BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

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*

Objective:To construct a prognostic predictive model for patients with moderate to severe traumatic brain injury (msTBI) based on regional cerebral oxygen saturation (rScO 2) and transcranial Doppler ultrasound (TCD) monitoring parameters and validate its effectiveness. Methods:A retrospective cohort study was conducted to analyze the clinical data of 161 patients with msTBI who were treated at Henan Provincial People′s Hospital from January 2021 to December 2022, including 104 males and 57 females, aged 19-76 years [(53.1±12.8)years]. Glasgow coma scale (GCS) score was 3-12 points [(7.0±1.9)points]. Both rScO 2 and TCD monitoring were performed. Based on the results of prognostic evaluation of patients with the modified Rankin scale (mRS) score at 90 days after discharge, the patients were divided into good prognosis group (mRS score≤3 points, n=88) and poor prognosis group (mRS score of 4-6 points, n=73). The following data of the two groups were collected: the general data, clinical data, rScO 2 monitoring parameters and TCD monitoring parameters. Univariate analysis was employed to compare the differences in the relevant prognostic indicators. Multivariate Logistic stepwise regression analysis was conducted to determine the predictors of poor prognostic outcomes in msTBI patients and regression equations were constructed. A nomogram predictive model based on regression equations was drawn with R language. The discriminability of the model was evaluated by drawing the receiver operating characteristic (ROC) curve, to calculate the area under the curve (AUC), sensitivity, specificity, and Jordan index of the model, and measuring the consistency index (C index). Hosmer-Lemeshow (H-L) goodness of fit test was conducted to evaluate the fit of the model, and the calibration curve was used to evaluate the calibration degree of the model. Decision curve analysis (DCA) was employed to evaluate the clinical benefit and applicability of the model. Results:There were significant differences between the two groups in the clinical data (cerebral hernia formation, GCS on admission, acute physiology and chronic health evaluation II (APACHE II) score on admission, Rotterdam CT score on admission, oxygenation index on admission, mean arterial pressure on admission), rScO 2 monitoring parameters (mean rScO 2, maximum rScO 2, rScO 2 variability), TCD monitoring parameters [peak systolic blood flow velocity (Vs), average blood flow velocity (Vm), pulse index (PI)] ( P<0.05 or 0.01). The results of multivariate Logistic stepwise regression analysis showed that cerebral hernia formation ( OR=9.28, 95% CI 3.40, 25.33, P<0.01), Rotterdam CT score on admission ( OR=1.92, 95% CI 1.32, 2.78, P<0.01), rScO 2 variability ( OR=4.66, 95% CI 1.74, 12.43, P<0.01), Vs ( OR=0.66, 95% CI 0.61, 0.75, P<0.01) and PI ( OR=20.07, 95% CI 4.17, 16.50, P<0.01) were predictive factors for poor prognosis in patients with msTBI. The regression equation was constructed with the forementioned 5 variables: Logit [ P/(1- P)]=2.23×"brain hernia formation"+0.65×"Rotterdam CT score on admission"+1.54×"rScO 2 variability"-0.42×"Vs"+3.00×"PI"-6.75. The AUC of prognostic predictive model of msTBI patients was 0.90 (95% CI 0.85, 0.95), with the sensitivity and specificity of 86.3% and 78.4%, Youden index of 0.65 and C index of 0.90. H-L goodness of fit test showed that the calibration degree of the predictive model was accurate ( χ2 =12.58, P>0.05). The average absolute error of the calibration curve was 0.025, showing that the calibration of the model was good. DCA results showed that this model had higher net return rate than the reference model within the probability range of risk threshold (20%-100%), with good clinical application value in evaluating the risk of poor prognosis of msTBI patients. Conclusion:The model constructed based on the combination of rScO 2 and TCD monitoring parameters (rScO 2 variability, Vs and PI) with multiple clinical indicators (cerebral hernia formation and Rotterdam CT score on admission) has good predictive performance for the prognosis of msTBI.

Objective:To evaluate the effects of fine particle matter(PM2.5)and ozone(O3)com-bined exposure on adenosine triphosphate(ATP)amount and ATPase activities in nasal mucosa of Spra-gue Dawley(SD)rats.Methods:Twenty male SD rats were divided into control group(n=10)and exposure group(n=10)by random number table method.The rats were fed in the conventional clean environment and the air pollutant exposure system established by our team,respectively,and exposed for 208 d.During the exposure period,the concentrations of PM2 5 and O3 in the exposure system were moni-tored,and a comprehensive assessment of PM2 5 and O3 in the exposure system was conducted by combi-ning self-measurement and site data.On the 208 d of exposure,the core,liver,spleen,kidney,testis and other major organs and nasal mucosal tissues of the rats were harvested.Each organ was weighed and the organ coefficient calculated.The total amount of ATP was measured by bioluminescence,and the ac-tivities of Na+-K+-ATPase and Ca2+-ATPase were detected by spectrophotometry.The t test of two inde-pendent samples was used to compare the differences among the indicator groups.Results:From the 3rd week to the end of exposure duration,the body weight of the rats in the exposure group was higher than that in the control group(P＜0.05),and there was no significant difference in organ coefficients be-tween the two groups.The average daily PM2 5 concentration in the exposure group was(30.68±19.23)μg/m3,and the maximum 8 h ozone concentration(O3-8 h)was(82.45±35.81)μg/m3.The chemi-luminescence value(792.4±274.1)IU/L of ATP in nasal mucosa of the rats in the exposure group was lower than that in the control group(1 126.8±218.1)IU/L.The Na+-K+-ATPase activity(1.53±0.85)U/mg in nasal mucosa of the rats in the exposure group was lower than that in the control group(4.31±1.60)U/mg(P＜0.05).The protein content of nasal mucosa in the control group and the exposure group were(302.14±52.51)mg/L and(234.58±53.49)mg/L,respectively,and the ac-tivity of Ca2+-ATPase was(0.81±0.27)U/mg and(0.99±0.73)U/mg,respectively.There was no significant difference between the groups.Conclusion:The ability of power capacity decreased in the rat nasal mucossa under the sub-chronic low-concentration exposure of PM2 5 and O3.

Cordycepin (Cpn), a natural active compound derived from the traditional Chinese medicine Cordyceps sinensis, has antifibrotic, antioxidant, and anti-inflammatory effects, but the impact of Cpn on pulmonary fibrosis and the downstream molecular mechanism remain unclear. In this study, A549 cells were induced by transforming growth factor β1 (TGFβ1) in vitro, the viability of A549 cells was evaluated by CCK-8 assay; and migration of A549 cells were detected by wound healing assay, invasion of A549 cells were detected by transwell assay. Molecular docking and molecular dynamics simulations were used to predict the interaction of histone deacetylase 7 (HDAC7) with vimentin and the association of Cpn with HDAC7. The pulmonary fibrosis model of mice was established by bleomycin in vivo to investigate the effect of Cpn on pathological changes of lung tissue. The impact of Cpn and molecular mechanism on pulmonary fibrosis were studied by Western blot assay, cell transfection assay, immunoprecipitation assay, immunofluorescence assay, immunohistochemistry and real-time quantitative PCR (RT-qPCR). All animal experiments were approved by the Shanghai Children's Medical Center Experimental Animal Ethics Committee (grant No. SCMC-LAWEC-2022-017). Results showed that Cpn had no toxic effect on A549 cells even at the concentration of 100 μmol·L^-1. Cpn inhibited migration and invasion of A549 cells and reduced deposition of collagen, the degree of lung inflammation and fibrosis in mice; in vivo and in vitro models, Cpn significantly reversed mRNA and protein expressions of epithelial-mesenchymal transition (EMT) and lung fibrosis markers collagen I, α-smooth muscle actin (α-SMA), N-cadherin, vimentin and E-cadherin and HDAC7. Deficiency of HDAC7 suppressed TGFβ1-induced EMT and expression of collagen I; vimentin interacted with HDAC7; and molecular docking experiment revealed that Cpn was interrelated with HDAC7. In conclusion, Cpn can target HDAC7 to mediate EMT and exert its anti-fibrotic effect, the inhibition of EMT and the improvement of pulmonary fibrosis provide a new idea and choice for the development of anti-pulmonary fibrosis drug.

Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

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.

OBJECTIVE: To explore the effects of overweight and obesity (overweight/obesity) on symptom severity and quality of life in Chinese patients with fibromyalgia syndrome (FMS). METHODS: A cross-sectional survey was used to collect general data on height, weight, gender and age of 435 FMS patients who visited the rheumatology clinic of Guang 'anmen Hospital from October 2018 to December 2021. The numbers of tender points, widespread pain index and symptom severity scale were used as diagnostic indicators of the disease. The pain visual analogue scale, Beck depression inventory, perceived stress scale (PSS), Pittsburgh sleep quality index (PSQI) and multidimensional fatigue scale were used to assess the severity of pain and negative emotions, stress perception, sleep quality, and fatigue symptoms of this disease. The revised fibromyalgia impact questionnaire, fibromyalgia symptom scale (FS) and quality of life assessment scale (36 item short-form health survey, SF-36) were used to evaluate the overall condition and quality of life of the FMS patients. At the same time, 50 healthy volunteers matched in gender and age were recruited as the control group. Covariance analysis was used to explore the effects of overweight/obesity on the FMS patients after adjusting for age and gender. RESULTS: According to the Chinese body mass index (BMI) standard, there were 242 (59%) and 170 (41%) FMS patients in the normal weight group and overweight/obesity group, respectively, with average BMI of (21.66±1.42) kg/m² and (26.25±1.83) kg/m², respectively. Compared with the normal weight FMS patients, the overweight/obesity patients had higher PSS scores (P=0.010), PSQI sub-dimension sleep efficiency scores (P < 0.001) and FS scores (P=0.025), and lower SF-36 sub-dimension physical functioning scores (P=0.041). However, there were no statistical differences in the above indicators between normal weight and overweight/obesity patients in the healthy control group (P > 0.05). CONCLUSION Compared with normal-weight FMS patients, overweight/obesity patients have higher levels of perceived stress, lower sleep efficiency, and more severe fibromyalgia symptoms, as well as a low quality of life characterized by decreased physiological function. It is important for overweight/obesity FMS patients to control BMI actively in order to improve sleep efficiency, psychological state, physical functioning, and the overall condition.
Humans ; Fibromyalgia/psychology* ; Quality of Life ; Cross-Sectional Studies ; Overweight/psychology* ; Obesity/psychology* ; Female ; Male ; Surveys and Questionnaires ; Pain Measurement ; Severity of Illness Index ; Fatigue/etiology* ; Sleep Quality ; Middle Aged ; Adult ; Depression/psychology*