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25 March 2024, Volume 40 Issue 6
Comments
Research status and challenges of insomnia disorder
Shuangyan LI,Bin ZHANG
2024, 40(6):  731-737.  doi:10.3969/j.issn.1006-5725.2024.06.001
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Insomnia disorder is the most common sleep disorder, which interacts with other diseases, causing health damage to human body and imposing a significant socio?economic burden. Currently, there have been further advancements in subtypes of insomnia disorder, comorbidity research, mechanistic hypotheses, assessment strategies, and treatment methods. With the advent of the information age, digital platforms can integrate early warning, accurate assessment and diagnosis, treatment methods, and later follow?up for insomnia disorder to establish a comprehensive and standardized system for the treatment and management of insomnia disorder, helping to alleviate a rising morbidity rate and save healthcare costs.

Symposiums
Clinical application progress of immunization and targeted therapy for Hepatocellular Carcinoma in special populations
Fazhu FEI,Jiajun LU,Shuai ZHANG,Hao LI,Bin REN
2024, 40(6):  738-742.  doi:10.3969/j.issn.1006-5725.2024.06.002
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Hepatocellular carcinoma (HCC) has become the second leading cause of cancer-related death worldwide, ranking 6th among all tumors. Due to the lack of obvious early symptoms, most patients are diagnosed in the advanced stage, and the clinical benefits of surgical resection and hepatic artery chemoembolization and radiofrequency ablation are very limited. In recent years, the advent of immune-targeted therapies has revolutionized the systemic and systemic treatment of patients with advanced HCC, however, there is a lack of strong clinical evidence on the safety and efficacy of immune and targeted therapies for special populations, including patients with human immunodeficiency virus (HIV) infection, active autoimmune disease, decompensated cirrhosis (Child B or C), patients with diabetes-associated metabolic syndrome, patients with portal hypertension, vascular invasion, or portal vein thrombosis (PVT), and patients with liver transplantation (LT).This article reviews the current research progress of immune and targeted drugs in special populations.

Expression and biological function of TRP signaling pathway in hepatocellular carcinoma
Zhipeng WU,Yuqin ZHANG,Minggang WANG,Rongzhen ZHANG,Dewen. MAO
2024, 40(6):  743-747.  doi:10.3969/j.issn.1006-5725.2024.06.003
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In recent years, the morbidity and mortality of hepatocellular carcinoma ( HCC ) have been increasing worldwide, and the treatment strategies for HCC are still insufficient, which highlights the importance of exploring the pathogenesis and progression of HCC. Transient receptor potential ( TRP ) pathway is an important non-selective cation pathway, which is closely related to inflammatory response and sensory conduction. At present, a number of studies have shown that TRP pathway is also involved in the occurrence and development of HCC, inducing HCC invasion and migration. However, the overall potential mechanism and possible signal transduction pathways of TRP pathway in HCC remain unclear. Therefore, this article discusses the abnormal expression of TRP pathway in HCC, and reviews the key biological events of TRP pathway involved in the formation and progression of HCC, such as chronic liver inflammation-fibrosis progression, HCC cell proliferation, migration, apoptosis and HCC stem cell generation, and looks forward to its application prospect in HCC treatment. The aim is to better understand the significance of TRP pathway in HCC, help to find new therapeutic targets and effective drugs, and open up a new situation for future clinical treatment.

Research advances in exosomal proteins, mRNA and non⁃coding RNA regulation of Hepatocellular Carcinoma
Yuxin CHENG,Liang LIU,Shiyu DONG,Shengchao LI,Meng ZHANG
2024, 40(6):  748-755.  doi:10.3969/j.issn.1006-5725.2024.06.004
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Exosomes are extracellular vesicles commonly detected in numerous body fluids and contain a variety of components such as proteins, nucleic acids, lipids, and metabolites. These components enable exosomes to mediate intercellular communication and impact diverse cellular processes. Recently, research has highlighted that exosomes have a significant regulatory role in numerous aspects of hepatocellular carcinoma (HCC) occurrence, development, and drug resistance. Non-coding RANs, a crucial component of exosomes, can regulate the HCC tumour microenvironment with a direct impact on biological behaviours such as tumour growth, metastasis, angiogenesis, and immunomodulation. To this end, exosomes present an interesting avenue for further research in the field of HCC therapy. It is anticipated to become a novel diagnostic, prognostic marker, or therapeutic target for hepatocellular carcinoma (HCC). Our review of the role played by exosomal components in HCC progression over the last five years aims to furnish references and innovative perspectives for early diagnosis, prognosis, and treatment of HCC.

Feature Reports:Hepatocellular Carcinoma
Study on the mechanism of fatty acid binding protein 5 binding Vimentin protein in the Hepatocellular Carcinoma cells
Yanping TANG,Kezhi LI,Zhengmin CAI,Hao TAO,Jiaying TANG,Xueyu LI,Yanjuan LI,Ji CAO
2024, 40(6):  756-761.  doi:10.3969/j.issn.1006-5725.2024.06.005
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Objective The aim of this study was to screen and verify the proteins interacting with Vimentin, investigate the regulatory relationship between FABP5 and candidate proteins, and further explore the mechanism of FABP5 in hepatocellular carcinoma. Methods Immunoprecipitation combined with tandem mass spectrometry (IP?MS) was used to screen the proteins that bind to FABP5. The binding relationship between FABP5 and candidate interacting proteins was verified from the exogenous and endogenous levels by Co?immune precipitation assay (Co?IP). RT?qPCR, Western blot and immunofluorescence were used to observe the effect of knockdown FABP5 on the transcription and translation of Vimentin in HCC cells. The effect of overexpressing FABP5 on the cytoskeleton of HCC cell was observed by phalloidin staining. Results 336 potential target proteins that bind to FABP5 were identified through IP?MS. Based on literature, five candidate proteins related to tumors were selected, namely PRDX1, PRSS3, PKM, HSP90AA1, and Vimentin. The binding relationship between FABP5 and Vimentin protein was confirmed through both exogenous and endogenous Co?IP. Knockdown FABP5 has no significant effect on the expression of Vimentin mRNA, but it can inhibit the expression of Vimentin protein, and overexpression of FABP5 can affect the cytoskeleton of HCC cell. Conclusions FABP5 promotes the migration and invasion of HCC cells by the regulation of Vimentin and the influence of cytoskeletal remodeling, and thus it is expected to be a potential target for anti?HCC and provide new ideas for the treatment of HCC.

Clinical efficacy of FOLFOX⁃HAIC combined with lenvatinib and PD⁃1 inhibitor in the treatment of intermediate and advanced Hepatocellular Carcinoma
Junhong XU,Hongbing YAO,Xueyao WANG,Wei GUO,Caijin LU,Jiaxing WU,Jianhui JIANG,Dongkang ZHAO
2024, 40(6):  762-767.  doi:10.3969/j.issn.1006-5725.2024.06.006
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Objective To investigate the clinical efficacy and safety of nivolumab (PD-1 inhibitor) in combination with lenvatinib and FOLFOX regimen [5-fluorouracil (5-FU), oxaliplatin (L-OHP), and calcium folinate (LV)] in the treatment of intermediate and advanced hepatocellular carcinoma (HCC) via hepatic arterial infusion chemotherapy (HAIC). Methods A total of 160 patients with intermediate and advanced HCC admitted to the Second Affiliated Hospital of Guilin Medical University from January 2021 to January 2023 were randomly divided into the control group and the observation group, with 80 patients in each group, using a random number table. The control group received once-daily oral lenvatinib and intravenous carrizumab infusions for 12 weeks as part of transcatheter arterial chemoembolization (TACE) therapy. The observation group was administered with FOLFOX regimen via HAIC chemotherapy, plus intravenous infusion of carrizumab for 12 weeks and once-daily oral lenvatinib. All the patients were followed up regularly. The clinical efficacy was evaluated using the mRECIST criteria. The objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and incidence of adverse reactions were compared between the two groups. Results There were no significant differences in the objective response rate and incidence of adverse reactions between the groups. The disease control rate, overall survival, and progression-free survival in the observation group were significantly higher than those in the control group (P < 0.05). Conclusions The FOLFOX-HAIC regimen in combination with nivolumab and lenvatinib is safe and effective for the treatment of intermediate and advanced HCC, without adverse reactions. It can prolong the overall survival and progression-free survival, and improve the patient′s quality of life.

Expression of nicastrin, N1ICD and hes1 proteins in normal and cancerous liver tissues of mice
Lu YAN,Tianwei SHI
2024, 40(6):  768-772.  doi:10.3969/j.issn.1006-5725.2024.06.007
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Objective To detecting the expression of nicastrin, N1ICD and hes1 proteins in normal liver tissues and liver cancer tissues of C57BL/6 mice. Methods Twelve 6-week-old male C57BL/6 mice were randomly equally divided into the control group and model group. In the model group, the in situ liver cancer model was established with injection of Hepa1-6 cells into the liver, and the control group was treated with injection of the same amount of normal saline. Liver cancer was verified by HE staining. The expression of nicastrin, N1ICD and hes1 proteins in the normal and cancerous liver tissues was detected by IHC and Western blot. Results IHC results showed that nicastrin, N1ICD and hes1 proteins were localized in the hepatic sinusoidal endothelial cells in the normal hepatocytes, but not expressed in the hepatocytes. The model group showed higher expression of nicastrin protein but lower expression of N1ICD and hes1 protein in the cancer cells compared with the control group. Conclusion NCSTN gene may play a carcinogenic role in mouse hepatocellular carcinoma, while notch1 and hes1 may play a carcinostasis role in the carcinoma.

Basic Research
Effects of Sanqi on Sortilin, TLRs and vascular calcification in rats with chronic renal failure
Zhimin HUANG,Liangxi LU,Yini JIANG,Xiaoyu LIU,Zhiying ZHANG,Jinyu WU
2024, 40(6):  773-779.  doi:10.3969/j.issn.1006-5725.2024.06.008
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Objective Taking Sortilin as the entry point, this study aims to explore the mechanism of vascular calcification in chronic renal failure (CRF) and explore the influence of Sanqi on Sortilin, TLRs and vascular calcification, and to provide an effective method for clinical reduction of cardiovascular events in CRF. Methods Thirty-six male SD rats were randomly divided into normal group, model group, low-, medium- and high-dose Sanqi group and calcitriol group, with 6 rats in each. The replicative CRF vascular calcification rat model was fed with adenine combined with high phosphorus diet. Aortic calcium salt deposition, serum creatinine (Scr), urea nitrogen (BUN), blood calcium (Ca), blood phosphorus (P), total cholesterol (TC), triglyceride (TG), TLRs and Sortilin protein in aorta and inflammatory factors were detected. Results In the model group, renal fibrosis was obvious and many adenine crystals were found in renal interstitium. Large deposits of calcium salts were found. Renal fibrosis and calcium salt deposition were alleviated in different degrees in all treatment groups. Compared with those in the normal group, the level of BUN, Cr, P, TG, TC, IFN-γ, IL-6, IL-10 and IL-17A in the serum of the model group was ascended (P < 0.01), while the level of Ca was descended (P < 0.01). Compared with those in the model group, the level of BUN, Cr, P, TG, TC, IFN-γ, IL-6, IL-10 and IL-17A in the serum of rats in the Sanqi medium and high dose group and calcitriol group was significantly decreased (P < 0.01), and the contents of Ca were significantly increased (P < 0.05 or P < 0.01). Compared with those in the normal group, the protein expression of BMP2, RUNX2, Sortilin, TLR7 and TLR9 in aortic tissue of rats in the model group was elevated (P < 0.01), while the protein expression of SM22α was declined (P < 0.01). Compared with those in the model group, the protein expression of BMP2, RUNX2, Sortilin, TLR7, and TLR9 in the low-, medium-, and high-dose Sanqi group and calcitriol group was decreased significantly (P < 0.01); the protein expression of SM22α was increased significantly (P < 0.05 or P < 0.01), and the high-dose Sanqi group and calcitriol group had more significant effects. Conclusion Sanqi can improve renal fibrosis and vascular calcification in CRF model rats, and its mechanism may be related to the regulation of biological functions of Sortilin and TLRs.

Tumor endothelial markers1 mediate endothelial cell angiogenesis and heart failure myocardial remodeling via MAPKs pathway
Ting XU,Wei HUANG,Li YANG,Hao. YU
2024, 40(6):  780-786.  doi:10.3969/j.issn.1006-5725.2024.06.009
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Objective To explore the role of endothelial cells in angiogenesis and myocardial remodeling in heart failure based on MAPKs pathway mediated by tumor endothelial marker 1 (TEM1). Methods Sixty-four mice were equally randomized into four groups: sham operation, myocardial infarction (MI), MI+sh-NC and MI+sh-TEM1. On the 7th day after MI, the changes of EndMT in the infarct border area were detected by immunofluorescence staining, and the cardiac function of mice was evaluated by echocardiography on the 28th day. Mouse aortic endothelial cells (MAECs) were divided into three groups: control, Vector and rTEM1. In addition, MAECs were pretreated with MAPK inhibitor SB203580, and the cells were treated with rTEM1 for 48 h. The changes of EndMT and MAPKs signaling pathways in endothelial cells were evaluated by Western blot. Results In the myocardium at the border of infarction, the level of TEM1-1 increased slightly on the 1st day after MI, reached the peak on the 7th day, and then decreased on the 28th day. Compared with Vector group, the expression of VE-Cadherin protein in the rTEM1 group decreased significantly (P < 0.05), and the levels of α-SMA and vimentin, relative migration distance, the number of invading cells, and the number of branching formation increased significantly (P < 0.05). SB203580 reversed these changes of MAECs induced by rTEM1. Compared with the MI group, the co-staining level of CD31+Vimentin+ in the MI+sh-TEM1 group decreased significantly (P < 0.01). On the 28th day, the LVEF and LVFS in the MI+sh-TEM1 group were significantly higher than those in MI group (P < 0.05). Compared with the MI group, the expressions of p-P38/P38 and p-JNK/JNK in the endothelial cells of the MI+sh-TEM1 group decreased. Conclusion EndMT and angiogenesis induced by TEM1 participate in the pathogenesis of cardiac fibroblasts induced by MI, which may be mechanically related to the activation of MAPKs signaling pathway.

ROBO3 deficiency promotes chemotherapy⁃induced transition of macrophage to foam cell
Yong LIU,XiaoLei CHENG,Xiangli CUI,Hao TANG,Huanzhen CHEN
2024, 40(6):  787-795.  doi:10.3969/j.issn.1006-5725.2024.06.010
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Objective To explore the effect of chemotherapeutic drugs doxorubicin or cisplatin on lipid metabolism of macrophages and its regulatory mechanism. Methods Macrophage RAW264.7 was treated with doxorubicin or cisplatin, and intracellular lipid level was detected by oil red O and ELISA; RNA sequence screening and Western blot were used to confirm the changes of gene expression after chemotherapeutic drug treatment; The effects of silencing ROBO3 on cellular lipid metabolism were explored, and changes in key target genes of lipid metabolism were detected by Q-PCR and western blot. Results Adriamycin or cisplatin induced disturbances in macrophage cholesterol metabolism and exacerbated macrophage foaminess. Further studies showed that the expression of the axon guidance factor receptor, ROBO3, increased and then decreased during the chemotherapeutic drug-induced macrophage foaming process. Further intervention with ROBO3 exacerbates oxldl-induced cholesterol accumulation and foam formation in macrophages. Mechanistically, ROBO3 deficiency promotes the expression of cholesterol synthesis-related gene DHCR24 and inhibits the expression of cholesterol elimination-related gene ABCG1, resulting in cholesterol accumulation in macrophages. Conclusion This study found that ROBO3 plays an important regulatory role in the disruption of cholesterol metabolism and its foaming process in macrophages induced by chemotherapeutic drugs, which may provide new targets and ideas for the prevention and treatment of chemotherapy-related atherosclerosis.

Clinical Research
Application of ultrasound⁃guided combined femoral nerve and femoral artery block on tourniquet response in lower extremity surgery
Xiaoqing FAN,Xiaojing ZHENG,Ling HU
2024, 40(6):  796-800.  doi:10.3969/j.issn.1006-5725.2024.06.011
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Objective To observe the safety and effectiveness of ultrasound?guided femoral nerve combined with femoral artery block to reduce tourniquet reaction in patients undergoing knee arthroplasty. Methods 100 patients(18 ~ 75 years old, body mass index 18 ~ 30 kg/m2)who were classified as grade Ⅰ?Ⅲ according to ASA standard and received unilateral total knee arthroplasty. The patients were randomly divided into two groups,the ultrasound?guided femoral nerve combined with femoral artery block with general anesthesia was utilized in group NA with 50 cases, and femoral nerve block alone with general anesthesia was used in group N with 50 cases. The target nerve block was guided by ultrasound before induction of anesthesia in both two groups,and anesthesia induction was performed after the block effect was etermined. Patients in two groups underwent surgery under general anesthesia of the laryngeal mask,and all patients under went self?controlled intravenous analgesia(PCIA). If a patient had a visual analogue score(VAS)score > 5 after surgery, flurbiprofenate 50 mg will be given intravenously as a remedy for analgesia. The patients' SBP,DBP and HR were recorded before anesthesia (T1), 1 min before tourniquet inflation (T2), 15 min after tourniquet inflation (T3), 30 min (T4), 45 min (T5), and 60 min (T6),the number of cases of tourniquet hypertension occurring in patients intraoperatively and the amount of nicardipine and esmolol were recorded, and the movement and static VAS scores at 2, 6, 12, and 24 h after surgery were recorded.the postoperative rescue analgesic requirements and the time of getting out of bed were recorded. The incidence of adverse reactions such as nausea,vomiting,deliriumand infection were also recorded. Results Compared with group N,SBP,DBP and HR were significantly lower in group NA at 45 and 60 min after tourniquet inflation, and the incidence of tourniquet hypertension and the amount of nicardipine and esmolol were also significantly lower (P < 0.05), and the time of getting out of bed was advanced (P < 0.05); the movement and static VAS scores,the time of the first remedial analgesia, and number of times of remedial analgesia, as well as the occurrence of nausea,vomiting,delirium and infection were not statistically significant. Conclusion Ultrasound?guided femoral nerve combined with femoral artery block can be safely and effectively used to reduce the reaction of tourniquet in patients with knee arthroplasty, and can shorten the time of getting out of bed after surgery, contributing to promoting postoperative rehabilitation.

Effect of laparoscopic salpingectomy on ovarian reserve function and serum neuropeptide Y and cortisol in patients with ectopic pregnancy
Rong SHI,Xianfang ZHENG,Qun TAO,Junmo CHEN,Xiaohua GE
2024, 40(6):  801-806.  doi:10.3969/j.issn.1006-5725.2024.06.012
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Objective To explore the effect of laparoscopic salpingectomy on ovarian reserve function and serum neuropeptide Y (NPY) and cortisol (Cor) in patients with ectopic pregnancy. Methods 82 patients with ectopic pregnancy who had visited Chaohu Hospital Affiliated to Anhui Medical University from June 2018 to June 2021 were randomly divided into two groups, with 41 in each group. The control group underwent laparoscopic salpingostomy and suturing for embryo retrieval, while the study group underwent laparoscopic salpingectomy. Surgical duration, intraoperative blood loss, time to postsurgical mobilization, length of hospital stay, serum NPY and Cor levels, antral follicle count (AFC), indexes for peak flow velocity and resistance of ovarian artery were compared between the two groups. Follow-up was conducted for two years after surgery, and the success rate of pregnancy and the ectopic pregnancy rate were recorded. Results The surgical duration in the study group was shorter than that in the control group (P < 0.05). The differences in serum NPY and Cor values between the two groups immediately after surgery and at postoperative week one were not statistically significant (P > 0.05). At postoperative months1 and 6, the peak flow velocity of the affected ovary was lower in the study group than in the control group, whereas the resistance index was higher (P < 0.05). At postoperative month 6, both groups showed an increase in peak flow velocity and a decrease in resistance index (P < 0.05). There were no statistically significant differences in AFC and the success rate of pregnancy between the two groups postoperatively (P > 0.05). The ectopic pregnancy rate in the study group was lower than that in the control group (P < 0.05). Conclusion As compared with laparoscopic salpingostomy, laparoscopic salpingectomy for ectopic pregnancy can also preserve postoperative ovarian antral follicle count (AFC), and it has greater advantage in reducing the risk of recurrent ectopic pregnancy after surgery.

Comparative study of percutaneous endoscopic treatment of L5/S1 disc herniation by two approaches
Zhiwei SHI,Jianming WU,Yahui NIU,Chen GONG
2024, 40(6):  807-813.  doi:10.3969/j.issn.1006-5725.2024.06.013
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Objective To compare the efficacy of percutaneous transforaminal approach and translaminar approach in the treatment of L5/S1 disc herniation (LDH) under endoscopic discectomy. Methods Adopted a retrospective case-control study, and selected 62 cases of patients with L5/S1 LDH who were treated with percutaneous endoscopic surgery in the spine surgery department of our hospital from June 2020 to December 2022, and the transforaminal approach was used. (TELD) in 32 cases (TELD group), and interlaminar approach (IELD) in 30 cases (IELD group). The observation indicators included intraoperative fluoroscopy times, operation time, hospitalization days, hospitalization expenses, leg pain VAS score, ODI score, modified MacNab curative effect evaluation and complications. Results All 62 patients successfully completed the operation and follow-up, and no serious complications occurred. There were statistically significant differences in operation time, fluoroscopy times, and hospitalization expenses between the two groups (P < 0.001), but there was no significant difference in hospitalization days between the two groups (P > 0.05). The lower extremity VAS scores at the last follow-up and the last follow-up were significantly improved compared with those before operation (P < 0.001), and the ODI scores of the two groups were significantly improved at 2 days, 1 month and at the last follow-up (P < 0.001). At the same time point, there was no statistical difference (P > 0.05); there was no significant difference in the excellent and good rate of surgery between the two groups (P > 0.05). 11 patients with high iliac crest in the TELD group successfully completed the surgery. Conclusions Both the endoscopic surgery through the intervertebral foramen and the interlaminar approach can achieve satisfactory results in the treatment of L5/S1 LDH. However, local anesthesia through the intervertebral foramen approach reduces hospitalization costs, and patients with high iliac crest can successfully complete the surgery by selecting a suitable puncture path. The translaminar approach has fewer fluoroscopy times and shorter surgical time, but there is a higher risk of dura mater and nerve damage, which requires careful operation for beginners.

Risk factors of peripheral infections of knee joint tumor prosthesis and predictive value of serum D⁃dimer and TLR2
Changzhi GUO,Tao SUN,Shuman HAN,Lingxiang WANG,Mengjing. NIU
2024, 40(6):  814-819.  doi:10.3969/j.issn.1006-5725.2024.06.014
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Objective To investigate the influencing factors of peripheral infections of knee joint tumor prosthesis as well as the value of serum D-D and TLR2 in predicting the infection risks so as to provide a reference for early diagnosis of tumorous periprosthetic infection (PJI) of knee joint. Methods The patients who were treated and followed up in our department from January 2008 to June 2020 were selected. According to the inclusion and exclusion criteria, 136 of the patients were selected. The data including age, gender, BMI, history of diabetes, smoking history, tumor location, stage of malignant tumor, operation time, osteotomy length, intraoperative bleeding, and the percentage of neutrophils, leukocytes, serum D-dimer, and serum TLR value 3 days after operation were collected. The risk factors of PJI and the diagnostic value of serum D-dimer and serum TLR were analyzed. Results The incidence of PJI was 11.76%. Postoperative chemotherapy and operation time ≥ 180 min were the risk factors of PJI (P < 0.05). The area under curve (AUC) of the combination of two indicators, serum D-dimer and serum TLR2 were 0.917, 0.894 and 0.778, respectively. The AUC of TLR2 was lower than that of the combination of two indicators (P < 0.05); The sensitivity was 0.975, 0.908 and 0.708, respectively, and the specificity was 0.75, 0.75, and 0.812, respectively. Conclusion Postoperative chemotherapy and operation time ≥ 180 min are the risk factors of PJI. The combination of D-dimer and TLR2 has good diagnostic value.

The association between vitamin intake and the progression of metabolic dysfunction⁃associated fatty liver disease
Renling YAO,Yixuan ZHU,Rui HUANG,Jie LI
2024, 40(6):  820-826.  doi:10.3969/j.issn.1006-5725.2024.06.015
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Objective There is a Few studies explored the association between vitamin intake and metabolic dysfunction?associated fatty liver disease (MAFLD), while the existing results were still contradictory. This study aimed to investigate the association between dietary vitamins and all?cause mortality as well as fibrosis risk in patients with MAFLD. Methods The data were extracted from the third National Health and Nutrition Examination Surveys 1988-1994. Dietary vitamins was assessed using a 24 h diet recall, including vitamin A, vitamin B6, vitamin B12, vitamin C, vitamin D, thiamin, riboflavin, folic acid and α?tocopherol. The non?alcoholic fatty liver disease fibrosis score (NFS) < -1.455 was considered as non?advanced fibrosis, while NFS ≥ -1.455 was considered as advanced fibrosis. Results A total of 3844 MAFLD participants were included in this study. The median time of follow?up was 310 months. 1739 participants (45.3%) were deceased during the follow?up. The intake of thiamin, riboflavin, α?tocopherol, VB6, and VB12 were significantly higher in patients with NFS?determined non?advanced fibrosis (P < 0.05). After adjusting, a significantly lower risk of fibrosis was found in patients with the highest quartile (> 11.5 mg/d) of α?tocopherol intake compared to the lowest intake group (P = 0.031). Compared to the lowest quartile group, the risk of mortality was reduced by 0.34 folds in the group consuming the highest quartile amount (> 130 mg/d) of VC (HRs: 0.66, 95% CI: 0.51 ~ 0.85, P = 0.001). Conclusions More α?tocopherol intake reduced fibrosis grade in MAFLD patients. VC intake may reduce all?cause mortality in patients with MAFLD.

The relationship between ulcerative colitis and the risk of hypothyroidism: A two⁃mendelian randomization study
Yin HUA,Xiaoyan WANG,Zhen WANG,Yongning XIN,Shousheng. LIU
2024, 40(6):  827-832.  doi:10.3969/j.issn.1006-5725.2024.06.016
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Objective To investigate assess the bidirectional causal relationship between ulcerative colitis (UC) and hypothyroidism using a two?sample Mendelian randomization (TSMR). Methods Single nucleotide polymorphism (SNP) data relevant to UC and hypothyroidism were retrieved from the Finnish Biobank and the IEU database, respectively. Independent SNPs strongly associated with UC were selected as instrumental variables. Causal associations between UC and hypothyroidism were evaluated using the inverse variance weighted (IVW) method, MR?Egger regression, and weighted median estimator. Additionally, MR?PRESSO was employed to assess the horizontal pleiotropy and outlier SNPs. Cochran′s Q test and funnel plots were performed to evaluate the heterogeneity among the SNPs. A leave?one?out analysis was conducted to examine the influence of individual SNPs on causal assessments. Results Four instrumental variables strongly associated with UC were identified. The IVW method indicated a causal relationship between UC and hypothyroidism (OR = 0.975, 95% CI: 0.924 ~ 0.990, P = 0.011). Cochran′s Q test yielded a Q statistic of 2.566 with a p?value of 0.463, suggesting no heterogeneity among the SNPs. Both MR?Egger (P = 0.523) and MR?PRESSO (P = 0.548) tests suggested the absence of horizontal pleiotropy. However, the results of the reverse TSMR did not support a reverse causal relationship. Conclusion The findings from the TSMR analysis reveal a negative causal relationship between UC and hypothyroidism.

Drugs and Clinic Practice
Efficacy and safety of botulinum toxin type A combined with pulsed radiofrequency in the treatment of postherpetic neuralgia
Lei HE,Yue ZHANG,Cehua OU,Fubo LI
2024, 40(6):  833-837.  doi:10.3969/j.issn.1006-5725.2024.06.017
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Objective Exploring the efficacy and safety of botulinum toxin type A (BTX?A) combined with pulsed radiofrequency(PRF) in the treatment of postherpetic neuralgia(PHN). Methods A total of 80 patients with PHN were collected. They were randomly divided into experimental group (Group B)and control group (Group C), Group B was treated with BTX?A intradermal injection combined with PRF, and Group C was treated with lidocaine intradermal injection combined with PRF. Numeric pain score (NRS), Simplified McGill Pain Questionnaire (SF?MPQ)and Sleep Quality Score (QS)were used to assess the patients' pain level and sleep quality preoperatively, 1, 3, and 7 days postoperatively, and 1, 2, and 3 months postoperatively. The patients' postoperative adverse reactions were collected. Interleukin?1β (IL?1β)and calcitonin gene?related peptide (CGRP)levels in patients' serum were measured preoperatively and 3 days postoperatively. Results The NRS scores, SF?MPQ scores, and QS scores of group B and group C were significantly lower at all postoperative time points compared to preoperative ones (P < 0.05). The NRS and SF?MPQ score were significantly lower in group B at 1, 2, and 3 months postoperatively compared with group C(P < 0.05); and group B had significantly lower QS scores at 2 and 3 months postoperatively (P < 0.05). The effective rate of pain relief at 3 months postoperatively in group B (90%) was statistically significant (P < 0.05) compared with group C (56.7%). No serious adverse reactions occurred in either group. The levels of IL?1β and CGRP in serum of patients in both groups were significantly decreased at 3 days after surgery compared with the preoperative period, and the degree of decrease of IL?1β and CGRP in group B was more significant than that in group C (P < 0.05). Conclusion BTX?A combined with PRF treatment for PHN can effectively reduce its pain level, improve the quality of sleep, and is safe.

Effect of desflurane post⁃conditioning on myocardial protection in patients undergoing cardiac surgery under cardiopulmonary bypass
Xiangmi HUANG,Ying CHEN,Deming WANG,Kunpeng WU
2024, 40(6):  838-843.  doi:10.3969/j.issn.1006-5725.2024.06.018
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Objective To observe and evaluate the protective effect of desflurane post?conditioning on myocardial injury during cardiopulmonary bypass and its influence on patients' postoperative recovery. Methods A total of 200 patients in need of cardiac surgery were selected as the experimental subjects, who were aged from 20 to 65 years old, and divided into ASA Ⅱ-Ⅲ and NYHA Ⅱ-Ⅲ by endotracheal intubation and extracorporeal circulation method under general anesthesia. The patients were randomly divided into desflurane post?treatment group (experimental group, group D) and control group (group C) after selection. With the successive opening of the aorta and superior vena cava, group D were given 5% desflurane by inhalation with mechanical ventilation. While group C inhaled pure oxygen without inhaling desflurane. The depth of intraoperative anesthesia was maintained between 40 ~ 50 during the operation. Radial artery blood was collected from patients in 24 h before surgery (T0), immediately after intubation (T1), and 1 h(T2), 6 h (T3), 12 h (T4) and 24 h (T5)after aortic opening to achieve the determination of troponin I (cTnI) and creatine kinase isoenzyme MB (CK?MB).On the premise of obtaining the informed consent of the patient, about 50 mg of right atrial appendage tissue was collected before aortic intubation (T1.5) and 1 hour after aortic opening (T2) to determine the apoptosis rate. Results (1)cTnI in group C at the time of T2, T3, T4 and T5 was apparently higher than group D (P < 0.05). (2)CK?MB in group C at the time of T3 was apparently higher than group D (P < 0.05). (3)The myocardial tissue results showed that there was a lower apoptosis rate in experimental group at the time of T2 (P < 0.05). Conclusion Desflurane post?conditioning has a myocardial protective effect during cardiac surgery under cardiopulmonary bypass.

Medical Examination and Clinical Diagnosis
Research on establishing gastric cancer lymph node metastasis prediction model based on machine learning and routine laboratory indicators
Jianliang YAN,Zeyu XIE,Rongrong JING,Ming. CUI
2024, 40(6):  844-849.  doi:10.3969/j.issn.1006-5725.2024.06.019
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Objective To establish a prediction model for lymph node metastasis (LNM) of gastric cancer based on routine laboratory indicators using machine learning algorithms. Methods This study collected data of 741 gastric cancer patients at Affiliated Hospital of Nantong University between January 2020 and January 2022 for model training and testing. Additionally, data of 102 gastric cancer patients between January 2023 and October 2023 were collected for model validation. XGBoost algorithm was used to calculate the importance of indicators and filter out a set of important indicators from 66 indicators. Five machine learning algorithms, including K-Nearest Neighbor, Support Vector Machine, Multilayer Perceptron, Random Forest and Adaboost, were constructed and trained for comparative analysis. Furthermore, the stability and accuracy of the model were further validated on the validation set. Results This study selected a set of important indicators composed of 9 routine laboratory indicators and trained the gastric cancer LNM prediction model, named V9. Additionally, through comparative experiments, it was found that the Adaboost algorithm based on the boosting strategy had the best performance, with evaluation metrics such as area under the curve, F1 score, accuracy, sensitivity, and specificity ranging from 0.833 to 0.968. The accuracy of the predictions on the validation set was 94.12%. Conclusion V9 was a gastric cancer LNM prediction model that has auxiliary clinical diagnostic value. It can be used to assess the risk of patients accurately and provide a basis for clinical decision-making.

Imaging findings of X⁃ray defecography and MR defecography in patients with solitary rectal ulcer syndrome
Guiting LI,Meiyu HU,Zhiming ZENG,Peiyi XIE,Xiaohui DI
2024, 40(6):  850-856.  doi:10.3969/j.issn.1006-5725.2024.06.020
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Objective The imaging findings of X?ray defecography (XRD) and magnetic resonance defecography (MRD) of patients with Solitary Rectal Ulcer syndrome (SRUS) were retrospectively analyzed to provide important information for clinical diagnosis and treatment. Methods 19 patients with SRUS confirmed by clinical, pathological and colonoscopy were included in this study. Among them, 15 patients underwent XRD and 7 patients underwent MRD, and 3 patients underwent both XRD and MRD. Data of all enrolled patients were collected and pelvic floor function was measured. Results In the results of XRD, 3 patients (20%) showed rectal intussusception. 8 patients (53.3%) showed external rectal prolapse and 2 patients (13.3%) showed moderate rectocele. In addition, there were 2 patients of puborectal muscle hypertrophy, and 1 patient of bladder prolapse and uterine prolapse, respectively. For MRD, 3 patients (42.9%) showed rectal mucosal prolapse (partial prolapse). At 4 patients (57.1%) with rectocele, 3 patients (all female) had moderate rectocele, 1 patient had mild rectocele. 3 patients were also observed related anterior and middle compartment organ descent. 2 patients of pubulorectal muscle hypertrophy, no sigmoidocoele. Conclusion Defecography can evaluate the structural and functional abnormalities of pelvic floor in SRUS patients, such as external rectal prolapse, rectal protrusion, rectal mucosal prolapse, and rectal intussusception, which has guiding significance for the treatment of SRUS patients。

Clinical Nursing
A cost⁃benefit analysis on nursing care in thoracoscopic sublobectomy without indwelling bladder catheter
Shunzhen ZHAO,Lingli BI,Xiaoxuan NI,Yiling TONG
2024, 40(6):  857-861.  doi:10.3969/j.issn.1006-5725.2024.06.021
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Objective To analyze the nursing cost effectiveness of non?indwelling bladder catheter in thoracoscopic sublobectomy, and in order to further determine the feasibility of patients undergoing sublobectomy without indwelling catheter. Methods We prospectively collected the clinical data on a total of 254 patients undergoing thoracoscopic sublobectomy in the department of pulmonary surgery of Guangdong Provincial People's Hospital from May 2021 to January 2023. The patients were randomly divided into a study group (128 patients without catheter) and a control group (126 patients with catheter). The nursing cost?effectiveness indexes and postoperative comfort scores were compared between the two groups. Results Seven patients in the experimental group and sixteen patients in the control group needed repeated placement of urinary catheter There were no significant differences in the general demographic and clinical data between the two groups (P > 0.05). The cost of materials related to urinary catheter, nursing cost, and total cost in the control group were higher than those in the study group. The total nursing time in the control group was longer than that in the study group. The per capita material cost, nursing cost and total cost in the control group were higher than those in the study group, and the differences were statistically significant (P < 0.01). The total score of the comfort scale and the physiological and environmental dimension of postoperative comfort were significantly higher in the study group than in the control group, with statistical significances (P < 0.05). Conclusions Thoracoscopic sublobectomy without indwelling bladder catheter can lower medical expense, reduce nursing workload, and improve postoperative comfort.

Reviews
Research progress in the treatment of AMPK regulating lipid accumulation in the treatment of nonalcoholic fatty liver disease
Pengshuai SUN,Feng ZHU,Lihong ZHENG,Haiqiang WANG
2024, 40(6):  862-866.  doi:10.3969/j.issn.1006-5725.2024.06.022
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Non?alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease and has posed significant challenges to global public health and medical care. Due to the unclear pathogenesis of NAFLD, lipid accumulation plays a key role in its development. AMPK, as a crucial molecule in lipid metabolism regulation, can improve lipid accumulation caused by NAFLD. This article describes the specific mechanisms of AMPK?related molecules in improving lipid accumulation and treating NAFLD, and lists the current experimental and therapeutic drugs related to AMPK. The potential of AMPK?related drugs in improving lipid accumulation and treating NAFLD is demonstrated, providing ideas and references for future research on AMPK?related drugs for treating NAFLD.

Research progress of bioactive glass in bone and soft tissue repair
Huangchao WU,Jin SUN,Juntao HUANG
2024, 40(6):  867-869.  doi:10.3969/j.issn.1006-5725.2024.06.023
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Bioactive glass (BG) has been used as a candidate for bone and soft tissue repair materials because of its compatibility, bioactivity and ability to form a crystalline hydroxyapatite layer. This paper introduces the mechanism of BG ion release, discusses the application of borosilicate bioactive glass (BBG) in bone and soft tissue repair, and provides an overview of the potential and clinical translational challenges faced by BBG in bone cement, scaffold, hydrogel, and fiber research applications.

Research progress of exosomes in distant metastasis and drug resistance of gastric cancer
Shu CHEN,Jinglei ZHANG,Kang RONG,Nan ZHANG,Weiyi SUN
2024, 40(6):  870-876.  doi:10.3969/j.issn.1006-5725.2024.06.024
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Gastric cancer (GC) is one of the most common tumors and the fourth leading cause of cancer-related death worldwide.Due to the lack of specific signs in early GC, most cases are diagnosed at an advanced stage, often accompanied by infiltration and distant metastasis. Although chemotherapy is the most commonly used treatment for gastric cancer, due to the emergence of drug resistance, many patients will still relapse after chemotherapy, resulting in poor prognosis.Exosome (EXOs) in the Tumor micro environment (TME) can participate in intercellular communication and play an important role in GC distant metastasis and drug resistance. At present, the detailed mechanism of GC distant metastasis and drug resistance is still unclear. Identifying the exosome-induced mechanism involved in GC distant metastasis and drug resistance can help us find more reliable treatment methods for GC metastasis and drug resistance.This article reviews the mechanism of exosome in GC distant metastasis and drug resistance, in order to provide help for the diagnosis, treatment and research of GC.