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.

Mass spectrometry imaging （MSI） is an emerging molecular imaging technique that combines high spatial resolution and the ability to acquire molecular information. This technology can directly obtain spatial distribution maps of metabolites, proteins, lipids and other molecules in tumor tissues, reveal the abnormal molecular changes during the occurrence and development of liver cancer, and make up for the deficiency of information at the molecular level in traditional imaging （such as CT, MRI）. In liver cancer research, MSI has demonstrated unique advantages and application potential in early diagnosis and screening, precise classification, tumor heterogeneity analysis, and exploration of molecular mechanisms. The principle characteristics of MSI technology and its latest progress in the early diagnosis, classification and molecular mechanism research of liver cancer were reviewed, and the current challenges and future development directions were discussed, which aimed to provide a new perspective and theoretical basis for an in-depth understanding of the pathological mechanism of liver cancer and promoted its precise diagnosis and treatment.

ObjectiveTo investigate the status and dietary intake risk of pesticide residues in fruits and vegetables sold in Wenzhou, Zhejiang Province from 2020 to 2023, so as to provide a scientific basis for the regulation and management of pesticide in the future. MethodsIn accordance with the requirements and methods specified in the “National Food Contamination and Hazardous Factor Risk Monitoring Work Manual” and the current corresponding national food inspection standards for various foods, a total of 807 samples of vegetables and fruits from various counties and districts of Wenzhou City were collected for testing and analysis. Eventually, 23 types of pesticides with a detection rate greater than 5% and those exceeding the standard were selected for dietary intake risk assessment. ResultsFrom 2020 to 2023, the overall detection rate of pesticide residues in fruits and vegetables monitored in Wenzhou was 71.62%, with an overall exceedance rate of 5.27%. From the results of the monitoring of pesticide residues in fruits and vegetables, fresh legume vegetables had the highest detection rate of 90.00%. Among the six major categories of pesticides monitored, fungicides in vegetables and fruits had the highest detection rates of 68.18% and 85.03%, respectively. The highest exceedance rate in vegetables was organophosphorus pesticides, accounting for 2.85%, while in fruits, neonicotinoid pesticides had the highest exceedance rate of 3.21%. From the perspective of sampling time, the peak detection rate of pesticide residues in fruits and vegetables in Wenzhou occurred in June and October. The index of food safety (IFS) of the 23 pesticides with a detection rate higher than 5% ranged from 0.000 7 to 0.694 2 based on the 95% monitoring value of pesticide residues, which were all less than 1. Calculated at maximum content, the IFS values of dithiocarbamate (calculated by CS₂), chlorothalonil and propiconazole were all greater than 1, indicating that the maximum detection values of the three pesticides exceeded the acceptable safety risk. The risk level of acute dietary intake of the 23 pesticides ranged from 1.26% to 52.65%. ConclusionThe overall situation of pesticide residues in fruits and vegetables sold in Wenzhou from 2020 to 2023 is favourable, but the exceedance rate of pesticide in some fruits and vegetables is high. Special attention should be paid to the pesticide residues of fungicides, neonicotinoid insecticides and organophosphorus pesticides in fresh legume vegetables, bulb vegetables and some fruits sold in Wenzhou, such as acetamiprid in bayberry and cowpea, dimethomorph in strawberry, chlorpyrifos in leek, etc., and monitoring of pesticide residues in food need to be strengthened.

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.

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.

Objective To establish an individualized nomogram model and evaluate its efficacy to provide a possible evaluation basis for the prognosis of lower third and abdominal part of oesophageal adenocarcinoma (EAC). Methods Lower third and abdominal part of EAC patients from 2010 to 2015 were chosen from the SEER Research Plus Database (17 Regs, 2022nov sub). The patients were randomly allocated to the training cohort and the internal validation cohort with a ratio of 7∶3 using bootstrap resampling. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) in EAC patients, which would be elected to construct the nomogram prediction model. C-index, calibration curve and receiver operating characteristic (ROC) curve were performed to evaluate its efficacy. Finally, the efficacy to evaluate the OS of EAC patients was compared between the nomogram prediction model and TNM staging system. Results In total, 3945 patients with lower third and abdominal part of EAC were enrolled, including 3475 males and 470 females with a median age of 65 (57-72) years. The 2761 patients were allocated to the training cohort and the remaining 1184 patients to the internal validation cohort. In the training and the internal validation cohorts, the C-index of the nomogram model was 0.705 and 0.713, respectively. Meanwhile, the calibration curve also suggested that the nomogram model had a strong capability of predicting 1-, 3-, and 5-year OS rates of EAC patients. The nomogram also had a higher efficacy than the TNM staging system in predicting 1-, 3-, and 5-year OS rates of EAC patients. Conclusion This nomogram prediction model has a high efficiency for predicting OS in the patients with lower third and abdominal part of EAC, which is higher than that of the current TNM staging system.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.