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.

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.

Objective:To investigate the feasibility and safety of intracardiac echocardiography(ICE)combined with total three-dimensional(T3D)technique in zero-fluoroscopy individualized transseptal puncture.Methods:A total of 112 patients with atrial fibrillation who underwent radiofrequency ablation in Yongchuan Hospital Affiliated to Chongqing Medical University from April 2021 to March 2024 were enrolled,and according to the method for transseptal puncture,they were randomly divided into ICE+T3D group with 56 patients and ICE group with 56 patients.The two groups were analyzed in terms of baseline data,time to atrial reconstruc-tion,time to coronary sinus electrode placement,frequency of ICE probe adjustment during transseptal puncture,duration of transsep-tal puncture,pretreatment time before ablation,incidence rate of complications,and the duration and dosage of X-ray exposure.Results:There were no significant differences in baseline data between the two groups.Compared with the ICE group,the ICE+T3D group had a significantly lower frequency of ICE probe adjustment during transseptal puncture(1.70±0.63 vs.5.34±1.71,P<0.001)and the duration of transseptal puncture(3.66±1.09 min vs.4.90±1.92 min,P<0.001).Compared with the ICE group,the ICE+T3D group had significantly longer time to atrial reconstruction(22.44±3.13 min vs.12.34±2.12 min,P<0.001)and pretreatment time be-fore ablation(49.41±3.52 min vs.37.65±4.04 min,P<0.001).In the ICE+T3D group,43(76.8%)patients achieved zero radiation during pretreatment before ablation,and 13 patients received X-ray due to the difficulty in catheter placement;compared with the ICE group,the ICE+T3D group had a significantly shorter duration of X-ray exposure(1.68±0.72 min vs.3.14±1.95 min,P=0.010)and a significantly lower dosage of X-ray exposure(6.28±2.78 mGy vs.23.85±21.32 mGy,P=0.004).During the stage of transseptal punc-ture,all patients in the ICE+T3D group achieved zero radiation,while 45 patients(80.4%)in the ICE patients received X-ray.In terms of complications,there were no life-threatening complications such as cardiac tamponade,perforation of the aorta by mistake,and embolization in either group,while there was one case(1.8%)of vascular complications in each group.Conclusions:ICE combined with T3D after integration and improvement is a safe and reliable procedure for zero-fluoroscopy individualized transseptal puncture.

Hepatocellular carcinoma is one of the most common malignant tumors in China.Hepatectomy continues to be one of the principal therapeutic modalities for early-stage hepatocellular carcinoma.The first elective hepatectomy was performed by Langenbuch in 1888 that marked the start of hepatic surgery.With the advances in studies on liver anatomy,in 1957,Goldsmith and colleagues proposed the concept of anatomical hepatectomy.In 1985,Makuuchi introduced the concept of anatomical subsegmentectomy.Over the past century,hepatic resection has evolved through multiple stages,including partial hepatectomy,hemi-hepatectomy,anatomical hepatectomy,anatomical subsegmentectomy and non-anatomical hepatectomy.Unfortunately,the long-term survival rates after hepatectomy of hepatocellular are still less than satisfactory.With recent development of studies on underlying liver diseases,mechanisms of hepatocarcinogenesis,and the tumor biological features of hepatocellular carcinoma,along with the breakthroughs in targeted therapy and immunotherapy for Hepatocellular carcinoma,the traditional concept of technically focused,anatomy-based hepatectomy is no longer sufficient to meet the demands of modern surgical treatment for hepatocellular carcinoma.Guided by the concept of scientific hepatectomy that combines local and systemic therapies,hepatectomy for HCC has been entered into a new era of hepatectomy with science.

Objective To observe the characteristic symptoms in breast cancer-bearing mice and the beneficial effect of ginger-processed Jiangxiangru polysaccharides on traditional Chinese medical symptoms.Methods Thirty-eight mice were used for modeling and divided into normal,model,positive,and low-,medium-,and high-dose ginger-processed Jiangxiangru polysaccharide groups.Mice in the normal group were not inoculated with tumors and mice in the normal and model groups received physiological saline intragastrically.Mice in the positive group received celecoxib solution intragastrically,and mice in the low-,medium-,and high-dose groups received the same dose but different concentrations of ginger-processed Jiangxiangru polysaccharide solution intragastrically.Changes in body weight and tumor size were recorded after 4 weeks of continuous administration.Symptoms were observed at the end of the experiment.RGB values in photographs of the tongues,tails,and claws from mice in each group were analyzed and recorded.The degrees of blood deficiency,yin deficiency,and tumor phlegm stasis were calculated based on the method of quantitative dialectical diagnosis.The tumors were isolated and weighed,and the tumor volume and inhibition rate were calculated to determine the beneficial effect of ginger-processed Jiangxiangru polysaccharides on traditional Chinese medical symptoms.Results Mice in the breast cancer model group showed signs of blood deficiency,yin deficiency,and phlegm stasis.Tumor size was significantly reduced in mice in the ginger-processed Jiangxiangru polysaccharide groups.Ginger-processed Jiangxiangru polysaccharides inhibited tumor growth and improved blood deficiency,yin deficiency,and tumor phlegm stasis in breast cancer-bearing mice,with the best result in the high-dose group.Conclusions Ginger-processed Jiangxiangru polysaccharides can improve the symptoms of blood deficiency,yin deficiency,and tumor phlegm stasis in breast cancer-bearing mice,especially at high doses.

A novel approach named hierarchical vascular morphology awareness and noisy label refine for hepatic vessel segmentation(HN-Seg)is proposed to achieve precise vessel segmentation while reducing dependency on high-quality labels.HN-Seg comprises of(1)hierarchical vascular morphology aware network which employs a multi-scale local morphology attention mechanism and a global morphology preservation loss function to ensure the integrity of overall vascular morphology,and(2)self-distillation noisy label refine module which leverages the uncertainty in model outputs to optimize noisy labels through uncertainty optimization and consistency regularization,thereby maximizing the knowledge extracted from images during training and refining noisy labels.Experimental results on the hepatic vessel dataset demonstrate that HN-Seg achieves superior segmentation performance,outperforming 6 methods(UNet,UNet++,UNETR,SwinUNetR,FRUNet,and MTCL).HN-Seg attains DSC and clDice scores of 0.727 and 0.773,showing improvements of 9.6%and 21.5%over the baseline method UNETR.

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 Explored the clinical efficacy and mechanism of improved CO2 fractional laser on treatment for refractory wounds.Methods A total of 122 patients with refractory wounds who were admitted to the hospital from May 2022 to May 2024 were selected and randomly divided into a conventional group(conventional dressing change treatment+photodynamic therapy+conventional CO2 fractional laser treatment)and an improved group(conventional dressing change treatment+photodynamic therapy+improved CO2 fractional laser treatment)by lottery,with 61 cases in each group.The serum C-reactive protein(CRP)and erythrocyte sedimentation rate(ESR)levels,the number of wound bacteria before treatment and after 1,2,and 3 weeks of treatment were compared between the two groups.The wound healing rates after 1,2,and 3 weeks of treatment were compared between the two groups.The clinical efficacy of the two groups was compared.The levels of wound exudate basic fibroblast growth factor(bFGF)and angiopoietin-1(Ang-1)before treatment and after 1,2,and 3 weeks of treat-ment were compared.The adverse reactions of the two groups were compared.Results Repeated measures analy-sis of variance showed that there were an interaction effect between groups and over time in the serum CRP and ESR levels,the number of wound bacteria in both groups(P<0.05).There were no significant differences in the serum CRP and ESR levels and the number of wound bacteria between the two groups before treatment(P>0.05).The serum CRP and ESR levels and the number of wound bacteria in the improved group were lower than those in the conventional group after 1,2,and 3 weeks of treatment(P<0.05).Repeated measures analysis of variance showed that there was an interaction effect between groups and over time in the wound healing rates of both groups(P<0.05).The wound healing rates in the improved group were higher than those in the conventional group after 1,2,and 3 weeks of treatment(P<0.05).The total clinical effective rate of the improved group was higher than that of the conventional group(P<0.05).Repeated measures analysis of variance showed that there was an inter-action effect between groups and over time in the levels of bFGF and Ang-1 in wound exudates of both groups(P<0.05).There was no significant difference in the levels of bFGF and Ang-1 in wound exudates between the two groups before treatment(P>0.05).The levels of bFGF and Ang-1 in wound exudates in the improved group were higher than those in the conventional group after 1,2,and 3 weeks of treatment(P<0.05).There were no signifi-cant differences in the incidence of pain,pruritus and rash between the two groups(P>0.05).Conclusions In the treatment of refractory wounds,the combination of improved CO2 fractional laser and photodynamic therapy could promote the secretion of wound exudate growth factors,inhibit wound bacterial growth and inflammatory response,accelerate wound healing,and improve clinical efficacy,with high safety.The mechanism of action is related to the promotion of wound exudate growth factor secretion.

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.