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.

C-Reactive protein(CRP)is an important acute-phase response protein,which is widely used in the assessment of inflammation and cardiovascular disease risk,and acts as a pathogenic factor directly involved in the disease process of certain conditions.Therefore,developing immunosuppressants targeting CRP or investigating its pathogenic mechanisms is of significant importance.Most B-cell epitopes are conformational epitopes,and studying conformational epitopes is typically challenging.To date,no methods have been reported for mapping the conformational epitopes of CRP in solution.In this study,a rapid strategy was developed for studying conformational epitopes by combining hydrogen/deuterium exchange mass spectrometry(HDX-MS)with multiparametric prediction of B-cell epitopes and protein secondary structure analysis.This approach was successfully applied to the binding sites and allosteric targets of the 115 kDa full pentameric CRP and the clinically used monoclonal antibody(mAb)5A8.The results showed that the amino acid residues 84-103,138-146,and 165-173 together form the potential conformational epitopes for mAb 5A8 on CRP,while the amino acid residues 21-32 and 175-178 were identified as potential allosteric targets.The discovery of the mAb 5A8 binding sites and allosteric targets was crucial for improving clinical diagnostic capabilities.Experimental results demonstrated that this workflow allowed rapid conformational epitope mapping of CRP under near-physiological conditions,with advantages such as high speed,high sensitivity,and high throughput.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

Objective:To investigate the levels of brain natriuretic peptide(BNP),angiotensin Ⅱ(AngⅡ)and Apelin in hypertensive patients with heart failure and their correlation with cardiac function.Methods:A total of 110 pa-tients with hypertension and heart failure(observation group),110 hypertensive patients(hypertension control group)and 100 healthy subjects undergoing physical examination simultaneously(healthy control group)admitted to Chongming Hospital Affiliated to Shanghai University of Medicine & Health Sciences between January 2021 and Oc-tober 2022 were enrolled.BNP,AngⅡ and Apelin levels were compared among above-mentioned groups.Pearson correlation analysis was employed to analyze association of above indexes with cardiac function.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of BNP,AngⅡ and Apelin combination for hy-pertension combined heart failure.Results:Compared with participants in healthy control group and hypertension control group,those in observation group had significant higher BNP,AngⅡ,Apelin and left ventricular end-dias-tolic diameter(LVEDd),and significant lower left ventricular ejection fraction(LVEF)(P＜0.001 all).Pearson correlation analysis showed that BNP,AngⅡ,Apelin were negatively correlated with LVEF(r=-0.607,-0.517,-0.549,P＜0.001 all),while they were positively correlated with LVEDd(r=0.695,0.676,0.677,P＜0.001 all).Compared with patients in class Ⅱ and class Ⅲ groups,those in class Ⅳ group had significant higher BNP[(501.42±65.58)pg/ml vs.(382.59±49.69)pg/ml vs.(409.58±53.58)pg/ml],AngⅡ[(3.24±0.84)ng/ml vs.(0.85±0.24)ng/ml vs.(1.06±0.41)ng/ml],Apelin[(6.53±0.71)pg/ml vs.(3.55±0.29)pg/ml vs.(4.98±0.56)pg/ml](P＜0.001 all).ROC curve indicated that the AUC of the combined diagnosis of BNP,AngⅡ and Apelin for hypertensive patients with heart failure of class Ⅲ～Ⅳ was 0.943(95％CI 0.882～0.978),which was significantly higher than that of single index(Z=2.960,6.099,4.653,P＜0.01 all).Conclusion:BNP,AngⅡ and Apelin combination has good performance in diagnosing hypertension complicated heart failure.

Aim To explore the mechanism of Bushen Tongfu prescription(BSTF)regulating gut microbiota and improving learning and memory ability of Alzhei-mer's disease(AD)model mice.Methods APP/PS1 mice were administered by BSTF for eight weeks.The spatial learning and memory ability of mice were detected by Morris water maze.The changes in the gut microbiota abundance and diversity of mice were detec-ted by 16S rDNA technology.The morphological chan-ges of hippocampus were observed by HE staining.The expression of the activation of microglia in hippocampus was detected by immunofluorescence.The expressions of pro-inflammatory factors of TLR4,NF-κB and IL-6 in brain tissue were detected by Western blot.Results Compared with the model group,the escape latency and swimming path were shortened,the times of target crossings after removing the platform increased in BSTF groups(P＜0.05),the α-diversity increased and the abundance of gut microbiota was regulated,the mor-phological structure and pathological damage of hipp-ocampal cells were improved,the co-expression of iN-OS/Iba1 decreased and the co-expression of Arg1/Iba1 increased significantly(P＜0.01),the transformation of M1 to M2 of microglial cells was promoted,and the expression of TLR4,NF-κB and IL-6 protein decreased significantly.Conclusions BSTF can improve the learning and memory ability of APP/PS1 mice,and its mechanism may be related to regulating the gut micro-biota and the LPS/TLR4/NF-κB pathway,inhibiting the activation of pro-inflammatory microglia,reducing inflammation in hippocampus and improving the patho-logical damage of hippocampal cells.

Objective:To investigate the levels of brain natriuretic peptide(BNP),angiotensin Ⅱ(AngⅡ)and Apelin in hypertensive patients with heart failure and their correlation with cardiac function.Methods:A total of 110 pa-tients with hypertension and heart failure(observation group),110 hypertensive patients(hypertension control group)and 100 healthy subjects undergoing physical examination simultaneously(healthy control group)admitted to Chongming Hospital Affiliated to Shanghai University of Medicine & Health Sciences between January 2021 and Oc-tober 2022 were enrolled.BNP,AngⅡ and Apelin levels were compared among above-mentioned groups.Pearson correlation analysis was employed to analyze association of above indexes with cardiac function.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of BNP,AngⅡ and Apelin combination for hy-pertension combined heart failure.Results:Compared with participants in healthy control group and hypertension control group,those in observation group had significant higher BNP,AngⅡ,Apelin and left ventricular end-dias-tolic diameter(LVEDd),and significant lower left ventricular ejection fraction(LVEF)(P＜0.001 all).Pearson correlation analysis showed that BNP,AngⅡ,Apelin were negatively correlated with LVEF(r=-0.607,-0.517,-0.549,P＜0.001 all),while they were positively correlated with LVEDd(r=0.695,0.676,0.677,P＜0.001 all).Compared with patients in class Ⅱ and class Ⅲ groups,those in class Ⅳ group had significant higher BNP[(501.42±65.58)pg/ml vs.(382.59±49.69)pg/ml vs.(409.58±53.58)pg/ml],AngⅡ[(3.24±0.84)ng/ml vs.(0.85±0.24)ng/ml vs.(1.06±0.41)ng/ml],Apelin[(6.53±0.71)pg/ml vs.(3.55±0.29)pg/ml vs.(4.98±0.56)pg/ml](P＜0.001 all).ROC curve indicated that the AUC of the combined diagnosis of BNP,AngⅡ and Apelin for hypertensive patients with heart failure of class Ⅲ～Ⅳ was 0.943(95％CI 0.882～0.978),which was significantly higher than that of single index(Z=2.960,6.099,4.653,P＜0.01 all).Conclusion:BNP,AngⅡ and Apelin combination has good performance in diagnosing hypertension complicated heart failure.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Aim To explore the mechanism of Bushen Tongfu prescription(BSTF)regulating gut microbiota and improving learning and memory ability of Alzhei-mer's disease(AD)model mice.Methods APP/PS1 mice were administered by BSTF for eight weeks.The spatial learning and memory ability of mice were detected by Morris water maze.The changes in the gut microbiota abundance and diversity of mice were detec-ted by 16S rDNA technology.The morphological chan-ges of hippocampus were observed by HE staining.The expression of the activation of microglia in hippocampus was detected by immunofluorescence.The expressions of pro-inflammatory factors of TLR4,NF-κB and IL-6 in brain tissue were detected by Western blot.Results Compared with the model group,the escape latency and swimming path were shortened,the times of target crossings after removing the platform increased in BSTF groups(P＜0.05),the α-diversity increased and the abundance of gut microbiota was regulated,the mor-phological structure and pathological damage of hipp-ocampal cells were improved,the co-expression of iN-OS/Iba1 decreased and the co-expression of Arg1/Iba1 increased significantly(P＜0.01),the transformation of M1 to M2 of microglial cells was promoted,and the expression of TLR4,NF-κB and IL-6 protein decreased significantly.Conclusions BSTF can improve the learning and memory ability of APP/PS1 mice,and its mechanism may be related to regulating the gut micro-biota and the LPS/TLR4/NF-κB pathway,inhibiting the activation of pro-inflammatory microglia,reducing inflammation in hippocampus and improving the patho-logical damage of hippocampal cells.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.