Objective To isolate pathogenic bacteria from the skin of a nude mouse exhibiting squamous skin scurfs, and perform bacterial identification, traceability analysis, and pathogenicity studies to provide a new approach for the diagnosis of pathogens in nude mice with squamous skin scurfs. MethodsSkin swab samples were collected from a nude mouse exhibiting squamous skin scurfs for nucleic acid testing, bacterial isolation and culture, biochemical identification, 16S rDNA gene amplification and sequencing, and whole genome sequencing to construct a phylogenetic tree. Fifteen BALB/c nude mice were randomized into a saline-treated control group, a high-concentration group treated with 1.8×10⁸ CFU/mL of the isolated bacterial suspension, and a low-concentration group treated with 1.8×10⁷ CFU/mL of the isolated bacterial suspension. Pathogenicity was assessed by animal infection experiments and observation of histopathological changes in skin tissue using HE staining. Results The nucleic acid test for Corynebacterium bovis was negative, excluding infection by this organism. The pathogen isolated on mannitol salt agar and blood agar, combined with Gram staining, suggested a Gram-positive Staphylococcus species. The isolated strain was identified by 16S rDNA sequencing and a fully automated microbial identification system as Staphylococcus xylosus. Phylogenetic tree analysis based on whole genome sequencing showed that the strain was most closely related to an isolate from leafy vegetables in South Korea (GenBank GCA_00207825.1). In the high-concentration group, squamous skin scurfs appeared on the head, neck, and back of nude mice on the 17th day post-infection, while in the low concentration group, similar symptoms appeared on the 20th day post-infection and gradually spread to other areas. The scaling symptoms were transient, lasting for 7 days in the high-concentration group and 3 days in the low-concentration group, after which the skin returned to normal. The infection rate was 33.33% in both the high- and low-concentration groups. No significant pathological changes were observed in the skin tissues of infected mice compared to the control group, indicating marked individual differences in the pathogenicity of the strain in nude mice. Conclusion A strain of Staphylococcus xylosus was isolated from the skin of a nude mouse exhibiting squamous skin scurfs. The strain is an opportunistic pathogen that causes transient squamous skin scurfs without significant histopathological changes, and there are individual differences in the sensitivity of nude mice to this strain. These findings can provide valuable data for pathogen identification in immunodeficient or gene knockout mice.

Objective To isolate pathogenic bacteria from the skin of a nude mouse exhibiting squamous skin scurfs, and perform bacterial identification, traceability analysis, and pathogenicity studies to provide a new approach for the diagnosis of pathogens in nude mice with squamous skin scurfs. MethodsSkin swab samples were collected from a nude mouse exhibiting squamous skin scurfs for nucleic acid testing, bacterial isolation and culture, biochemical identification, 16S rDNA gene amplification and sequencing, and whole genome sequencing to construct a phylogenetic tree. Fifteen BALB/c nude mice were randomized into a saline-treated control group, a high-concentration group treated with 1.8×10⁸ CFU/mL of the isolated bacterial suspension, and a low-concentration group treated with 1.8×10⁷ CFU/mL of the isolated bacterial suspension. Pathogenicity was assessed by animal infection experiments and observation of histopathological changes in skin tissue using HE staining. Results The nucleic acid test for Corynebacterium bovis was negative, excluding infection by this organism. The pathogen isolated on mannitol salt agar and blood agar, combined with Gram staining, suggested a Gram-positive Staphylococcus species. The isolated strain was identified by 16S rDNA sequencing and a fully automated microbial identification system as Staphylococcus xylosus. Phylogenetic tree analysis based on whole genome sequencing showed that the strain was most closely related to an isolate from leafy vegetables in South Korea (GenBank GCA_00207825.1). In the high-concentration group, squamous skin scurfs appeared on the head, neck, and back of nude mice on the 17th day post-infection, while in the low concentration group, similar symptoms appeared on the 20th day post-infection and gradually spread to other areas. The scaling symptoms were transient, lasting for 7 days in the high-concentration group and 3 days in the low-concentration group, after which the skin returned to normal. The infection rate was 33.33% in both the high- and low-concentration groups. No significant pathological changes were observed in the skin tissues of infected mice compared to the control group, indicating marked individual differences in the pathogenicity of the strain in nude mice. Conclusion A strain of Staphylococcus xylosus was isolated from the skin of a nude mouse exhibiting squamous skin scurfs. The strain is an opportunistic pathogen that causes transient squamous skin scurfs without significant histopathological changes, and there are individual differences in the sensitivity of nude mice to this strain. These findings can provide valuable data for pathogen identification in immunodeficient or gene knockout mice.

Objective:To investigate the efficacy of sintilimab combined with paclitaxel and docetaxel in the treatment of advanced non-small cell lung cancer (NSCLC).Methods:Prospective cohort study was performed. A total of 90 patients with advanced NSCLC receiving second-line treatment in Baotou Cancer Hospital from October 2019 to October 2022 were prospectively selected. All patients were divided into the study group (sintilimab combined with paclitaxel and docetaxel as second-line treatment, 45 cases) and the control group (paclitaxel or docetaxel alone, 45 cases) according to random number table method. The short-term efficacy, serum cytokine levels, quality of life and T-cell subsets of the two groups were compared. The survival of patients within 6 months was followed up. Kaplan-Meier method was used to analyze the overall survival (OS) of both groups, and log-rank test was used to make comparison among groups.Results:There were 25 males (55.56%) in the study group with the age of (63±5) years and 28 males (62.22%) in the control group with the age of (65±6) years. There were no statistically significant differences in the gender, age, Eastern Cooperative Oncology Group scores, the body mass (all P>0.05). The total effective rate was 88.89% (40/45) in the study group and 71.11% (32/45) in the control group, and the difference was statistically significant ( χ2 = 4.44, P = 0.035). The levels of serum vascular endothelial growth factor (VEGF) and carbohydrate antigen 125 (CA125) of both groups after treatment were lower than those before treatment (all P<0.001); the levels of VEGF and CA125 in the study group after treatment were lower than those in the control group [VEGF: (223±15) pg/ml vs. (289±15) pg/ml, t=20.82, P<0.001;CA125: (23±6) ng/ml vs. (75±4) ng/ml, t=51.28, P<0.001].Quality of life scale score, Karnofsky score of both groups after treatment were higher than those before treatment (all P<0.05); quality of life scale score and Karnofsky score in the study group after treatment were higher than those in the control group [quality of life scale score: (63±6) scores vs. (51±5) scores, t=10.29, P<0.001; Karnofsky score: (80.5±5.7) scores vs.(78.8±3.7) scores, t=1.70, P=0.041]. T-cell subsets indicators of both groups after treatment were higher than those before treatment (all P<0.001). T-cell subsets indicators in the study group after treatment were higher than those in the control group [CD3 + cell proportion: (68±5)% vs. (65±5)%, t=2.52, P = 0.014; CD4 + cell proportion:(42.5±1.7)% vs. (36.5±3.7)%, t=9.91, P<0.001;CD4 +/CD8 +: 1.78±0.54 vs. 1.46±0.27, t=3.56, P<0.001]. There was no significant difference in the incidence of adverse reactions between the two groups [11.11% (5/45) vs. 15.55% (7/45), χ2=0.39, P=0.534]. The follow-up time was 6 months. The OS in the study group was better than that in the control group ( χ2=3.86, P = 0.044). Conclusions:Sintilimab combined with taxoid chemotherapy drugs is effective in the second-line treatment of advanced NSCLC, and it improves immune function and shows a favorable safety.

Objective: To investigate the association between 24 h movement behaviors (physical activity, sleep, and screen time) and fundamental motor skills (FMS) in preschool children, in order to provide the reference and basis for ensuring the longterm development of childrens motor skills. Methods: A total of 607 children aged 3 to 5 years old were selected from 6 kindergartens of 6 urban districts in Taiyuan in March 2022, through a combination of convenient sampling and stratified cluster random sampling method, and the baseline test was conducted to collect data on the childrens 24 h movement behaviors and FMS; the followup test after one year was carried out in March 2023 to collect FMS data. The test of gross motor development-3rd was used to assess the childrens FMS levels. Physical activity and sleep duration were measured using ActiGraph GT3X+ accelerometers, while screen time was reported by parents. Pearson correlation analysis, hierarchial and binary Logistic regression analyses were used to analyze the association of 24 h movement behavior with FMS. Results: The results of baseline showed that total of physical activity (TPA) at baseline was positively associated with manipulation skills, mobility skills and total score of TGMD-3 (β=0.40, 3.87, 4.27, P<0.01). The followup results after one year indicated that lowintensity physical activity (LPA) and screen time at baseline were negatively associated with increased TGMD-3 scores one year later (β=-1.93, -0.79, P<0.01). Conversely, baseline moderatetovigorousintensity physical activity (MVPA), TPA and sleep duration were positively associated with increased TGMD-3 scores after one year (β=4.62, 4.51, 3.19, P<0.01). The followup results showed that meeting 2 or 3 items of the 24 h movement behavior guidelines was significantly associated with an increased likelihood of achieving motor skill proficiency (OR=2.31, 3.32, P<0.01) compared to not meeting any 24 h movement behavior guideline after one year. Conclusions MVPA and enough sleep could positively affect FMS improvement, whereas LPA and long screen time could negatively affect FMS improvement at one year followup. Schools and families should ensure that preschool children meet the recommended standards of the 24 h movement behavioral guidelines to promote longterm development of FMS.

Objective: To explore the factors affecting the prevalence of HIV-associated neurocognitive disorders (HAND) among HIV/AIDS patients, so as to provide insights into developing HAND prevention measures. Methods: HIV/AIDS patients aged 18 years and above in the Infection Department of Nanjing Second Hospital were selected.Demographic data, treatment regimen and blood biochemical indicators were collected. Depression was evaluated using Patient Health Questionnaire Depression Scale, frailty was evaluated using Chinese version of Tilburg Frailty Indicator, and HAND was evaluated by Montreal Cognitive Assessment Scale. Factors affecting HAND were analyzed using a multivariable logistic regression model. Results: Totally 440 questionnaires were allocated and 426 valid questionnaires were recovered, with an effective rate of 96.82%. The median age of patients investigated was 33.00 (interquartile range, 10.00) year. There were 407 males, accounting for 95.54%; 232 patients with bachelor degree or above, accounting for 54.46%; 171 patients with HAND, accounting for 40.14%. Multivariable logistic regression analysis showed that educational level (bachelor degree or above, OR=0.291, 95%CI: 0.157-0.541), depression (OR=2.499, 95%CI: 1.530-4.083), frailty (OR=2.121, 95%CI: 1.307-3.441) and treatment regimen including efavirenz (OR=2.223, 95%CI: 1.367-3.615) were the influencing factors for HAND among HIV/AIDS patients. Conclusion Educational level, depression, frailty and use of efavirenz may be associated with HAND risk.

Objective To explore the correlation of CPNE3 expression with long-term prognosis of patients with gastric cancer(GC)and the possible mechanism.Methods We retrospectively collected the data of 104 GC patients undergoing radical surgery in our hospital from February,2013 to October,2017.TCGA database and immunohistochemistry were used to analyze CPNE3 expression level in GC tissues and its effects on tumor progression and long-term prognosis of the patients.GO analysis was performed to predict the biological role of CPNE3 in GC.We also conducted cell experiments with MGC803 cells and observed the effects of CPNE3 knockdown,CPNE3 overexpression and LY294002(a PI3K/AKT inhibitor)treatment on cell apoptosis and cellular expressions of apoptotic proteins using flow cytometry and Western blotting.Results TCGA analysis and immunohistochemistry both showed high expressions of CPNE3 in GC(P<0.05).The patients with high CPNE3 expressions had a reduced 5-year survival(P<0.01),and a high CPNE3 expression,CEA level≥5 μg/L,CA19-9 level≥37 kU/L,T3-T4 stage,and N2-N3 stage were all independent risk factors for a lowered 5-year survival rate after surgery.The sensitivity and specificity of CPNE3 for predicting 5-year mortality was 79.59%and 74.55%,respectively(P<0.05).GO analysis predicted that CPNE3 negatively regulated GC cell apoptosis.In MGC803 cells,CPNE3 knockdown significantly increased cell apoptosis,enhanced Bax and Cleaved Caspase-3 expressions and decreased Bcl-2 expression,while CPNE3 overexpression produced the opposite results(P<0.05).The cellular expressions of p-PI3K and p-AKT were significantly decreased following CPNE3 knockdown and increased following CPNE3 overexpression(P<0.05).Treatment with LY294002 obviously attenuated the inhibitory effect of CPNE3 overexpression on apoptosis of MGC803 cells(P<0.05).Conclusion CPNE3 is highly expressed in GC tissues and affects the long-term prognosis of the patients possibly by inhibiting GC cell apoptosis through activation of PI3K/AKT signaling.

Objective To investigate the effects of kuwanon G(KG)on proliferation,apoptosis,migration and invasion of gastric cancer cells and the molecular mechanisms.Methods The effects of KG on proliferation and growth of gastric cancer cells were assessed with CCK-8 assay and cell clone formation assay,by observing tumor formation on the back of nude mice and using immunohistochemical analysis of Ki-67.The effect of KG on cell apoptosis was analyzed using Annexin V-FITC/PI apoptosis detection kit,Western blotting and TUNEL staining.The effects of KG on cell migration and invasion were detected using Transwell migration and invasion assay and Western blotting for matrix metalloproteinase(MMP).The role of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway in KG-mediated regulation of gastric cancer cell proliferation,migration,and invasion was verified by Western blotting and rescue assay.Results KG significantly inhibited proliferation and reduced clone formation ability of gastric cancer cells in a concentration-dependent manner(P<0.05).KG treatment also increased apoptosis,enhanced the expressions of cleaved caspase-3 and Bax,down-regulated Bcl-2,lowered migration and invasion capacities and inhibited the expression of MMP2 and MMP9 in gastric cancer cells(P<0.05).Mechanistic validation showed that KG inhibited the activation of the PI3K/AKT/mTOR pathway,and IGF-1,an activator of the PI3K/AKT/mTOR pathway,reversed the effects of KG on proliferation,migration and invasion of gastric cancer cells(P<0.05).Conclusion KG inhibits proliferation,migration and invasion and promotes apoptosis of gastric cancer cells at least in part by inhibiting the activation of the PI3K/AKT/mTOR pathway.

Hepatocellular carcinoma(HCC)is the most common type of primary liver cancer and the third leading cause of cancer-related deaths,and it is a serious threat to human health and has become a clinical problem that needs to be solved urgently.Extracellular vesicles(EV)are membrane vesicles containing multiple components and play an important role in the development and progression of HCC.This article summarizes the effect of EVs of different origins on HCC and analyzes the mechanism of action of EV on HCC,so as to provide new perspectives for the diagnosis and treatment of HCC.

Treatment resistance of hepatocellular carcinoma(HCC)is an important factor restricting its treatment outcome.Autophagy is a process involving multiple steps and targets and is closely associated with the proliferation and apoptosis of tumor cells.At the same time,there is significant crosstalk between autophagy and tumor treatment resistance.Therefore,autophagy may be one of the key factors hindering tumor cell death after medical intervention.Transforming growth factor-β(TGF-β),epithelial-mesenchymal transition(EMT),and long non-coding RNA(lncRNA)are important factors leading to drug resistance of HCC.This article discusses the possible mechanism of TGF-β,EMT,and lncRNA mediating complex molecular networks and inducing drug resistance of HCC,in order to provide new ideas for improving the sensitivity of HCC treatment.

After kidney transplantation,the recipients have been under long-term immunosuppression due to the use of immunosuppressive drugs,and they are high-risk population of Pneumocystis jirovecii pneumonia(PJP).The risk of PJP is the highest within 6 months after kidney transplantation and after intensified anti-rejection therapy.Fever,dry cough,progressive dyspnea and hypoxemia are common clinical manifestations of PJP after kidney transplantation.Trimethoprim-sulfamethoxazole(TMP-SMX)can effectively prevent and treat PJP,and significantly reduce the incidence rate and fatality of PJP.To standardize the diagnosis,treatment and prevention of PJP after kidney transplantation,Branch of Organ Transplantation of Chinese Medical Association organized relevant Chinese experts to formulate the"Guidelines for Clinical Diagnosis and Treatment of Pneumocystis Jirovecii Pneumonia After Kidney Transplantation in China"based on clinical concerns,aiming to provide guidance for the prevention and comprehensive clinical treatment of PJP after kidney transplantation.