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.

AIM:Clopidogrel and aspirin are com-monly used drugs for the secondary prevention of cerebrovascular disease.Due to drug resistance,their preventive effect is often affected.This article explores the clinical value of clopidogrel and aspirin pharmacogenetic genetic testing in the secondary prevention of ischemic stroke.METHODS:220 pa-tients with mild ischemic stroke or TIA admitted to our hospital from 2021.7 to 2022.9 were included and randomly divided into individualized treatment group and clopidogrel conventional treatment group(control group).The patients were followed up for one year to observe stroke recurrence and hemorrhagic events.RESULTS:(1)Compared with the control group,the recurrence rate of ischemic stroke in the individualized treatment group after 1-year follow-up was slightly lower(5.82％vs.7.92％,P＞0.05),the risk of cerebral hemorrhage was simi-lar,but the risk of other occurrences was increased(6.79％vs.0.99％,P＜0.05).(2)COX regression analy-sis showed that ESRS(HR 2.576,95％CI 1.226-5.413,P=0.013)and history of hypertension(HR 5.517,95％CI 1.624-18.737,P=0.006)were associated with recurrence of ischemic stroke,independent of anti-thrombotic regimen(HR 0.918,95％CI 0.291-2.894,P=0.883).CONCLUSION:Aspirin GPIBA,PTGS1,and ITGB3 gene polymorphisms have limited signifi-cance in guiding antiplatelet medication.Selecting aspirin maintenance therapy for clopidogrel CYP2C19*2*3 allele carriers cannot significantly re-duce the risk of recurrence of minor ischemic stroke and may increase other bleeding risks.COX regression analysis shows that ESRS and history of hypertension are independent risk factors for stroke recurrence.

Objective To analyze the risk factors of poor prognosis in patients with extended-spectrum β-lactamase producing enterobacterales(ESBL-E)bloodstream infection,and establish a nomogram prediction model to provide help for clinical diagnosis and treatment.Methods A total of 235 patients with ESBL-E bloodstream infection were collected from the First People's Hospital of Jiande City.According to their prognosis,the patients were divided into survival group(n=211)and death group(n=224).The clinical data of the patients were collected,and the independent risk factors of poor prognosis were screened by multivariate Logistic regression analysis.The nomogram was established and verified.Results The mortality of ESBL-E bloodstream infection patients with shock,respiratory failure,diabetes and leukemia,ICU admission,hypoproteinemia,increased or decreased white blood cells,and thrombocytopenia was higher(P＜0.05).Multivariate Logistic regression analysis showed that combined shock,respiratory failure and leukemia were independent risk factors for death from ESBL-E bloodstream infection.Conclusion The nomogram prediction model of adverse prognostic risk factors in patients with ESBL-E bloodstream infection can provide help for clinicians to judge the poor prognosis in the early stage,and it is of reference significance to take early intervention measures to reduce the mortality of patients.

Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

Objective To analyze the timeliness of the start time of the first elective operation in a hospital and observe its impact on the operating room cost.Methods Make statistics and analysis on the opening of the first operation in a hospital,record the on-time opening rate of the first operation,analyze the reasons for the delay in the opening time of the first operation,formulate corresponding intervention measures and set up a"management team to improve the efficiency of operating room use".The on-time rate of the first operation,operation,cost control and the satisfaction of surgeons and patients were compared before and after the operation.Results The overall punctuality rate of the first operation was 53.74％,among which the colorectal sur-gery department had the highest punctuality rate of 63.16％,while the minimally invasive surgery department had the lowest punctuality rate of 45.45％.The main reasons for the delay of first operation(35.29％),failed anesthesia(30.88％),and the termination of the operation(17.65％);compared with before implementation,higher overtime time of nurses,shorter opening time and expected time,decreased interval between operation(P＜0.05),lower frequency of centralized delivery and unnecessa-ry consumables cost within 1 month after implementation(P＜0.05),and higher satisfaction of patients and physicians after im-plementation(P＜0.05).Conclusion By improving the first elective operation on time,can effectively reduce the cost of the operating room,shorten the nurse overtime time,at the same time improve the satisfaction of doctors and patients,and improve the management efficiency of the operating room,the first operation on time improved,interval time and unnecessary consumables costs are significantly reduced,optimize the use efficiency of the operating room resources.

Objective:To investigate the effect of cornus officinalis glycoside on intestinal mucosal barrier in septic rats and its possible mechanism of action.Methods:A total of 90 Sprague-Dawley (SD) rats were randomly divided into a sham operation group, a model group, a dexamethasone group (10 mg/kg), a low-dose group of cornus officinalis glycoside (12.5 mg/kg), a medium dose group of cornus officinalis glycoside (25 mg/kg), and a high-dose group of cornus officinalis glycoside (50 mg/kg), with 15 rats in each group. Except for the sham surgery group, all other groups of rats were treated with cecal ligation and puncture (CLP) to prepare sepsis models. Drug intervention was administered via tail vein injection, and serum and ileal tissue were collected from rats 24 hours after surgery. Hematoxylin eosin staining (HE) was used to observe the pathological damage of the small intestinal mucosa; Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of intestinal fatty acid binding protein (I-FABP) and diamine oxidase (DAO), markers of mucosal barrier permeability, as well as the levels of small intestinal mucosal secreted immunoglobulin (sIgA) in serum; The FITC Dextran tracer method was used to detect intestinal mucosal permeability; ELISA method was used to detect the expression levels of interleukin-1 β (IL-1β), interleukin-6 (IL-6), interleukin-18 (IL-18), and tumor necrosis factor -α (TNF-α) in serum; Western blot was used to detect the protein expression levels of nuclear transcription factor (NF-κB) p65, p-NF-κB p65, NOD like receptor heat protein domain associated protein 3 (NLRP3), and cysteine containing aspartic protease 1 (caspase-1) in small intestine tissue.Results:HE staining results showed that compared with the sham surgery group, the model group rats had a loss of intestinal mucosal structure, shortened villi, and infiltration of inflammatory cells; Compared with the model group, the intestinal mucosal structure of rats in the middle and high dose groups of cornus officinalis glycoside and dexamethasone group was relatively intact, with tightly arranged villi and reduced infiltration of inflammatory cells. However, the pathological improvement of intestinal mucosal structure, villi arrangement, and infiltration of inflammatory cells in rats in the low dose group of cornus officinalis glycoside was not significant. The levels of I-FABP and DAO in the serum of the model group rats were significantly higher than those in the sham operation group (all P<0.05), and the level of sIgA in the intestinal mucosa was lower than that in the sham operation group ( P<0.05). The serum levels of I-FABP and DAO in the high-dose and dexamethasone groups of cornus officinalis glycosides were lower than those in the model group (all P<0.05), and the intestinal mucosal sIgA level was higher than that in the model group ( P<0.05). However, there was no statistically significant difference in the serum levels of I-FABP, DAO, and intestinal mucosal sIgA between the low-dose cornus officinalis glycosides group and the model group (all P>0.05). The serum FITC Dextran content in the model group rats was higher than that in the sham operation group ( P<0.05); The levels of FITC Dextran in the serum of rats in the middle and high dose groups of cornus officinalis glycoside and dexamethasone group were lower than those in the model group (all P<0.05), while there was no statistically significant difference in the levels of FITC Dextran in the serum of rats in the low dose group of cornus officinalis glycoside compared with the model group ( P>0.05). The levels of IL-1 β, TNF - α, IL-6, and IL-18 in the serum of the model group rats were higher than those in the sham operation group (all P<0.05); The levels of IL-1 β, TNF-α, IL-6, and IL-18 in the serum of rats in the high-dose and dexamethasone groups of cornus officinalis glycoside were lower than those in the model group (all P<0.05), while there was no statistically significant difference in various indicators between the low-dose cornus officinalis glycoside group and the model group (all P>0.05). The protein expression levels of p-NF-κB p65/NF-κB p65, NLRP3, and caspase-1 in the small intestine tissue of the model group rats were higher than those in the sham operation group (all P<0.05); The protein expression levels of p-NF-κB p65/NF-κB p65, NLRP3, and caspase-1 in the small intestine tissues of rats in the high-dose and dexamethasone groups of cornus officinalis glycoside were lower than those in the model group ( P<0.05), while there was no statistically significant difference in the protein expression levels between the low-dose cornus officinalis glycoside group and the model group (all P>0.05). Conclusions:Cornus officinalis glycoside has a certain improvement effect on intestinal mucosal barrier dysfunction in septic rats, and its mechanism may be related to the inhibition of NF-κ B/NLRP3 signaling pathway activation.

Objective To investigate the effect of eosinophil(EOS)/neutrophil(NER)in peripheral blood on asthma recurrence in children with bronchial asthma(BA)after treatment.Methods A prospective cohort study was conducted in the study.BA children admitted to the hospital from February 2020 to February 2022 were selected as the research objects.All children were treated regularly and their condition was under con-trol.After a follow-up of 6 months,the recurrence of the children was recorded.EOS/NER,interleukin(IL)-4 and IL-5 of children with and without relapse before treatment and at 1 week of treatment were compared.Lo-gistic regression analysis model was established to test the effect of EOS/NER on the recurrence of asthma in children with BA after treatment.The receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of EOS/NER,IL-4 and IL-5 before treatment for the recurrence risk of BA children after treatment.Results A total of 128 children with BA were included.25 cases recurred after 6 months of follow-up,with a recurrence rate of 19.53%.EOS/NER,IL-4 and IL-5 of BA children after 1 week of treatment were lower than those before treatment(P<0.05).EOS/NER,IL-4 and IL-5 of recurrent children before treat-ment and 1 week after treatment were higher than those of non-recurrent children(P<0.05).There were no statistically significant differences in EOS/NER,IL-4,IL-5 levels between children of different genders,age groups,and treatment regimens before and after 1 week of treatment(P>0.05).Increased EOS/NER,in-creased level of IL-4 and increased level of IL-5 had effect on the recurrence of BA children after treatment and may be risk factors for recurrence(OR>1,P<0.05).The ROC curve showed that area under the curve of EOS/NER before treatment for predicting the recurrence was 0.810(95%CI:0.724-0.896,P<0.001)in BA patients after 6 months of treatment,with moderate predictive value.Conclusion EOS/NER before treat-ment in BA children may be an independent risk factor for recurrence after treatment,and has moderate pre-dictive value for recurrence risk.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Purpose To explore the predictive value of nomogram model for invasive breast cancer with axillary lymph node metastasis.Materials and Methods Retrospective analysis was made on 122 patients suspected to be breast cancer in the General Hospital of Ningxia Medical University from September 2020 to March 2022.According to whether there was axillary lymph node metastasis,all subjects were divided into 57 patients in the metastasis group and 65 patients in the non-metastasis group.All lesions were pathologically confirmed by surgery.The two groups received synthesis of magnetic resonance imaging(syMRI),dynamic contrast enhancement magnetic resonance imaging(DCE-MRI)and diffusion weighted imaging(DWI)scans.The syMRI parameters[including T1,T2,proton density(PD)],DCE-MRI time signal intensity curve,apparent diffusion coefficient(ADC)value of breast lesions were measured.Compared the difference of parameters between the two groups,and screened the independent risk factors of invasive breast cancer with axillary lymph node metastasis.Results Logistic regression results showed that Ki-67(OR=2.971,95%CI 1.306-6.762,P=0.009),lesion size(OR=1.652,95%CI 1.067-2.556,P=0.024),ADCratio(OR=1.685,95%CI 1.014-2.801,P=0.044),T2ratio(OR=3.015,95%CI 1.433-6.340,P=0.003),PDratio(OR=2.782,95%CI 1.471-5.262,P=0.002)were independent risk factors for invasive breast cancer with axillary lymph node metastasis.The comparison of the five models showed that the Logistic regression model had the best performance,with the area under curve of 0.729(95%CI 0.621-0.789),the accuracy,specificity and sensitivity were 70.65%,62.79%and 77.55%,respectively.The accuracy of the nomogram model was tested,and C-index=0.844,the accuracy of the nomogram model established was good,cut-off risk was 0.468,and the cut-off score was 143.50,which means that when the total score exceeds 143.50,the risk of axillary lymph node metastasis would be higher than 46.8%.Conclusion Nomogram model has a good predictive ability for invasive breast cancer patients with axillary lymph node metastasis.