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.

Pancreatic ductal adenocarcinoma （PDAC） has an extremely poor prognosis， and resistance to gemcitabine is one of the key reasons for treatment failure， with an underlying mechanism closely associated with lipid metabolic reprogramming in tumor cells. This article aims to systematically elaborate on the multidimensional drug resistance network constructed by such reprogramming and the feasibility of targeted intervention. Lipid metabolic reprogramming comprehensively remodels the metabolic homeostasis of PDAC cells by enhancing lipid uptake， de novo synthesis， storage， and oxidative catabolism in a synergistic manner. This process alters membrane lipid composition to impede drug influx and promote efflux， thereby reducing intracellular drug concentration. Meanwhile， it activates pathways involving sterol regulatory element-binding protein and peroxisome proliferator-activated receptor δ， couples lipid synthesis with cell survival， stemness， and anti-apoptotic capacity， and synergizes with autophagy to provide survival support through “lipophagy”. In addition， it reshapes the tumor microenvironment through “lipid hijacking” and the secretion of immunosuppressive mediators. Based on the above mechanisms， targeting key lipid metabolic enzymes （such as fatty acid synthase， stearoyl-CoA desaturase， carnitine palmitoyltransferase 1） or their upstream regulators has shown certain potential in reversing such drug resistance in preclinical studies. Although clinical translation faces the challenges such as systemic toxicity， metabolic redundancy in tumors， and patient heterogeneity， the development of biomarkers， intelligent drug delivery systems， and combined therapies may provide new ideas for overcoming drug resistance.

Objective:To investigate the effect of laparoscopic splenectomy and azygoportal disconnection (LSD) on liver synthesis and development of liver cirrhosis.Methods:This is a prospective case series study.The clinical data of liver cirrhotic patients with portal hypertension who received LSD at the Department of Hepatobiliary Surgery of Northern Jiangsu People′s Hospital Affiliated to Yangzhou University from September 2014 to January 2016 were included. This study analyzed the diameter of the portal vein, the velocity of portal blood flow, the routine blood parameters, the liver function, the synthetic proteins of liver (antithrombin Ⅲ (AT-Ⅲ), protein S, protein C), and the serum content of liver fibrotic markers(collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase). Repeated measures ANOVA was used for comparison between multiple groups, and least significance difference was used for post-hoc multiple comparison.Results:A total of 106 patients were included in the study, including 70 males and 36 females, aged (51.8±9.8) years(range: 28 to 75 years).Compared with the preoperative results, the diameter of portal vein and the velocity of portal vein decreased after surgery ( F=14.03, 12.15, respectively, both P<0.01). Compared with the preoperative results, the total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score and classification were improved ( F=17.96, 56.01, 66.63, 35.83, 33.49, and 27.50, respectively, all P<0.01), and the AT-Ⅲ, protein S, protein C,collagen type Ⅳ, procollagen type Ⅲ, laminin and hyaluronidase levels were also improved ( F=47.87, 36.26, 18.02, 2.79, 14.58, 44.35, and 14.38, respectively, all P<0.01). Compared with the preoperative period, the diameter of portal vein was reduced from the first week to the 24 th month after surgery ( t=5.45 to 9.39, all P<0.01). Compared with the preoperative period, the velocity of portal vein blood from the first week after surgery to the 24 th month after surgery was decreased ( t=4.02 to 8.43, all P<0.01). Compared with the preoperative period, routine blood parameters (white blood count, hemoglobin, platelet count), liver function (total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score), liver synthetic protein (AT-Ⅲ, protein S, protein C) and liver fibrotic markers (collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase) were improved to varying degrees at the 24th month after surgery ( t=-20.46 to 11.93, all P<0.01). Conclusion:Preliminary findings show that LSD can reduce portal vein pressure, restore blood cell number, and improve liver synthesis function and the degree of liver fibrosis in patients with portal hypertension in liver cirrhosis.

Objective:To investigate the effect of laparoscopic splenectomy and azygoportal disconnection (LSD) on liver synthesis and development of liver cirrhosis.Methods:This is a prospective case series study.The clinical data of liver cirrhotic patients with portal hypertension who received LSD at the Department of Hepatobiliary Surgery of Northern Jiangsu People′s Hospital Affiliated to Yangzhou University from September 2014 to January 2016 were included. This study analyzed the diameter of the portal vein, the velocity of portal blood flow, the routine blood parameters, the liver function, the synthetic proteins of liver (antithrombin Ⅲ (AT-Ⅲ), protein S, protein C), and the serum content of liver fibrotic markers(collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase). Repeated measures ANOVA was used for comparison between multiple groups, and least significance difference was used for post-hoc multiple comparison.Results:A total of 106 patients were included in the study, including 70 males and 36 females, aged (51.8±9.8) years(range: 28 to 75 years).Compared with the preoperative results, the diameter of portal vein and the velocity of portal vein decreased after surgery ( F=14.03, 12.15, respectively, both P<0.01). Compared with the preoperative results, the total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score and classification were improved ( F=17.96, 56.01, 66.63, 35.83, 33.49, and 27.50, respectively, all P<0.01), and the AT-Ⅲ, protein S, protein C,collagen type Ⅳ, procollagen type Ⅲ, laminin and hyaluronidase levels were also improved ( F=47.87, 36.26, 18.02, 2.79, 14.58, 44.35, and 14.38, respectively, all P<0.01). Compared with the preoperative period, the diameter of portal vein was reduced from the first week to the 24 th month after surgery ( t=5.45 to 9.39, all P<0.01). Compared with the preoperative period, the velocity of portal vein blood from the first week after surgery to the 24 th month after surgery was decreased ( t=4.02 to 8.43, all P<0.01). Compared with the preoperative period, routine blood parameters (white blood count, hemoglobin, platelet count), liver function (total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score), liver synthetic protein (AT-Ⅲ, protein S, protein C) and liver fibrotic markers (collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase) were improved to varying degrees at the 24th month after surgery ( t=-20.46 to 11.93, all P<0.01). Conclusion:Preliminary findings show that LSD can reduce portal vein pressure, restore blood cell number, and improve liver synthesis function and the degree of liver fibrosis in patients with portal hypertension in liver cirrhosis.

Acori Tatarinowii Rhizoma is the dried rhizome of Acorus tatarinowii in the family of Tennantiaceae, which has the efficacy of opening up the orifices and expelling phlegm, awakening the mind and wisdom, and resolving dampness and opening up the stomach. Modern studies have shown that volatile oil is the main active ingredient of Acori Tatarinowii Rhizoma, and α-asarone and β-asarone have been proved to be the active ingredients in the volatile oil of Acori Tatarinowii Rhizoma, with pharmacological effects such as anti-Alzheimer's disease, antiepileptic, anti-Parkinson's disease, antidepressant, anticerebral ischemia/reperfusion injury, anti-thrombosis, lipid-lowering, and antitumor. By summarising and outlining the pharmacological effects of α-asarone and β-asarone and elucidating the possible mechanisms of their pharmacological effects, we can provide theoretical basis for the further research and clinical application of Acori Tatarinowii Rhizoma.
Allylbenzene Derivatives ; Acorus/chemistry* ; Anisoles/chemistry* ; Rhizome/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Humans ; Animals

The development of bone in human body and the maintenance of bone mass in adulthood are regulated by a variety of biological factors. Myocyte enhancer factor 2C (MEF2C), as one of the many factors regulating bone tissue development and balance, has been shown to play a key role in bone development and metabolism. However, there is limited systematic analysis on the effects of MEF2C on bone tissue. This article reviews the role of MEF2C in bone development and metabolism. During bone development, MEF2C promotes the development of neural crest cells (NC) into craniofacial cartilage and directly promotes cartilage hypertrophy. In terms of bone metabolism, MEF2C exhibits a differentiated regulatory model across different types of osteocytes, demonstrating both promoting and other potential regulatory effects on bone formation, with its stimulating effect on osteoclasts being determined. In view of the complex roles of MEF2C in bone tissue, this paper also discusses its effects on some bone diseases, providing valuable insights for the physiological study of bone tissue and strategies for the prevention of bone diseases.
Humans ; MEF2 Transcription Factors/physiology* ; Bone and Bones/metabolism* ; Animals ; Bone Development/physiology* ; Osteogenesis/physiology* ; Myogenic Regulatory Factors/physiology*

Drug toxicity is closely related to both clinical drug safety and new drug development. Therefore, it is vital to understand the mechanisms of drug toxicity fully and to use appropriate research models with advanced technologies. Zebrafish has become an important vertebrate animal model for high-throughput drug screening and toxicity assessment. At the same time, zebrafish has an intact biological complexity, reflecting the whole organism's toxicity, which gives it an advantage over other high-throughput models in toxicity studies. Despite the gradual increase in toxicity studies utilizing zebrafish, a comprehensive and systematic review of the underlying mechanisms and new techniques is still lacking. This review aims to analyze common toxicity mechanisms in zebrafish models, such as oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis, and macroscopic changes in biological processes like lipid metabolism disorders and neurotransmitter expression abnormalities. It also introduces new technologies applied in toxicity assessment, such as gene editing, novel fluorescence imaging technology, 3D imaging technology, and novel automated technology for high-throughput screening, such as fish capsules. In addition, it also summarizes the advantages and disadvantages of the model. By doing so, it will provide new suggestions for the development and improvement of the model, make it better serve the toxicity study of clinical drugs and provide a more comprehensive perspective for drug toxicity study, thus promoting the development of the field of drug toxicity study.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective To analyze the characteristic influencing factors for enlarged perivascular spaces(EPVS)in different regions of acute ischemic stroke(AIS)patients and explore their un-derlying pathogenesis.Methods A total of 172 AIS patients admitted to our department from September 2020 to September 2023 were consecutively enrolled.According to the distribution of EPVS,they were divided into basal ganglia EPVS group(n=103)and non-basal ganglia EPVS group(n=69),as well as centrum semiovale EPVS group(n=77)and non-centrum semiovale EPVS group(n=95).General information,NIHSS score at onset,TOAST classification,fasting blood glucose,liver function,coagulation function,and homocysteine(Hcy)level were collected in all the patients.Multivariate logistic regression analysis was used to identify independent influen-cing factors for EPVS in different regions.Results The basal ganglia EPVS group had significant-ly advanced age and larger proportion of hypertension than the non-basal ganglia EPVS group,while the centrum semiovale EPVS group had smaller proportion of hyperhomocysteinemia,and larger ratios of smoking and alcohol consumption,higher alanine aminotransferase(ALT)level,and longer thrombin time than the non-centrum semiovale EPVS group(P＜0.05,P＜0.01).Mul-tivariate logistic regression analysis showed that hypertension(OR=2.093,95％CI:1.045-4.192,P=0.037)and age(OR=1.071,95％CI:1.016-1.130,P=0.011)were independent influ-encing factors for basal ganglia EPVS,while alcohol consumption(OR=2.418,95％CI:1.097-5.330,P=0.029)and thrombin time(OR=1.593,95％CI:1.129-2.249,P=0.008)were inde-pendent influencing factors for centrum semiovale EPVS.Conclusion EPVS in different regions of AIS patients are associated with distinct risk factors.Age and hypertension are primary influen-cing factors for basal ganglia EPVS,while alcohol consumption and prolonged thrombin time are significant factors for centrum semiovale EPVS.

Objective To investigate the correlation of the characteristics of symptomatic middle cerebral artery plaques with the risk of stroke recurrence based on high-resolution vessel wall imaging(HR-VWI).Methods Totally 83 patients hospitalized for acute ischemic stroke(AIS)and transient ischemic attack(TIA)at Jingmen People's Hospital and Yichang Central People's Hospital from January 2019 to August 2022 were selected prospectively,who all underwent the treatment with antiplatelet aggregation and intensive lipid lowering by statins.During the follow-up,AIS or TIA recurrences were determined in case of newly found symptoms of neurological impairment in the same supply area of the responsible vessel or new infarct foci confirmed by cranial diffusion weighted imaging(DWI).The patients with AIS or TIA recurrences were enrolled into a recurrence group,and the remained ones were divided into a non-recurrence group.The recurrence group went through HR-VWI scanning within two weeks of recurrence and statin treatment,and the non-recurrence group was examined with HR-VWI half a year after receiving statin treatment.All the patients had their clinical indexes compared before and after statin treatment,the baseline data of the two groups underwent univariate analysis,and Logistic regression analysis was performed for the high-risk factors related to recurrence.SPSS 22.0 software was used for statistical analysis.Results After six months of statin treatment,all the patients were improved in TC,TG,luminal stenosis rate,high T1WI signal,plaque burden,plaque enhancement rate and NIHSS score,with the differences being significant(all P＜0.05).Univariate analysis showed the recurrence group had higher plaque enhancement rates(P=0.012)and higher plaque burden(P=0.047)when compared with the non-recurrence group,with the differences being significant;the two groups were not statistically different in luminal stenosis rate,high T1WI signal,plaque thickness and remodeling index(all P＞0.05).Multivariate logistic regression analysis indicated the plaque enhancement rate was independently correlated with stroke recurrence within 6 months(P=0.027).Conclusion HR-VWI can effectively assess MCA plaque characteristics in recurrent stroke patients,and high plaque enhancement rate faciliates the evaluation of stroke recurrence.[Chinese Medical Equipment Journal,2025,46(2):63-67]