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 determine the prognostic biomarkers and new therapeutic targets of the lung adenocarcinoma (LUAD), based on which to establish a prediction model for the survival of LUAD patients. Methods An integrative analysis was conducted on gene expression and clinicopathologic data of LUAD, which were obtained from the UCSC database. Subsequently, various methods, including screening of differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA), were employed to analyze the data. Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to establish an assessment model. Based on this model, we constructed a nomogram to predict the probable survival of LUAD patients at different time points (1-year, 2-year, 3-year, 5-year, and 10-year). Finally, we evaluated the predictive ability of our model using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves. The validation group further verified the prognostic value of the model. Results The different-grade pathological subtypes' DEGs were mainly enriched in biological processes such as metabolism of xenobiotics by cytochrome P450, natural killer cell-mediated cytotoxicity, antigen processing and presentation, and regulation of enzyme activity, which were closely related to tumor development. Through Cox regression and LASSO regression, we constructed a reliable prediction model consisting of a five-gene panel (MELTF, MAGEA1, FGF19, DKK4, C14ORF105). The model demonstrated excellent specificity and sensitivity in ROC curves, with an area under the curve (AUC) of 0.675. The time-dependent ROC analysis revealed AUC values of 0.893, 0.713, and 0.632 for 1-year, 3-year, and 5-year survival, respectively. The advantage of the model was also verified in the validation group. Additionally, we developed a nomogram that accurately predicted survival, as demonstrated by calibration curves and C-index. Conclusion We have developed a prognostic prediction model for LUAD consisting of five genes. This novel approach offers clinical practitioners a personalized tool for making informed decisions regarding the prognosis of their patients.

ObjectiveTo investigate a suspected outbreak of healthcare-associated infection with carbapenem-resistant Klebsiella pneumoniae (CRKP) in a geriatric emergency ward, and to provide references for the prevention and control of multidrug-resistant bacteria in a hospital in Shanghai. MethodsOn-site epidemiological investigation, combined with environmental hygiene monitoring and pulsed field gel electrophoresis (PFGE) molecular typing method, were adopted to investigate a suspected outbreak of CRKP infection in the geriatric emergency ward of a hospital from October to November 2022, aiming at finding out factors caused the outbreak before taking corresponding control measures. ResultsA total of 3 cases of healthcare-associated CRKP infection were identified, of which 2 cases were homologous to a previous case of community-associated CRKP infection. What’s more, the 2 cases lived in the same ward with the latter and with adjacent beds, but the third case was non-homologous to the community-associated infection case. A total of 46 samples were collected from the environmental surfaces and the hands of healthcare workers, of which 7 samples tested positive for CRKP and were identical to the strains from the 2 healthcare-associated infection cases and the 1 community-associated infection case, originating from the bedrails, bedside tables, surface of non-invasive ventilator, bed curtains and panels of monitoring equipment, with a detection rate of 15.22%. But none of the 11 samples from the hands of healthcare workers tested positive for CRKP. The outbreak was effectively controlled after taking specific prevention and control measures such as strengthening personnel management, intensifying environmental cleaning and disinfection and strictly enforcing hand hygiene among healthcare workers. Subsequently, no similar new cases were reported during the 14-day follow-up period. ConclusionIncomplete environmental cleaning and disinfection, as well as inadequate enforcement of hand hygiene among heatheare workers may have contributed to the suspected outbreak of CRKP in the geriatric emergency ward. Early warning and timely investigation of suspected outbreaks of multidrug-resistant bacteria are crucial for preventing and controlling such outbreaks in hospitals.

Objective To explore the differential diagnostic value of three-dimensional CT values in active pulmonary tuberculosis(APTB)and inactive pulmonary tuberculosis(IPTB).Methods A retrospective analysis was conducted on 96 patients with pulmonary tuberculosis.According to whether the pulmonary tuberculosis lesions were active,the patients were divided into APTB group(n=61)and IPTB group(n=35).The baseline data,CT signs,and three-dimensional CT values were compared between two groups.Additionally,the results of three-dimensional CT values and conventional CT reading method in evaluating the activity of pulmonary tuberculosis were compared,and the accuracy,sensitivity and specificity of using three-dimensional CT values and conventional CT reading method to evaluate the activity of pulmonary tuberculosis were further analyzed.Results APTB group showed a higher incidence of bilateral pulmonary lesions than IPTB group(P<0.05).Compared with IPTB group,APTB group had higher proportions of blurred boundaries,parenchymal cavities,ground-glass opacities,and tree-in-bud signs(P<0.05),but lower proportions of parenchymal bronchiectasis,parenchymal calcifications,and fibrous strip shadows(P<0.05).The three-dimensional CT values in APTB group were lower than those in IPTB group(P<0.05).Significant differences were observed between conventional CT reading method and three-dimensional CT values in evaluating the activities of pulmonary parenchymal calcifications and thick-wall cavities(P<0.05).Specifically,three-dimensional CT values correctly identified 92 cases of tuberculosis lesions,including 59 cases of APTB and 33 cases of IPTB,and the remaining 4 misidentified lesions were calcified,consolidated and nodular lesions.Conventional CT reading method correctly identified 68 cases of tuberculosis lesions,including 43 cases of APTB and 25 cases of IPTB.The sensitivity,specificity,and accuracy of three-dimensional CT values were all higher than those of conventional CT reading method(P<0.05).Conclusion Three-dimensional CT values can effectively determine the activity of pulmonary tuberculosis,exhibiting high sensitivity,specificity,and accuracy.

Japanese encephalitis virus(JEV)belongs to the genus Flavivirus and the family Flavi-viridae,and is classified as a single-stranded,positive-sense RNA virus.The disease known as Japa-nese encephalitis(JE),which results from JEV infection,is a viral zoonosis that is prevalent worldwide and poses a significant public health concern.JEV infection activates a variety of signa-ling pathways,leading to a series of changes that are crucial to the virus's pathogenesis.Among these pathways,Toll-like receptors(TLRs)are particularly significant,and their diverse range and complex signal transduction mechanisms present substantial challenges for the prevention and con-trol of JEV.Currently,there is no specific treatment for JEV.Although some vaccines have been developed to prevent JE,eradicating JEV remains difficult due to its zoonotic transmission cycle and the limited efficacy of the available vaccines.This article reviews the alterations in various TLR signaling pathways induced by JEV infection in the host,aiming to provide insights into the patho-genic mechanisms of JEV and to identify potential new antiviral targets.

Porcine reproductive and respiratory syndrome virus(PRRSV)is the pathogen of porcine reproductive and respiratory syndrome(PRRS),and its infection mainly causes abortion,stillbirth in sows and piglet respiratory infections,which are widely prevalent in the world and seriously jeopardize the development of the world's animal husbandry industry.PRRSV infection of the host is capable of inducing significant immunosuppression,and in recent years,the study of the mecha-nism of PRRSV immunosuppression has become a hot topic,with studies showing that numerous PRRSV proteins are involved in the regulation of host innate immunity and elucidating the mecha-nism by which PRRSV proteins modulate host innate immunity.In this paper,we reviewed the progress of research on the interaction mechanism between PRRSV proteins and host innate im-munity to provide a theoretical basis for a comprehensive understanding of the pathogenesis of PRRSV and the prevention and control of PRRS.