Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective To explore the effect of stratified out-of-hospital health management led by case health manager on the health behaviour ability of the patients with chronic diseases.Methods A convenience sampling method was employed to select 481 patients with chronic diseases who underwent physical examinations at outpatient department of a Tier-IIIA hospital from April 2022 to April 2023.A health management team led by case health managers conducted questionnaire survey to investigate the individual characteristics of the patients,established personal record based on the physical examination,and implemented stratified out-of-hospital health management for the patients.The intervention lasted for 12 months.The health behaviour ability and chronic disease self-management efficacy of the patients before and after the intervention were compared with.Results After the case manager-led stratified out-of-hospital health management,the health behaviour ability of patients with chronic diseases was stronger than that before the implementation,the self-management efficacy of chronic diseases was better than that before the implementation,and the patients'satisfaction was higher than that before the implementation(all P<0.001).Conclusion Stratified out-of-hospital health management led by a case health manager can improve the health behaviour ability and self-management efficacy of the patient with chronic diseases,thereby improve the patients'satisfaction.

Objective:To explore the application value of coronary CT angiography(CCTA)combined with serum levels of Krueppel like factor 4(KLF4)and histone deacetylase 4(HDAC4)in assessment of coronary artery steno-sis severity in patients with coronary heart disease(CHD).Methods:A total of 152 CHD patients admitted to Suzhou High tech District People's Hospital between December 2021 and December 2023 were prospectively selected.According to coronary angiography(CAG)quantitative analysis method,patients with CHD were divided into mild stenosis group(n=57),moderate stenosis group(n=49)and severe stenosis group(n=46).Kappa consistency a-nalysis was used to determine the consistency between CCTA detection and CAG in determining the degree of coro-nary stenosis.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of CCTA combined with serum KLF4 and HDAC4 levels for the degree of coronary artery stenosis.Results:Compared to pa-tients in mild stenosis group,those in moderate stenosis group and severe stenosis group had significantly lower levels of KLF4 and HDAC4(P＜0.01 all),and those in severe stenosis group had significantly lower levels of KLF4 and HDAC4 compared to those in moderate stenosis group(P＜0.01 all).According to CCTA diagnosis,there were 53 cases with mild stenosis,53 cases with moderate stenosis and 46 cases with severe stenosis.The consistency rate with CAG diagnosis was 80.92％(123/152),which was relatively high(Kappa=0.713,P＜0.001).The accuracy of CCTA in diagnosing mild,moderate and severe stenosis was 88.16％(134/152),85.53％(130/152)and 88.16％(134/152)respectively.ROC curve analysis indicated the area under the curve(AUC)of CCTA combined with ser-um KLF4 and HDAC4 in the diagnosis of moderate and severe coronary artery stenosis was 0.949(95％CI 0.901～0.978),which was significantly higher than those of CCTA(AUC=0.867,95％CI 0.802～0.916),serum KLF4(AUC=0.895,95％CI 0.825～0.939)and HDAC4(AUC=0.809,95％CI 0.738～0.869)alone(Z=2.806,P＜0.001;Z=2.065,P=0.039;Z=3.552,P＜0.001,respectively).Conclusion:In patients with coronary heart dis-ease,serum levels of KLF4 and HDAC4 are closely related to the degree of coronary artery stenosis.The combina-tion of CCTA,serum KLF4 and HDAC4 levels has good performance in predicting the degree of coronary artery stenosis.

Objective:To determine the diagnosis of microtia-associated syndrome through genetic testing.Methods:Peripheral venous blood samples were collected from members of a two-generation family with a syndrome associated with ear malformations (3 patients and 1 normal control). Pathogenic mutations were identified using whole exome sequencing analysis, Sanger sequencing validation, and bioinformatics analysis. Based on the genetic diagnosis and a review of the literatures, the patients′ clinical phenotypes were thoroughly evaluated to confirm the clinical diagnosis.Results:All three patients carried a novel heterozygous insertion mutation (c.1171_1172insGGCC: p.Pro391fs) in the paired box 1 ( PAX1) gene. This mutation showed genotype-phenotype co-segregation within the family and was predicted to be pathogenic. Consequently, the family was diagnosed with autosomal dominant otofaciocervical syndrome 2. The clinical phenotypes of the patients included not only ear malformations and conductive hearing loss but also branchial cleft fistula, preauricular fistula, bilateral facial asymmetry, spinal deformities, and short stature, which were major symptoms of otofaciocervical syndrome 2. Imaging also revealed previously unreported phenotypes, including parotid gland malformation and facial nerve dysplasia. Conclusion:The heterozygous insertion in PAX1 (c.1171_1172insGGCC: p.Pro391fs) found in this family causes otomandibular-cervical syndrome type 2 in an autosomal dominant manner, leading to congenital anomalies affecting external and middle ear, craniofacial region, and spine.

With the rapid development of minimally invasive techniques in surgery, arti-ficial intelligence (AI), particularly deep learning, is playing an increasingly important role in mini-mally invasive surgery. By automated analysis of surgical videos, AI can efficiently perform key tasks such as instrument recognition, surgical phase identification, action analysis, anatomical structure recognition, intraoperative diagnosis, adverse event monitoring and smart desmoking. These appli-cations provide essential support for real-time monitoring, surgical navigation and skill assessment during surgery. The authors summarize the current research progress of AI in minimally invasive surgery, including its applications in the fields of hepatobiliary and pancreatic surgery, as well as gastrointestinal surgery. It also explores the potential of AI in enhancing surgical safety, efficiency and skill assessment. By synthesizing the latest research achievements of AI technology in the field of surgery, as well as analyzing its technical challenges and risks, it aims to provide guidance for future innovations and clinical applications, promoting the advancement and implementation of AI in minimally invasive surgery.

Through a systematic review of the literature on the treatment of eczema with Binghuang Fule Ointment, the "6+1" assessment model was used to comprehensively evaluate its clinical value, providing a basis for decisions on the allocation of medical resources, rational clinical medication use, and hospital procurement and supply of Chinese patent medicines in China. Based on the relevant standards in the Guidelines for the Management of Clinical Evidence and Value Evaluation of Drugs, diversified research methods were adopted, including evidence-based medical evidence, questionnaire surveys, and pharmacoeconomic evaluations. These methods were combined with both qualitative and quantitative research approaches, and the multi-criteria decision analysis(MCDA) model was applied to perform a comprehensive evaluation of Binghuang Fule Ointment in treating eczema. Safety was evaluated based on evidence adequacy assessments and known risk evaluations, and thus the safety was rated as grade A, indicating that its risk is controllable, its safety is good, and there is sufficient evidence to confirm its safety. The evidence of effectiveness came from the results of Meta-analysis, which showed that Binghuang Fule Ointment + conventional treatment/Binghuang Fule Ointment vs conventional treatment had better clinical effective effect, and the effectiveness was rated as grade A. The economic evaluation, integrating evidence value and evidence quality results, thus the economy was rated as grade B. Innovation was evaluated based on three primary indexes and 18 secondary indexes, with Binghuang Fule Ointment's innovation rated as grade B, indicating a good level of innovation. Suitability was assessed through a questionnaire survey and Chinese patent medicine information service data, and Binghuang Fule Ointment's suitability was rated as grade B, indicating good suitability. Accessibility was assessed based on the proportion of Binghuang Fule Ointment's daily cost relative to the median disposable income of urban and rural residents. The proportion was only 0.05% in urban residents' median disposable income, and 0.14% in rural residents' median disposable income. Accessibility was rated as grade B, reflecting good accessibility. Binghuang Fule Ointment was prescribed by a senior Tibetan doctor with many years of clinical experience at the People's Hospital of Tibet Autonomous Region. Its traditional Chinese medicine characteristics were rated as grade B. Based on the results from the "6+1" evaluation dimensions, the comprehensive value score of Binghuang Fule Ointment was calculated using CSC v2.0 software, yielding a score of 0.79, which corresponds to a class A, indicating good clinical value.
Humans ; Ointments ; Drugs, Chinese Herbal/therapeutic use* ; Eczema/economics*

Kidney-Yang deficiency syndrome is a common geriatric disease that underlies chronic conditions such as diabetic nephropathy, chronic kidney disease, and osteoporosis. As age progresses, the kidney-Yang deficiency syndrome showcases increasingly pronounced manifestations, emerging as a key factor in the comorbidities experienced by elderly patients and affecting their quality of life and overall health status. Traditional Chinese medicine(TCM) has been extensively utilized in the treatment of kidney-Yang deficiency syndrome, with Epimedii Folium, Cinnamomi Cortex, and Lycii Fructus widely used in clinical settings. Despite the complexity of the molecular mechanisms involved in treating kidney-Yang deficiency syndrome, the potential therapeutic value of TCM remains compelling. Delving into the mechanisms of TCM treatment of kidney-Yang deficiency syndrome by regulating the neuro-endocrine-immune system can provide a scientific basis for targeted treatments of this syndrome and lay a foundation for the modernization of TCM. The pathophysiology of kidney-Yang deficiency syndrome involves multiple systems, including the interaction of the neuro-endocrine-immune system, the decline in renal function, the intensification of oxidative stress responses, and energy metabolism disorders. Understanding these mechanisms and their interrelationships can help untangle the etiology of kidney-Yang deficiency syndrome, aiding clinicians in making more precise diagnoses and treatments. Furthermore, the research on the specific applications of TCM in research on these pathological mechanisms can enhance the international recognition and status of TCM, enabling it to exert a greater global influence.
Humans ; Yang Deficiency/physiopathology* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Kidney Diseases/physiopathology* ; Neurosecretory Systems/physiopathology* ; Animals ; Kidney/physiopathology* ; Endocrine System/physiopathology* ; Immune System/physiopathology*

Poor water solubility is the primary obstacle preventing the development of many pharmacologically active compounds into oral preparations. Self-nanoemulsifying drug delivery systems(SNEDDS) have become a widely used strategy to enhance the oral bioavailability of poorly soluble drugs by inducing a supersaturated state, thereby improving their apparent solubility and dissolution rate. However, the supersaturated solutions formed in SNEDDS are thermodynamically unstable systems with solubility levels exceeding the crystalline equilibrium solubility, making them prone to drug precipitation in the gastrointestinal tract and ultimately hindering drug absorption. Therefore, maintaining a stable supersaturated state is crucial for the effective delivery of poorly soluble drugs. Incorporating polymers as precipitation inhibitors(PPIs) into the formulation of supersaturated self-nanoemulsifying drug delivery systems(S-SNEDDS) can inhibit drug aggregation and crystallization, thus maintaining a stable supersaturated state. This has emerged as a novel preparation strategy and a key focus in SNEDDS research. This review explores the preparation design of SNEDDS and the technical challenges involved, with a particular focus on polymer-based S-SNEDDS for enhancing the solubility and oral bioavailability of poorly soluble drugs. It further elucidates the mechanisms by which polymers participate in transmembrane transport, summarizes the principles by which polymers sustain a supersaturated state, and discusses strategies for enhancing drug absorption. Altogether, this review provides a structured framework for the development of S-SNEDDS preparations with stable quality and reduced development risk, and offers a theoretical reference for the application of S-SNEDDS technology in improving the oral bioavailability of poorly soluble drugs.
Solubility ; Administration, Oral ; Polymers/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Emulsions/chemistry* ; Biological Availability ; Animals ; Pharmaceutical Preparations/administration & dosage*

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major health concern in northwest China; however, the impact of particulate matter (PM) exposure during sand-dust storms (SDS) remains poorly understood. Therefore, this study aimed to investigate the association between PM exposure on SDS days and COPD hospitalization risk in arid regions. METHODS: Data on daily COPD hospitalizations were collected from 323 hospitals from 2018 to 2022, along with the corresponding air pollutant and meteorological data for each city in Gansu Province. Employing a space-time-stratified case-crossover design and conditional Poisson regression, we analyzed 265,379 COPD hospitalizations. RESULTS: PM exposure during SDS days significantly increased COPD hospitalization risk [relative risk ( RR) for PM _2.5, lag 3:1.028, 95% confidence interval ( CI): 1.021-1.034], particularly among men and the elderly, and during the cold season. The burden of PM exposure on COPD hospitalization was substantially high in Northwest China, especially in the arid and semi-arid regions. CONCLUSION Our findings revealed a positive correlation between PM exposure during SDS episodes and elevated hospitalization rates for COPD in arid and semi-arid zones in China. This highlights the urgency of developing region-specific public health strategies to address adverse respiratory outcomes associated with SDS-related air quality deterioration.
Humans ; China/epidemiology* ; Pulmonary Disease, Chronic Obstructive/chemically induced* ; Particulate Matter/analysis* ; Hospitalization/statistics & numerical data* ; Male ; Female ; Middle Aged ; Aged ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Spatio-Temporal Analysis ; Adult ; Sand ; Air Pollution

This study aimed to identify ideal pharmaceutical candidates featuring strong anti-HIV-1 activity and desirable drug-like characteristics. Our endeavor involved the implementation of a bioisosterism strategy, leading to the discovery of an assemblage of halogen-containing biphenyl-diarylpyrimidines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors. Notably, compound A12 demonstrated exceptional efficacy against both WT HIV-1 (EC₅₀ = 1.9 nmol/L) and seven mutant strains (EC₅₀ = 1.7-157 nmol/L), surpassing that of the lead compound 6 and comparable to etravirine. Furthermore, this analog exhibited minimal adverse effects with significantly reduced cytotoxicity (CC₅₀ = 195 μmol/L) and a high selectivity index (SI = 102,608), superior to those of etravirine (CC₅₀ > 4.6 μmol/L, SI > 1436) and rilpivirine (CC₅₀ = 3.98 μmol/L, SI = 3989). It displayed low inhibition of CYP (IC₅₀ = 6.99-25 μmol/L) and hERG (IC₅₀ > 40 μmol/L), indicating a safer profile compared to etravirine and rilpivirine. No acute toxicity or organ pathological damage was observed at a single dose of 2 g/kg. Additionally, A12 exhibited favorable oral bioavailability (F = 29.2%) and an extended elimination half-life (T _1/2 = 13.56 h), enabling convenient oral administration at minimal doses. These findings indicated that A12 could serve as a promising drug candidate for HIV treatment.