Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1 : 1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.001). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.

OBJECTIVES: To evaluate the clinical efficacy of human biological dressing (human acellular dermal matrix) transplantation in the management of refractory wounds among middle-aged and elderly patients. METHODS: A retrospective observational study was conducted involving 104 middle-aged and elderly patients (74 males, 30 females; aged 56-95 years) with refractory wounds treated at the First Affiliated Hospital of Wenzhou Medical University from January 2023 to December 2024. Following debridement, wound areas ranged from 1.0 to 48.0 cm². All patients received vacuum sealing drainage for 7 days, followed by human biological dressing transplantation. Subsequently, depending on the wound condition and the patient's preference, autologous skin grafting (ASG) or wound dressing changes were employed to promote wound healing. Outcome measures included: post-human biological dressing coverage of exposed tendons/bones and occurrence of tendon infection/osteomyelitis; survival rate of ASG at postoperative day 7; healing time in patients managed with wound dressing changes alone; patient satisfaction; and changes in pain intensity, sleep disturbance, and anxiety scores assessed before and 1 month after human biological dressing transplantation using the Edmonton Symptom Assessment Scale. RESULTS: After human biological dressing transplantation, 103 patients exhibited robust granulation tissue formation achieving complete coverage of the exposed tendons/bones, with no instances of tendon/bone necrosis, infection, or osteomyelitis. Among these, 51 patients underwent successful ASG at (44.4±13.0) d post-human biological dressing transplantation (success rate 100.00%), 52 patients achieved primary wound healing through dressing changes alone within (62.6±13.4) d post-human biological dressing transplantation. One patient experienced human biological dressing dissolution and detachment due to gluteal wound infection, resulting in non-healing. The overall cure rate was 99.04%. Patient satisfaction survey showed that 95 patients were very satisfied, 8 were satisfied, and 1 was dissatisfied (satisfaction rate 99.04%). Pain, sleep disturbance, and anxiety scores at 1 month post-human biological dressing transplantation were significantly reduced compared to pre-transplantation scores (all P<0.05). CONCLUSIONS Human biological dressing transplantation demonstrate excellent outcomes in treating refractory wounds in middle-aged and elderly patients and can serve as an effective therapeutic strategy for managing refractory wounds.
Humans ; Aged ; Male ; Middle Aged ; Female ; Aged, 80 and over ; Retrospective Studies ; Wound Healing ; Biological Dressings ; Skin Transplantation ; Acellular Dermis ; Wounds and Injuries/surgery* ; Treatment Outcome

OBJECTIVES: To evaluate the effectiveness and safety of deucravacitinib in Chinese patients with moderate-to-severe plaque psoriasis. METHODS: This retrospective study included 41 patients with moderate-to-severe plaque psoriasis treated with deu-cravacitinib 6 mg once daily for 16 weeks at the First Affiliated Hospital of Wenzhou Medical University between January and September 2024. Effectiveness was assessed by the psoriasis area and severity index (PASI), static physician's global assessment (sPGA), palmoplantar psoriasis area and severity index (PPASI), modified nail psoriasis severity index (mNAPSI), and dermatology life quality index (DLQI) at baseline, 4, 8, 12 and 16 weeks after treatment. Adverse events during treatment were recorded. Laboratory parameters, including complete blood count, liver and kidney function, electrolytes, and lipids, were assessed at baseline, 8, 16 weeks after treatment to evaluate safety. Univariate and multivariate logistic regression analyses were performed to explore factors associated with achieving PASI75 at week 16, using baseline characteristics as independent variables. RESULTS: Significant reductions from baseline in PASI and DLQI scores were observed from week 4 through week 16 (all P<0.01). Overall response rates for PASI75, PASI90, PASI100, sPGA 0 or 1 grade, and DLQI 0 or 1 point increased progressively over the treatment period. 75, 90, and 100 refer to a score reduction of at least 75%, at least 90%, and 100%, respectively, from baseline. Response rates of PASI75, PASI90, PASI100 for the scalp, limbs, and trunk, PPASI75, PPASI90, PPASI100 for palmoplantar lesions, and mNAPSI75, mNAPSI90 for nail lesions increased progressively over time but with different trends. Scalp lesions improved most markedly from week 4, followed by the limbs, whereas improvements in trunk and palmoplantar lesions were relatively slower. Nail lesions responded more slowly, with only 20% of patients achieving marked improve-ment at week 16. Deucravacitinib demonstrated good tolerability and compatibility with concomitant medications. No severe adverse events were reported, indicating a favorable safety profile. Multivariate logistic regression analysis revealed no significant association between the achievement of PASI75 response at week 16 and patient age, body mass index, disease duration, or baseline PASI, sPGA, or DLQI scores (all P>0.05). CONCLUSIONS In this real world study of Chinese patients with moderate-to-severe plaque psoriasis, deucravacitinib demonstrated favorable effectiveness and safety over 16 weeks of treatment.
Humans ; Psoriasis/drug therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; China ; Adult ; Treatment Outcome ; Severity of Illness Index ; Quality of Life ; Aged

Liver fibrosis is a common outcome of various chronic hepatic insults,characterized by excessive extracellular matrix(ECM)deposition.The precise mechanisms,however,remain largely undefined.This study identified an elevated expression of platelet-activating factor acetylhydrolase 1B3(Pafah1b3)in liver tissues from both carbon tetrachloride(CCl4)-treated mice and patients with cirrhosis.Deletion of Pafah 1b3 significantly attenuated CCl4-induced fibrosis,hepatic stellate cell(HSC)activation,and acti-vation of transforming growth factor-β(TGF-β)signaling.Mechanistically,PAFAH1B3 binds to mothers against decapentaplegic homolog 7(SMAD7),disrupting SMAD7's interaction with TGF-β receptor 1(TβR1),which subsequently decreases TβR1 ubiquitination and degradation.Pharmacological inhibition using 3-IN-P11,a specific Pafah1b3 inhibitor,conferred protective effects against CCl4-induced fibrosis in mice.Furthermore,Pafah 1b3 deficiency reduced hepatic inflammation.Overall,these results establish a pivotal role for Pafahl b3 in modulating TGF-β signaling and driving HSC activation.

Ferroptosis of chondrocytes is a significant contributor to osteoarthritis(OA),for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis.Here,we screen for anti-ferroptotic drugs in Food and Drug Administration(FDA)-approved drug library via a high-throughput manner in chondrocytes.We identified a group of FDA-approved anti-ferroptotic drugs,among which vitamin K showed the most powerful protective effect.Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix(ECM)degradation in chondrocytes.Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus(DMM)mouse model.Mechanistically,transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6(Gas6).Furthermore,exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase(AXL)/phosphatidylinositol 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)axis.Together,we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis,indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

Ferroptosis has been shown to mediate the development of fibrosis.Polyphyllin Ⅶ(PP7),a bioactive component of Paris polyphylla,exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis.In this study,treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells(HSCs),which could be suppressed by a ferroptosis inhibitor.In addition,it promoted HSC ferroptosis by suppressing glutathione(GSH)peroxidase 4(GPX4)and enhanced the expression of CX3C chemokine ligand 1(CX3CL1).Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4.Notably,CX3CL1 directly interacted with GPX4,triggering HSC ferroptosis.The transcription factor hypermethylated in cancer 1(Hic1),which binds to the Cx3cl1 promoter,increased the expression of CX3CL1.Its absence resulted in downregulation of CX3CL1,sup-pressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation.HIC1 was found to directly interact with PP7 at the GLY164 site.Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes.HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo.These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.

Combined vaccines can simplify the vaccination process, improve coverage rates, reduce the risk of adverse events following immunization, lower social costs, and improve the timeliness of childhood vaccination. This article focuses on multi-component vaccines based on the diphtheria-tetanus-pertussis containing vaccine. Globally, multiple combined vaccines have been developed and marketed, but the development of combined vaccine is still in its infancy stage in China, with limited vaccine types and doses available. The research, development, and application of combined vaccines still face numerous challenges in China, including technical challenges in research and development, as well as insufficient motivation for research and development. Additionally, the high cost of existing combined vaccines, coupled with low public awareness and weak vaccination intentions, significantly hinders their widespread application, China should continue to rigorously implement the Vaccine Administration Law of the People's Republic of China, promote innovative development of combined vaccines, increase public awareness, strengthen child guardians' confidence in vaccination, and improve the accessibility and affordability of combined vaccines to protect public health across all life stages.

Objective:Using surface-based morphometry (SBM), this study longitudinally tracks dynamic changes in whole-brain cortical morphological parameters in depression patients before and after vortioxetine treatment. Through three-dimensional topological characterization, we investigate the neuroanatomical correlations between cortical structural reorganization and improvements in affective symptoms and cognitive functions.Methods:Prospectively collected clinical data from 22 outpatients with depression (10 males and 12 females, aged 18-50 years, mean age 28.1±9.1) who attended Beijing Huilongguan Hospital clinic from October 2018 to December 2019. An age-matched healthy control group ( n=21; 10 males and 11 females, aged 22-44 years, mean age 30.8±6.6) was recruited concurrently. The Hamilton Rating Scale for Anxiety (HAMA), the 17-item Hamilton Depression Scale (HAMD 17), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to evaluate the severity of depressive symptoms and cognitive function in patients. Structural magnetic resonance imaging (sMRI) was performed to assess brain structural indices in depression patients before and after vortioxetine treatment, as well as in healthy controls. Whole-brain cortical structure measurements were calculated for all subjects using CAT12 software. Paired-sample t-tests were used to compare changes in cortical structure and clinical scale scores in depression patients before and after treatment, and two-sample t-tests were conducted to compare whole-brain cortical structure differences between patients (pre-and post-treatment) and healthy controls. Multiple regression analysis in SPM 12 was applied to examine the correlation between post-treatment cortical structural indices and clinical and cognitive scale scores in patients. Spearman correlation analysis was used to evaluate the correlation between changes in whole-brain cortical structure and cognitive function before and after vortioxetine treatment. Results:After vortioxetine treatment, patients with depression exhibited significant reductions in HAMA and HAMD 17 scores, along with significant increases in immediate memory, delayed memory, and total RBANS scores, with statistically significant differences observed ( t=8.43, 12.28, -4.71, -2.41, -3.86 respectively; all P<0.05), while there were no significant changes in visual span, language function, or attention ( P>0.05). Compared to healthy controls, depression patients showed a significantly reduced gyrification index in the right insula/superior temporal gyrus before treatment (28.74±1.20 vs 27.44±1.17; t=4.47, P<0.001), but no significant differences in whole-brain cortical structure were observed before and after treatment or between post-treatment patients and healthy controls ( P>0.05). Correlation analysis indicated that fractal dimension was negatively correlated with HAMA and HAMD 17 scores after treatment, while gyrification index was positively correlated with HAMD 17 ( rpartial=-0.79, -0.83, 0.72; P<0.05). Visual span was positively correlated with fractal dimension ( rpartial=0.78) and negatively correlated with gyrification index ( rpartial=-0.73, P<0.05). Sulcal depth was negatively correlated with attention and RBANS total scores ( rpartial=-0.77, -0.75; P<0.05). Additionally, changes in gyrification index in the left fusiform gyrus were positively correlated with changes in attention ( r=0.51), changes in gyrification index in the left posterior cingulate gyrus were positively correlated with changes in immediate memory ( r=0.58), and changes in sulcal depth in the left superior frontal gyrus were negatively correlated with changes in language ability ( r=-0.79) (both P<0.05). Conclusion:Vortioxetine treatment can improve anxiety and depressive symptoms in depression patients, as well as enhance certain cognitive functions, while also affecting cortical structure in the specific cortical area. Changes in cortical structure after vortioxetine treatment are closely related to clinical symptom improvement and cognitive function changes.

Combined vaccines can simplify the vaccination process, improve coverage rates, reduce the risk of adverse events following immunization, lower social costs, and improve the timeliness of childhood vaccination. This article focuses on multi-component vaccines based on the diphtheria-tetanus-pertussis containing vaccine. Globally, multiple combined vaccines have been developed and marketed, but the development of combined vaccine is still in its infancy stage in China, with limited vaccine types and doses available. The research, development, and application of combined vaccines still face numerous challenges in China, including technical challenges in research and development, as well as insufficient motivation for research and development. Additionally, the high cost of existing combined vaccines, coupled with low public awareness and weak vaccination intentions, significantly hinders their widespread application, China should continue to rigorously implement the Vaccine Administration Law of the People's Republic of China, promote innovative development of combined vaccines, increase public awareness, strengthen child guardians' confidence in vaccination, and improve the accessibility and affordability of combined vaccines to protect public health across all life stages.

To further standardize the management of vaccination units, the Specifications for Vaccination (2023 version) proposes hierarchical management. However, guidelines for establishing, implementing, and evaluating such a framework remain underdeveloped. This paper systematically reviews the current status of hierarchical management in vaccination units, clarifies its feasibility and necessity, and proposes an implementation scheme.