Objective In order to understand the current resistance status of Aedes albopictus(Ae. albopictus) adult population to commonly used insecticides and the resistance dynamics development in Zhejiang Province and provide a theoretical basis for the scientific and rational use of hygienic insecticides. Methods Resistance determination was carried out using the diagnostic dose method(GB/T 26347-2010)recommended by WHO in the adult mosquito contact cylinder method to monitor the resistance of Ae. albopictus field populations in 11 cities and districts in Zhejiang Province in 2024. Results The monitoring result showed that adult Ae. albopictus in 11 areas were resistant or suspected resistant populations to both cis-cypermethrin and permethrin; suspected and resistant populations to the organophosphate insecticide malathion were as high as 81.82%; while suspected resistance to the carbamate insecticide residual carbofuran accounted for 45.45%, and the rest of the monitoring sites were sensitive to it. Conclusions The result suggest that the generalized resistance of Ae. albopictus populations to pyrethroids and organophosphorus insecticides in the field in Zhejiang Province needs to be highly emphasized. In future mosquito vector and mosquito-borne disease control, insecticides should be selected based on the resistance monitoring information, while following scientific guidelines for insecticide use.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

The study aimed to construct the second and third generation chimeric antigen receptor T cells (CAR-T) targeting the c-mesenchymal-epithelial transition factor (c-Met) protein, and observe their killing effect on human serous ovarian cancer cell SKOV-3. The expression of MET gene in ovarian serous cystadenocarcinoma, the correlation between MET gene expression and the abundance of immune cell infiltration, and the effect of MET gene expression on the tissue function of ovarian serous cystadenocarcinoma were analyzed by bioinformatics. The expression of c-Met in ovarian cancer tissues and adjacent tissues was detected by immunohistochemical staining. The second and third generation c-Met CAR-T cells, namely c-Met CAR-T(2G/3G), were prepared by lentivirus infection, and the cell subsets and infection efficiency were detected by flow cytometry. Using CD19 CAR-T and activated T cells as control groups and A2780 cells with c-Met negative expression as Non target groups, the kill efficiency on SKOV-3 cells with c-Met positive expression, cytokine release and cell proliferation of c-Met CAR-T(2G/3G) were explored by lactate dehydrogenase (LDH) release, ELISA and CCK-8 respectively. The results showed that MET gene expression was significantly up-regulated in ovarian cancer tissues compared with normal tissues, which was consistent with the immunohistochemistry results. However, in all pathological stages, there was no obvious difference in MET expression and no correlation between MET gene expression and the race and age of ovarian cancer patients. The second generation and third generation c-Met CAR-T cells were successfully constructed. After lentivirus infection, the proportion of CD8⁺ T cells in c-Met CAR-T(2G) was upregulated, while there was no significant change in the cell subsets of c-Met CAR-T(3G). The LDH release experiment showed that the kill efficiency of c-Met CAR-T(2G/3G) on SKOV-3 increased with the increase of effect-target ratio. When the effect-target ratio was 20:1, the kill efficiency of c-Met CAR-T(2G) reached (42.02 ± 5.17)% (P < 0.05), and the kill efficiency of c-Met CAR-T(3G) reached (51.40 ± 2.71)% (P < 0.05). ELISA results showed that c-Met CAR-T released more cytokine compared to CD19 CAR-T and activated T cells (P < 0.05). Moreover, the cytokine release of c-Met CAR-T(3G) was higher than c-Met CAR-T(2G) (P < 0.01). The CCK-8 results showed that after 48 h, the cell number of c-Met CAR-T(2G) was higher than that of c-Met CAR-T(3G) (P < 0.01). In conclusion, both the second and third generation c-Met CAR-T can target and kill c-Met-positive SKOV-3 cells, with no significant difference. c-Met CAR-T(2G) has stronger proliferative ability, and c-Met CAR-T(3G) releases more cytokines.
Humans ; Female ; Ovarian Neoplasms/immunology* ; Proto-Oncogene Proteins c-met/metabolism* ; Receptors, Chimeric Antigen/immunology* ; Cell Line, Tumor ; Cystadenocarcinoma, Serous/immunology* ; T-Lymphocytes/immunology*

Objective To investigate the efficacy of lacosamide combined with ketogenic diet in the treatment of pediatric epilepsy and its impacts on the levels of serum glial fibrillary acidic protein(GFAP)and specific protein of the central nervous system(S-100β).Methods A total of 64 chil-dren with epilepsy from July 2022 to April 2024 were selected and randomly divided into conventional group(n=32)receiving oral lacosamide tablets and combined group(n=32)receiving ketogenic di-et therapy based on the conventional group.The efficacy,cognitive function,and intelligence of chil-dren in both groups after treatment,as well as the levels of serum GFAP and S-100β,the frequency of seizures,and electroencephalogram(EEG)findings before and after treatment were evaluated.Results After treatment,the number of alpha waves,the Full-scale Intelligence Quotient(FIQ)of the Wechsler Intelligence Scale for Children,and the Montreal Cognitive Assessment(MoCA)scores increased in both groups,with a greater increase in the combined group compared to the conventional group,and the differences were statistically significant(P＜0.05).The levels of serum S-100β and GFAP,the frequency of seizures,and the number of cases with slow waves and epileptiform waves decreased after treatmen,and these indicators were lower in the combined group than in the conventional group,with sta-tistically significant differences(P＜0.05).The total effective rate was 90.63％in the combined group and 68.75％in the conventional group,with a statistically significant difference(P＜0.05).The incidence of adverse reactions was 12.50％in the combined group and 9.38％in the conventional group,with no statistically significant difference(P＞0.05).Conclusion Lacosamide combined with ketogenic diet shows good efficacy in the treatment of pediatric epilepsy,and the combined therapy improves neurological function by synergistically reducing the levels of GFAP/S-100β.

Objective To explore the correlation between blood biochemical indexes and blood pressure levels among college students in Kunming City.Methods In November 2021,a cluster sampling method was used to survey 4,781 college students at a university in Yunnan Province.Data collected included height,weight and blood pressure,and blood samples were collected for blood biochemical testing.The Mann-Whitney U test and Kruskal-Wallis H test were used to compare the distribution differences of hypertension among college students with different demographic characteristics,while a generalized linear model was used to analyze the correlation between blood biochemical indicators and blood pressure levels.Results The prevalence rate of hypertension among college students was 8.45%(404/4 781).After adjusting confounding variables,blood glucose(GLU,β=1.48,95%CI:0.75～2.20)and serum Total Protein(TP,β=0.25,95%CI:0.19～0.32)were found to be correlated with systolic blood pressure(SBP)levels(all P<0.05);blood glucose(GLU,β=1.25,95%CI:0.64～1.86)and serum total protein(TP,β=0.28,95%CI:0.23～0.34)were correlated with diastolic blood pressure(DBP)level(P<0.05).Stratified group analysis by sex showed that,after controlling for confounding factors,TP(β=0.32,95%CI:0.18～0.45)was correlated with SBP levels in male students;TP(β=0.32,95%CI:0.21～0.43)was correlated with DBP levels in male students(P<0.05).GLU(β=2.18,95%CI:1.29～3.07)and TP(β=0.23,95%CI:0.15～0.31)were correlated with SBP levels in female students;GLU(β=1.48,95%CI:0.73～2.24)and TP(β=0.26,95%CI:0.20～0.33)were correlated with DBP levels in female students(all P<0.05).Conclusion Our findings suggest that blood glucose and serum total protein level are correlated with blood pressure levels in female college students,while serum total protein level are correlated with blood pressure levels in male college students.

In recent years,the market share of food and medicine homology substances has continued to grow,and various types of contamination issues have become the focus of attention both inside and outside the industry.The contamination not only affects the original medicinal quality,but also leads to the accumulation of toxic substances in the human body,causing acute and chronic severe hazards such as vomiting,poisoning and cancer.Therefore,the development of biosensors that can conveniently,accurately and sensitively detect various pollutants in food and medicine homology substances has become a research hotspot.Aptasensors based on metal-organic frameworks(MOFs)with advantages such as strong specificity,rapid response and simple operation,have been widely used in detection of various pollutants.This review focused on the research progress of aptasensors based on MOFs for detection of food and medicine homology contamination in the past few years,and provided a detailed comparison and analysis for detection of chemical pollutants(such as pesticide residues,heavy metal residues,mycotoxins,etc.)and microbial contamination in food and medicine homology substances.Besides,the development trend and possible challenges of MOFs aptasensors in detection of food and medicine homology substances in the future were discussed,which was anticipated to provide a reference for the development of new MOFs aptasensors.

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.

Objective:Kawasaki disease shock syndrome（KDSS）and macrophage activation syndrome（MAS）are both severe forms of Kawasaki disease. The coexistence of these two critical illnesses is extremely rare，which can be life-threatening in severe cases. The purpose of this study is to summarize the clinical features of children with KDSS complicated with MAS，and provide a basis for precise diagnosis and treatment.Methods:A retrospective analysis was conducted on the clinical manifestations，laboratory tests，imaging characteristics，treatment，and prognosis of 10 children with KDSS and MAS admitted to Beijing Children's Hospital，Capital Medical University from January 2021 to June 2024.Results:Among the 10 children，six were male and four were female，and the age of onset was three months to eleven years old. Acute kidney injury was observed in five patients. Laboratory tests revealed significant increases in serum ferritin，C-reactive protein，B-type natriuretic peptide，aspartate aminotransferase，alanine aminotransferase，creatinine，triglycerides，and interferon-γ，while platelet count and albumin were significantly decreased. Six patients had cardiac enlargement，three had reduced ejection fraction，seven had pericardial effusion，and seven had coronary artery damage. All children were treated with immunoglobulin and methylprednisolone pulse therapy，as well as vasoactive drug infusion to improve circulation and maintain blood pressure. All children were discharged after clinical improvement，and most had a good prognosis.Conclusion:Children with KDSS may develop MAS，which present a complex and rapidly progressing condition often accompanied by a significant increase in ferritin levels. Early diagnosis and treatment can lead to a favorable prognosis.

Objective To investigate the association between baseline depression and the risk of type 2 diabetes mellitus(T2DM)in middle-aged and elderly people in Chengguan District of Lanzhou.Methods A total of 4471 residents who were followed up in Chengguan District,Lanzhou City from August 2014 to July 2016 in the 2011 REACTION study were selected as the research subjects.According to the 9-item patient health questionnaire(PHQ-9),they were divided into the non-depression group with a score of 0～4 points(ND,n=3827),the mild depression group with a score of 5～10 points(MD,n=546)and the moderate to severe depression group with a score of≥10 points(MSD,n=98).The general data and biochemical indicators of the three groups were compared.The correlation between depression status and glycolipid metabolism indicators was analyzed.The follow-up results of the three groups with different baseline glucose metabolism status populations were compared.Logistic regression was used to analyze the influencing factors of progression in different glucose metabolism populations.Results The married rate in the ND,MD and MSD groups decreased sequentially(P<0.05),while the rate of living alone and the PHQ-9 score increased(P<0.05).The female population,family history of DM,coronary heart disease,LDL-C and TC in the MD group were higher than those in the ND group(P<0.05),while the age,BMI,WHR,FPG and 2 hPG in the MD group were lower than those in the ND group(P<0.05).The family history of DM in the MSD group was higher than those in the ND group(P<0.05),drinking and LDL-C in the MSD group were higher than those in the MD group(P<0.05),the BMI was lower than that in the ND group(P<0.05).Spearman correlation analysis showed that the baseline PHQ-9 score was negatively correlated with FPG level(r=-0.039,P<0.05),and positively correlated with HDL-C and TC(r=0.049,0.031,P<0.05).There was no significant difference in the incidence of pre-DM and T2DM at the end of follow-up among the three groups with different baseline glucose metabolism(P>0.05).Logistic regression analysis showed that after adjusting for confounding factors,the risk of pre-DM and T2DM in normal glucose tolerance people with different depression status and the risk of T2DM in pre-DM patients were not increased.Conclusions Depressive state may not be the main factor affecting the occurrence of T2DM in middle-aged and elderly people in Chengguan District of Lanzhou.

Lipoatrophic diabetes(LD) is a rare and distinct form of diabetes characterized by notable clinical heterogeneity. It is often considered one of the manifestations of lipodystrophy syndrome(LDS). In clinical practice, LD is frequently misdiagnosed as type 2 diabetes; however, its management protocols and prognostic outcomes differ significantly from those of other diabetes subtypes. Therefore, timely and accurate diagnosis is of great clinical importance. This paper presents two detailed case reports of female patients with LD. Through an in-depth analysis of their clinical features, it also provides an comprehensive review of the key clinical manifestations of LDS, potential pathogenic mechanisms, and current approaches to genetic diagnosis. The aim is to enhance clinicans′ awareness of LDS and improve corresponding diagnostic and therapeutic strategies.