OBJECTIVE:Elevated blood pressure increases the risk of cardiovascular diseases.Isometric exercise training has been shown to significantly reduce resting blood pressure,but the factors influencing its effectiveness remain unclear,and specific application guidelines are yet to be established.This study aims to evaluate the impact of isometric exercise training on resting blood pressure through meta-analysis,explore its moderating factors,and provide evidence-based recommendations based on its dose-response relationship.METHODS:Following the PRISMA guidelines,a systematic search was conducted in PubMed,Embase,Cochrane Library,Scopus,and Web of Science databases using keywords"Isometric exercise training,""Systolic blood pressure,"and"Diastolic blood pressure,"covering literature up to September 2024.Randomized controlled trials involving isometric exercise training and resting blood pressure were included.Three independent researchers performed literature screening and data extraction,assessing bias risk and quality grades using the Risk of Bias 2.0 tool and GRADE framework.Main effect pooling,publication bias assessment,subgroup,and regression analysis were conducted using R software(version 4.3.4).RESULTS:A total of 28 articles(comprising 32 randomized controlled trials)involving 977 participants were included.(1)Meta-analysis results indicated that isometric exercise training significantly reduced resting systolic blood pressure(MD=-8.01,95％CI=-9.22 to-6.80,P＜0.01,I2=18.20％,low evidence grade)and diastolic blood pressure(MD=-3.46,95％CI=-4.64 to-2.28,P＜0.01,I2=0％,moderate evidence grade)compared to no exercise.(2)Subgroup analysis results revealed significant influences of gender,health status,exercise modality,frequency,intensity,duration,sets per session,rest duration,and baseline blood pressure on the main effects for both systolic(P＜0.01)and diastolic blood pressure(P＜0.05).(3)Regression analysis results did not show any significant influencing factors,but body mass index(β=-4.11,P=0.091)showed a significant negative trend on the main effect for systolic blood pressure.(4)No significant publication bias was observed in the meta-analysis results(P＞0.05).CONCLUSION:(1)Isometric exercise training significantly lowers systolic(low evidence grade)and diastolic(moderate evidence grade)blood pressure with clinically meaningful thresholds.(2)Participant characteristics(gender,health status,baseline blood pressure,and body mass index)and isometric exercise training protocols(modality,frequency,intensity,duration,cycle,sets per session,and rest duration)influence its antihypertensive effects.(3)The article recommends the optimal blood pressure management prescription:three sessions per week,with four sets per session,each set lasting 2 minutes with a 2-minute rest,at an intensity of 95％HRpeak using isometric wall squat exercises;the intervention period can be adjusted around a 6-week node.Future high-quality research is urgently needed to further validate and support these conclusions.

OBJECTIVE:Elevated blood pressure increases the risk of cardiovascular diseases.Isometric exercise training has been shown to significantly reduce resting blood pressure,but the factors influencing its effectiveness remain unclear,and specific application guidelines are yet to be established.This study aims to evaluate the impact of isometric exercise training on resting blood pressure through meta-analysis,explore its moderating factors,and provide evidence-based recommendations based on its dose-response relationship.METHODS:Following the PRISMA guidelines,a systematic search was conducted in PubMed,Embase,Cochrane Library,Scopus,and Web of Science databases using keywords"Isometric exercise training,""Systolic blood pressure,"and"Diastolic blood pressure,"covering literature up to September 2024.Randomized controlled trials involving isometric exercise training and resting blood pressure were included.Three independent researchers performed literature screening and data extraction,assessing bias risk and quality grades using the Risk of Bias 2.0 tool and GRADE framework.Main effect pooling,publication bias assessment,subgroup,and regression analysis were conducted using R software(version 4.3.4).RESULTS:A total of 28 articles(comprising 32 randomized controlled trials)involving 977 participants were included.(1)Meta-analysis results indicated that isometric exercise training significantly reduced resting systolic blood pressure(MD=-8.01,95％CI=-9.22 to-6.80,P＜0.01,I2=18.20％,low evidence grade)and diastolic blood pressure(MD=-3.46,95％CI=-4.64 to-2.28,P＜0.01,I2=0％,moderate evidence grade)compared to no exercise.(2)Subgroup analysis results revealed significant influences of gender,health status,exercise modality,frequency,intensity,duration,sets per session,rest duration,and baseline blood pressure on the main effects for both systolic(P＜0.01)and diastolic blood pressure(P＜0.05).(3)Regression analysis results did not show any significant influencing factors,but body mass index(β=-4.11,P=0.091)showed a significant negative trend on the main effect for systolic blood pressure.(4)No significant publication bias was observed in the meta-analysis results(P＞0.05).CONCLUSION:(1)Isometric exercise training significantly lowers systolic(low evidence grade)and diastolic(moderate evidence grade)blood pressure with clinically meaningful thresholds.(2)Participant characteristics(gender,health status,baseline blood pressure,and body mass index)and isometric exercise training protocols(modality,frequency,intensity,duration,cycle,sets per session,and rest duration)influence its antihypertensive effects.(3)The article recommends the optimal blood pressure management prescription:three sessions per week,with four sets per session,each set lasting 2 minutes with a 2-minute rest,at an intensity of 95％HRpeak using isometric wall squat exercises;the intervention period can be adjusted around a 6-week node.Future high-quality research is urgently needed to further validate and support these conclusions.

Objectives: . This study aimed to explore the role of the Pcdh15 gene in hearing maintenance and to examine the effects of its deficiency on cochlear structure, cochlear function, and hearing loss in mice. Methods: . CRISPR/Cas9 technology was used to generate Pcdh15 knockout (KO) mice. Auditory function was evaluated using hearing tests, while histological approaches were employed to assess morphological changes in cochlear hair cells and spiral ganglion neurons (SGNs). RNA sequencing (RNA-seq) was performed on cochlear tissue from postnatal day 18 (P18) wild-type (WT) and Pcdh15 KO mice to identify differentially expressed genes (DEGs). These DEGs were subjected to functional annotation and pathway analysis, with particular emphasis on oxidative phosphorylation (OXPHOS). Reactive oxygen species (ROS) levels were quantified using flow cytometry and DCFH-DA assays. Results: . Pcdh15 KO mice exhibited progressive sensorineural hearing loss, which worsened to profound deafness by P18. Notably, cochlear hair cells and SGNs showed substantial loss and pronounced morphological abnormalities, particularly within the basal high-frequency region. RNA-seq analysis identified 1,359 DEGs, including 1,024 downregulated and 335 upregulated genes. Pathway analysis indicated that Pcdh15 deficiency was associated with inhibition of the OXPHOS pathway, potentially disrupting mitochondrial respiratory chain complexes I, III, IV, and V and thereby impairing energy production and ATP metabolism. In addition, early-stage cochleae from KO mice demonstrated elevated ROS levels and increased oxidative stress, suggesting that redox imbalance may contribute to hearing damage. Conclusion . Pcdh15 plays a critical role in hearing maintenance. Its deficiency is associated with severe hearing loss and marked cochlear abnormalities, which are linked to inhibition of OXPHOS, disruption of energy metabolism, and exacerbation of oxidative stress. Together, these findings provide new insights into the mechanisms underlying hearing loss and suggest potential targets for therapeutic intervention.

ObjectiveTo systematically quantify the multidimensional effect of virtual reality-based exergaming (VREG) on health outcomes among individuals with cognitive impairment under the framework of the International Classification of Functioning, Disability and Health (ICF). MethodsMeta-analysis was conducted in accordance with the PRISMA statement. PubMed, Cochrane Library, Embase, Scopus, Web of Science, CNKI, Wanfang Data and VIP were researched for randomized controlled trials (RCTs) investigating VREG for cognitive impairment, with the search deadline set on February 1, 2026. The Cochrane Risk of Bias 2.0 tool was adopted to evaluate the methodological quality of included studies. A three-level meta-analytic model was implemented with R 4.4.2. The GRADE framework was further used to rate the certainty of pooled evidence. ResultsA total of 22 RCTs were included. VREG might improve global cognitive function (SMD = 0.69, 95%CI 0.11 to 1.28, P = 0.022), memory (SMD = 0.47, 95%CI 0.07 to 0.87, P = 0.023), attention (SMD = 0.62, 95%CI 0.23 to 1.01, P = 0.004), executive function (SMD = 0.42, 95%CI 0.09 to 0.75, P = 0.013), balance (SMD = 0.54, 95%CI 0.07 to 1.00, P = 0.027), muscle strength (SMD = 0.63, 95%CI 0.37 to 0.88, P = 0.001), mobility (SMD = 0.29, 95%CI 0.04 to 0.54, P = 0.024) and quality of life (SMD = 0.29, 95%CI 0.03 to 0.56, P = 0.029). No significant effect was observed for depressive symptoms, comprehensive physical fitness and fall risk (all P > 0.05). Subgroup and meta-regression analyses indicated that session duration < 45 minutes produced the largest improvement in attention (SMD = 0.95, 95%CI 0.55 to 1.34, P < 0.001); intervention cycles of twelve to 24 weeks were optimal for mobility (SMD = 0.85, 95%CI 0.44 to 1.25, P < 0.001); age negatively correlated to balance improvement (β = -0.11, 95%CI -0.20 to -0.02, P = 0.020), suggesting less intervention benefits among older participants. ConclusionVREG is an effective non-pharmacological intervention to improve multidimensional physical and mental health in people with cognitive impairment. Protocols featuring short single sessions with long-term duration should be prioritized.

ObjectiveTo observe the clinical efficacy of tonifying kidney and replenishing essence on asthenozoospermia patients with the syndrome of kidney essence deficiency and the effects of this method on the adenosine 5′-monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin complex 1 （mTORC1） signaling pathway. MethodsSeventy-two eligible asthenozoospermia patients with the syndrome of kidney essence deficiency treated in the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from February 2023 to January 2024 were selected and randomly assigned into an observation group and a control group， with 36 patients in each group. The observation group received oral administration of Guilu Tianjing capsules， while the control group received oral administration of L-carnitine oral solution. The treatment course lasted for 4 weeks in both groups. The observed indicators included sperm progressive motility rate （PR）， total sperm motility （PR+NP）， percentage of normal mitochondrial membrane potential （MMP）， and traditional Chinese medicine （TCM） symptom scores before and after treatment in both groups. A three-month follow-up was instituted to record the conception status of the patients’ spouses. Additionally， eight patients were randomly selected from the eligible patients in the observation group， and four healthy males with normal semen routine examination results were included as the control group for the determination of protein expression. Western blotting was conducted to assess the expression of AMPK， phosphorylated （p）-AMPK， regulatory-associated protein of mTOR （RAPTOR） and p-RAPTOR， and PTEN-induced putative kinase 1 （PINK1） in sperms from the observation group before and after treatment， as well as in the sperms of the control group. ResultsThe pregnancy rate of spouses in the observation group was 9.09% （3/33）， which was higher than that （3.33%， 1/30） in the control group. The total response rate was 84.8% （28/33） in the observation group and 66.7% （20/30） in the control group， with no statistically significant difference. After treatment， both groups were improved considering PR， PR+NP， MMP， and TCM symptom scores （P<0.01）. Moreover， the observation group exhibited more pronounced decreases in TCM symptom scores than the control group （P<0.05）， while the changes in PR， PR+NP， and MMP showed no statistical significance between groups. Compared with the control group， the asthenozoospermia group exhibited upregulations in phosphorylation levels of AMPK and RAPTOR and protein level of PINK （P<0.01）. The administration of Guilu Tianjing Capsules led to downregulations in the phosphorylation levels of AMPK and RAPTOR and protein level of PINK1 （P<0.01）. However， the protein levels of AMPK and RAPTOR demonstrated no significant difference between before and after treatment. During the study period， neither group of patients exhibited any notable adverse reactions. ConclusionGuilu Tianjing capsules can enhance the sperm motility and percentage of normal mitochondrial membrane potential in asthenozoospermia patients with the syndrome of kidney essence deficiency by downregulating the AMPK/mTORC1 signaling pathway， lowering the protein level of PINK1， and inhibiting excessive activation of mitophagy.

ObjectiveTo observe the clinical efficacy of tonifying kidney and replenishing essence on asthenozoospermia patients with the syndrome of kidney essence deficiency and the effects of this method on the adenosine 5′-monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin complex 1 （mTORC1） signaling pathway. MethodsSeventy-two eligible asthenozoospermia patients with the syndrome of kidney essence deficiency treated in the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from February 2023 to January 2024 were selected and randomly assigned into an observation group and a control group， with 36 patients in each group. The observation group received oral administration of Guilu Tianjing capsules， while the control group received oral administration of L-carnitine oral solution. The treatment course lasted for 4 weeks in both groups. The observed indicators included sperm progressive motility rate （PR）， total sperm motility （PR+NP）， percentage of normal mitochondrial membrane potential （MMP）， and traditional Chinese medicine （TCM） symptom scores before and after treatment in both groups. A three-month follow-up was instituted to record the conception status of the patients’ spouses. Additionally， eight patients were randomly selected from the eligible patients in the observation group， and four healthy males with normal semen routine examination results were included as the control group for the determination of protein expression. Western blotting was conducted to assess the expression of AMPK， phosphorylated （p）-AMPK， regulatory-associated protein of mTOR （RAPTOR） and p-RAPTOR， and PTEN-induced putative kinase 1 （PINK1） in sperms from the observation group before and after treatment， as well as in the sperms of the control group. ResultsThe pregnancy rate of spouses in the observation group was 9.09% （3/33）， which was higher than that （3.33%， 1/30） in the control group. The total response rate was 84.8% （28/33） in the observation group and 66.7% （20/30） in the control group， with no statistically significant difference. After treatment， both groups were improved considering PR， PR+NP， MMP， and TCM symptom scores （P<0.01）. Moreover， the observation group exhibited more pronounced decreases in TCM symptom scores than the control group （P<0.05）， while the changes in PR， PR+NP， and MMP showed no statistical significance between groups. Compared with the control group， the asthenozoospermia group exhibited upregulations in phosphorylation levels of AMPK and RAPTOR and protein level of PINK （P<0.01）. The administration of Guilu Tianjing Capsules led to downregulations in the phosphorylation levels of AMPK and RAPTOR and protein level of PINK1 （P<0.01）. However， the protein levels of AMPK and RAPTOR demonstrated no significant difference between before and after treatment. During the study period， neither group of patients exhibited any notable adverse reactions. ConclusionGuilu Tianjing capsules can enhance the sperm motility and percentage of normal mitochondrial membrane potential in asthenozoospermia patients with the syndrome of kidney essence deficiency by downregulating the AMPK/mTORC1 signaling pathway， lowering the protein level of PINK1， and inhibiting excessive activation of mitophagy.

Objectives:To investigate the predictive value of Murray's law-based quantitative flow ratio(μQFR)in side branches for long-term clinical prognosis in patients with non-left main bifurcation lesions who underwent simple main branch stenting,and to provide a potential functional assessment standard for intervention decision-making on coronary bifurcation lesions.Methods:A retrospective analysis was conducted in 408 patients with non-left main bifurcation lesions who underwent simple main branch stenting at Lianyungang First People's Hospital and Nanjing First Hospital between July 2018 and January 2021.The study utilized third-generation QFR software to analyze pre-and post-procedure anatomical and functional parameters of the target lesion's main branch and key branches.The primary endpoint was target vessel failure(TVF)events during the 3-year follow-up.Patients were stratified into TVF and non-TVF groups.Baseline characteristics,procedural data,and pre-/post-procedural parameters of target vessels were compared between groups.Multivariable Cox regression was performed to identify predictors of TVF.Diagnostic efficacy of predictors was evaluated using area under the receiver operating characteristic(ROC)curve(AUC)with DeLong's method for comparison.Patients were dichotomized based on the optimal cutoffof post-procedural side branch μQFR,with TVF incidence rates compared via Cox regression and Kaplan-Meier analysis.Results:During 3-year follow-up,54 patients(13.2%)experienced TVF(TVF group),data were compared with 354 patients(86.76%)without TVF(non-TVF group).The TVF group showed higher post-procedural side branch diameter stenosis([32.93±17.80]%vs.[22.62±11.96]%,P<0.001)and lower μQFR(0.80±0.10 vs.0.89±0.07,P<0.001).Multivariate Cox regression identified higher post-procedural side branch μQFR as an independent protective factor against 3-year TVF(per 0.01 increase:HR=0.903,95%CI:0.850-0.959,P<0.001).ROC curves indicated that post-procedural side branch μQFR had moderate diagnostic efficacy for predicting 3-year TVF(AUC=0.769,95%CI:0.678-0.861,P<0.001),with a significantly higher AUC value than post-operative side branch area stenosis and minimal lumen diameter(both P<0.001),the optimal cutoffvalue was 0.84.Multivariate Cox regression and Kaplan-Meier survival analysis revealed markedly higher 3-year TVF rates in patients with μQFR≤0.84 compared to patients with μQFR>0.84(HR=4.007,95%CI:2.342-6.855,P<0.001;28.3%vs.7.9%,log-rank P<0.001).Conclusions:For patients with bifurcation lesions not involving the left main,the immediate post-procedural side branch μQFR could better predict 3-year TVF than anatomical indices.Maintaining post-stenting side branch μQFR>0.84 may optimize clinical outcomes when using a single-stent strategy.

Objective:To explore the effect of vitamin D supplement on chronic musculoskeletal pain (CMP) in patients with ankylosing spondylitis (AS) through a cohort study and provide evidence for optimizing vitamin D supplement strategies in AS management.Methods:Based on the large-scale prospective cohort of the UK Biobank, a total of 1 497 middle-aged and older patients diagnosed with AS were included. Patients were categorized into three groups according to their baseline vitamin supplements usage: non-vitamin supplement group ( n=978), vitamin D supplement group ( n=65), and other vitamin supplements group ( n=454). The occurrence of CMP was obtained by baseline pain survey and follow-up data from 2019—2020 and 2022—2023. A generalized linear mixed model (GLMM) was used to analyze the association between vitamin D supplement and CMP occurrence, with odds ratio ( OR) and its 95% confidence intervals ( CI) calculated. To verify robustness of the study findings, propensity score matching was employed to match participants in the vitamin D supplementation group with those in the non-vitamin supplement group and the other vitamin supplements group for sensitivity analysis. Results:After adjusting for confounding factors such as demographic characteristics, lifestyle, and co-morbidities, GLMM analysis did not find significant association between vitamin D supplement and the risk of CMP occurrence in AS patients [ OR(95% CI)=0.85(0.48, 1.48), P=0.555]. However, GLMM analysis indicated that male AS patients had a lower likelihood of developing CMP compared to female patients [ OR(95% CI)=0.69(0.56, 0.86), P<0.001]. Additionally, current smoking [ OR(95% CI)=1.46(1.06, 2.03), P=0.022] and poorer overall health status-categorized as general [ OR(95% CI)=2.32(1.85, 2.90)] or poor [ OR(95% CI)=2.31(1.68, 3.18), P<0.001] were associated with an increased risk of CMP occurrence. In the sensitivity analysis, no significant association was observed between vitamin D supplement and CMP. Conclusion:Vitamin D supplement does not reduce the risk of CMP occurrence in middle-aged and old AS patients. However, female, smoking, and poor overall health status are identified as risk factors for CMP in AS patients. Future research should focus on large-scale real-world studies, particularly in younger AS populations, to further investigate the relationship between vitamin D supplement and CMP, thereby providing more targeted intervention strategies.

Objective:To establish a rapid and precise dose measurement method with EBT4 film and ensure its measurement accuracy to be within the required range through strict operational procedures for the purpose of addressing the two essential issues of poor measurement accuracy and timeliness of EBT film under FLASH conditions.Methods:After storing under different humidity conditions for a certain period of time, the film was exposed to radiation for analyzing the influence of air humidity on the intrinsic performance of EBT film. By means of repeated scanning operations and the film angle rotation, the influences of repeated scanning and film placement angle were analuzed. Parabolic correction method was used to reduce the spatial position influence during the scanning process. By analying the relationship between net optical density (netOD) and absorbed dose through the comparison of three fitting method, the optimal fitting curve was selected. After irradiation of the same batch of films for 5 min and 24 h, the film doses were calibrated and then compared with ionization chamber-measured result. The rapid and precise film dosimetry method was used to measure both the percentage depth dose from X-rays at ultra-high dose rate and the dose distribution at a depth of 2 cm in water.Results:Air humidity had the greatest influence on the intrinsic performance of EBT film (approximately 20%). The average deviation of repeated scans is within 0.5%. The angle at which the film is placed significantly affected the readouts of the film with the maximum influence approximately 70%. The net optical density combined with polynomial fitting can control the fitting residuals of 1-16 Gy within 3%. The change rate of light channels at 5 min already mostly met the requirements of the rapid mode (< 0.5%). Compared with the measurement result obtained using the reference ionization chamber, the deviations of the 5 min or 24 h dose calibration curves were all within 2%.Conclusions:The EBT4 film can be employed as a precise dosimeter to quickly measure the FLASH radiation dose. Rapid and precise FLASH dose measurements can meet the stringent requirements of both preclinical and clinical FLASH research.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.