Objective To analyze the factors affecting the prognosis of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) undergoing immunotherapy and construct an individualized prognostic nomogram prediction model. Methods A retrospective analysis was conducted on the clinical data of 385 patients with driver gene-negative, locally advanced or metastatic NSCLC who received first-line immune checkpoint inhibitors. Univariate and multivariate Cox regression analyses were used to identify prognostic risk factors, and a prognostic nomogram model was established. The predictive performance of the model was evaluated using the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves and area under the curve (AUC), and calibration curves. The cutoff value of the nomogram was calculated to stratify patients by risk. Survival curves were calculated by Kaplan-Meier analysis. Results Age (HR=1.775, 95%CI: 1.265-2.490), degree of differentiation (HR=0.365, 95%CI: 0.257-0.519), low PD-L1 expression (HR=0.661, 95%CI: 0.455-0.960), high PD-L1 expression (HR=0.423, 95%CI: 0.297-0.603), SCC-Ag (HR=1.549, 95%CI: 1.109-2.163), and CONUT score (HR=2.527, 95%CI: 1.797-3.554) were independent risk factors affecting overall survival (OS) of patients with NSCLC undergoing immunotherapy. The nomogram prediction model constructed on the basis of these factors had a C-index of 0.767. Time-dependent ROC curves for survival showed that the AUCs for 1-, 2-, and 3-year OS were 0.830, 0.853, and 0.886, respectively. Calibration curves indicated that the nomogram-predicted survival rates were in good agreement with the actual outcomes. The cutoff value for the study’s nomogram prediction model was 136.60 points, and survival curves showed statistically significant differences between different risk groups (P<0.05). Conclusion The nomogram model established in this study can effectively predict the prognosis of patients with driver gene-negative locally advanced or metastatic NSCLC treated with first-line immunosuppressive therapy. It provides a new tool for assessing prognosis and aids clinicians in formulating individualized treatment plans.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

The abnormal accumulation, structural change, and spread of tau protein in the brain are now considered important factors in the progression of Alzheimer’s disease (AD) and many other tau-related neurodegenerative diseases. Clinical and pathological studies have shown that the amount and distribution of abnormal tau protein are closely related to synaptic damage, neuronal loss, and cognitive decline. Therefore, tau protein has become an important target for disease-modifying therapy. However, tau is difficult to target because it has no fixed structure, lacks a clear active site, undergoes many post-translational modifications, and forms different abnormal structures in different diseases and disease stages. Therefore, the effective and selective removal of harmful tau species is both a major opportunity and a major challenge in drug discovery for neurodegenerative diseases. Proteolysis-targeting chimeras (PROTACs) offer a new strategy to deal with this problem. Unlike traditional inhibitors, PROTACs do not simply block protein function. Instead, they bring the target protein close to an E3 ubiquitin ligase, which leads to ubiquitination and degradation of the target protein by the proteasome. This event-driven mechanism may be especially useful for disease-related proteins such as tau protein, which are hard to inhibit with traditional small molecules. In recent years, tau protein-targeting PROTACs and related degradation strategies have shown promising effects in cell and animal models. These effects include reducing abnormal tau protein levels, lowering synaptic toxicity, regulating disease-related signaling pathways, and improving behavioral or cognitive outcomes. These studies support targeted tau protein degradation as a promising therapeutic approach, although many problems still need to be solved before clinical use. In this review, we summarize recent progress in the development of tau protein-targeting PROTACs and discuss the main factors that affect their design and activity. We focus on the choice of tau protein-binding ligands, their binding sites, and their ability to recognize abnormal tau protein rather than normal tau protein. We also discuss the selection of E3 ligase recruiters, linker length and structure, ternary complex formation, and structure-activity relationships that influence degradation potency and selectivity. In addition, we introduce new strategies beyond traditional proteasomal degradation, including the regulation of tau protein phosphorylation and autophagy-based clearance. These approaches may be more suitable for different tau species or different stages of disease. A major challenge for tau protein-targeting PROTACs is delivery to the central nervous system. Many PROTACs have high molecular mass, large polar surface area, flexible structures, and may be removed by efflux transporters. As a result, they often have poor ability to cross the blood-brain barrier and may not reach enough free drug levels in the brain. Therefore, the therapeutic potential of tau protein-targeting PROTACs depends not only on their ability to degrade tau protein in vitro, but also on whether they can achieve long-lasting, selective, and safe target engagement in important brain regions after practical administration. Future studies should focus on improving selectivity for abnormal tau protein, understanding E3 ligase function in neural cells, designing brain-penetrant molecules, developing better delivery methods, and testing these drugs in models that better reflect human disease. Overall, tau protein-targeting PROTACs are a promising and fast-developing strategy for treating tau-related diseases. However, their successful clinical translation will require progress in chemical biology, medicinal chemistry, neuroscience, drug delivery, and translational medicine.

Objective To construct a diagnostic and prognostic model for malignant pleural effusion (MPE) in patients with non-M1b stage (AJCC 7th edition) non-small cell lung cancer (NSCLC) by machine learning. Methods Retrospective analysis was conducted on patients diagnosed with NSCLC in the Surveillance, Epidemiology, and End Results database from 2010 to 2015, excluding those in the M1b stage. Two sets of data were collected: data 1 (patients with non-M1b stage NSCLC, n=47 392) was used to construct the MPE diagnostic model; and data 2 (patients with M1a stage NSCLC and MPE, n=2 422) was used to construct a prognostic model. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to screen feature variables, with a training set and validation set ratio of 7:3. Models were built using eight machine learning algorithms, with evaluation metrics including accuracy, precision, recall, F1 score, area under the ROC curve (AUC), decision curve, calibration curve, and precision recall curve (PR), with ROC-AUC as the main evaluation metric. Results The incidence of MPE in patients with non-M1b stage NSCLC was 5.12%, and the 1-year survival rate of patients with MPE was 32.5%. LASSO regression identified nine diagnostic-related variables and 12 prognostic-related variables. The AUC values of the models constructed by eight machine learning algorithms all exceeded 0.70. The random forest model performed the best in the diagnostic model (training set AUC=0.908, validation set AUC=0.897), and the XGBoost model showed the best performance in the prognostic model (training set AUC=0.905, validation set AUC=0.875). Other evaluation indicators showed good results and balanced distribution. SHAP feature importance analysis showed that tumor size, lymph node metastasis, and histological type were important influencing factors for the occurrence of MPE, and chemotherapy intervention was the most remarkably prognostic factor. Conclusion The random forest diagnostic model constructed in this study can effectively predict the risk of MPE in patients with non-M1b stage NSCLC, and the XGBoost prognostic model can predict the prognosis of M1a-stage NSCLC patients with concurrent MPE.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective:To investigate the trends in detection, treatment, and outcomes of rifampicin-resistant tuberculosis (TB) in Jiangsu Province from 2013 to 2023, assess the effectiveness of control policies and measures for drug-resistant TB, and provide evidence for better control of drug-resistant TB.Methods:Data and indicators related to the screening, diagnosis, treatment, and outcomes of rifampicin-resistant TB in Jiangsu Province from 2013 to 2023 were obtained from the Tuberculosis Management Information System. The Joinpoint regression method was employed to analyze the trends over this period, and annual percent change (APC) and average annual percent change (AAPC) were calculated. A comparative analysis was also conducted to evaluate the changes before and after implementing relevant policies and measures.Results:From 2013 to 2023, the number of registered rifampicin-resistant TB patients in Jiangsu Province showed a consistent upward trend (APC=AAPC=1.45%, P=0.035). The screening rates for drug resistance among new TB patients in high-risk groups and the proportion of molecular biological testing for drug resistance all exhibited increasing trends, with a notable turning point occurring in 2018. The trend of the treatment enrollment rate for rifampicin-resistant TB patients experienced a significant shift in 2020, showing a marked increase from 2013 to 2020 (APC=12.91%, P=0.008). The treatment success rate of rifampicin-resistant TB patients also showed a significant upward trend after a turning point in 2020 (APC=9.94%, P=0.004). Conclusion:From 2013 to 2023, significant progress was seen in preventing and treating rifampicin-resistant TB in Jiangsu Province, with relevant policies and measures proving to be highly effective.

Objective Utilizing patient journey mapping to decipher disease management behaviors,barriers,and needs in young and middle-aged liver transplant recipients,providing implications for self-management optimization and quality of life improvement.Methods Using purposive sampling,12 young and middle-aged liver transplant patients who attended outpatient clinics or were hospitalized in liver transplant center of a tertiary hospital in Qingdao were selected for semi-structured interviews from September to November 2024.Thematic extraction and analysis were performed using Colaizzi's 7-step analysis,ultimately resulting in the development of a patient journey map.Results The journey stages were divided into transplantation decision-making period,transplantation waiting period,perioperative period,and post-discharge management period,and the journey key elements were designed as behaviors,barriers,and needs.A total of 25 themes were extracted,including behaviors(such as referrals to higher-level hospitals,verification of treatment options),barriers(such as lack of decision-making autonomy,health information-seeking barriers),and needs(such as shared decision-making,financial assistance).Ultimately,resulting in a map of the disease management journey for young and middle-aged liver transplant recipients.Conclusion The behaviors,barriers,and needs in disease management among young and middle-aged liver transplant recipients demonstrate distinct phase-specific patterns.Healthcare providers should deliver precise and dynamic interventions tailored to each clinical phase,aiming to foster optimal self-management behaviors,address phase-specific banriers,and meet evolving patient needs throughout the transplant continuum.

Epidermal growth factor receptor(EGFR)gene exon 20 insertion(ex20ins)mutation is a common driver gene activation mutation in non-small cell lung cancer(NSCLC).Tumors harboring this gene mutation are characterized by high heterogeneity,high malignancy,low detectability,poor response to conventional therapies,and poor prognosis.In recent years,significant progress has been made in the study of EGFR ex20ins mutation.The wide application of next-generation sequencing has improved the detection rate.The U.S.Food and Drug Administration(FDA)has approved the relevant indications of amivantamab in NSCLC patients with EGFR ex20ins mutation.A variety of new drugs have also achieved good results in previous studies.This article will summarize the structural characteristics,detection methods and clinical treatment progress of NSCLC patients with EGFR ex20ins mutations,hoping to provide help for the choice of clinical treatment for such patients.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.