Vascular cognitive impairment (VCI), caused by cerebrovascular dysfunction, severely impacts the quality of life in the elderly population, yet effective therapeutic approaches remain limited. Mitophagy, a selective mitochondrial quality-control mechanism, has emerged as a critical focus in neurological disease research. Accumulating evidence indicates that mitophagy modulates oxidative stress, neuroinflammation, and neuronal apoptosis. Key signaling pathways associated with mitophagy—including PINK1/Parkin, BNIP3/Nix, FUNDC1, PI3K/Akt/mTOR, and AMPK—have been identified as potential therapeutic targets for VCI. This review summarizes the mechanistic roles of mitophagy in VCI pathogenesis and explores emerging therapeutic strategies targeting these pathways, aiming to provide novel insights for clinical intervention and advance the development of effective treatments for VCI.

Objective To explore the short-term efficacy of endoscopic submucosal dissection (ESD) in the treatment of early carcinoma in the remnant stomach. Methods A retrospective study was conducted on 45 patients with early residual gastric cancer underwent ESD at the Endoscopy Center of Zhongshan Hospital, Fudan University from December 2014 to April 2024, with a total of 45 lesions. The patients were divided into an anastomotic group (n=15) and a non-anastomotic group (n=30) based on the location of tumor occurrence, and their clinical data, endoscopic diagnosis and treatment, and histopathological conditions were compared between the two groups. Results All 45 patients had lesions with redness and erosion. There were 9 cases of poor lifting of submucosal injection in the anastomotic group and 2 cases in the non-anastomotic group, respectively, and the difference was statistically significant (P<0.05). ESD surgery was performed on 13 lesions in the anastomotic group and 28 lesions in the non-anastomotic group, with surgery times of 80.00 (50.00, 100.00) min and 55.00 (43.75, 80.00) min, respectively. The difference in surgery time between the two groups was statistically significant (P=0.03). Among the 45 patients, ESD surgery achieved curative resection in 35 cases, including 11 cases in the anastomotic group and 24 cases in the non-anastomotic group, with no statistically significant difference. Conclusions Careful preoperative evaluation of early carcinoma in the remnant stomach is essential to prevent oversight. Lesions at anastomotic sites and suture lines present higher technical challenges for complete resection. ESD is safe and effective, with auxiliary traction technique available when necessary.

The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods: This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results: Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = –0.356, p < 0.001 and r = –0.342, p < 0.001, respectively). Physical performance in patients aged <60 years showed significant dose-response relationships with HL. After adjusting for confounders, the odds ratios (95% confidence intervals) for HL across the TUGT quartiles (lowest to highest) were 1.00 (reference), 1.15 (0.73–1.81), 1.69 (1.07–2.70), and 2.87 (1.69–4.88) (p for trend = 0.005). Conclusion: Lower prevalence of HL was associated with a faster TUGT and a stronger handgrip strength in patients on MHD.

ObjectiveTo screen out the extended spectrum beta-lactamase （ESBL）-producing Escherichia coli with the strongest biofilm-forming ability through experiments， and discuss the effect of modified Dayuansan （MDYS） combined with imipenem-cilastatin and cilastatin sodium on the biofilm of E. coli. MethodThe paper diffusion and crystal violet staining methods were used to identify 19 clinically isolated strains of drug-resistant E. coli-induced enzymes and the biofilm-forming ability. The induced enzymes and the E. coli with the strongest biofilm-forming ability were screened out. The minimum inhibitory concentration （MIC） value of MDYS and imipenem-cilastatin and cilastatin sodium was determined by 2，3-bis（2-methoxy-4-nitro-5-sulfophenyl）-2H-tetrazolium-5-carboxamide （XTT） assay. The 1/2， 1/4， and 1/8 MIC of the water extract of MDYS， imipenem-cilastatin and cilastatin sodium alone， and MDYS combined with imipenem-cilastatin and cilastatin sodium was determined by methyl thiazolyl tetrazolium （MTT） assay to obtain the optimum concentration of drugs. BioFlux dynamically observed the effect of the optimum combined drug concentration on the number of bacteria in the biofilm and the biofilm formation of E. coli， and observed the distribution of live/dead bacteria with a laser confocal scanning microscope. Finally， the morphological changes in bacteria after drug treatment were observed statically by scanning electron microscopy. ResultE5E7 strain was ESBL enzyme and the E. coli with the strongest biofilm-forming ability. The results of MTT assay showed that the MIC values of the water extracts of imipenem-cilastatin and cilastatin sodium and MDYS were 1 mg·L^-1 and 250 g·L^-1， respectively. The results of XTT assay showed that compared with the blank group， the 1/2， 1/4， and 1/8 MIC MDYS groups and the combined drug groups significantly decreased the number of bacteria in the biofilm （P<0.01）. The inhibitory effect diminished as the concentration of imipenem-cilastatin and cilastatin sodium decreased. Compared with the imipenem-cilastatin and cilastatin sodium group with the same concentration， the combined drug group improved the inhibitory effect on the number of bacteria in the biofilm （P<0.01）. Compared with the MDYS group with the same concentration， 1/2 MIC imipenem-cilastatin and cilastatin sodium combined with 1/2， 1/4， and 1/8 MIC MDYS， 1/4 MIC imipenem-cilastatin and cilastatin sodium combined with 1/2 and 1/4 MIC MDYS， and 1/8 MIC imipenem-cilastatin and cilastatin sodium combined with 1/2 and 1/4 MIC MDYS decreased the number of bacteria （P<0.05， P<0.01）. The results of BioFlux showed that compared with the blank group， the 1/2 and 1/8 MIC imipenem-cilastatin and cilastatin sodium groups had an insignificant effect on the area of biofilm， whereas the 1/2 and 1/4 MIC MDYS groups significantly decreased the area of biofilm. The results under the scanning electron microscopy showed that as compared with the blank group and the imipenem-cilastatin and cilastatin sodium group， the division cycle was significantly longer under the action of MDYS combined with imipenem-cilastatin and cilastatin sodium. The length of the division cycle in the combined drug group was higher than that in drug alone group. ConclusionIn vitro studies reveal that MDYS combined with commonly-used antibiotics can inhibit the biofilm status of multi-drug resistant E. coli， and MDYS has the effect of enhancing sensitization and inhibiting bacteria with synergistic antibiotics.

Objective:To compare the numerical rating scales (NRS) and Oswestry disability index (ODI) of denosumab in Chinese postmenopausal osteoporosis patients after 3 months, and analyze the early adverse reactions to provide reference for clinical diagnosis and treatment.Methods:Using a prospective study method, 260 patients with postmenopausal osteoporosis who were outpatients and inpatients in the Second Affiliated Hospital of Soochow University from September 2020 to October 2021 were selected, and general information, including age, height, weight, bone mineral density, history of fragility fractures, and use of anti-osteoporosis drugs. All subjects received denosumab 60 mg subcutaneously, and were given calcium and vitamin D at the same time. Pain was scored by NRS before treatment and 3 months after treatment, and functional improvement was assessed by ODI.Results:After 3 months of denosumab treatment in postmenopausal women with osteoporosis, among patients with different age groups, different degrees of osteoporosis, history of fragility fractures, and history of use of anti-osteoporosis drugs, NRS score and ODI score were lower than those before treatment, and the difference was statistically significant ( P<0.05). In addition, in patients with a history of fragility fractures (mainly vertebral fractures), the NRS scores and the ODI score decreased more significantly, and the difference was statistically significant ( P<0.05); the NRS score and ODI score decreased more significantly in patients with severe osteoporosis than in patients with osteoporosis, and the difference was statistically significant ( P<0.05); the BMD value of lumbar spine was negatively correlated with the reduction of NRS score before and after treatment ( P=0.042). In this study, 260 patients had musculoskeletal pain in 6 (2.3%), fatigue in 5 (1.9%), rash in 4 (1.5%), urinary tract infection in 2 (0.7%), and dizziness in 2 (0.7%), 2 case of fever (0.7%), 1 case of hypocalcemia (0.4%), a total of 22 cases of adverse reactions were reported, and the overall adverse reaction rate was 8.5%. Conclusion:Denosumab can improve pain symptoms and functional disability early in the clinical application of Chinese postmenopausal women with osteoporosis, and the incidence of adverse reactions is low. Especially for postmenopausal female osteoporosis patients with severe osteoporosis, low lumbar spine bone density, and a history of fragility fractures (mainly vertebral fractures), the application effect is more significant.

Objective:To explore the relationship between anxiety and mental resilience of caregivers for community-dwelling dementia patients.Methods:Patients in four communities who met the diagnostic criteria for Alzheimer's disease(AD)were randomly selected and their caregivers served as study subjects.General characteristics, anxiety and resilience of caregivers(n=592)were investigated with a questionnaire developed by ourselves, the Generalized Anxiety Disorder-7 Scale(GAD-7), and the Conner-Davidson Resilience Scale(CDRISC).Results:There were 592 subjects in the study, with 185 cases(31.3%)having anxiety.Differences in manifestations of anxiety existed between caregivers for AD patients in different age groups( P<0.01). Anxiety levels were also influenced by AD patient caregivers' gender, educational level and blood relationship to the patient( P<0.05). The differences were reflected in tenacity( F=72.58), strength( F=82.19), optimism( F=12.57)and the total elasticity score( F=162.88). The Spearman correlation was used to analyze the association of caregiver anxiety with caregivers' general characteristics and domains of psychological resilience.The results showed that anxiety was negatively correlated with gender( r=-0.09, P<0.05), education level( r=-0.112, P<0.01), blood relationship( r=-0.122, P<0.01), psychoelasticity and three other domains( r=-0.457, -0.495, -0.208, -0.60, all P<0.01), but was positively correlated with age( r=0.127, P<0.01). Logistic regression analysis showed that psychoelasticity was a protective factor for anxiety in caregivers for community-dwelling AD patients( β=-0.323, P<0.05). Conclusions:While treating Alzheimer's patients, clinicians can consider psychotherapy measures to improve the psychological resilience of their caregivers.

In the original publication, Figure 4G was incorrectly published. The correct version of Figure 4G is presented in this correction. This correction does not affect the conclusions of the paper.

High-voltage-activated (HVA) Ca channels are widely expressed in the nervous system. They play an important role in pain conduction by participating in various physiological processes such as synaptic transmission, changes in synaptic plasticity, and neuronal excitability. Available evidence suggests that the HVA channel is an important therapeutic target for pain management. In this review, we summarize the changes in different subtypes of HVA channel during pain and present the currently available evidence from the clinical application of HVA channel blockers. We also review novel drugs in various phases of development. Moreover, we discuss the future prospects of HVA channel blockers in order to promote "bench-to-bedside" translation.

The present study was designed to examine the therapeutic effects of Botulinum neurotoxin A (BoNT/A) on depression-like behaviors in mice and to explore the potential mechanisms. These results revealed that a single facial injection of BoNT/A induced a rapid and prolonged improvement of depression-like behaviors in naïve and space-restriction-stressed (SRS) mice, reflected by a decreased duration of immobility in behavioral despair tests. BoNT/A significantly increased the 5-hydroxytryptamine (5-HT) levels in several brain regions, including the hippocampus and hypothalamus, in SRS mice. BoNT/A increased the expression of the N-methyl-D-aspartate receptor subunits NR1 and NR2B in the hippocampus, which were significantly decreased in SRS mice. Furthermore, BoNT/A significantly increased the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus, hypothalamus, prefrontal cortex, and amygdala, which were decreased in SRS mice. Finally, BoNT/A transiently increased the levels of phosphorylated extracellular signal-regulated kinase (p-ERK) and cAMP-response element binding protein (p-CREB), which were suppressed in the hippocampus of SRS mice. Collectively, these results demonstrated that BoNT/A treatment has anti-depressant-like activity in mice, and this is associated with increased 5-HT levels and the activation of BDNF/ERK/CREB pathways in the hippocampus, supporting further investigation of BoNT/A therapy in depression.

Objective To evaluate the safety and efficacy of botulinum toxin type A for injection in the treatment of post-stroke upper limb spasticity (dosage was 200 U,or 240 U if combined with thumb spasticity).Methods The study was a multi-center,stratified block randomized,double-blind,placebocontrolled trial.All the qualificd subjects were from 15 clinical centers from September 2014 to February 2016.They were randomized (2∶1) to injections of botulinum toxin type A made in China (200-240 U;n =118) or placebo (n =60) in pivotal phase after informed consent signed.The study was divided into two stages.The pivotal trial phase included a one-week screening,12-week double-blind treatment,followed by an expanded phase which included six-week open-label treatment.The tone of the wrist,finger,thumb flexors was assessed at baseline and at weeks 0,1,4,6,8,12,16 and 18 using Modified Ashworth Scale (MAS),disability in activities of daily living was rated using the Disability Assessment Scale and impaction on pain,muscle tone and deformity was assessed using the Global Assessment Scale.The primary endpoint was the score difference between botulinum toxin type A and placebo groups in the tone of the wrist flexor using MAS at six weeks compared to baseline.Results Muscle tone MAS score in the wrist flexor of botulinum toxin type A and placebo groups at six weeks changed-1.00 (-2.00,-1.00) and 0.00 (-0.50,0.00) respectively from baseline.Botulinum toxin type A was significantly superior to placebo for the primary endpoint (Z =6.618,P ＜ 0.01).The safety measurement showed 10 subjects who received botulinum toxin type A had 13 adverse reactions,with an incidence of 8.47％ (10/118),and three subjects who received placebo had three adverse reactions,with an incidence of 5.00％ (3/60) during the pivotal trial phase.All adverse reactions were mild to moderate,none serious.There was no significant difference in adverse reactions incidence between the botulinum toxin type A and the placebo groups.During the expanded phase three subjects had four adverse reactions and the incidence was 1.95％.All adverse reactions were mild,none serious.Conclusion Botulinum toxin type A was found to be safe and efficacious for the treatment of post-stroke upper limb spasticity.Clinical Trial Registration:China Drug Trials,CTR20131191