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.

AIM To observe the effects of Yiqi Jiedu Tongluo Formula(YQJDTL)on renal microvascular endothelial function and prevention of renal injury in a rat model of type 2 diabetes mellitus(T2DM).METHODS The SD rats were randomly divided into a normal group and a model group.The model group was administered with high-fat diet combined with a single intraperitoneal injection of STZ to establish the T2DM model.The successfully modeled rats were randomly divided into the model group,the canagliflozin group(9 mg/kg),and the low-dose and high-dose YQJDTL groups(4.77,9.45 g/kg).The corresponding doses of the drug were administered by gavage for a total of 12 weeks,during which the rats underwent observation of their general condition and blood glucose changes.After the end of administration,the rats had their levels of renal index,24-hour UP,serum SCr,BUN,TC,TG,HDL-C,LDL-C,ET-1 and NOS measured;their changes in renal microvasculature and the degree of renal fibrosis observed using HE staining,Masson staining,PAS staining,and PASM staining;their ultrastructure of the glomeruli observed using transmission electron microscopy;their renal protein expressions of TGF-β,SMAD2,SMAD3,Col-1,VEGFA and PKC detected by immunohistochemical staining and Western blot;and their renal mRNA expressions of VEGFA,TGF-β,SMAD2 determined by RT-qPCR.RESULTS Compared with the model group,the high-dose YQJDTL group showed decreased levels of renal index,blood glucose,TG,TC,HDL,24 h UP,BUN,SCr and ET-1(P＜0.05,P＜0.01);increased LDL and NOS levels(P＜0.05,P＜0.01);reduced renal inflammatory infiltration and fibrosis degree,inhibited fusion of foot processes and thickening of basement membrane;decreased renal protein expressions of TGF-β,SMAD2,SMAD3,VEGFA,PKC and Col-1(P＜0.05,P＜0.01);and decreased mRNA expressions of VEGFA,TGF-β and SMAD2(P＜0.01).CONCLUSION In the rat models of T2DM,YQJDTL can reduce their levels of blood glucose and lipids by improving the renal indices levels and the renal microvascular endothelial functions to alleviate renal fibrosis and microangiopathy as well,and the mechanism may be associated with the down-regulated expressions of TGF-β/SMAD and VEGF pathway-related proteins.

Objective The aim of this study was to explore the predictive value of the systemic inflammatory immune nutri-tion score(SIINS)for the prognosis of immunotherapy for advanced gastric cancer.Methods A retrospective analysis was conducted on the clinical data of 202 patients with advanced gastric cancer who received treatment with programmed death-1(PD-1)inhibitors at the Harbin Medical University Cancer Hospital from October 2018 to July 2022.The LASSO regression analysis was used to screen prognostic indicators,construct SIINS indicator,determine the optimal cutoff value for predicting prognosis using subject operating characteristic curves,and divide patients into the high SIINS and low SIINS groups.Independent prognostic factors for overall survival(OS)were determined using univariate and multivariate Cox regression analyses.Results Four indicators,including lymphocyte count,lactate dehydrogenase,and neutrophil lymphocytes,were selected to construct the SIINS index.The prognosis of patients in the high SIINS group was significantly lower than that in the low SIINS group(P<0.05).The results of the multifactorial Cox regression a-nalysis showed that the Eastern Cooperative Oncology Group(ECOG)score,Geriatric Nutritional Risk Index(GNRI),SIINS,treatment regimen,and number of treatment lines(P<0.05)could serve as the independent predictive prognosis of immunotherapy for advanced gastric cancer.Conclusion SIINS can predict the prognosis of patients with advanced gastric cancer treated with PD-1 inhibitors.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Advances in genomics,biochemistry,and genetics have deepened our understanding of epigenetic mechanisms.These mechanisms play a crucial role in life,heredity,and evo-lution.Their growing significance is driving biomedical research toward personalized and precise medicine.Renal diseases,par-ticularly chronic kidney disease and acute kidney injury,require new treatment strategies.Their subtle clinical symptoms and challenges in early diagnosis limit current therapeutic options.Research on epigenetic modifications in renal diseases is expan-ding rapidly.This field is emerging as a promising approach for kidney disease treatment.The transition from basic mechanistic studies to clinical applications is underway.Epigenetic modifica-tions hold great potential for improving early diagnosis,enabling personalized treatment,and advancing precision medicine in re-nal diseases.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Advances in genomics,biochemistry,and genetics have deepened our understanding of epigenetic mechanisms.These mechanisms play a crucial role in life,heredity,and evo-lution.Their growing significance is driving biomedical research toward personalized and precise medicine.Renal diseases,par-ticularly chronic kidney disease and acute kidney injury,require new treatment strategies.Their subtle clinical symptoms and challenges in early diagnosis limit current therapeutic options.Research on epigenetic modifications in renal diseases is expan-ding rapidly.This field is emerging as a promising approach for kidney disease treatment.The transition from basic mechanistic studies to clinical applications is underway.Epigenetic modifica-tions hold great potential for improving early diagnosis,enabling personalized treatment,and advancing precision medicine in re-nal diseases.

Objective:To examine the manifestations and causes of administrative burden among primary healthcare professionals,and to explore its impact on job burnout through the mediating role of role conflict,providing theoretical and empirical support for governance-level burden-reduction strategies.Methods:An exploratory sequential mixed-methods design was employed,focusing on primary healthcare professionals in Shandong Province.In the first phase,in-depth interviews were conducted with 175 participants;in the second phase,a questionnaire survey of 1,096 participants and follow-up interviews with 107 participants were carried out.Results:The proportions of respondents who reported"heavy"or"very heavy"burdens were 62.7%for inspection,54.8%for documentation,51.8%for reporting,and 24.4%for meetings.Structural equation modeling showed that administrative burden had a direct effect on job burnout(0.150)and an indirect effect through role conflict(0.093).Qualitative findings further indicated that administrative burden largely stemmed from public health traceability requirements and medical insurance policies,and operated through both resource-based and value-based conflicts.Conclusions:Primary healthcare professionals face considerable administrative burdens,which may heighten job burnout through role conflict.Governance reforms should optimize inspection and assessment,streamline data reporting,refine record-keeping,and promote collaborative governance to break the chain of institutional pressure leading to burnout.

Objective:This article introduces a novel technique for totally laparoscopic, right thoracic approach, esophagojejunostomy for digestive tract reconstruction.Methods:A retrospective analysis was conducted on the clinical data of patients with adenocarcinoma of the esophagogastric junction who successfully underwent totally laparoscopic esophagojejunostomy via the right thoracic approach at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, between February 2022 and March 2022.The surgical procedure was performed as follows:(1)Following total laparoscopic resection of the gastric tumor and lymph node dissection, the specimen was transected distal to the tumor margin. The specimen was then placed into a retrieval bag and extracted through the umbilical observation port.(2)Dissection was continued through the esophageal hiatus to mobilize the esophagus. The tumor-bearing tissue, along with the esophagus, was delivered into the thoracic cavity via the esophageal hiatus.(3)The jejunum was transected 20 cm distal to the ligament of Treitz. The distal Jejunum was mobilized for 15-20 cm and subsequently delivered into the thoracic cavity through the esophageal hiatus.(4)A Roux-en-Y jejunojejunostomy was constructed 45-50 cm distal to the cut end of the distal jejunal limb; the mesenteric defect was closed, and the duodenal stump was reinforced.(5)The patient was repositioned into the left lateral decubitus position. Port placement was established as follows: the observation port at the 7th intercostal space (ICS) in the right midaxillary line, the main operating port at the 4th ICS in the anterior axillary line, and the assistant operating port at the 9th ICS in the scapular line.(6)The main operating port incision was enlarged. Using a purse-string instrument, the esophagus was clamped and transected at least 5 cm proximal to the upper tumor margin, and the specimen was removed. (7)The distal jejunum was delivered into the thoracic cavity via the esophageal hiatus. Under total laparoscopic visualization, esophagojejunostomy was completed.Results:Both patients who underwent totally laparoscopic esophagojejunostomy via the right thoracic cavity successfully completed the procedure without conversion to laparotomy, unplanned reoperation, or any intraoperative/postoperative complications. The patients recovered well postoperatively, with no evidence of abdominal or thoracic hemorrhage. Postoperative computed tomography (CT) scans of the chest and abdomen confirmed the absence of anastomotic leakage or other related complications.Conclusions:The esophagojejunostomy was performed totally laparoscopically via the right thoracic cavity. This approach overcomes the drawback of significant trauma associated with open surgery while ensuring safe esophageal resection margins and thorough lymph node dissection. This technique offers advantages including minimal invasiveness, accelerated postoperative recovery, and a reduced incidence of reflux esophagitis. To our knowledge, no similar method of digestive tract reconstruction has been reported in the literature. Its novelty and clinical potential may offer new therapeutic options for patients with Siewert type II adenocarcinoma of the esophagogastric junction (AEG).

Objective:To examine the manifestations and causes of administrative burden among primary healthcare professionals,and to explore its impact on job burnout through the mediating role of role conflict,providing theoretical and empirical support for governance-level burden-reduction strategies.Methods:An exploratory sequential mixed-methods design was employed,focusing on primary healthcare professionals in Shandong Province.In the first phase,in-depth interviews were conducted with 175 participants;in the second phase,a questionnaire survey of 1,096 participants and follow-up interviews with 107 participants were carried out.Results:The proportions of respondents who reported"heavy"or"very heavy"burdens were 62.7%for inspection,54.8%for documentation,51.8%for reporting,and 24.4%for meetings.Structural equation modeling showed that administrative burden had a direct effect on job burnout(0.150)and an indirect effect through role conflict(0.093).Qualitative findings further indicated that administrative burden largely stemmed from public health traceability requirements and medical insurance policies,and operated through both resource-based and value-based conflicts.Conclusions:Primary healthcare professionals face considerable administrative burdens,which may heighten job burnout through role conflict.Governance reforms should optimize inspection and assessment,streamline data reporting,refine record-keeping,and promote collaborative governance to break the chain of institutional pressure leading to burnout.