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 investigate the epidemiological characteristics and risk factors of non-alcoholic fatty liver disease in Jincheng between 2015 and 2020. Methods Clinical data of 8,578 medical check-ups at Physical Examination Center of ou hospital from January 2015 to December 2020 were retrospectively selected. The prevalence of non-alcoholic fatty liver disease in the last 5 years was recorded, and Logistic regression was utilized to identify the risk factors for the development of non-alcoholic fatty liver disease. Results The overall prevalence of non-alcoholic fatty liver disease in Jincheng was 14.57% in 2015-2020. The prevalence of non-alcoholic fatty liver disease was higher in men than in women (16.99% vs 10.98%) and highest in the 40-59 age group (18.76%). No statistical difference was reported in blood urea nitrogen (BUN) and serum creatinine (Scr) between groups (P>0.05), while statistical difference was found in diabetes, hypertension, body mass index (BMI), waist circumference, weekly exercise frequency, daily vegetable intake, triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT) and uric acid (UA) between two groups (P<0.05). Multivariate Logistic regression analysis denoted that BMI (OR=2.794, 95% CI: 1.745-4.550), waist circumference (OR=2.586, 95% CI: 1.585-4.299), diabetes (OR=0.644, 95% CI: 1.425-2.781), hypertension (OR=1.479, 95% CI: 1.121-2.290), weekly exercise ≥6h (OR=0.617, 95% CI: 0.519-0.709), daily vegetable intake ≥300g (OR=0.590, 95% CI: 0.467-0.652), TG (OR=1.481, 95% CI: 1.122-1.996), TC (OR=1.562, 95% CI:1.143-2.135), LDL-C (OR=1.440, 95% CI: 1.139-2.048), HDL-C (OR=0.656 , 95% CI: 0.587-0.783) , ALT (OR=1.591, 95% CI: 1.056-2.183), and UA (OR=1.412, 95% CI: 1.009-1.887) were risk factors for non-alcoholic fatty liver disease (P<0.05) . Conclusion The prevalence of non-alcoholic fatty liver disease in Jincheng City from 2015 to 2020 is 14.57%, the prevalence of males is higher than that of females, and the prevalence rate is the highest in the 40-59 age group. Moreover , diabetes mellitus , hypertension , BMI , waist circumference , weekly exercise , daily vegetable intake , serum TG, TC, LDL-C, HDL-C, ALT, and UA are all associated with the risk of the disease.

Objective To investigate the clinical feasibility and safety of endoscopic ultrasonography(EUS)combined with modified endoscopic mucosal resection(EMR)in the treatment of rectal neuroendo-crine tumors(RNETs).Methods A total of 48 patients diagnosed with RNETs by colonoscopy in the depart-ment of gastroenterology in this hospital from December 2021 to June 2023 were selected as the study objects.Patients were randomly divided into the study group(EUS combined with modified EMR,n=16),the control 1 group(traditional EMR,n=16)and the control 2 group[endoscopic submucosal dissection(ESD),n=16].The operation time,R0 resection rate and postoperative complications of each group were observed.Endoscop-ic ultrasonography was followed up 3 and 6 months after surgery to determine whether there was any recur-rence.Results The operative time of the study group[(17.813±0.379)min]was significantly shorter than that of the control 2 group[(36.250±3.296)min],the difference was statistically significant(P＜0.05),but compared with the control 1 group[(16.375±1.996)min],there was no significant difference(P＞0.05).The incidence of complications in the study group(6.2％)was significantly lower than that in the control 2 group(37.5％),the difference was statistically significant(P＜0.05).while the incidence of complications in the study group was not significantly higher than that in the control 1 group(12.5％,P＞0.05).R0 removal rate in the study group(93.8％)was significantly higher than that in the control 1 group(62.5％)and the control 2 group(75.0％),the difference was statistically significant(P＜0.05).Conclusion EUS combined with modified EMR has more advantages than EMR and ESD in the treatment of RNETs,and has certain fea-sibility and safety,which is convenient for clinical application.

Objective:To explore the CT and MRI features of Rosai-Dorfman disease (RDD) in nasal cavity and paranasal sinus.Methods:The study was a cross-sectional study. From July 2007 to August 2023, the imaging findings of 23 patients with pathologically confirmed sinonasal RDD were retrospectively analyzed in the Eye & ENT Hospital of Fudan University. Among 23 patients, there were nine males and 14 females with 44±16 years old. Imaging features including tumor location, the extent, density, signal, enhancement pattern of tumors, bone change, abnormal lesions in peripheral lymph nodes and other regions were recorded. The apparent diffusion coefficient (ADC) value of lesions in patients performed diffusion weighted imaging (DWI) were measured.Results:For the 23 cases, totally 20 patients showed bilateral sinonasal involvement and three patients had unilateral lesions. Totally nine patients had lesions confined to the nasal cavity and paranasal sinuses, and 14 patients had lesions with extrasinonasal invasion, including orbit (6 cases), nasolacrimal duct (9 cases), anterior skull base (3 cases), nasal dorsum subcutaneous tissue (2 cases) and hard palate (1 case). Soft tissue lesions on the posterior wall of the subglottic trachea were found in 2 cases and intracranial lesions were found in 1 case. Totally 10 patients were accompanied by lymph nodes enlargement. The lesions showed isodense on all 20 non-contrast enhanced CT images, and mild enhancement in three cases, moderate enhancement in seven cases and significant enhancement in seven cases on CT enhancement images. Bone changes were found in 19 of 20 patients on CT, showing mild bone destruction in five cases and bone destruction with hyperplasia in 14 cases. The lesions showed isointense on T 1WI in all 14 cases. The lesions were graded as isointense in nine cases, hypointense in four cases and hyperintense in one case on T 2WI. The lesions displayed moderate to obvious homogeneous enhancement on enhanced MRI. The lesions showed significant diffusion limitation and ADC value was (0.66±0.08)×10 -3 mm 2/s in 11 cases on DWI. Conclusions:The CT and MRI imaging characteristics of sinonasal RDD are diffuse masses on both sides of nasal cavity and paranasal sinuses, accompanied by bone hyperplasia. The lesions show isointense or hypointense on T 2WI, and may involve adjacent tissues and may be accompanied by lymph nodes enlargement in the retropharyngeal and neck.

In recent years，the incidence and prevalence of non-tuberculous mycobacterial（NTM）infections have been on the rise，posing a serious threat to public health and presenting significant challenges for disease management. Currently，the treatment outcomes for NTM disease are poor，one of the main reasons being the high resistance of NTM pathogens to various anti-mycobacterial drugs. Novel therapeutic strategies targeting the host rather than the NTM pathogens themselves may help improve cure rates and reduce mortality. This article summarizes the latest research findings on host factors related to the incidence of NTM disease，including age，pulmonary diseases，immune function，genetic factors and lifestyle，which aids in the early identification of high-risk populations and provides a theoretical basis for developing targeted prevention and treatment strategies and optimizing treatment plans.

Objective:To preliminarily evaluate the efficacy and safety of a domestically developed bilateral interventional ultrasound renal denervation (RDN) system in patients with uncontrolled hypertension despite antihypertensive medication.Methods:A multicenter, single-arm trial was conducted. Patients with uncontrolled hypertension (≥2 antihypertensive drugs) were enrolled from April 2023 to April 2024 at the Second Affiliated Hospital of Chongqing Medical University, West China Hospital of Sichuan University, and the Second Affiliated Hospital of Harbin Medical University. RDN was performed using the UltraCure? bilateral interventional ultrasound system via femoral or brachial artery access. Multi-segmental "quadrant-based" ablation was performed in bilateral main renal arteries and branches/accessory arteries (diameter≥4 mm). Primary endpoints were changes in office systolic blood pressure (SBP) and 24-hour daytime SBP at 2-and 6-months post-procedure. The primary safety endpoints included the incidence of major adverse events, device-related adverse events, and puncture site complications.Results:Ten patients, mean aged 47.1 years, including 9 male, successfully completed RDN. At 2 and 6 months post-procedure, office SBP decreased by (19.7±15.2) mmHg ( P=0.002, 1 mmHg=0.133 kPa) and (13.8±13.9) mmHg ( P=0.013) from baseline, while the 24-hour daytime SBP decreased by (13.4±10.6) mmHg ( P=0.004) and (11.2±9.2) mmHg ( P=0.004). Apart from one case of a limited distal renal artery dissection, no other serious device/procedure-related adverse events were observed. At 6-month follow-up, the estimated glomerular filtration rate remained stable ((85.3±18.3) ml·min -1·1.73 m -2 vs. (82.3±19.2) ml·min -1·1.73 m -2, P=0.41). No renal artery stenosis was detected. Conclusions:The domestic interventional ultrasound RDN system could effectively reduce office and ambulatory blood pressure in patients with uncontrolled hypertension, demonstrating a favorable safety profile. Long-term efficacy requires confirmation through large-scale randomized controlled trials.

ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

Objective To analyze correlation of endolymphatic hydrops (EH) in the inner ear with age in Meniere’s disease (MD) patients. Methods A retrospective analysis were underwent in 101 definite unilateral MD patients. They were divided into young-age (＜18 years old) group, middle-age (18-45 years old) group and elder-age (＞45 years old) group. All patients underwent inner ear three-dimensional inversion-recovery with real reconstruction (3D-real IR) imaging 4 hours after intravenous gadolinium injection. EH rates among different groups were compared. Results The positive rates of EH in the young-age group, middle-age group and elder-age group were 68.2% (15/22), 54.5% (18/33) and 56.5% (26/46), respectively (P＝0.567). There was no difference in the positive rates of EH in vestibule and cochlea among three groups. There was no difference in the rates of mild and significant EH in vestibule and cochlea among three groups. Conclusions Age might not be related to the occurrence of EH in the inner ear in MD patients.

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

Kidney stones are a urinary system disease with a high incidence,among which calcium oxalate stones are the most common.Metabolic disorders such as hypertension,diabetes,obesity,hyperlipidemia,and hyperuricemia can cause changes in oxalate,uric acid,and pH and calcium ion concentrations in the urine through multiple pathways including inducing oxidative stress and inflammatory responses by generating reactive oxygen species,ultimately affecting the formation of calcium oxalate stones.This article reviews the possible pathways and mechanisms by which metabolic diseases influence the formation of calcium oxalate stones,providing new ideas for the clinical prevention and treatment of calcium oxalate stones.
Humans ; Calcium Oxalate/metabolism* ; Kidney Calculi/etiology* ; Metabolic Diseases/complications*