BACKGROUND:In recent years,epidemiological studies have shown that obesity is a risk factor for knee osteoarthritis,and fatty acid intake,metabolism and biosynthesis are closely related to the development of obesity.However,the causal relationship between fatty acids and osteoarthritis is still unknown.OBJECTIVE:Using the Mendelian randomization analysis to investigate the causal relationship between five fatty acid phenotypes and knee osteoarthritis.METHODS:The genome-wide association study data on fatty acid ratios from the UK Biobank(met-D)and genome-wide association study data on knee osteoarthritis from the EBI-A database were pooled together.Single nucleotide polymorphisms were used as instrumental variables and sensitive single nucleotide polymorphisms were selected for analysis.Two-sample Mendelian randomization analysis was conducted to evaluate the causal relationship between fatty acids and knee osteoarthritis outcome risk.We used inverse variance weighting method,MR-Egger regression method,weighted median method,weighted model method,and simple model method to study the causal relationship between fatty acids and knee osteoarthritis.Further inverse Mendelian randomization analysis was performed in the same way to ensure the validity of the results.RESULTS AND CONCLUSION:The forward analysis and inverse variance weighting method showed a causal relationship between three types of fatty acid phenotypes and knee osteoarthritis.Among them,the proportion of saturated fatty acids to total fatty acids was positively correlated with the risk of knee osteoarthritis(odds ratio[OR]=1.825,95%confidence interval(CI):1.230,2.706,P=0.003),the proportion of omega 3 polyunsaturated fatty acids to total fatty acids was negatively correlated with the risk of knee osteoarthritis(OR=0.822,95%CI:0.688 8,0.981,P=0.03),and the proportion of omega 6 polyunsaturated fatty acids to total fatty acids was positively correlated with the risk of knee osteoarthritis(OR=1.268,95%CI:1.079,1.491,P=0.004).There were two types of fatty acid phenotypes that do not have a causal relationship with knee osteoarthritis,including total fatty acids(OR=0.925,95%CI:0.804-1.066,P=0.283)and the proportion of monounsaturated fatty acids to total fatty acids(OR=0.877,95%CI:0.756-1.018,P=0.084).The reverse analysis results indicated that when knee osteoarthritis was used as exposure data,there was no significant causal relationship with the phenotype of fatty acids.The sensitivity analysis results showed that the P-values of the bidirectional Mendelian randomization Cochran's Q-test and MR Egger regression were both greater than 0.05,indicating that there was no significant heterogeneity or pleiotropy in the causal effect analysis between fatty acid phenotype and knee osteoarthritis.To conclude,reducing the content of saturated fatty acids and omega 6 polyunsaturated fatty acids and increasing the content of omega 3 polyunsaturated fatty acids can reduce the risk of knee osteoarthritis.This provides valuable clues for studying the biological mechanisms of knee osteoarthritis and exploring the early prevention and treatment of knee osteoarthritis,as well as providing new directions for the development of interventional drugs.

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

BACKGROUND:In recent years,epidemiological studies have shown that obesity is a risk factor for knee osteoarthritis,and fatty acid intake,metabolism and biosynthesis are closely related to the development of obesity.However,the causal relationship between fatty acids and osteoarthritis is still unknown.OBJECTIVE:Using the Mendelian randomization analysis to investigate the causal relationship between five fatty acid phenotypes and knee osteoarthritis.METHODS:The genome-wide association study data on fatty acid ratios from the UK Biobank(met-D)and genome-wide association study data on knee osteoarthritis from the EBI-A database were pooled together.Single nucleotide polymorphisms were used as instrumental variables and sensitive single nucleotide polymorphisms were selected for analysis.Two-sample Mendelian randomization analysis was conducted to evaluate the causal relationship between fatty acids and knee osteoarthritis outcome risk.We used inverse variance weighting method,MR-Egger regression method,weighted median method,weighted model method,and simple model method to study the causal relationship between fatty acids and knee osteoarthritis.Further inverse Mendelian randomization analysis was performed in the same way to ensure the validity of the results.RESULTS AND CONCLUSION:The forward analysis and inverse variance weighting method showed a causal relationship between three types of fatty acid phenotypes and knee osteoarthritis.Among them,the proportion of saturated fatty acids to total fatty acids was positively correlated with the risk of knee osteoarthritis(odds ratio[OR]=1.825,95%confidence interval(CI):1.230,2.706,P=0.003),the proportion of omega 3 polyunsaturated fatty acids to total fatty acids was negatively correlated with the risk of knee osteoarthritis(OR=0.822,95%CI:0.688 8,0.981,P=0.03),and the proportion of omega 6 polyunsaturated fatty acids to total fatty acids was positively correlated with the risk of knee osteoarthritis(OR=1.268,95%CI:1.079,1.491,P=0.004).There were two types of fatty acid phenotypes that do not have a causal relationship with knee osteoarthritis,including total fatty acids(OR=0.925,95%CI:0.804-1.066,P=0.283)and the proportion of monounsaturated fatty acids to total fatty acids(OR=0.877,95%CI:0.756-1.018,P=0.084).The reverse analysis results indicated that when knee osteoarthritis was used as exposure data,there was no significant causal relationship with the phenotype of fatty acids.The sensitivity analysis results showed that the P-values of the bidirectional Mendelian randomization Cochran's Q-test and MR Egger regression were both greater than 0.05,indicating that there was no significant heterogeneity or pleiotropy in the causal effect analysis between fatty acid phenotype and knee osteoarthritis.To conclude,reducing the content of saturated fatty acids and omega 6 polyunsaturated fatty acids and increasing the content of omega 3 polyunsaturated fatty acids can reduce the risk of knee osteoarthritis.This provides valuable clues for studying the biological mechanisms of knee osteoarthritis and exploring the early prevention and treatment of knee osteoarthritis,as well as providing new directions for the development of interventional drugs.

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 µg/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 µg/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

BACKGROUND: Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated. METHODS: The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry. RESULTS: ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 . CONCLUSION ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.
Animals ; Mice ; Carcinoma in Situ ; Chalcones/pharmacology* ; Ferroptosis ; Gallbladder Neoplasms/genetics* ; Glutathione Disulfide ; Kelch-Like ECH-Associated Protein 1 ; Mice, Nude ; NF-E2-Related Factor 2/genetics* ; Reactive Oxygen Species ; Humans

Objective:Using ultrasound imaging technology to evaluate the contraction characteristics of diaphragm in patients with chronic low back pain.Methods:Twenty nine patients with chronic low back pain and 26 healthy persons recruited from the rehabilitation department of the Third Affiliated Hospital of Sun Yat-sen University from November 2019 to April 2020 were selected and divided into the low back pain (LBP) group and the healthy control group. The thickness of the diaphragm (Tdi) of the subjects during deep breathing was evaluated by portable color Doppler ultrasound equipment under different body positions. The subjects were required to perform maximum inspiration for total lung capacity (TLC) and expiration for functional residual capacity (FRC) in the supine and standing position, respectively. The end-inspiratory diaphragm thickness (TdiTLC) and end-expiratory diaphragm thickness (TdiFRC) were recorded, and the diaphragmatic thickening fraction (DTF) was calculated. The general data of subjects with lower back pain and the correlation between Oswestry Dysfunction Index (ODI) and diaphragm function were analyzed; The diaphragm function of healthy control group and LBP group were compared; The receiver operating characteristic (ROC) curve of Tdi and DTF in the diagnosis of lower back pain were analyzed.Results:ODI lifting score was negatively correlated with standing TdiTLC ( r=-0.50, P<0.01). In intra-group comparison, the TdiTLC and TdiFRC values of healthy subjects in standing position were increased compared with those in supine position ( t=6.115, 7.314, all P<0.001); In standing position, TdiTCL and TdiFRC values in LBP group were increased compared with those in supine position ( t=2.834, 4.673, all P<0.01). In comparison between groups, TdiTLC values in supine and standing position of LBP group were significantly lower than those in healthy control group ( t=2.597, 3.338, all P<0.05); In standing position, TdiFRC of patients in LBP group was significantly lower than that of healthy control group ( t=2.098, P=0.041) and DTF value of patients in LBP group was significantly lower than that of healthy control group ( t=2.902, P=0.006). When TdiTCL≤3.3 mm in supine position was used to predict low back pain, the diagnostic sensitivity and specificity were 78.6% and 53.8%, respectively, and the area under the curve was 0.661. When TdiTCL≤4.5 mm in standing position was used to predict low back pain, the diagnostic sensitivity and specificity were 95.7% and 46.2%, respectively, and the area under the curve was 0.759. When DTF≤81.3% in standing position was used to predict low back pain, the diagnostic sensitivity and specificity were 52.2% and 84.6%, respectively, and the area under the curve was 0.698. Conclusions:It is found in our study that the diaphragm contractile function of patients with lower back pain is worse than that of normal subjects, and the difference was significant in standing position. We suggest that the right-side ultrasound image acquisition in the patient′s standing position is helpful to ensure the accuracy and objectivity of the measurement results. TdiTCL≤4.5 mm or DTF≤81.3% in standing position can be used as one of the reference indexes for the combined diagnosis of chronic low back pain.

OBJECTIVE：To explore high-alert drug management mode of our hospital ，and to provide reference for the management and utilization of this category in medical institutions. METHODS ：According to High-alert Drug Catalog （2019 edition）issued by Hospital Pharmacy Committee of Chinese Pharmaceutical Association ，the high-alert drug catalog of our hospital and their risk points were formulated. Relevant training and assessment were conducted for physicians ，pharmacists and nurses throughout the hospital. Using qualification rate of high-alert drug management and utilization as index ，the effectiveness of high-alert drug management and utilization were compared before and after optimization. RESULTS ：In our hospital ，the risk of high-alert drugs was controlled by establishing inspection and supervision group ，pharmacist education ，information management ， prescription review and individualized administration ，medication guidance ，prescription review and medication error reporting and other measures and with continuous optimization. Compared with before optimization ，qulification rate of high-alert drug management and utilization increased from 37.3％ to 80.1％ in clinical departments （P＜0.01），and that increased from 59.2％ to 85.0％ in pharmacy department （P＜0.01）. There were still some problems ，such as the inconsistency of high-alert drugs accounts and materials ，the failure to report all medication errors in time ，the imperfect establishment of prescription review software rules ， the insufficient medication guidance ，and the lack of individual medication varieties. CONCLUSIONS ：By optimizing the management of high-alert drugs ，the management and utlization of this category is improved effectively in clinical departments and pharmacy departments of our hospital.

The feasibility and safety of intracardiac echocardiography (ICE)-guided catheter ablation for atrial fibrillation (AF) using a minimal/zero-fluoroscopy approach have recently been reported. This approach helps to reduce ionizing radiation exposure and orthopedic complications resulting from using lead aprons. The objectives of this planned prospective, multicenter randomized controlled trial (RCT) (paroxysmal AF (PAF)-ICE trial; ChiCTR2000033624) are to evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF and the impact on occupational hazards among lab staff.Patients will be randomized in a 1:1 ratio to 2 groups: minimal fluoroscopy group ( n = 216) and traditional approach group ( n = 216). In the minimal fluoroscopy group, an ICE catheter will be used for geometry/anatomic construction, transseptal puncture, catheter tracking, and effusion monitoring. Pulmonary vein isolation (PVI) will be performed using an open-irrigated radiofrequency SmartTouch Surround Flow or SmartTouch catheter (Biosense Webster, Diamond Bar, California, USA), and confirmed by a multipolar Lasso or PentaRay catheter (Biosense Webster). In the traditional approach group, an ICE catheter will not be used. Transseptal puncture will be performed under fluoroscopic guidance, with all geometries constructed by mapping the catheters. The primary efficacy endpoint is freedom from AF recurrence (without antiarrhythmic medications) at 12 months after ablation. Other endpoints include duration of lead apron use, measures of intra-procedural efficiency, and peri-procedural complications. This RCT will evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF, also evaluate the benefits to lab staff (regarding reducing occupational hazards) related to this "minimal/zero-fluoroscopy" and "leadless" mode.

The feasibility and safety of intracardiac echocardiography (ICE)-guided catheter ablation for atrial fibrillation (AF) using a minimal/zero-fluoroscopy approach have recently been reported. This approach helps to reduce ionizing radiation exposure and orthopedic complications resulting from using lead aprons. The objectives of this planned prospective, multicenter randomized controlled trial (RCT) (paroxysmal AF (PAF)-ICE trial; ChiCTR2000033624) are to evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF and the impact on occupational hazards among lab staff.Patients will be randomized in a 1:1 ratio to 2 groups: minimal fluoroscopy group ( n = 216) and traditional approach group ( n = 216). In the minimal fluoroscopy group, an ICE catheter will be used for geometry/anatomic construction, transseptal puncture, catheter tracking, and effusion monitoring. Pulmonary vein isolation (PVI) will be performed using an open-irrigated radiofrequency SmartTouch Surround Flow or SmartTouch catheter (Biosense Webster, Diamond Bar, California, USA), and confirmed by a multipolar Lasso or PentaRay catheter (Biosense Webster). In the traditional approach group, an ICE catheter will not be used. Transseptal puncture will be performed under fluoroscopic guidance, with all geometries constructed by mapping the catheters. The primary efficacy endpoint is freedom from AF recurrence (without antiarrhythmic medications) at 12 months after ablation. Other endpoints include duration of lead apron use, measures of intra-procedural efficiency, and peri-procedural complications. This RCT will evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF, also evaluate the benefits to lab staff (regarding reducing occupational hazards) related to this "minimal/zero-fluoroscopy" and "leadless" mode.