Objective To explore the therapeutic effect and mechanism of umbilical cord mesenchymal stem cells (UC-MSC) in rats with primary graft dysfunction after lung transplantation. Methods Twenty-four male Lewis rats were randomly divided into donor and recipient groups, with 12 rats in each group. The recipients were further divided into 3 groups: blank control group, negative control group, and treatment group, with 4 rats in each group. The color, size and texture of the transplanted lungs were observed 72 h after lung transplantation. The ventilation status and progression of consolidation in the transplant lungs of rats in each group were evaluated by micro-CT. Plasma, transplant lung tissue and alveolar lavage fluid samples of recipient rats were collected. The wet/dry ratio of lung tissue was measured to evaluate the degree of pulmonary edema. Hematoxylin-eosin (HE) staining was used to evaluate the degree of lung tissue damage. Terminal deoxyribonucleic acid transferase mediated dUTP nick end labeling (TUNEL) staining was used to evaluate cell apoptosis. Myeloperoxidase (MPO) activity in lung tissue was detected, and enzyme-linked immunosorbent assay (ELISA) was used to detect interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α levels in plasma and alveolar lavage fluid. Results The appearance of the transplant lungs in the negative control group was significantly different from that of the autologous lungs, while the transplant lungs in the treatment group were almost identical in color to the autologous lungs compared to the blank control group. Compared with the negative control group, the treatment group showed reduced alveolar exudate and more intact airway epithelial cell structure. No alveolar exudate was observed in the blank control group, and the structure of the airways and alveoli remained normal. The treatment group had lower apoptosis rate of airway epithelial cells, lung tissue wet/dry ratio, and MPO activity compared to the negative control group (all P < 0.05). The levels of IL-6 and TNF-α in the bronchoalveolar lavage fluid of the treatment group were lower than those in the negative control group, while the level of IL-10 was higher than that in the negative control group and the blank control group (all P < 0.05). There were no statistically significant differences in the levels of cytokines in plasma among each group (all P > 0.05). Conclusions UC-MSC may effectively alleviate the severity of primary graft dysfunction in rats by reducing the apoptosis rate of cells in lung tissue and inhibiting inflammatory responses.

ObjectiveTo investigate the variation of drug resistance genes in human immunodeficiency virus (HIV)-1 strains in Huzhou City, Zhejiang Province, so as to provide a basis for guiding the adjustment of treatment plans for ADIS patients or patients infected with HIV. MethodsA total of 555 samples were collected from 396 newly diagnosed HIV/AIDS patients who did not receive antiviral treatment from 2021 to 2023, in addition to 159 HIV/AIDS patients who received antiviral treatment for at least twelve months but failed during the same period.Reverse transcription polymerase chain reaction (RT-PCR) and nested polymerase chain reaction (nested PCR) were used to amplify the pol region gene of HIV-1. Lastly, the sequenced data were submitted to the HIV resistance database of Stanford University in the United States for resistance gene mutation analysis. ResultsDrug resistance mutations were detected in samples from 97 newly diagnosed HIV/AIDS patients and 77 patients with failed treatment, with the main subtypes being CRF01AE and CRF07-BC. The mutation rates of drug resistance genes in the patients untreated and patients with failed treatment were 24.49% (97/396) and 48.43% (77/159), respectively. Drug resistance gene mutations against protease inhibitor (PI), nucleotide reverse transcriptase inhibitor (NRTI), and non-nucleoside reverse transcriptase inhibitor (NNRTI) were detected both in the untreated and failed treatment group. The drug resistance rates of untreated and failed treatment patients were 10.61% (42/396) and 45.28% (72/159), respectively. ConclusionThe pre-treatment drug resistance rate of HIV-1 strains in Huzhou City is at a moderate level, and which is at a relatively low level nationwide after antiviral treatment. The resistance genes in the region exhibit diverse and complex characteristics, and the prevalence of drug resistance is in the process of upward and evolution compared to the monitoring results in the previous years. It is necessary to continue to monitor the occurrence and development of drug resistant strains, and to adjust treatment plans in time to prevent the occurrence of transmissible drug resistance.

OBJECTIVES: To investigate the role of SF3B3 in gastric cancer (GC) progression and prognosis and its possible mechanisms. METHODS: SF3B3 expression levels in pan-cancer and GC were analyzed using TIMER2.0, GEPIA, and UALCAN databases and validated using immunohistochemistry in GC tissues. Survival curves of GC patients were established using Kaplan-Meier Plotter and the data of a patient cohort our hospital. The independent risk factors for 5-year postoperative survival were identified using Cox regression, and their predictive values were evaluated using ROC analysis. SF3B3-associated biological processes were predicted by bioinformatics enrichment analyses. In GC HGC-27 cells, the effects of lentivirus-mediated SF3B3 knockdown and overexpression on cell proliferation and migration were investigated, and the changes in the key glycolytic proteins and extracellular acidification rate (ECAR) were detected. The influence of SF3B3 expression level on tumorigenesis and glycolytic protein expression in vivo were evaluated in a nude mouse xenograft model. RESULTS: High expression of SF3B3 in GC was associated with poor patient prognosis (P<0.05). The factors affecting 5-year survival outcomes following gastric oncological resection included high SF3B3 expression, a CEA level ≥5μg/L, a CA19-9 level ≥37 kU/L, tumor stage T3-4, and lymph node metastasis stage N2-3 (P<0.05). Bioinformatics analysis showed significant enrichment of SF3B3 in glycolysis. In HGC-27 cells, SF3B3 knockdown significantly inhibited while SF3B3 overexpression enhanced cell proliferation, migration, and invasion. SF3B3 knockdown obviously decreased the expressions of HK2, PKM2 and LDHA proteins and ECAR in HGC-27 cells, whereas SF3B3 overexpression produced the opposite effect. In nude mouse xenograft models, SF3B3 knockdown significantly reduced tumor mass and downregulated expression of HK2, PKM2 and LDHA proteins, and SF3B3 overexpression induced the opposite changes. CONCLUSIONS SF3B3 overexpression is associated with poor prognosis of GC patients and promotes GC cell proliferation, migration and invasion possibly by enhancing glycolysis.
Stomach Neoplasms/diagnosis* ; Humans ; Cell Proliferation ; Prognosis ; Animals ; Mice, Nude ; Cell Line, Tumor ; Mice ; Cell Movement ; Male ; Female

Senecavirus A (SVA) is a major viral pathogen causing disease in pigs, and effective monitoring of SVA infection is critical for disease control. In this study, we aimed to develop a reliable ELISA method for rapidly detecting neutralizing antibodies against SVA. We used HEK293F cells to express an SVA-specific porcine Fab antibody and verified the biological activity of the Fab antibody by indirect ELISA, immunofluorescence assay, virus neutralization test, and Western blotting. The Fab antibody was biotinylated and used as a competitive antibody to establish a competitive ELISA (C-ELISA) for detecting neutralizing antibodies against SVA. We then evaluated the C-ELISA in terms of sensitivity, specificity, repeatability, and result agreement rate with the VNT. The results showed that we successfully prepared an SVA-specific porcine Fab antibody, which showed high affinity for SVA. We named this antibody 1M33Fab and designated it as Bio-1M33Fab after biotin labeling. The assay conditions were optimized as follows: the coating concentration of SVA particles being 1 μg/mL, the working concentration of Bio-1M33Fab being 0.5 μg/mL, the optimal serum dilution of 1:10, and the optimal dilution of enzyme-labeled avidin being 1:30 000. At a percent inhibition (PI) of 47%, the assay demonstrated the highest sensitivity (96.88%) and specificity (100%), with no cross-reactivity observed with the positive sera of major porcine viral diseases. The intra-assay coefficient of variation ranged from 1.12% to 7.34%, while the inter-assay coefficient of variation ranged from 1.10% to 8.97%, indicating good repeatability. In the detection of 224 clinical pig serum samples, C-ELISA and VNT showed a result agreement rate of 93.75%. In conclusion, we successfully develop a C-ELISA method for detecting neutralizing antibodies against SVA by using a porcine-derived Fab antibody, which lays a foundation for the development of detection kits.
Animals ; Swine ; Antibodies, Neutralizing/immunology* ; Enzyme-Linked Immunosorbent Assay/methods* ; Immunoglobulin Fab Fragments/immunology* ; Antibodies, Viral/immunology* ; Picornaviridae/immunology* ; Humans ; HEK293 Cells ; Swine Diseases/diagnosis* ; Picornaviridae Infections/diagnosis*

Objective In recent decades,China has implemented a series of policies to address air pollution.We aimed to assess the health effects of these policies on stroke burden attributable to ambient fine particulate matter(PM2.5). Methods Joinpoint regression was applied to explore the temporal tendency of stroke burden based on data from the Global Burden of Disease 2019 study. Results The age-standardized rates of disability-adjusted life year(DALY)for stroke attributable to ambient PM2.5 in China,increased dramatically during 1990-2012,subsequently decreased at an annual percentage change(APC)of-1.98[95%confidence interval(CI):-2.26,-1.71]during 2012-2019.For ischemic stroke(IS),the age-standardized DALY rates doubled from 1990 to 2014,and decreased at an APC of-0.83(95%CI:-1.33,-0.33)during 2014-2019.Intracerebral hemorrhage(ICH)showed a substantial increase in age-standardized DALY rates from 1990 to 2003,followed by declining trends,with APCs of-1.46(95%CI:-2.74,-0.16)during 2003-2007 and-3.33(95%CI:-3.61,-3.06)during 2011-2019,respectively.Conversely,the age-standardized DALY rates for subarachnoid hemorrhage(SAH)generally declined during 1990-2019. Conclusion Our results clarified the dynamic changes of the ambient PM2.5-attributable stroke burden in China during 1990-2019,highlighting the health effects of air quality improvement policies.

Objective To explore the regulatory role of Abelson interactor 2(ABI2)in progression and prognosis of gastric cancer.Methods TIMER2.0,GEPIA,Kaplan-Meier Plotter and DAVID databases were used to analyze ABI2 expression in pan-cancer and its association with the prognosis of gastric cancer.Gastric cancer and adjacent tissues from 120 patients undergoing radical gastrectomy in our hospital between January,2016 and October,2018 were examined for ABI2 expression and its correlation with disease progression and prognosis.MGC-803 cell models of ABI2 knockdown and overexpression were established for observing the changes in cell proliferation,migration,and invasion,and the impact of ABI2 expression modulation on xenograft growth was evaluated in nude mice.Results Database analysis and examination of the clinical samples showed that ABI2 was highly expressed in gastric cancer tissues.Survival analysis suggested that gastric cancer patients with a high expression of ABI2 had a reduced postoperative 5-year survival rate(P<0.0001),and further Cox univariate and multivariate survival analyses indicated that a high ABI2 expression was an independent risk factor affecting the patients survival outcomes(P=0.022,HR=1.887,95%CI:1.096-3.249).Enrichment analysis suggested the involvement of ABI2 in Wnt signaling.In MGC-803 cells,ABI2 overexpression promoted cell proliferation and xenograft growth in nude mice,increased the expressions of vimentin and N-cadherin,and lowered E-cadherin expression,while ABI2 knockdown produced the opposite effects.Mechanistic analysis revealed that ABI2 overexpression promoted the expressions of Wnt2 and β-catenin in both MGC-803 cells and the xenografts,and their expressions were significantly lowered by ABI2 knockdown.Conclusion ABI2 is highly expressed in gastric cancer,which affects long-term prognosis of the patients,possible due to its regulatory effect on Wnt signaling to promote proliferation,migration and invasion of gastric cancer cells.

Objective To investigate the correlation of CEP192 expression with prognosis of gastric cancer and biological behaviors of gastric cancer cells.Methods Public databases and clinical tissue samples were used to examine CEP192 expression level in gastric cancer.Kaplan-Meier survival curves,univariate and multivariate Cox regression analyses,ROC curves and bioinformatics analyses were used to explore the risk factors affecting the 5-year postoperative survival,the correlation of CEP192 expression level with the patients'survival,and its biological role in gastric cancer development.In gastric cancer MGC-803 cells with lentivirus-mediated CEP192 interference or overexpression,cell proliferation and expressions of PLK1,CDK1 and Cyclin B1 were examined with CCK-8 assay and Western blotting.The effects of CEP192 knockdown or overexpression on tumorigenesis of MGC-803 cells was observed in nude mice,and the expressions of PLK1,CDK1 and Cyclin B1 in the xenografts were detected.Results CEP192 was highly expressed in gastric cancer and associated with poor prognosis of the patients(P<0.05).High expression of CEP192,CEA≥5 ng/mL,CA199≥37 IU/mL,T3-4 stage,and N2-3 stage were independent risk factors affecting the patients'5-year postoperative survival(P<0.05).Bioinformatics analyses suggested that CEP192 was involved in several vital biological processes and positively regulated cell cycle progression.In MGC-803 cells,CEP192 knockdown significantly inhibited cell proliferation and lowered the expression levels of PLK1,CDK1,and Cyclin B1,while its overexpression produced the opposite effects.In the nude mouse models,CEP192 knockdown resulted in lowered tumorigenic potential of MGC-803 cells and decreased protein levels of PLK1,CDK1,and Cyclin B1 in the xenografts,while CEP192 overexpression in MGC-803 cells caused the opposite changes.Conclusion CEP192 overexpression is correlated with unfavorable outcomes of gastric cancer patients and promotes gastric cell proliferation by regulating the key proteins during G2/M phase transition.

Objective:To explore the value of dual-layer detector spectral CT quantitative parameters in evaluating the treatment response of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC).Methods:The study was a cross-sectional study. From May 2021 to March 2023, a total of 52 patients with LARC who received complete nCRT and were pathologically confirmed rectal adenocarcinoma at the Guangdong Province Hospital of Traditional Chinese Medicine were retrospectively enrolled. Each patient underwent spectral CT examination before and after nCRT, including plain scan, arterial phase (AP), and venous phase (VP) scans. According to the tumor regression grade, the patients were divided into the good response ( n=20) and the poor response group ( n=32). Measurements of the primary tumor′s spectral CT parameters, including effective atomic number (Z eff) at plain scan, iodine concentration (IC), CT values of 40 keV and 100 keV virtual monochromatic image (VMI) at dual-enhanced phases, were taken before and after nCRT. Additionally, the normalized iodine concentration (NIC), spectral curve slope (λHU), and the change rate of the above parameters before and after nCRT were calculated. The independent sample t-test or Mann-Whitney U test was used to compare the differences between the two groups. The receiver operating characteristic (ROC) curve was used to assess the efficacy of various metrics in evaluating the tumor treatment response of nCRT. A binary logistic regression analysis of combined parameter results was performed for the parameters with the areas under curve (AUC)>0.75, and the AUC of the combined parameter was evaluated. Results:There were significant differences in NIC AP and λHU VP before nCRT, NIC VP and λHU VP after nCRT, and the change rates of Z eff, NIC AP, NIC VP and λHU AP between the good response group and the poor response group ( P<0.05). The remaining parameters showed no statistically significant difference ( P>0.05). The ROC curve results showed that the AUCs of the above 8 parameters for evaluating tumor treatment response of nCRT were 0.702, 0.655, 0.695, 0.769, 0.738, 0.807, 0.791, and 0.677, respectively. The AUC of the combined model of the three parameters with AUC>0.75 (λHU VP after nCRT, the change rate of NIC AP and NIC VP) was 0.869, with 80.0% sensitivity and 84.4% specificity. Conclusion:The quantitative parameters derived from spectral CT may provide new markers for evaluating the response to nCRT treatment in patients with LARC. The multi-parameter combined model can improve diagnostic efficacy.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective To analyze the pathogenic bacteria and drug resistance of peritoneal dialysis-associated peritonitis(PDAP),and provide a clinical reference for the rational use of antibiotics.Methods The demographic data of PDAP patients admitted to the peritoneal dialysis(PD)Center of the First Affiliated Hospital of Soochow University from July 1,2015 to December 30,2021 were collected,and the pathogens,drug resistance and prognosis were retrospectively analyzed.Results A total of 150 episodes of PDAP occurred in 92 patients.The positive rate of PD fluid culture was 61.33％,including 65 cases(70.65％)of Gram-positive(G+)bacteria,mainly Staphylococcus and Streptococcus.Gram-negative(G-)bacteria were in 16 cases(17.39％),mainly Escherichia coli and Enterobacter cloacae.There were 11 cases(11.96％)of multiple infections,including 5 cases of combined fungal infection.From 2016 to 2021,the incidence of G+bacteria-related PDAP decreased from 14 to 8 cases.G+strains were resistant to methicillin(35.00％),and were sensitive to linezolid(100.00％),teicoplanin(100.00％)and rifampicin(100.00％).The sensitivity rate to vancomycin was 98.59％.G-strains were sensitive to ceftazidime(86.36％),ceftizoxime(88.89％)and amikacin(100.00％).The MIC of vancomycin against Staphylococcus showed an upward trend in 2019-2021.The overall cure rate of PDAP was 81.33％in patients who responded to antibiotic treatment,and the cure rate of G+bacteria was higher than that of multiple infections(89.23％vs.36.36％,P＜0.01).The outcome of patients with multiple infections,especially those with concurrent fungal infection was poor.Conclusion The incidence of PDAP in the PD center has shown a decreasing trend in recent years.G+bacteria are still the main pathogenic bacteria causing PDAP,and they are highly resistant to methicillin,so vancomycin should be used as empirical therapy.For G-bacteria,cefotaxime and amikacin can be chosen as empirical therapy.There is a drift in the MIC values of vancomycin against Staphylococcus in the study period,so it is necessary to monitor the MIC of vancomycin against Staphylococcus and its changing trend.