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 aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

ObjectiveColorectal cancer (CRC) is a highly heterogeneous malignancy, and traditional Chinese medicine (TCM) syndrome differentiation is widely used in its clinical management. However, the biological basis underlying different TCM syndromes remains insufficiently understood. This study aimed to investigate the proteomic differences between qi-blood deficiency syndrome (QBDS) and damp-heat syndrome (DHS) in CRC patients and to establish a “syndrome-differential protein-herbal component” network for exploring potential molecular mechanisms and therapeutic targets associated with syndrome-specific treatment strategies. MethodsTumor tissue samples were collected from 10 patients with pathologically confirmed CRC, including 5 patients diagnosed with QBDS and 5 with DHS according to standardized TCM syndrome differentiation criteria. Tandem mass tag (TMT)-based quantitative proteomics was employed to identify differentially expressed proteins (DEPs) between the two syndrome groups. Functional enrichment analyses, including Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, were performed to characterize the biological functions and signaling pathways associated with the identified DEPs. Least absolute shrinkage and selection operator (LASSO) regression analysis was further applied to screen key syndrome-related proteins and construct a core protein prediction model. Subsequently, molecular docking was conducted to evaluate the binding affinities between representative herbal compounds, astragaloside IV and berberine, and the identified core proteins. Finally, cell counting kit-8 (CCK-8) assays were performed in HCT 116 and HT-29 colorectal cancer cell lines to validate the anti-proliferative activities of these compounds in vitro. ResultsA total of 44 DEPs were identified between QBDS and DHS tissues, including 21 upregulated and 23 downregulated proteins in the QBDS group relative to the DHS group. Functional enrichment analyses revealed that these proteins were primarily associated with antiviral immune responses, regulation of inflammatory signaling, NF‑κB signaling pathways, cholesterol metabolism, and other biological processes relevant to tumor progression and host immune regulation. LASSO regression analysis identified eight core proteins with potential syndrome-specific significance. Among them, ST7, GPCPD1, and PODXL were closely associated with QBDS, whereas FAT1, GRB7, KRT7, MAFF, and MMP8 were associated with DHS. Molecular docking demonstrated favorable interactions between astragaloside IV and QBDS-related proteins, with binding energies lower than -5 kcal/mol, indicating stable binding activity. Berberine exhibited even lower binding energies and stronger binding specificity toward DHS-related core proteins. In vitro experiments further confirmed that both compounds inhibited CRC cell proliferation, while berberine displayed significantly greater anti-proliferative efficacy. The lowest 48 h IC₅₀ value of berberine reached 15.21 mg/L in CRC cells, indicating a stronger growth-inhibitory effect than astragaloside IV. ConclusionCRC patients with QBDS and DHS exhibit distinct proteomic characteristics, suggesting that different TCM syndromes possess unique molecular signatures. The identified core proteins may serve as potential biomarkers for syndrome differentiation, while astragaloside IV and berberine may exert therapeutic effects through targeting syndrome-specific molecular networks. These findings provide preliminary proteomic evidence supporting syndrome-guided precision integrative medicine in CRC and offer new insights into the biological basis of TCM syndrome differentiation and individualized therapeutic strategies.

Objective:To analyze transcranial sonography（TCS）imaging characteristics of rats with 6-hydroxydopamine hydrochloride（6-OHDA）and explore the correlations between the imaging characteristics with motor deficits and pathological changes.Methods:Twenty-nine male SD rats were divided into 3 groups：8 in the no-treatment control（NC）group，10 in the Sham group and 11 in the 6-OHDA group. The model for Sham/Parkinson's disease（PD）was established by stereotacticly injecting saline/6-OHDA containing ascorbic acid to bilateral substantia nigra pars compacta（SNpc）. After three weeks，the models were stable. At the fourth week and seventh week，the behavioral testing was accomplished. The TCS examination was performed weekly at the same time for four weeks. At the eighth week，the rats were sacrificed for pathology.Results:①Behavioral testing：6-OHDA group showed asymmetric motor deficits and the difference was significant compared with the NC group and Sham group（both P<0.001）. ②TCS examination：compared with the NC and Sham group，there were asymmetric substantia nigra hyperechogenicity（SNH）in 6-OHDA group（both P<0.05）；meanwhile the area of SNH in the left was significantly larger in the right side（ P<0.05）.No significant change in SNH area was found during the continuous observation period of weeks 4-7. For 6-OHDA group，the area of SNH was negatively correlated with the number of forelimb wall-touches（ r=-0.825， P＜0.001）. ③Pathological examination：compared with NC group and sham group，the substantia nigra（SN）of 6-OHDA group showed a series of pathological events，including dopaminergic（DA）neurons asymmetrically decreasing，asymmetric ironion deposition and the number of active microglia increasing（all P＜0.05）. Correlation analysis showed that the area of SNH was negatively correlated with the number of DA neurons survivors（ r=-0.689， P=0.013），while the activation of microglial and the deposition of iron were positively correlated with the area of SNH（ r=0.915，0.735；all P＜0.001）. Conclusions:Asymmetric SNH of 6-OHDA PD rats is a representation of asymmetric motor deficits，and the mechanism is related to a catalogue of asymmetric pathological changes in SN，which comprise DA neurons decreasing，asymmetric iron ions deposition，microglial activating.

Objective:This study investigates the utility of ultrasound in diagnosing eosinophilic fasciitis (EF).Methods:A retrospective analysis was conducted on the clinical and ultrasound data of 109 EF patients seen at the center between January 1, 2006, and March 31, 2024. The diagnostic efficacy of ultrasound for EF was evaluated by comparing forearm fascia ultrasound findings among EF patients, systemic sclerosis (SSc) patients, and healthy controls (HC).Results:Among the 109 EF patients (male-to-female ratio 2.2︰1), the median age of onset was 36 (29, 48) years, with a median disease duration of 7 (3, 12) months. The study also included 20 SSc patients [median age 49 (35, 61) years] and 20 HC individuals [median age 48 (29, 54) years]. Ultrasound assessments of forearm fascia in EF patients revealed a median fascial thickness of 1.9 (1.4, 2.4) mm. The median fascial thickness was 0.8 (0.7, 0.9) mm in SSc patients and 0.7 (0.5, 0.9) mm in HC individuals. Fascial thickness in EF patients was greater than in SSc ( Z=-11.16, P<0.001) and HC groups ( Z=-11.87, P<0.001). There was a correlation between fascia thickness and C-reactive protein ( r=0.148, P=0.004), erythrocyte sedimentation rate ( r=0.143, P=0.005), and immunoglobulin G ( r=0.120, P=0.020) in EF patients. Receiver operating characteristic (ROC) curve analysis demonstrated a sensitivity of 84.0% and specificity of 95.9% for EF diagnosis, with an area under the curve (AUC) of 0.921 and a cut-off value of 1.005 mm. Conclusion:Ultrasound detection of forearm fascial thickening (>1 mm) aids in diagnosing eosinophilic fasciitis, indicating that ultrasound is a supplementary diagnostic tool for EF.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To investigate the clinical efficacy and safety of venetoclax(VEN)in combination with hypomethylating agent(HMA)in the treatment of patients with high-risk myelodysplastic syndromes(MDS).Methods:A total of 30 patients with high-risk MDS who received the combination of VEN and HMA from March 2019 to November 2022 were included.The overall response rate(ORR),modified overall response rate(mORR),overall survival(OS),progression-free survival(PFS),and adverse events of all included patients were evaluated.Results:Among the 30 high-risk MDS patients treated with VEN combined with HMA regimen,24 cases achieved complete response(CR)/marrow complete response(mCR),2 cases achieved partial response(PR),the ORR was 24/30,the median OS was 28.1 months,and the median PFS was 28.1 months.In addition,patients who achieved complete remission/marrow complete remission after treatment had a significantly longer OS than those who did not.Moreover,12 patients were treated with allogeneic hematopoietic stem cell transplantation(allo-HSCT).There were grade 3 or higher hematologic adverse events including thrombocytopenia(14 cases),neutropenia(14 cases),febrile neutropenia(10 cases)and anemia(7 cases)as well as gastrointestinal adverse events of any grade,such as vomiting(7 cases),diarrhea(5 cases),and constipation(4 cases).Conclusion:VEN in combination with HMA is an effective and safe treatment option in patients with high-risk MDS.This regimen combined with allo-HSCT can improve the prognosis of these patients.Continuous attention to the monitoring and management of adverse events is essential for the patients'safety in this combination therapy.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective:To explore the effectiveness of immersive virtual reality (VR)-guided core stability-assisted training in improving the balance of ischemic stroke survivors.Methods:Sixty-six hemiplegic ischemic stroke survivors were randomly divided into a conventional rehabilitation training group (CON) of 32 and an immersive VR-guided core stability-assisted training group (VR-TOT) of 34. In addition to basic internal medical treatment, the CON group underwent conventional rehabilitation therapy, while the VR-TOT group received VR-guided core stability-assisted training. Before and after 4 weeks of the treatments, the subjects′ balance was evaluated using the Fugl-Meyer balance scale. A three-dimensional force platform was used to collect the sway amplitude, sway speed, peripheral area and total trajectory length of the center of pressure COP of the bilateral plantar in the left-right and anterior-posterior directions while the subjects stood with the eyes open and closed.Results:After the treatments, the average Fugl-Meyer balance scores of both groups had improved significantly. In the eyes-open condition, after the treatment, there was a significant decrease in the average COP sway amplitude in the anteroposterior direction on the hemiplegic side among the CON group, as well as in both the mediolateral and anteroposterior directions on both sides in the VR-TOT group. The sway velocity in the anteroposterior direction on the hemiplegic side had decreased significantly in both groups, and the sway velocity in both the mediolateral and anteroposterior directions on the non-hemiplegic side had also decreased significantly. In the CON group the peripheral area on the non-hemiplegic side had decreased and the total trajectory length had shortened significantly. In the VR-TOT group there were significant decreases in the peripheral area on both sides and in the total trajectory length on both sides. Comparing the two groups after treatment, the peripheral area on the hemiplegic side in the VR-TOT group was significantly smaller. In the eyes-closed condition, the sway amplitude of the COP on the hemiplegic side in the anteroposterior direction and on the non-hemiplegic side in both the mediolateral and anteroposterior directions had decreased significantly in the VR-TOT group after the treatment. The average sway velocity had decreased significantly in the anteroposterior direction on the non-hemiplegic side in the CON group. In the VR-TOT group this was observed in the anteroposterior direction on the hemiplegic side and in both the mediolateral and anteroposterior directions on the healthy side. In the CON group the average peripheral area of the COP on the hemiplegic side had decreased, and the total trajectory length had shortened, both significantly. In the VR-TOT group, the peripheral area on the non-hemiplegic side had decreased significantly as well.Conclusions:Core stability-assisted training based on immersive virtual reality can effectively improve the balance of ischemic stroke survivors. It shows promise for clinical application.

Objective:To analyze the genetic characteristics of hemagglutinin（HA）and neuraminidase（NA）of influenza A（H1N1）pdm09 viruses in Kunming during the 2022-2023 influenza season.Methods:A total of 15 strains of A（H1N1）pdm09 influenza virus isolated from sentinel hospital surveillance and from outbreaks from April 2022 to March 2023 in Kunming were chosen for sequencing. The genetic analysis，which included sequence alignment，homology analysis，construction of phylogenetic tree and amino-acid mutations analysis，was carried out using MAFFT version 7，MegAlign and MEGA 11.Results:Fourteen strains isolated during the 2022-2023 influenza season in Kunming belong to clade 6B.1A.5a.2a，and A/Kunming/284/2023 belonged to clade 6B.1A.5a.2a.1. They all diverged from the northern hemisphere vaccine strain A/Wisconsin/588/2019 in clade 6B.1A.5a.2 recommended by WHO during the 2022-2023 influenza season. Comparing with the HA of the vaccine strain：A186T and Q189E，which might cause the reduction of vaccine protection，were identified in Sb of 14 strains；P137S，K142R in Ca and A186T，Q189E in Sb were identified in A/Kunming/284/2023 and two strains isolated from Thailand. The four mutations at tow antigenic sites identified immune escape at the molecular level. Q189E in the 190-helix and E224A in the 220-loop，which might change the pathogenicity of A（H1N1）pdm09 viruses，were identified in 15 strains. Comparing with NA of the vaccine strain：S200N in 14 strains and S339L in 1 strain were identified in antigenic sites. The two mutations might reduce the protection of antibodies induced by NA.Conclusion:Strengthening influenza surveillance and timely detecting new variants in Kunming contributes to preventing the importation of foreign strains and issuing early warnings for influenza outbreaks.