Non-alcoholic fatty liver disease （NAFLD） is a chronic liver disease closely related to metabolism， which is mainly characterized by abnormal lipid deposition in hepatocytes. In recent years， with the increasing prevalence of obesity and metabolic syndrome， NAFLD has become one of the most common chronic diseases in the world. The pathogenesis of NAFLD is complex and varied， involving the cross-regulation of multiple signaling pathways such as glucose-lipid metabolism， oxidative stress， and inflammation. The TLR4 signaling pathway plays a key role in the development and progression of NAFLD， and abnormal activation of this pathway accelerates the deterioration of NAFLD by promoting the release of pro-inflammatory cytokines， inducing oxidative stress， and exacerbating insulin resistance. Studies have shown that traditional Chinese medicine （TCM） can regulate the TLR4 signaling pathway to alleviate the symptoms and pathological features of NAFLD. The present review summarizes the experimental research progress in the TCM regulation of the TLR4 signaling pathway in treating NAFLD in the past 5 years， covering a wide range of TCM active ingredients （such as polysaccharides， terpenoids， alkaloids， flavonoids） and compound prescriptions. The active ingredients and compound prescriptions of TCM can effectively ameliorate lipid metabolism disorders， reduce insulin resistance， regulate intestinal flora， and inhibit inflammation and oxidative stress by regulating the TLR4 signaling pathway via multiple targets and pathways， thus slowing down the progression of NAFLD. Through in-depth analysis of the pathological mechanisms of NAFLD and exploration of the potential of TLR4 signaling pathway as a therapeutic target， we can provide theoretical support for the application of TCM in the treatment of NAFLD， as well as new perspectives and directions for future clinical research and new drug development， thereby promoting the innovation and development of therapeutic strategies for NAFLD.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective:To explore the biomechanical stability of a novel anchor-loop internal fixation system in the treatment of acromioclavicular joint dislocation using cadaveric specimens.Methods:The acromioclavicular ligaments were severed in 12 complete shoulder joint specimens, in which the quasi-static non-destructive cycle experiment was performed until the coracoclavicular ligaments failed. The failure intensities of the coracoclavicular ligaments were recorded. Next, the 12 specimens were randomly divided into groups A, B, C and D ( n=3), in which 4 different internal fixation materials were used respectively to reduce and fix the acromioclavicular joint. Group A was subjected to 3.5 mm clavicular hook locking compression plate, group B to 5 mm soft tissue with wire anchor, group C to 10 mm Endobutton steel plate, and group D to the novel anchor-loop internal fixation system (5 mm soft tissue with wire anchor + 10 mm Endobutton steel plate). An X-ray machine was used to evaluate the reduction and internal fixation of the acromioclavicular joint. After the shoulder specimens were securely fastened by a homemade fixation jig to a 100 KN electronic universal mechanical testing machine, each experimental specimen was subjected to a destructive static tensile mechanic determination in the vertical direction at a loading speed of 100 mm/min. The load-displacement curves were recorded and drawn by a computer connected with the biomechanical testing machine. The failure strength and failure causes were recorded for each internal fixation. Results:The fracture strength of the coracoclavicular ligament in 12 cadaver specimens was (374.6±0.8) N. The mechanical load of internal fixation failure was (409.5±2.6) N in group A, (297.8±3.4) N in group B, (375.2±3.1) N in group C and (376.2±3.1) N in group D. The internal fixation failure was due to clavicular fracture in 2 specimens and to acromial fracture in 1 specimen in group A, to anchor protrusion in all the 3 specimens in group B, to coracoid base fracture in all the 3 specimens in group C, and to anchor protrusion in all the 3 specimens in group D. The mechanical loads of internal fixation failure were significantly different among the 4 experimental groups ( P<0.05). The mechanical load of internal fixation failure in group D was significantly different from that in groups A and B ( P<0.05). Conclusions:Our self-developed novel anchor-loop internal fixation system can effectively reposit the acromioclavicular joint to treat acromioclavicular joint dislocation, because it conforms to the biomechanical characteristics of the acromioclavicular joint, and is easy to handle. Therefore, its feasibility is high.

Objective To establish a prediction model for in-hospital mortality risk in patients with sepsis-induced coagulopathy based on LASSO regression.Methods Patients with sepsis-induced coagulopathy ad-mitted to intensive care unit(ICU)at Beth Israel Deaconess Medical Center during 2008 to 2019 were selected from the Medical Information Market for Intensive Care(MIMIC)-Ⅳ database(version 2.1)for retrospective study.The study subjects were randomly divided into modeling group and verification group,and the feature variables were screened by LASSO regression.The feature variables were analyzed by multivariate Logistic re-gression to determine independent risk factors,and the nomogram prediction model was established at the same time.The model performance was evaluated by drawing calibration curve and receiver operating charac-teristic(ROC)curve,as well as decision curve analysis.Results A total of 4 994 patients with sepsis-induced coagulopathy admitted to ICU for the first time were enrolled in this study.They were randomly divided into a model group(n=3 495)and a validation group(n=1 499)at a ratio of 7:3.Multivariate Logistic regres-sion analysis showed that age,mean respiratory rate,mean corpuscular hemoglobin concentration,red blood cell count,platelet count,prothrombin time,anion gap,acute physiological score Ⅲ and acute kidney injury were independent risk factors for in-hospital mortality of patients with sepsis-induced coagulopathy.Based on the above independent risk factors,a nomographic prediction model was constructed.The area under the ROC curve and 95％confidence interval of the nomogram in the modeling group and validation group were 0.864(0.849-0.880)and 0.877(0.852-0.901),respectively.The sensitivity was 0.795 and 0.763,and the speci-ficity was 0.779 and 0.843,respectively.The calibration curve suggested that the predicted probability was ba-sically consistent with the actual probability,and the decision curve analysis showed that it had good clinical net benefits within a wide range of threshold.Conclusion The nomogram model based on MIMIC-Ⅳ database has good predictive value for predicting the in-hospital mortality of patients with sepsis-induced coagulopathy and can be used to guide clinical work.

Objective:To design and synthesize peptide inhibitors targeting transient receptor potential vanilloid 1(TRPV1)ion channel,and to validate their function.Methods:Based on previous studies on the relation of molecular structure and function of red head toxin(RhTx),a series of peptides were rationally designed and synthesized,with positive charged amino acids linked to the N terminus of RhTx.These Nplus-RhTx peptides were functionally validated by patch-clamp recordings in live cells.Results:Among the 8 synthesized Nplus-RhTx peptides,four inhibited TRPV1 ion channel activated by capsaicin with IC50 of(188.3±4.7),(193.6±18.0),(282.8±11.9)and(299.5±6.4)μmol/L,respectively.Conclusion:It is feasible to develop TRPV1 peptide inhibitors by using rational design based on N terminal residues of RhTx.

Objective To investigate the effect of body mass index(BMI)on the clinicopathological characteristics of patients with idiopathic membranous nephropathy(IMN).Methods A total of 261 patients with IMN were divided into the normal group(66 cases),the overweight group(105 cases)and the obese group(90 cases)according to BMI.Clinical and renal pathological data of patients were compared between the three groups.The correlation between BMI and clinicopathological indexes was analyzed by Pearson or Spearman's correlation.The influencing factors of estimated glomerular filtration rate(eGFR)were analyzed by multiple linear regression,and the influencing factors of interstitial fibrosis(IF),tubular atrophy(TA),glomerulosclerosis(GS)and mesangial cell proliferation(MCP)were analyzed by binary Logistic regression.Results Compared with the normal group,the prevalence of diabetes mellitus,triglycerides(TG)and low-density lipoprotein cholesterol(LDL-C)were elevated in the overweight group.The prevalence of hypertension,hemoglobin(HGB),uric acid(UA),LDL-C,TG,24-h urinary protein(UTP)and serum complement 3(C3)were elevated,and high-density lipoprotein cholesterol(HDL-C)was decreased in the obese group(P＜0.05).The prevalence of hypertension,UA,TG and serum C3 were elevated in the obese group compared to the overweight group(P＜0.05).The glomerular basement membrane(GBM)thickness was higher in the obese group and the overweight group than that in the normal group,and the proportion of GS and IF was higher in the obese group than that in the normal group(P＜0.05).BMI was positively correlated with hypertension,TG,LDL-C,serum C3,UTP,GS,IF,MCP and deposition in the mesangial region of C3,and negatively correlated with HDL-C(P＜0.05).Multiple linear regression analysis showed that age,blood urea nitrogen(BUN),anti-phospholipase A2 receptor antibody(anti-PLA2R),UTP and TA were independent risk factors of eGFR.Binary Logistic regression analysis showed that elevated BMI,age,UTP and serum creatinine(Scr)were independent risk factors for IF.Age,Scr and elevated UA were independent risk factors for TA.Elevated BMI and decreased eGFR were independent risk factors for GS.Elevated BMI was an independent risk factor for MCP.There was no significant difference in the treatment protocol of IMN patients between the three groups.Conclusion Obesity can exacerbate multiple clinical and pathological outcomes in IMN patients.

Objective To analyze the hip joint biomechanies of the acetabular anatomical reconstruction and nonanatomi-cal reconstruction in total hip arthroplasty(THA)for Crowe type Ⅲ developmental dysplasia of the hip(DDH)by finite ele-ment method,which provided theoretical foundation and experimental basis for the anatomical acetabular reconstruction dur-ing THA in clinical practice.Methods One patient with left end-stage hip arthritis secondary to Crowe type Ⅲ DDH was se-lected in this study,who underwent total hip arthroplasty in the orthopedic department of the First Affiliated Hospital of Bengbu Medical College in April 2020.This patient was female,57 years old.The preoperative and postoperative three dimentional CT scan of the patient's pelvis were performed.Fourteen acetabular cup models with different anteversion,inclination and rotation center height were established in Mimics and 3-Matic software.The boundary and load conditions were set in Abaqus software.The Von Mises and stress distribution of the hip joint were calculated and observed.Results In the Crowe type Ⅲ DDH THA,if the hip rotation center was restored anatomically and the acetabular cup's inclination was set as 40°,the cup's anteversion var-ied from 5° to 25°,the lowest Von Mises value of acetabular cup and polyethylene liner occured in 20°anteversioin;if the hip rotation center was restored anatomically and the acetabular cup's anteversion was set as 15°,the cup's inclination varied from 35° to 55°,the lowest Von Mises value of acetabular cup and polyethylene liner occured in 35° inclination;if the acetabular cup's anteversion and inclination were set as 15°and 40°respectively,the up migration of hip rotaion center varied from 0 mm to 20 mm,the lowest Von Mises value of acetabular cup and polyethylene liner occured in 10 mm up migration.In all fourteen models,the Von Mises value of the acetabulum,acetabulum cup and polyethylene liner were lowest when the acetabular cup's anteversion and inlcination were 15°,35° respectively,as well as the rotation center was restored anatomically.Conclusion In total hip arthroplasty for Crowe type Ⅲ DDH,the anatomical restoration of hip rotation center with 15° anteversion and 35° in-clination of the acetabular cup are suggested,bone graft above the acetabular cup and additional screws are recommended si-multaneously to further reduce the Von Mises of hip joint.

Objective:To evaluate the risk factors for the formation of parastomal Hernias(PSH)using meta-analysis,and to provide a theoretical basis for the prevention and treatment of PSH.Methods:Case control or Cohort study of PSH risk factors were collected by searching PubMed,CNKI,Wanfang data and other databases.Extract relevant data and perform meta-analysis using RevMan 5.3.Results:The results included a total of 16 studies,with a total sample size of 2411 cases,including 670 in the PSH group and 1741 in the non PSH group.The results showed that advanced age,female gender,BMI≥25,hypertension,COPD/chronic cough,diabetes,and postoperative Hypoproteinemia could increase the risk of PSH(P＜0.05);Smoking,previous ab-dominal surgery history,preoperative radiotherapy/chemotherapy etc.,were not significantly asso-ciated with the occurrence of PSH(P＞0.05).Conclusion:The current evidence shows that ad-vanced age,female gender,BMI≥25,hypertension,COPD/chronic cough,diabetes,postoperative Hypoproteinemia are risk factors for PSH,and extraperitoneal stoma can reduce the occurrence of PSH.

【Objective】 To estimate the prevalence, associated factors and patterns of multimorbidity of non-communicable diseases among adults in Shaanxi Province so as to provide evidence for the prevention and control of non-communicable diseases. 【Methods】 We used the data of adults aged 18 years and older collected in the baseline survey of Shaanxi Project in the Regional Ethnic Cohort Study in Northwest China. Multinomial logistic regression was used to explore the associated factors for multimorbidity. Exploratory factor analysis was used to extract patterns of multimorbidity. 【Results】 The prevalence of multimorbidity was 10.7% among the 44 442 participants. Age increase, being males, urban residence, and being overweight or obesity were positively associated with multimorbidity. Compared with women, men had a higher risk of multimorbidity. The OR and 95% CI was 1.25 (1.12-1.39). The risk of multimorbidity increased with age among adults. Compared with participants aged 18.0-34.9 years, the ORs and 95% CIs of those aged 35.0-44.9, 45.0-54.9, 55.0-64.9, and ≥65.0 years were 4.73 (3.47-6.46), 15.61 (11.60-21.00), 41.39 (30.76-55.70) and 90.04 (66.58-121.77), respectively. The primary multimorbidity patterns among adults in Shaanxi were cardiovascular-metabolic multimorbidity (5.4%), viscero-articular multimorbidity (1.0%), and respiratory multimorbidity (0.3%). 【Conclusion】 More than one in ten adults in Shaanxi Province had multimorbidity, and the predominant pattern of multimorbidity was cardiovascular-metabolic multimorbidity. The prevention and control of non-communicable diseases should be reinforced in middle-aged and older people, males, people living in the urban, and overweight or obese people. More attention should be paid to the prevention and control of cardiovascular-metabolic diseases.

【Objective】 To evaluate the dietary quality with the dietary balance index (DBI_16) and the association between dietary quality and bone mass among middle-aged and elderly people in Gansu Province so as to provide evidence for improving dietary quality and bone health status of Gansu population. 【Methods】 Based on the information of the type and quantity of food intake and the bone mass of middle-aged and elderly people aged 35 years and above collected by the Gansu Project in the Regional Ethnic Cohort Study in Northwest China, DBI_16 was used to evaluate the intake level of cereals, vegetables, fruits, milk, beans, fish and shrimp, eggs and other foods, and the degree of inadequate, excessive and unbalanced dietary intake of the participants. Multiple linear regression was used to evaluate the associations of three component indexes of DBI_16, high bound score (DBI_HBS), low bound score (DBI_LBS), diet quality distance (DBI_DQD), and seven single indexes of DBI_16 with bone mass. 【Results】 Analyses of the dietary and bone mass data of 11,840 participants showed that 44.8% of participants consumed excessive amounts of cereals compared to the dietary recommendation. 96.3%, 90.6%, 90.1%, 71.9%, 95.1% and 60.3% of participants’ intake of vegetables, fruits, milk, soybeans, fish and shrimp, and eggs, respectively, were inadequate. 47.7% participants consumed less than 10 types of food. 2.3% participants’ DBI_LBS levels were appropriate. 54.7% participants’ DBI_HBS levels were appropriate. Only 1.2% participants’ DBI_DQD reached a balanced level. The bone mass level in the study population was (2.5±0.6) kg [(2.8±0.5) kg for men and (2.3±0.5) kg for women]. After adjusting for sociodemographic characteristics, lifestyle, total dietary energy intake and body mass index, DBI_LBS and DBI_DQD were negatively associated with bone mass [β and 95% CI was -0.002 01 (-0.003 62--0.000 40) and -0.001 76 (-0.003 09--0.000 43), respectively]. 【Conclusion】 Dietary intake imbalance is common among middle-aged and elderly people in Gansu Province, and the more severe the dietary intake imbalance, the lower the bone mass level.