ObjectiveTo investigate the association of liver fibrosis scores and inflammation markers with gallstones in patients with metabolic dysfunction-associated fatty liver disease （MAFLD）， as well as the mediating role of liver fibrosis scores in the relationship between inflammation markers and gallstones. MethodsA total of 14 567 patients who received physical examination and were diagnosed with MAFLD in Subei People’s Hospital from January 2014 to June 2023 were enrolled in this study， and according to the results of abdominal color Doppler ultrasound， they were divided into gallstone group with 1 724 patients and non-gallstone group with 12 843 patients. Related clinical data were collected from all patients， including demographic data， medical history， family history， physical examination， Color Doppler ultrasound， and biochemical parameters. The biomarkers associated with metabolic disorders and insulin resistance included triglyceride-glucose index （TyG）， TyG-body mass index （BMI） index， atherogenic index of plasma （AIP）， and non-high-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol ratio （NHHR）； the biomarkers associated with inflammation and nutritional status included neutrophil-to-lymphocyte ratio （NLR）， neutrophil percentage-to-albumin ratio （NPAR）， and monocyte-to-lymphocyte ratio （MLR）； the biomarkers for assessing liver fibrosis degree and liver function included albumin-bilirubin （ALBI） score， NAFLD fibrosis score （NFS）， fibrosis-4 （FIB-4） index， and aspartate aminotransferase-to-platelet ratio index （APRI）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Multivariate Logistic regression analysis， restricted cubic spline analysis， and mediating effect analysis were used to assess the association of liver fibrosis markers and inflammation markers with the risk of gallstones. ResultsThe prevalence rate of gallstones was 11.8% among the MAFLD patients. There were significant differences between the gallstone group and the non-gallstone group in sex， age， smoking history， diabetes， hypertension， lymphocytes， platelets， glucose， albumin， serum uric acid， alanine aminotransferase， aspartate aminotransferase， red blood cell， NLR， NPAR， MLR， NFS， FIB-4 index， and ALBI score （all P<0.05）. The multivariate Logistic regression analysis showed that NLR （odds ratio ［OR］=1.091， 95% confidence interval ［CI］： 1.028　—　1.160， P<0.05）， NPAR （OR=1.073， 95%CI： 1.042　—　1.105， P<0.05）， MLR （OR=1.142， 95%CI： 1.057　—　1.232， P<0.05）， NFS （OR=1.239， 95%CI： 1.190　—　1.291， P<0.05）， and FIB-4 index （OR=1.326， 95%CI： 1.241　—　1.417， P<0.05） were influencing factors for the prevalence rate of gallstones. The restricted cubic spline analysis showed a significant non-linear association between NFS/FIB-4 index and the risk of gallstone （non-linear P<0.05）. The mediating effect analysis further showed that the association of NLR， MLR， and NPAR with gallstones was partially mediated by NFS or FIB-4 index， with a mediating effect accounting for 36.79%、28.09%、29.67% and 18.31%、17.70、11.57%， respectively. ConclusionNFS and FIB-4 index have a non-linear association with the prevalence rate of gallstones in MAFLD patients， and they also mediate the association of NLR， NPAR， and MLR with the risk of gallstone.

BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.

[摘 要] 目的：探讨核仁小RNA（snoRNA）71A通过TLR3/PD-L1通路对食管鳞状细胞癌（ESCC）细胞增殖、迁移及侵袭能力的影响。方法：qPCR检测52例ESCC患者的配对肿瘤组织、癌旁组织，以及人ESCC细胞中SNORA71A的表达情况。将反义寡核苷酸（SNORA71A-ASO-29、SNORA71A-ASO-102和NC-ASO）或小干扰RNA（siTLR3、siTLR3-NC）分别转染至人ESCC TE-1细胞，分别记为SNORA71A-ASO1组、SNORA71A-ASO2组、NC-ASO组及siTLR3组、siNC组。另外将过表达质粒pcDNA3.1-SNORA71A和pcDNA3.1空载体质粒分别转染至TE-1细胞，分别记为SNORA71A组和Vector组。细胞功能学实验（MTS实验、划痕愈合实验，以及Transwell侵袭实验）评估各组细胞在敲低或过表达SNORA71A后增殖、迁移和侵袭能力的变化。高通量转录组测序筛选SNORA71A下游作用靶基因，基因本体论（GO）和京都基因与基因组百科全书（KEGG）功能富集分析预测SNORA71A下游作用靶基因可能参与的生物学过程和信号通路。qPCR检测测序筛选出的下游作用靶基因TLR3在ESCC组织以及细胞中的表达。同时，qPCR和WB检测TE-1细胞在敲低或过表达TLR3后PD-L1 mRNA和蛋白质表达变化。细胞功能学实验检测TLR3敲低对SNORA71A所促进的TE-1细胞恶性生物行为（增殖、迁移、侵袭）的影响。结果：在52例ESCC患者的肿瘤组织以及ESCC细胞中SNORA71A表达均呈高水平（P < 0.01或P < 0.05）。敲低SNORA71A抑制TE-1细胞增殖、迁移和侵袭（P < 0.01或P < 0.05），过表达SNORA71A则促进TE-1细胞增殖、迁移和侵袭（P < 0.01或P < 0.05）。高通量转录组测序筛选到TLR3为SNORA71A下游作用靶基因。TLR3在ESCC组织以及TE-1细胞中呈低表达（P < 0.01或P < 0.05）。TLR3正向调控PD-L1 mRNA和蛋白质表达（P < 0.01或P < 0.05）。细胞功能学实验中，TLR3可以部分削弱SNORA71A对PD-L1表达的调控（P < 0.01）。结论：SNORA71A通过调控TLR3/PD-L1通路调节TE-1细胞增殖、迁移和侵袭。

ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

ObjectiveTo investigate the association between noninvasive liver fibrosis markers and carotid plaque （CP） in patients with lean metabolic dysfunction-associated fatty liver disease （MAFLD）， and to provide a basis for screening high-risk populations. MethodsA total of 957 patients with lean MAFLD who underwent physical examination in Subei People’s Hospital from January 2021 to June 2023 was enrolled as the observation cohort， with the presence or absence of CP as the outcome， and fibrosis-4 （FIB-4） index and nonalcoholic fatty liver disease fibrosis score （NFS） were used to assess liver fibrosis degree. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression analysis， the restricted cubic spline analysis， the receiver operating characteristic curve， and the mediation effect analysis were used to investigate the association between liver fibrosis degree and CP. ResultsThe prevalence rate of CP was 36.6% in the lean MAFLD population. Compared with the non-CP group（n=607）， the CP group （n=350） had a significantly higher proportion of male patients， a significantly higher proportion of patients with smoking/diabetes/hypertension， and significantly higher levels of age， creatinine， blood urea nitrogen， triglycerides， fasting blood glucose， aspartate aminotransferase， aspartate aminotransferase/alanine aminotransferase ratio， NFS， and FIB-4 index， as well as significantly lower levels of platelet count and albumin （all P<0.05）. The multivariate logistic regression analysis showed that after adjustment for confounding factors， FIB-4 index （odds ratio［OR］=2.979， 95% confidence interval［CI］：2.141 — 4.219， P<0.001） and NFS （OR=1.747， 95%CI： 1.499 — 2.046， P<0.001） were positively correlated with CP. Both FIB-4 index and NFS had a good value in predicting CP. Hypertension had a significant indirect effect on the prevalence rate of CP through its impact on liver fibrosis markers， and its mediating effect accounted for 39.5% — 40.8% of the total effect （P<0.001）. ConclusionIn patients with lean MAFLD， NFS and FIB-4 index are significantly positively correlated with the prevalence rate of CP， and they can be used as potential epidemiological predictive indicators. Liver fibrosis markers may play a mediating role in the association between hypertension and CP. Interventions targeting hypertension and liver fibrosis markers may help to prevent and delay the progression of CP.

BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.

ObjectiveThis paper aims to conduct the feature analysis and correlation analysis on the ocular collateral features and differential metabolites in patients with chronic hepatitis B （CHB） complicated by glucose metabolism disorder （GMD），particularly those with the damp-heat syndrome type，by integrating shadowless scleral imaging and metabolomics technologies. MethodsA total of 313 patients were recruited from the Hepatology and Endocrinology Outpatient Departments of Public Health Clinical Center of Chengdu according to the inclusion/exclusion criteria，and they were divided into a CHB group and a CHB complicated by GMD groups （damp-heat syndrome group and non-damp-heat syndrome group）. All patients underwent high-definition ocular image acquisition and feature extraction using an intelligent analysis system for shadowless scleral imaging to analyze the differences in the counting of morphological feature scores of ocular collaterals among groups. By using a digital sampling method，24 patients from each group were randomly selected，along with 20 healthy volunteers，for untargeted metabolomic analysis of peripheral serum. Differential metabolites were identified，statistically analyzed，and subjected to potential biomarker analysis and pathway enrichment. Spearman method was performed to conduct the correlation analysis on the differential ocular collateral features and differential metabolites，followed by correlation network construction. ResultsCompared with those in the CHB group，patients with CHB complicated by GMD showed significant changes in ocular collateral feature scores such as "hillock"，"blood vessels"，and "pale dusky coloration" （P<0.05）. In comparison with those in the healthy group，metabolites including N-acetylglucosamine，acetylhomoserine，and myo-inositol （AUC>0.7） were identified as potential biomarkers for the disease. Compared with those in the CHB complicated by GMD group with non-damp-heat syndrome，patients with damp-heat syndrome exhibited significant changes in feature scores of "plaques"，"yellow coloration"，"spleen"，and "gallbladder" （P<0.05）. In comparison with those in the healthy group，metabolites such as O²′-4a-cyclic tetrahydrobiopterin，theobromine，xanthurenic acid，and L-glutamic acid 5-phosphate （AUC>0.7） were identified as potential biomarkers for the damp-heat syndrome type. The Spearman correlation analysis reveals weak to moderate linear correlations between the differential scleral collateral features and metabolites. By constructing a "disease-syndrome" network of ocular diagnosis and metabolites，"xanthurenic acid-gallbladder" and "theobromine-plaque/yellow coloration" were identified as specific molecular-phenotypic correlated biomarker clusters for CHB complicated by GMD with dampness-heat syndrome. ConclusionPatients with CHB complicated by GMD demonstrate differential ocular diagnostic features and serum metabolites corresponding to disease states and dampness-heat syndrome. These objective biomarkers can guide both clinical syndrome differentiation and medication. The macro-micro integration based on ocular feature clusters and potential metabolic biomarkers offers an innovative approach to a combined traditional Chinese and Western medicine diagnosis and treatment model for this disease.

Objective: To explore the association between mental health status and adverse childhood experiences (ACEs) among sexual minority college students, so as to provide a scientific basis for mental health education and health promotion in universities. Methods: From January to February 2024, convenience and cluster sampling methods were used to select 1 792 college students from 11 colleges in Guangxi. A self reporting method was applied to identify 476 sexual minority individuals. The Symptom Check-List 90 (SCL-90) and the Simplified Chinese Adverse Childhood Experiences International Questionnaire (SC-ACE-IQ) were employed to assess mental health and ACEs. Multivariate Logistic regression analysis was conducted to examine the associations. Results: The detection rates of all psychological issues among sexual minority college students in Guangxi were significantly higher than those of non sexual minority college students ( χ 2=56.01-91.39, all P <0.01). Except for physical neglect, bullying, and community violence, sexual minority students exhibited higher reporting rates of other ACEs types compared to nonsexual minority students ( χ 2= 4.52-13.34, all P <0.05). The total ACEs score for college students was 1.00 (1.00, 2.00), while the SCL-90 total score was 96.00 (113.00, 160.00). Spearman correlation analysis revealed a positive correlation between ACEs total scores and SCL-90 total scores ( r=0.29, P <0.05). Additionally, all ACEs subscales, including emotional neglect, physical neglect, emotional abuse, sexual abuse, parental loss, domestic violence, and community violence were positively correlated with corresponding SCL-90 subscale scores ( r =0.05-0.22, all P <0.05). Multivariate Logistic regression analysis showed that family violence increased the risk of mental health issues for sexual minority students ( OR=1.61, 95%CI =1.26-2.09); emotional neglect ( OR= 1.05 , 95%CI =1.00-1.10), physical neglect ( OR=1.20, 95%CI =1.06-1.35), sexual abuse ( OR=1.49, 95%CI =1.15-1.93) increased mental health risks for non sexual minority students (all P <0.05). The cumulative effects of ACEs were all statistically significant in the total sample and both subgroups (all P <0.05). Conclusion Mental health status among sexual minority college students in Guangxi is associated with ACEs, and their well being requires active attention

OBJECTIVE: To compare the clinical efficacy of acupuncture with yin-yang regulation method versus local acupuncture in treating chronic low back pain (CLBP) in elderly patients with lumbar disc herniation (LDH), and to evaluate the changes in the multifidus muscle before and after treatment using musculoskeletal ultrasound. METHODS: A total of 128 elderly patients with CLBP due to LDH were randomly assigned to an observation group (64 cases, 2 cases dropped out) and a control group (64 cases, 2 cases dropped out). The control group received local acupuncture at bilateral L₃-L₅ Jiaji points (EX-B2), Shenshu (BL23), Dachangshu (BL25), Weizhong (BL40), Yaoyangguan (GV3), and ashi points. The observation group received acupuncture with yin-yang regulation method, which included an abdominal protocol with Baihui (GV20), Zhongwan (CV12), Qihai (CV6), Guanyuan (CV4), bilateral Tianshu (ST25), and Dahe (KI12), etc., and a lumbar protocol with Baihui (GV20), Dazhui (GV14), Jizhong (GV6), Yaoyangguan (GV3), and ashi points, etc., alternated bilaterally. Both groups were treated once every other day, three times per week, for a total of 12 sessions. The visual analogue scale (VAS) score, Oswestry disability index (ODI) score, and the indexs of musculoskeletal ultrasound multifidus muscle (resting and functional thickness and Young's modulus values) were observed before and after treatment, and the clinical efficacy was evaluated in the two groups. RESULTS: After 1 and 4 weeks of treatment, both groups showed lower VAS scores compared to baseline (P<0.05), the VAS scores in the observation group were lower than those in the control group (P<0.001). ODI scores in both groups were decreased after 1 and 4 weeks of treatment compared to baseline (P<0.05), with a further reduction at 4 weeks of treatment compared to 1 week of treatment (P<0.05); the observation group showed lower ODI score than the control group after 1 week of treatment (P<0.001). After treatment, both groups demonstrated increased resting and functional multifidus muscle thickness bilaterally compared to baseline (P<0.01), with an increased right-side thickness change rate (P<0.01), though no significant difference was observed between groups (P>0.05). Compared to baseline, after treatment, the observation group exhibited decreased Young's modulus values for bilateral resting and functional multifidus muscle (P<0.01), while the control group showed reductions only in bilateral resting and right-side functional Young's modulus values (P<0.01). After treatment, the bilateral functional Young's modulus values in the observation group were lower than that in the control group (P<0.05), and the bilateral resting and functional changes in Young's modulus values were greater in the observation group than those in the control group (P<0.01). The overall effective rate was 93.5% (58/62) in the observation group, which was higher than 79.0% (49/62) in the control group (P<0.05). CONCLUSION Acupuncture with yin-yang regulation method effectively alleviates pain, improves functional disability, increases multifidus muscle thickness, and reduces Young's modulus values in elderly patients with CLBP due to LDH, which has superior therapeutic effect compared to local acupuncture.
Humans ; Low Back Pain/physiopathology* ; Male ; Acupuncture Therapy ; Female ; Aged ; Intervertebral Disc Displacement/physiopathology* ; Middle Aged ; Yin-Yang ; Lumbar Vertebrae ; Acupuncture Points ; Treatment Outcome

Based on the theory of "three regions and sanjiao" in traditional Chinese medicine (TCM), the acupuncture-moxibustion differentiation and treatment system is explored and constructed for spasm syndrome, so as to provide a clearer guiding framework for TCM treatment of spasm syndrome. This disorder is caused essentially by the invasion of pathogenic wind, and located in brain marrow. The key regions of illness cover five zang organs and five tissues, and the core pathogenesis is associated with wind disturbance in brain marrow. In differentiation, spasm syndrome refers to overall transmission (from the upper to the lower) and local transmission (from exterior to interior). This disorder can be classified into sanjiao spasm (heart-lung spasm of the upper jiao, liver-spleen spasm of the middle jiao, and liver-kidney spasm of the lower jiao) and three-region spasm (skin-vessel spasm of the upper region, tendon-muscle spasm of the middle region, and tendon-bone spasm of the lower region). Based on "three regions and sanjiao" theory of acupuncture and moxibustion, 7 "expelling-wind" points can be selected in terms of the etiology of this disease. Baihui (GV20)-toward-Taiyang (EX-HN5) needling is applied to regulate the brain marrow, focusing on the core location of illness; and regarding the key location of illness, the combination of back-shu and front-mu points and that of jing-well and xing-spring points are adopted to regulate five zang organs. The five needling techniques (half needling, leopard-spot needling, joint needling, Hegu needling and shu needling) are used to regulate five tissues.
Humans ; Acupuncture Therapy ; Spasm/diagnosis* ; Moxibustion ; Acupuncture Points ; Medicine, Chinese Traditional ; Diagnosis, Differential