OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

ObjectiveTo explore the potential mechanism of Shenqi Jianxin Formula （参芪健心方） in the treatment of chronic heart failure （CHF） from the perspective of regulating mitochondrial autophagy via the PTEN-induced kinase 1 （PINK1）/E3 ubiquitin ligase （Parkin） pathway. MethodsMale SD rats were subjected to abdominal aortic constriction to establish the CHF model. Twenty-four successfully modeled rats were randomly divided into the model group， sacubitril/valsartan group， and low- and high-dose Shenqi Jianxin Formula groups， with 6 rats in each group. Six other rats were set as the sham surgery group， which were only separated the abdominal aorta and then closed the abdomen. Rats in the low-dose and high-dose Shenqi Jianxin Formula groups were given intragastric administration of Shenqi Jianxin Formula suspension at doses of 4.41 g/（kg·d） and 17.64 g/（kg·d）， respectively； the sacubitril/valsartan group received intragastric administration of sacubitril/valsartan sodium tablet suspension at 10 mg/（kg·d）； the sham surgery group and the model group were given normal saline at 10 ml/（kg·d） via intragastric gavage. The intervention lasted for 4 consecutive weeks. Cardiac function indices including left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were detected， and serum brain natriuretic peptide （BNP） content was measured. HE staining and Masson staining were used to observe myocardial histopathological changes. Transmission electron microscopy was employed to examine the ultrastructure of cardiac tissues. Quantitative real-time polymerase chain reaction （Rt-qPCR） was performed to determine the mRNA expressions of PINK1/Parkin pathway-related factors and autophagy-associated proteins including Beclin-1， p62， and microtubule-associated protein 1 light chain 3 （LC3） in myocardial tissues. ResultsCompared with the sham surgery group， the model group showed significant decreases in LVEF and LVFS levels， an increase in serum BNP content， down-regulated mRNA and protein expressions of PINK1， Parkin and Beclin-1 in cardiac tissues， up-regulated mRNA and protein expressions of p62， as well as significant reductions in LC3B mRNA expression， phosphorylated PTEN-induced kinase 1 （p-PINK1） and phosphorylated E3 ubiquitin ligase （p-Parkin） protein levels， and the ratio of microtubule-associated protein 1 light chain 3-Ⅱ to microtubule-associated protein 1 light chain 3-Ⅰ （LC3Ⅱ/LC3Ⅰ） （P＜0.05）. Pathological results revealed obvious myocardial cell edema， necrosis and degeneration， increased disorder of myocardial fiber arrangement， extensive inflammatory cell infiltration， moderate to severe mitochondrial swelling， a few mitochondrial vacuolar changes， and no obvious autophagy in the field of vision in the model group. Compared with the model group， all the above indicators were significantly improved in the high-dose Shenqi Jianxin Formula group and the sacubitril/valsartan group （P＜0.05）. Moreover， the improvement of each index in the high-dose Shenqi Jianxin Formula group was superior to that in the low-dose group （P＜0.05）. In the high-dose Shenqi Jianxin Formula group， myocardial myofibrils were arranged regularly with orderly orientation， the striated structure was clear， and necrotic cells significantly reduced. ConclusionShenqi Jianxin Formula can activate the PINK1/Parkin signaling pathway in myocardial tissues， enhance mitochondrial autophagy， and clear dysfunctional mitochondria， thereby improving cardiac function and delaying the progression of CHF.

Objective To analyze the risk factors of delayed bleeding after colonic polyp resection.Methods 700 patients with colonic polyps admitted to General medical treatment Hanzhong 3201 hospital from January 2022 to May 2023 were included as the research object,and all patients were treated with colonoscopy polypectomy.According to whether Post-procedural bleeding(PPB)occurred after operation,they were divided into two groups:the group with PPB occurrence(n=85 cases)and the group without PPB occurrence(n=615 cases).The general data,clinical data and operation-related data of the two groups were analyzed by univariate analysis.Multivariate Logistic regression was used to analyze the risk factors of postoperative PPB,and receiver operating characteristic curve was drawn to analyze the predictive value of risk factors.Results 700 patients in this study were all treated by colon polypectomy,and 85 patients(12.14％)developed PPB within 30 days after operation,that is,the incidence of PPB in this study was 12.14％.There was significant difference in sex,age,hypertension and treatment history of thrombosis between the two groups(P＜0.05).There was significant difference in the morphology,diameter and surgical methods between the two groups(P＜0.05).Multivariate Logistic regression analysis showed that polyp morphology(stalk),polyp diameter(＞1 cm),Endoscopic mucosal resection(EMR)and Endoscopic submucosal dissection(ESD)were the risk factors for postoperative PPB(P＜0.05).The ROC curve showed that the area under curve of polypoid-shaped is 0.653,95％CI is 0.616-0.688,the AUC of polyp-diameter is 0.741,95％CI is 0.707-0.773;and in the way of operation,the AUC of argon plasma coagulation/ESD is 0.730,95％CI is 0.713-0.802,the AUC of EMR/ESD is 0.541,95％CI is 0.498-0.584,the AUC of APC/EMR is 0.604 and 95％CI is 0.565-0.641.Conclusion Polyp pedicled,diameter＞1 cm,EMR and ESD are the risk factors for postoperative PPB.

Objective:To investigate the prenatal echocardiographic features of fetuses diagnosed with Ebstein anomaly (EA), identify prognostic factors affect the fetal and neonatal mortality, and evaluate the clinical value of the Simpson Andrews Sharland prognostic score (SAS prognostic score).Methods:A retrospective cohort study was conducted on 37 fetuses diagnosed with EA via prenatal and postnatal echocardiography at Guangdong Provincial People′s Hospital from June 2012 to June 2024. The echocardiographic features of EA patients were summarized. According to the patients′ survival statuses during the fetal and neonatal periods, they were divided into survival group and death group for a comparative analysis of key echocardiographic parameters, as well as SAS prognostic score. Also, receiver operator characteristic (ROC) curve was employed to assess the predictive abilities of various indicators. Finally, based on the medium-and long-term prognostic outcomes of EA cases, the predictive value of the SAS system was evaluated. The t test, Mann-Whitney U test, and Fisher exact test were used for group comparison. Results:Regarding the 37 EA cases, the gestational age at the initial diagnosis was (29±4) weeks. All of EA fetuses exhibited echocardiographic characterized by tricuspid regurgitation (TR) originating below the native tricuspid annulus with the severity varied, accompanied by manifestations such as right atrial enlargement. Of all cases, 5 cases (14%) died prenatally, and 32 cases (86%) were born alive. Postnatally, 4 cases died preoperatively, 1 case died postoperatively, and 27 cases survived. Compared with the survival group, the death group had a significantly higher average SAS prognostic score (6.9±1.1 vs. 2.0±1.5, t=9.17, P<0.001), right atrium (RA) to left atrium (LA) transverse diameter ratio (2.0±0.5 vs. 1.3±0.2, t=4.87, P=0.001) and TR area to RA area ratio (0.8±0.2 vs. 0.4±0.2, t=5.27, P<0.001). According to the ROC analysis, the optimal predictive value indicators are RA to LA transverse diameter ratio (AUC=0.93, 95% CI 0.81-1.00) and the TR area-to-RA area ratio (AUC=0.93, 95% CI 0.85-1.00); the optimal cut-point values were 1.5 and 0.5, respectively. Of 32 born alive cases, 21 cases (66%) didn′t undergo surgery, 2 cases (6%) underwent bidirectional Glenn surgery, and one case (3%) underwent tricuspid valvuloplasty. All 17 cases with SAS score≤2 survived, while all 9 cases with SAS score≥6 died. Among the 11 cases with a score from 3 to 5, 8 cases achieved a biventricular outcome. Conclusions:The typical echocardiographic feature of EA fetuses is that the originating point of TR is below the native tricuspid annulus and the severity can vary. The SAS score is essential for tiered prognosis. When the SAS is 3-5, dynamic monitoring for TR and RA enlargement should be employed to help guide prenatal intervention and reduce fetal and neonatal mortality.

Aim To investigate the anti-Zika virus(ZIKV)mechanism of diterpenoid compound 9 from Euphorbia helioscopia in vitro.Methods The cytotox-icity of compound 9 was evaluated using the CCK-8 as-say.A ZIKV-infected Vero cell model was established,and the antiviral activity was assessed through RT-qPCR,plaque assay,Western blot,and immunofluores-cence.Furthermore,the mechanism of action was elu-cidated using multi-cell line validation,nanoparticle tracking analysis,cellular thermal shift assay,and mo-lecular docking.Results In Vero cells,compound 9 exhibited an EC50 of(3.95±0.15)μmol·L-1 and a CC50 of(272.12±8.56)μmol·L-1,demonstrating significantly higher antiviral efficacy than the positive control drug ribavirin(RBV).Its virus inactivation effect was time-dependent and could significantly re-duce viral load and plaque formation.Studies revealed that compound 9 altered the physicochemical properties of ZIKV particles,including reducing surface charge and increasing particle size distribution.Additionally,it significantly enhanced the thermal stability of the prM protein.Molecular docking analysis indicated that compound 9 formed a high-affinity interaction with the prM protein(binding energy:-38.52 kJ·mol-1)and stabilized its structure through hydrophobic interac-tions.Conclusion Compound 9 exerts in vitro anti-ZIKV activity by directly inactivating the virus,disrup-ting viral particle integrity,and targeting the prM pro-tein.

Objective:To investigate the prospective associations between plasma metabolites and the risks of all-cause and cause-specific mortality among Chinese adults.Methods:This study analyzed plasma metabolomics data from 2 183 healthy adults in the China Kadoorie Biobank (CKB), measured using targeted mass spectrometry. Cox proportional hazards regression models were used to examine the associations between 630 metabolites and the risk of all-cause mortality. Cause-specific hazard regression models evaluated the associations between metabolites and cardiovascular disease (CVD) risks, cancer, and other-cause mortality. Stepwise regression was used to identify key metabolites independently associated with all-cause mortality, and the area under the receiver operating characteristic curve (AUC) was calculated to assess the improvement in predictive performance when these metabolites were added to traditional risk prediction models.Results:The mean age of the participants was (53.2±9.8) years, 65.1% of whom were female. During a median follow-up of 14.5 years, 231 deaths occurred. A total of 44 metabolites were significantly associated with the risk of all-cause mortality [false discovery rate (FDR)-adjusted P<0.05], primarily including triglycerides, ceramides, and amino acids. Additionally, 29 and 15 metabolites were found to be associated with cancer and other-cause mortality, respectively, but no metabolites were significantly associated with CVD mortality after FDR corrections. Adding 14 metabolites independently associated with all-cause mortality into the traditional prediction model significantly improved its predictive performance. Specifically, incorporating metabolites into the traditional model, which already included laboratory biomarkers, increased the AUC to 0.798 (95% CI: 0.755-0.843), an improvement of 0.088 compared to the traditional model ( P<0.001). Conclusions:Multiple metabolites are significantly associated with mortality risk and can substantially improve the accuracy of mortality risk prediction models. These findings provide new insights into the physiological mechanisms of aging and offer valuable clues for personalized health risk assessment.

Objective:To analyze the epidemiological characteristics and trend of hospitalization of the patients with herpes zoster in Beijing from 2017 to 2022.Methods:In this retrospective study, the information of hospitalization of herpes zoster patients were collected from all medical institutions at the first level and above in Xicheng, Changping, and Miyun districts of Beijing. The age and gender specific hospitalization rates and age-standardized hospitalization rates were calculated. Joinpoint regression model was used to explore the trend of the hospitalization rates, and the influencing factors of the hospital stay length and complications were analyzed.Results:The age-standardized hospitalization rate of the patients with herpes zoster was 10.82/100 000-18.43/100 000 in Beijing from 2017 to 2022 [annual percent change (APC) =5.86%, 95% CI: -2.80%-15.98%]. The age-standardized hospitalization rate of the cases with herpes zoster as the main diagnosis showed an upward trend (APC=11.35%, 95% CI: 7.21%-16.23%). The age-standardized hospitalization rate showed an upward trend in women (APC=14.34%, 95% CI: 7.95%-22.37%). The hospitalization rate showed a downward trend in age group 30-39 years (APC=-24.92%, 95% CI: -48.56% - -1.85%) and showed upward trends in age group 70-79 years and 80-109 years (APC=23.18%, 95% CI: 13.53%-35.58%; APC=4.90%, 95% CI: 1.18%-9.19%). Complications occurred in 66.28% (680/1 026) of the patients. The median hospital stay length was 9 (5,15) days, and the patients with high age (≥80 years) and two or more complications had longer hospital stay, which were 12 (6, 23) and 14 (7, 27) days respectively ( P<0.001). Conclusions:The hospitalization rate in women and the elderly aged ≥70 years with herpes zoster as the main diagnosis showed upward trends in Beijing in recent years. The elderly aged ≥80 years usually had longer hospital stay, showing a relatively disease burden level. More attention should be paid to development of intervention strategies, such as vaccine, for this population.

Objective:To evaluate the safety and feasibility of double-port laparoscopic cholecystectomy (LC) combined with transcystic common bile duct (CBD) exploration using ultrafine choledochoscopy on patients with gallbladder stones and common bile duct stones.Methods:Clinical data of 35 patients undergoing double-port LC combined with transcystic CBD exploration using ultrafine choledochoscopy in Anhui No.2 Provincial People’s Hospital from December 2021 to June 2024 were retrospectively analyzed, including 8 males and 27 females, aged (45.8±18.1) years. In all patients, the diameter of the gallbladder duct was greater than 3 mm, the maximum diameter of the stones was less than 10 mm, and the number of stones was less than 5, and the gallbladder ducts were normal. Magnetic resonance cholangiopancreatography (MRCP) was used to measure the diameter of CBD, the number and the maximum diameter of stones. The operative time, intraoperative blood loss, postoperative anal exhaust time, postoperative hospital stay and complications (including abdominal infection, biliary tract infection, bile leakage, bleeding, etc.) of all patients were analyzed. The incidence of bile duct stenosis, residual stone or stone recurrence were followed up by telephone or outpatient review.Results:MRCP measurement indicated that the common bile duct diameter of patients was (8.1±1.3) mm. Single CBD stone occurred in 27 cases (77.1%, 27/35), and the mean maximum diameter of CBD stones was (3.9±1.3) mm. All patients successfully underwent the procedure. The operative time was (80.1±10.9) min, the intraoperative blood loss was (25.5±10.2) ml, the recovery time of postoperative anal exhaust was (17.3±4.7) h, and the postoperative hospital stay was (2.5±0.6) d. There were no complications such as abdominal and biliary tract infection, bile leakage and bleeding. All patients were followed up for 1-30 months, with a median follow-up time of 12 months. No biliary stricture, residual stones or recurrence occured during the follow-ups.Conclusion:In selected cases, double-port LC combined with transcystic CBD exploration using ultrafine choledochoscopy could be safe and feasible, with less trauma, quick recovery and short operative time.

In protein engineering, while computational models are increasingly used to predict mutation effects, their evaluations primarily rely on high-throughput deep mutational scanning (DMS) experiments that use surrogate readouts, which may not adequately capture the complex biochemical properties of interest. Many proteins and their functions cannot be assessed through high-throughput methods due to technical limitations or the nature of the desired properties, and this is particularly true for the real industrial application scenario. Therefore, the desired testing datasets, will be small-size (∼10-100) experimental data for each protein, and involve as many proteins as possible and as many properties as possible, which is, however, lacking. Here, we present VenusMutHub, a comprehensive benchmark study using 905 small-scale experimental datasets curated from published literature and public databases, spanning 527 proteins across diverse functional properties including stability, activity, binding affinity, and selectivity. These datasets feature direct biochemical measurements rather than surrogate readouts, providing a more rigorous assessment of model performance in predicting mutations that affect specific molecular functions. We evaluate 23 computational models across various methodological paradigms, such as sequence-based, structure-informed and evolutionary approaches. This benchmark provides practical guidance for selecting appropriate prediction methods in protein engineering applications where accurate prediction of specific functional properties is crucial.

Animal experiments are crucial in evaluating the preclinical safety and efficacy of new dental materials, drugs, instruments, and equipment by identifying and eliminating potential health risks to humans. An international team of several dental experts formulated a guideline named Preferred Reporting Items for Animal Studiesin Endodontology (PRIASE) 2021. Consisting of 11 domains, 43 individual items, and a flowchart. PRIASE provides guidance for animal experiments in dentistry and improves the quality of experiment design and reporting. This work introduces the process and basic content of the guideline and interprets the key items of its checklist with specific examples to provide reference for the reporting of animal experiment in dentistry in China.
Animals ; Animal Experimentation/standards* ; Checklist ; China ; Endodontics ; Guidelines as Topic ; Research Design