression experiment was used to analyze the risk factors of recessive blood loss in patients with lumbar disc herniation after operation. Internal data were used to verify the clinical efficacy of Nomogram model. Results There was no significant difference in gender, BMI and other general data between the two groups (P > 0.05). Compared with the negative group, the patients in the positive group were older, and they had more perioperative blood transfusions, larger number of surgical segments, higher TC and TG levels, and lower postoperative hemoglobin levels (P < 0.05). The AUCs of age, number of operative segments, TC, TG and postoperative hemoglobin were 0.611, 0.607, 0.602, 0.673, 0.791, respectively, with the optimal cutoff values 39 years, 2 segments, 4.96 mmol/L, 6.79 mmol/L, 107 g/L, respectively. Age (> 39 years), perioperative blood transfusion, number of operative segments (> 2 segments), TC (> 4.96 mmol/L), TG (> 6.79 mmol/L), and hemoglobin difference (> 44 g/L) were all risk factors for recessive blood loss in the patients (P < 0.05). Nomogram model predicted the risk of occult blood loss in the patients after surgery by a C-index of 0.775 (95% CI: 0.669 ~ 0.848), with a risk threshold of recessive blood loss > 0.07. Nomogram model predictively yielded clinical net benefits as well. Conclusion Age (> 39 years), perioperative blood transfusion, number of operative segments (> 2 segments), TC (> 4.96 mmol/L), TG (> 6.79 mmol/L), and hemoglobin difference (> 44 g/L) are all risk factors that affect the occurrence of recessive blood loss in patients with lumbar disc herniation after surgery. Nomogram model based on the above variables can better predict the occurrence of recessive blood loss in those patients.

Construction of a column chart model for predicting postoperative delirium in patients with lumbar vertebral fractures based on novel inflammatory composite scoring
Mengxin XU,Wei WANG,Rongxiong. DAI
2023, 39(18):  2306-2311.  doi:10.3969/j.issn.1006-5725.2023.18.004
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Objective To explore the use of a novel inflammatory composite scoring system with a column chart model to predict the risk of postoperative delirium in patients with lumbar spine fractures. Methods 251 patients with lumbar spine fracture who had been admitted to our hospital and had undergone surgical treatment from June 2020 to December 2022 were selected as study subjects, and then divided into a postoperative delirium group (n = 55) and a delirium-free group (n = 196) according to the patients' conditions. The clinical data of the two groups were recorded and subjected to univariate analysis. ROC curve was used to analyze the predictive value of the indexes for postoperative delirium in the patients; logistic regression was used to analyse the independent risk factors for postoperative delirium and construct a columnar graph model; the calibration curves were used for the internal validation of the model; the consistency index (C-index) was calculated; and the decision curve was used to evaluate the predictive efficiency of the model. Results The differences between the two groups in terms of age, surgical duration, intraoperative bleeding, and inflammatory response markers NLR, PLR, and CAR were statistically significant (P < 0.05). The AUCs of age, surgical time, intraoperative bleeding, NLR, PLR, and CAR were 0.788, 0.714, 0.797, 0.824, 0.839, and 0.811, respectively; and the AUC of the constructed N.P.Cs scoring scale was 0.963. Age, intraoperative bleeding, and N.P.Cs were independent risk factors affecting postoperative delirium in patients with lumbar spine fractures. The calibration curve of the column-line diagram prediction model was close to the original and ideal curves, with a C-index of 0.847 (95% CI:0.811 ~ 0.903); the threshold value of the column-line diagram prediction model was greater than 0.17, providing a net clinical benefit. Conclusion Age, intraoperative bleeding, and N.P.Cs are independent risk factors for postoperative delirium in patients with lumbar spine fractures. The column chart prediction model based on this construction can provide guidance for the prevention and treatment of postoperative delirium in patients with lumbar spine fractures.

Basic Research
Effect of BMI-1 inhibitor PTC-596 on proliferation, cell cycle, and apoptosis of human breast cancer MCF-7cells
Yuling LI,Jianlin YANG,Zhi CUI,Jing WANG,Yafeng LV,Chunyu. CAO
2023, 39(18):  2317-2322.  doi:10.3969/j.issn.1006-5725.2023.18.006
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Objective To investigate the effect of a novel BMI-1 inhibitor PTC-596 on the proliferation, cell cycle, and apoptosis of human breast cancer MCF-7 cells. Methods MCF-7 cells treated with 0 nmol/L PTC-596 were used as control group; MCF-7 cells treated with 25, and 50 nmol/L PTC-596 as experimental group. The CCK8 assay was used to evaluate the celular proliferation ability; DCFH-DA probe/flow cytometry (FCM) was performed to detect the change of cellular reactive oxygen species (ROS). PI single-staining/FCM was used to analyze cell cycle; PI/FITC -Annexin V/FCM to analyze the proportion of apoptotic cells. JC-1/FCM was performed to detect the change of mitochondrial membrane potential(MMP); western blot to analyze the expression of BMI-1, cell cycle related proteion(CyclinD1, CyclinB1, and P21) and apoptosis related proteion (Bax, Bcl-2, and c-PARP). Results PTC-596 could significantly inhibit MCF-7 cell proliferation, with the IC50 value of 49.33 ± 7.02 nmol/L(24 h). BMI-1 expression was significantly decreased in the low- and high- drug concentration experimental group (P < 0.01). The relative expression of CyclinB1 and P21 in the experimental groups were increased (P < 0.01), while the expression of CyclinD1 was decreased (P < 0.01), and cell mitosis was inhibited (P < 0.01), resulting in G2/M cycle arrest (P < 0.01). At the same time, the accumulation of reactive oxygen species was increased (P < 0.01); mitochondrial membrane potential was decreased (P < 0.01). Bax expression was up-regulated (P < 0.01), while Bcl-2 expression was down-regulated (P < 0.01); c-PARP was increased (P < 0.01), and the proportion of apoptotic cells was significantly increased from 2.04% to 10.56% and 26.74% (P < 0.01). Conclusion PTC-596 can effectively inhibit the proliferation of human breast cancer MCF-7cells, and its mechanism may be closely related to the inhibition of BMI-1, the induction of cell cycle arrest, and the endogenous mitochondrial apoptosis.

Regulatory effect of LPAR1 gene on tissue factor and plasminogen activator inhibitor-1 in LPSstimulated type II alveolar epithelial cells
Ying LIU,Xianjun CHEN,Chuan XIAO,Jia YUAN,Qing LI,Lu LI,Jinfeng YANG,Feng. SHEN
2023, 39(18):  2323-2329.  doi:10.3969/j.issn.1006-5725.2023.18.007
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Objective To investigate the dynamic expression characteristics of lysophosphatidic acid receptor 1 (LPAR1), a differentially expressed gene, in type Ⅱ alveolar epithelial cells (AEC Ⅱ) stimulated by lipopolysaccharide (LPS), and the role of the gene in the regulation of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1). Methods RNA-seq sequencing was performed on RLE-6TN cells after injured by LPS, and then using bioinformatics analysis, identify the differentially expressed gene LPAR1 in the NF-κB signaling pathway. LPAR1 gene was dynamically expressed in RLE-6TN cells at 6, 12, 24, 48 and 72 h after LPS stimulation. On this basis, the expression of LPAR1 gene was knocked down by lentiviral transfection to observe the effect of the gene on the expression of TF and PAI-1. Results The expression of LPAR1 in RLE-6TN cells started to increase after 6 h of stimulation, peaked at 24 h, and then gradually decreased. LPAR1 gene levels were successfully knocked down through lentiviral transfection. After 24 hours of LPS stimulation, the expression levels of TF and PAI-1 mRNA and protein in the cells increased significantly compared with normal controls, with statistical significance (P < 0.05), and then after knocking down LPAR1 gene, the expression levels of TF and PAI-1 decreased significantly (P < 0.05) and approached normal control values(P > 0.05). Conclusion The LPAR1 gene has a regulatory effect on TF and PAI-1 in LPS-stimulated RLE-6TN cells. The gene is expected to be a new target for correcting fibrin deposition in the alveoli of ARDS.

miR-4505 downregulates cell proliferation and migration in Hirschsprung′s disease by targeting SOX-10
Kai WU,Jianjun WANG,Jixian HE,Qinming CHEN,Daiyue YU,Yi LU,Kaisi FAN,Mengzhen ZHANG,Liucheng. YANG
2023, 39(18):  2330-2334.  doi:10.3969/j.issn.1006-5725.2023.18.008
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Objective To explore the role and molecular mechanism of miR-4505 in Hirschsprung disease(HSCR). Methods Stenotic and dilated colon segments of HSCR patients operated at Zhujiang Hospital of Southern Medical University were collected.qRT-PCR was performed to detected the expression of miR-4505 in colon tissuesspecimens.The miR-NC,miR-4505 mimics and miR-4505 inhibitors were transfected into human neuroblastoma cell line SH-SY5Y,followed by qRT-PCR to examine the expression of miR-4505 after transfection, CCK-8 assay and Transwell assay to detect the effect of miR-4505 on the proliferation and migration of SH-SY5Y cells.The downstream target genes of miR-4505 were predicted through bioinformatics and detected by dual luciferase reporter gene assay; the target genes were verified by Western blot and Immunohistochemistry. Results miR-4505 was highly expressed in the stenotic colon compared to the dilated segment (t = 11.25,P < 0.001). Overexpression of miR-4505 inhibited cell proliferation and migration, and conversely,downregulation of miR-4505 enhanced cell proliferation and migration. Target gene prediction and dual-luciferase reporter gene assay suggested that the 3′-UTR of SOX-10 was a direct target of miR-4505. Moreover, Western blot confirmed that miR-4505 decreased SOX-10 protein levels in cells, while immunohistochemistry proved that SOX-10 was lowly expressed in HSCR disease colontissues. Conclusion Our study demonstrated that miR-4505 was differentially expressed between the diseased and dilated segments of HSCR.miR-4505 could inhibited cell proliferation and migration,and its role in HSCR may be achieved by suppressing the downstream SOX-10 gene expression.

Effect of Xuebijing on lung tissue damage induced by Klebsiella pneumoniae in rats with severe pneumonia through miR⁃155/JAK2/STAT1 signaling pathway
Fei WEI,Xiangyu WANG,Zhiyong LIU
2023, 39(18):  2335-2341.  doi:10.3969/j.issn.1006-5725.2023.18.009
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Objective To investigate the effect of Xuebijing on rats with severe pneumonia (SP) and its possible mechanism. Methods Forty SP rats were randomly divided into model group, miRNA-155 agonist group (miRNA-155 agonist, 80 mg/kg), Xuebijing low-dose group (Xuebijing injection, 4 mg/kg), Xuebijing high-dose group (Xuebijing injection, 8 mg/kg), miR-155 agonist + Xuebijing group (miR-155 agonist 80 mg/kg, Xuebijing injection 8 mg/kg), with 8 rats in each. Eight healthy rats were included into control group. Control group and model group were injected with the same amount of normal saline through caudal vein. After 7 days of continuous administration, lung coefficient (LI), interleukin-1β (IL-1β) level, receptor tyrosine kinase 2 (JAK2), signal transduction and transcriptional activator 1 (STAT1) protein expression were detected in each group. Results Compared with those in the model group, the level of LI and IL-1β, p-JAK2/JAK2 and p-STAT1/STAT1 in lung tissue were increased in miR-155 agonist group (P < 0.05). The level of LI and IL-1β, P-JAK2 /JAK2 and P-Stat1/STAT1 in lung tissue were decreased in low and high dose Xuebijing group and miR-155 agonist + Xuebijing group (P < 0.05). Compared with those in miR-155 agonist group, the level of LI and IL-1β, P-JAK2 /JAK2 and P-Stat1/STAT1 in lung tissue were decreased in Xuebijing low and high dose group, and miR-155 agonist + Xuebijing group (P < 0.05). Compared with those in Xuebijing low dose group, the level of LI, IL-1β, p-JAK2/JAK2 and p-STAT1/STAT1 in lung tissue were increased in Xuebijing high dose group (P < 0.05). Compared with those in Xuebijing group, LI and IL-1β level, P-JAK2 /JAK2 and P-Stat1 /STAT1 in lung tissue were increased in miR-155 agonist + Xuebijing group (P < 0.05). Conclusion Xuebijing can reduce lung injury in SP rats, possibly by inhibiting the expression of miR-155 and thereby reducing the JAK2/STAT1 signaling pathway.

Effects of T follicular helper cells and IL⁃21 on proliferation and cell cycle of HaCaT cellsinpsoriasis
Sitong LI,Ao WANG,Yanping BAI,Ying. WANG
2023, 39(18):  2342-2348.  doi:10.3969/j.issn.1006-5725.2023.18.010
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Objective To observe the effects of T follicular helper cells and the main functional cytokines IL?21 on the proliferation and cell cycle of HaCaT cells cultured in vitro in patients with psoriasis. Methods Fifteen patients with psoriasis vulgaris and 10 healthy controls were defined as psoriasis group and healthy control group, respectively. CD4+CXCR5+ Tfh cells from psoriatic patients and healthy controls were separated by flow cytometry and co?cultured with HaCaT cells at 1∶1. IL?21 or IL?21 neutralizing antibodies were added and the HaCaT cells were collected after 72 h of intervention. The cell proliferation was measured by the CCK?8 and the cell cycle and Ki?67 expression of HaCaT cells were detected by flow cytometry. Results IL?21 promoted the proliferation of HaCaT cells (P < 0.05) and increased the proportion of HaCaT cells in S phase and decreased the proportion of cells in G0/G1 phase (P < 0.05). When Tfh cells were co?cultured with HaCaT cells, the proliferation activity of HaCaT cells in psoriasis group and healthy control group was significantly higher than that in control group (P < 0.000 1), and the proliferation activity of HaCaT cells in psoriasis group was higher than that in IL?21 neutralization antibody group (P < 0.000 1). In psoriasis group, IL?21 neutralizing antibody group compared with Tfh?HaCaT co?culture group show that it could block HaCaT cells in G0/G1 phase, reduce the number of cells in S phase, and then inhibit the proliferation of HaCaT cells. Conclusion IL?21 promoted the HaCaT cell proliferation invitro; Tfh cells inpsoriasispatients promoted the proliferation of keratinocytes invitro, and blocking IL?21 inhibitd this promoting effect. In summary, Tfh cells may promote theproliferation of keratinocytes through producing IL?21, thereby promoting the development and progression of psoriasis.

Clinical Research
To construct and validate a predictive model for failed air enema reduction in children with emergency intussusceptions
Dongxue LI,Dehuan LI,Yiming SUN,Guangzhong HU,Qing HUANG,Jiaji LIU,Lin. JIANG
2023, 39(18):  2349-2356.  doi:10.3969/j.issn.1006-5725.2023.18.011
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Objective To establish a prediction model for failure of intussusception in children under fluoroscopy. Methods In this study, 439 children with intussusception were retrospectively included in our hospital, with 362 successful and 77 unsuccessful air enema. The total samples were randomly divided into 308 training sets and 131 verification sets according to a ratio of 7∶3. The parameters and clinical information of children with air enema were collected, the variables were screened by single factor Logistic regression analysis, and then the prediction model was constructed by multi?factor Logistic regression analysis and the Nomo diagram was drawn. The differentiation, calibration and decision curve of the model were evaluated. Results Statistical differences were found between the successful and unsuccessful groups except gender and intestinal obstruction (all P < 0.05). The independent risk factors screened by multivariate Logistic regression analysis were age, course of disease, intestinal obstruction, head position and empty irrigation pressure for modeling. The model had good differentiation in predicting the failure of recirculation, with AUC = 0.854 (95%CI: 0.799 ~ 0.909), truncation value of 0.24, sensitivity and specificity of 79% and 80%, respectively. The calibration curve showed that the risk predicted by the model was highly consistent with the actual situation. Hosmer Lemeshow test χ2 = 8.159, P = 0.518; The decision curve shows that the model has clinical applicability. Conclusion Air enema pressure combined with clinical information has a better ability to predict the risk of failure of enema reduction, which can provide some references for clinical decision?making in children with emergency intussusception.

Relationship between prenatal body mass index and pregnancy outcomes in singleton pregnant women with preeclampsia
Yanxuan XIAO,Lili ZHANG,Jiaqi LI,Yunting ZHUANG,Yao SONG,Wenhui LI,Tian TAN,Haitao CHEN,Zhijian. WANG
2023, 39(18):  2357-2361.  doi:10.3969/j.issn.1006-5725.2023.18.012
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Objective To explore the clinical characteristics and pregnancy outcomes of singleton pregnant women with preeclampsia and with different prenatal body mass index(BMI), and analyze the relative risk of prenatal BMI as a risk factor for adverse outcomes. Methods A retrospective analysis was conducted on the clinical data of 479 singleton pregnant women with preeclampsia that delivered in Nanfang Hospital from January 2016 to December 2021. They were divided into group A (BMI < 26 kg/m2), group B (26 ≤ BMI < 28 kg/m2), group C (28 ≤ BMI < 30 kg/m2), group D (30 ≤ BMI < 32 kg/m2), and group E (BMI≥32 kg/m2) according to prenatal BMI. The general situation, pregnancy complications and pregnancy outcomes in each group were compared. Results The proportion of adverse outcomes such as severe preeclampsia, placental abruption, fetal growth restriction, and NICU transfer ratio in group A was increased, and these patients terminated pregnancy earlier. In group E, the proportion of cesarean delivery, gestational diabetes and macrosomia was increased, and there was more blood loss during operation and 24 hours after delivery. Patients of Group C had the lowest proportion of induced abortion or stillbirth. Compared with group C, BMI ≥ 32 kg/m2 was a risk factor for gestational diabetes; BMI < 26 kg/m2 was a risk factor for placental abruption and fetal growth restriction, while BMI < 26 kg/m2 or BMI ≥30 kg/m2 was the risk factor for the neonatals′ NICU admission. Conclusion There is correlation between prenatal BMI and adverse pregnancy outcomes in pregnant women with preeclampsia, and the appropriate range of BMI is 26 ~ 30 kg/m2.

Evaluation value of monitoring changes of ultrasonic elastic imaging parameters before and after CDT combined with ART in patients with acute deep venous thrombosis of lower extremities
Jianghao PAN,Jianming SUN,Jiaming SONG,Guangyin FU,Yong LEI,Xiaojie. ZHANG
2023, 39(18):  2362-2367.  doi:10.3969/j.issn.1006-5725.2023.18.013
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Objective To analyze the value of monitoring changes in ultrasound elastography parameters before and after treatment with catheter contact thrombolysis (CDT) combined with AngioJet mechanical thrombus aspiration (ART) in patients with acute lower extremity deep vein thrombosis (DVT) for the assessment of efficacy. Methods One hundred patients with DVT admitted to Hengshui people′s hospital from August 2021 to August 2022 were selected, and all patients received CDT combined with ART and postoperative medication for 10 d. Patients were observed for swelling of the affected limb before and after 10 d of treatment, ultrasound elastography parameters. Patients were divided into ineffective group and effective group according to different curative effects, and baseline data and ultrasonic elastography parameters before treatment were compared between the two groups; the subject operating curve (ROC) was plotted, and the area under the curve (AUC) values were calculated to test the predictive value of ultrasound elastography parameters for treatment ineffectiveness in DVT patients; Spearman's analysis of ultrasound elastography parameters and treatment ineffectiveness in DVT patients was performed using a bivariate correlation variable The correlation between ultrasound elastography parameters and treatment ineffectiveness in DVT patients was analyzed using the bicorrelation variable Spearman. Results After 100 patients with DVT were treated with CDT combined with ART, 34(34.00%) were effective, 53(53.00%) were effective, and 13(13.00%) were ineffective; After treatment, the circumference difference of the affected side thigh and the circumference difference of the affected side calf of DVT patients were smaller than before treatment, and the ultrasonic elastography score, strain value and Young's modulus value were lower than before treatment (P < 0.05). The ultrasonic elastography score, strain value and Young's modulus in the ineffective group were higher than those in the effective group before treatment (P < 0.05). The ROC curve shows that the ultrasonic elastography score, strain value, Young's modulus level and combined detection have certain predictive value in predicting the clinical efficacy of DVT patients (AUC = 0.803, 0.793, 0.771), and the combined detection is the highest (AUC = 0.946). Among them, the combined test was the highest; using Spearman analysis of dual correlation variables, the results showed that ultrasound elastography score, strain value, and Young's modulus value were positively correlated with treatment ineffectiveness in patients with DVT (r > 0, P<0.05). Conclusion Ultrasound elastography parameters can effectively predict clinical outcomes after CDT combined with ART in DVT patients, and changes in ultrasound elastography parameters were positively correlated with treatment ineffectiveness.

The prognostic value of serum DCLK1 and sTim⁃3 in patients undergoing radical prostatectomy for prostate cancer
Minyu HUANG,Jun WU,Tianzi QIN,Wei ZHOU,Lize SU,Rong QIU,Lu. HUANG
2023, 39(18):  2368-2372.  doi:10.3969/j.issn.1006-5725.2023.18.014
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Objective To investigate the prognosis of serum bicorticotin-like kinase 1 (DCLK1) and soluble T cell immunoglobulin mucin molecule 3 (sTim-3) in patients undergoing radical prostatectomy. Methods This study selected 80 patients who underwent radical prostatectomy in our hospital from June 2016 to June 2019 as the research group, and another 80 healthy individuals who underwent physical examination during the same period as the control group; enzyme linked immunosorbent assay (ELISA) was applied to detect serum levels of DCLK1 and sTim-3; The relationship between serum DCLK1 and sTim-3 and pathologic features and prognosis of patients undergoing radical prostatectomy was analyzed. Results The serum levels of DCLK1 and sTim-3 in the study group were obviously higher than those in the control group (P < 0.05). Serum DCLK1 and sTim-3 levels were positively correlated (P < 0.05). Both were positively correlated with PSA level and Gleason score (P < 0.05).Serum DCLK1 and sTim-3 expression levels were associated with PSA levels, Gleason scores, and TNM stages (P < 0.05). The serum levels of DCLK1 and sTim-3 in the prognostic death group were significantly higher than those in the prognostic survival group (P < 0.05). Patients with high expression of DCLK1 and sTim-3 had lower survival rates than those with low expression. According to Cox regression analysis, high expression of DCLK1 and sTim-3 was a risk factor affecting the prognosis of patients undergoing radical prostatectomy (P < 0.05). According to the ROC curve, the AUC that jointly predicted the prognosis of patients undergoing radical prostatectomy was better than that of DCLK1 and sTim-3 respectively. Conclusion DCLK1 and sTim-3 are obviously elevated in the serum of prostate cancer patients, and their combination can better evaluate the prognosis of patients undergoing radical prostatectomy.

Effect of fasting plasma glucose level on the prognosis of disease in patients with HBV⁃related acute⁃on⁃chronic liver failure
Haibin WANG,Hui LI,Xiaolei CHEN,Na LIU,Quanmei LI,Yu ZOU,Chunmei LI,Jingquan GAN,Changhui WU,Huaxian CHEN,Xiang LIU,Ming. GONG
2023, 39(18):  2373-2378.  doi:10.3969/j.issn.1006-5725.2023.18.015
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Objective To explore the effect of fasting blood glucose(FPG) on the prognosis of disease in patients with HBV-related acute-on-chronic liver failure. Methods The clinical data of 109 HBV-related ACLF patients admitted to the Department of Infectious Diseases of a tertiary a hospital in Yunnan Province were retrospectively analyzed, and grouped according to different FPG levels and prothrombin international standardized ratio(PT-INR) of prothrombin. ANOVA test, Chi-square test, Spearman correlation analysis and binary logistic regression were used to analyze the effect of FPG level on the prognosis of disease of HBV-related ACLF patients. Results The incidence and mortality of HBV-related ACLF complications (HE, hyponatremia, SBP) in low FPG group were higher than those in normal FPG and high FPG group (P < 0.05). The incidence of low FPG and mortality of patients in middle-late stage group were higher than those in pre-early stage group (P < 0.05). Child-Pugh score, MELD score and INR were positively correlated (P < 0.001). Binary Logistic regression analysis showed that low FPG and normal FPG were independent risk factors for disease progression in HBV-related ACLF patients (OR = 0.174, 95%CI: 0.066 ~ 0.461,P < 0.05). Conclusion Low FPG increases the risk of worsening disease progression in patients with HBV-related ACLF, while high FPG may play a role in protecting liver function.

D⁃dimer and lactic acid combined with sPECAM⁃1 in the prediction of poor prognosis in patients with sepsis⁃related disseminated intravascular coagulation
Ziwen WANG,Wenjing ZHAO,Yali. CHAO
2023, 39(18):  2379-2383.  doi:10.3969/j.issn.1006-5725.2023.18.016
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Objective To investigate the predictive value of D?dimer (D?D), lactic acid, and soluble platelet endothelial adhesion molecule?1 (sPECAM?1) in patients with sepsis?associated disseminated intravascular coagulation (DIC). Methods According to the prognosis of patients at 28 days, 300 patients with sepsis?related DIC in the ICU of the Affiliated Hospital of Xuzhou Medical University were gathered and split into death and survival groups. The two groups' general statistics, APACHEⅡ score, serum D?D, lactate, and sPECAM?1 levels were compared. The operating characteristic curve (ROC) was used to evaluate the predictive value of serum D?D, lactate, and sPECAM?1 on the poor prognosis of patients with sepsis?related DIC. Results The 28?day mortality rate of patients with sepsis?related DIC was 22%, and the death group had higher APACHEⅡ scores, serum D?D, lactate, and sPECAM?1 levels than the survival group (P < 0.05). Multivariate logistic regression results showed that serum D?D, lactic acid and sPECAM?1 were risk factors for 28?day death in patients with sepsis?related DIC.The AUC of serum D?D, lactic acid, and sPECAM?1 was 0.863 (95%CI: 0.768 ~ 0.958), 0.831 (95%CI: 0.734 ~ 0.928), 0.774 (95%CI: 0.653 ~ 0.896), respectively. The AUC of the combination of serum D?D, lactic acid and sPECAM?1 was 0.965 (95%CI: 0.928 ~ 1.000), with the sensitivity 0.864 and the specificity 0.974, each of which were greater than the individual predictions. Conclusion In patients with sepsis?related DIC, higher serum D?D, lactate, and sPECAM?1 levels were highly correlated with 28?day death.In patients with sepsis?related DIC, higher serum D?D, lactate, and sPECAM?1 levels were highly correlated with 28?day death. The combination of serum D?D, lactate, and sPECAM?1 levels provided a high predictive value for the prognosis of sepsis?related DIC and might be employed in therapeutic treatment.

Drugs and Clinic Practice
Analyze of the value of bifidum in the treatment of sepsis caused by pulmonary infection based on intestinal immunity
Ming LI,Wei SU,Shiheng. MA
2023, 39(18):  2384-2388.  doi:10.3969/j.issn.1006-5725.2023.18.017
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Objective To analyze the effects of bifidum on intestinal flora and related immune function markers in patients with sepsis caused by lung infection, and to provide data for supporting clinical application. Methods One hundred and forty-three cases of sepsis caused by lung infection were randomly divided into two groups, including 71 cases of control group (received conventional treatment) and 72 cases of study group (received bifidum in addition to conventional treatment). Critical illness scores [Acute Physiological and Chronic health (APACHEⅡ) score and Sequential Organ failure (SOFA) score] were evaluated before treatment and at 7 days after treatment, respectively. Fecal samples were collected to analyze the colonies of LactobacillusbifidumEnterobacterenterococcusEscherichia coli and Clostridium. Peripheral blood was collected and the level of T lymphocyte subpopulation in blood was determined by flow cytometry. The plasma D-lactic acid and bacterial endotoxin levels were detected by intestinal barrier function biochemical index analysis system. The plasma levels of procalcitonin (PCT), hypersensitive C-reactive protein (hs-CRP) and interleukin-6 (IL-6) were also determined by ELISA. Results Before treatment, there were no significant differences in critical disease score, intestinal flora number, intestinal function, T lymphocyte subsets and inflammatory factors between the two groups (P > 0.05). After treatment, APACHEⅡ and SOFA scores in both groups were significantly reduced, and APACHEⅡ scores in the study group were significantly lower than those in the control group (P < 0.05). After treatment, the number of Lactobacillusbifidum and CD3+T% levels in both groups increased, while the number of enterococcusEscherichia coli, intestinal function score, D-lactic acid, endotoxin, TNF-ɑ, IL-6 and IL-1β levels decreased. The levels of Lactobacillus, bifidum and CD3+T% in the study group were higher than those in the control group, while the levels of Escherichia coli, D-lactic acid, endotoxin, hs-CRP and IL-6 in the study group were lower than those in the control group (P < 0.05). Conclusion Adding bifidum in the clinical treatment of sepsis caused by lung infection can improve the distribution of intestinal flora to a certain extent and alleviate the damage of intestinal barrier function caused by inflammation, which may be helpful to promote the repair of patients.

The clinical value of PD1 inhibitor combined with furoquantinib and TAS⁃102 posterior therapy for advanced colorectal cancer
Xiaoqin SU,Xi CHEN,Haihua FAN,Congfei JI,Tingting NI,Yang YU,Jia. CHEN
2023, 39(18):  2389-2394.  doi:10.3969/j.issn.1006-5725.2023.18.018
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Objective To explore the clinical value and safety of PDI inhibitor combined with furoquantinib and TAS-102 in the treatment of advanced colorectal cancer. Methods This study is a retrospective analysis, collected a total of 30 late stage colorectal cancer cases that failed standard treatment. Among the 30 case, 12 cases were set as the observation group, and 18 cases were set as the control group. The observation group was treated with PD1 inhibitor combined with furoquantinib and TAS-102, while the control group was treated with PD1 inhibitor combined with furoquantinib. PD1 inhibitors include Xindilizumab 200 mg, Tirelizumab 200 mg, or Sepalizumab 240 ng. 3 ~ 5 mg Furoquantinib is received orally for two weeks and stopped for one week. TAS-102 (25 mg/m2) was taken orally after breakfast and dinner on days 1 to 5 and 8 to 12, with a cycle of 21 days. Data were organized data to analyze the objective response rate (ORR), disease control rate (DCR), adverse reactions of the two groups, and patients were regularly followed up to observe their progression free survival (PFS). Results Until the end of follow-up (March 20, 2023), the ORR and DCR of the control group were 11.11%, 33.33%, and the median PFS was 6.2 months. The objective response rate of the observation group was 25.00%, white DCR was 83.33%, and median PF was 8.6 months. There was no significant difference in 0RR between the two groups,while the differences in DCR and PFS were statistically significant. The main adverse reactions in both groups were rash, liver dysfunction, gastrointestinal ulcers, hypothyroidism, and oral ulcers. The adverse reactions in both groups were mild. Compared with the control group, 3 patients in the observation group had abdominal pain, which was relieved after drug reduction, and 8 patients had 1-2 levels of bone marrow depression, which recovered after colony-stimulating factor treatment. Conclusions Compared with PD1 inhibitor combined with furoquantinib, the combination of TAS102 on this basis can prolong the survival period of patients with advanced colorectal cancer and tolerate adverse reactions. This regimen has the potential to become a new strategy for the third line treatment of advanced colorectal cancer.

Medical Examination and Clinical Diagnosis
The differential diagnosis of pancreatic duct a ladenocarcinoma and pancreatic neuroendocrine tumors using 18F⁃FDG PET/CT combined with serum CA19⁃9, CEA and NSE
Lichun ZHENG,Huan ZHANG,Cheng GU,Xinyu SHEN,Xiaoming ZHANG,Xiangliu. OUYANG
2023, 39(18):  2395-2400.  doi:10.3969/j.issn.1006-5725.2023.18.019
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Objective To discuss the value of 18F?FDG PET/CT combined with serum CA19?9, CEA and NSE in the differential diagnosis pancreatic ductal adenocarcinoma(pDAC) and pancreatic neuroendocrine tumors(pNETs). Methods Retrospective analys is of patients who were diagnosed as pDAC or pNETs by pathology, including the clinical data, 18F?FDG PET/CT images and the level of tumor markers CA19?9, CEA and NSE, and compared age, sex, size and location of the lesions, the involvement of pancreatic ductal, the morphology of the lesionson PET image, SUVmax, surrounding lymphatic metastasis and hepatic metastasis and the level of serum CA19?9, CEA, NSE between the two groups, and figure out the effective indicators in differential diagnosis. The diagnostic efficacy of 18F?FDG PET/CT imaging SUVmax combined with serum CA19?9, CEA and NSE was compared. Results There were 74 patients were included. The age were between 46 and 82(66.48 ± 8.84), and 32 were male, 32 were female. 46 patients were pDAC, 28 were pNETs. The mean value of SUVmax were (5.55 ± 2.01) in pDAC group, (4.62 ± 2.01) in pNETs group. It was not statistically significant between the two groups in sex, morphology of the lesions in PET image, SUVmax, surrounding lymphatic metastasis(P > 0.05), and was statistically significant in age, size of the lesions, location of the lesions, the involvement of pancreatic ductal hepatic metastasis and serum CA19?9, CEA, NSE(P < 0.05). The diagnostic efficacy of SUVmax combined with serum CA19?9, CEA and NSE was improved compared with SUVmax, which SUVmax combined with CA19?9 had the best diagnostic efficacy with the AUC of ROC curve was 0.891 (95%CI: 0.816~0.967, P < 0.001). Conclusion The using of 18F?FDG PET/CT combined with serum CA19?9, CEA, NSE has a high differential diagnosis value in pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors, that make up the shortage of using 18F?FDG PET/CT alone, which the diagnostic efficiency of SUVmax combined with CA19?9 was the best.

Diagnostic value of ultrasound texture analysis in T stage of rectal cancer
Yaning XIE,Dehui WEN,Likun WANG,Qi WANG,Xueliang. WU
2023, 39(18):  2401-2404.  doi:10.3969/j.issn.1006-5725.2023.18.020
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Objective To investigate the diagnostic value of ultrasound texture analysis in T stage of rectal cancer. Methods The preoperative ultrasound images of 31 patients with rectal cancer confirmed by surgery or pathology were selected, and the region of interest (ROI) was delineated by mazda software. The software automatically calculated the texture characteristic parameters of mean, kurtosis, skewness, contrast, entropy, variance sum, autocorrelation, energy and deficit distance, compared the differences of texture parameters of rectal cancer in different stages, and drew the subject's working characteristic curve (ROC) for the statistically significant parameters, compared the area under the curve (AUC), and evaluated its diagnostic efficiency. Results It was statistically shown that kurtosis, skewness, contrast, entropy, variance sum and autocorrelation were all influencing factors of T stage of rectal cancer, and the skewness, entropy, variance sum and autocorrelation of advanced rectal cancer (pT3-4 stage) were higher than those of early rectal cancer (pT1-2 stage) (P < 0.05), while the kurtosis and contrast were lower than those of early rectal cancer (P < 0.05). Among them, entropy has a higher diagnostic efficiency, and the AUC value is 0.88. Conclusion Ultrasound texture analysis can provide a more objective imaging basis for T staging of rectal cancer, and the texture characteristics of advanced rectal cancer are more complex than those of early rectal cancer.

Reviews
The neuroregulatory effects and potential applications of urolithins in mental disorders
Zhengyuan HUANG,Lirong ZHAO,Kexuan ZHANG,Gaohua WANG,Benhong. ZHOU
2023, 39(18):  2405-2410.  doi:10.3969/j.issn.1006-5725.2023.18.021
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Mental disorders are a group of complex neurological conditions with unclear etiologies, characterized by abnormalities in cognitive, emotional, volitional, and behavioral functions. The prevalence of mental disorders is increasing, whereas the development of effective drugs has been slow, greatly impacting the mental and physical well-being and quality of life in patients. Consequently, the development and application of new drugs have become a hot topic in current research. In recent years, urolithins, as natural bioactive compounds, have garnered widespread attention among researchers. By crossing the blood-brain barrier, urolithins play neuroprotective roles including anti-inflammatory, antioxidant, and anti-apoptotic effects. They are considered potential small molecules for modulating the nervous system, with potential clinical applications for symptom improvement and rehabilitation in mental disorders. However, no research on the application of urolithins for mental disorders has been currently reported. In this review, we summarize the recent domestic and international research on the neuroregulatory mechanisms and therapeutic potential of urolithins for mental disorders, aiming to provide new directions for research in mental disorders and offer novel insights for the development and clinical conversion of urolithin-based treatments for mental disorders.

Research progress of mild therapeutic hypothermia in neonatal moderate to severe hypoxic-ischemic encephalopathy
Manjun LI,Jing ZHANG,Shuchun YU,Wei. DENG
2023, 39(18):  2411-2415.  doi:10.3969/j.issn.1006-5725.2023.18.022
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Neonatal hypoxic-ischemic encephalopathy refers to brain damage caused by perinatal asphyxia, which can cause death and permanent neurological impairment in severe cases. Therapeutic hypothermia reduces death or disability in term and near-term infants with moderate to severe hypoxic-ischaemic encephalopathy. The latest studies have further refined the key parameters of hypothermia, including the timing, depth of cooling, duration, subsequent rate of rewarming, and prevention of fever during delivery and resuscitation. The key to improving neurodevelopmental outcomes is early postnatal diagnosis and initiation of hypothermia. This article will review the research progress of mild therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy, and introduce commonly used hypothermia induction methods, clinical challenges and future development directions.

Progress in the treatment of fracture nonunion
Guoyun BU,Tongtong LI,Zengliang. WANG
2023, 39(18):  2416-2420.  doi:10.3969/j.issn.1006-5725.2023.18.023
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Fracture is a common disease in orthopaedic clinical practice, and about 3% to 5% of fractures will develop non-union. Non-union of fractures will not only affect the quality of life of patients, but also increase the risk of death, and increase the economic burden of social health. In view of the treatment of fracture nonunion has always been a hot spot in the field of orthopedics at home and abroad, this article reviews the risk factors, monitoring and prediction of fracture nonunion and the progress of treatment, aiming to provide useful reference to the clinical diagnosis and treatment of fracture nonunion.