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:To evaluate the efficacy and safety of blinatumomab in adult patients with relapsed/refractory(R/R)or measurable residual disease(MRD)positive B-cell acute lymphoblastic leukemia(B-ALL)in the real world.Methods:The clinical data of 30 B-ALL patients received at least 1 course of blinatumomab therapy in the Chinese PLA General Hospital from January 1st,2021 to December 31st,2023 were retrospectively analyzed,including pre-treatment baseline clinical feature,post-treatment complete response(CR),CR with partial hematologic recovery(CRh),CR with incomplete hematologic recovery(CRi),complete MRD response rate,MRD response rate(MRD＜10-4),overall survival(OS),and disease-free survival(DFS),as well as drug-related adverse reactions.Results:Among 5 patients who were not assessed 4 were MRD negative and 1 did not receive bone marrow biopsy.In the R/R B-ALL group(13 cases),11 patients achieved CR/CRh/CRi and 10 patients achieved complete MRD response.In MRD+group(12 cases),9 patients achieved overall MRD response and 7 patients achieved complete MRD response.The median follow-up time was 8.4(95％CI:6.3-10.4)months.The median OS was 15.5(95％CI:0.7-30.3)months in the R/R group,while not reached in the MRD+group.The median DFS of the two groups were not reached.Drug-related adverse reactions occurred in 22 patients,and pyrexia was the most common(13 cases).Grade ≥3 adverse reactions occurred in 15 patients,and neutropenia was the most common(9 cases).Cytokine release syndrome occurred in 6 patients,including 5 cases with grade 1 and 1 case with grade 3.No patients interrupted therapy or died due to drug-related adverse reactions.Conclusion:Blinatumomab is effective in the treatment of R/R or continuous MRD+B-ALL with acceptable adverse reactions.

This study analyzed the burden and trends in enteric infections in China from 1990 to 2021 from a One Health perspec-tive.Data on mortality associated with enteric infections were extracted from the 2021 Global Burden of Disease(GBD)database.The analysis focused on assessing the mortality rates of enteric infectious diseases attributed to various etiologies and risk factors,along with the age and sex distribution,from 1990 to 2021.Average annual percentage change(AAPC)was used to assess the total changes in disease burden.The age-standardized mortality rate of intestinal infections in China decreased from 9.642/100 000 in 1990 to 0.439/100 000 in 2021,with an AAPC of-57.103%(95%CI:-57.118%to-57.088%).In 2021,Rotavirus,Norovirus,and Crypto-sporidium were the top three etiologies contributing to disease burden,with mortality rates of 1.020/100 000,0.040/100 000 and 0.079/100 000,respectively.A significant variation in etiology distribution was observed across age groups:Rotavirus,Shigella,and Crypto-sporidium dominated among children under 5 years of age,whereas Cryptosporidium,Norovirus,and Clostridioides difficile were more prevalent in older populations.Risk factor analysis indicated that unsafe water sources and poor sanitation accounted for 73.394%of all enteric disease-related deaths.In conclusion,the burden of enteric infections in China markedly declined from 1990 to 2021,and sig-nificant variations in the etiological spectrum and disease burden were observed across age groups.The persistent effects of unsafe wa-ter sources and poor sanitation underscore the need for targeted interventions to further decrease the burden of these diseases.Our find-ings highlight the success of public health interventions in decreasing the burden of enteric infections in China,while emphasizing the need for targeted measures to address disparities in high-risk populations and improve environmental sanitation.

Objective To investigate the differences in demographic characteristics,reproductive health status,and the distribution of pregnancy-related diseases between couples conceived via assisted reproductive technology(ART)and naturally conceived couples,and to analyze the impact of ART treatment on the incidence of preterm birth(PTB)in singleton and twin and multiple pregnancies.Methods We conducted a retrospective analysis of the maternal and infant cohort data of Jing'an District from 2013 to 2020.Based on the conception method,the subjects were categorized into two groups:the ART group and the natural conception group.Chi-square test was applied to compare baseline characteristics and disease distributions differences between the two groups,and logistic regression models were used to evaluate the association between ART and the PTB risks.A causal mediation model was used to evaluate the mediating effect of twin and multiple pregnancy in the relationship between ART and PTB.Results A total of 117 717 parturients were included,6 265 in the ART group and 111 452 in the natural conception group.Compared with the natural conception group,couples in the ART group were significantly older and had a higher prevalence of reproductive system diseases.The incidences of diabetes and hypertensive disorders during pregnancy in ART parturient were 13.76%and 9.99%,respectively,which were significantly higher than 7.88%and 4.75%in the natural conception group(both P<0.001).The overall PTB rate in the ART group was 14.81%,higher than 5.35%in the natural conceptions group(P<0.001).The PTB rate in ART for singleton pregnancies in the ART group was 6.40%,higher than 4.83%in the natural conception group(P<0.001),while the PTB rate in ART for twin and multiple pregnancies in the ART group was 53.97%,lower than 60.42%in the natural conception group(P<0.05).Mediation analysis showed that 97.99%of the effect of ART on PTB was mediated by twin and multiple pregnancy,with ART increasing the PTB risk by 3.44 times through multiple pregnancy.Conclusion The overall PTB rate of ART recipients is higher than that of natural recipients,but ART does not increase the PTB risk in singleton and twin and multiple pregnancies.Twin and multiple pregnancy is the key mediating factor contributing to PTB in ART-conceived recipients.Compared with naturally conceived couples,ART conception couples own more advanced maternal age,and have higher risks of suffering gestational diabetes,gestational hypertension,and PTB.

Objective:To analyze the dynamic changes of serum exosome miR-552 and miR-653 levels in pa-tients with gastric cancer before and after chemotherapy and their relationship with clinical benefit.Methods:IA total of 128 patients with gastric cancer received chemotherapy from January 2022 to January 2024.According to the chemo-therapy effect,the two groups were divided into disease progression group and disease remission group.The levels of serum exosome miR-552 and miR-653 before and after chemotherapy were detected in the two groups,the risk fac-tors affecting the chemotherapy effect of gastric cancer patients were screened,the risk nomogram model was con-structed,and the efficacy was evaluated.Results:The proportion of TNM stage(Ⅲ+Ⅳ),lymph node metastasis,dis-tant metastasis,tumor size(>5 cm),invasion depth(T3/T4)and tumor growth pattern(invasive type)in disease progres-sion group was higher than that in disease remission group(P<0.05).The levels of serum exosomes miR-552 and miR-653 in disease progression group were higher than those in remission group before and after chemotherapy(P<0.05).Compared with before chemotherapy,miR-552 and miR-653 levels in both groups decreased(P<0.05).Logistic regres-sion analysis showed that TNM stage,lymph node metastasis,distant metastasis,tumor size,invasion depth,miR-552 and miR-653 were all risk factors affecting the chemotherapy efficacy of gastric cancer(P<0.05).ROC curve results showed that the AUC,95%CI,sensitivity and specificity of risk nomogram model to predict chemotherapy efficacy of gastric cancer were 0.867,0.672～0.991,92.80%and 80.40%,respectively(P<0.001).Calibration curve results showed that both predicted and actual predicted values were near the ideal curve,and the Hosmer-Lemeshow goodness of fit curve test χ2=1.869,P=0.782.Conclusion:The levels of serum exosomes miR-552 and miR-653 are closely related to the chemotherapy efficacy of gastric cancer,and dynamic monitoring of the above indexes is helpful for the evaluation of the disease and prognosis of gastric cancer.In this study,the risk nomogram model constructed based on the above indexes and other risk factors has high predictive value and clinical practicability for chemotherapy efficacy in patients with gastric cancer.

This study analyzed the epidemiological characteristics of imported malaria in Yunnan Province from 2020 to 2023,to provide scientific evidence for formulating measures to decrease imported malaria and prevent re-establishment of malaria transmission.Malaria data reported by the China Disease Prevention and Control Information System were analyzed to determine parasite species;sources of infection;temporal,spatial,and population distributions;and importation routes.A total of 828 malaria cases were reported in the province.Plasmodium vivax and Plasmodium falciparum accounted for 89.98％and 8.33％of cases,respectively.A total of 47.58％of cases were imported from Myanmar,and all P.falciparum malaria ca-ses were from Africa.Thirteen(81.25％)prefectures or municipalities reported malaria,among which Dehong,Baoshan,Kunming,and Lincang reported 94.32％of cases.A total of 52.54％of cases were in young men.The proportion of cross-bor-der personnel flow,land input,and aircraft input were 88.89％and 11.11％respectively.A total of 98.19％of patients sought medical care within 7 days after fever onset,and 82.85％initiated diagnosis for malaria,and 84.90％of diagnoses were con-firmed by health facilities at or below the county level.Imported malaria is a major challenge in preventing re-establishment of transmission in Yunnan.Most imported cases involved cross-border malaria transmission of mainly Plasmodium vivax between China and Myanmar.To achieve malaria elimination,vigilance of health staff in malaria diagnosis and treatment should be pro-moted,and intensive malaria health education should be provided to people traveling to malaria endemic territories,to enable individual protection,and timely diagnosis and treatment after return from endemic countries.

Objective To investigate the effects of ischemia time and storage periods on RNA quality in fresh-frozen breast cancer(BC)and esophageal cancer(EC)tissue samples in order to establish evidence-based protocols for biobank sample management.Methods The tumor(T)and paired normal(N)tissue samples from 6 cases of BC and 6 cases of EC were collected and cryopreserved in Biobank,Shantou Central Hospital.Mirror paraffin-embedded tissues were simultaneously prepared into sections for morphological analysis.The samples were divided into two groups of<15 min and 15-30 min according to ischemia time,and RNA quality was analyzed at 4 storage periods of 8-10 months(T1),14-16 months(T2),26-28 months(T3)and 38-40 months(T4).Results In 96 analyzed samples,93.8%(90/96)exhibited high quality(RIN≥6),with 89.6%(43/48)in BC and 97.9%(47/48)in EC.Significant differences in RIN were observed between BC group and EC group(8.050 vs.8.600,P=0.009).In EC group,RIN value was significantly negatively correlated with RNA yield(P<0.001).Moreover,RIN values of tumor-normal pairs exhibited markedly significant differences(7.550 vs.9.000,P<0.001).In contrast,no significant difference was detected in BC group(8.200 vs.7.700,P=0.348).Statistical analysis showed that RIN value was positively correlated with 28S/18S(P<0.001),but had no correlation with tumor content(P=0.676)and necrotic content(P=0.055).Neither ischemia time(<15 min vs.15-30 min:8.200 vs.8.300,P=0.932)nor storage periods(T1-T4:8.400,7.700,8.450,8.600,P=0.163)compromised RNA quality.Conclusion Organ origin and tissue type could influence RNA quality of fresh-frozen tissue samples.However,limited ischemia time(≤30 min)and long-term storage period(38-40 months)do not adversely affect RNA quality in fresh-frozen breast cancer and esophageal cancer tissue samples.

This study analyzed the epidemiological characteristics of imported malaria in Yunnan Province from 2020 to 2023,to provide scientific evidence for formulating measures to decrease imported malaria and prevent re-establishment of malaria transmission.Malaria data reported by the China Disease Prevention and Control Information System were analyzed to determine parasite species;sources of infection;temporal,spatial,and population distributions;and importation routes.A total of 828 malaria cases were reported in the province.Plasmodium vivax and Plasmodium falciparum accounted for 89.98％and 8.33％of cases,respectively.A total of 47.58％of cases were imported from Myanmar,and all P.falciparum malaria ca-ses were from Africa.Thirteen(81.25％)prefectures or municipalities reported malaria,among which Dehong,Baoshan,Kunming,and Lincang reported 94.32％of cases.A total of 52.54％of cases were in young men.The proportion of cross-bor-der personnel flow,land input,and aircraft input were 88.89％and 11.11％respectively.A total of 98.19％of patients sought medical care within 7 days after fever onset,and 82.85％initiated diagnosis for malaria,and 84.90％of diagnoses were con-firmed by health facilities at or below the county level.Imported malaria is a major challenge in preventing re-establishment of transmission in Yunnan.Most imported cases involved cross-border malaria transmission of mainly Plasmodium vivax between China and Myanmar.To achieve malaria elimination,vigilance of health staff in malaria diagnosis and treatment should be pro-moted,and intensive malaria health education should be provided to people traveling to malaria endemic territories,to enable individual protection,and timely diagnosis and treatment after return from endemic countries.

This study analyzed the burden and trends in enteric infections in China from 1990 to 2021 from a One Health perspec-tive.Data on mortality associated with enteric infections were extracted from the 2021 Global Burden of Disease(GBD)database.The analysis focused on assessing the mortality rates of enteric infectious diseases attributed to various etiologies and risk factors,along with the age and sex distribution,from 1990 to 2021.Average annual percentage change(AAPC)was used to assess the total changes in disease burden.The age-standardized mortality rate of intestinal infections in China decreased from 9.642/100 000 in 1990 to 0.439/100 000 in 2021,with an AAPC of-57.103%(95%CI:-57.118%to-57.088%).In 2021,Rotavirus,Norovirus,and Crypto-sporidium were the top three etiologies contributing to disease burden,with mortality rates of 1.020/100 000,0.040/100 000 and 0.079/100 000,respectively.A significant variation in etiology distribution was observed across age groups:Rotavirus,Shigella,and Crypto-sporidium dominated among children under 5 years of age,whereas Cryptosporidium,Norovirus,and Clostridioides difficile were more prevalent in older populations.Risk factor analysis indicated that unsafe water sources and poor sanitation accounted for 73.394%of all enteric disease-related deaths.In conclusion,the burden of enteric infections in China markedly declined from 1990 to 2021,and sig-nificant variations in the etiological spectrum and disease burden were observed across age groups.The persistent effects of unsafe wa-ter sources and poor sanitation underscore the need for targeted interventions to further decrease the burden of these diseases.Our find-ings highlight the success of public health interventions in decreasing the burden of enteric infections in China,while emphasizing the need for targeted measures to address disparities in high-risk populations and improve environmental sanitation.

Objective To investigate the effects of ischemia time and storage periods on RNA quality in fresh-frozen breast cancer(BC)and esophageal cancer(EC)tissue samples in order to establish evidence-based protocols for biobank sample management.Methods The tumor(T)and paired normal(N)tissue samples from 6 cases of BC and 6 cases of EC were collected and cryopreserved in Biobank,Shantou Central Hospital.Mirror paraffin-embedded tissues were simultaneously prepared into sections for morphological analysis.The samples were divided into two groups of<15 min and 15-30 min according to ischemia time,and RNA quality was analyzed at 4 storage periods of 8-10 months(T1),14-16 months(T2),26-28 months(T3)and 38-40 months(T4).Results In 96 analyzed samples,93.8%(90/96)exhibited high quality(RIN≥6),with 89.6%(43/48)in BC and 97.9%(47/48)in EC.Significant differences in RIN were observed between BC group and EC group(8.050 vs.8.600,P=0.009).In EC group,RIN value was significantly negatively correlated with RNA yield(P<0.001).Moreover,RIN values of tumor-normal pairs exhibited markedly significant differences(7.550 vs.9.000,P<0.001).In contrast,no significant difference was detected in BC group(8.200 vs.7.700,P=0.348).Statistical analysis showed that RIN value was positively correlated with 28S/18S(P<0.001),but had no correlation with tumor content(P=0.676)and necrotic content(P=0.055).Neither ischemia time(<15 min vs.15-30 min:8.200 vs.8.300,P=0.932)nor storage periods(T1-T4:8.400,7.700,8.450,8.600,P=0.163)compromised RNA quality.Conclusion Organ origin and tissue type could influence RNA quality of fresh-frozen tissue samples.However,limited ischemia time(≤30 min)and long-term storage period(38-40 months)do not adversely affect RNA quality in fresh-frozen breast cancer and esophageal cancer tissue samples.