Objective:To investigate the effects and underlying mechanisms of Stat3 knockout in donor T cells on acute gastrointestinal graft-versus-host disease (GI-aGVHD) .Methods:BALB/c mice were exposed to lethal irradiation and transplanted with bone marrow and spleen cells from BALB/c mice (syngeneic control group), C57BL/6 mice (wild-type T cell group, WT group), or C57BL/6J-Stat3 em1cyagen mice (Stat3 gene knockout T cell group, Stat3-KO group) via tail vein injection to establish the aGVHD model. The survival rate, body weight changes, and clinical scores of mice were monitored. Cytometric bead array (CBA) was used to detect the concentrations of serum cytokines. Lymphocytes were isolated from tissues for flow cytometric analysis. H&E staining was performed to observe intestinal pathological changes. FITC-dextran assay was conducted to assess intestinal permeability. Immunohistochemistry was used to evaluate the expression of Ki67 and Muc2. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was employed to analyze the gene expression levels of Olfm4, Lysozyme, and Muc2 in the small intestine. Metabolomics was conducted to detect metabolites in serum and intestinal tissues. An in vitro GI-aGVHD organoid model was established by coculturing intestinal organoids with allogeneic T cells, where the number and area of small intestinal organoids were recorded. The GVL effect was assessed using luciferase-transfected ALL cells (ALL/Luc) and bioluminescent imaging. Results:Compared with the WT group, Stat3 knockout T cells alleviated body weight loss, reduced symptoms—such as hunchback and diarrhea—in mice, improved survival rate ( P<0.05), and reduced serum interleukin (IL) -2, IL-6, interferon-γ, tumor necrosis factor-α, IL-17A, and IL-10 levels (all P<0.05), intestinal inflammatory cell infiltration ( P<0.05), and intestinal mucosal permeability. Further, Muc2 and Ki67 expression levels in the small intestine of the Stat3 knockout group were markedly increased, and Olfm4, Lysozyme, and Muc2 gene expression levels were significantly increased (all P<0.05). In vitro, the Stat3 knockout group demonstrated better organoid development than the WT group. Metabolomic analyses indicated that Stat3 knockout in T cells may affect the pathways associated with bile acid secretion and unsaturated fatty acids. ALL/Luc cells in the GVL mouse model proliferated rapidly in the TCD-BM group; however, 80% of the mice in the Stat3-KO group survived tumor-free for >100 days ( P<0.05) . Conclusion:Knocking out Stat3 in graft T cells reduces T cell damage to intestinal stem cells, thereby ultimately alleviating GI-aGVHD while maintaining a stable GVL effect.

Non-human primate animal models are core tools for the study of highly pathogenic microorganisms and are irreplaceable in the fields of pathology and drug discovery.However,anatomical sampling of non-human primate infection models in high-level biosafety laboratories carries potential risk and related risk assessment and control measures require clarification.Based on biosafety regulations and practical experience,we systematically discuss the risk control strategies of anatomical operations with respect to personal protection,instrument selection,anatomical specifications,documentation,and personnel training.Our review will help to improve the management of high-level biosafety laboratories,reduce the risk of pathogen escape and human infection,and provide support for the safe research of highly pathogenic microorganisms.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

Objective To compare the short-term outcomes and postoperative complications of endoscopic submucosal dissection(ESD)and endoscopic mucosal resection(EMR)in the treatment of early colorectal cancer.Methods A total of 110 patients with early colorectal cancer who were admitted to Suining Central Hospital from June 2020 to June 2022 were prospectively enrolled and randomly assigned to two groups by random number table.Of them,58 patients underwent ESD and 52 patients underwent EMR.Operation related indexes,inflammatory factors(interleukin-6[IL-6],tumor necrosis factor-α[TNF-α],and C-reactive protein[CRP])before operation and 3 days after operation,and postoperative quality of life index(QL-Index)were compared between the two groups.The complications of the two groups were observed.Results The operation time,hospital stay,postoperative exhaust time,defecation time,and intraoperative blood loss in ESD group were lower than those in EMR group,and the rates of complete resection and en bloc resection in ESD group were higher than those in EMR group(P<0.05).The levels of IL-6,TNF-α and CRP were increased 3 d after operation in both groups,but the levels of IL-6,TNF-α and CRP in ESD group were lower than those in EMR group(P<0.05).The total score of QL-Index and the scores of activity,daily activities,health,and overall situation in ESD group were significantly higher than those in EMR group(P<0.05).The incidence of complications in ESD group was higher than that in EMR group,without significant difference(P>0.05).Conclusion The pocket ESD can effectively promote postoperative rehabilitation,increase resection rate,reduce postoperative inflammation,and improve the quality of life of patients with early colorectal cancer,and there is no obvious complication.

In this work, starting from 4-hydroxycoumarin, three series of 22 coumarin derivatives, among which 8 have not been reported in the literature, were synthesized and their in vitro anti-inflammatory activities and mechanisms of action were preliminarily investigated using mouse macrophage model. The results showed that most of the derivatives could significantly inhibit the production of pro-inflammatory factor NO, with compounds 2e, 2f, 2g, 2h, 2i, 2j, 4e, and 4f showing better anti-inflammatory activity than the positive control drug dexamethasone. Further experiments showed that compounds 2h and 4f significantly inhibited the production of pro-inflammatory factors IL-6, TNF-α and IL-1β in RAW264.7 macrophages, and could, therefore, be used as lead compounds for further studies.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

Objective To evaluate the reliability and validity of the Chinese version of the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS)in patients with maintenance hemodialysis(MHD).Methods The general information and medical history of 84 MHD patients were collected,and the Mini-Mental State Exam(MMSE),Montreal Cognitive Assessment Scale(MoCA),and RBANS were conducted.The reliability of the scale was assessed by Cronbach α and split-half reliability.The structure and convergent validity of the scale were assessed by confirmatory factor analysis,and the RBANS scores'correlation to MoCA and MMSE scores was analyzed by Spearman correlation analysis.The predictive value of the RBANS total score on cognitive impairment(CI)was analyzed by receiver operating characteristic(ROC)curve.Results The Cronbach's alpha coefficient of the RBANS total scale was 0.896,split-half reliability was 0.911,and reliability for the five dimensions of the RBANS ranged from 0.618 to 0.791.Confirmatory factor analysis indicated that the overall fit of the five-dimensional model of the RBANS scale was acceptable(χ2/df=1.587,root mean square error of approximation=0.084,comparative fit index=0.967,incremental fit index=0.968,Tucker-Lewis index=0.947,goodness of fit index=0.891).The average variance extracted(AVE)for the five dimensions of the RBANS ranged from 0.525 to 0.863,while the composite reliability(CR)ranged from 0.733 to 0.926,indicating good convergent validity of the scale.Furthermore,Spearman correlation analysis revealed that the total RBANS score was negatively correlated to the age of MHD patients and positively correlated to years of education,as well as the total scores of MMSE and MoCA(all P<0.01).The ROC curve analysis indicated that the area under the curve(AUC)for the total RBANS score in predicting CI was 0.891(P<0.01),suggesting a high predictive value.Conclusion The Chinese version of RBANS has good reliability and validity in MHD patients,and can be used as a measure of cognitive function in MHD patients.

OBJECTIVE To investigate the effects and underlying mechanisms of Yiqi Huoxue Decoction(YQHX)on mitochon-drial midzone division and peripheral fission in myocardial tissue after myocardial infarction(MI).METHODS A total of 48 male SPF-grade C57BL/6N mice were randomly divided into a sham-operated group(Sham,n=12)and a left anterior descending coronary ar-tery ligation MI model(n=36).After MI surgery,mice deemed to have successfully developed the model were randomly divided into a model group(MI,n=12),a YQHX group(n=12),and an empagliflozin group(EMPA,n=12)based on echocardiographic results.Four weeks after infarction,cardiac function and structural changes were comprehensively evaluated using echocardiography imaging,serum myocardial injury biomarkers,and hematoxylin-eosin(HE)staining.Transmission electron microscopy(TEM)was employed to observe mitochondrial ultrastructural,morphological,and quantitative changes at the peri-infarct zone.Myocardial mitochondria and cytoplas-mic fractions were isolated from myocardial tissue using a mitochondrial extraction kit,and the spatial expression changes of mitochon-drial fission-related proteins in both mitochondria and cytoplasm of the peri-infarct myocardium were analyzed by Western blot.These proteins included dynamin-related protein 1(Drp1),its phosphorylated form at serine 616(P-Drp1-Ser616),mitochondrial fission fac-tor(MFF),and mitochondrial fission protein 1(Fis1).RESULTS Compared with the MI group,mice in the YQHX group exhibited sig-nificantly increased left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)(P<0.000 1),as well as decreased left ventricular internal dimension-diastole(LVIDd)and left ventricular end-systolic diameter(LVIDs)(P<0.05,P<0.01),suggesting improved cardiac function.Additionally,serum levels of lactate dehydrogenase(LDH)and creatine kinase-MB(CK-MB)were significantly reduced in the YQHX group(P<0.05,P<0.001),indicating cardio-protective effects of YQHX against ischemic in-jury.HE staining showed that YQHX improved cellular morphology,suggesting structural improvement.TEM showed that YQHX sig-nificantly improved mitochondrial swelling and reduced mitochondrial fragmentation in the marginal zone of myocardial infarction,thereby preserving mitochondrial ultrastructure.Furthermore,Western blot showed that YQHX treatment significantly downregulated P-Drp1-Ser616 expression(P<0.05)in the cytoplasm.Interestingly,YQHX treatment significantly downregulated mitochondrial Fis1 expression(P<0.05),thereby inhibiting peripheral mitochondrial fission.Meanwhile,YQHX treatment significantly increased MFF ex-pression in mitochondria(P<0.01),which may promote mitochondrial midzone fission.CONCLUSION YQHX improves cardiac structure and function after MI,potentially by promoting myocardial mitochondrial midzone fission and inhibiting mitochondrial periph-eral fission in ischemic cardiomyocytes.

Objective To translate the English version of communicative effectiveness index(CETI)into Chinese and validate its reliability and validity for use in the elderly population.Methods The English version of CETI was translated into Chinese and back-translated using the Brislin translation model.After adjustments and pilot testing,a Chinese version of CETI was created.Between January and March 2024,a total of 395 elderly individuals aged 60 years and over were recruited from Jiangsu and Henan Provinces via convenience sampling.A total of 30 elderly people were retested with the Chinese version of CETI after two weeks of primary test to assess the reliability and validity of the scale.Results The Chinese version of CETI comprised two dimensions:conversational comprehensibility(5 items)and conversational initiative(4 items).The Cronbach α coefficient of the scale was 0.831with the split-half reliability 0.785 and the test-retest reliability 0.909.The Cronbach α coefficients of each dimension ranged from 0.641 to 0.778.The test-retest reliability of each dimension ranged from 0.889 to 0.936.The KMO value of exploratory factor analysis was 0.893,Bartlett's sphericity test valueχ 2=583.291(P<0.01),and the total explanatory rate of variation was 63.305%.Conclusion The Chinese version of CETI has good reliability and validity.It is suitable to be used in the assessment of the status of verbal communicative function in the elderly.