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.

This study assessed the role and mechanism of the recombinant Bacillus Calmette-Gue?rin vaccine(rBCG)with c-di-AMP adjuvant in regulating metabolism and immunity in epididymal white adipose(eWAT)in mice.Male C57BL/6 mice were intravenously immunized with BCG and rBCG,and their body weights were monitored.eWAT was isolated from the mice,and the stromal vascular fractions(SVFs)cell number was counted with a hemocytometer.Sections of mouse adipose tissue were prepared,and the size,number,and morphology of eWAT adipocytes and crown-like structure(CLS)formation were compared under a microscope after HE staining.The transcription levels of lipid metabolism-associated factors,cytokines and aging-associated genes in each group were determined with qRT-PCR.The body weights of mice gradually increased after immunization with BCG and rBCG.The proportions of eWAT increased,and the SVFs cell number decreased,in rBCG immunized mice.HE staining indicated that BCG immunization promoted hyperplasia,whereas rBCG immunization promoted hypertrophy of eWAT adipocytes;moreover,both BCG and rBCG immunization induced CLS formation in eWAT.The qRT-PCR results indicated that rBCG immunization inhibited the expression of genes associated with lipolysis and energy expenditure in eWAT.BCG immunization had little effect on cytokine transcription,whereas rBCG significantly induced the transcription of IFN-γ and IL-1Ra,and inhibited that of IL-15 and IL-2,but did not induce the expression of aging-associated genes.Thus,rBCG immunization induced eWAT adipocyte hypertrophy,which was associated with the inhibition of eWAT lipolysis and the regulation of cytokine expression.

Objective:To investigate the preferences and influencing factors of Traditional Chinese Medicine(TCM)health management services among community healthcare workers,providing a reference for promoting and spreading TCM health management services in communities.Methods:Based on a discrete choice experiment,a questionnaire survey was conducted among 596 community healthcare workers across 9 administrative districts in Beijing.A mixed logit model was used to analyze their preferences.Results:Changes in post-tax monthly income,expected efficacy,single-service duration,technical difficulty,patient compliance,and insurance coverage significantly influenced community doctors'service preferences.Changes in post-tax monthly income had the highest relative importance(35.11%),followed by insurance coverage(34.87%).Preferences varied among healthcare workers with different professional titles,backgrounds,weekly working hours,and whether the service was included in performance evaluations.Conclusion:Both economic and non-economic factors influence community healthcare workers'service preferences to varying degrees.Optimizing the combination of TCM health management service attributes can enhance community healthcare workers'willingness to provide such services.It is recommended to use a combination of economic and non-economic incentive measures and develop differentiated strategies for healthcare workers with different characteristics to meet their service preferences and promote the development of TCM health management services in communities.

Objective:To investigate the preferences and influencing factors of Traditional Chinese Medicine(TCM)health management services among community healthcare workers,providing a reference for promoting and spreading TCM health management services in communities.Methods:Based on a discrete choice experiment,a questionnaire survey was conducted among 596 community healthcare workers across 9 administrative districts in Beijing.A mixed logit model was used to analyze their preferences.Results:Changes in post-tax monthly income,expected efficacy,single-service duration,technical difficulty,patient compliance,and insurance coverage significantly influenced community doctors'service preferences.Changes in post-tax monthly income had the highest relative importance(35.11%),followed by insurance coverage(34.87%).Preferences varied among healthcare workers with different professional titles,backgrounds,weekly working hours,and whether the service was included in performance evaluations.Conclusion:Both economic and non-economic factors influence community healthcare workers'service preferences to varying degrees.Optimizing the combination of TCM health management service attributes can enhance community healthcare workers'willingness to provide such services.It is recommended to use a combination of economic and non-economic incentive measures and develop differentiated strategies for healthcare workers with different characteristics to meet their service preferences and promote the development of TCM health management services in communities.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Aim To investigate the effects of m6A demethylase ALKBH5 on cardiomyocytes pyroptosis in mice with myocardial infarction(MI).Methods The MI model of left anterior descending coronary artery ligation surgery was established by knocking down ALKBH5 using adeno-associated virus,and the hypox-ia model of mouse cardiomyocytes(HL-1)was estab-lished by knocking down small interfering RNA.The effects of ALKBH5 on the pyroptosis of MI mice and hypoxic HL-1 cells were observed.Subsequently,mechanism studies were conducted at the cellular lev-el,and the binding of ALKBH5 and IGF2BP2 to NL-RP3 mRNA was detected through RNA pull down and RNA immunoprecipitation(RIP)experiments.The MeRIP-qPCR method was used to determine the effects of ALKBH5 on the mRNA m6A level of NLRP3.Acti-nomycin D for RNA stability experiments were conduc-ted to detect the effects of ALKBH5 and IGF2BP2 on the stability of NLRP3 mRNA.Results Knocking down ALKBH5 in vivo and in vitro both inhibited NL-RP3 inflammasome activation and alleviated pyroptosis in MI mice and hypoxic HL-1 cells.Mechanistically,the results showed that NLRP3 mRNA could bind to ALKBH5 protein in HL-1 cells;knocking down ALK-BH5 could increase the m6A level of NLRP3 and re-duce the stability of NLRP3 mRNA;subsequently,it was confirmed that NLRP3 mRNA and IGF2BP2 pro-tein bound to each other;knocking down IGF2BP2 in-creased the mRNA stability of NLRP3.The Rescue ex-periment showed that knocking down IGF2BP2 re-versed the decrease in NLRP3 mRNA expression caused by knocking down ALKBH5.Conclusions ALKBH5 mediated m6A modification of NLRP3 pro-motes cardiomyocytes pyroptosis in mice with myocardi-al infarction.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective To investigate the effect of cordyceps sinensis(CS)on the activation of fibroblasts through IL-6 trans-signaling pathway and its specific mechanism in the treatment of renal fibrosis.Methods Renal fibrosis mouse model was established by unilateral ischemia/reperfusion(UIR),and the mice were administered intragastrically CS,soluble glycoprotein 130 Fc(sgp130Fc)or Hyper-IL-6.Masson's trichrome staining was utilized to identify tubulointerstitial fibrosis.PAS staining was utilized to assess the extent of renal injury.Western blot was employed to analyze the expression levels of fibrosis markers[alpha-smooth muscle actin(α-SMA),fibronectin(FN)]and proteins associated with IL-6 trans-signaling pathway[phosphorylated signal transducer and activator of transcription 3(p-STAT3),soluble interleukin-6 receptor(sIL-6R)].The expression and localization of proteins were additionally detected by immunohistochemistry,immunofluorescence and qPCR.The effect of cordyceps sinensis extract cordycepin on IL-6 trans-signaling in fibroblasts was further investigated in vitro.Results The results from in vivo experiments showed that administration of CS during the chronic phase demonstrated a beneficial protective impact on inflammation and fibrosis in the affected kidney,and serum creatinine levels and collagen deposition were decreased.Western blot analysis revealed a decrease in the expression levels of α-SMA,FN,as well as IL-6 trans-signaling pathway protein p-STAT3,sIL-6R in the treatment group.Additionally,the mRNA expression levels of chemokines monocyte chemoattractant protein-1(MCP-1)and C-X-C motif chemokine ligand 12(CXCL12)were also decreased in the CS treatment group.Additionally,Hyper-IL-6 can partially counteract the therapeutic effects of CS.In vitro experiments further demonstrated that cordycepin inhibited the secretion of IL-6 from NRK-52E.Combined treatment of recombinant IL-6 and sIL-6R protein activated NRK-49F,leading to a significant increase in α-SMA,FN,and p-STAT3 expression levels.Cordycepin or sgp130Fc treatment significantly inhibited the proliferation of fibroblasts induced by IL-6 trans-signaling pathway.Conclusion CS can significantly reduce IL-6 secretion by renal tubular epithelial cells and inhibit the activation of IL-6 trans-signaling pathway in fibroblasts,thereby ameliorating renal interstitial fibrosis.

Objective To explore the value of 3D and 2D radiomics features models based on multiparameter MRI in predicting Ki-67 expression(with 14%and 20%as the critical values,respectively)in breast cancer.Methods The MRI images of 147 patients with pathologically confirmed Luminal breast cancer were analyzed retrospectively.The patients were randomly divided into training set and test set according to the ratio of 7︰3.The 3D and 2D radiomics features of intratumor and peritumor were extracted from diffusion weighted imaging(DWI),dynamic contrast enhancement(DCE)mask(S0)and DCE phase 3(S3)images.Then the models were constructed by multiple pipeline combinations of three feature normalization methods,two feature dimensionality reduction methods,four feature selection methods,and ten classifiers.The receiver operating characteristic(ROC)curve and the area under the curve(AUC)were used to evaluate the prediction performance of the models in order to select the best 3D and 2D single parame-ter(DWI,S0,S3)and multiparameter combination(S0+S3,S0+DWI,S3+DWI,S0+S3+DWI)models.Finally,the differ-ences between the models were compared by De Long test.Results With 14%as the critical value,the AUC of 3D and 2D models in the training set were 0.726-0.824 and 0.707-0.835,respectively,and those in the test set were 0.724-0.82 and 0.701-0.805.With 20%as the critical value,the AUC of 3D and 2D models in the training set were 0.743-0.868 and 0.793-0.881,respectively,and those in the test set were 0.738-0.853 and 0.743-0.814.There was no significant statistical difference between 3D and 2D models with the same parameter in the two critical values standards.Conclusion The multiparameter MRI-based radiomics models can bet-ter predict the expression of Ki-67 in breast cancer,and the models based on intratumor and peritumor 3D and 2D features have the same prediction efficiency.

A 52-year-old male patient with recurrent Hodgkin′s lymphoma was treated with a combination therapy of gemcitabine, oxaliplatin, and sintilimab for 6 cycles, and sintilimab monotherapy for 15 cycles. Because of disease progression, the therapy was switched to decitabine (10 mg intravenous infusion on day 1-5) and penpulimab (200 mg intravenous infusion on day 8), with 21 days as one cycle. On the 5th day after the last administration of the 10th cycle, the patient experienced discomfort such as headache and poor appetite; on the 7th day, he suddenly developed unconscious and faint. The patient had a body temperature of 38.1 ℃ and mild yellowish skin and mucous membranes throughout the body. Laboratory tests showed platelet count 9×10 9/L, red blood cell count 4.1×10 12/L, hemoglobin 113 g/L, prothrombin time 15.6 s, blood creatinine 101.6 μmol/L, total bilirubin 61.1 μmol/L, and creatine kinase isoenzyme 43 U/L. Based on laboratory and imaging examinations, immune checkpoint inhibitors causing acquired thrombotic thrombocytopenic purpura was considered. The patient underwent 3 times of plasma exchanges, and received intravenous infusion of methylprednisolone 80 mg once daily and other symptomatic treatments for 5 days. The patient′s yellowish skin and mucous membranes throughout the body disappeared. The glucocorticoid was decreased gradually. Two months later, the patient′s laboratory test indicators such as platelet count and total bilirubin returned to normal.