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.

BACKGROUND:Cannabidiol is effective in ameliorating the body's inflammatory response,but no clear mechanistic studies have been conducted to ameliorate skeletal muscle inflammation induced by exhaustive exercise. OBJECTIVE:To explore the mechanism by which cannabidiol improves skeletal muscle inflammation during exhaustive exercise by using transcriptome sequencing technology. METHODS:Thirty-six Sprague-Dawley rats were randomly divided into six groups:blank control group,exercise coconut oil group,exercise control group,50 mg/kg cannabidiol group,60 mg/kg cannabidiol group,and 70 mg/kg cannabidiol group,with six rats in each group.Except for rats in the blank control group,rats in each group were subjected to swimming exercise for 9 days to produce the exhaustive exercise model.At the end of each swimming exercise,rats in the cannabidiol groups were given 2 mL of fat-soluble cannabidiol at different concentrations(50,60,and 70 mg/kg)by gavage;rats in the exercise coconut oil group were given the same volume of coconut oil by gavage until the end of the exercise on the 9th day;and rats in the blank control group and the exercise control group were not given any special treatment.The levels of inflammatory factors and differentially expressed genes in the skeletal muscle of rats in each group were determined using ELISA and transcriptome sequencing techniques.Differentially expressed genes obtained were subjected to KEGG analysis,and the accuracy of the sequencing data was verified by fluorescence quantitative PCR. RESULTS AND CONCLUSION:The results of ELISA showed that the contents of interleukin-6(P<0.05),tumor necrosis factor-α(P<0.01),interleukin-10 and other inflammatory factors in the exercise group increased significantly compared with the blank control group and the coconut oil group.After cannabidiol intervention,the mass concentrations of interleukin-6 and tumor necrosis factor-α showed a sequential decrease with increasing cannabidiol concentration.By comparing GO and KEGG databases,the functional properties of differentially expressed genes were analyzed,and the results showed that the differentially expressed genes were mainly involved in the tumor necrosis factor signaling pathway and the Toll-like receptor signaling pathway.RT-qPCR results showed that the trends of five randomly selected differentially expressed genes were in agreement with the transcriptome sequencing results.To conclude,cannabidiol can improve skeletal muscle inflammation caused by exhaustive exercise.

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 investigate the levels of serum soluble CD14 subtype(Presepsin)and serum amyloid protein A(SAA)in patients with colorectal cancer after laparoscopic surgery,and their predictive value for early anastomotic leakage.Methods From October 2021 to April 2024,126 patients with laparoscopic colorectal cancer were divided into the non-anastomotic leakage group(control group,n=103)and the anastomotic leakage group(observation group,n=23)based on whether anastomotic leakage occurred within 3 days after the operation.Clinical information was collected from both groups and compared between groups.Enzyme linked immunosorbent assay(ELISA)was applied to detect the postoperative serum levels of Presepsin and SAA in two groups.Pearson method was applied to investigate the correlation between postoperative serum levels of Presepsin and SAA in patients with colorectal cancer after laparoscopic surgery.The multivariate Logistic regression model was applied to analyze the key factors influencing the occurrence of anastomotic leakage in the early postoperative period in patients with colorectal cancer after laparoscopic surgery.The receiver operating characteristic curve(ROC curve)was applied to evaluate the predictive value of serum Presepsin and SAA levels for early anastomotic leakage in colorectal cancer patients after laparoscopic surgery.Results Compared with the control group,the proportion of patients with tumours≥7 cm from the anus was significantly reduced and intraoperative bleeding was significantly increased in the observation group,the differences were statistically significant(P<0.05).The postoperative levels of serum Presepsin and SAA in the observation group were obviously higher than those in the control group,the differences were statistically significant(P<0.05).There was an obvious positive correlation between serum levels of Presepsin and SAA in patients with colorectal cancer after laparoscopic surgery(r=0.749,P=0.016).Serum Presepsin levels higher than 389.23 pg/mL and SAA expression levels higher than 25.10 mg/L were independent risk factors for the occurrence of early anastomotic leakage after surgery in patients with colorectal cancer after laparoscopic surgery.A tumor distance from the anus of≥7 cm was a protective factor.The area under the curve(AUC)of serum Presepsin and SAA alone and in combination for detecting early anastomotic leakage in patients with colorectal cancer after laparoscopic surgery was 0.834(95%CI:0.757～0.894),0.801(95%CI:0.720～0.866),and 0.897(95%CI:0.830～0.944).The combined detection was superior to the separate detection of Presepsin and SAA(Zcombination-Presepsin=2.085,Zcombination-SAA=2.010,both P<0.05).Conclusion Serum levels of Presepsin and SAA are elevated in patients with colorectal cancer after laparoscopic surgery,and their combined detection has high predictive value for early anastomotic leakage.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

OBJECTIVE To explore the effectiveness and possible mechanism of Shangke Lengtong Patch in treating knee osteo-arthritis with cold-dampness arthralgia obstruction.METHODS A total of 70 patients who met the inclusion criteria of knee osteoar-thritis with cold-dampness arthralgia obstruction in the Orthopedics Department of Affiliated Hospital of Nanjing University of Chinese Medicine from November to December 2024 were randomly divided into an experimental group and a control group,with 35 cases in each group.During the treatment,1 case dropped out of the experimental group,3 cases dropped out of the control group,and 1 case was discontinued.The experimental group was treated with Shangke Lengtong Patch,and the control group was treated with Compound Nanxing Zhitong Ointment.The WOMAC scores and TCM syndrome scores of the two groups before and after treatment were compared to comprehensively evaluate the clinical efficacy.The changes in the expression levels of CGRP,substance P,HMGB1,IL-1β,CX-CL12,and CXCR4 in the serum of the two groups were detected by ELISA.RESULTS After 3,7,and 14 d of treatment,the WOMAC scores and TCM syndrome scores of the two groups were significantly reduced(P<0.05,P<0.01),and the score of aggrava-ted cold in the experimental group was better than that in the control group at 7 d of treatment(P<0.05);after 14 d of treatment,the expression levels of CGRP,substance P,HMGB1,IL-1β,CXCL12,and CXCR4 in the serum of the two groups were significantly re-duced(P<0.05),and there was no statistical difference between the two groups.CONCLUSION Shangke Lengtong Patch can sig-nificantly relieve the pain symptoms of knee osteoarthritis patients with cold-dampness arthralgia obstruction and improve the joint func-tion of patients.It may improve synovial inflammation by inhibiting the HMGB1/CXCL12/CXCR4 pathway,thereby exerting a thera-peutic effect.

[Purpose]To analyze the trend of prostate cancer mortality in China from 2011 to 2020,and to predict the prostate cancer mortality trend from 2021 to 2030.[Methods]The data were collected from the National Mortality Surveillance System(NMSS)from 2011 to 2020,the burden of prostate cancer in China from 2011 to 2020 were analyzed by the number of deaths,age-standardized mortality rate(ASMR),years of life lost(YLL)and age-standardized YLL rate.Joinpoint regression model was used to calculate the average annual percentage change(AAPC)to describe the trend of change.The Bayesian age-period-cohort model was used to predict the mor-tality rate of prostate cancer from 2021 to 2030 and estimate the number of deaths of prostate can-cer in the future.Decomposition analysis was carried out to explore the potential drivers of changes of mortality.[Results]The number of prostate cancer deaths in China in 2020 was 30 805 with an ASMR of 5.56/105.The ASMR for prostate cancer in urban and rural areas was 6.56/105 and 4.84/105,respectively.From 2011 to 2020,the number of prostate cancer deaths,ASMR and age-standardized YLL rate of prostate cancer in China showed an upward trend,AAPC was 5.4％(95％CI:4.7％～6.1％),1.5％(95％CI:1.4％～1.6％)and 1.1％(95％CI:1.1％～1.2％),respective-ly.The ASMR of prostate cancer was higher in the eastern region than those in the central and western regions.Prostate cancer deaths increased in both urban and rural areas among people aged 60 years old and above.In 2030,it is predicted the ASMR of prostate cancer would increase to 5.74/105.Population aging,changes in age-specific mortality rates,and natural population growth accounted for 24.75％,2.77％,and 7.45％of the changes in total deaths of prostate can-cer,respectively.[Conclusion]The burden of prostate cancer is increasing in China.Targeted measures should be implemented in high-risk areas and high-risk groups to effectively reduce the disease burden caused by prostate cancer.

Phototherapy plays a significant role in vitiligo treatment.Narrow-band ultraviolet B(NB-UVB)remains the first-line phototherapy for non-segmental vitiligo in clinical practice.In recent years,visible light has emerged as a novel therapeutic approach for vitiligo.Studies indicate that helium-neon laser demonstrates superior efficacy in segmental vitiligo,blue light is more effective for localized vitiligo,and NB-UVB is better suited for generalized or extensive vitiligo.Different phototherapy modalities exhibit distinct mechanisms of action,involving multiple biological proteins and signaling pathways in melanocyte activation and repigmentation.This review sum-marizes recent advances in phototherapy for vitiligo treatment.