BACKGROUND:Promoting skin wound healing is a huge challenge facing global public health.To promote faster and higher-quality wound healing,it is necessary to explore more advantageous dressings to address this problem.OBJECTIVE:To investigate the hemostatic properties of acellular dermal matrix hydrogel and its effect on skin wound healing.METHODS:(1)Acellular dermal matrix hydrogel was prepared,and the differences in microscopic morphology and main components between it and acellular dermal matrix were analyzed.(2)Acellular dermal matrix hydrogel and chitosan hydrogel were used to cover the femoral artery puncture site of rats,and the bleeding quality and coagulation time were recorded.Acellular dermal matrix hydrogel and chitosan hydrogel were mixed with rat anticoagulated blood,and the coagulation index within 30 minutes was detected.(3)A full-thickness skin defect model with a diameter of 12 mm was made on the back of 18 SD rats,and they were randomly divided into 3 groups,with 6 rats in each group:the model group used PBS to clean the wound,and the control group and the experimental group used chitosan hydrogel and acellular dermal matrix hydrogel to cover the wound,respectively.The hydrogel dressing was changed every day,and the treatment was continued for 14 days,and the wound healing was observed.On day 3 after modeling,immunofluorescence staining of inducible nitric oxide synthase(M1 macrophages)and CD206(M2 macrophages)was performed on the wound surface.On day 14 after modeling,hematoxylin-eosin staining,Masson staining,and CD31 immunohistochemical staining were performed on the wound surface.RESULTS AND CONCLUSION:(1)Scanning electron microscopy revealed that the acellular dermal matrix hydrogel had a porous structure,and the Fourier transform infrared spectrum showed that it had the same main components as the acellular dermal matrix.(2)Both acellular dermal matrix hydrogel and chitosan hydrogel had obvious hemostatic ability in vivo.In the in vitro coagulation experiments,the coagulation index of acellular dermal matrix hydrogel was significantly higher than that of chitosan hydrogel.(3)In the rat skin full-thickness defect model,both acellular dermal matrix hydrogel and chitosan hydrogel could improve the wound healing rate.Hematoxylin-eosin and Masson staining results showed that acellular dermal matrix hydrogel could reduce the infiltration of inflammatory cells in the center of the wound.Both acellular dermal matrix hydrogel and chitosan hydrogel could decrease scar width and increase collagen deposition rate.CD31 immunohistochemical staining results showed that both hydrogels could promote angiogenesis in the wound site.Immunofluorescence staining results showed that both hydrogels could reduce the proportion of M1 macrophages and increase the proportion of M2 macrophages,and the effect of acellular dermal matrix hydrogel was stronger than that of chitosan hydrogel.(4)The results show that the acellular dermal matrix hydrogel has good hemostatic properties and the ability to promote wound healing.

Objective To explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). Methods The Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. Gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox regression, least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients’ 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. Results Differentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poorer prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. The scRNA-seq analysis showed that RORA and KLF10 were mainly expressed in natural killer cells. Conclusion The prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.

BACKGROUND:Promoting skin wound healing is a huge challenge facing global public health.To promote faster and higher-quality wound healing,it is necessary to explore more advantageous dressings to address this problem.OBJECTIVE:To investigate the hemostatic properties of acellular dermal matrix hydrogel and its effect on skin wound healing.METHODS:(1)Acellular dermal matrix hydrogel was prepared,and the differences in microscopic morphology and main components between it and acellular dermal matrix were analyzed.(2)Acellular dermal matrix hydrogel and chitosan hydrogel were used to cover the femoral artery puncture site of rats,and the bleeding quality and coagulation time were recorded.Acellular dermal matrix hydrogel and chitosan hydrogel were mixed with rat anticoagulated blood,and the coagulation index within 30 minutes was detected.(3)A full-thickness skin defect model with a diameter of 12 mm was made on the back of 18 SD rats,and they were randomly divided into 3 groups,with 6 rats in each group:the model group used PBS to clean the wound,and the control group and the experimental group used chitosan hydrogel and acellular dermal matrix hydrogel to cover the wound,respectively.The hydrogel dressing was changed every day,and the treatment was continued for 14 days,and the wound healing was observed.On day 3 after modeling,immunofluorescence staining of inducible nitric oxide synthase(M1 macrophages)and CD206(M2 macrophages)was performed on the wound surface.On day 14 after modeling,hematoxylin-eosin staining,Masson staining,and CD31 immunohistochemical staining were performed on the wound surface.RESULTS AND CONCLUSION:(1)Scanning electron microscopy revealed that the acellular dermal matrix hydrogel had a porous structure,and the Fourier transform infrared spectrum showed that it had the same main components as the acellular dermal matrix.(2)Both acellular dermal matrix hydrogel and chitosan hydrogel had obvious hemostatic ability in vivo.In the in vitro coagulation experiments,the coagulation index of acellular dermal matrix hydrogel was significantly higher than that of chitosan hydrogel.(3)In the rat skin full-thickness defect model,both acellular dermal matrix hydrogel and chitosan hydrogel could improve the wound healing rate.Hematoxylin-eosin and Masson staining results showed that acellular dermal matrix hydrogel could reduce the infiltration of inflammatory cells in the center of the wound.Both acellular dermal matrix hydrogel and chitosan hydrogel could decrease scar width and increase collagen deposition rate.CD31 immunohistochemical staining results showed that both hydrogels could promote angiogenesis in the wound site.Immunofluorescence staining results showed that both hydrogels could reduce the proportion of M1 macrophages and increase the proportion of M2 macrophages,and the effect of acellular dermal matrix hydrogel was stronger than that of chitosan hydrogel.(4)The results show that the acellular dermal matrix hydrogel has good hemostatic properties and the ability to promote wound healing.

The application of immunosuppressants has significantly reduced the incidence rate of rejection reaction after liver transplantation， but the clinical efficacy of immunosuppressants is greatly affected by individual differences between patients. This article systematically reviews the recent research advances in the interaction between immunosuppressants and gut microbiota， with a focus on the regulatory role and mechanism of intestinal microflora communities on the efficacy of immunosuppressants. Studies have shown that intestinal microbiome is one of the key factors influencing the efficacy of immunosuppressive therapy after liver transplantation. This review aims to provide a theoretical basis for in-depth research in this field and provide new insights for developing individualized immunosuppressive treatment regimens based on the regulation of intestinal microflora.

Neurological diseases have high morbidity and disability rates， posing a severe threat to human health. Cli nical manifestations include motor， sensory， cognitive and conscious disorders. Chaihu jia longgu muli decoction is derived from Treatise on Febrile Diseases ， with the effects of harmonizing Shaoyang， activating Yang and clearing heat， and tranquilizing the mind. This paper systematically reviews the research progress in clinical application and mechanism of Chaihu jia longgu muli decoction in the field of neurological diseases. It has been found that the decoction shows favorable efficacy in various neurological diseases such as insomnia， depression， epilepsy， vertigo， migraine and vascular dementia. The specific mechanisms are related to regulating neurotransmitter levels， repairing neuronal function， alleviating neuroinflammation， improving mitochondrial dysfunction and regulating intestinal flora. In the future， standardized prospective follow-up cohorts should be established， and core outcome indicators should be clearly defined to strengthen the evidence base. Furthermore， multidisciplinary research should be leveraged to expand the therapeutic value of Chaihu jia longgu muli decoction in the management of neurological diseases.

Objective To describe the clinical characteristics and nutritional management status of hospitalized elderly patients with multimorbidity in a tertiary hospital's geriatric center in 2024, and to analyze the correlation between nutritional status and hospitalization outcomes, thereby providing a basis for optimizing nutritional management pathways for this population. Methods A retrospective study was conducted, including 2 937 elderly patients with multimorbidity. Data on general information, clinical indicators, nutritional risk screening and assessment, nutritional therapy, and costs were collected for descriptive analysis. The relationship between nutritional status (based on BMI and serum albumin levels) and hospitalization outcomes was explored. Results The average age of the patients was (77.45±10.70) years, with 57.17% being male. The average number of chronic diseases diagnosed was (11.56±5.08) per patient, and 26.01% were critically ill. The nutritional risk screening rate was 80.40%, with a screening positivity rate of 33.44%. The nutritional assessment rate was 31.63%, and the malnutrition prevalence was 23.08%. The low BMI group had the longest median hospital stay [15 (9.75, 22) days] and the highest hospitalization costs [15 057.2 (8 980.48, 28 160.46) CNY]. Serum albumin levels were negatively correlated with hospital stay duration (rs=-0.276, P< 0.01) and hospitalization costs (rs=-0.276, P<0.01). Conclusion Hospitalized elderly patients with multimorbidity are characterized by multiple comorbidities and high healthcare resource consumption. While the nutritional risk screening rate is relatively high, there remains room for improvement in nutritional assessment and therapy. It is necessary to strengthen standardized management throughout the entire process. Nutritional status is a significant variable affecting hospital stay duration and costs, with poorer nutritional status significantly associated with prolonged hospitalization and higher costs, suggesting that it may be an important factor influencing hospitalization outcomes.

The JAK2 V617F mutation is a key molecular event in myeloproliferative neoplasms and is strongly associated with an increased risk of thrombosis. This review aims to summarize the underlying mechanisms, clinical manifestations, and management strategies for thrombosis driven by the JAK2 V617F mutation. Relevant recent studies are analyzed to evaluate the effect of the mutation on molecular signaling, hematopoietic cell function, inflammatory activation, endothelial injury, and coagulation imbalance. Findings indicate that the JAK2 V617F mutation induces the persistent activation of the JAK-STAT pathway, leading to erythroid clonal expansion, platelet hyperreactivity, and enhanced neutrophil chemotaxis, along with excessive inflammatory cytokine release, NET formation, and platelet-leukocyte aggregation. These processes collectively promote endothelial dysfunction and hypercoagulation, ultimately contributing to arterial and venous thrombosis. Clinically, affected patients may present with coronary artery events deep vein thrombosis, and portal vein thrombosis, often accompanied by high recurrence rates and poor outcomes. In conclusion, the JAK2 V617F mutation drives thrombosis via multiple intertwined mechanisms, suggesting that future therapeutic strategies should integrate anticoagulation, anti-inflammation therapy, NET inhibition, and targeted JAK-STAT pathway blockade to improve patient survival.

ObjectiveTo construct and validate a risk assessment model for post-transplant diabetes mellitus （PTDM） using multiple machine learning algorithms， and to realize the early identification of PTDM. MethodsA retrospective analysis was performed for the clinical data of the patients who underwent allogeneic liver transplantation in The First Hospital of Shanxi Medical University from April 1， 2020 to December 31， 2024， and they were randomly divided into a training set and a validation set at a ratio of 7∶3. The LASSO regression analysis combined with 5-fold cross-validation was used for feature selection. Seven machine learning models were developed in the training set， i.e.， logistic regression （LR）， decision tree （DT）， Naive Bayes （NB）， random forest （RF）， K-nearest neighbor （KNN）， extreme gradient boosting （XGBoost）， and adaptive boosting （AdaBoost）. In the validation set， various methods were used to assess the predictive performance of each model， such as accuracy， precision， recall rate， specificity， F1 score， area under the receiver operating characteristic curve （AUROC）， and area under the precision-recall curve （AUPRC）. The Brier score and decision curve analysis were used to assess the calibration and clinical practicability of the models， and the SHAP method was used to analyze feature importance. The independent-samples t test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsA total of 135 liver transplant recipients were enrolled， among whom 26 developed PTDM， and there were 94 patients in the training set and 41 in the validation set. Feature extraction and screening identified 7 key features of sex， overweight or obesity， anhepatic phase， time of operation， length of hospital stay， early postoperative hypomagnesemia， and impaired fasting glucose （IFG）. In the validation set， the XGBoost model showed the best predictive performance， with an AUROC of 0.907 （95% confidence interval ［CI］： 0.807 — 0.989）， an AUPRC of 0.649 （95%CI： 0.339 — 0.955）， an accuracy of 0.878， a precision of 0.667， a recall rate of 0.750， an F1-score of 0.706， a specificity of 0.909， and a Brier score of 0.104. The decision curve analysis showed that when the threshold probability was below 0.667， application of the XGBoost model in clinical decision-making provided relatively high net benefit. The SHAP analysis showed that the length of hospital stay ranked first in terms of feature importance， followed by time of operation， overweight or obesity， sex， IFG， anhepatic phase， and early postoperative hypomagnesemia. ConclusionThe risk assessment model for PTDM in liver transplant recipients based on XGBoost algorithm has excellent performance and can effectively identify high-risk individuals； however， multicenter large-sample data are needed for further validation.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective:To compare the enrichment effects of ultrafiltration, polyethylene glycol (PEG) precipitation, aluminum salt precipitation, and anionic membrane adsorption-elution on viruses in drinking water.Methods:Using phage MS2 as the target virus, three different concentrations of drinking water samples were prepared, and the samples were enriched by ultrafiltration 1, ultrafiltration 2, PEG precipitation, aluminum salt precipitation, and anionic membrane adsorption-elution method, respectively. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to quantify MS2 nucleic acid in pre and post concentrated samples and the recovery rates of MS2 in samples with high, medium and low concentrations were compared among the five methods.Results:Comparing the MS2 enrichment recovery rates of individual enrichment method in water samples of different concentrations, ultrafiltration method 1, PEG precipitation method, aluminum salt precipitation method, and membrane adsorption-elution method were not affected by the sample concentration, and the differences of the recovery rates for the three concentration water samples among the four methods were not statistically significant ( P>0.05). The MS2 enrichment recovery rates of the five enrichment methods were significantly different in all concentration samples ( P<0.05). The recovery rates of ultrafiltration method 1 were higher in all three concentration samples, followed by aluminum salt precipitation and anionic membrane adsorption-elution, PEG precipitation were higher in high concentration samples, but lower in low and medium concentration samples, and the recovery rates of ultrafiltration method 2 were the lowest in all three concentration samples. Comparing the Ct values of MS2 in the enriched samples by five methods, the Ct values of ultrafiltration method 1 were the smallest in the three concentration water samples. There was no statistically significant difference in MS2 Ct values among the five enrichment methods in the medium and high concentration water samples ( P>0.05). In low concentration simulated water samples, only the difference of MS2 Ct value between ultrafiltration method 1 and ultrafiltration method 2 was statistically significant ( Z=16.000, P=0.016). Conclusions:Considering the operation simplicity, operation time and virus recovery rate after enrichment, ultrafiltration was the most effective method for virus enrichment in drinking water.