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 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.

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 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.

Objective To investigate the impact of mitophagy,mediated by the long non-coding RNA SNHG16(LncRNA SNHG16)on diabetes-associated cognitive impairment(DCI).Methods 29 male C57BL/J mice were randomly divided into normal control(NC)group,DCI group and DCI+mitochondrial autophagy inhibitor(DCI+Mdivi-1)group.Morris water maze and new object recognition test were used to detect the cognitive function of mice,qRT-CPR was used to detect the expression of LncRNA SNHG16 and mitochondrial autophagy marker mRNA.Western blot were used to detect the expression of related protein.The mouse hippocampal neurons HT22 were divided into control(Con)group,high glucose(HG)group,HG+SNHG16 silencing(HG+sh-SNHG16)group and HG+no-load control(HG+sh-NC)group.CCK8 method and lactate dehydrogenase(LDH)method were used to detect neuronal damage.JC-1 method was used to detect mitochondrial membrane potential.Results Compared with NC group,the expression of LncRNA SNHG16 and the expression of autophagy-related gene 5,PTEN-induced putative kinase 1(PINK1),Parkin and microtubule associated protein light chain 3(LC3)Ⅱ/Ⅰ increased(P<0.05),while the expression of mitochondrial autophagy-related proteins P62 and mitochondrial outer membrane transposase 20(TOMM20)decreased in T2DM group.Compared with DCI group,the cognitive dysfunction of mice improved,and the expression level of LncRNA SNHG16 decreased in the DCI+Mdivi-1 group(P<0.05).The expressions of LncRNA SNHG16,LC3 Ⅱ/Ⅰ,PINK1 and Parkin were higher in HG group than in Con group(P<0.05),while the cell survival rate and TOMM20 protein expression were lower in HG group than in Con group(P<0.05).Silence of LncRNA SNHG16 can restore the activity of HT22 cells and mitochondrial membrane potential,and reduce the level of mitochondrial autophagy under HG condition.Conclusions The expression level of LncRNA SNHG16 was up-regulated in the hippocampus brain region of mice with diabetic cognitive dysfunction,and mitophagy was overactivated.Silencing of LncRNA SNHG16 inhibits mitophagy in hippocampal neurons and alleviates HG induced hippocampal neuronal damage.

Objective:To explore the effect of the forward moving pelvic floor exercise program in urinary incontinence management among patients undergoing radical prostatectomy.Methods:From June 2022 to January 2024, 150 patients undergoing radical prostatectomy of the Urology Surgery Department, the First Affiliated Hospital of Zhengzhou University were selected using convenience sampling. Patients were randomly divided into an observation group and a control group, with 75 cases in each group. Control group received conventional perioperative management for prostate cancer, while observation group implemented a forward moving pelvic floor exercise program in addition to conventional management. The incidence of urinary incontinence, urinary control capabilities before and after intervention (including maximum urinary flow rate, average urinary flow rate, voided urine volume, and residual urine volume), and quality of life scores [evaluated using the Chinese version of the Incontinence Quality of Life Questionnaire (I-QOL) ] were compared between two groups of patients.Results:The incidence of urinary incontinence of observation group was lower than that of control group. Furthermore, patients with urinary incontinence in observation group exhibited significantly lower urine leakage volume and fewer episodes of urinary incontinence over 24 hours at one month postoperatively compared to control group, with statistically significant differences ( P<0.05). There were no statistically significant differences in maximum urinary flow rate, average urinary flow rate, voided urine volume, or residual urine volume between the two groups before intervention ( P>0.05). Following intervention, both groups demonstrated increased maximum urinary flow rate, average urinary flow rate, and voided urine volume compared to baseline, with observation group exhibiting higher values than control group ( P<0.05), and residual urine volume of both groups decreased compared to baseline, with observation group showing lower values than control group, these differences were statistically significant ( P<0.05). The difference in I-QOL scores between the two groups before intervention was not statistically significant ( P>0.05). Following intervention, I-QOL scores decreased in both groups, but observation group had higher score than control group, and the difference was statistically significant ( P<0.05) . Conclusions:The forward moving pelvic floor exercise program effectively reduces the incidence of urinary incontinence in patients undergoing radical prostatectomy, alleviates the severity of incontinence, and improves both urodynamic outcomes and quality of life.

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

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.

Chronic thromboembolic pulmonary hypertension(CTEPH)is a severe form of pulmonary hypertension(PH),and is classified as the fourth major category of pulmonary arterial hypertension.CTEPH is primarily caused by chronic thrombosis,leading to the obstruction of blood flow in the pulmonary arteries and result ing in a sustained increase in pulmonary artery pressure.The unclear pathogenesis of CTEPH,however,means that its early diagnosis is challenging,treatment options are limited,and prognosis assessment is often inaccurate.In-depth research into these mechanisms will thus improve our understanding of the pathophysiological processes of CTEPH,and also provide a theoretical basis for developing new therapeutic strategies.This review focuses on the current method of establishing CTEPH rat models and their advantages and disadvantages,offering researchers a reference for selecting and constructing CTEPH rat models.