BACKGROUND:Bone tissue loss caused by tumors and trauma can have an adverse effect on postoperative rehabilitation.Therefore,scaffold materials are usually implanted during treatment.However,the existing implant materials are relatively simple and lack antibacterial properties.Early implantation may lead to iatrogenic autoinfection and have an adverse effect on osteogenesis.OBJECTIVE:To construct a KR-12-a5 polypeptide-nanohydroxyapatite-small intestinal submucosa composite scaffold and evaluate its feasibility as a material for promoting bone defect repair.METHODS:The small intestinal submucosa scaffold and the small intestinal submucosa scaffold containing 25,50,and 100 mg/mL nanohydroxyapatite(referred to as nHA-SIS scaffold)were prepared by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysuccinimide cross-linking method.The appropriate scaffold was screened for subsequent experiments by mechanical property testing.The antibacterial properties of KR-12-a5 polypeptide solution against Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum were detected.The nHA-SIS scaffolds were immersed in 250,500,and 1 000 μg/mL KR-12-a5 peptide solutions for 24 hours,and then freeze-dried to obtain peptide-loaded nanohydroxyapatite-porcine small intestinal submucosa composite scaffolds(denoted as P-nHA-SIS scaffolds).The sustained-release properties of the three groups of scaffolds were characterized.The nHA-SIS scaffolds and the three groups of P-nHA-SIS scaffolds were co-cultured with Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum for 24 hours or 48 hours.The scaffolds with strong antibacterial ability were screened by live and dead bacteria staining and scanning electron microscopy for subsequent experiments.The degradation properties and water absorption rates of the uncross-linked small intestinal submucosa scaffolds,cross-linked small intestinal submucosa scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were characterized.The extracts of cross-linked small intestinal submucosal scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were co-cultured with MC3T3-E1 cells.CCK-8 assay and live-dead cell staining were performed.The effects of the extracts of the three scaffolds on the migration of MC3T3-E1 cells were detected by Transwell chamber assay.RESULTS AND CONCLUSION:(1)The elastic modulus and compressive strength of 25,50,and 100 mg/mL nHA-SIS scaffolds were higher than those of small intestinal submucosal scaffolds(P＜0.05),among which the elastic modulus and compressive strength of 25 mg/mL nHA-SIS scaffolds were the highest,and this group of scaffolds were selected for subsequent experiments to load peptides.(2)KR-12-a5 peptide had strong antibacterial activity against common bacteria in bone defects(Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum).The three groups of P-nHA-SIS scaffolds all had sustained release properties.With the increase of peptide mass concentration,the antibacterial property of P-nHA-SIS scaffold was enhanced.Among them,the P-nHA-SIS scaffold loaded with 500 μg/mL peptide had achieved a satisfactory antibacterial effect,and this group of scaffolds would be selected in the future.(3)The degradation rate of the three groups of cross-linked scaffolds was lower than that of the uncross-linked scaffolds,and the water absorption rate was greater than that of the uncross-linked scaffolds.P-nHA-SIS scaffolds could promote the proliferation and migration of MC3T3-E1 cells without affecting the activity of MC3T3-E1 cells.(4)The results show that P-nHA-SIS scaffolds have strong antibacterial properties and the ability to promote the proliferation and migration of MC3T3-E1 cells,and are expected to be used in bone defect repair.

BACKGROUND:Bone tissue loss caused by tumors and trauma can have an adverse effect on postoperative rehabilitation.Therefore,scaffold materials are usually implanted during treatment.However,the existing implant materials are relatively simple and lack antibacterial properties.Early implantation may lead to iatrogenic autoinfection and have an adverse effect on osteogenesis.OBJECTIVE:To construct a KR-12-a5 polypeptide-nanohydroxyapatite-small intestinal submucosa composite scaffold and evaluate its feasibility as a material for promoting bone defect repair.METHODS:The small intestinal submucosa scaffold and the small intestinal submucosa scaffold containing 25,50,and 100 mg/mL nanohydroxyapatite(referred to as nHA-SIS scaffold)were prepared by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysuccinimide cross-linking method.The appropriate scaffold was screened for subsequent experiments by mechanical property testing.The antibacterial properties of KR-12-a5 polypeptide solution against Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum were detected.The nHA-SIS scaffolds were immersed in 250,500,and 1 000 μg/mL KR-12-a5 peptide solutions for 24 hours,and then freeze-dried to obtain peptide-loaded nanohydroxyapatite-porcine small intestinal submucosa composite scaffolds(denoted as P-nHA-SIS scaffolds).The sustained-release properties of the three groups of scaffolds were characterized.The nHA-SIS scaffolds and the three groups of P-nHA-SIS scaffolds were co-cultured with Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum for 24 hours or 48 hours.The scaffolds with strong antibacterial ability were screened by live and dead bacteria staining and scanning electron microscopy for subsequent experiments.The degradation properties and water absorption rates of the uncross-linked small intestinal submucosa scaffolds,cross-linked small intestinal submucosa scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were characterized.The extracts of cross-linked small intestinal submucosal scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were co-cultured with MC3T3-E1 cells.CCK-8 assay and live-dead cell staining were performed.The effects of the extracts of the three scaffolds on the migration of MC3T3-E1 cells were detected by Transwell chamber assay.RESULTS AND CONCLUSION:(1)The elastic modulus and compressive strength of 25,50,and 100 mg/mL nHA-SIS scaffolds were higher than those of small intestinal submucosal scaffolds(P＜0.05),among which the elastic modulus and compressive strength of 25 mg/mL nHA-SIS scaffolds were the highest,and this group of scaffolds were selected for subsequent experiments to load peptides.(2)KR-12-a5 peptide had strong antibacterial activity against common bacteria in bone defects(Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum).The three groups of P-nHA-SIS scaffolds all had sustained release properties.With the increase of peptide mass concentration,the antibacterial property of P-nHA-SIS scaffold was enhanced.Among them,the P-nHA-SIS scaffold loaded with 500 μg/mL peptide had achieved a satisfactory antibacterial effect,and this group of scaffolds would be selected in the future.(3)The degradation rate of the three groups of cross-linked scaffolds was lower than that of the uncross-linked scaffolds,and the water absorption rate was greater than that of the uncross-linked scaffolds.P-nHA-SIS scaffolds could promote the proliferation and migration of MC3T3-E1 cells without affecting the activity of MC3T3-E1 cells.(4)The results show that P-nHA-SIS scaffolds have strong antibacterial properties and the ability to promote the proliferation and migration of MC3T3-E1 cells,and are expected to be used in bone defect repair.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Background and Aims:Body mass index(BMI),an important indicator of nutrition and health,is closely associated with postoperative complications.This study was performed to investigate the relationship between preoperative BMI and severe complications in patients undergoing liver resection for hepatolithiasis,aiming to provide preoperative guidance for clinicians,reduce the risk of postoperative complications,and ensure surgical safety and efficacy.Methods:The clinical data of 484 patients with hepatolithiasis who underwent liver resection between May 2006 and December 2022 at the First Affiliated Hospital of Army Medical University and Beijing Tsinghua Changgung Hospital were retrospectively collected.Patients were classified into low BMI group(≤18.4 kg/m2),normal BMI group(18.5-24.9 kg/m2),and high BMI group(≥25.0 kg/m2)based on preoperative BMI.Baseline characteristics,overall complications,severe complications,and other postoperative outcomes were compared between the normal BMI group and the low group as well as the high BMI group.Risk factors for severe complications after liver resection were analyzed.Results:Among the 484 patients,79(16.3％)were in the low BMI group,328(67.8％)in the normal BMI group,and 77(15.9％)in the high BMI group.The high BMI group had significantly higher ASA score,preoperative albumin level,and proportion of hypertension compared to the normal BMI group(all P＜0.05).Baseline characteristics in the low BMI group showed no significant differences compared to the normal BMI group(all P＞0.05).The incidence rates of overall complications were not significantly among the three groups(P＞0.05).However,the high BMI group had significantly higher incidence rates of severe complications(Clavien-Dindo grade Ⅲ-Ⅳ),postoperative infections,liver failure,and bile leakage compared to the normal BMI group;the low BMI group had significantly higher rates of perioperative blood transfusion,postoperative infections,liver failure,and reoperation compared to the normal BMI group(all P＜0.05).Univariate and multivariate Logistic regression analyses identified high BMI and preoperative total bilirubin ≥54 pmol/L as independent risk factors for severe complications after liver resection in patients with hepatolithiasis(both P＜0.05).Conclusion:Preoperative BMI is closely associated with the occurrence of complications after liver resection in patients with hepatolithiasis,with high BMI being an independent risk factor for severe complications.To mitigate the risk of severe complications,clinical practice should prioritize monitoring and management of individuals with high BMI and other risk factors

Objective To explore the application efficacy of refined management on antimicrobial agents in a chest specialty hospital.Methods Multiple measures were implemented through perfecting management systems and processes,as well as conducting knowledge training,such as multi-dimensional specialized prescription reviewing,optimizing information systems,and implementing grid-based management of clinical pharmacist.A refined manage-ment mode for antimicrobial agents in a chest specialty hospital has been established.Antimicrobial management in-dicators for the whole hospital and each clinical specialty in 2023(before management)and 2024(after manage-ment)were analyzed.Results Compared with 2023,antimicrobial use rate among hospitalized patients in 2024 de-creased from 47.48％to 45.92％,and antimicrobial use density(AUD)decreased from 46.28 defined daily doses(DDDs)/(100 person·day)to 39.73 DDDs/(100 person·day).The ratio of antimicrobial cost to total drug cost decreased from 12.71％to 9.51％,and the per capita cost of antimicrobial use decreased from 1 344.18 Yuan to 975.52 Yuan.The use rate of prophylactic antimicrobial agents for class Ⅰ incision surgery increased from 84.48％to 89.52％,and the rationality rate increased from 69.25％to 94.53％.The management indicators of each clinical specialty improved significantly.Conclusion Through adopting a series of refined management measures,antimi-crobial management modes that are suitable for the actual situation of the hospital has been constructed,and obvious efficacy was achieved.Clinical application of antimicrobial agents is more standardized and rational.

The essential public health services is an important component of China's health risk governance system.It possesses both institutional and emotional attributes and addresses potential risk factors in health risk governance by forming a rational pathway and an emotional pathway:essential public health services guide-trust in government enhancement-improve health risk governance capacity.The rational pathway strengthens calculative trust through institutional reinforcement mechanisms,fostering the public's cognitive trust in government departments.The emotional pathway follows the principle of satisfaction,strengthening non-calculative trust through emotional communication and cultivating the public's emotional trust in government departments.By reinforcing both cognitive and emotional trust among the public,essential public health services improved the level of health information reserves and the guidance of medical service order,thereby improving health risk governance capacity.

Objective:To analyze the drug resistance status and related risk factors in elderly patients with pulmonary tuberculosis,and to construct and validate a drug resistance risk prediction model for elderly pulmonary tuberculosis patients,providing evidence for early clinical identification of high-risk populations.Methods:A retrospective study was conducted,consecutively enrolling 315 pulmonary tuberculosis patients aged ≥60 years from January 2019 to December 2021.Based on drug susceptibility test results,patients were divided into drug-resistant group(85 cases)and drug-sensitive group(230 cases).Data on demographic characteristics,clinical manifestations,comorbidities,imaging features,and previous treatment history were collected.Univariate and multivariate logistic regression analyses were performed to identify drug resistance-related factors,and a prediction model was constructed accordingly.The model was internally validated using the concordance index(C-index)and Bootstrap method.Results:Among 315 elderly pulmonary tuberculosis patients,the drug resistance rate was 26.98％,predominantly mono-resistance(48.24％)and multidrug-resistance(28.24％).Multivariate logistic regression analysis showed that previous anti-tuberculosis treatment history[OR=4.537,95％CI(1.962-10.498),P=0.005],diabetes mellitus[OR=3.286,95％CI(1.547-6.979),P=0.002],pulmonary cavitation[OR=4.158,95％CI(1.926-8.973),P＜0.001],pleural effusion[OR=2.563,95％CI(1.218-5.390),P=0.013],and tracheobronchial tuberculosis[OR=2.819,95％CI(1.352-5.876),P=0.006]were independent risk factors for drug resistance in elderly pulmonary tuberculosis.The prediction model constructed based on these factors had a C-index of 0.815(95％CI:0.762-0.868).Conclusion:The drug resistance rate is high among elderly pulmonary tuberculosis patients.Previous anti-tuberculosis treatment history,diabetes mellitus,pulmonary cavitation,pleural effusion,and tracheobronchial tuberculosis are independent risk factors for drug resistance in elderly pulmonary tuberculosis.The prediction model constructed based on these factors has good predictive value for identifying high-risk populations,which is helpful for early clinical intervention and individualized treatment strategy formulation.

Objective·To explore the antitumor effects and potential mechanisms of combining phosphoinositide 3-kinase,FYVE-type zinc finger containing(PIKfyve)inhibitor YM201636 with the stimulator of interferon genes(STING)agonist diABZI in STING pathway-deficient melanoma.Methods·The mRNA and protein expression levels of STING in human cancer cell lines were obtained from the Cancer Cell Line Encyclopedia(CCLE)and UniProt databases.Based on median expression values,melanoma cell lines with high STING mRNA but low protein expression were identified.Quantitative real-time PCR(qRT-PCR)and Western blotting were performed to validate STING mRNA and protein expression in human melanoma cells.The murine melanoma cell line YUMM1.7,characterized by low STING protein expression,was selected through Western blotting.The ability of YM201636 to restore STING protein expression in YUMM1.7 cells was evaluated.STING agonist diABZI was then applied in combination with YM201636 to analyze the synergistic tumor cell-killing effect through CCK-8 assay.Western blotting was used to detect the phosphorylation of TANK-binding kinase 1(TBK1)and interferon regulatory factor 3(IRF3),and qRT-PCR was used to evaluate type Ⅰ interferon expression.A mouse melanoma model was established and treated with YM201636,diABZI,or their combination.Tumor volume was measured,and treatment efficacy was assessed.RNA sequencing and immunofluorescence staining were performed to analyze immune cell infiltration in the tumor microenvironment.Results·Database analyses,qRT-PCR,and Western blotting confirmed that some human melanoma cell lines exhibited high STING mRNA expression but low STING protein levels.YM201636 significantly increased STING protein expression in YUMM1.7 cells(P<0.001).Combined treatment with YM201636 and diABZI significantly enhanced phosphorylation of TBK1 and IRF3(P<0.05),indicating effective activation of the STING signaling pathway.This combination also promoted the expression of type Ⅰ interferons(P<0.001)and enhanced tumor cell killing in vitro.In vivo,the combination therapy markedly suppressed melanoma growth compared to monotherapy.Immune profiling of the tumor microenvironment revealed significantly increased infiltration of CD4? T cells and CD8? T cells in the combination treatment group(P<0.05).Conclusion·The PIKfyve inhibitor YM201636 could restore STING protein expression in STING-deficient melanoma and enhance the antitumor efficacy of the STING agonist diABZI,offering a promising therapeutic strategy for tumors with defective STING signaling.

Objective:To investigate the relationship between nerve growth factor (NGF) concentration in follicular fluid and abnormal menstrual cycle in infertile patients with polycystic ovary syndrome (PCOS).Methods:A retrospective cohort study was conducted on 100 infertile patients with PCOS who underwent in vitro fertilization and embryo transfer (IVF-ET) at Department of Obstetrics and Gynecology, Peking University Third Hospital from March 2017 to June 2019. For comparison, the 100 patients with PCOS were divided into low NGF group ( n=50) and high NGF group ( n=50) based on the median NGF concentration (1 644.03 ng/L) in follicular fluid. Baseline characteristics, menstrual status and clinical outcomes of assisted reproductive technology were compared. We performed multiple linear regression analysis to examine the effect of NGF in follicular fluid on menstrual cycle length for multivariate analysis. Results:1) PCOS patients in the low NGF group had significantly higher body mass index [(27.24±5.17) kg/m 2] and white blood cell count [7.31(5.99, 8.43)×10 9/L ] than those in the high NGF group [(25.03±4.46) kg/m 2, P=0.024; 5.95(5.08,7.01)×10 9/L, P=0.001], while high-density lipoprotein cholesterol [1.15 (0.98, 1.36) mmol/L] and basic follicle-stimulating hormone level [6.51 (5.10,7.95) U/L] in the low NGF group were significantly lower than those in the high NGF group [1.36 (1.09,1.52) mmol/L, P=0.039;6.51 (5.10,7.95)U/L, P=0.040]. 2) PCOS patients in the low NGF group had significantly higher menstrual cycle length [60.00 (35.00, 180.00) d] than the high NGF group [32.50 (27.00,67.50) d, P=0.001]. 3) Multiple linear regression analysis revealed that after adjustment for body mass index, age, infertility duration, infertility type, and glucose and lipid metabolic parameters, the NGF concentration in the follicular fluid independently and negatively correlated with menstrual cycle length ( P<0.05). 4) The NGF concentration in follicular fluid was not correlated with assisted reproductive outcomes. Conclusion:NGF concentration in follicular fluid is closely related to the degree of menstrual cycle abnormalities in patients with PCOS.

Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder, with symptoms of menstrual disorders, hirsutisms, acne, and obesity. Studies have found that PCOS patients have a higher prevalence of anxiety, depression and sleep disorders than non-PCOS women, which may be related to the abnormal innervation. Meanwhile, it has been found that PCOS patients exhibit lower central level and higher peripheral levels of monoamine neurotransmitters (5-hydroxytryptamine, dopamine and norepinephrine). These imbalances can affect various clinical manifestations of PCOS, including the formation and development of metabolic and reproductive disorders, as well as anxiety and sleep disorders, through multiple pathways. This review summarizes recent research progress on the role of monoamine neurotransmitters in the physiological characteristics and clinical manifestations of PCOS patients, aiming to provide new insights into the neuroendocrine characteristics and pathogenesis of the syndrome.