Triple-negative breast cancer(TNBC)is a highly aggressive and prognostically unfavorable subtype.Tertiary lymphoid structure(TLS)within the tumor microenvironment,comprising dendritic cells,B cells,T cells,and other immune cells,modulate the tumor immune response.The heterogeneity of TLS in TNBC,such as density,structural maturity,and molecular expression patterns,affects the tumor immune microenvironment and,consequently,treatment responses and clinical outcomes.Studies indicate a positive correlation between the density and maturity of TLS and the pathological complete response(pCR)of TNBC patients,with TLS enhancing the quantity of tumor-infiltrating immune cells and improving anti-tumor immune responses,thereby increasing sensitivity to chemotherapy and immunotherapy.Recent research has found that mature TLS are associated with effective immune responses,becoming significant predictors of treatment response.The combination of TLS with immune checkpoint inhibitors has shown promising prospects.Research demonstrates that promoting the formation or enhancing the functionality of TLS can improve anti-tumor immune effects and enhance treatment outcomes for TNBC patients.Targeting TLS may reduce immune evasion and increase the sensitivity to immunotherapy.However,clinical application of TLS still faces challenges,particularly the impact of their heterogeneity on treatment response.Current assessment methods for TLS are not standardized,lacking a uniform standard and diagnostic system,which limits their widespread application.Future research should focus on resolving these issues by developing standardized assessment tools and further exploring the role of TLS in immune escape and resistance mechanisms.This review aimed to summarize and analyze the existing research progress on TLS in TNBC,in order to provide new ideas for the development of personalized immunotherapy strategies.

In current clinical practice, various dermal templates and skin substitutes are used to enhance wound healing. However, the role of wound commensal microbiome in regulating scaffold performance and the healing process remains unclear. In this study, we investigated the influence of both natural and synthetic scaffolds on the wound commensal microbiome and wound repair in three distinct models including diabetic wounds, burn injuries, and germ-free (GF) wounds. Remarkably, synthetic electrospun polycaprolactone (PCL) scaffolds were observed to positively promote microbiome diversity, leading to enhanced diabetic wound healing compared to the natural scaffolds Integra® (INT) and MatriDerm® (MAD). In contrast, both natural and synthetic scaffolds exhibited comparable effects on the diversity of the microbiome and the healing of burn injuries. In GF wounds with no detectable microorganisms, a reversed healing rate was noted showing natural scaffold (MAD) accelerated wound repair compared to the open or the synthetic scaffold (PCL) treatment. Furthermore, the response of the wound commensal microbiome to PCL scaffolds appears pivotal in promoting anti-inflammatory factors during diabetic wound healing. Our results emphasize that the wound commensal microbiome, mediated by different scaffolds plays an important role in the wound healing process.

Objective To investigate the changes of fibrinogen/albumin ratio(FAR)and uric acid/high-density cholesterol ratio(UHR)in elderly patients with type 2diabetic kidney disease(DKD),as well as the value of the above indexes for early diagnosis of DKD.Methods 310 elderly type 2diabetes mellitus(T2DM)patients were selected and divided into 106 cases in the simple T2DM group,121 cases in the early DKD group and 83 cases in the clinical DKD group according to the urinary microalbumin/urine creatinine ratio(UACR),and the general data and laboratory data of the three groups were compared.Results With the increase of proteinuria,FAR and UHR were significantly elevated,and FAR and UHR were higher in the early DKD group and clinical DKD group than in the sim-ple T2DM group,and FAR was higher in the clinical DKD group than in the early DKD group,and the differences were statistically signif-icant(P＜0.05).Spearman's correlation analysis showed that both UHR and FAR were positively correlated with UACR(r=0.174,P=0.002;r=0.445,P＜0.001),UA(r=0.783,P＜0.001;r=0.147,P=0.010),Cr(r=0.392,P＜0.001;r=0.332,P＜0.001),and negatively correlated with eGFR(r=-0.114,P=0.045;r=-0.374,P＜0.001).In addition,UHR was positively correlated with FAR(r=0.147,P=0.010).The results of multiple Logistic regression analysis showed that long disease course,high glycated hemoglo-bin level,high systolic blood pressure,high FAR,and high UHR were risk factors for the occurrence of DKD(P＜0.05);among which long disease course,high FAR,and high UHR were risk factors for the occurrence of early DKD(P＜0.05).ROC curve analysis sugges-ted that FAR and UHR combined with disease duration had an important diagnostic value for the occurrence of early DKD(AUC=0.803,95％CI:0.752-0.853).Conclusion Elevated FAR and UHR are closely related to the development of DKD and may be independent risk factors for the occurrence of early DKD.Monitoring FAR and UHR in combination with urine microalbumin testing is benefical for the early diagnosis of DKD.

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

Triple-negative breast cancer(TNBC)is a highly aggressive and prognostically unfavorable subtype.Tertiary lymphoid structure(TLS)within the tumor microenvironment,comprising dendritic cells,B cells,T cells,and other immune cells,modulate the tumor immune response.The heterogeneity of TLS in TNBC,such as density,structural maturity,and molecular expression patterns,affects the tumor immune microenvironment and,consequently,treatment responses and clinical outcomes.Studies indicate a positive correlation between the density and maturity of TLS and the pathological complete response(pCR)of TNBC patients,with TLS enhancing the quantity of tumor-infiltrating immune cells and improving anti-tumor immune responses,thereby increasing sensitivity to chemotherapy and immunotherapy.Recent research has found that mature TLS are associated with effective immune responses,becoming significant predictors of treatment response.The combination of TLS with immune checkpoint inhibitors has shown promising prospects.Research demonstrates that promoting the formation or enhancing the functionality of TLS can improve anti-tumor immune effects and enhance treatment outcomes for TNBC patients.Targeting TLS may reduce immune evasion and increase the sensitivity to immunotherapy.However,clinical application of TLS still faces challenges,particularly the impact of their heterogeneity on treatment response.Current assessment methods for TLS are not standardized,lacking a uniform standard and diagnostic system,which limits their widespread application.Future research should focus on resolving these issues by developing standardized assessment tools and further exploring the role of TLS in immune escape and resistance mechanisms.This review aimed to summarize and analyze the existing research progress on TLS in TNBC,in order to provide new ideas for the development of personalized immunotherapy strategies.

Objective:Hearing loss can seriously affect mental health status, and this study aims to investigate the influence of hearing health status on depressive symptoms among middle-aged and older individuals in the community.Methods:From June to December 2023, a stratified random sampling method was employed to select 1 238 community-dwelling middle-aged and elderly people aged 45 years and above from four cities (Hangzhou, Shanghai, Baoding, and Zhengzhou) as research subjects. A questionnaire survey was conducted to collect the subjects′ basic information, hearing health status [assessed by the Hearing Handicap Inventory for Adults-Screening Version (HHIA-S)], and depressive symptoms [assessed by the Geriatric Depression Scale-15 (GDS-15)]. T-tests, rank-sum tests and chi-square tests were used for univariate analysis, while, multiple linear regression and binary Logistic regression were applied to analyze the relationship between hearing health status and depressive symptoms.Results:A total of 1 183 community-dwelling middle-aged and elderly people aged 45 years and above were included in the final analysis (464 males and 719 females, aged from 45 to 96 years). The detection rate of hearing loss was 35.3%(418/1 183), while, the detection rate of depressive symptoms was 9.89%(117/1 183). Age, level of interaction with children, self-rated health, perceived loneliness, and hearing health significantly influenced depressive symptoms among older adults residing in the community ( P<0.05). Individuals with moderate to severe hearing loss ( β=2.04, 95% CI: 1.47, 2.62) exhibited higher GDS-15 scores compared to those without hearing impairment. Furthermore, after correcting for sex, age, marital status, monthly per capita family income, education, residence, smoking status, alcohol use, use of psychotropic medication (anxiolytic or depressant), number of illness, self-health assessment, and autonomy, middle-aged and older adults with mild to moderate hearing loss ( OR=2.89, 95% CI: 1.76, 4.88) and severe hearing loss ( OR=5.79, 95% CI: 3.05, 11.01) demonstrated an increased likelihood of experiencing depression. Conclusions:The degree of hearing loss in community-dwelling middle-aged and elderly individuals is closely associated with the risk of depressive symptoms. Therefore, it is imperative to enhance hearing health screening and to provide mental health support to individuals with hearing loss, in order to mitigate the onset and progression of depressive symptoms.

Objective:To investigate the clinical features and prognosis associated risk factors of non-eosinophilic esophagitis eosinophilic gastrointestinal diseases (non-EoE EGID) in children.Methods:A retrospective cohort study was conducted. Clinical data, including symptoms, laboratory test results, endoscopic findings, treatment and prognosis of 48 children diagnosed with non-EoE EGID at Children′s Hospital, Zhejiang University School of Medicine from May 2015 to March 2023 were collected. Patients were grouped according to the eosinophils (EOS) diagnostic threshold of new guideline for non-EoE EGID. Independent sample t tests, Wilcoxon rank-sum test, chi-squared test or Fisher exact test were used for intergroup comparisons. Kaplan-Meier method was used to plot the survival curve of disease recurrence in children with non-EoE EGID. Log-Rank test and the proportional hazards model were respectively used for univariate analysis and multivariate analysis. Results:Of the 48 children with non-EoE EGID, there were 38 males and 10 females. Twenty-six patients (54%) with onset age >6-10 years accounted for the highest proportion. The most common symptom was abdominal pain, occurring in 34 patients (71%). Laboratory test results showed that 32 patients (67%) had increased EOS count in peripheral blood. A total of 35 imaging examination showed thickened intestinal wall in 17 patients (49%) and bowel dilatation in 3 patients (9%). Twenty-five patients (52%) received glucocorticoid treatment. The serum albumin level in the high diagnostic threshold group was lower than that in the low diagnostic threshold group ( Z=2.17, P=0.030), no statistically significant difference was found in other clinical characteristics (all P>0.05). The 1-year, 2-year, and 3-year recurrence-free survival rates for non-EoE EGID children were (81±6)%, (81±6)%, and (44±13)% respectively. Multivariate analysis showed that bowel dilatation ( HR=5.87, 95% CI 1.06-32.48) was an independent predictor of disease recurrence. Conclusions:A higher proportion of non-EoE EGID patients are male. The most common symptom is abdominal pain, and the peripheral blood EOS counts are often elevated. Among children with non-EoE EGID, those with higher pathological EOS counts have lower serum albumin levels. Bowel dilatation is a risk factor for disease recurrence in non-EoE EGID children.

OBJECTIVE To investigate and analyze the current management of drug clinical trial institutions in Jiangxi Province and the situation of undertaking drug clinical trials after the implementation of the filing system.METHODS A survey was conducted on 38 new institutions(obtained qualifications during the implementation of the filing system)and old institutions(obtained qualifications during the implementation of the recognition system)that had completed drug clinical trial institution qualification filing for more than one year in Jiangxi Province.The survey focused on the basic information of the institutions,the number of registered principal investigator(PI),institutional hardware and information construction,personnel allocation and training,and drug registration clinical trials undertaken by the institutions.RESULTS Of 38 institutions surveyed,there were 22 general hospitals and 16 specialized hospitals;there were 24 old institutions and 14 new institutions.Whether in general hospitals or specialized hospitals,the old institutions were better than the new institutions in the number of approved beds,the number of outpatients,the number of inpatients,the number of specialties,and the number of PI;both old and new institutions had separate offices;all new institutions were set up with GCP pharmacy.The adoption of clinical trial management system in new institutions is significantly less than in old institutions.In the general hospital,both the number of full-time managers and the number of quality controllers in old institutions were significantly more than in the new institutions,while the opposite was true at the level of specialized hospitals.In terms of centralized training on GCP,new institutions were all better than the old ones.Whether in general hospitals or specialized hospitals,the number of drug registration clinical trial projects undertaken by new institutions was significantly less than that of old ones.CONCLUSIONS The new institutions are worse than the old institutions in comprehensive strength and information construction of hospitals,and the number of clinical trials undertaken by new institutions is also less than old institutions.

Objective:To investigate the clinical manifestations, pathological features, treatment methods and prognosis of primary renal synovial sarcoma (PRSS) in order to improve the clinical understanding and treatment level of the disease.Methods:The clinical data, pathological features, immunohistochemical indexes, SYT gene detection, treatment and follow-up results of 21 patients with PRSS reported in the First Affiliated Hospital of Soochow University from 2018 to 2023 were retrospectively analyzed. Kaplan-Meier method was used to calculate the relationship between age and cumulative survival rate. Results:The male to female ratio of PRSS patients was 16∶5, the ratio of left and right kidneys was 7∶14, the median age was 50 years old, the mean age was 44.5 years old, the median tumor length diameter was 9.7 cm, and the mean tumor length diameter was 6.7 cm. 57%(12/21) reported low back pain and 48%(10/21) reported gross hematuria. Immunohistochemical examination showed 100% positive for Vimentin(16/16), BCL-2(18/18) and TLE-1(10/10), 69%(9/13) and 85%(6/7) positive for CD99 and CD56, respectively. Genetic testing found SYT translocation signal in 92% of cases (12/13). Next generation sequencing (NGS) detected SS18- SSX1 fusion in 2 cases and SS18- SSX2 fusion in 1 case. SS18- SSX1+ S18- SSX2 fusion was found in 1 case, and one case of SS18- NEDD4 fusion occurred. Preoperative neoadjuvant chemotherapy was performed in 2 cases, postoperative chemotherapy in 11 cases, postoperative chemoradiotherapy in 2 cases, and surgery only in 5 cases. All patients were followed up for 3 to 42 months, and 4 cases were lost to follow-up. Patients with younger onset had a longer cumulative survival time. Patients had a median survival time of 13 months and a mean survival time of 15.4 months. Conclusions:PRSS is more common in middle-aged men, the right kidney is easy to occur, the length of the mass is usually >7 cm, most cases can be initially diagnosed by pathologic morphology, immunophenotype, fluorescence in situ hybridization or NGS STY gene detection can provide accurate diagnosis. The prognosis of PRSS is very poor, and the cumulative survival rate is negatively correlated with the age of onset. Surgical resection combined with chemotherapy is the main treatment for PRSS.

Objective To investigate the changes of fibrinogen/albumin ratio(FAR)and uric acid/high-density cholesterol ratio(UHR)in elderly patients with type 2diabetic kidney disease(DKD),as well as the value of the above indexes for early diagnosis of DKD.Methods 310 elderly type 2diabetes mellitus(T2DM)patients were selected and divided into 106 cases in the simple T2DM group,121 cases in the early DKD group and 83 cases in the clinical DKD group according to the urinary microalbumin/urine creatinine ratio(UACR),and the general data and laboratory data of the three groups were compared.Results With the increase of proteinuria,FAR and UHR were significantly elevated,and FAR and UHR were higher in the early DKD group and clinical DKD group than in the sim-ple T2DM group,and FAR was higher in the clinical DKD group than in the early DKD group,and the differences were statistically signif-icant(P＜0.05).Spearman's correlation analysis showed that both UHR and FAR were positively correlated with UACR(r=0.174,P=0.002;r=0.445,P＜0.001),UA(r=0.783,P＜0.001;r=0.147,P=0.010),Cr(r=0.392,P＜0.001;r=0.332,P＜0.001),and negatively correlated with eGFR(r=-0.114,P=0.045;r=-0.374,P＜0.001).In addition,UHR was positively correlated with FAR(r=0.147,P=0.010).The results of multiple Logistic regression analysis showed that long disease course,high glycated hemoglo-bin level,high systolic blood pressure,high FAR,and high UHR were risk factors for the occurrence of DKD(P＜0.05);among which long disease course,high FAR,and high UHR were risk factors for the occurrence of early DKD(P＜0.05).ROC curve analysis sugges-ted that FAR and UHR combined with disease duration had an important diagnostic value for the occurrence of early DKD(AUC=0.803,95％CI:0.752-0.853).Conclusion Elevated FAR and UHR are closely related to the development of DKD and may be independent risk factors for the occurrence of early DKD.Monitoring FAR and UHR in combination with urine microalbumin testing is benefical for the early diagnosis of DKD.