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.

Background and purpose:According to the latest data from the National Cancer Center,the incidence rate and mortality of lung cancer in China rank first among all malignant tumors,and 85%are non-small cell lung cancer(NSCLC).In recent years,immunotherapy based on programmed cell death protein-1(PD-1)/programmed death ligand-1(PD-L1)immune checkpoint inhibitors(ICIs)has made breakthrough progress in lung cancer,bringing more survival benefits to lung cancer patients.This study aimed to evaluate the cost-effectiveness of three major PD-L1 testing assays in guiding immunotherapy for patients with NSCLC,and to provide empirical evidence to guide the selection of cost-effective diagnosis and ICIs monotherapy regimens for NSCLC patients in China.Methods:From a healthcare system perspective,a decision-tree model was constructed to simulate the cost and effectiveness(percentage of the patients who were successfully diagnosed and who were correctly prescribed and underwent correct treatment according to China treatment guidelines)of employing Ventana PD-L1 IHC(SP263)assay,PD-L1 IHC 22C3 pharmDx,and Dako 22C3 antibody concentrate in early to mid-stage and advanced NSCLC patients in China,respectively.The cost-effectiveness of SP263 assay compared to other testing methods was assessed through the incremental analysis.The robustness of the base case analysis results was validated by using one-way sensitivity analysis and probabilistic sensitivity analysis.Results:When considering atezolizumab monotherapy following chemotherapy for early to mid-stage(Ⅱ A-Ⅲ B)NSCLC patients,in comparison to the 22C3 assay or 22C3 antibody concentrate,the SP263 assay incurred an additional cost of 9 449 yuan per successfully diagnosed and treated patient.The SP263 assay,which can guide multiple ICIs monotherapies(e.g.,atezolizumab,pembrolizumab)for advanced(Ⅳ)NSCLC patients,was dominant by achieving a higher percentage of successfully diagnosed and treated patients at a lower cost compared to Dako 22C3 assay and Dako 22C3 antibody concentrate.One-way sensitivity analysis and probabilistic sensitivity analysis both confirmed the robustness of the results.Conclusion:The Ventana PD-L1 IHC SP263 assay was cost-effective,compared to Dako PD-L1 IHC 22C3 assay and Dako 22C3 antibody concentrate for the immunotherapy treatment for both stage Ⅱ A-Ⅲ B and stage Ⅳ NSCLC patients in China.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.

Objective:To assess the efficacy and safety of “one-stop” procedures combining radiofrequency catheter ablation and left atrial appendage closure by guidance of intracardiac echocardiography(ICE) in elderly patients with atrial fibrillation.Methods:A retrospective cohort study was conducted on patients who underwent ICE-guided “one-stop” procedures at the Department of Cardiology, General Hospital of Northern Theater Command between December 2020 and January 2023. Patients were divided into elderly group (age≥60 years old) and non-elderly group (age 18-59 years old). The clinical characteristics, acute success rate, peri-operative complications and follow-up data between two groups were compared. Multivariate logistic regression analysis was used to analyze whether age was the influencing factor for perioperative complications and atrial fibrillation recurrence.Results:A total of 213 atrial fibrillation patients were enrolled, including 158 (74.18%) in the elderly group (age: (68.3±5.0) years; 56.96% male) and 55 (25.82%) in the non-elderly group (age: (53.7±5.2) years; 81.82% male). The elderly group had lower proportions of males, persistent atrial fibrillation, and left atrial spontaneous echocardiographic contrast compared to the non-elderly group ( P<0.05). CHA 2DS 2-VASc and HAS-BLED scores were higher in elderly group ( P<0.05). The acute success rate,“one-stop” procedure time, fluoroscopy time and the rate of peri-operative complications (6 (3.80%) in elderly group vs. 2 (3.64%) in non-elderly group) were similar between two groups (all P>0.05). The average time of clinical and telephone interviews in elderly group and non-elderly group was (16.9±6.1) months and (17.9±5.9) months, respectively. There was no significant difference in the rate of atrial fibrillation recurrence or clinical events between two groups (47 (30.72%) vs. 14 (26.42%), P=0.554; 10 (6.54%) vs. 2(3.77%), P=0.689, respectively). Iatrogenic atrial septal defects in 3-month transesophageal echocardiography follow up were detected in 44 patients (36.97%) in elderly group and 9 patients (19.57%) in non-elderly group ( P=0.032). Multivariate logistic regression analysis results showed that age was not the influencing factor for peri-operative complications and atrial fibrillation recurrence ( P=0.905 and P=0.676, respectively). Conclusion:Intracardiac echocardiography-guided “one-stop” procedures in the treatment of atrial fibrillation in elderly patients are safe and effective.

Objective:To investigate the efficacy and safety of ablation index-guided radiofrequency catheter ablation (RFCA) and second-generation cryoballoon ablation (CBA) in elderly patients with atrial fibrillation (AF).Methods:This retrospective cohort study included 1 986 patients undergoing pulmonary vein isolation for AF at General Hospital of Northern Theater Command from August 2016 to May 2020, comprising 760 RFCA cases and 1 226 CBA cases. Elderly patients were defined as those aged 60 years or older, while non-elderly patients were those under 60 years of age. All patients were followed up for 3 years after the procedure to assess AF recurrence rates. Kaplan-Meier survival curves were plotted and compared by log-rank test. Multivariate logistic regression was used to analyze the influencing factors of AF recurrence.Results:Among 1 986 AF patients (aged (58.7±10.2) years; 1 307 males, 65.81%; 987 elderly patients, 49.70%), the overall AF recurrence rate was 24.37% (484/1 986). Kaplan-Meier analysis demonstrated a higher AF recurrence rate in the elderly group compared to the non-elderly group (log-rank P=0.007). In the RFCA group, AF recurrence rate was 22.50% (171/760), with no significant difference between the elderly (24.44%, 88/360) and non-elderly (20.75%, 83/400) subgroups ( P=0.223). In the CBA group, recurrence rates were 25.53% (313/1 226), with significantly higher recurrence in elderly patients (28.55%, 179/627) than non-elderly (22.37%, 134/599) ( P=0.013). Multivariate logistic regression analysis revealed that advanced age was not an independent predictor of AF recurrence ( P=0.447). Longer AF duration and larger left atrial diameter were independent risk factors for recurrence, while male sex was a protective factor (all P<0.05). Conclusion:Pulmonary vein isolation with second-generation CBA and RFCA guided by ablation index are safe and effective in the treatment of AF in elderly patients.

Aim To investigate the mechanism of ultra-fine garlic powder(UGP)in ameliorating dyslipidemia and aortic inflammation and fibrosis in atherosclerotic(AS)mice.Methods A 10-week ApoE-/-mouse AS model was constructed,cardiac index was meas-ured,and aortic histopathological changes were ob-served by oil red O staining.Serum inflammatory factor levels were detected by ELISA,and the expression of JNK,NF-κB,ERK and their phosphorylated proteins were detected by Western blot.Results Cardiac in-dex and other indicators as well as aortic lesions were worsened in the AS group,as compared with the normal control group.Compared with the AS group,the UGP treatment group and the traditional garlic grinding pow-der(TGP)treatment group significantly decreased total cholesterol(TC),triglyceride(TG),low-density lipo-protein cholesterol(LDL-C),atherosclerosis index(AI1,AI2),and coronary cardiac index and restored high-density lipoprotein cholesterol(HDL-C)levels,and the area of aortic lesions,inflammation and fibrosis were significantly improved,and at the same time,sig-nificantly inhibited the expression of TNF-α,IL-1β,and IL-6,as well as the expression of p-JNK,p-NF-κB and p-ERK proteins.The therapeutic effect of the UGP group was superior to that of the TGP group.Conclu-sion UGP can significantly inhibit the formation of aortic endothelial AS plaques,reduce the levels of in-flammation and fibrosis,and regulate blood lipids in a-orta of AS mice.

Background and purpose:According to the latest data from the National Cancer Center,the incidence rate and mortality of lung cancer in China rank first among all malignant tumors,and 85%are non-small cell lung cancer(NSCLC).In recent years,immunotherapy based on programmed cell death protein-1(PD-1)/programmed death ligand-1(PD-L1)immune checkpoint inhibitors(ICIs)has made breakthrough progress in lung cancer,bringing more survival benefits to lung cancer patients.This study aimed to evaluate the cost-effectiveness of three major PD-L1 testing assays in guiding immunotherapy for patients with NSCLC,and to provide empirical evidence to guide the selection of cost-effective diagnosis and ICIs monotherapy regimens for NSCLC patients in China.Methods:From a healthcare system perspective,a decision-tree model was constructed to simulate the cost and effectiveness(percentage of the patients who were successfully diagnosed and who were correctly prescribed and underwent correct treatment according to China treatment guidelines)of employing Ventana PD-L1 IHC(SP263)assay,PD-L1 IHC 22C3 pharmDx,and Dako 22C3 antibody concentrate in early to mid-stage and advanced NSCLC patients in China,respectively.The cost-effectiveness of SP263 assay compared to other testing methods was assessed through the incremental analysis.The robustness of the base case analysis results was validated by using one-way sensitivity analysis and probabilistic sensitivity analysis.Results:When considering atezolizumab monotherapy following chemotherapy for early to mid-stage(Ⅱ A-Ⅲ B)NSCLC patients,in comparison to the 22C3 assay or 22C3 antibody concentrate,the SP263 assay incurred an additional cost of 9 449 yuan per successfully diagnosed and treated patient.The SP263 assay,which can guide multiple ICIs monotherapies(e.g.,atezolizumab,pembrolizumab)for advanced(Ⅳ)NSCLC patients,was dominant by achieving a higher percentage of successfully diagnosed and treated patients at a lower cost compared to Dako 22C3 assay and Dako 22C3 antibody concentrate.One-way sensitivity analysis and probabilistic sensitivity analysis both confirmed the robustness of the results.Conclusion:The Ventana PD-L1 IHC SP263 assay was cost-effective,compared to Dako PD-L1 IHC 22C3 assay and Dako 22C3 antibody concentrate for the immunotherapy treatment for both stage Ⅱ A-Ⅲ B and stage Ⅳ NSCLC patients in China.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.