ObjectiveTo investigate the therapeutic effect of sitravatinib on carbon tetrachloride （CCl₄）-induced liver fibrosis in mice. MethodsA total of 30 male C57BL/6J mice， aged 8 weeks， were randomly divided into control group， CCl₄ model group， and low- （5 mg/kg）， middle- （10 mg/kg）， and high-dose （20 mg/kg） sitravatinib groups. All mice except those in the control group were given intraperitoneal injection of CCl₄ for 4 consecutive weeks to induce liver fibrosis， and since the first day of modeling， the mice in the low-， middle-， and high-dose sitravatinib groups were given sitravatinib at the corresponding dose by gavage every day. The serum levels of total cholesterol （TC）， triglyceride （TG）， and alanine aminotransferase （ALT） were measured for the mice in each group； hepatic hydroxyproline content was measured； HE staining， Masson staining， and Sirius Red staining were used to observe liver histopathological changes； quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression levels of α-smooth muscle actin （α-SMA） and collagen type I alpha 1 （Col1a1） in liver tissue. The therapeutic effect of sitravatinib was assessed based on the above results. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had significant increases in the levels of TC， TG， and ALT （all P<0.05）， and there were no significant differences in the levels of TC， TG， and ALT between the model group and the low-， middle-， and high-dose sitravatinib groups （all P>0.05）. Hepatic hydroxyproline content decreased after sitravatinib intervention， with a significant difference between the middle-/high-dose sitravatinib groups and the CCl₄ model group （both P<0.05）. Histopathological staining showed that the sitravatinib treatment groups had a reduction in collagen deposition， along with thinning and fragmentation of fibrous septa， and in the high-dose sitravatinib group， 4 mice had a fibrosis stage of S0—S1 and 2 mice had a fibrosis stage of S2—S3， suggesting a certain degree of alleviation of liver fibrosis degree compared with the CCl₄ model group （mainly S3—S4）. The measurement of related molecules showed that sitravatinib downregulated the mRNA and protein expression levels of α-SMA and Col1a1 （all P<0.05）. ConclusionSitravatinib can effectively alleviate CCl₄-induced liver fibrosis in mice， possibly by inhibiting hepatic stellate cell activation and collagen synthesis.

BACKGROUND:Inter-limb asymmetry is a common phenomenon observed during human growth and development.Prolonged specialized training can lead to specific adaptations in inter-limb asymmetry among athletes.OBJECTIVE:To review the formation causes,manifestations,and impacts of inter-limb asymmetry on sports performance,and provide an overview of the relevant assessment methods and intervention strategies.METHODS:A literature search was conducted in the CNKI,WanFang,PubMed,and Web of Science databases from their inception to September 2024.The search terms included"asymmetry,asymmetries,asymmetric,asymmetrical,imbalance,strength,power,force,jump,sprint,athletic performance,anthropometry,injury"in English and Chinese.After excluding duplicate publications,irrelevant content,and conference papers,a total of 131 articles were finally included for analysis.RESULTS AND CONCLUSION:(1)Inter-limb asymmetry can be influenced by various factors including genetics,task demands,training regimens,injuries,fatigue,and limb preference.These factors lead to being primarily manifested in anatomical structure,strength performance,and task-specific asymmetry.(2)An increase in inter-limb asymmetry can result in impaired performance in bilateral in-phase symmetric movements.However,the relationship between increased inter-limb asymmetry and bilateral out-of-phase symmetric movements remains unclear and requires further investigation.(3)Training interventions have been shown to effectively mitigate inter-limb asymmetry,with unilateral training demonstrating superior outcomes compared with bilateral training.The choice of training methods and content should be tailored to meet the specific demands of the sport.(4)To further clarify the relationship between inter-limb asymmetry and athletic performance,it is recommended that future research adopt the concept of"task specificity"in inter-limb asymmetry.This includes standardizing study designs,selecting sensitive testing methods and indicators,unifying calculation methods to provide more high-quality evidence,and establishing categorized warning threshold standards for inter-limb asymmetry in different sports.

Rheumatoid arthritis （RA） is a common autoimmune disease characterised clinically by symmetrical joint pain， swelling， and stiffness. Long-term chronic synovial inflammation can lead to severe joint damage and even disability， thereby affecting quality of life for patients. Current clinical treatment of RA emphasises an integrated approach combining traditional Chinese and Western medicine， with traditional Chinese medicine offering certain advantages in reducing disease activity of RA， preventing relapses， and other aspects. Modern clinical evidence confirms that Guizhi Shaoyao Zhimutang （GSZT） is effective in improving symptoms such as immune metabolism， joint stiffness， and joint pain in RA patients. Pharmacological studies have revealed that GSZT primarily contains components such as cinnamaldehyde， total glucosides of paeony， total alkaloids of Aconiti Lateralis Radix Praeparata， glycyrrhetinic acid， zingiberone， isoimperatorin， ephedra polysaccharides， and cedrol. It improves RA symptoms via multiple mechanisms and targets， including enhancing immune responses， exerting anti-inflammatory and analgesic effects， regulating relevant signalling pathways， inhibiting cell apoptosis， and suppressing bone destruction. This paper reviewed the syndrome patterns and pharmacological basis of GSZT in the treatment of RA， as well as its clinical applications and related mechanisms， thereby providing a theoretical basis and reference for the further development and utilisation of GSZT in the treatment of RA.

Rheumatoid arthritis （RA） is a common autoimmune disease characterised clinically by symmetrical joint pain， swelling， and stiffness. Long-term chronic synovial inflammation can lead to severe joint damage and even disability， thereby affecting quality of life for patients. Current clinical treatment of RA emphasises an integrated approach combining traditional Chinese and Western medicine， with traditional Chinese medicine offering certain advantages in reducing disease activity of RA， preventing relapses， and other aspects. Modern clinical evidence confirms that Guizhi Shaoyao Zhimutang （GSZT） is effective in improving symptoms such as immune metabolism， joint stiffness， and joint pain in RA patients. Pharmacological studies have revealed that GSZT primarily contains components such as cinnamaldehyde， total glucosides of paeony， total alkaloids of Aconiti Lateralis Radix Praeparata， glycyrrhetinic acid， zingiberone， isoimperatorin， ephedra polysaccharides， and cedrol. It improves RA symptoms via multiple mechanisms and targets， including enhancing immune responses， exerting anti-inflammatory and analgesic effects， regulating relevant signalling pathways， inhibiting cell apoptosis， and suppressing bone destruction. This paper reviewed the syndrome patterns and pharmacological basis of GSZT in the treatment of RA， as well as its clinical applications and related mechanisms， thereby providing a theoretical basis and reference for the further development and utilisation of GSZT in the treatment of RA.

BACKGROUND:Inter-limb asymmetry is a common phenomenon observed during human growth and development.Prolonged specialized training can lead to specific adaptations in inter-limb asymmetry among athletes.OBJECTIVE:To review the formation causes,manifestations,and impacts of inter-limb asymmetry on sports performance,and provide an overview of the relevant assessment methods and intervention strategies.METHODS:A literature search was conducted in the CNKI,WanFang,PubMed,and Web of Science databases from their inception to September 2024.The search terms included"asymmetry,asymmetries,asymmetric,asymmetrical,imbalance,strength,power,force,jump,sprint,athletic performance,anthropometry,injury"in English and Chinese.After excluding duplicate publications,irrelevant content,and conference papers,a total of 131 articles were finally included for analysis.RESULTS AND CONCLUSION:(1)Inter-limb asymmetry can be influenced by various factors including genetics,task demands,training regimens,injuries,fatigue,and limb preference.These factors lead to being primarily manifested in anatomical structure,strength performance,and task-specific asymmetry.(2)An increase in inter-limb asymmetry can result in impaired performance in bilateral in-phase symmetric movements.However,the relationship between increased inter-limb asymmetry and bilateral out-of-phase symmetric movements remains unclear and requires further investigation.(3)Training interventions have been shown to effectively mitigate inter-limb asymmetry,with unilateral training demonstrating superior outcomes compared with bilateral training.The choice of training methods and content should be tailored to meet the specific demands of the sport.(4)To further clarify the relationship between inter-limb asymmetry and athletic performance,it is recommended that future research adopt the concept of"task specificity"in inter-limb asymmetry.This includes standardizing study designs,selecting sensitive testing methods and indicators,unifying calculation methods to provide more high-quality evidence,and establishing categorized warning threshold standards for inter-limb asymmetry in different sports.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

Objective To investigate the factors influencing international normalized ratio (INR)>3.0 in patients undergoing warfarin anticoagulation therapy after mechanical heart valve replacement. Methods A retrospective analysis was performed on the clinical data of patients who underwent mechanical heart valve replacement surgery and received warfarin anticoagulation therapy at West China Hospital of Sichuan University from January 1, 2011 to June 30, 2022. Based on the discharge INR values, patients were divided into two groups: an INR≤3.0 group and an INR>3.0 group. The factors associated with INR>3.0 at the time of discharge were analyzed. Results A total of 8901 patients were enrolled, including 3409 males and 5492 females, with a median age of 49.3 (43.5, 55.6) years. The gender, body mass index (BMI), New York Heart Association (NYHA) cardiac function grading, INR, glutamic oxaloacetic transaminase, and preoperative prothrombin time (PT) were statistically different between the two groups (P<0.05). Multivariate logistic regression analysis revealed that lower BMI, preoperative PT>15 s, and mitral valve replacement were independent risk factors for INR>3.0 at discharge (P<0.05). Conclusion BMI, preoperative PT, and surgical site are factors influencing INR>3.0 at discharge in patients undergoing warfarin anticoagulation therapy after mechanical heart valve replacement. Special attention should be given to patients with lower BMI, longer preoperative PT, and mitral valve replacement to avoid excessive anticoagulation therapy.

OBJECTIVE To evaluate the effectiveness and safety of warfarin anticoagulation therapy guided by gene test in patients undergoing left ventricular assist device （LVAD） implantation， and to analyze the influencing factors of warfarin anticoagulation efficacy. METHODS Patients who underwent LVAD implantation at the Heart and Vascular Center of Northern Jiangsu People’s Hospital from January 2023 to October 2024 and required warfarin anticoagulant therapy were selected as the study subjects. They were divided into genetic testing group （n＝51） and empirical treatment group （n＝17） based on whether they underwent CYP2C9 and VKORC1 gene test. The gene test group was given warfarin based on the predicted dose calculated by gene test， while the empirical treatment group was given warfarin by clinical doctors based on international normalized ratio （INR） experience， all patients were given warfarin once a day. Follow-up observation was conducted for 6 months to compare the effectiveness [time in therapeutic range（TTR）， the time required to reach INR for the first time， the incidence of embolic events， the incidence of INR＜1.5 events] and safety （the incidence of major and minor bleeding events，the incidence of INR＞3.5 events） of warfarin treatment between two groups of patients. According to whether the patient’s TTR was ≥60%， they were divided into TTR≥60% group （n＝20） and TTR＜60% group （n＝48）. Univariate and multivariate binary Logistic regression analysis were used to determine the factors affecting the anticoagulant effect of warfarin in patients. RESULTS The TTR of patients in the gene test group was significantly higher than that in the empirical treatment group （P＜0.05）. The incidence of INR＜1.5 events in the gene test group was significantly lower than in the empirical treatment group （P＜0.05）. The incidence of minor bleeding events and INR＞3.5 events in the gene test group were lower than in the empirical treatment group， but the difference was not statistically significant （P＞0.05）. The results of multivariate binary Logistic regression analysis showed that gene test was an independent protective factor for warfarin anticoagulant therapy [odds ratio （OR）＝10.842， 95% confidence interval （CI）： 1.211-27.037， P＝0.033]， and the combination of statins was an independent risk factor for warfarin anticoagulant therapy [OR＝0.196， 95%CI： 0.045-0.861， P＝0.031]. CONCLUSIONS Under the guidance of gene test， warfarin anticoagulation therapy for LVAD patients after implantation can improve TTR， shorten the anticoagulation target time， and has good safety； meanwhile， it should be noted that the combination of statins may enhance the anticoagulant effect of warfarin， thereby increasing the risk of bleeding in patients.

Objective To analyze the status of persistent human papillomavirus (HPV) infection and the distribution of viral subtypes in the Zhengzhou region. Methods Clinical data of 55239 patients who underwent HPV-DNA genotyping tests from 2018 to 2024 were collected. On the basis of HPV follow-up results, patients were divided into three groups: 849 cases of infection with the same HPV type, 255 cases of persistent infection with different HPV types, and 857 cases of transient HPV infection. Results Among the 9232 initially-screened patients who were positive with HPV, the high-risk HPV (HR-HPV) positive rate was 84.6% (7813/9232), and predominant subtypes were HPV-16 (20.8%), HPV-52 (17.2%), and HPV-53 (9.6%). The low-risk HPV (LR-HPV) positive rate was 15.4% (1419/9232), mainly HPV-81 (28.1%) and HPV-42 (27.0%). Among the 1961 follow-up cases, the rates of persistent and non-persistent infections with the same HPV type were 35.7% (701/1961) and 7.5% (148/1961), respectively. The rates of persistent and non-persistent infections with different HPV types were 10.9% (214/1961) and 2.1% (41/1961), respectively. Meanwhile, 43.7% (857/1961) tested negative upon follow-up. Among the 701 cases of persistent infection with the same HPV type, HR-HPV accounted for 85.7% (601/701), and LR-HPV accounted for 14.3% (100/701). Among the 214 cases of persistent infection with different HPV types, 89.7% (192/214) were high-risk transitions, and 10.3% (22/214) were low-risk transitions. Regardless of HPV types, HR-HPV was more likely to cause persistent infection than LR-HPV. In addition, over 60% of HR-HPV persistent infections resolved within 18 months, 30% developed into persistent infections, and only 15% of patients had persistent infections that last more than 24 months. Conclusion Persistent HPV infections are predominantly high-risk types. Most patients clear the infection within 18 months, approximately 30% develop persistent infections, and about 15% of patients have persistent infections that last more than 24 months. However, the HR-HPV persistent infection rates across different age groups slightly differ.

Objective: To analyze the association between alcohol consumption and lumbar disc herniation (LDH), so as to provide a reference for the development of prevention and treatment strategies for LDH. Methods: From May to July 2022, permanent residents aged ≥18 years from eight counties (cities/districts) in Gansu Province were selected using a multistage stratified random sampling method. Data on basic characteristics, alcohol consumption in the past 30 days, hypertension, and diabetes mellitus were collected through questionnaire surveys. LDH was determined based on imaging findings, combined with disease history or clinical symptoms. Multivariable logistic regression model was used to analyze the association between alcohol consumption and LDH, with subgroup analyses conducted by gender, age, ethnicity, and altitude of residence. Propensity score matching (PSM) was utilized for sensitivity analysis. Results: A total of 4 545 individuals were surveyed. There were 2 026 (44.58%) males and 2 519 (55.42%) females. The mean age was (44.82±15.33) years. The study participants were predominantly of Han ethnicity, with 2 598 persons accounting for 57.17%. The altitude of residence was mainly above 3 500 m, with 1 941 persons accounting for 42.71%. There were 574 alcohol drinkers, accounting for 12.63%. LDH was detected in 1 035 cases, with a detection rate of 22.77%. Multivariable logistic regression analysis showed that after adjusting for gender, age, physical activity, and hypertension, compared to non-drinking residents, alcohol-consuming residents exhibited a 27.6% reduction in the risk of LDH (OR=0.724, 95%CI: 0.544-0.963). No significant interaction effects on LDH risk were observed between alcohol consumption and gender, age, ethnicity, or altitude of residence (all Pfor interaction >0.05). The results of the sensitivity analysis indicated that compared to non-drinking residents, alcohol-consuming residents exhibited a 38.8% reduction in the risk of LDH (OR=0.612, 95%CI: 0.382-0.976). Conclusion Alcohol consumption was statistically associated with a lower risk of LDH.