Objective To investigate the effect of angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and AngII receptor (ATR) gene polymorphisms combined with climatic factors on the incidence of essential hypertension (EH) in Tibetan population in Gannan area. Methods A follow-up study was conducted to select 671 Tibetan people in Gannan area who were physically examined in April 2019 at the Health Management Center of the Second Hospital of Lanzhou University and agreed to be enrolled as a fixed cohort, and the blood pressure values of the enrolled subjects were measured after 3.5 years of follow-up, and a total of 501 cases were obtained. At the same time, the peripheral blood of all subjects was collected and the polymorphisms of AGT, ACE and ATR genes were detected by gene chip technology, and the possible interactions were analyzed by logistic regression model, fork generation method and multifactor-dimensionality reduction (MDR). Results Sunshine time was a protective factor for the incidence of hypertension in the Tibetan population of Gannan (OR=0.781), while relative humidity (OR=1.182), air pressure (OR=1.338) and temperature (OR=1.449) were the risk factors for the incidence of hypertension. According to the results of partial correlation analysis, temperature had no effect on the incidence of hypertension after controlling air pressure. There was an additive interaction between high air pressure and the polymorphisms of rs699 (OR=1.650, 95%CI: 1.293-2.399, P<0.001) and rs5049 (OR=1.711, 95%CI: 1.337-4.920, P<0.001) genes of AGT gene; there was a multiplicative interaction between relative humidity and rs699 (OR=0.472, 95%CI: 0.120-0.783, P<0.05);there was a multiplicative interactions between the altitude ≥ 3000m and rs699 (OR=1.503, 95%CI: 1.220-3.174, P<0.01), rs5049 (OR=1.673, 95%CI: 1.380-3.961, P<0.001) or rs2148582 (OR=0.519, 95%CI: 0.284-0.716, P<0.05).However, there was no interaction between climatic factors and ACE or ATR gene polymorphisms on the incidence of hypertension. Conclusion Climatic factors and altitude ≥3 000 m are closely related to the incidence of hypertension in the Tibetan population of Gannan area, and the interaction between AGT gene polymorphisms and climatic factors affects the incidence of hypertension in the population of this area.

ObjectiveTo investigate the alleviating effect of calcium cyanamide （CaCN₂） soil fumigation on replanting problems of Rehmannia glutinosa. MethodsNewly soil （NP） was used as the control group， while three treatment groups were established： replanted soil （RP）， newly soil treated with CaCN₂ （120 g·m²， tillage depth 25 cm） （NPCC）， and replanted soil treated with CaCN₂ （RPCC）. R. glutinosa was cultivated in all groups. At harvest， the tuber agronomic traits （number of enlarged roots， maximum root diameter， fresh weight， dry weight） were measured. The content of catalpol and rehmannioside D was quantified by ultra-high-performance liquid chromatography （UPLC） to evaluate medicinal quality. Rhizosphere soil available nutrients and enzyme activities were analyzed by assay kits. The community structure and composition of fungi and bacteria in rhizosphere soil were assessed via internal transcribed spacer 2 （ITS2） sequencing and 16S rDNA sequencing， respectively. ResultsCompared with NP， the RP group showed obviously reduced in tuber agronomic traits and quality indicators （P0.05）. However， the RPCC group showed significant improvement in agronomic traits and a notable increase in rehmannioside D content compared to RP （P0.05）. The contents of available phosphorus and potassium in RPCC and NP groups were obviously lower than those in RP （P0.05）. The polyphenol oxidase soil （S-PPO） activity in RP was obviously lower than in NP （P0.05）， while sucrose soil （S-SC）， acid phosphatase soil （S-ACP）， and S-PPO activities in RPCC were obviously higher than in RP （P0.05）. Microbial richness and diversity in RP were obviously higher than in NP （P0.05）， whereas no significant differences were observed between the RPCC and NP. The relative abundances of fungal genera Nectria， Myrothecium， Tomentella， and bacterial genus Skermanella were obviousl lower in RPCC and NP than in RP （P0.05）. Correlation analysis that S-ACP activity was positively correlated with the content of rehmannioside D （P0.05）. Fungal genera Engyodontium and Alternaria， and bacterial genera Pir4 lineage， Pirellula， Methyloversatilis， Brevundimonas， Ralstonia， and Acidibacter were obviously positively correlated with tuber dry weight （P0.05）. Conversely， fungal genera Pseudaleuria， Nectria， Haematonectria， Ceratobasidium， and bacterial genera Streptomyces， Skermanella， RB41， Gemmatimonas， and Bacillus were obviously negatively correlated with dry weight （P0.05）. The fungal genus Alternaria and bacterial genera Brevundimonas， Ralstonia， Acidibacter， and Dongia showed positive correlations with medicinal quality of R.glutinosa tuber， while fungal genera Pseudaleuria， Nectria， Stachybotrys， Fusarium， Gibberella， Ceratobasidium， and bacterial genera Sphingomonas， Skermanella， RB41， Gemmatimonas， and Bacillus were obviously negatively correlated （P0.05）. ConclusionCaCN₂ soil fumigation can significantly improve enzyme activities in replanted Rehmannia rhizosphere soil， enhance the utilization of available nutrients， reshape microbial community structure of replanted R.glutinosa at the family and genus level， and notably improve tuber agronomic traits and medicinal quality. This study provides a novel approach to alleviating replanting problems and offers insights for the integrated development of standardized cultivation techniques， including soil disinfection， nutrient-targeted regulation， and microbial inoculant application.

OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

Dental caries, a chronic disease characterized by tooth decay, occupies the second position in terms of disease burden and is primarily caused by cariogenic bacteria, especially Streptococcus mutans, because of its acidogenic, aciduric, and biofilm-forming capabilities. Developing novel targeted anti-virulence agents is always a focal point in caries control to overcome the limitations of conventional anti-virulence agents. The current study represents an up-to-date review of in silico approaches of drug design against dental caries, which have emerged more and more powerful complementary to biochemical attempts. Firstly, we categorize the in silico approaches into computer-aided drug design (CADD) and AI-assisted drug design (AIDD) and highlight the specific methods and models they contain respectively. Subsequently, we detail the design of anti-virulence drugs targeting single or multiple cariogenic virulence targets of S. mutans, such as glucosyltransferases (Gtfs), antigen I/II (AgI/II), sortase A (SrtA), the VicRK signal transduction system and superoxide dismutases (SODs). Finally, we outline the current opportunities and challenges encountered in this field to aid future endeavors and applications of CADD and AIDD in anti-virulence drug design.

Objective: To explore the intervention effect of schoolbased horticultural activities combined with fancy rope skipping on the health behaviour of fourthgrade primary school students, so as to provide a reference method for childrens health promotion. Methods: Eightyfive primary school students in grade 4 of a primary school in Changsha City were selected in March 2023 by using multistage cluster random sampling method and randomly divided into an intervention group (43 students) and a control group (42 students). The intervention group implemented a 12week comprehensive intervention of "schoolbased gardening combined with pattern skipping, once a week 90 min/time including routine practice (weeks 1-5,7-11; the contents were vegetable and plant management, theoretical knowledge learning of pattern skipping practice, etc.) and parent-child activities (weeks 6 and 12; vegetable salad making, synchronized jumping rope competition, etc.), and the control group maintained the regular curriculum. Moderate to vigorous physical activity (MVPA) and sleep duration were monitored by accelerometers in grade 4 primary school students, combined with questionnaires to assess fruit and vegetable intake and video screen behaviour, and generalised estimating equations were used to analyse the data. Results: After the intervention, there were interaction effect for school day MVPA time (Wald χ2group×time=8.27), vegetable intake (Wald χ2group×time=4.35), and video screen time (Wald χ2group×time=13.27) in both groups (P<0.01). After the intervention, the MVPA time in the intervention group increased from 30.00 (20.00,60.00) min to 40.00 (30.00, 60.00) min from school day; vegetable intake increased from 99.85 (33.95, 229.48) g to 190.15 (131.05, 279.48) g; and video screen time increased from 225.00 (110.00, 313.75) min to 60.00 (30.00, 142.50) min (Z=-4.51, -2.00, -3.84, P<0.05). However, there were no statistical differences in MVPA time, fruit intake and sleep time before and after intervention in the intervention group on weekends (Z=-1.35, -0.85, -0.24, P>0.05). Conclusion Schoolbased horticultural activities combined with an integrated intervention of fancy rope skipping can significantly improve physical activity, vegetable intake and video screen behaviours on weekdays in grade 4 primary school children, in order to provide a basis for multidimensional health promotion.

Objective:To explore the clinical utility of peripheral immune-inflammatory markers in predicting late-life depression with cognitive impairment(LLD+ CI + ). Methods:A cross-sectional study was conducted between January 2020 and December 2021, collecting demographic data, peripheral blood inflammatory markers, and cognitive function scores from 40 patients with LLD+ CI + , 38 patients with late-life depression without cognitive impairment(LLD+ CI -), and 26 healthy controls(HCs). Logistic regression analysis and receiver operating characteristic(ROC)curve analysis were employed to assess the value of peripheral blood inflammatory markers in differentiating LLD+ CI + . Results:Patients with LLD+ CI + exhibited significantly different levels of lymphocytes, C-reactive protein(CRP), systemic immune-inflammation index(SII), systemic inflammation response index(SIRI), neutrophil-to-high-density lipoprotein cholesterol ratio(NHR), and neutrophil-to-lymphocyte ratio (NLR)compared with the LLD+ CI - group and the HGs group( F=4.000, 11.642, 13.541, 10.441, 6.623, 4.193; P=0.022, 0.003, 0.001, 0.005, 0.036, 0.018). The multivariate logistic regression analysis of factors influencing LLD+ CI + revealed that elevated levels of CRP( OR=4.933, 95% CI: 1.385-17.563, P=0.014), SII( OR=5.534, 95% CI: 1.336-22.927, P=0.018), and NLR( OR=3.386, 95% CI: 1.470-7.797, P=0.004)constitute risk factors for geriatric depression with cognitive impairment, while an increased lymphocyte count( OR=0.206, 95% CI: 0.058-0.725, P=0.014)serves as a protective factor.Further analysis identified CRP, lymphocytes, SII, and NLR as significant predictors for LLD+ CI + , with areas under the curve (AUC) values of 0.849(95% CI: 0.760-0.934), 0.847(95% CI: 0.761-0.933), 0.860(95% CI: 0.777-0.943), and 0.857(95% CI: 0.777-0.938), respectively, in distinguishing LLD with or without cognitive impairment. Conclusions:Peripheral immune-inflammatory markers represent an economical and effective approach for investigating the pathophysiological changes and predictive factors associated with LLD+ CI + .These findings provide valuable insights into the underlying mechanisms and potential therapeutic avenues.

To enhance the trustworthiness,security,and convenience of research data management and pro-mote the deep utilization of clinical research data,it introduces core technologies such as data sandboxing,ze-ro-trust architecture,elastic resource scheduling in cloud computing,and data lakes to construct a clinical research trusted data space with trusted management,resource interaction,and value co-creation capabilities.This trusted data space provides a secure and efficient platform for data processing and analysis through strict network access control,dynamic authentication,data anonymization,and digital watermarking technologies.It ensures the secure flow and precise traceability of research data throughout its lifecycle,effectively facilitating resource interaction and value co-creation.The implementation offers a valuable technical reference and practical guidance for other hospitals aiming to build trusted research data platforms.

Objective:To identify and validate secreted effector proteins of Chlamydia psittaci ( C. psittaci) through bioinformatic prediction and experimental verification, and to characterize their subcellular localization in host cells. Methods:Potential effector proteins were predicted using bioinformatics tools. Candidate effectors were fused to β-lactamase through the constructed expression vectors, and these vectors were transformed into C. psittaci. The secretion of these candidate effectors was evaluated by β-lactamase translocation assays. Eukaryotic expression vectors of confirmed effectors were transfected into host cells to determine their intracellular localization patterns. Results:Bioinformatic analysis identified 29 candidate effector proteins. Experimental validation confirmed the secretion of five effectors, with four exhibiting cytoplasmic localization and one displaying nuclear localization in host cells.Conclusion:This study characterizes five novel C. psittaci secreted effector proteins, providing critical insights for investigating the molecular pathogenesis of psittacosis.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.