Background: and Purpose Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions. Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states. Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis. Conclusions Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

OBJECTIVE To investigate the effect and mechanism of Tangzhi formula（TZF） on improving glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats.METHODS Thirty SPF-grade SD rats were used to establish a T2DM rat model through high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After successful modeling， the rats were divided into the model group， metformin group （positive control， 0.18 g/kg）， and TZF low-， medium-， and high-dose groups （5， 10， and 20 g/kg）， with 6 rats in each group. An additional 6 rats were selected as the blank group. The rats in each group were orally administered the corresponding volume of drug solution or saline， and continuous dosing was performed for 6 weeks， once daily. Fasting blood glucose （FBG）， area under the curve of oral glucose tolerance test （OGTT-AUC）， area under the curve of intraperitoneal insulin tolerance test （IPITT-AUC）， serum total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） levels were measured. Hematoxylin-eosin （HE） staining and oil red O staining were used to observe hepatic pathological morphology and lipid deposition. Differentially expressed proteins in liver tissues were screened by proteomics analysis， and key proteins in signaling pathways were verified by Western blot and immunofluorescence staining.RESULTS Compared with the blank group， the levels of FBG， OGTT-AUC， IPITT-AUC， LDL-C， TG， and TC in the model group were significantly increased （ P ＜0.05）， while HDL-C level was significantly decreased （ P ＜0.05）； the liver tissues showed disordered hepatic cords， punctate necrosis of hepatocytes， and significant lipid deposition， the NAFLD activity score and positive area of lipid droplets were significantly increased（ P ＜0.05）. Compared with the model group， the above indicators in TZF low-， medium-， and high-dose groups and metformin group were significantly reversed （ P ＜0.05）； hepatic pathological injury and lipid deposition were alleviated. Proteomics results showed that a total of 442 differentially expressed proteins were screened between the model group and the blank group， and 358 differentially expressed proteins were screened between the TZF high-dose group and the model group. Among these differentially expressed proteins， multiple proteins closely related to glucose and lipid metabolism showed a reversal trend after TZF intervention. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the peroxisome proliferator-activated receptor （PPAR） signaling pathway was significantly enriched. The validation experiment results showed that TZF could significantly up-regulate the expression of PPARα， PPARγ， and apolipoprotein A1 （ApoA1） in rat liver tissues （ P ＜0.05）， and down-regulate the expression of stearoyl-CoA desaturase 1 （SCD1） and perilipin 2 （PLIN2） （ P ＜0.05）.CONCLUSIONS TZF can improve glucose and lipid metabolism disorders in T2DM rats； its mechanism may be related to the activation of the PPAR signaling pathway and the regulation of downstream lipid metabolism-related proteins SCD1， PLIN2， and ApoA1.

BACKGROUND: Physical activity, sedentary behavior (SB), and sleep duration are associated with brain health. Effects of those on developing Parkinson's disease (PD) are poorly investigated. This study aimed to examine the independent and joint associations of physical activity, SB, sleep with PD risk. METHODS: We analyzed data on 401,697 participants from the UK Biobank cohort, which was enrolled in 2006-2010. Physical activities were measured based on a questionnaire. Sleep and SB time were defined through self-reported total number of hours. Models fitted with restricted cubic spline were conducted to test for linear and non-linear shapes of each association. Cox proportional hazards regression models were used to estimate the association of three modifiable behaviors. RESULTS: Our analytic sample included 401,697 participants with 3030 identified cases of PD (mean age, 63 years; 62.9% male). PD risk was 18% lower in the high total physical activity group (95% CI, 0.75-0.90), 22% lower in the high leisure-time physical activity (LTPA) group (95% CI, 0.71-0.86) compared with the low level and 14% higher in the high sleep duration group (95% CI, 1.05-1.24) compared to moderate group. Total SB time was irrelevant with PD risk, while high TV viewing showed a 12% increase of PD risk compared to the low group (95% CI, 1.02-1.22). Low computer use (0 h/day) was associated with a 14% higher risk compared to 1 h/day use (95% CI, 1.04-1.26). Those associations were independent. A combination of 7 h/day sleep, moderate-to-high computer use, and moderate-to-vigorous intensity of LTPA showed lowest PD risk (HR, 0.70; 95% CI, 0.57-0.85). CONCLUSIONS Physical activity, SB, and sleep were associated with PD risks separately. Our findings emphasize the possibility for changing these three daily activities concurrently to lower the risk of PD. These findings may promote an active lifestyle for PD prevention.
Humans ; Parkinson Disease/physiopathology* ; Male ; Sedentary Behavior ; Female ; Middle Aged ; Exercise/physiology* ; Prospective Studies ; Sleep/physiology* ; Aged ; Surveys and Questionnaires ; Proportional Hazards Models ; Risk Factors

BACKGROUND: Neuroticism has been associated with numerous health outcomes. However, most research has focused on a single specific disorder and has produced controversial results, particularly regarding mortality risk. Here, we aimed to examine the association of neuroticism with morbidity and mortality and to elucidate how neuroticism affects trajectories from a healthy state, to one or more neuroticism-related disorders, and subsequent mortality risk. METHODS: We included 483,916 participants from the UK Biobank at baseline (2006-2010). Neuroticism was measured using the Eysenck Personality Questionnaire. Three clusters were constructed, including worry, depressed affect, and sensitivity to environmental stress and adversity (SESA). Cox proportional hazards regression and multistate models were used. Linear regression was used to examine the association between neuroticism and immune parameters and neuroimaging measures. RESULTS: High neuroticism was associated with 37 non-overlapping diseases, including increased risk of infectious, cardiometabolic, neuropsychiatric, digestive, and respiratory diseases, and decreased risk of cancer. After adjustment for sociodemographic variables, physical measures, healthy behaviors, and baseline diagnoses, moderate-to-high neuroticism was associated with a decreased risk of all-cause mortality. In multistate models, high neuroticism was associated with an increased risk of transitions from a healthy state to a first neuroticism-related disease (hazard ratio [HR] [95% confidence interval (CI)] = 1.09 [1.05-1.13], P  <0.001) and subsequent transitions to multimorbidity (1.08 [1.02-1.14], P  = 0.005), but was associated with a decreased risk of transitions from multimorbidity to death (0.90 [0.84-0.97], P for trend = 0.006). The leading neuroticism cluster showing a detrimental role in the health-illness transition was depressed affect, which correlated with higher amygdala volume and lower insula volume. The protective effect of neuroticism against mortality was mainly contributed by the SESA cluster, which, unlike the other two clusters, did not affect the balance between innate and adaptive immunity. CONCLUSION This study provides new insights into the differential role of neuroticism in health outcomes and into new perspectives for establishing mortality prevention programs for patients with multimorbidity.
Humans ; Neuroticism/physiology* ; Male ; Female ; Middle Aged ; Aged ; Proportional Hazards Models ; Surveys and Questionnaires ; Adult ; Risk Factors

Objective:To evaluate surgical strategies and clinical outcomes in supra-labyrinthine cholesteatoma management, providing evidence-based guidance for therapeutic decision-making. Methods:Seven patients with supra-labyrinthine cholesteatoma in our hospital from 2021 to 2023 were enrolled in this study. The clinical manifestations, imaging findings, and surgical outcomes of patients were retrospectively analyzed. A systematic literature review focused on surgical anatomy correlations and imaging-based approach selection. Results:All seven cases of supra-labyrinthine cholesteatoma were unilateral. Preoperative otoendoscopy, CT, and intraoperative findings confirmed that they were classified as supral-abyrinthine cholesteatoma according to Sanna's classification. Two cases were operated entirely with otoendoscopy, three cases used a postauricular approach with microscopic assistance, and two cases involved a combined approach with endoscopy and microscopy. Hearing reconstruction with ossicular prosthesis was performed in five cases, while two cases did not undergo hearing reconstruction due to preoperative anacusis confirmed by both subjective and objective hearing tests. In all seven cases, various segments of the facial nerve were exposed during surgery, but postoperative facial nerve function remained intact, hearing was preserved, no cerebrospinal fluid leakage occurred, and no recurrences have been observed to date（as of June 2024）. Conclusion:With the advancement of imaging techniques and microsurgical technology, early diagnosis and surgical methods for supral-abyrinthine cholesteatoma have significantly improved. Compared to traditional approaches, the newer methods reduce unnecessary complications and offer advantages such as minimal surgical trauma, superior hearing preservation rates, and shorter recovery times with better postoperative neural function. This study reviews recent literature on petroclival cholesteatomas, combined with our own cases, to analyze the classification of supral-abyrinthine cholesteatoma and surgical approach selection. The findings aim to optimize treatment strategies and guide appropriate surgical methods, ultimately improving patient prognosis and quality of life.
Humans ; Cholesteatoma/surgery* ; Ear, Inner/surgery* ; Retrospective Studies ; Treatment Outcome

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

Objective To investigate the regulatory mechanism of the central nervous system in patients with refractory overactive bladder (rOAB) using diffusion tensor imaging (DTI) and graph theory analysis. Methods A total of 43 rOAB patients (rOAB group) and 46 matched healthy controls (HC group) were recruited during May and Nov.2024. All participants were scanned with DTI, and surveyed with the overactive bladder symptom score (OABSS), and overactive bladder questionnaire (OAB-q). Their age, gender, height, weight, and educational years were collected.DTI plus graph theory analysis was employed to explore the alterations in global and local topological properties of the brain structural network in rOAB patients. Brain regions showing significant group differences in structural metrics [specifically, the right paracentral lobule (PCL.R) ]were further used as seed points for functional connectivity (FC) analysis. Correlations between the nodal clustering coefficient (NCp) of the identified region, FC strength, OABSS, and OAB-q score were investigated. Results The OABSS [8 (6,10) vs.0 (0,1) ]and OAB-q [71 (53,80) vs.20 (19,24) ]were higher in the rOAB group than the HC group (P<0.001). Graph theory analysis revealed no statistically significant differences in global network metrics between the two groups (P>0.05). However, the NCp was significantly higher in the PCL.R of rOAB group compared to HC group (P<0.05, FDR-corrected).FC analysis using the PCL.R as a seed region demonstrated significantly reduced FC value in the left cerebellar crus Ⅱ (Cerebelum_Crus2_L) of the rOAB group (P<0.05, FDR-corrected). Partial correlation analysis showed that the NCp of PCL.R was positively correlated with both OABSS (r=0.255, P=0.018) and OAB-q score (r=0.257, P=0.017). Conversely, the FC of Cerebelum_Crus2_L was significantly negatively correlated with OABSS (r=-0.545, P<0.001) and OAB-q score (r=-0.535, P<0.001). Conclusion Patients with rOAB exhibit distinct brain structural network alterations compared to healthy individuals, primarily manifestation in the NCp value of PCL.R increased, and the FC intensity of Cerebelum_Crus2_L is significantly weakened. These alterations in the topological properties of the structural network may be implicated in the pathogenesis of rOAB.

Objective:To investigate the impact of delayed ileostomy closure (>6 months) on postoperative complications in patients with ulcerative colitis (UC) undergoing ileal pouch-anal anastomosis (IPAA) .Methods:Using propensity score matching. Clinical data of UC patients who underwent IPAA and subsequent ileostomy closure at Jinling Hospital from January 2014 to December 2021 were retrospectively analyzed. Patients were categorized into a routine group (2 to ≤6 months) and a delayed group (>6 months) based on the timing of ileostomy closure. A 1∶1 propensity score matching analysis was performed to compare early (≤30 days) and late (>30 days) postoperative complications between the two groups.Results:A total of 225 UC patients who underwent IPAA and ileostomy closure were included, comprising 129 males (57.3%) and 96 females (42.7%). After propensity score matching, 88 patients were included in the analysis, with 44 patients in each group. There was no significant difference in the overall incidence of early postoperative complications (11.4% vs. 15.9%, P = 0.534) or late postoperative complications (43.2% vs. 43.2%, P = 1.000) between the delayed and routine groups. Additionally, no significant differences were observed in other postoperative complications (all P > 0.05) . Conclusion:Delayed ileostomy closure following IPAA does not significantly increase the risk of postoperative complications in UC patients.

To satisfy the growing healthcare demands of the public, it is essential to develop a public service platform for vaccination. This initiative aligns with national policies, optimizes resource allocation, innovates service models, enhances service efficiency, and reduces service costs. Drawing on relevant national policies and regulatory requirements, as well as the notable achievements and practical experiences gained through the exploration and innovation of vaccination service models across various regions, this paper proposes expert recommendations. It defines the essential components and functional specifications for public service platforms, focusing on public needs such as electronic vaccination record management, appointment management, the promotion of electronic vaccination certificates, vaccination certificate verification for school enrollment, vaccination site navigation, and science communication and public engagement. The recommendations aim to serve as a reference for the development of vaccination public service platforms nationwide.

Objective To evaluate the efficacy of cefoperazone-sulbactam(CS)combined with ulinastatin in the treatment for stroke-associated pneumonia(SAP)after endovascular treatment of acute large vessel occlusive stroke(AIS-LVO).Methods This study retrospectively included patients who developed SAP after endovascular treatment of AIS-LVO admitted to the intensive care unit of the Department of Neurology at the First Affiliated Hospital of Xi'an Jiaotong University from March 2022 to December 2023.Patients were randomly divided into the ulinastatin group(combined application of ulinastatin and CS)and the control group(sole application of CS)using a random number table.Baseline and clinical data,including sex,age,infarct laterality,culprit vessel,trial of Org 10172 in acute stroke treatment(TOAST)classification,baseline National Institutes of Health stroke scale(NIHSS)score,baseline Glasgow coma scale(GCS)score,medical history(hypertension,diabetes,coronary heart disease,atrial fibrillation,past history of stroke),history of smoking and alcohol consumption,admission baseline blood pressure,laboratory test results at admission(including red blood cell count,white blood cell count,neutrophil count,platelet count,random blood glucose levels,albumin,creatinine,low-density lipoprotein cholesterol,uric acid,and D-dimer),and endovascular therapies(including mechanical retrieval of thrombus,stenting,balloon dilatation,arterial thrombolysis and combination therapy)were collected from both groups.After the diagnosis of SAP,patients in both groups underwent conventional treatment such as sputum expectoration and clearance,antipyretic and antitussive treatment,oxygen therapy,respiratory support,fluid and nutrition support,along with CS anti-infective therapy.In contrast to the control group,the ulinastatin group additionally received continuous ulinastatin treatment for at least 7 days.The adverse reactions of the two groups after initiating SAP treatment including allergic reactions(such as sudden dyspnea,skin redness,and shock),decrease in peripheral white blood cell count(below 4.0 × 109/L),nausea and vomiting,diarrhea,rash and/or itching,and liver enzymes(aspartate aminotransferase or alanine aminotransferase)elevation(more than twice the upper limit of normal)were compared between the two groups.The efficacy indicators encompassing arterial blood gas analysis(oxygenation index)and inflammatory factor indicators(interleukin-6[IL-6],procalcitonin)after 7 days of SAP treatment,pneumonia-related symptoms and signs before and after SAP treatment(including body temperature,heart rate,respiratory rate,sputum volume and characteristics,changes in lung rales,etc.),imaging examinations(such as head CT and chest CT).The evaluation of therapeutic efficacy is classified as(1)markedly effective:following treatment,significant relief was observed on pneumonia-related symptoms and signs,with body temperature returned to normal,and arterial blood gas analysis and inflammatory factor indicators returned to normal levels;post-treatment imaging studies reveal that over 2/3 of lung inflammation has been absorbed;(2)effective:after treatment,some improvement was observed in pneumonia-related symptoms and signs,with mild improvement in arterial blood gas analysis and inflammatory factor indicators;post-treatment imaging studies reveal some absorption of lung inflammation;(3)ineffective:no improvement or further deterioration of pneumonia-related symptoms,arterial blood gas analysis,and inflammatory factor indicators after treatment.The arterial blood gas analysis,inflammatory factor indicators and efficacy indicators were evaluated and compared between the control and the ulinastatin group.Compare the prognosis(improvement of the lesion in the chest CT after 7 days of treatment,length of stay in the intensive care unit,total length of hospital stay,and modified Rankin scale[mRS]score assessed via telephone follow-up or outpatient revisit 90 days after endovascular treatment[with an mRS score ≤2 indicating a good prognosis],as well as mortality).Results A total of 99 patients with AIS-LVO who developed SAP after endovascular treatment were included in this study,with 69 males(69.7％)and 30 females(30.3％),and an average age of(68±10)years.Among them,there were 46 cases in the ulinastatin group and 53 cases in the control group.(1)No statistically significant differences were observed in baseline or clinical characteristics between the two groups(all P＞0.05).(2)The overall effective(markedly effective and effective)rate of SAP treatment was greater in the ulinastatin group than that in the control group(89.1％[41/46]vs.69.8％[37/53],P=0.019).(3)No statistically significant differences were observed in serum IL-6 levels,procalcitonin levels,or arterial oxygenation index between the ulinastatin group and the control group before treatment(all P＞0.05).seven days after treatment,the levels of serum IL-6([21.13±14.86]ng/L vs.[64.39±52.95]ng/L)and procalcitonin([0.12±0.11]μg/L vs.[0.31±0.20]μg/L)in the ulinastatin group were significantly lower compared to those before treatment(all P＜0.01),and the arterial oxygenation index was significantly higher than that before treatment([359.35±92.56]mmHg vs.[273.34±95.65]mmHg,P＜0.01).Seven days after treatment,the levels of serum IL-6([21.13±14.86]ng/L vs.[31.90±21.95]ng/L)and procalcitonin([0.12±0.11]μg/L vs.[0.26±0.24]μg/L)in the ulinastatin group were significantly lower than those in the control group(all P＜0.01),and the arterial oxygenation index was significantly higher than that of the control group([359.35±92.56]mmHg vs.[314.81±81.97]mmHg,P=0.020).(4)In the ulinastatin group,there was 1 case of nausea and vomiting,1 case of itching and/or rash,and 1 case of elevated liver enzymes,resulting in an adverse reaction rate of 6.5％(3/46).In the control group,there were 2 cases of nausea and vomiting,1 case of itching and/or rash,and 1 case of elevated liver enzymes,resulting in an adverse reaction rate of 7.5％(4/53).No statistically significant differences were observed in the adverse reaction rate between the two groups(P＞0.05).(5)After 7 days of treatment,the ulinastatin group exhibited a greater improvement rate in chest CT lesions compared to the control group(93.5％[43/46]vs.77.4％[41/53],P=0.026).No statistically significant differences were observed between the two groups in terms of the length of stay in the intensive care unit or the total length of hospital stay(both P＞0.05).Additionally,the 90-day mortality rate after intravascular treatment was lower in the ulinastatin group compared to the control group(6.5％[3/46]vs.20.8％[11/53],P=0.040).No statistically significant differences were observed in the good prognosis rate between the two groups(P=0.119).Conclusions Combined treatment with CS and ulinastatin can improve the clinical symptoms,inhibit inflammatory factors and reduce mortality rate in SAP patients after receiving endovascular treatment for AIS-LVO.The results of this study still need to be further confirmed by large-scale prospective studies.