ObjectiveThis study aimed to elucidate the mechanistic role of Staphylococcus aureus in the pathogenesis of atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by pruritus and barrier dysfunction. A key focus was screening traditional Chinese medicine (TCM) active components with dual antibacterial and antipruritic efficacy, followed by systematic evaluation of their in vitro antibacterial activity. Additionally, a novel drug delivery system was constructed to enable localized efficient drug delivery, inhibiting S. aureus proliferation and alleviating its induced pruritus, thereby providing new strategies for targeted AD therapy. MethodsMale C57BL/6J mice aged 6-8 weeks (body weight 18-22 g) were used to establish an AD model via repeated oxazolone sensitization. On day 14, microbial samples were collected from the lesional area (1 cm²) using sterile cotton swabs, followed by vortex mixing, serial dilution, and plating on 5% sheep blood agar plates (incubated at 37°C for 24 h). Single colonies with complete transparent β-hemolytic zones were isolated and identified as vancomycin-intermediate S. aureus (VISA) via 16S rRNA sequencing. An S. aureus mono-infection animal model was then established by applying gauze saturated with bacterial suspension (McFarland turbidity 0.1) to the nape and back skin of mice. The pruritic phenotype and inflammatory cell infiltration induced by S. aureus were evaluated using comprehensive approaches including behavioral assays (e.g., scratching frequency recording), hematoxylin-eosin (HE) staining, and toluidine blue staining. The in vitro antibacterial efficacy of the TCM monomer pseudolaric acid B (PAB) and double network hydrogel (DN) was separately assessed by disk diffusion assay, while the minimum inhibitory concentration (MIC) of PAB was determined via broth dilution method. Further validation of the pharmacodynamic characteristics of the composite system (PAB@DN, composed of PAB and DN) was conducted through behavioral assays, HE staining, and dermatitis scoring, with its drug release profile evaluated by mass spectrometry analysis. Based on scratching behavioral analysis and dermatitis scoring, the optimal ratio and concentration of PAB@DN were optimized. ResultsThe S. aureus load in AD lesional tissues was significantly higher than in normal skin ((5.3±0.33)×10⁶ CFU vs. (3.6±0.26)×10⁷ CFU, P<0.001). In the S. aureus mono-infection group, mice exhibited a 6.7-fold increase in scratching frequency compared to the control group. HE staining revealed marked epidermal thickening ((10.4±2.39) μm vs. (85.6±1.95) μm, P<0.000 1), and toluidine blue staining showed a 23-fold increase in mast cell degranulation. Pseudolaric acid B exhibited a significant concentration-dependent inhibitory effect onS. aureus growth, with its in vitro antibacterial effect being 57% that of the antibiotic cefepime (inhibition zone diameter: PAB (1.885±0.036) cm vs. cefepime (3.636±0.005) cm, P<0.000 1) and a minimum inhibitory concentration (MIC) of 1 g/L. The carrier double network hydrogel (DN) itself lacked direct antibacterial activity (no significant difference in inhibition zone diameter compared to the control) but effectively ameliorated the dry symptoms of AD-like lesions. The PAB@DN composite system demonstrated a synergistic effect compared to individual components, resulting in a 50% reduction in scratching behavior, an 86% decrease in dermatitis score, and a 60% reduction in epidermal thickening. It also reduced the S. aureus load in mouse skin by approximately 34%, with the optimal effective formulation being PAB at 1 g/L loaded onto DN. ConclusionS. aureus colonization plays a critical driving role in the onset and progression of AD. Using an S. aureus infection model, this study confirmed that the pseudolaric acidB-hydrogel composite delivery system (PAB@DN) can effectively alleviate S. aureus-induced pruritus and skin damage, providing experimental evidence for microbiota-targeted therapy of AD.

Objective To evaluate the test-retest reliability of the ballistic push-up(BPU)test and establish predictive models for upper-limb strength and explosive power in young males.Methods A total of 71 male college students performed assessments of upper-limb bench press 1 repetition maximum(1RM)strength,bench press explosive power,and two BPU tests with a 48-hour interval.BPU test data were recorded using a three-dimensional(3D)force platform and motion capture system to calculate concentric metrics such as peak force(PF)and mean velocity(MV).The intraclass correlation coefficient(ICC)was used to examine the retest reliability of the BPU test.The Pearson correlation coefficient was used to evaluate the correlation of the BPU metrics with upper-limb strength and explosive power.Predictive models for upper-limb strength and explosive power were created using stepwise regression analysis.Results BPU metrics showed a good test-retest reliability(ICC=0.764-0.935).PF and MV,along with body weight(BW),were effective predictors of bench press 1RM in young males:bench press 1RM=0.129PF-16.772[R2=0.790,standard error of the estimate(SEE)=8.17 kg];bench press 1RM=1.511BW+87.15 MV-110.136(R2=0.767,SEE=8.60 kg).PF and BW were also predictors of bench press explosive power:bench press explosive power=2.755BW+0.287PF-17.351(R2=0.620,SEE=46.1 W).Conclusions The BPU test demonstrates a good test-retest reliability,and PF and MV from the BPU test can be used to predict upper-limb strength and explosive power in young males.

AKT,also known as Protein Kinase B(PKB),plays a critical role in cell proliferation and metabolism.There are three isoforms of AKT:AKT1,AKT2,and AKT3.The effects of these isoforms on the pluripotency and differentiation of mouse embryonic stem cells(mESCs)remain unclear.This study aims to explore the impact of three AKT isoform-specific knockouts on the self-renewal and differen-tiation of mouse embryonic stem cells.Using CRISPR/Cas9 gene-editing technology,AKT isoform-spe-cific knockout cell lines were established.The phenotypic and molecular changes were analyzed through Western blotting,flow cytometry,qRT-PCR,CCK-8 assays,Alkaline Phosphatase(AP)staining,and RNA-seq.The construction of AKT isoform-specific knockout cell lines was successful.The loss of AKT1 and AKT2 inhibited the proliferation of mESCs.The knockout of any single AKT isoform did not affect the expression of pluripotency genes at both mRNA or protein levels.However,during embryoid body forma-tion,the deletion of any of the three AKT isoforms affected the mRNA expression levels of genes in all three germ layers.Transcriptome analysis showed that compared to wild-type mESCs,995,547,and 429 differentially expressed genes(|log2FC|≧1,P＜0.05)were identified inAKT1,AKT2,and AKT3 isoform-specific knockout cells,respectively.There was some overlap in the differentially expressed genes regulated by these three isoforms.In conclusion,the independent knockout of AKT isoforms does not af-fect the maintenance of pluripotency in mouse embryonic stem cells,but they are crucial for differentia-tion.The three AKT isoforms can collectively regulate gene expression while retaining their own regulato-ry specificity.This study provides a foundation for understanding the unique and overlapping roles of AKT isoforms in stem cell biology,highlighting their importance in maintaining stem cell function and differen-tiation.

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.

Objective To evaluate the test-retest reliability of the ballistic push-up(BPU)test and establish predictive models for upper-limb strength and explosive power in young males.Methods A total of 71 male college students performed assessments of upper-limb bench press 1 repetition maximum(1RM)strength,bench press explosive power,and two BPU tests with a 48-hour interval.BPU test data were recorded using a three-dimensional(3D)force platform and motion capture system to calculate concentric metrics such as peak force(PF)and mean velocity(MV).The intraclass correlation coefficient(ICC)was used to examine the retest reliability of the BPU test.The Pearson correlation coefficient was used to evaluate the correlation of the BPU metrics with upper-limb strength and explosive power.Predictive models for upper-limb strength and explosive power were created using stepwise regression analysis.Results BPU metrics showed a good test-retest reliability(ICC=0.764-0.935).PF and MV,along with body weight(BW),were effective predictors of bench press 1RM in young males:bench press 1RM=0.129PF-16.772[R2=0.790,standard error of the estimate(SEE)=8.17 kg];bench press 1RM=1.511BW+87.15 MV-110.136(R2=0.767,SEE=8.60 kg).PF and BW were also predictors of bench press explosive power:bench press explosive power=2.755BW+0.287PF-17.351(R2=0.620,SEE=46.1 W).Conclusions The BPU test demonstrates a good test-retest reliability,and PF and MV from the BPU test can be used to predict upper-limb strength and explosive power in young males.

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.

Objective To compare the effect of small optical zone orthokeratology lenses(OK lenses)and repeated low-level red-light(RLRL)therapy in controlling myopia progression for adolescents,and the therapeutic effectiveness of RLRL is evaluated.Methods A retrospective analysis was conducted on the clinical data of 80 adolescent myopic patients in the First Affiliated Hospital of Army Medical University.The patients were divided into the RLRL group and the OK lenses group according to different intervention methods,with 40 cases in each group.Patients in the RLRL group received RLRL therapy combined with single-vision spectacles,and patients in the OK lenses group were treated with OK lenses.The changes of spherical equivalent(SE),axial length and subfoveal choroidal thickness(SFCT)1,3,6,and 12 months after treatment compared with the baseline,and color vision of patients were assessed.Based on the mean baseline axial length of the RLRL group,the patients in this group were subdivided into the short axial group and the long axial group,and the changes of the axial length and SFCT were further analyzed.Results The diopter 1,3,6,and 12 months after treatment in the RLRL group were not significantly different from the baseline(P>0.05).Axial lengths of patients in the RLRL group progressively shortened after treatment and returned close to the baseline 12 months after treatment.In contrast,axial lengths of patients in the OK lens continued to grow within 12 months after treatment;the axial lengths at each time point after treatment of patients in the two groups were significantly different from the baseline(P<0.05).The changes of axial length of patients in the RLRL group at each time point after treatment were significantly smaller than those in the OK lenses group(P<0.05).The SFCT changes of patients in the RLRL group at each time point after treatment were all greater than those in the OK lenses group(P<0.05).The SFCT at each time point after treatment in the RLRL group were significantly different from the baseline(P<0.05),whereas the SFCT at each time point after treatment in the OK lenses group were not significantly different from the baseline(P>0.05).The changes of axial length at each time point after treatment of patients in the long axial group were all greater than those in the short axial group(P<0.05);the SFCT changes 6 months after treatment of patients in the long axial group was greater than that in the short axial group(P<0.05);the SFCT at each time point after treatment of patients in the two groups were signifi-cantly different from the baseline(P<0.05).Color vision tests revealed no abnormities after treatment in the RLRL group and the OK lenses group.Conclusion RLRL therapy is effective in controlling myopia progression and demonstrates superior axial length control compared to orthokeratology lenses.

Objective To compare the effect of small optical zone orthokeratology lenses(OK lenses)and repeated low-level red-light(RLRL)therapy in controlling myopia progression for adolescents,and the therapeutic effectiveness of RLRL is evaluated.Methods A retrospective analysis was conducted on the clinical data of 80 adolescent myopic patients in the First Affiliated Hospital of Army Medical University.The patients were divided into the RLRL group and the OK lenses group according to different intervention methods,with 40 cases in each group.Patients in the RLRL group received RLRL therapy combined with single-vision spectacles,and patients in the OK lenses group were treated with OK lenses.The changes of spherical equivalent(SE),axial length and subfoveal choroidal thickness(SFCT)1,3,6,and 12 months after treatment compared with the baseline,and color vision of patients were assessed.Based on the mean baseline axial length of the RLRL group,the patients in this group were subdivided into the short axial group and the long axial group,and the changes of the axial length and SFCT were further analyzed.Results The diopter 1,3,6,and 12 months after treatment in the RLRL group were not significantly different from the baseline(P>0.05).Axial lengths of patients in the RLRL group progressively shortened after treatment and returned close to the baseline 12 months after treatment.In contrast,axial lengths of patients in the OK lens continued to grow within 12 months after treatment;the axial lengths at each time point after treatment of patients in the two groups were significantly different from the baseline(P<0.05).The changes of axial length of patients in the RLRL group at each time point after treatment were significantly smaller than those in the OK lenses group(P<0.05).The SFCT changes of patients in the RLRL group at each time point after treatment were all greater than those in the OK lenses group(P<0.05).The SFCT at each time point after treatment in the RLRL group were significantly different from the baseline(P<0.05),whereas the SFCT at each time point after treatment in the OK lenses group were not significantly different from the baseline(P>0.05).The changes of axial length at each time point after treatment of patients in the long axial group were all greater than those in the short axial group(P<0.05);the SFCT changes 6 months after treatment of patients in the long axial group was greater than that in the short axial group(P<0.05);the SFCT at each time point after treatment of patients in the two groups were signifi-cantly different from the baseline(P<0.05).Color vision tests revealed no abnormities after treatment in the RLRL group and the OK lenses group.Conclusion RLRL therapy is effective in controlling myopia progression and demonstrates superior axial length control compared to orthokeratology lenses.

Objective To describe and analyze the current status,changing trend and influencing factors of the disease burden of cervical,endometrial and ovarian cancer in China from 1990 to 2021.Methods Data on incidence,mortality,disability-adjusted life year(DALY),and other indicators for cervical,endometrial and ovarian cancer were collected from the 2021 Global Burden of Disease database.Joinpoint regression models were used to analyze time trends,and age-period-cohort(APC)models assessed their impact on incidence and mortality.Spearman correlation analysis was performed to evaluate the relationship between the sociodemographic index(SDI)and the cancer indicators.Finally,the attributable risk factors for the disease burden were analyzed.Results From 1990 to 2021,age-standardized incidence rates of cervical and endometrial cancers in China significantly increased,while ovarian cancer showed no significant change.Age-standardized mortality,DALY,and years of life lost due to premature death(YLL)decreased significantly.The disease burden was heavier in middle-aged and older groups.APC model indicated an increase in cervical cancer incidence and a decrease in mortality over time.Furthermore,the incidence risks of cervical and endometrial cancers were elevated in successive birth cohorts,whereas a lower risk was observed for ovarian cancer.Correlation analysis showed significant associations between cancer incidence and mortality with SDI.Obesity has significantly contributed to the disease burden of common gynecologic cancers in China.Conclusion Mortality rates of cervical,endometrial and ovarian cancer have declined,while the incidence of cervical and endometrial cancers has significantly increased.The trends in incidence and mortality are influenced by age,period and cohort effects.Future efforts should focus on controlling risk factors like obesity to reduce the disease burden.

AKT,also known as Protein Kinase B(PKB),plays a critical role in cell proliferation and metabolism.There are three isoforms of AKT:AKT1,AKT2,and AKT3.The effects of these isoforms on the pluripotency and differentiation of mouse embryonic stem cells(mESCs)remain unclear.This study aims to explore the impact of three AKT isoform-specific knockouts on the self-renewal and differen-tiation of mouse embryonic stem cells.Using CRISPR/Cas9 gene-editing technology,AKT isoform-spe-cific knockout cell lines were established.The phenotypic and molecular changes were analyzed through Western blotting,flow cytometry,qRT-PCR,CCK-8 assays,Alkaline Phosphatase(AP)staining,and RNA-seq.The construction of AKT isoform-specific knockout cell lines was successful.The loss of AKT1 and AKT2 inhibited the proliferation of mESCs.The knockout of any single AKT isoform did not affect the expression of pluripotency genes at both mRNA or protein levels.However,during embryoid body forma-tion,the deletion of any of the three AKT isoforms affected the mRNA expression levels of genes in all three germ layers.Transcriptome analysis showed that compared to wild-type mESCs,995,547,and 429 differentially expressed genes(|log2FC|≧1,P＜0.05)were identified inAKT1,AKT2,and AKT3 isoform-specific knockout cells,respectively.There was some overlap in the differentially expressed genes regulated by these three isoforms.In conclusion,the independent knockout of AKT isoforms does not af-fect the maintenance of pluripotency in mouse embryonic stem cells,but they are crucial for differentia-tion.The three AKT isoforms can collectively regulate gene expression while retaining their own regulato-ry specificity.This study provides a foundation for understanding the unique and overlapping roles of AKT isoforms in stem cell biology,highlighting their importance in maintaining stem cell function and differen-tiation.