Objective To investigate the effect of aerobic exercise preconditioning on cardiac function in mice bearing subcutaneous transplantable tumors and explore the potential molecular mechanisms.Methods Twenty-four 6-week-old male BALB/c mice were selected.After an acclimation period,they were randomly assigned to a control group(C),a tumor group(M)and an exercise-preconditioning plus tumor group(EM),each of eight.The EM group underwent a 4-week aerobic exercise interven-tion.Meanwhile,the C group received 0.2 ml of physiological saline injected subcutaneously on the dorsum of the proximal left hind limb,while the M and EM groups were inoculated at the same site with 0.2 ml of a CT26.WT colon carcinoma cell suspension.Three weeks after inoculation,cardiac function was assessed by transthoracic echocardiography.Hearts were then harvested for hematoxylin-eo-sin staining to evaluate cardiomyocyte cross-sectional area(CSA),while Western blot was performed to determine the expression of proteins related to myocardial protein synthesis and degradation.Results(1)Compared with group C,group M exhibited significantly lower body weight and heart weight(P<0.05),and reduced left ventricular ejection fraction(LVEF),fractional shortening(FS)and stroke vol-ume(SV)(P<0.05),as well as cardiomyocyte CSA(P<0.01)and total mTOR(P<0.01),phosphory-lated mTOR(p-mTOR)(P<0.01)and the p-mTOR/mTOR ratio(P<0.05),but a significant increase in the expression of the muscle ring finger 1(MuRF-1)and the muscle atrophy F-box(MAFbx/Atrog-in-1)(P<0.01 and P<0.05,respectively).(2)Compared with group M,group EM showed significant-ly greater heart weight(P<0.05);increased left ventricular posterior wall thickness at end-diastole(LVPWd),LVEF,FS and SV(P<0.05),as well as the larger cardiomyocyte CSA and total mTOR,p-mTOR and the p-mTOR/mTOR ratio(P<0.05),but reduced MuRF-1 and Atrogin-1 expression(P<0.05).Conclusion Four weeks of aerobic exercise preconditioning ameliorated myocardial atrophy and improved systolic cardiac function in mice bearing subcutaneously transplanted CT26 tumors.Such beneficial effects may be associated with exercise-induced down regulation of the protein degradation mediators MuRF-1 and Atrogin-1 and up regulation of total mTOR and p-mTOR.

Objective To investigate the effects of aerobic exercise and different exercise habits on skeletal muscle function and the possible molecular mechanisms in colorectal cancer-loaded mice.Methods Thirty-five 5-week-old BABL/c male mice were acclimatized to feeding for 1 week and then divided randomly into the following groups:control(D),tumor(M),exercise preconditioning(QAM),lifetime exercise(AM),and exercise(HAM)groups(n=7 mice per group).Mice in the QAM and AM groups underwent aerobic exercise regimen 1 from weeks 2～6.At week 7,mice in the experimental groups received 0.2 mL of CT26 colon cancer cell suspension subcutaneously in the dorsal aspect of the left hind limb,while control mice received 0.2 mL of saline at the corresponding site.Mice in the AM and HAM groups were subjected to aerobic exercise regimen 2 for weeks 7～9.The general status and skeletal muscle mass and function were monitored in all mice throughout the experiments.After completion of the experiment,samples were collected and the cross-sectional area of gastrocnemius muscle fibers(CSA)was measured by hematoxylin and eosin staining and expression levels of proteins related to synthesis and catabolism of the gastrocnemius muscle were analyzed by Western Blot.Results(1)The weight ratio of the gastrocnemius muscle was significantly lower in mice in the M,QAM,and HAM groups compared with group D,and was significantly higher in AM mice compared with M,QAM,and HAM mice.(2)Grip strength,endurance,skeletal muscle circumference,and CSA were significantly lower in group D mice compared with the other groups,and was most enhanced in group HAM.Endurance and CSA were consistently enhanced in groups QAM,AM,and HAM.(3)Muscle RING-finger protein-1(MuRF1)expression levels were significantly lower in groups M,QAM,AM,and HAM than in group D,significantly lower in groups AM and HAM than in group M,and significantly lower in group HAM than in group QAM.(4)Fibronectin type Ⅲ domain-containing protein 5(FNDC5)expression levels were significantly lower in group M than in groups D and QAM.(5)Peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression levels were significantly lower in the QAM and HAM groups compared with group M.(6)Expression levels of phospho(p)-AMP-activated protein kinase(AMPK)/AMPK and p-AMPK were significantly higher in group QAM than in groups D and M,p-AMPK expression significantly lower in groups AM and HAM was than in group QAM,and AMPK expression was significantly lower in groups QAM,AM,and HAM than in group D.Conclusions Exercise preconditioning and continuous aerobic exercise can improve skeletal muscle mass and function in CT26 colon cancer-loaded mice by activating AMPK phosphorylation to stimulate skeletal muscle secretion of FNDC5,thereby regulating the expression of MuRF1 protein.

Objective To investigate the effects of aerobic exercise and different exercise habits on skeletal muscle function and the possible molecular mechanisms in colorectal cancer-loaded mice.Methods Thirty-five 5-week-old BABL/c male mice were acclimatized to feeding for 1 week and then divided randomly into the following groups:control(D),tumor(M),exercise preconditioning(QAM),lifetime exercise(AM),and exercise(HAM)groups(n=7 mice per group).Mice in the QAM and AM groups underwent aerobic exercise regimen 1 from weeks 2～6.At week 7,mice in the experimental groups received 0.2 mL of CT26 colon cancer cell suspension subcutaneously in the dorsal aspect of the left hind limb,while control mice received 0.2 mL of saline at the corresponding site.Mice in the AM and HAM groups were subjected to aerobic exercise regimen 2 for weeks 7～9.The general status and skeletal muscle mass and function were monitored in all mice throughout the experiments.After completion of the experiment,samples were collected and the cross-sectional area of gastrocnemius muscle fibers(CSA)was measured by hematoxylin and eosin staining and expression levels of proteins related to synthesis and catabolism of the gastrocnemius muscle were analyzed by Western Blot.Results(1)The weight ratio of the gastrocnemius muscle was significantly lower in mice in the M,QAM,and HAM groups compared with group D,and was significantly higher in AM mice compared with M,QAM,and HAM mice.(2)Grip strength,endurance,skeletal muscle circumference,and CSA were significantly lower in group D mice compared with the other groups,and was most enhanced in group HAM.Endurance and CSA were consistently enhanced in groups QAM,AM,and HAM.(3)Muscle RING-finger protein-1(MuRF1)expression levels were significantly lower in groups M,QAM,AM,and HAM than in group D,significantly lower in groups AM and HAM than in group M,and significantly lower in group HAM than in group QAM.(4)Fibronectin type Ⅲ domain-containing protein 5(FNDC5)expression levels were significantly lower in group M than in groups D and QAM.(5)Peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression levels were significantly lower in the QAM and HAM groups compared with group M.(6)Expression levels of phospho(p)-AMP-activated protein kinase(AMPK)/AMPK and p-AMPK were significantly higher in group QAM than in groups D and M,p-AMPK expression significantly lower in groups AM and HAM was than in group QAM,and AMPK expression was significantly lower in groups QAM,AM,and HAM than in group D.Conclusions Exercise preconditioning and continuous aerobic exercise can improve skeletal muscle mass and function in CT26 colon cancer-loaded mice by activating AMPK phosphorylation to stimulate skeletal muscle secretion of FNDC5,thereby regulating the expression of MuRF1 protein.

OBJECTIVE To investigate the effects of parthenolide （PLT） on systemic inflammation and intestinal injury in rats with acute pancreatitis （AP） by regulating the Kelch-like epichlorohydrin-associated protein 1 （Keap1）/nuclear factor-erythroid-2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. METHODS AP rat model was established by injecting 3.5% sodium taurine cholate solution （1 mL/kg） into the biliary pancreatic duct， and modeled rats were divided into AP group， PLT （300 µg/kg） group， dexamethasone （2 mg/kg） group， inhibitor （11 mg/kg Nrf2 inhibitor ML385） group， and PLT+inhibitor group （300 µg/kg PLT+11 mg/kg ML385）， with 10 rats in each group. Another 10 rats were taken as a sham operation group. Each group was given relevant medicine or normal saline via tail vein/intraperitoneal injection once. After 24 h， serum lipase and amylase levels， the levels of oxidative stress index [superoxide dismutase （SOD） and malondialdehyde （MDA）] and inflammatory factors [interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α）] were detected. The histopathological changes in colon mucosa and pancreas were observed， and Chiu and Schmidt scores were performed. The cell apoptosis in colon mucosa and the protein expressions of Keap1， Nrf2 and HO-1 were detected. RESULTS Compared with the sham operation group， there was obvious inflammatory cell infiltration in colon mucosa and pancreatic tissue， cell shedding or tissue necrosis and severe bleeding； serum levels of lipase， amylase， MDA， IL-1β， IL-6 and TNF-α， Chiu and Schmidt scores， apoptotic rate and protein expression of Keap1 in colonic mucosa were significantly increased or up-regulated， while SOD level and protein expressions of Nrf2 20230993） and HO-1 were decreased or down-regulated significantly （P＜0.05）. Compared with the AP group， the above indexes in the PLT group and dexamethasone group were significantly improved， while those in the inhibitor group further deteriorated （P＜0.05）. Inhibitor could significantly reverse the improvement effect of PLT on the above indexes in AP rats （P＜ 0.05）. CONCLUSIONS PLT inhibits inflammation and oxidative stress in AP rats， alleviates intestinal damage， and its mechanism may be related to inhibiting protein expression of Keap1 and activating Nrf2/HO-1 signaling pathway.

Objective:To analyze the prevalence of human respiratory syncytial virus（RSV）and the evolutionary characteristics of the adhesion glycoprotein（G）gene in Xi'an from 2023 to 2024.Methods:Respiratory specimens were collected from patients with acute respiratory infections in Xi'an between October 2023 to October 2024. RSV nucleic acid screening was performed using real-time fluorescence quantitative PCR；full-length G gene sequencing was conducted on nucleic acid-positive specimens. Genotyping characterization of the obtained sequences was performed using Nextclade v3.10.0 software.Results:A total of 2 548 respiratory tract infection samples were collected，with 104 cases（4.08%，104/2 548）testing positive for RSV. The highest RSV positivity rate was observed in children aged ≤1 year（12.24%，18/147），and significant difference in positivity rates were found among age groups（χ 2=37.868， P<0.001）. Since October 2023，RSV has seen an epidemic peak during January to February 2024，and gradually declined thereafter，with no positive cases from May to September 2024. Among the 43 RSV-positive samples，12 strains were identified as subtype A（all genotype A.D.3），and 31 strains were subtype B（14 genotype B.D.4.1.1 and 17 genotype B.D.E.1）. Conclusion:From October 2023 to October 2024，RSV had an epidemic peak in January and February in Xi＇an，with subtype B being the predominant circulating type.

Objective:To analyze the prevalence of human respiratory syncytial virus（RSV）and the evolutionary characteristics of the adhesion glycoprotein（G）gene in Xi'an from 2023 to 2024.Methods:Respiratory specimens were collected from patients with acute respiratory infections in Xi'an between October 2023 to October 2024. RSV nucleic acid screening was performed using real-time fluorescence quantitative PCR；full-length G gene sequencing was conducted on nucleic acid-positive specimens. Genotyping characterization of the obtained sequences was performed using Nextclade v3.10.0 software.Results:A total of 2 548 respiratory tract infection samples were collected，with 104 cases（4.08%，104/2 548）testing positive for RSV. The highest RSV positivity rate was observed in children aged ≤1 year（12.24%，18/147），and significant difference in positivity rates were found among age groups（χ 2=37.868， P<0.001）. Since October 2023，RSV has seen an epidemic peak during January to February 2024，and gradually declined thereafter，with no positive cases from May to September 2024. Among the 43 RSV-positive samples，12 strains were identified as subtype A（all genotype A.D.3），and 31 strains were subtype B（14 genotype B.D.4.1.1 and 17 genotype B.D.E.1）. Conclusion:From October 2023 to October 2024，RSV had an epidemic peak in January and February in Xi＇an，with subtype B being the predominant circulating type.

Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.

Objective To investigate the effect of aerobic exercise preconditioning on cardiac function in mice bearing subcutaneous transplantable tumors and explore the potential molecular mechanisms.Methods Twenty-four 6-week-old male BALB/c mice were selected.After an acclimation period,they were randomly assigned to a control group(C),a tumor group(M)and an exercise-preconditioning plus tumor group(EM),each of eight.The EM group underwent a 4-week aerobic exercise interven-tion.Meanwhile,the C group received 0.2 ml of physiological saline injected subcutaneously on the dorsum of the proximal left hind limb,while the M and EM groups were inoculated at the same site with 0.2 ml of a CT26.WT colon carcinoma cell suspension.Three weeks after inoculation,cardiac function was assessed by transthoracic echocardiography.Hearts were then harvested for hematoxylin-eo-sin staining to evaluate cardiomyocyte cross-sectional area(CSA),while Western blot was performed to determine the expression of proteins related to myocardial protein synthesis and degradation.Results(1)Compared with group C,group M exhibited significantly lower body weight and heart weight(P<0.05),and reduced left ventricular ejection fraction(LVEF),fractional shortening(FS)and stroke vol-ume(SV)(P<0.05),as well as cardiomyocyte CSA(P<0.01)and total mTOR(P<0.01),phosphory-lated mTOR(p-mTOR)(P<0.01)and the p-mTOR/mTOR ratio(P<0.05),but a significant increase in the expression of the muscle ring finger 1(MuRF-1)and the muscle atrophy F-box(MAFbx/Atrog-in-1)(P<0.01 and P<0.05,respectively).(2)Compared with group M,group EM showed significant-ly greater heart weight(P<0.05);increased left ventricular posterior wall thickness at end-diastole(LVPWd),LVEF,FS and SV(P<0.05),as well as the larger cardiomyocyte CSA and total mTOR,p-mTOR and the p-mTOR/mTOR ratio(P<0.05),but reduced MuRF-1 and Atrogin-1 expression(P<0.05).Conclusion Four weeks of aerobic exercise preconditioning ameliorated myocardial atrophy and improved systolic cardiac function in mice bearing subcutaneously transplanted CT26 tumors.Such beneficial effects may be associated with exercise-induced down regulation of the protein degradation mediators MuRF-1 and Atrogin-1 and up regulation of total mTOR and p-mTOR.

Objective:To explore the clinical application value of multiple cytogenetic and molecular genetic techniques in the diagnosing of chromosomal microstructural abnormalities.Methods:The proband was a 30-year-old man. He went to Reproductive Medicine Center of Shenzhen Zhongshan Urology Hospital in July 2021 because of a 7-year history of primary infertility. Chromosome karyotype was analyzed by conventional G-banding technique. One case was found to be suspected of microstructural aberration in X chromosome. The origin and structural characteristics of this X chromosome structural aberration was identified by high-resolution G-banding, copy number variation sequencing (CNV-seq), C-banding and fluorescence in situ hybridization (FISH). The pregnancy outcome of this case was followed up. Results:Conventional G-banding karyotype of peripheral blood lymphocytes was initially diagnosed as 46, Y, ?inv(X)(p22.3p22.2). The final karyotype of proband was interpreted as 46, Y, der(X) t(X; Y)(p22.3; q12) mat by high-resolution G-banding karyotype analysis, CNV-seq, C-banding analysis and FISH detection. His spouse had conceived singleton pregnancy via in vitro fertilization and embryo transfer. Prenatal diagnosis had been performed. Karyotype of amniotic fluid was 46, X, der(X) t(X; Y)(p22.3; q12) pat. No structural malformation was detected prenatally by ultrasound. The neonate was phenotypically normal one month after birth. Conclusion:The combined application of multiple cytogenetic and molecular genetic techniques can provide a reliable technical platform for characterizing the microscopic structural aberrations of chromosomes, and an important genetic basis for exploring the phenotype, prognosis and offspring risk of such patients.

Objective:To investigate the genetic and evolutionary characteristics of hemagglutinin (HA) and neuraminidase (NA) genes of influenza B/Victoria (BV) virus in Xi′an city from 2019 to 2023.Methods:Twenty-five BV strains isolated from the Xi′an influenza surveillance network laboratory between 2019 and 2023 were collected. The HA and NA genes were sequenced using MiniSeq high-throughput sequencing platform. An evolutionary tree was constructed using bioinformatics software to analyze homology and mutation sites, and to predict N-glycosylation sites online. The antigenicity of the strains was analyzed through hemagglutination inhibition tests.Results:The BV influenza in Xi′an exhibited a distinct seasonal transmission pattern from 2019 to 2023, with peak prevalence occurring during the winter and spring seasons. The evolutionary analysis of the HA genes shows that the strains from Xi′an in 2019 belong to the V1A.3 branch, and the strains from 2021 to 2023 belong to the V1A.3a.2 branch. Analysis of antigenic sites showed that there were variations in 6 sites of 3 antigenic determinants in the HA proteins of the BV strains from 2021-2022 compared to 2019, and 2 sites of 1 antigenic determinant changed in the HA proteins in 2023 compared to 2021-2022. The evolutionary analysis of the NA genes indicates that the BV strains from Xi′an in 2019 belong to the A. 1.1 branch. By 2021 and 2022, it had evolved into the A. 1.2 clade, and by 2023, it had further evolved into the B clade and its derivatives, with no strains showing mutations associated with resistance to NA inhibitors. Antigenic analysis indicated that the majority of BV strains in Xi′an were similar to the strains included in the vaccine composition. Furthermore, glycosylation analysis showed that the potential N-glycosylation sites in the HA proteins of BV strains from 2021-2023 were reduced by one compared to those from 2019, and only a few strains from 2023 displayed alterations in the potential N-glycosylation sites of the NA proteins.Conclusions:The HA and NA genes of the BV strains from 2019 to 2023 are continuously mutating and evolving into new branches. Since 2021, V1A.3a.2 has become the dominant evolutionary branch of the HA genes, while the evolutionary branches of the NA genes from 2019 to 2023 have been continuously changing.