Alzheimer's disease (AD), a prototypical neurodegenerative disorder, encompasses multifaceted pathological processes. As pivotal cellular structures within the central nervous system, ion channels play critical roles in regulating neuronal excitability, synaptic transmission, and neurotransmitter release. Extensive research has revealed significant alterations in the expression and function of ion channels in AD, implicating an important role of ion channels in the pathogenesis of abnormal Aβ deposition, neuroinflammation, oxidative stress, and disruptions in calcium homeostasis and neural network functionality. This review systematically summarizes the crucial roles and underlying mechanisms of ion channels in the onset and progression of AD, highlighting how these channel abnormalities contribute to AD pathophysiology. We also discuss the therapeutic potential of ion channel modulation in AD treatment, emphasizing the importance of addressing multifactorial nature and heterogeneity of AD. The development of multi-target drugs and precision therapies is proposed as a future direction of scientific research.
Alzheimer Disease/therapy* ; Humans ; Ion Channels/physiology* ; Oxidative Stress ; Animals ; Amyloid beta-Peptides/metabolism* ; Synaptic Transmission ; Calcium/metabolism*

OBJECTIVE: To explore the safety and effectiveness of separation surgery in patients with neurological symptoms of spinal metastases. METHODS: From January 2020 to December 2022, 14 patients with neurological symptoms of spinal metastases underwent separation surgery, including 7 males and 7 females, aged from 30 to 76 years old with an average of (61.57±12.16) years old. In comparison with eleven patients underwent conservative treatment during the same period, including 6 males and 5 femals, aged from 46 to 88 years old with an average of (66.55±12.32) years old. The changes in visual analogue scale (VAS), Frankel grades, Karnofsky scores, and quality of life score (QOL) before and after treatment were compared between two groups. RESULTS: Fourteen patients in the separation surgery group underwent surgery successfully, with surgery time of (218.57±50.00) minutes and intraoperative blood loss of (864.29±332.97) ml, 2 patients developed delayed hematoma and recovered well finally after emergency surgery, the follow-up time was 3 to 36 months, after separation surgery, the pain was significantly relieved, and neurological function recovered well in the patients. Three months after treatment, the VAS in the separation surgery group (1.43±0.76) scores was significantly lower than that in the conservative treatment group (8.64±0.51) scores (P<0.05);and the Frankel grades, Karnofsky scores, and QOL scores in the separation surgery group were significantly better than those in the conservative treatment group(P<0.05). CONCLUSION For patients with obvious neurological symptoms of spinal metastases, separation surgery not only can rapidly relieve nerve compression but also carry relatively low surgical risks, and improve the quality of life of patients.
Humans ; Female ; Male ; Middle Aged ; Aged ; Spinal Neoplasms/complications* ; Adult ; Aged, 80 and over ; Quality of Life

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

With the improvement of China's socioeconomic status,the issue of aging has become increasingly prominent,making cerebral infarction a common disease among the elderly.In recent years,research on cerebral infarction has gradually deepened,shifting focus from merely protecting and repairing neurons to emphasizing the complex interplay between inflammatory response and autophagy in the brain vascular unit,covering various aspects such as the blood-brain barrier,astrocytes,microglia,and autophagy.This shift in research direction has provided us with a profound understanding of the mechanisms underlying cerebral infarction,offering strong support for innovative future treatment strategies.In this review,we delved into the importance of the interplay between inflammatory response and autophagy in the pathogenesis of cerebral infarction,emphasized the intricate interactions among these biological components,which might lay the groundwork for more effective managements and treatments of cerebral infarction.By comprehensively reviewing existing literatures,we proposed future research directions,aiming to provide more scientific and systematic guidance for the clinical management and treatment of cerebral infarction.

Objective:To investigate the current situation and correlation of perceived social support,achievement motivation,and depression among nursing graduates of a medical college in Anhui Province.Methods:A convenient sampling method was used to select 286 graduates from the School of Nursing in a medical college in Anhui Province as the research subjects.They were investigated using a general information questionnaire,the Perceived Social Support Scale,the Achievement Motivation Scale,and the Self-Rating Depression Scale.SPSS 23.0 and SPSS process plug-in were used to conduct correlation analysis and mediation effect test.Results:Perceived social support and achievement motivation were negatively correlated with depression(r=-0.413,-0.306,P＜0.01).Perceived social support was positively correlated with achievement motivation(r=0.323,P＜0.01).Achievement motivation partially mediated the relationship between perceived social support and depression,with a mediating effect of 14.99%of the total effect.Conclusion:The perceived social support among nursing graduates can have a direct impact on depression,and can also predict depression through the indirect effect of achievement motivation.

Twelve compounds were isolated from the ethyl acetate fraction of the 80% aqueous ethanol extract of the roots and stems of Dalbergia rimosa Roxb. by silica gel, MCI, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Their structures were identified by spectral analysis such as UV, IR, MS, 1D/2D NMR and by comparison with literature information as dalbergiquinol A (1), dalbergiquinol B (2), R-(-)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol (3), neokhriol A (4), mucronulatol (5), (3R)-7,2′,3′-trihydroxy-4′-methoxy-isoflavane (6), isomucronulatol (7), (3S)-violanone (8), 3′-O-methylviolanone (9), eryvarin M (10), (±)-α,3,4,2′,4′-pentahydroxydihydrochalcone (11) and (-)-butin (12). Compound 1 and 2 are new compounds, and compounds 3-12 were isolated from this plant for the first time. Compounds 1, 2, 4, 6, 8, 11, 12 showed good scavenging effect on DPPH free radical.

Objective:Super-enhancer-associated genes may be closely related to the progression of osteosarcoma,curcumin exhibits a certain inhibitory effect on tumors such as osteosarcoma.This study aims to investigate the effects of curcumin on osteosarcoma in vitro and in vivo,and to determine whether curcumin can inhibit the progression of osteosarcoma by suppressing the expression of super-enhancer-associated genes LIM and senescent cell antigen-like-containing domain 1(LIMS1),secreted protein acidic and rich in cysteine(SPARC),and sterile alpha motif domain containing 4A(SAMD4A). Methods:Human osteosarcoma cell lines(MG63 cells or U2OS cells)were treated with 5 to 50 μmol/L curcumin for 24,48,and 72 hours,followed by the methyl thiazolyl tetrazolium(MTT)assay to detect cell viability.Cells were incubated with dimethyl sulfoxide(DMSO)or curcumin(2.5,5.0 μmol/L)for 7 days,and a colony formation assay was used to measure in vitro cell proliferation.After treatment with DMSO or curcumin(10,15 μmol/L),a scratch healing assay and a transwell migration assay were performed to evaluate cell migration ability.Real-time reverse transcription polymerase chain reaction(real-time RT-PCR)and Western blotting were used to detect mRNA and protein expression levels of LIMS1,SPARC,and SAMD4A in the cells.An osteosarcoma-bearing nude mouse model was established,and curcumin was administered via gavage for 14 days to assess the impact of curcumin on tumor volume and weight in vivo.Real-time RT-PCR was used to measure mRNA expression levels of LIMS1,SPARC,and SAMD4A in the cancer and adjacent tissues from 12 osteosarcoma patients. Results:After treating cells with different concentrations of curcumin for 24,48,and 72 hours,cell viability were all significantly decreased.Compared with the DMSO group,the colony formation rates in the 2.5 μmol/L and 5.0 μmol/L curcumin groups significantly declined(both P＜0.01).The scratch healing assay showed that,compared with the DMSO group,the migration rates of cells in the 10 μmol/L and 15 μmol/L curcumin groups were significantly reduced.The exception was the 10 μmol/L curcumin group at 24 h,where the migration rate of U2OS cells did not show a statistically significant difference(P＞0.05),while all other differences were statistically significant(P＜0.01 or P＜0.001).The transwell migration assay results showed that the number of migrating cells in the 10 μmol/L and 15 μmol/L curcumin groups was significantly lower than that in the DMSO group(both P＜0.001).In the in vivo tumor-bearing mouse experiment,the curcumin group showed a reduction in tumor mass(P＜0.01)and a significant reduction in tumor volume(P＜0.001)compared with the control group.Compared with the DMSO group,the mRNA expression levels of LIMS1,SPARC,and SAMD4A in the 10 μmol/L and 15 μmol/L curcumin groups were significantly down-regulated(all P＜0.05).Additionally,the protein expression level of LIMS1 in U2OS cells in the 10 μmol/L curcumin group was significantly lower than that in the DMSO group(P＜0.05).Compared with adjacent tissues,the mRNA expression level of SPARC in osteosarcoma tissues was significantly increased(P＜0.00l),while the mRNA expression levels of LIMS1 and SAMD4A did not show statistically significant differences(both P＞0.05). Conclusion:Curcumin inhibits the proliferation and migration of osteosarcoma both in vitro and in vivo,which may be associated with the inactivation of super-enhancer-associated gene LIMS1.

Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.

Genitourinary tract malignant lymphoma is rare, and primary malignant lymphoma of the lower urinary tract is even rarer. This article reported a female patient with primary diffuse large B-cell lymphoma in the urethra. The patient was admitted due to progressive dysuria, because ultrasound indicated a lesion in the urethra, transurethral resection of the lesion was performed, which revealed diffuse large B-cell lymphoma of the urethra. R-CHOP chemotherapy regimen of four cycles was performed after surgery, and urination symptoms relieved. There was no recurrence or metastasis after 6 months of follow-up.

AIM To study the lignans and terpenoids from Alangium chinense(Lour.)Harms subsp.pauciflorum Fang.METHODS The 70%ethanol extract was isolated and purified by various column chromatography,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Twenty-four compounds were isolated and identified and identified as(+)-pinoresinol)(1),medioresinol(2),syringaresinol(3),dehydrodiconifery alcohol-9′-β-D-glucopyranoside(4),7,9,9′-trihydroxy-3,3′-dimethoxy-8-O-4′-neolignan-4-O-β-D-glucopyranoside(5),citrusin B(6),dihydrodehydrodiconiferyl alcohol-4-O-β-D-glucopyranosides(7),5-methoxy-(+)-isolariciresinol(8),rel-(7R,8S)-3,3′,5-trimethoxy-4′,7-epoxy-8,5′-neolignan-4,9,9′-triol-9-β-D-glucopyranoside(9),(+)-lyoniresinol-3α-O-β-D-glucopyranoside(10),longifloroside B(11),(7S,8R)-1-[4-O-(β-D-glucopyranosyl)-3-methoxyphenyl]-2-[4-(3-hydroxypropyl)-2,6-dimethoxyphenoxy]-1,3-propanediol(12),(7R,8S)-4,9,9′-trihydroxyl-3-methoxyl-7,8-dihydrobenzofuran-1′-propylneolignan-3′-O-β-D-glucopyranoside(13),(7S,8R)-4,9,9′-trihydroxy-3,3′,5-trimethoxy-8,4′-oxy-neolignan-4-O-β-D-glucopyranoside(14),cedrusin-4-O-β-D-glucopyranoside(15),2,6,2′,6′-tetramethoxy-4,4′-bis(2,3-epoxy-1-hydroxypropyl)biphenyl(16),3-oxo-11α,12α-epoxy-olean-28,13β-olide(17),mansonone E(18),mansonone G(19),mansonone H(20),roseoside(21),bullatantriol(22),3-O-α-L-arabinopyranosyl-28-O-β-D-glucopyranosyl pomolic acid(23),Hederagenin(24).CONCLUSION Compounds 1-16 are lignans,and 17-24 are terpenoids.Compounds 3-9,11-17,22-24 are isolated from Alangium genus for the first time;compounds 1,2,10,18-21 are first isolated from this plant.