In a healthy human, the airway mucus forms a thin, protective liquid layer covering the surface of the respiratory tract. It comprises a complex blend of mucin, multiple antibacterial proteins, metabolic substances, water, and electrolytes. This mucus plays a pivotal role in the lungs' innate immune system by maintaining airway hydration and capturing airborne particles and pathogens. However, heightened mucus secretion in the airway can compromise ciliary clearance, obstruct the respiratory tract, and increase the risk of pathogen colonization and recurrent infections. Consequently, a thorough exploration of the mechanisms driving excessive airway mucus secretion is crucial for establishing a theoretical foundation for the eventual development of targeted drugs designed to reduce mucus production. Across a range of lung diseases, excessive airway mucus secretion manifests with unique characteristics and regulatory mechanisms, all intricately linked to mucin. This article provides a comprehensive overview of the characteristics and regulatory mechanisms associated with excessive airway mucus secretion in several prevalent lung diseases.
Humans ; Mucus/metabolism* ; Mucins/physiology* ; Lung Diseases/metabolism* ; Respiratory Mucosa/metabolism* ; Pulmonary Disease, Chronic Obstructive/physiopathology* ; Asthma/physiopathology* ; Cystic Fibrosis/physiopathology* ; Mucociliary Clearance/physiology*

Wastewater-based epidemiology has emerged as a transformative surveillance tool for estimating substance consumption and monitoring disease prevalence, particularly during the COVID-19 pandemic. It enables the population-level monitoring of illicit drug use, pathogen prevalence, and environmental pollutant exposure. In this perspective, we summarize the key challenges specific to the Chinese context: (1) Sampling inconsistencies, necessitating standardized 24-hour composite protocols with high-frequency autosamplers (≤ 15 min/event) to improve the representativeness of samples; (2) Biomarker validation, requiring rigorous assessment of excretion profiles and in-sewer stability; (3) Analytical method disparities, demanding inter-laboratory proficiency testing and the development of automated pretreatment instruments; (4) Catchment population dynamics, reducing estimation uncertainties through mobile phone data, flow-based models, or hydrochemical parameters; and (5) Ethical and data management concerns, including privacy risks for small communities, mitigated through data de-identification and tiered reporting platforms. To address these challenges, we propose an integrated framework that features adaptive sampling networks, multi-scale wastewater sample banks, biomarker databases with multidimensional metadata, and intelligent data dashboards. In summary, wastewater-based epidemiology offers unparalleled scalability for equitable health surveillance and can improve the health of the entire population by providing timely and objective information to guide the development of targeted policies.
China/epidemiology* ; Humans ; Wastewater/analysis* ; COVID-19/epidemiology* ; Public Health ; Wastewater-Based Epidemiological Monitoring ; SARS-CoV-2

Colitis-associated cancer(CAC)is a specific type of colorectal cancer that develops from inflammatory bowel disease(IBD).Myeloid-derived suppressor cells(MDSCs)are a group of myeloid cells with immunosuppressive properties,and MDSCs in the tumor microenvironment proliferate and activate during the development of colitis-associated cancer,inhibiting T-cell production and impairing their function,which impedes the immunotherapeutic effect of colitis-associated cancer.In this paper,we review the immunosuppressive mechanisms of MDSCs in the development of inflammatory bowel disease to colitis-associated cancers and the current drugs targeting MDSCs for immunotherapy of inflammatory colorectal cancers,with a view to providing new strategies for the treatment of colitis-associated cancers.

Objective To investigate the effects of cinbufagin(CB)on the proliferation,migration and invasion ability as well as epithelial-mesenchymal transition(EMT)of human colon cells HCT116.Methods Logarithmically grown HCT116 cells were randomly divided into blank group and experimental-L,-M,-H groups;the blank group did not receive any treatment(0 nmol·L-1),and experimental-L,-M,-H groups were cultured in 1 640 medium containing 17.5,35 and 70 nmol·L-1 cinbufagin for 48 h.Cell counting kit-8(CCK-8)was used to detect the effect of cinbufagin on the survival rate of HCT116 cells;cloning assay was used to detect the effect of cinbufagin on the proliferation of HCT116 cells;cell scratch assay and Transwell assay were used to detect the effect of cinbufagin on the migration and invasive ability of HCT116 cells;Western blot was used to detect the expression levels of janus kinase 2(JAK2)/signal transducers and activators of transcription 3(STAT3)pathway and EMT-related proteins of HCT116 cells.Results The number of clone formation in blank group and experimental-L,-M,-H groups were 122.67±24.42,73.67±15.82,44.33±4.51 and 21.67±1.53;the rates of migration of scratches were(44.64±9.15)％,(26.91±2.94)％,(19.28±1.52)％and(6.33±2.30)％;the number of invaded cells were 120.33±1.15,58.33±9.07,33.33±1.53 and 18.33±3.21;the relative protein expression of phosphorylated JAK-2(p-JAK-2)/JAK-2 were 1.02±0.06,0.94±0.05,0.75±0.22 and 0.49±0.22;relative protein expression of phosphorylated STAT3(p-STAT3)/STAT3 were 0.89±0.10,0.72±0.04,0.65±0.06 and 0.52±0.18;relative protein expression of E-cadherin were 0.30±0.14,0.41±0.13,0.49±0.14 and 0.69±0.17;relative protein expression of N-cadherin were 0.96±0.11,0.78±0.04,0.69±0.12 and 0.40±0.15;Snail relative protein expression were 0.89±0.08,0.62±0.15,0.44±0.15 and 0.27±0.09;Vimentin relative protein expression were 0.92±0.09,0.76±0.13,0.63±0.01 and 0.43±0.09,respectively.The above indexes in experimental-H group showed statistically significant differences compared to blank group(all P＜0.05).Conclusion HCT116 can inhibit the invasion and metastasis of human colorectal cancer cells HCT116 by inhibiting epithelial-mesenchymal transition through JAK2/STAT3 pathway.

Objective To explore the mechanism of inhibition of colorectal cancer cells HT29 proliferation,migration and invasion by bufalin through Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods Human colorectal cancer HT29 cells were randomly divided into control group and experimental-L,-M,-H groups.The cells in the control group were not treated,and the cells in the experimental-L,-M,-H groups were treated with 2.5,5.0 and 10.0 μmol·L-1 bufalin for 48 h.After HT29 cells were infected with FLAG STAT3 lentivirus,the cells were divided into lentivirus infection group and experiment-H(10.0 pmol·L-1 bufalin)+lentivirus infection group.Cell viability was detected by cell counting kit 8(CCK-8).Cloning experiment to verify cell proliferation rate;Transwell experiment verified the migration ability of cells after bufalin treatment;the transfection efficiency of lentivirus and the expression of cell-related proteins were detected by Western blot.Results After 48 h of drug action,the number of cells in the control group,experimental-L,-M,-H groups were 1 003.25±255.53,698.00±152.25,562.13±31.56 and 449.50±82.40,respectively;the number of invasive cells were 932.00±188.84,742.22±108.64,514.67±124.82 and 343.56±86.42,respectively;the protein expression level of p-JAK2 were 1.37±0.27,0.97±0.06,0.74±0.06 and 0.39±0.12,respectively.The number of cells in the control group,experimental-H group,lentivirus infection group,and experimental-H+lentivirus infection group were 906.88±211.71,389.00±143.08,1 279.38±210.34 and 604.75±12.52,respectively;the number of invasive cells were 671.22±44.74,246.11±28.16,1 080.78±119.13 and 574.78±16.23,respectively.Compared with the control group,there were statistically significant differences in the number of cell proliferation,the number of cell invasion and the relative levels of p-JAK2 in the experimental-M and-H groups(all P＜0.05).Compared with the control group,the number of cell proliferation and the number of cell invasion in the experimental-H group,the lentivirus infection group,and the high-dose experimental+lentivirus infection group were statistically significant(all P＜0.05).Conclusion Bufalin can inhibit the proliferation,migration and invasion of colorectal cancer by activating the JAK2/STAT3 signalling pathway.

Objective To analyze the atrioventricular synchronization rate after implantation of Micra AV leadless pacemaker,and the impact of postoperative programming optimization on atrioventricular synchronization rate.Methods A prospective cohort study was conducted to select patients with complete atrioventricular block who underwent Micra AV leadless pacemaker implantation at Beijing Anzhen Hospital from August 2022 to June 2023.Programming optimization were performed at 1 week,1 month,and 3 months postoperatively,and atrioventricular synchronization rate,electrical parameters,and echocardiography were recorded.Results A total of 68 patients with complete atrioventricular block implanted with Micra AV were selected,with an average age of(68.2±9.7)years,including 47 males(69.1％).All patients were successfully implanted with Micra AV,and there were no serious postoperative complications;The average threshold,sense,and impedance parameters were stable during 1 week,1 month,and 3 months after the procedure;There was no significant difference in the EF value of postoperative echocardiography(P=0.162);The average atrioventricular synchronization rates at 1 week,1 month,and 3 months postoperatively were(75.2％vs.83.8％vs.91.6％,P=0.001).Conclusions As an mechanical atrial sensing,Micra AV requires personalized adjustment of relevant parameters;Postoperative follow-up programming optimization plays an important role in the atrioventricular synchronization and comfort level in patients with complete atrioventricular block after implantation of Micra AV leadless pacemaker.

Objectives:To evaluate the safety and efficacy of implantation of subcutaneous implantable cardioverter defibrillator(S-ICD)after transvenous lead extraction(TLE)in ICD patients without pacing indications. Methods:All patients who underwent TLE at Peking University People's Hospital from June 2018 to October 2023 were consecutively included.TLE indication,S-ICD implantation indication,defibrillation threshold(DFT)test,complications and postoperative follow-up were collected and analyzed. Results:A total of 11 patients with TV-ICD underwent S-ICD implantation after TLE,eight patients were males and median age were 56(44,65)years.The indications for TLE were infection and lead dysfunction.Nine patients were implanted with S-ICD for secondary prevention,and the most common cause of implantation was ion channelopathies(5 cases).The operative time for S-ICD was 51(48,58)minutes and no perioperative complications were noted.Eight patients underwent DFT testing,and 100%were successful.During a median follow up of 30(9,39)months,a total of six appropriate treatments occurred in two patients,and no complications occurred,including inappropriate treatment,ineffective treatment,infection,lead malfunction and death. Conclusions:Our study provides evidence for S-ICD implantation as a replacement after TV-ICD removal.The S-ICD implantation after TLE is safe and effective.

Parkinson's disease(PD)is the most common neurodegenerative disease,and Lewy bodies(LBs)is the most typical pathological change.α-synuclein(α-syn),as the main component of LBs,is considered as the pathogenic factor of PD.According to the transmission hypothesis,pathological α-syn can be transported from damaged neurons to normal neurons,leading to pathological misfolding and aggregation of α-syn in recipient neurons,resulting in cascading neuronal damage.According to the hypothesis of gut-brain axis,pathological α-syn can be produced in the intestine,and uploaded to the central nervous system via the vagus nerve.In this paper,the role of α-syn in the pathogenesis of PD is summarized,in order to provide reference for the study of intervention targets of PD.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Objective:To evaluate the safety of leadless pacemaker implantation in super-elderly patients.Methods:Eleven patients with average age of 90 (86, 92) years who underwent leadless pacemaker implantation in the Department of Cardiology, Peking University People′s Hospital from March 2021 to May 2022 were included. The clinical data and implantation information were collected. The complications (cardiac tamponade, myocardial infarction, cerebral infarction, pulmonary embolism, pacemaker reinfection, femoral vein hematoma) and death of patients were documented at 24 h, 3 d, and 1, 3, 6 months after pacemaker implantation.Results:There were 9 males and 2 females with the body mass index of 21(19, 23)kg/m 2. The underlying diseases were hypertension, diabetes, coronary heart disease, chronic kidney disease, chronic obstructive pulmonary disease, previous cerebral infarction and moderate to severe tricuspid regurgitation in 9, 9, 9, 6, 4, 4, 4 patients, respectively. The left ventricular ejection fraction was 49% (45%, 52%), the hemoglobin concentration was 118 (114, 122)g/L, 4 patients were taking anticoagulant drugs, and 6 patients were taking antiplatelet drugs. Eight patients were newly implanted with a leadless pacemaker, 2 patients were implanted after removal the old ones, and 1 case was implanted at the same time as removal. The implantation time was 45(40, 47) minutes, the X-ray exposure time was 14 (13, 15) minutes, the release time was 1 (1, 2), the threshold value was 0.50(0.38, 0.75)V/0.24 ms, the impedance was 730 (700, 770) Ω, and the perceived R-wave amplitude 8.2(6.7, 12.8) mV. During the follow-up period of 8 (6, 10) months, no patient had pacemaker dysfunction; and the threshold, R wave sensing, and impedance were stable and maintained within the normal range. No cardiac tamponade, myocardial infarction, cerebral infarction, pulmonary embolism, pacemaker reinfection or death occurred perioperatively and during the follow-up period; 1 patient had hematoma after femoral vein puncture, which improved after compression treatment. Conclusion:This single-center and small-sample study shows that leadless pacemaker implantation is safe for super-elderly patients.