This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Drug-induced liver injury(DILI)is one of the major challenges in drug development and clinical practice,and effective prevention and con-trol measures remain lacking.Research has shown that DILI is primarily mediated by immune respons-es.Human leukocyte antigen(HLA)alleles are cur-rently the strongest genetic factors reported to be associated with DILI.Due to the low positive predic-tive value of HLA alleles,preemptive HLA genetic screening has limited clinical utility in preventing DILI.However,its high negative predictive value makes it valuable for DILI diagnosis and causality assessment.In recent years,polymorphisms in im-mune-related genes-such as those involved in anti-gen processing and presentation pathways,T-cell receptors,immunostimulatory molecules,and cyto-kines-have been found to be associated with DILI.Future studies combining these genes with HLA analysis may provide deeper mechanistic insights into DILI and facilitate their translational applica-tion in clinical practice,ultimately improving drug safety.

OBJECTIVE To investigate the intervention effects of tissue-bone homeostasis manipulation(TBHM)on peripatellar biomechanical parameters and knee joint function in knee osteoarthritis(KOA)patients.METHODS Sixty patients with KOA(Kell-gren-Lawrence grade Ⅱ-Ⅲ)were recruited from the Acupuncture-Moxibustion Rehabilitation Department,Anhui University of Chi-nese Medicine between October 2024 and May 2025.Participants were randomized into a TBHM group(n=30)or a transcutaneous e-lectrical neuromuscular stimulation(TENS)group(n=30).Using two-way repeated measures ANOVA,biomechanical indicators,in-cluding rectus femoris tension,vastus medialis tension,vastus lateralis tension,patellar ligament tension,lateral patellar displacement(LPD),medial patellar displacement(MPD),normalized patellar mobility(LPD/patellar width[PW],MPD/PW),knee flexion range of motion,and functional indicators,including KOOS subscales,time up and go test(TUGT),were compared between groups at baseline and after 6 weeks of intervention.RESULTS After intervention,all biomechanical and knee joint function indicators in the TBHM group were significantly improved(P<0.05,P<0.01),while only the vastus medialis tension,TUGT and KOOS Pain,ADL and QoL scores in the control group were significantly improved(P<0.01).The improvement amplitudes of biomechanical indicators in the TBHM group,including rectus femoris tension,vastus lateralis tension,patellar ligament tension,MPD/PW,LPD/PW and knee flexion range of motion were better than those in the control group(P<0.05,P<0.01).In the functional evaluation,the interaction effects of the TBHM group in all dimensions of the KOOS score and TUGT were statistically significant(P<0.05,P<0.01).Post-hoc simple effect analysis confirmed that there were significant differences in the above indicators between the two groups after intervention(P<0.05),and all indicators showed a significant main effect of time(P<0.01),suggesting that the intervention measures had contin-uous and cumulative curative effects.CONCLUSION TBHM effectively improves joint function and quality of life in KOA patients by restoring dynamic equilibrium in soft tissue tension and patellar mobility,ultimately achieving the therapeutic goal of concurrent tis-sue-bone management.

Objective To compare the differences in clinical features and treatment choices between periph-eral spondyloarthritis(pSpA)and axial spondyloarthritis(axSpA),and better understand the clinical charac-teristics and medication needs of pSpA.Methods Our study is a retrospective cohort study.The patients who first visited the First Medical Center of Chinese PLA General Hospital between January 2016 and December 2022 and were diagnosed with axSpA or pSpA according to the classification criteria established by the Assess-ment of SpondyloArthritis International Society were selected as the study subjects.Demographic data,clinical characteristics,laboratory tests,and treatment information of these patients were obtained through the electronic medical records management system and the intelligent management system for spondyloarthritis.The research compared the distribution of swollen and tender joints between pSpA and axSpA patients,as well as that between pSpA1(excluding patients with psoriatic arthritis)and axSpA patients.Additionally,we analyzed differences in clinical features and treatment options among these groups.Results A total of 1639 pa-tients were included in the study,of which 184 had pSpA(including 97 with psoriatic arthritis),and 1455 had axSpA.Compared to axSpA patients,pSpA patients had fewer male patients(62.5％vs.79.7％,P＜0.001),later onset age(33.8 years vs.22.0 years,P＜0.001),shorter diagnostic delays(6.0 months vs.14.2 months,P=0.004),more associated peripheral arthritis(71.7％vs.9.3％,P＜0.001)and dac-tylitis(6.5％vs.0.3％,P＜0.001),more cases of psoriasis(52.7％vs.1.1％,P＜0.001)and a more common family history of psoriasis(11.4％vs.3.4％,P＜0.001).pSpA patients had higher levels of in-flammatory markers but a lower positive rate of human leukocyte antigen(HLA)-B27(43.5％vs.87.4％,P＜0.001).A positive HLA-B27 was associated with an earlier onset age,fewer cases of psoriasis,and a fami-ly history of ankylosing spondylitis.pSpA patients had a higher proportion of using conventional synthetic dis-ease-modifying antirheumatic drugs(csDMARDs),biologic disease-modifying antirheumatic drugs(bDMARDs),and oral glucocorticoids,and they also more frequently used a combination of bDMARDs and csDMARDs(19.0％vs.12.2％,P=0.009)or multiple csDMARDs(65.8％vs.12.5％,P＜0.001).Compared to axSpA patients,pSpA1 patients(excluding psoriatic arthritis)did not show significant differences in the prevalence of psoriasis,uveitis,family history of psoriasis,or the use of bDMARDs,but the subgroup analysis of other variables was consistent with the results of pSpA patients.Conclusions pSpA patients tend to have a later onset of disease,a lower proportion of male and HLA-B27 positivity,more associ-ated peripheral arthritis,dactylitis,psoriasis,and a more common family history of psoriasis.The disease bur-den in terms of treatment for pSpA is not lower than that for axSpA.Due to the presence of more peripheral symptoms,psoriasis,and higher levels of inflammation,they also require more medication.

OBJECTIVE To investigate the intervention effects of tissue-bone homeostasis manipulation(TBHM)on peripatellar biomechanical parameters and knee joint function in knee osteoarthritis(KOA)patients.METHODS Sixty patients with KOA(Kell-gren-Lawrence grade Ⅱ-Ⅲ)were recruited from the Acupuncture-Moxibustion Rehabilitation Department,Anhui University of Chi-nese Medicine between October 2024 and May 2025.Participants were randomized into a TBHM group(n=30)or a transcutaneous e-lectrical neuromuscular stimulation(TENS)group(n=30).Using two-way repeated measures ANOVA,biomechanical indicators,in-cluding rectus femoris tension,vastus medialis tension,vastus lateralis tension,patellar ligament tension,lateral patellar displacement(LPD),medial patellar displacement(MPD),normalized patellar mobility(LPD/patellar width[PW],MPD/PW),knee flexion range of motion,and functional indicators,including KOOS subscales,time up and go test(TUGT),were compared between groups at baseline and after 6 weeks of intervention.RESULTS After intervention,all biomechanical and knee joint function indicators in the TBHM group were significantly improved(P<0.05,P<0.01),while only the vastus medialis tension,TUGT and KOOS Pain,ADL and QoL scores in the control group were significantly improved(P<0.01).The improvement amplitudes of biomechanical indicators in the TBHM group,including rectus femoris tension,vastus lateralis tension,patellar ligament tension,MPD/PW,LPD/PW and knee flexion range of motion were better than those in the control group(P<0.05,P<0.01).In the functional evaluation,the interaction effects of the TBHM group in all dimensions of the KOOS score and TUGT were statistically significant(P<0.05,P<0.01).Post-hoc simple effect analysis confirmed that there were significant differences in the above indicators between the two groups after intervention(P<0.05),and all indicators showed a significant main effect of time(P<0.01),suggesting that the intervention measures had contin-uous and cumulative curative effects.CONCLUSION TBHM effectively improves joint function and quality of life in KOA patients by restoring dynamic equilibrium in soft tissue tension and patellar mobility,ultimately achieving the therapeutic goal of concurrent tis-sue-bone management.

Drug-induced liver injury(DILI)is one of the major challenges in drug development and clinical practice,and effective prevention and con-trol measures remain lacking.Research has shown that DILI is primarily mediated by immune respons-es.Human leukocyte antigen(HLA)alleles are cur-rently the strongest genetic factors reported to be associated with DILI.Due to the low positive predic-tive value of HLA alleles,preemptive HLA genetic screening has limited clinical utility in preventing DILI.However,its high negative predictive value makes it valuable for DILI diagnosis and causality assessment.In recent years,polymorphisms in im-mune-related genes-such as those involved in anti-gen processing and presentation pathways,T-cell receptors,immunostimulatory molecules,and cyto-kines-have been found to be associated with DILI.Future studies combining these genes with HLA analysis may provide deeper mechanistic insights into DILI and facilitate their translational applica-tion in clinical practice,ultimately improving drug safety.

To compare the differences in clinical features and treatment choices between peripheral spondyloarthritis(pSpA) and axial spondyloarthritis(axSpA), and better understand the clinical characteristics and medication needs of pSpA.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.