Objective To examine the time window effect of high-load exerciseon skeletal muscle in-flammation genes,and identify the key genes and signaling pathways involved in this process.Methods Forty-eight Sprague-Dawley rats were randomly assigned to a control group(group C,n=8)and an ex-ercise group(group E,n=40).Gastrocnemius muscles were collected immediately(group E0),12h(group E12),24h(group E24),48h(group E48),and 72 h(group E72)after exercise for transcrip-tome sequencing.Differentially expressed genes(DEGs)were identified,and enrichment analysis was carried out using the Gene Ontology(GO)and the Kyoto Encyclopedia of Genes and Genomes(KEGG)annotations.Meanwhile,inflammation-related genes were obtained from databases,and differ-entially expressed inflammation-related genes(DEIRGs)were done through identifying their intersec-tion with DEGs.Moreover,the Mfuzz algorithm was used for time series clustering to obtain subsets with similar characteristics.GO and KEGG analyses,along with protein interaction network analysis,were performed to obtain key DEIRGs,followed by secondary functional enrichment to analyze changes in expression of key genes over time and identify key signaling pathways.Results Seven DEIRG clus-ters were obtained through Mfuzz time series clustering of skeletal muscle inflammation genes after high-load exercise.Overall,the expression of DEGs in cluster 5 was downregulated,while that in cluster 7 was upregulated.The expression of DEGs in clusters 3 and 4 was upregulated at E0 and rap-idly downregulated at E12.In contrast,the expression of DEGs in cluster 2 and 6 were downregulated at E0 and rapidly upregulated at E12.The expression of DEGs in cluster 1 was upregulated at E0,rapidly downregulated at E12,and remained upregulated at E24.Screening identified TP53,STAT3,CD44,AKT1,KDR,GJA1,CYCS,HIF1A,IQGAP3,FASN,and TFRC as key DEIRGswhich were enriched in apoptosis,HIF-1,apoptosis,ferroptosis,MAPK,VEGF,PI3K-Akt,insulin resistance,FoxO,AMPK and the JAK-STAT signaling pathway.Conclusion Inflammation-related genes exhibit temporal dynamic changes in exercise-induced muscle damage and show significant time window effects at 12 h after exercise.The key targets STAT3,AKT1 and HIF-1A react to exercise-induced muscle damage through the JAK-STAT,PI3K-Akt,HIF-1 and VEGF signaling pathways,and promote tissue repair.

AIM:To investigate the mechanism through which aerobic exercise improves inflammatory senes-cence in SAMP8 mice via Janus kinase 3(JAK3)-signal transducer and activator of transcription 5α(STAT5α)signaling pathway and to provide novel insights for anti-inflammatory aging interventions.METHODS:Sixteen 28-week-old SAMP8 mice were randomly divided into model(Mod)group and exercise(Exe)group,with 8 mice in each group.Addi-tionally,8 senile SAMR1 mice served as control(Con)group.The mice in Exe group underwent an 8-week aerobic training regimen on a treadmill.We monitored the changes in hair quality and body weight,immune organ indexes,histomorpho-logical alterations in immune organs,the expression levels of spleen aging marker P16,and the serum and spleen levels of inflammatory factors[tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)]and aging indicator IL-2.Moreover,we examined the alterations in the mRNA and protein expression of IL-2,JAK3 and STAT5α in the spleen.RESULTS:(1)Compared with Con group,the mice in Mod group exhibited decreased hair luster and volume,with some instances of alopecia areata,increased body weight,markedly reduced spleen and thymus indexes,evident atrophy and senescence of immune organs,and markedly decreased concentration of IL-2 in the serum and spleen.The expression of P16 in the spleen,and the serum and spleen levels of inflammatory factors TNF-α and IL-1β were significantly increased.The mRNA expression of IL-2 and IL-2 receptor subunit gamma(IL-2RG)in the spleen was markedly decreased,whereas that of JAK3 and STAT5α was markedly increased.Furthermore,the protein expression of IL-2 in the spleen was markedly de-creased,whereas that of STAT5α and JAK3 was markedly increased.(2)Compared with Mod group,the mice in Exe group showed relatively vigorous hair growth and better hair luster,lower body weight,markedly increased spleen and thy-mus indexes,and delayed immune organ aging.The concentration of IL-2 in the serum and spleen was markedly in-creased,while the expression of P16 in the spleen was markedly decreased.The levels of TNF-α and IL-1β in the serum and spleen were markedly decreased.The mRNA expression of IL-2 and IL-2RG in the spleen was markedly increased,whereas that of JAK3 and STAT5α was markedly decreased.The protein levels of IL-2 were markedly increased,whereas those of STAT5α and JAK3 were markedly decreased.CONCLUSION:Aerobic exercise can delay inflammatory aging in mice possibly through the JAK3-STAT5α signaling pathway.

Objective:To explore the value of the vesical imaging-reporting and data system (VI-RADS) score based on multiparametric MRI (mpMRI) combined with quantitative tumor MRI parameters in assessing the muscle invasion of bladder cancer.Methods:The study was a case-control study. The data of 87 bladder cancer patients confirmed by pathology who underwent mpMRI of the bladder were retrospectively collected from the First Medical Center of Chinese PLA General Hospital between January 2019 and April 2023 The pathological findings were used as the gold standard to categorize them into the muscle invasive bladder cancer (MIBC) group (29 cases) and non-muscle invasive bladder cancer (NMIBC) group (58 cases). Quantitative parameters were measured based on preoperative mpMRI images, including the length of tumor bladder wall contact, the perpendicular distance between the bladder tumor and the tangent of the bladder wall, the maximal diameter of the bladder tumor, and the volume of the bladder tumor. Bladder cancer was classified according to the VI-RADS scoring criteria. The Mann-Whitney U test was used for intergroup comparisons. Multivariate logistic regression analysis was performed to obtain the independent risk factors related to muscle invasion of bladder cancer and to establish the model. The receiver operating characteristic curves were analyzed for MRI quantitative parameters and logistic regression models, and area under the curve (AUC) comparisons were performed using the DeLong test. Results:The differences in tumor bladder wall contact length, perpendicular distance from the tumor to the tangent line of the bladder wall, maximum diameter, bladder tumor volume, and the VI-RADS scores were statistically significant between the MIBC group and the NMIBC group ( P<0.05). Multifactorial logistic regression analysis showed that tumor bladder wall contact length ( OR=21.07, 95% CI 3.56-124.89, P=0.001) and VI-RADS score ( OR=11.90, 95% CI 3.53-40.12, P<0.001) were the independent risk factors for evaluating the muscle invasion of bladder cancer. The difference between the VI-RADS score and the tumor bladder wall contact length for assessing muscular infiltration of bladder cancer had AUCs of 0.802 (95% CI 0.704-0.899) and 0.759 (95% CI 0.652-0.865). The combined model of VI-RADS score combined with tumor bladder wall contact length had an AUC of 0.891 (95% CI 0.812-0.970), which was higher than the diagnostic efficacy of applying tumor bladder wall contact length or VI-RADS score alone ( Z=3.05, 2.37, P=0.002, 0.018). Conclusion:Tumor contact length with the bladder wall is an independent risk factor for assessing muscle invasion of bladder cancer and the combination of VI-RADS score may enhances diagnostic accuracy.

Objective To examine the time window effect of high-load exerciseon skeletal muscle in-flammation genes,and identify the key genes and signaling pathways involved in this process.Methods Forty-eight Sprague-Dawley rats were randomly assigned to a control group(group C,n=8)and an ex-ercise group(group E,n=40).Gastrocnemius muscles were collected immediately(group E0),12h(group E12),24h(group E24),48h(group E48),and 72 h(group E72)after exercise for transcrip-tome sequencing.Differentially expressed genes(DEGs)were identified,and enrichment analysis was carried out using the Gene Ontology(GO)and the Kyoto Encyclopedia of Genes and Genomes(KEGG)annotations.Meanwhile,inflammation-related genes were obtained from databases,and differ-entially expressed inflammation-related genes(DEIRGs)were done through identifying their intersec-tion with DEGs.Moreover,the Mfuzz algorithm was used for time series clustering to obtain subsets with similar characteristics.GO and KEGG analyses,along with protein interaction network analysis,were performed to obtain key DEIRGs,followed by secondary functional enrichment to analyze changes in expression of key genes over time and identify key signaling pathways.Results Seven DEIRG clus-ters were obtained through Mfuzz time series clustering of skeletal muscle inflammation genes after high-load exercise.Overall,the expression of DEGs in cluster 5 was downregulated,while that in cluster 7 was upregulated.The expression of DEGs in clusters 3 and 4 was upregulated at E0 and rap-idly downregulated at E12.In contrast,the expression of DEGs in cluster 2 and 6 were downregulated at E0 and rapidly upregulated at E12.The expression of DEGs in cluster 1 was upregulated at E0,rapidly downregulated at E12,and remained upregulated at E24.Screening identified TP53,STAT3,CD44,AKT1,KDR,GJA1,CYCS,HIF1A,IQGAP3,FASN,and TFRC as key DEIRGswhich were enriched in apoptosis,HIF-1,apoptosis,ferroptosis,MAPK,VEGF,PI3K-Akt,insulin resistance,FoxO,AMPK and the JAK-STAT signaling pathway.Conclusion Inflammation-related genes exhibit temporal dynamic changes in exercise-induced muscle damage and show significant time window effects at 12 h after exercise.The key targets STAT3,AKT1 and HIF-1A react to exercise-induced muscle damage through the JAK-STAT,PI3K-Akt,HIF-1 and VEGF signaling pathways,and promote tissue repair.

AIM:To investigate the mechanism through which aerobic exercise improves inflammatory senes-cence in SAMP8 mice via Janus kinase 3(JAK3)-signal transducer and activator of transcription 5α(STAT5α)signaling pathway and to provide novel insights for anti-inflammatory aging interventions.METHODS:Sixteen 28-week-old SAMP8 mice were randomly divided into model(Mod)group and exercise(Exe)group,with 8 mice in each group.Addi-tionally,8 senile SAMR1 mice served as control(Con)group.The mice in Exe group underwent an 8-week aerobic training regimen on a treadmill.We monitored the changes in hair quality and body weight,immune organ indexes,histomorpho-logical alterations in immune organs,the expression levels of spleen aging marker P16,and the serum and spleen levels of inflammatory factors[tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)]and aging indicator IL-2.Moreover,we examined the alterations in the mRNA and protein expression of IL-2,JAK3 and STAT5α in the spleen.RESULTS:(1)Compared with Con group,the mice in Mod group exhibited decreased hair luster and volume,with some instances of alopecia areata,increased body weight,markedly reduced spleen and thymus indexes,evident atrophy and senescence of immune organs,and markedly decreased concentration of IL-2 in the serum and spleen.The expression of P16 in the spleen,and the serum and spleen levels of inflammatory factors TNF-α and IL-1β were significantly increased.The mRNA expression of IL-2 and IL-2 receptor subunit gamma(IL-2RG)in the spleen was markedly decreased,whereas that of JAK3 and STAT5α was markedly increased.Furthermore,the protein expression of IL-2 in the spleen was markedly de-creased,whereas that of STAT5α and JAK3 was markedly increased.(2)Compared with Mod group,the mice in Exe group showed relatively vigorous hair growth and better hair luster,lower body weight,markedly increased spleen and thy-mus indexes,and delayed immune organ aging.The concentration of IL-2 in the serum and spleen was markedly in-creased,while the expression of P16 in the spleen was markedly decreased.The levels of TNF-α and IL-1β in the serum and spleen were markedly decreased.The mRNA expression of IL-2 and IL-2RG in the spleen was markedly increased,whereas that of JAK3 and STAT5α was markedly decreased.The protein levels of IL-2 were markedly increased,whereas those of STAT5α and JAK3 were markedly decreased.CONCLUSION:Aerobic exercise can delay inflammatory aging in mice possibly through the JAK3-STAT5α signaling pathway.

Objective:To explore the value of the vesical imaging-reporting and data system (VI-RADS) score based on multiparametric MRI (mpMRI) combined with quantitative tumor MRI parameters in assessing the muscle invasion of bladder cancer.Methods:The study was a case-control study. The data of 87 bladder cancer patients confirmed by pathology who underwent mpMRI of the bladder were retrospectively collected from the First Medical Center of Chinese PLA General Hospital between January 2019 and April 2023 The pathological findings were used as the gold standard to categorize them into the muscle invasive bladder cancer (MIBC) group (29 cases) and non-muscle invasive bladder cancer (NMIBC) group (58 cases). Quantitative parameters were measured based on preoperative mpMRI images, including the length of tumor bladder wall contact, the perpendicular distance between the bladder tumor and the tangent of the bladder wall, the maximal diameter of the bladder tumor, and the volume of the bladder tumor. Bladder cancer was classified according to the VI-RADS scoring criteria. The Mann-Whitney U test was used for intergroup comparisons. Multivariate logistic regression analysis was performed to obtain the independent risk factors related to muscle invasion of bladder cancer and to establish the model. The receiver operating characteristic curves were analyzed for MRI quantitative parameters and logistic regression models, and area under the curve (AUC) comparisons were performed using the DeLong test. Results:The differences in tumor bladder wall contact length, perpendicular distance from the tumor to the tangent line of the bladder wall, maximum diameter, bladder tumor volume, and the VI-RADS scores were statistically significant between the MIBC group and the NMIBC group ( P<0.05). Multifactorial logistic regression analysis showed that tumor bladder wall contact length ( OR=21.07, 95% CI 3.56-124.89, P=0.001) and VI-RADS score ( OR=11.90, 95% CI 3.53-40.12, P<0.001) were the independent risk factors for evaluating the muscle invasion of bladder cancer. The difference between the VI-RADS score and the tumor bladder wall contact length for assessing muscular infiltration of bladder cancer had AUCs of 0.802 (95% CI 0.704-0.899) and 0.759 (95% CI 0.652-0.865). The combined model of VI-RADS score combined with tumor bladder wall contact length had an AUC of 0.891 (95% CI 0.812-0.970), which was higher than the diagnostic efficacy of applying tumor bladder wall contact length or VI-RADS score alone ( Z=3.05, 2.37, P=0.002, 0.018). Conclusion:Tumor contact length with the bladder wall is an independent risk factor for assessing muscle invasion of bladder cancer and the combination of VI-RADS score may enhances diagnostic accuracy.

BACKGROUND:A high-load exercise can trigger the degradation of titin,leading to skeletal muscle damage.MyoD participates in skeletal muscle generation and plays an important role in the repair of skeletal muscle damage. OBJECTIVE:To observe the expression changes of MyoD,BMAL1 and titin in skeletal muscles at different times during a high-load exercise,as to clarify the role of MyoD and BMAL1 in exercise-induced skeletal muscle damage. METHODS:Twenty-four 8-week-old Sprague-Dawley rats were randomly divided into a control group(n=4)and an exercise group(n=20).Rats in the exercise group were subjected to downhill running(90 minutes).Soleus muscle samples were collected at 0,12,24,48,and 72 hours after exercise.The mRNA expressions of BMAL1 and MyoD were measured by real-time fluorescence quantitative PCR.The ultrastructure of skeletal muscle fibers was observed by transmission electron microscope.Immunofluorescence was used to observe the co-localization of MyoD and BMAL1 as well as BMAL1 and titin. RESULTS AND CONCLUSION:After the single high-load centrifugal exercise,the sarcomere of the soleus muscle was widened and the Z-line was blurred and water wave-like,both of which were most serious at 12 hours after exercise and basically recovered at 72 hours.The results of real-time fluorescent quantitative PCR showed that BMAL1 mRNA expression in the exercise group increased first and then tended to normal,while the mRNA expression of MyoD decreased first and then increased.Immunofluorescence co-localization observation indicated that the co-localization of BMAL1 and MyoD was obviously observed at 12 and 24 hours after exercise,and the co-localization of BMAL1 and titin was observed at 0,12,and 24 hours.All the findings indicate that MyoD and BMAL1 are jointly involved in the repair of exercise-induced skeletal muscle damage probably via titin.

Objective To explore the potential regulatory mechanism of resistance exercise in senescence accelerated-prone 8 mice(SAMP8)by evaluating the effects of exercise on the expression of long non-coding RNA(lncRNA)and mRNA in quadriceps muscles by RNA-sequencing(RNA-seq)technology.Methods Twenty-eight-week-old male SAMP8 mice were divided into a model group(M group)and resistance-exercise group(R group)(n=6 mice per group).Another eight normally aging SAMR1 mice of the same age were used as the control group(C group).Mice in R group received 8 weeks of increasing weight climbing exercise training.Relative grip strength was measured every week and the rotarod test was performed every 2 weeks.Histological changes in the right quadriceps femoris were observed by hematoxylin-eosin staining and the left quadriceps was used for RNA-seq.Differentially expressed lncRNA and mRNA were screened and analyzed for enrichment by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses.Finally,key differentially expressed genes were analyzed by quantitative reverse transcription-polymerase chain reaction to verify the accuracy of the RNA-seq result.Results(1)Relative grip strength and rotarod test time were significantly decreased in M group compared with C group(P＜0.01),but were significantly increased after 8 weeks of Rgroup compared with M group(P＜0.01).(2)The cross-sectional area of the muscle fibers was significantly lower in M group compared with C group,as shown by HE staining(P＜0.01),while the cross-sectional area of the muscle fibers was significantly increased in the R group compared with M group(P＜0.01).(3)Differential expression analysis identified 182 upregulated and 218 downregulated lncRNA,and 454 upregulated and 289 downregulated mRNA between M group and R group.The KEGG pathways of lncRNA target genes that were differentially expressed between M group and R group were significantly enriched in intestinal immune network for IgA production,nuclear factor-kappa B signaling pathway,and inflammatory bowel disease.Conclusions(1)This study demonstrated that resistance exercise can improve skeletal muscle function in SAMP8 mice with sarcopenia.We identified lncRNA and mRNA that were differentially expressed as a result of resistance exercise,and which might be potential targets of sarcopenia therapy.(2)Furthermore,analyzing the biological functions of the target genes of the differentially expressed lncRNA and mRNA may further our understanding of the mechanism of resistance exercise for improving sarcopenia.

Objective To investigate the clinical significance of children bronchial asthma detection by using negative expiratory pressure (NEP) technique.Methods The children with bronchial asthma admitted to Department of Pediatrics of Zhejiang Provincial Integrated Traditional Chinese and Western Medicine Hospital from March 2016 to March 2018 were enrolled.They were divided into mild group (0-4 scores) and severe group (5-12 scores) according to asthma clinical scoring criteria.The children undergoing physical examination at the same period were served as healthy control group.NEP technique and tidal volume (VT) were detected by the pulmonary function instrument.Respiratory flow-volume curves (F-V curves) without NEP were compared with tidal F-V curves after NEP application to assess expiratory flow limitation (EFL).EFL index was calculated according to the percentage of expiratory VT after EFL and expiratory VT when NEP was not used.Pearson correlation method was used to analyze the relationship between EFL index and severity of bronchial asthma.Receiver operating characteristic (ROC) curve was plotted to analyze the value of EFL index in evaluating the severity of bronchial asthma in children.Results A total of 86 children with bronchial asthma were enrolled in the study,and 84 patients completed the test and 2 children withdrew due to other diseases.Finally,84 patients were included in the final analysis,including 41 mild and 43 severe children.Forty-two healthy children in the same period were served as healthy control group.There was no significant difference in gender or age among the groups,and no adverse reactions occurred during the test.The EFL index of children with bronchial asthma was significantly higher than that of the healthy control group,and it was increased with the severity of the disease [mild group compared with healthy control group:(30.60± 6.03)％ vs.(6.64 ± 2.37)％,severe group compared with healthy control group:(33.70 ± 5.41)％ vs.(6.64 ± 2.37)％,both P ＜ 0.05].There was no significant difference in respiratory rate (RR) or VT between mild group or severe group and healthy control group [RR (times/min):31.45 ± 4.18,32.81 ± 4.07 vs.31.97 ± 4.01,VT (mL/kg):6.29 ± 1.14,5.96 ± 0.90 vs.6.30 ± 1.20,all P ＞ 0.05].It was shown by the correlation analysis that EFL index was positively correlated with the severity of asthma (r =0.836,P =0.000).It was shown by ROC curve analysis that the area under ROC curve (AUC) of EFL index for predicting the severity of bronchial asthma in children was 0.801 [95％ confidence interval (95％C/) =0.725-0.878];when the best cut-off value of EFL index was 29.21％,the sensitivity was 85.7％,the specificity was 69.2％,the positive predictive value was 75.1％,and the negative predictive value was 60.2％.Conclusions The EFL index measured by NEP technology was closely related to the severity of bronchial asthma.The higher the EFL index,the more serious of the condition.The severity of bronchial asthma could be early judged by EFL index,which provided a basis for the evaluation and treatment of bronchial asthma.

Objective To discuss the influence of temperature on the effects of cleaning rigid cystoscope. Methods Totally 225 sets of rigid cystoscope which were used for cystoscopy in the Urologic Laparoscopy Center of the First Affiliated Hospital of Zhengzhou University from January 2017 to June 2017 were selected, each of them included four detection points: endoscope, scope lemma, obturator and cross-structure. They were randomly divided into three groups, each group including 75 sets of cystoscope and 300 detection points. The Twist'n Fill'TM cleaner distributor developed by 3M Company was used to control the temperature at 21-30 ℃ for Group A, 31-40 ℃ for Group B and 41-50 ℃ for Group C. The cleaning results were tested through the Clean-Trace ATP Surface Test and ATP Water Test developed by 3M Company. Results The cleaning yields of Group A, B and C were 65.67%, 75.67% and 96.00% respectively, the difference was statistically significant (χ2=86.748; P<0.05). Conclusions Multi-enzymatic detergent shows the best effect at the temperature of 41-50 ℃, and it is advised that this temperature be used in cleaning rigid cystoscope.