ObjectiveCerebral ischemic injury triggers a complex pathological cascade characterized by excessive reactive oxygen species (ROS) accumulation, persistent oxidative stress, and sustained neuroinflammation in the injured brain microenvironment. These events collectively drive mitochondrial dysfunction, microglial overactivation, pro-inflammatory cytokine release, and progressive neuronal apoptosis, ultimately leading to severe and irreversible neurological deficits. However, conventional therapeutic strategies face critical limitations, including poor blood-brain barrier penetration, insufficient local drug concentration, uncontrolled drug release, and off-target systemic side effects. To address this pathological process, we rationally designed and fabricated an injectable ROS-responsive hydrogel loaded with polydopamine nanoparticles (PDA NPs) for spatiotemporally controlled antioxidation, anti-inflammation, and neuroprotection in the ischemic injury microenvironment. The present study aimed to systematically characterize the physicochemical properties, ROS-responsive drug release behavior, biocompatibility, and neuroprotective efficacy of this composite hydrogel system in vitro. MethodsPDA NPs were fabricated via oxidative self-polymerization. The ROS-responsive hydrogel was cross-linked using N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1,N1,N3,N3-tetramethylpropane-1, 3-diaminium (TSPBA) and polyvinyl alcohol (PVA). Morphology, particle size, Zeta potential, and structure of PDA NPs were characterized by dynamic light scattering (DLS), Zeta potential analysis, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Microstructure, rheological properties, shear-thinning behavior, and ROS-triggered release profiles of the hydrogel were examined by SEM and rheometry. Biocompatibility was evaluated using HT22 mouse hippocampal neurons with CCK-8 and live/dead staining. An oxygen-glucose deprivation/reoxygenation (OGD/R) model was established to simulate ischemic injury in vitro. ROS levels and neuronal apoptosis were detected by DHE staining and TUNEL assay. Microglial polarization and pro-inflammatory cytokine expression were analyzed using immunofluorescence and RT-qPCR in BV-2 microglia. Transwell co-culture was used to verify the indirect neuroprotection mediated by modulated microglia. ResultsCharacterization results confirmed that the as-prepared PDA NPs were monodispersed spherical nanoparticles with uniform diameter and negative surface potential, demonstrating favorable dispersibility and robust ROS-scavenging activity. The TSPBA-PVA hydrogel exhibited a highly porous interconnected network, suitable mechanical strength, and obvious shear-thinning behavior, supporting its application as an injectable implant. More importantly, the hydrogel displayed typical ROS-responsive degradation and on-demand PDA NP release in a ROS-concentration-dependent manner. In vitro cellular experiments demonstrated that the PDA NP-loaded hydrogel possessed excellent biocompatibility with HT22 cells. In the OGD/R model, the hydrogel significantly reduced intracellular ROS accumulation and markedly suppressed neuronal apoptosis. Furthermore, the composite hydrogel effectively redirected BV-2 microglia from the pro-inflammatory M1 toward the anti-inflammatory M2 phenotypes, downregulated the expression of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6, and reduced inflammatory damage. Transwell co-culture assays further validated that M2-polarized microglia mediated by the hydrogel significantly enhanced the survival of OGD/R-injured HT22 neurons and attenuated apoptosis. ConclusionIn this study, we successfully developed a novel injectable ROS-responsive hydrogel loaded with PDA NPs for synergistic antioxidative and anti-inflammatory neuroprotection. This intelligent hydrogel system enables ROS-triggered on-demand release of PDA NPs, efficiently scavenges excessive ROS, inhibits oxidative stress injury, modulates microglial polarization, and suppresses neuroinflammation, thereby exerting robust neuroprotective effects in vitro. This biomaterial platform provides a promising strategy for the targeted and controlled delivery of bioactive nanomaterials in the central nervous system diseases and establishes a solid experimental foundation for the development of in situ injectable therapies for ischemic brain injury.

Objective This study aimed to investigate the seasonal variation of mosquitoes in Yantai, Shandong Province, and provide a scientific basis for mosquito and mosquito-borne disease control. Methods From March to November for each of the years between 2020 and 2023, adult mosquitoes were collected from different habitats, including parks, hospitals, urban residential areas, rural households and livestock sheds, in 13 counties of Yantai City using a mosquito trap lamp method, among which, female mosquitoes were separated and identified, and the numbers were counted. We used the circular distribution method to analyze the temporal distribution characteristics of mosquito density. Results The γ values obtained for mosquitoes in Yantai from 2020 to 2023, the distribution of mosquitoes in different habitats, and dominant mosquito species in different months showed strong seasonality, with values ranging from 0.7461 to 0.8531(P ＜ 0.05). The peak period of seasonal variation in mosquitoes occurred from June 28thto September 13th, with August 5thbeing identified as the peak day. The peak periods of seasonal variation in mosquitoes in residential areas, parks, hospitals, peasant households, and animals sheds were observed from June 24thto September 14th, June 25thto September 10th, June 22ndto September 12th, July 1stto September 9th, and July 2ndto September 17th, respectively, with corresponding peak days on August 4th,3rd, 2nd, 5th, and 9th, respectively. The peak periods of Culex pipiens pallens, Aedes albopictus, and Anopheles sinensis were from June 26thto September 11th, June 28thto September 17th, and July 12thto September 17th, respectively, with corresponding peak days on August 3rd,7th, and 14th, respectively. Conclusions Our findings in this study revealed that the peak of mosquito activity in Yantai was concentrated in early August, with a peak period extending from June 28thto September 13th, and there were differences between different habitats(with peak periods for rural households and livestock sheds occurring later than those in residential areas, parks, and hospitals). Moreover, with respect to the mosquito species, populations of Cx. pipiens pallens and Ae. albopictus peaked earlier than those of An. sinensis. Based on these findings, we recommend that city-wide mosquito control work should commence in late June, and include appropriate early prevention and control measures for key habitats, such as livestock sheds, and dominant mosquito species, such as Cx. pipiens pallens, to minimize the density of mosquito vectors and the risk of disease transmission.

AIM To investigate the effects of Qifu Yixin Granules on cardiac inflammation in a rat model of heart failure.METHODS The rats were induced into chronic heart failure(CHF)models by 6-week intraperitoneal injection of doxorubicin followed by the random assignment of the successful rat models into the model group,the captopril group(22.5 mg/kg),and the low-dose,medium-dose,and high-dose Qifu Yixin Granules groups(2.84,5.67,11.34 g/kg),in contrast to the normal rats of the blank group.The rats had their body weight monitored;their cardiac function assessed by echocardiography;their serum levels of NT-proBNP,TNF-α,IL-6,IL-1 and CRP measured by ELISA;their cardiac morphological alterations observed by HE and Masson staining;their cardiac protein expressions of TLR4,MyD88 and NF-κB detected by immunohistochemistry and Western blot;and their cardiac mRNA expressions of TLR4,MyD88 and NF-κB measured by RT-qPCR.RESULTS Compared to the blank group,the model group exhibited significantly reduced body weight,LVEF and LVFS(P＜0.01),alongside significantly elevated LVEDD,LVESD,and serum concentrations of NT-proBNP,TNF-α,IL-6,IL-1 and CRP(P＜0.01).Additionally,the model group displayed greater myocardial inflammatory cell aggregation,increased collagen deposition(P＜0.01);and upregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P＜0.01).Compared to the model group,the groups intervened with captopril or medium/high dose Qifu Yixin Granules demonstrated significantly increased body weight,LVEF and LVFS(P＜0.05,P＜0.01);significantly reduced LVEDD,LVESD,and serum levels of the aforementioned indicators(P＜0.05,P＜0.01);mitigated inflammation and collagen deposition(P＜0.05,P＜0.01);and downregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P＜0.05,P＜0.01).CONCLUSION Qifu Yixin Granules attenuate cardiac inflammation and improve cardiac function in doxorubicin-induced CHF rats;this therapeutic effect is mediated by inhibiting the activation of the TLR4/MyD88/NF-κB signaling pathway.

Objective:To evaluate the association between hypertension duration and risk for chronic kidney disease in residents in China.Methods:Participants aged 18-74 years from the sixth round of China Chronic Disease and Risk Factor Surveillance in 2018 were included. The age/date at hypertension diagnosis was reported by them, and hypertension duration was calculated based on the age at diagnosis and the age at survey. The hypertension duration was calculated as 0 year (i.e., normotensive participants), 0.1- year, 5.0- years, 10.0- years, and ≥15.0 years. Serum creatinine, urinary albumin, and urinary creatinine levels were measured, and chronic kidney disease was diagnosed when glomerular filtration rate was <60 ml·min -1·(1.73 m 2) -1 and/or urine albumin-to-creatinine ratio was ≥30 mg/g. Multivariable logistic regression analysis, which took intra-group correlation into account, was used to evaluate the association of hypertension duration with chronic kidney disease. Results:A total of 140 662 residents were finally included in the analysis. After adjusting the confounders, including blood pressure, the odds ratio of chronic kidney disease was 1.16 (95% CI: 1.09-1.23), 1.33 (95% CI: 1.20-1.48), 1.33 (95% CI: 1.18-1.49), and 1.43 (95% CI: 1.29-1.60) in study subjects with hypertension durations of 0.1-4.9 years, 5.0-9.9 years, 10.0-14.9 years, and ≥15.0 years, respectively, in comparison with normotensive people. This result was further supported by the positive association between hypertension duration and chronic kidney disease in people with previously diagnosed hypertension. The results of restricted cubic spline suggested that the risk for chronic kidney disease showed a steep increase within 0.1- 4.9 years after hypertension diagnosis, then showed neither increase nor decrease. The above association seemed to be stronger in those with hypertension diagnosed age <45 years. Compared with those with hypertension duration of 0.1-4.9 years, the odds ratio was 1.38 (95% CI: 1.04-1.84), 1.22 (95% CI: 0.91-1.65), and 1.47 (95% CI: 1.04-2.07) in those with hypertension durations of 5.0-9.9 years, 10.0-14.9 years, and ≥15.0 year, respectively. In those with hypertension diagnosis at ≥45 years, the corresponding odds ratio was 1.08 (95% CI: 0.98-1.19), 1.08 (95% CI: 0.97-1.21), and 1.16 (95% CI: 1.02-1.32), respectively. Conclusions:Hypertension duration is positively associated with the risk for chronic kidney disease in residents in China, and this association is independent of blood pressure level. Early diagnosis of hypertension and long-term control of blood pressure are effective strategies for secondary prevention of hypertension-related chronic kidney disease.

Objective:To understand the prevalence of chronic kidney disease (CKD) and influencing factors in adults with hypertension in China and provide evidence for the management of CKD in hypertension patients.Methods:The prevalence data of CKD in hypertension patients in China were collected from China Chronic Disease and Risk Factor Surveillance in 2018, the data of 68 829 hypertension patients were analyzed. After complex weighting, the prevalence of CKD in the study population was compared. A multivariate logistic regression model was used to explore the influencing factors of CKD in adults with hypertension.Results:The prevalence of CKD in the hypertension patients was 18.2% (95% CI: 17.4%-19.0%) and increased with age, and the prevalence was 16.4% in men and 20.6% in women ( P<0.001). In different age groups, CKD at stage G1 mainly occurred in those aged 18-44 and 45-59 years, with the prevalence of 10.8% and 7.8%, respectively, while CKD at stages G2 and G3a mainly occurred in those aged >60 years, with the prevalence of 9.4% and 9.7%. Multivariate logistic regression results showed that in the hypertension patients, being aged ≥60 years, being women, smoking (including current and ever smoking), physical inactivity, being underweight or obese, and suffering from diabetes, dyslipidemia and hyperuricemia were the potential risk factors for CKD (all P<0.05). Conclusion:The prevalence of CKD was higher in people with hypertension than in general population in China, and age, gender, smoking status, physical activity level, and suffering from diabetes, dyslipidemia, and hyperuricemia or not were significant influencing factors. It is necessary to strengthen health education and kidney function testing in adults with hypertension and develop comprehensive CKD prevention and control measures targeting high-risk population.

Objective:To investigate the trends in insulin resistance, as represented by the triglyceride-glucose index (TyG index), among Chinese adult residents from 2010 to 2018 and to explore influencing factors.Methods:China Chronic Disease and Risk Factor Surveillance was conducted in 2010, 2013, and 2018, using a multi-stage stratified cluster random sampling method across all 31 provinces (autonomous regions and municipalities) in China. This study sampled 98 712 adults in 2010, 176 534 adults in 2013, and 184 876 adults in 2018, all aged ≥18 years, totaling 406 933 participants. Individuals with a TyG index > P75 were classified as having insulin resistance. The mean TyG index and the prevalence of insulin resistance were calculated for different years, sexes, age groups, provinces (autonomous regions and municipalities), and subgroups for 2018. Linear and logistic regression models were used to test trends in means and rates over time, and multivariate logistic regression models were conducted to analyze potential factors associated with insulin resistance. All analyses were adjusted for complex sampling weights based on the study design. Results:From 2010 to 2018, the mean TyG index among Chinese adults increased from 8.44±0.63 to 8.70±0.64, with significant upward trends observed across different age groups, sexes, and urban-rural residencies (all P<0.001). The mean TyG index was higher among males, urban residents, and those aged 45-59. There were significant differences in the mean TyG indices and prevalence of insulin resistance across provinces (autonomous regions and municipalities) (all P<0.05). Higher insulin resistance prevalence was independently associated with being male, aged ≥45 years, living in urban areas, excessive alcohol consumption, and insufficient physical activity (all P<0.05). Conclusions:From 2010 to 2018, the level of insulin resistance, as indicated by the TyG index, showed an increasing trend among Chinese adults. Males, individuals aged ≥45 years, urban residents, and individuals with unhealthy lifestyles such as excessive alcohol consumption or insufficient physical activity should be the focus of efforts to prevent and control metabolic diseases related to insulin resistance.

Objective To investigate the role of the neutrophil-to-lymphocyte ratio(NLR)in predicting the in-hospital mortality risk of patients with acute aortic dissection(AAD)in multicenter hospitals.Methods A multicenter retrospective cohort study was conducted.Clinical data were collected from 2642 AAD patients who were hospitalized in five teaching hospitals:Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology,Henan Provincial People's Hospital,Fuwai Central China Cardiovascular Hospital,the Third Affiliated Hospital of Xinxiang Medical University,and the Second Affiliated Hospital of Chongqing Medical University between August 2010 and December 2021.According to the quartiles of serum NLRlevels,the patients were divided into four groups:first quartile(Q1,n=660),second quartile(Q2,n=661),third quartile(Q3,n=661),and fourth quartile(Q4,n=660).The clinical characteristics and biochemical indicators of each group were compared.Partial correlation analysis was used to assess the relationship between NLR and cardiovascular parameters.Restricted cubic splines,Kaplan-Meier survival analysis,and Cox regression models were employed to evaluate the association between NLR levels and in-hospital mortality risk in AAD patients.Results The median age of all patients was 54[interquartile range(IQR):46-63]years,including 2096 males and 546 females.Compared with Q1-Q3 groups,patients inQ4group had a lower incidence of smoking history and diabetes history,and were more likely to have DeBakey type Ⅰ AAD(P＜0.05).Additionally,the levels of aspartate aminotransferase,high-density lipoprotein cholesterol,creatinine,and D-dimer in Q4 group were higher,while the levels of triglycerides and C-reactive protein(CRP)were lower(P＜0.01).The results of partial correlation analysis showed that the plasma NLR level was positively correlated with D-dimer(r=0.43,P＜0.01)and creatinine(r=0.16,P＜0.01).The restricted cubic spline function in the Cox model revealed a significant non-linear relationship between the plasma NLR level and clinical outcomes in AAD patients(P＜0.01).Kaplan-Meier survival analysis indicated that patients in Q4 group had the highest in-hospital mortality rate compared with Q1-Q3 groups(P＜0.0001).Furthermore,multivariate Cox regression analysis demonstrated that compared with Q1 group,the hazard ratio(HR)of NLR in Q4 group was 1.77(95％CI 1.33-2.37,P＜0.001),which was an independent risk factor for the primary endpoint events.Conclusion A higher plasma NLR level is significantly associated with the occurrence of cardiovascular events in AAD patients,and this association remains significant even after adjusting for potential confounding factors such as the multicenter visiting hospitals.

Objective This research was performed to identify rodent-borne pathogens in Hekou Port,Yunnan Province.Methods Rodents were captured using cages and dissected to collect their lungs,liver,spleen,and other viscera.Eight pathogens,including Yersinia pestis,Leptospira,Bartonella,and Anaplasmataceae,were identified using polymerase chain reaction amplification.Amplified pathogen sequences from positive samples were sequenced,and BLAST homology searches were conducted using GenBank to confirm pathogen identities.A phylogenetic tree of the identified pathogens was constructed using the neighbor joining method.Results The total of 31 rodents,identified as Rattus tanezumi,R.norvegicus,and Mus musculus,were captured.Among these,R.tanezumi was the dominant species,accounting for 64.52％of the total.Two pathogens,Leptospira interrogans and Neoehrlichia mikurensis,were detected,with positivity rates of 9.68％and 29.03％,respectively.No other pathogens were detected.The overall positivity rate for rodent-borne pathogens was 35.48％.Conclusions The single 16S rRNA gene fragment is insufficient for the molecular identification of all Neoehrlichia species.Accurate species identification should be based on a combined analysis of multiple genes.The prevalence of rodent-borne pathogens in Hekou Port indicates the necessity for enhanced surveillance of rodent-borne diseases and implementation of additional prevention and control measures in border ports.

Objective:To explore the association between pre-diabetes and glomerular hyperfiltration status in residents in China.Methods:The study subjects were the non-diabetes population in China Chronic Disease and Risk Factor Surveillance in 2018. According to the definition of prediabetes, the study subjects were divided into normoglycemic and pre-diabetes groups, and multivariate factorial logistic regression model was used to analyze the association between prediabetes and the risk for glomerular hyperfiltration and glomerular filtration rate decline, respectively. Restricted cubic spline was used to explore the dose-response relationship between different glycemic indexes and the risk for glomerular hyperfiltration.Results:A total of 129 735 eligible study subjects aged 18 to 74 years were included, including 45 336 persons with prediabetes. After adjusting for confounders, the OR for glomerular hyperfiltration in the prediabetes group was 1.26 (95% CI: 1.20-1.32) compared with the normoglycemic group, and prediabetes was not associated with decreased glomerular filtration rate ( OR=1.03, 95% CI: 0.96-1.12). Age-stratified results showed a 28% increase of risk for glomerular hyperfiltration in prediabetes group compared with normoglycemic group in those aged 18-59 year ( OR=1.28, 95% CI: 1.21-1.35), and a 15% increase of risk in old adults aged 60-74 years ( OR=1.15, 95% CI: 1.05-1.25); the risk for glomerular hyperfiltration in women with prediabetes ( OR=1.38, 95% CI: 1.29-1.47) was higher than that in men with prediabetes ( OR=1.14, 95% CI: 1.06-1.22); and the risk for prediabetes glomerular hyperfiltration was higher in those with insufficient physical activity ( OR=1.29, 95% CI: 1.22-1.36) than in those who were physically active ( OR=1.16, 95% CI: 1.04-1.29). Restricted cubic spline results showed that fasting plasma glucose, glycosylated hemoglobin and glomerular hyperfiltration risk all showed U-shaped associations, and 2 hours blood glucose glomerular hyperfiltration risk after taking sugar showed an approximate J-shaped association. Conclusions:The risk for glomerular hyperfiltration exists in the prediabetes population, and prediabetes is not associated with the decrease in glomerular filtration rate. Hyperglycemia control at an early and reversible stage is important to prevent glomerular hyperfiltration developing to hypofiltration and renal impairment.

To achieve rapid and visual detection of Plasmodium vivax,a detection method based on recombinase polymerase amplification(RPA)technology and lateral flow dipstick(LFD)was established and evaluated.Targeting the conserved sequence of the P.vivax 18S rRNA gene(GenBank:DQ660817.1)as the target sequence,primers and probes were designed with Primer Premier 5,and the P.vivax recombinant plasmid(pUCPv)was constructed as the standard.A sensitive and specific RPA-LFD-based rapid visual detection method for P.vivax nucleic acids was established.The plasmid standard was serially diluted 10-fold to concentrations of 1×103,1×102,1×101,1×10?,and 1×10?1 copies/μL for sensitivity testing.To evaluate specificity,whole blood DNA samples from patients infected with Plasmodium falciparum,Plasmodium malariae,Plasmodium ovale,or Leishmania donovani,as well as healthy participants,were tested by RPA-LFD.Additionally,The assay′s accuracy was evaluated by testing whole blood DNA samples from 24 confirmed P.vivax-infected patients.This study successfully established a sensitive,specific,and rapid visual RPA-LFD method for detecting P.vivax nucleic acids.The assay can complete P.vivax detection within 20 minutes under isothermal conditions at 39 ℃,achieving a sensitivity of 1 copy/μL.There is no significant cross reaction with parasites such as other Plasmodium species and L.donovani,and the specificity is 100%.All 24 DNA samples from confirmed P.vivax patients were detected,showing a 100%detection rate.The developed RPA-LFD assay exhibits excellent sensitivity and specificity,requires only simple heating equipment,and is user-friendly.This rapid visual detection method is particularly suitable for P.vivax screening in low-resource settings.