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.

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.

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.

Objective:To investigate the impact of lifestyle, apolipoprotein E (ApoE) gene, and their interaction on the risk for cognitive frailty in the elderly population in China.Methods:The study participants were from the Chinese Longitudinal Healthy Longevity Survey. The information about their lifestyles were collected by questionnaire survey, and a weighted lifestyle score was constructed based on β coefficients associated with specific lifestyles to assess the combined lifestyle. ApoE genotypes were assessed by rs429358 and rs7412 single nucleotide polymorphisms. Cognitive frailty was assessed based on cognitive function and physical frailty. Cox proportional hazards regression model was used to analyze the association of lifestyle and ApoE gene with the risk for cognitive frailty and evaluate the multiplicative and additive interactions between lifestyle and ApoE gene. Results:A total of 5 676 elderly persons, with median age [ M ( Q1, Q3)] of 76 (68, 85) years, were included, in whom 615 had cognitive frailty. The analysis by Cox proportional hazards regression model indicated that moderate and high levels of dietary diversity could reduce the risk for cognitive frailty by 18% [hazard ratio ( HR)=0.82, 95% CI: 0.68-1.00] and 28% ( HR=0.72, 95% CI: 0.57-0.91), respectively; moderate and high levels of physical activity could reduce the risk by 31% ( HR=0.69, 95% CI: 0.56-0.85) and 23% ( HR=0.77, 95% CI: 0.64-0.93), respectively. Healthy lifestyle was associated with a 40% reduced risk for cognitive frailty ( HR=0.60, 95% CI: 0.46-0.78). ApoE ε4 allele was associated with a 26% increased risk for cognitive frailty ( HR=1.26, 95% CI: 1.02-1.56). No multiplicative or additive interactions were found between lifestyle and ApoE gene. Conclusions:Dietary diversity and regular physical activity have protective effects against cognitive frailty in elderly population. Healthy lifestyle can reduce the risk for cognitive frailty in elderly population regardless of ApoE ε4 allele carriage status.

Computational fluid dynamics (CFD) is an emerging technology applied in the field of cardiovascular medicine, which can obtain hemodynamic data by simulating the blood flow in the patient′s heart for cardiac function assessment and disease diagnosis. Left ventricular function plays a key role in the occurrence and development of cardiomyopathies and coronary disease. CFD can reconstruct the left ventricular anatomic structures of patients to clarify pathophysiologic mechanisms and analyze hemodynamic parameters to evaluate left ventricular function, verify surgical efficacy, and guide surgical strategy, which has a positive effect on achieving early diagnosis and reducing mortality from cardiomyopathies and coronary disease. At present, there are still technical limitations in the large-scale clinical application of CFD, and various solutions are being developed and tested, and further improvement and refinement are needed.

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.

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.

ObjectiveThis study explores the efficacy and pharmacological mechanism of Wujiwan in rats with inflammatory bowel disease （IBD） from the perspectives of the peroxisome proliferator-activated receptor γ （PPARγ） signaling pathway and T-cell immunity， providing reference for the treatment of IBD with traditional Chinese medicine. MethodThe study involved administering 2，4，6-trinitrobenzenesulfonic acid （TNBS） enemas to 35 rats to induce acute IBD. After 24 hours， the animals were divided into the following groups： normal group， model group， Wujiwan treatment group， and positive drug control group. Each group received gastric gavage for 8 consecutive days before the rats were dissected to compare the disease activity index （DAI） of the rat colon tissue， the colon mucosal damage index （CMDI）， and the spleen index. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β）， interleukin-10 （IL-10）， and tumor necrosis factor-α （TNF-α） in the serum. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of T-bet （T-box expressed in T cells） and Gata3 （Gata-binding protein-3） in the colon tissue. Western blot analysis was conducted to detect the protein expression levels of PPARγ， T-bet， and nuclear factor-κB p65 （NF-κB p65） in the rat colon. ResultThe rat model of IBD was successfully established. Compared with the model group， the Wujiwan treatment group showed reduced DAI， CMDI， and spleen index， decreased content of TNF-α in the serum（P<0.01）， significantly increased content of IL-10（P<0.01）， and elevated mRNA content of T-bet and Gata3（P<0.05） in the colon tissue. The expression of PPARγ protein was augmented（P<0.05）， and the expression of T-bet and NF-κB p65 protein was decreased（P<0.05，P<0.01）. ConclusionWujiwan activates or upregulates PPARγ expression in IBD rats to inhibit the generation of pro-inflammatory factors， participates in the inflammatory immune process， and alleviates inflammatory reactions. Its mechanism may involve regulating the NF-κB pathway through PPARγ， enhancing Th2 cell transcription expression， and reducing Th1 cell transcription.