ObjectiveTo analyze the output and efficiency of chronic disease management services for hypertension and diabetes in community health service institutions in Shanghai, to evaluate the allocation and efficiency of chronic disease management resources, and to provide references for improving the efficiency of chronic disease management in Shanghai’s communities. MethodsA total of 73 community health institutions from 15 districts of Shanghai were selected. Based on the chronic disease management resource data of community health institutions in 2019, 2021, and 2023, descriptive methods and the BCC model in Data Envelopment Analysis (DEA) were used to analyze the resource allocation, service output, and the efficiency of chronic disease management services in community health institutions in Shanghai. ResultsFrom 2019 to 2023, the indicators of resource allocation and service output of community health service institutions in Shanghai all showed upward trends. In terms of service efficiency, the average number of chronic disease patients managed by each health technician decreased from 237 to 231, and the number of patients served per 1 000 working hours decreased from 54 to 44. DEA efficiency analyses showed that the average overall efficiency increased from 0.867 in 2019 to 0.886 in 2021 and then decreased to 0.811 in 2023. The average technical efficiency decreased from 0.901 to 0.847, which was the main reason for the decline in overall efficiency. The average scale efficiency showed an initial increase followed by a decrease, rising from 0.961 in 2019 to 0.977 in 2021 and dropping back to 0.955 in 2023. The number of strong effective districts (overall efficiency=1.000) decreased from 6 in 2019 to 3 in 2023, and the efficiency differences between districts expanded. The range of overall efficiency widened from 0.622‒1.000 to 0.513‒1.000, indicating a decline in overall efficiency and an increase in inter-district heterogeneity. ConclusionFrom 2019 to 2023, the total volume of resource allocation and service output for chronic disease management in community health service institutions in Shanghai increased continuously. However, both the service output efficiency and the overall resource allocation efficiency declined, driven primarily by a decrease in technical efficiency, and accompanied by widening inter‑district disparities.

ObjectiveType 2 diabetes mellitus (T2DM) often causes severe hepatic metabolic complications, dominated by metabolic associated fatty liver disease (MAFLD). Persistent hepatic steatosis and oxidative stress further trigger steatohepatitis and progressive liver damage, increasing the mortality risk of diabetic patients. Aerobic exercise effectively improves hepatic lipid metabolism and antioxidant capacity, but poor patient adherence restricts its long-term clinical application. Mitochondrial-derived mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) is a key peptide regulating insulin sensitivity and hepatic redox homeostasis. This study aimed to explore the protective mechanism of MOTS-c against T2DM-related liver injury and its combined beneficial effect with aerobic exercise via the NRF2/PPARγ signaling axis. This study aimed to investigate whether MOTS-c cooperates with aerobic exercise to alleviate T2DM-associated hepatic oxidative stress and metabolic dysfunction by activating the NRF2/PPARγ axis, and to clarify the molecular and transcriptomic characteristics of their combined intervention. MethodsStable MOTS-c overexpression and knockdown HepG2 cell lines were constructed using lentiviral transfection. An oleic acid-induced cellular lipid accumulation model and NRF2-knockout cell model were applied to verify the NRF2-dependent mechanism ofMOTS-c. Intracellular lipid deposition, triglyceride levels, antioxidant enzyme activities, and the expression of NRF2/PPARγ pathway-related genes and proteins were detected. In vivo, a T2DM rat model with obvious hepatic steatosis was established via a high-fat and high-sucrose diet combined with streptozotocin injection. Model rats received aerobic exercise, MOTS-c intraperitoneal injection, or combined intervention. We detected systemic glycolipid metabolic indicators, hepatic histopathological changes, and the expression of core proteins in the hepatic NRF2/PPARγ axis. Hepatic transcriptomic sequencing was performed to screen differentially expressed genes (DEGs) and enrich key pathways co-regulated by MOTS-c and aerobic exercise. ResultsCellular results showed that MOTS-c overexpression significantly reduced oleic acid-induced lipid deposition, enhanced antioxidant enzyme activity, and upregulated NRF2 and PPARγ expression. Conversely, MOTS-c knockdown aggravated hepatic lipid accumulation and oxidative damage and inhibited NRF2/PPARγ pathway activation. NRF2 knockout completely eliminated the protective effects of MOTS-c on lipid metabolism and redox balance, confirming its NRF2-dependent regulatory mechanism. In T2DM rats, both MOTS-c supplementation and aerobic exercise effectively improved insulin resistance, corrected glycolipid metabolic disorders, and alleviated hepatic steatosis, while consistently activating the hepatic NRF2/PPARγ axis. Compared with single intervention, the combined treatment showed a better improvement trend in hepatic metabolic and oxidative injury, without definitive synergistic effects. Transcriptomic analysis revealed that the co-regulated DEGs of MOTS-c and aerobic exercise were primarily enriched in lipid metabolism and PPAR signaling pathways, with multiple antioxidant and lipid-regulating genes significantly modulated by combined intervention. ConclusionMOTS-c exhibits obvious exercise-mimetic hepatoprotective effects in T2DM. It activates the hepatic NRF2/PPARγ axis to strengthen antioxidant defense, stabilize lipid metabolism, and relieve T2DM-associated hepatic steatosis and oxidative damage. Furthermore, MOTS-c produces additive beneficial effects with aerobic exercise, showing a superior intervention trend on diabetic liver dysfunction. This study identifies the NRF2/PPARγ axis as the core mechanism of MOTS-c-regulated hepatic protection, elucidates the transcriptomic basis of combined intervention, and provides a reliable theoretical basis and potential therapeutic target for clinical intervention in T2DM-complicated MAFLD.

ObjectiveTo investigate the effects of berberine hydrochloride on the expression of urease genes ureA and ureB in Helicobacter pylori （H. pylori） and its biofilm. MethodsThe standard strain 26695 of H. pylori， which was preserved in our laboratory， along with the drug-resistant strains H390， e660， H57， and H389 of H. pylori that were isolated from clinical sources were revived. The minimum inhibitory concentration （MIC） of berberine hydrochloride against the planktonic cells of the aforementioned five strains of H. pylori was determined using the broth dilution method. The combined inhibitory effect of berberine hydrochloride and amoxicillin against the aforementioned four strains of clinically resistant H. pylori was assessed using the checkerboard method. TheMIC of berberine hydrochloride against the biofilms of H. pylori strains 26695 and H390 was determined using the broth dilution method. Planktonic cells and biofilms of the aforementioned H. pylori strains 26695 and H390 were co-incubated with berberine hydrochloride at concentrations of 0.5MIC， MIC， and 2MIC for 2， 8， and 24 hours， respectively. Subsequently， urease activity was measured， and the expression levels of the ureA and ureB genes were detected using RT-qPCR. ResultsBerberine hydrochloride exhibited inhibitory effects against both planktonic cells of the antibiotic-sensitive strain 26695 and the antibiotic-resistant strains H390， e660， H57， and H389 of H. pylori. It also demonstrated inhibitory effects against the biofilms formed by strains 26695 and H390. Furthermore， the combined inhibitory effect of berberine hydrochloride and amoxicillin against antibiotic-resistant strains of H. pylori was either synergistic or additive. Berberine hydrochloride inhibited urease activity in both planktonic cells and biofilms of the H. pylori strains 26695 and H390. Furthermore， berberine hydrochloride downregulated the relative expression levels of the ureA and ureB genes in H. pylori and its biofilms. The relative expression levels of the ureA and ureB genes exhibited a dose- and time-dependent decrease with increasing concentrations of berberine hydrochloride and longer co-incubation times （P<0.05）. ConclusionBerberine hydrochloride inhibits both planktonic cells and biofilms of H. pylori. When combined with amoxicillin， it exerts additive or synergistic effects against H. pylori. Furthermore， by inhibiting urease activity and downregulating the expression of the ureA and ureB genes in H. pylori， berberine hydrochloride contributes to the reduction in growth of both planktonic cells and biofilms.

Neurodegenerative diseases (NDs), particularly Alzheimer’s disease (AD) and Parkinson’s disease (PD), and cardiovascular diseases (CVDs), including heart failure (HF) and coronary artery disease (CAD), are major chronic disorders associated with population aging. Their frequent coexistence in clinical practice suggests that they may not progress independently, but may instead be linked through bidirectional pathological communication within the brain-heart axis. Epidemiological evidence underscores this clinical burden: systematic reviews and meta-analyses have reported pooled relative risks for dementia of approximately 1.27 among individuals with a history of CAD and 1.60 among those with HF, while the pooled prevalence of cognitive impairment and dementia in patients with HF has been estimated at approximately 41.42% and 19.79%, respectively. This review synthesizes current evidence on the mechanistic links, disease-state manifestations, biomarkers, and potential therapeutic strategies involved in the comorbidity between NDs and CVDs from the perspective of the brain-heart axis. The brain and heart communicate through autonomic, neuroendocrine, neuroimmune, vascular, and humoral pathways. Sympathetic activation, parasympathetic withdrawal, vagal dysfunction, cerebral hypoperfusion, endothelial injury, blood-brain barrier (BBB) alterations, peripheral immune activation, and circulating inflammatory mediators may jointly contribute to cross-organ pathological signaling. Oxidative stress and inflammatory response are not specific to the brain-heart axis; rather, they may act as candidate amplifying processes within this network. Mitochondrial dysfunction and NADPH oxidase activation can increase the generation of reactive oxygen species and reactive nitrogen species, which may activate nuclear factor-κB, the NLRP3 inflammasome, and mitogen-activated protein kinase/c-Jun N-terminal kinase signaling. These pathways can promote the release of interleukin-1β, interleukin-6, tumor necrosis factor‑α, and other inflammatory mediators, which may in turn aggravate mitochondrial injury, endothelial dysfunction, immune cell activation, and further oxidant generation. Cytokines, chemokines, oxidized lipids, mitochondrial DNA, damage-associated molecular patterns, and extracellular vesicles may transmit these signals between the cardiovascular and central nervous systems, whereas autonomic reflexes provide an additional route for bidirectional amplification. Distinct disease states illustrate different manifestations of this network. The association between AD and CVDs may involve vascular risk factors, impaired amyloid-β clearance, abnormal cholesterol homeostasis, cerebral microvascular injury, neuroinflammation, and endothelial dysfunction. HF-related cognitive impairment may be linked to reduced cardiac output, recurrent cerebral hypoperfusion, hypoxia-related signaling, BBB dysfunction, circulating inflammation, and impaired autonomic feedback. In PD, cardiovascular autonomic dysfunction and abnormalities in heart rate and blood pressure regulation may interact with vascular injury, reduced cerebral perfusion, inflammation, and oxidative stress. However, the relationship between PD and CAD remains heterogeneous and may be modified by age, ethnicity, medication use, metabolic factors, and coexisting diseases. Biomarker evaluation should therefore move beyond isolated indicators. Traditional markers, including malondialdehyde, superoxide dismutase, glutathione, C-reactive protein, and interleukin-6, reflect systemic oxidative or inflammatory burden but lack sufficient specificity to distinguish primary neurodegeneration, cardiovascular injury, or a comorbid state involving both. Greater clinical value may be obtained from cross-system panels that combine oxidative stress and inflammatory markers with cardiac stress or injury biomarkers, such as N-terminal pro-B-type natriuretic peptide; glial or neuronal biomarkers, such as glial fibrillary acidic protein and neurofilament light chain; BBB- or endothelial injury-related biomarkers; and omics-derived candidates, including microRNAs, long non-coding RNAs, DNA methylation signatures, metabolites, and proteins. Multi-omics integration and artificial intelligence-assisted analysis may support risk stratification, disease monitoring, and prediction of treatment response. However, these approaches require standardized analytical platforms, validation in independent cohorts, and careful distinction between associative findings and causal mechanisms. Potential interventions include antioxidant, anti-inflammatory, mitochondria-targeted, and multi-target combination strategies, together with emerging approaches such as nanodelivery, CRISPR/Cas9- or CRISPR/dCas9-based regulation, mesenchymal stem cell-mediated mitochondrial transfer, and ergothioneine supplementation. Nevertheless, most available evidence is indirect, preclinical, or derived from other disease indications, and no single drug or technology can currently be regarded as specific to brain-heart axis comorbidity. The clinical relevance of these strategies will depend on whether they can be matched to dominant pathological phenotypes and improve both neurological and cardiovascular outcomes. Overall, comorbidity between NDs and CVDs is more appropriately understood as a heterogeneous cross-organ regulatory network than as a disorder driven by a single pathway. Future research should prioritize multicenter longitudinal cohorts, standardized clinical phenotyping, validation of cross-system biomarker panels, and mechanism-guided interventions in clearly defined patient subgroups, with integrated assessment of cognitive function, cardiovascular events, quality of life, long-term safety, and treatment response.

Objective:To investigate multi-system involvement in Kennedy′s disease and its association with disease progression.Methods:We retrospectively reviewed the clinical, laboratory, and electrophysiological data from 48 genetically confirmed patients with Kennedy′s disease at the Department of Neurology, First Medical Center of the Chinese PLA General Hospital, between February 2016 and February 2024. The disease progression rate was calculated based on the functional scores at baseline and follow-up. Correlation analyses and multiple linear regression models were employed to assess the relationships among clinical variables and to identify potential predictors of disease progression.Results:The age of muscle weakness onset ranged from 16 to 66 years (mean 42±11 years), with a diagnostic delay of 5.0 (3.0, 9.8) years. Lower limb weakness was the most common initial symptom in 72.9% (35/48) of patients, and 37.5% (18/48) exhibited non-motor manifestations prior to the onset of weakness. Core motor manifestations included bulbar weakness (89.6%, 43/48) and symmetric proximal limb weakness (83.3%, 40/48), frequently accompanied by gynecomastia (74.2%, 23/31) and sexual dysfunction (64.6%, 31/48). The median CAG repeat length was 43 (42, 46), which showed a significant negative correlation with the age at onset ( r=-0.406, P=0.004). Patients with CAG repeats > 43 had a higher prevalence of sexual dysfunction. Elevated serum muscle enzymes were observed in 97.9% (47/48), and abnormal sex hormone levels were detected in 81.2% (39/48). Sensory neuropathy was present in 68.1% (32/47), with CAG repeat length inversely correlating with compound muscle action potential (CMAP) amplitudes in the median ( β=-0.29; t=-2.27, P=0.029) and ulnar ( β=-0.22; t=-2.23, P=0.031) nerves. Low-frequency repetitive nerve stimulation (RNS) revealed a decrement in 43.3% (13/30) of patients, most commonly affecting the axillary and spinal accessory nerves. The disease progression rate was 1.3±0.3 (range: 0.5-2.0). Furthermore, serum creatine kinase-MB (CK-MB) levels were negatively correlated with disease progression rate ( r=-0.303, P=0.036). Conclusions:Kennedy′s disease presents with diverse initial manifestations and frequent multi-system involvement. Non-motor manifestations may precede muscle weakness, serving as valuable clues for early diagnosis. Widespread sex hormone abnormalities (particularly testosterone/luteinizing hormone dysregulation) support the role of androgen insensitivity in disease pathogenesis. Sensory neuropathies are frequent and not length-dependent. The presence of decremental responses on low-frequency RNS suggests neuromuscular junction dysfunction, which may underlie motor impairment in patients with Kennedy′s disease. Finally, serum CK-MB may serve as a potential biomarker for disease progression.

Objective:To investigate the measurement differences between mainstream and sidestream partial pressure of end tidal carbon dioxide(PetCO2)monitoring techniques in mechanically ventilated patients,as well as the correlation with partial pressure of arterial blood carbon dioxide(PaCO2)and clinical applicability,and to provide a basis for the rational selection of monitoring methods in the clinic.Methods:A total of 169 patients who underwent invasive mechanical ventilation in the operating room of the First Affiliated Hospital of Bengbu Medical University from August to November 2024 were selected to be monitored by three monitoring techniques of mainstream PetCO2,sidestream PetCO2 and PaCO2,respectively,and the 243 sets of valid pairwise data monitored by the three monitoring techniques were recorded,analyzed for correlation and deviation,and performed PaCO2 and PetCO2 were stratified and analyzed.Likert scales were used to analyze the subjective ratings of the 3 monitoring techniques of mainstream PetCO2,sidestream PetCO2,and PaCO2 by the 31 health care professionals who used the study.Results:Both mainstream and sidestream PetCO2 correlated with PaCO2(r=0.554,0.515,P<0.05),and mainstream PetCO2 correlated better than sidestream;mainstream PetCO2 was lower than the concurrent PaCO2 by 6.00 mmHg,and the 95%limit of agreement(95%LoA)was±6.28 mmHg,both lower than that of sidestream by 8.24 mmHg and±7.41 mmHg.8.24 mmHg and±7.41 mmHg.The dispersion of sidestream PetCO2 monitoring values was greater,especially at high PaCO2 levels.Mainstream method PetCO2 had the highest correlation with PaCO2 in gynecologic patients(r=0.820,P<0.05),and sidestream method PetCO2 underestimated PaCO2 more markedly in gastrointestinal and hepato-biliary-pancreatic surgery patients.The deviation of oxygenation index≤300 mmHg was significantly greater than that of patients with oxygenation index>300 mmHg,and the tendency of underestimation was more significant at high PaCO2.31 healthcare experts evaluated that the mainstream PetCO2 monitoring method was outstanding in terms of accuracy and real-time,and that the sidestream method of PetCO2 monitoring was advantageous in terms of ease of operation and management of consumables.Conclusion:In patients who receive mechanical ventilation,the precision,accuracy and real-time of mainstream PetCO2 monitoring are better,which is suitable for patients with rapid changes in disease condition or patients at risk of hypercapnia.The sidestream method is suitable for non-intubated or transported patients,but it is easy to be underestimated at high PaCO2,and it needs to be corrected regularly in combination with arterial blood gas.The clinical application should rationally choose monitoring method after a comprehensive assessment based on the patient's disease condition,oxygenation status,and the scenario of use.

OBJECTIVE: High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory. Nogo-A is an important axonal growth inhibitory factor. However, its function in high-altitude hypoxia and its mechanism of action remain unclear. METHODS: In an in vivo study, a low-pressure oxygen chamber was used to simulate high-altitude hypoxia, and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway. Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats, and synaptic damage in the hippocampus and changes in oxidative stress levels were observed. In vitro, SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion (OGD/R) models. RESULTS: Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats, triggered oxidative stress in the hippocampal tissue, and reduced the dendritic spine density of hippocampal neurons. Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress, synaptic damage, and the learning and memory impairment induced by high-altitude exposure. CONCLUSION: Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure. GRAPHICAL ABSTRACT available in www.besjournal.com.
Animals ; Oxidative Stress ; Hippocampus/metabolism* ; Rats ; Nogo Proteins/genetics* ; Male ; Rats, Sprague-Dawley ; Hypoxia/metabolism* ; Altitude ; Synapses ; Humans ; Altitude Sickness/metabolism*

OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

To investigate the molecular mechanisms underlying the mechanosensitive ion channel PI-EZO2 in osteoarthritis(OA),we developed a lentiviral vector for endogenous PIEZO2 overexpression and established a stable PIEZO2-high-expressing immortalized human primary chondrocyte line.By map-ping the open reading frame of the PIEZO2 locus and designing sequence-specific sgRNA,we employed the CRISPR/Cas9 synergistic activation mediator(SAM)system to precisely integrate transcriptional ac-tivation elements into the PIEZO2 promoter region.Lentiviral-mediated targeted genomic integration en-sured endogenous PIEZO2 overexpression,confirmed by mCherry fluorescence tracing coupled with flow cytometric sorting,which revealed membrane-specific localization of PIEZO2 protein(localization effi-ciency:78.49％).Quantitative PCR demonstrated a 17-fold upregulation of PIEZO2 mRNA,while Western blotting validated enhanced membrane-localized protein expression.Strikingly,PIEZO2-overex-pressing chondrocytes exhibited hallmark OA metabolic phenotypes compared to wild-type controls:typeⅡ collagen mRNA expression decreased to 50％of baseline levels,whereas matrix metalloproteinase 13(MMP13)mRNA surged by 20-fold.These alterations recapitulated the pathological matrix metabolic phenotype observed in biomechanical OA models induced by cyclic mechanical stress(10％strain,0.5 Hz,8 h/day for 2 consecutive days).Collectively,we successfully generated a human chondrocyte model with stable PIEZO2 overexpression,which faithfully mirrors mechanotransduction-driven OA progression.This engineered cellular system provides a robust platform for dissecting PIEZO2-mediated mechanosig-naling networks and advancing targeted therapeutic discovery.

Objective To analyze the specific reasons for the suspension and termination of domestic medical device clinical trial projects.Based on the analysis results,provide reference suggestions and improvement measures for all parties in-volved in the trials.Methods Data collection method was used to collect samples of domestic medical device clinical trials,and visits were made to multiple medical institutions.For projects that were suspended or terminated,specific reasons were obtained through on-site interviews with research teams and clinical trial institution staff,reviewing"Project Suspension/Termination Let-ters"stored in the investigator's folder,and telephone consultations with clinical research associates(CRAs)of the projects.A contract research organization(CRO)commercial company was also visited,and specific reasons for project suspension or termi-nation were obtained through on-site interviews or telephone consultations with project managers,CRA-related personnel,etc.Descriptive analysis was used to summarize the reasons for suspension and termination and their rates.Results Statistical analy-sis showed that the suspension and termination rate of medical device clinical trials in China was 17.30％,with a rate of 16.04％in samples collected from medical institutions and 21.30％in samples collected from CRO companies.The reasons leading to the overall suspension and termination of domestic medical device clinical trials included sponsor strategy adjustments,medical insti-tution or research team issues,product or design defects,switching to registration using data from similar products,trial result-re-lated factors,third-party service provider issues,other reasons,safety-related factors,pandemic reasons,regulatory updates,and difficulties in obtaining informed consent.Conclusion The reasons for the suspension and termination of domestic medical de-vice clinical trial projects are complex and diverse,with a statistical analysis showing a rate of 17.30％in China.