BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

This study evaluated the potential of OPC-167832 as a new method for the treatment of Mycobacterium fortuitum infec-tion.Drug sensitivity tests were conducted with the broth microdilution method to determine the minimum inhibitory concentration(MIC)of OPC-167832 against standard strains of M.fortuitum and 44 clinical isolates of M.fortuitum.A DprE1 overexpression strain was constructed,and the effect in the MIC of OPC-167832 against M.fortuitum were explored.Intracellular germicidal tests and checkerboard tests were conducted to verify the ability of OPC-167832 to kill intracellular M.fortuitum,and its interaction with five drugs:amikacin,clarithromycin,imipenem,moxifloxacin,and clofazimine.The MIC50 and MIC90 against 44 clinical isolates of M.fortuitum were 0.031 25 μg/mL and 0.062 5μg/mL,respectively.The epidemiological cut-off value(ECOFF)was 0.062 5 μg/mL.Overexpression of DprE1 led to resistance to OPC-167832 in M.fortuitum.After 24 hours of incubation,the intracellular bacterial in-hibition rate of OPC-167832 at a 1 μg/mL concentration was 81.37%,exceeding the 74.05%inhibition rate of amikacin at a 1 μg/mL concentration.OPC-167832 showed strong inhibitory activity against M.fortuitum in vitro and in macrophages,and might provide a promising treatment for M.fortuitum infection.

Objective This study aimed to provide an effective scientific basis for prevention and control of cockroaches on aircrafts by identifying cockroach-carried pathogens,and assess the insecticidal efficacy of gel bait mediated cockroach control on aircrafts,to provide technical guidance for aircraft disinsection.Methods Cassette-trapping was used to trap cockroaches,and the carried pathogens were detected using bacterial cultivation techniques.The gel bait mediated killing rate was calculated after 1,7,and 30 d by field application of gel bait.Results A total of 411 cockroaches were captured,and all were identified as Blattella germanica.26 strains of pathogenic bacteria were isolated from the trapped cockroaches.The killing rates of cockroaches were 58.8％-96.3％with 1-30 day application of gel bait.Statistically significant differences were observed in cockroach killing rates on different days(χ2=58.95,P<0.01).Conclusions B.germanica carry a large variety of pathogenic bacteria and opportunistic pathogens and are thus important infectious disease carriers.Gel bait agents have proven to be very effective against cockroaches on aircrafts.

Objective To investigate the characteristics of changes in pain-anxiety-depression-fatigue symptom clusters and their possible associated factors in adolescents with acute lymphoblastic leukemia(ALL)during early chemotherapy.Methods A prospective longitudinal study was conducted from Nov 2019 to Oct 2021,enrolling newly diagnosed adolescent ALL patients from 5 tertiary or pediatric specialty hospitals in Shanghai,Zhejiang Province,Sichuan Province,Anhui Province and Guangdong Province.Patient-reported pain,anxiety,depression,and fatigue were collected at five time points within the first nine weeks of chemotherapy using the PROMIS Pediatric-25 instrument.Latent profile analysis(LPA)and latent transition analysis(LTA)were applied to explore the latent classes of symptom clusters,their transition probabilities over time,and possible risk or protective factors associated with class membership.Results A total of 134 ALL cases were enrolled,and symptom clusters at all the 5 time points(T1-T5)were consistently classified into three groups of mild,moderate and severe symptoms.The severe symptoms group accounted for the largest proportion at each time point(54.5%,59.7%,66.4%,49.3%,and 47.0%,respectively),while the mild and moderate symptoms groups showed an initial decline followed by an increase.Among participants,40.2%maintained the same symptom status,and 77.4%experienced at least one episode of severe symptom status during the trajectory.Religious affiliation(T5)and family monthly income>5 000 Yuan(T2,T4 and T5)served as protective factors against severe symptoms.Higher baseline fatigue(T1)was associated with membership in the severe symptoms group at subsequent time points.Conclusion Pain-anxiety-depression-fatigue symptoms in adolescents with ALL during early chemotherapy can be categorized into mild,moderate and severe symptoms with dynamic transitions over time.Higher baseline fatigue was associated with increased risk of severe symptoms,whereas higher family income and religious affiliation appeared protective effects.

Objective To investigate the characteristics of changes in pain-anxiety-depression-fatigue symptom clusters and their possible associated factors in adolescents with acute lymphoblastic leukemia(ALL)during early chemotherapy.Methods A prospective longitudinal study was conducted from Nov 2019 to Oct 2021,enrolling newly diagnosed adolescent ALL patients from 5 tertiary or pediatric specialty hospitals in Shanghai,Zhejiang Province,Sichuan Province,Anhui Province and Guangdong Province.Patient-reported pain,anxiety,depression,and fatigue were collected at five time points within the first nine weeks of chemotherapy using the PROMIS Pediatric-25 instrument.Latent profile analysis(LPA)and latent transition analysis(LTA)were applied to explore the latent classes of symptom clusters,their transition probabilities over time,and possible risk or protective factors associated with class membership.Results A total of 134 ALL cases were enrolled,and symptom clusters at all the 5 time points(T1-T5)were consistently classified into three groups of mild,moderate and severe symptoms.The severe symptoms group accounted for the largest proportion at each time point(54.5%,59.7%,66.4%,49.3%,and 47.0%,respectively),while the mild and moderate symptoms groups showed an initial decline followed by an increase.Among participants,40.2%maintained the same symptom status,and 77.4%experienced at least one episode of severe symptom status during the trajectory.Religious affiliation(T5)and family monthly income>5 000 Yuan(T2,T4 and T5)served as protective factors against severe symptoms.Higher baseline fatigue(T1)was associated with membership in the severe symptoms group at subsequent time points.Conclusion Pain-anxiety-depression-fatigue symptoms in adolescents with ALL during early chemotherapy can be categorized into mild,moderate and severe symptoms with dynamic transitions over time.Higher baseline fatigue was associated with increased risk of severe symptoms,whereas higher family income and religious affiliation appeared protective effects.

This study evaluated the potential of OPC-167832 as a new method for the treatment of Mycobacterium fortuitum infec-tion.Drug sensitivity tests were conducted with the broth microdilution method to determine the minimum inhibitory concentration(MIC)of OPC-167832 against standard strains of M.fortuitum and 44 clinical isolates of M.fortuitum.A DprE1 overexpression strain was constructed,and the effect in the MIC of OPC-167832 against M.fortuitum were explored.Intracellular germicidal tests and checkerboard tests were conducted to verify the ability of OPC-167832 to kill intracellular M.fortuitum,and its interaction with five drugs:amikacin,clarithromycin,imipenem,moxifloxacin,and clofazimine.The MIC50 and MIC90 against 44 clinical isolates of M.fortuitum were 0.031 25 μg/mL and 0.062 5μg/mL,respectively.The epidemiological cut-off value(ECOFF)was 0.062 5 μg/mL.Overexpression of DprE1 led to resistance to OPC-167832 in M.fortuitum.After 24 hours of incubation,the intracellular bacterial in-hibition rate of OPC-167832 at a 1 μg/mL concentration was 81.37%,exceeding the 74.05%inhibition rate of amikacin at a 1 μg/mL concentration.OPC-167832 showed strong inhibitory activity against M.fortuitum in vitro and in macrophages,and might provide a promising treatment for M.fortuitum infection.

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.

Analgesia is an important link in the treatment of severe patients after neurosurgery and plays a vital role in improving the prognosis of the patients.Understanding the status quo and influencing fac-tors of pain in severe patients after neurosurgery helps to predict the occurrence of pain,which is crucial for determining the new pain assessment methods and auxiliary analgesic methods and developing novel analgesic drugs.This paper reviews the pain status,pain evaluation and analgesic methods of severe patients after neuro-surgery in recent years so as to understand the pain management current status of the patients with severe neurological conditions and provide reference for the medical staff to implement the analgesic programs.