BACKGROUND: The use of potentially inappropriate medications (PIMs) is a major concern for medication safety as it may entail more harm than potential benefits for older adults. This study aimed to explore the prescribing rate, healthcare utilization, and expenditure of older adults using PIMs in China. METHODS: A cross-sectional analysis was conducted using a national representative database of all medical insurance beneficiaries across China, extracting ambulatory visit records of adults aged 65 years and above between 2015 and 2017. Descriptive analysis was conducted to measure the rate of patients exposed to PIM, prescribing rate of each PIM, average annual outpatient visits per patient, average total medication costs for each visit, average annual cost of PIMs for each patient, and average annual medication costs for each patient. Generalized linear model with logit link function and binomial distribution was used to examine the adjusted associations between PIMs and independent variables. RESULTS: In total, 845,278 (33.2%) participants were identified to be exposed to at least one PIM. Patients aged 75-84 years (38.1%, 969,809/2,545,430) and ≥85 years (37.9%, 964,718/2,545,430) were more likely to be prescribed with PIMs. Beneficiaries of the Urban Employee Basic Medical Insurance (UEBMI) and living in eastern and southern regions were more frequently prescribed with PIMs. Compared with patients without PIM exposure (7.5 visits, drug cost of RMB 1545.0 Yuan), patients with PIM exposure showed higher adjusted average annual number of outpatient visits (10.7 visits, β = 3.228, 95% confidence interval [CI] = 3.196-3.261) and higher annual drug costs (RMB 2461.8 Yuan, Coef. = 916.864, 95% CI = RMB 906.292-927.436 Yuan). CONCLUSIONS The results showed that the use of PIM among older adults was common in China. This study suggests that the use of PIM could be considered as a clear target, pending multidimensional efforts, to promote rational prescribing for older adults.
Humans ; Aged ; Cross-Sectional Studies ; Aged, 80 and over ; Male ; Female ; China ; Inappropriate Prescribing/economics* ; Patient Acceptance of Health Care/statistics & numerical data* ; Potentially Inappropriate Medication List/statistics & numerical data* ; Health Expenditures/statistics & numerical data*

BACKGROUND: Bile acids (BAs) facilitate the progression of gastric intestinal metaplasia (GIM). Long non-coding RNAs (lncRNAs) dysregulation was observed along with the initiation of gastric cancer. However, how lncRNAs function in GIM remains unclear. This study aimed to explore the role and mechanism of lncRNA PVT1 in GIM, and provide a potential therapeutic target for GIM treatment. METHODS: We employed RNA sequencing (RNA-seq) to screen dysregulated lncRNAs in gastric epithelial cells after BA treatment. Bioinformatics analysis was conducted to reveal the regulatory mechanism. PVT1 expression was detected in 21 paired biopsies obtained under endoscopy. Overexpressed and knockdown cell models were established to explore gene functions in GIM. Molecular interactions were validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (Ch-IP). The levels of relative molecular expression were detected in GIM tissues. RESULTS: We confirmed that lncRNA PVT1 was upregulated in BA-induced GIM model. PVT1 promoted the expression of intestinal markers such as CDX2 , KLF4 , and HNF4α . Bioinformatics analysis revealed that miR-34b-5p was a putative target of PVT1 . miR-34b-5p mimics increased CDX2 , KLF4 , and HNF4α levels. Restoration of miR-34b-5p decreased the pro-metaplastic effect of PVT1 . The interactions between PVT1 , miR-34b-5p, and the downstream target HNF4α were validated. Moreover, HNF4α could transcriptionally activated PVT1 , sustaining the GIM phenotype. Finally, the activation of the PVT1 /miR-34b-5p/ HNF4α loop was detected in GIM tissues. CONCLUSIONS BAs facilitate GIM partially via a PVT1/miR-34b-5p/HNF4α positive feedback loop. PVT1 may become a novel target for blocking the continuous development of GIM and preventing the initiation of gastric cancer in patients with bile reflux.
Humans ; RNA, Long Noncoding/metabolism* ; MicroRNAs/metabolism* ; Hepatocyte Nuclear Factor 4/genetics* ; Bile Acids and Salts ; Kruppel-Like Factor 4 ; Metaplasia/metabolism*

Objective:To evaluate the potential causal relationship between tinnitus and the risk of Alzheimer's disease(AD)onset using the two-sample Mendelian randomization(MR)method and to clarify its mechanism of action,so as to provide new ideas for early warning of AD.Methods:Genome-wide association study(GWAS)database was used to search the keywords"tinnitus"and"Alzheimer"to obtain the related datasets of exposure factor tinnitus and outcome AD;the tinnitus datasets included ukb-d-4803_11,ukb-d-4803_12,ukb-d-4803_13,ukb-b-14254 and ukb-a-384;the AD datasets included ieu-b-5067,ieu-b-2,ieu-a-297,ebi-a-GCST90027158 and ebi-a-GCST002245.The single nucleotide polymorphisms(SNPs)closely and independently associated with tinnitus were screened as instrumental variables(IVs),and the SNPs associated with AD were used as outcomes.Inverse variance weighted(IVW)method was used to conduct MR analysis to evaluate its odds ratio(OR)value,95%confidence interval(CI)and P value;P<0.05 indicated significant causal relationship.Sensitivity detection used Cochran's Q test to detect the heterogeneity of IVs to evaluate its Q value,df value and P value;when IVW method P>0.05,it indicated no significant heterogeneity;MR-Egger intercept was used to detect horizontal pleiotropy;when the intercept was 0 or close to 0 and P>0.05,it indicated no significant horizontal pleiotropy;meanwhile,leave-one-out method was used for sensitivity analysis.Finally,visualization results were performed using forest plot,scatter plot,funnel plot and leave-one-out plot.Results:A total of 286 SNPs were screened as IVs.All instrumental variables satisfied F>10,suggesting no weak instrumental variable;after screening by PhenoScanner web tool,all SNPs were unrelated to confounding factors.When the tinnitus and AD datasets were ukb-d-4803 and ebi-a-GCST90027158 respectively,there was a significant positive correlation between tinnitus and the risk of AD onset(IVW:OR=1.842,95%CI:1.065-3.188,P=0.029);Cochran's Q test suggested no significant heterogeneity of IVs(Q=9.788,df=10.000,P=0.459);MR-Egger intercept indicated no horizontal pleiotropy(Egger intercept=-0.006,P=0.147);leave-one-out method showed stable results,and no SNP with significant influence on the results was detected.Conclusion:There is a positive causal relationship between tinnitus and the risk of AD onset.Neuroinflammation accompanied by persistent microglial activation to varying degrees may be the common pathogenesis of tinnitus and AD;in addition,depression may also act as an upstream factor to hyperactivate the hypothalamic-pituitary-adrenal(HPA)axis,leading to the progression of relationship between tinnitus and AD.

Objective To systematically integrate the best evidence on pulmonary rehabilitation nursing for patients with tracheostomy after stroke(TAS),so as to provide evidence-based basis for clinical practice.Methods Following evidence-based medicine principles,we conducted a systematic search of literatures related to pulmonary rehabilitation nursing for patients with TAS in databases including UpToDate,BMJ Best Practice,PubMed,China National Knowledge Infrastructure(CNKI),Wanfang Database,VIP Database,and China Biology Medicine(CBM).Literature types included guidelines,expert consensus,systematic reviews,meta-analyses,evidence summaries,and original studies,with the search period spanning from the inception of the database to Jan.2025.Two researchers independently assessed the quality of the included literatures using standardized tools such as Appraisal of Guidelines for Research and Evaluation-Ⅱ and Joanna Briggs Institute tools,followed by grading and synthesizing evidences meeting the criteria.Results A total of 20 articles were included,including 6 guidelines,5 expert consensuses,4 meta-analyses,3 clinical decision-making papers,1 systematic review,and 1 randomized controlled trial.A total of 32 recommendations were formed,covering 6 dimensions:airway management(8 items),comprehensive pulmonary rehabilitation training(8 items),basic treatment(5 items),safety management(4 items),extubation nursing(3 items)and prevention of complications during the peri-extubation period(4 items).The evidence grades ranged from grade A(strong recommendation)to grade B(recommendation).Conclusion This study systematically synthesizes core elements of pulmonary rehabilitation nursing for patients with TAS through evidence-based methodology.The established multidimensional evidence framework provides scientific guidance for improving respiratory function,reducing complications,and optimizing extubation decisions.Clinicians are advised to adapt these recommendations to local contexts for practical implementation.

Acute ischemic stroke is the most common type of stroke, characterized by high mortality, disability, and recurrence rates. Intravenous thrombolysis is the core treatment method. Among them, alteplase is effective as the standard drug, but it has limitations such as narrow time window, high risk of bleeding, and the need for continuous infusion. The new generation of improved drug tenecteplase has the advantages of single intravenous injection and higher fibrin specificity, making it a potential alternative drug to alteplase. In addition, endovascular therapy compensates for the low recanalization rate of large vessel occlusion on the basis of intravenous thrombolysis. This article reviews the clinical progress of teneplase in the treatment of acute ischemic stroke, aiming to provide reference for optimizing the treatment plan of acute ischemic stroke.

BACKGROUND:Tendinopathy is a musculoskeletal disorder characterized by pain and decreased mobility,with pathological changes of disturbed collagen and hyperplasia of the vasculature.Tendinopathy tends to occur in athletes,physical workers,and the elderly.One of the mechanisms of tendinopathy is the"failed healing response",and part of what causes the failed healing response is the erroneous differentiation of tendon stem/progenitor cells. OBJECTIVE:By reviewing the relevant literature,we introduce the characteristics of tendon stem/progenitor cells,summarize the factors that affect the differentiation of tendon stem/progenitor cells to tendon cells and those that lead to mis-differentiation of tendon stem/progenitor cells(differentiation to adipocytes,osteocytes and chondrocytes),and also describe the limitations of tendon stem/progenitor cells in clinical applications. METHODS:PubMed and Web of Science databases were searched for the terms"tendon stem/progenitor cells,tendinopathy,tendon injury,differentiation".The relevant literature was screened by reading and 109 articles were included for the analysis of the results. RESULTS AND CONCLUSION:(1)Tendon stem/progenitor cells are a type of stem cells that can spontaneously differentiate into tendons and have the ability to self-renew,clone,and multi-differentiate.Various external conditions acting on tendon stem/progenitor cells can lead them to differentiate in diverse directions.The specific factors that regulate the fate of tendon stem/progenitor cells are not known with certainty.When stem cell renewal and differentiation in tendons becomes abnormal,it can lead to failure of tendon healing and consequently to tendinopathy.(2)Aging,changes in extracellular matrix composition,excessive mechanical stimulation,prostaglandin E2 and interleukin-6 as well as interleukin-10 and some systemic diseases may be important in regulating the mis-differentiation of tendon stem/progenitor cells.(3)Possible favorable factors that promote the differentiation of tendon stem/progenitor cells to tenocytes are:some growth factors and cytokines,moderate mechanical stimulation and topography of the extracellular matrix,low oxygen tension,drugs,and several transcriptional genes and proteins.(4)The most desirable therapeutic tools are the regulation of endogenous tendon stem/progenitor cells or the stimulation of endogenous tendon stem/progenitor cell proliferation and differentiation by exogenous tendon stem/progenitor cells.(5)Understanding the factors that regulate mis-differentiation of tendon stem/progenitor cells may provide insight into the pathogenesis of tendinopathy and identify therapeutic targets.Elaborating on the induction of tendon stem/progenitor cell differentiation into tendons could facilitate their use in tissue engineering.

Objective:To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China.Methods:The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia.Results:The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% ( HR=1.22, 95% CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% ( HR=0.67, 95% CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion:Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

Objective To explore the effects of wogonin on cognitive function and neuroinflamma-tion in VaD rats by regulating AMPK/SIRT1 pathway.Methods 90 VaD rats were randomly di-vided into model group,low-,medium-and high-dose wogonin groups(50,100,200 mg/kg),and high dose+AMPK inhibitor(20 mg/kg)group,18 animals per group.Another 18 normal rats served as sham operation group.ELISA was utilized to measure the contents of IL-1β,TNF-α and IL-6 in hippocampal tissues.Western blotting was conducted to detect the expression of Iba-1,p-AMPK,AMPK and SIRT1 in hippocampal tissues.Results Compared with the sham operation group,the model group had longer escape latency,and elevated contents of IL-1β,TNF-α and IL-6,number of Iba-1 positive cells and expression level of Iba-1 protein in hippocampal tissue,shorter stay time at original platform,and lower expression of p-AMPK/AMPK and SIRT1 in hippocampal tissues(P＜0.05).Treatment of three doses of wogonin,in a dose-dependent man-ner,reduced escape latency,and decreased levels of IL-1β,TNF-α and IL-6,number of Iba-1 posi-tive cells and expression of Iba-1 protein in hippocampal tissue,but longer stay time at original platform,and enhanced expression of p-AMPK/AMPK and SIRT1 protein in hippocampal tissue when compared with the model group(P＜0.05).The high dose+AMPK inhibitor group showed longer escape latency(47.64±5.39 s vs 26.45±3.27 s),shorter stay time at original platform(21.78±3.51 s vs 35.22±5.02 s),increased levels of IL-1β,TNF-α and IL-6,number of Iba-1 positive cells and expression of Iba-1 protein in hippocampal tissue,and lower expression levels of p-AMPK/AMPK and SIRT1 in hippocampal tissue when compared with the high-dose group(P＜0.05).Conclusion Wogonin may improve cognitive function and hippocampal tissue patho-logical damage in VaD rats by activating the AMPK/SIRT1 pathway,and inhibit neuroinflammation.

Objectives:To compare the biomechanical effects on the cervical spine between the insertion of a cervical interfacet self-locking cage(CILC)for anterior cervical interbody fusion and the insertion of a Zero-profile anterior cervical interbody fusion device(Zero-P)through the finite element method.Methods:Extracting the thin-layer cervical CT scan data of a 24-year-old male volunteer,and excluding any history of cervical spine trauma,surgery,cervical spondylosis,and imaging-diagnosed cervical spine deformities.Establishing a three-dimensional finite element model(blank model)of the normal lower cervical spine.The validity of the model was verified by comparing the range of motion(ROM)with those reported in previous studies.Based on this model,finite element models were constructed for single-segment posterior CILC insertion and fusion and Zero-P insertion and fusion.The surgical segment was set as the C4/5 segment,and CILC and Zero-P were implanted respectively to fuse and construct model.The lower endplate of the C7 vertebral body was fixed,and an axial load of 73.6N was applied to simulate the head's weight.A 1.0N·m torque was applied to the upper surface of the C2 vertebral body to simulate the overall movement of the C2-C7 finite element models,including flexion,extension,lateral bending,and axial rotation.The ROM of the segment and the stress changes in the adjacent segment intervertebral discs and facet joints were analyzed in all four motion directions for the blank model,CILC model,and Zero-P model.Results:The ROMs of the established three-dimensional finite element model of the lower cervical spine in all motion directions were consistent with previously published studies,therefore its validity was verified.Compared with the blank mod-el,the ROMs in all directions of the fusion segment was significantly reduced in both the CILC and Zero-P models.The ROM of the adjacent segments and the peak stress in the intervertebral discs and facet joints of the adjacent segments were higher in all motion directions compared with the blank model,with no significant difference in the degree of ROM increase between the CILC and Zero-P models.The peak stress increase in the intervertebral discs of adjacent segments in the CILC model was smaller than that in the Zero-P model.In the CILC model,the peak stress values of the C3/4 segment during flexion,extension,lateral bending,and rotation increased from pre-fixation values of 2.181,3.358,3.636,and 3.950MPa to post-fixation values of 2.532,3.881,4.463,and 4.917MPa,respectively.The peak stress values of the C5/6 segment during flexion,extension,lateral bending,and rotation increased from pre-fixation values of 1.558,3.996,3.778,and 3.660 MPa to post-fixation values of 1.864,4.131,4.183,and 4.266MPa,respectively.In the Zero-P model,the peak stress values of the C3/4 segment during flexion,extension,lateral bending,and rotation increased from preoperative values of 2.181,3.358,3.636,and 3.950MPa to 2.977,4.241,4.654,and 5.509MPa,respectively.The peak stress values of the C5/6 segment during flexion,extension,lateral bending,and rotation increased from pre-fixation values of 1.558,3.996,3.778,and 3.660MPa to post-fixation values of 2.314,5.214,4.469,and 4.739MPa,respectively.The peak stress increase in the adjacent facet joints in all motion directions was greater in the CILC model than in the Zero-P model.Conclusions:CILC insertion results in less impact on adjacent segment disc stress compared to Zero-P and provides reliable fixation,making it a suitable option for treating adjacent segment disease after cervical surgery.

OBJECTIVES: The magnesium depletion score (MDS) is considered more reliable than traditional approaches for predicting magnesium deficiency in humans. We explored the associations of MDS and dietary magnesium intake with diabetes. METHODS: We obtained data from 18,853 participants in the National Health and Nutrition Examination Survey 2011-2018. Using multivariate regression and stratified analysis, we investigated the relationships of both MDS and magnesium intake with diabetes. To compute prevalence ratios (PRs), we employed modified Poisson or log-binomial regression. We characterized the non-linear association between magnesium intake and diabetes using restricted cubic spline analysis. RESULTS: Participants with MDS ≥2 exhibited a PR of 1.26 (95% confidence interval [CI], 1.19 to 1.34) for diabetes. Per-standard deviation (SD) increase in dietary magnesium intake was associated with a lower prevalence of diabetes (PR, 0.91; 95% CI, 0.87 to 0.96). Subgroup analyses revealed a positive association between MDS ≥2 and diabetes across all levels of dietary magnesium intake, including the lowest (PR, 1.35; 95% CI, 1.18 to 1.55), middle (PR, 1.23; 95% CI, 1.12 to 1.35), and highest tertiles (PR, 1.25; 95% CI, 1.13 to 1.37; pinteraction<0.001). Per-SD increase in magnesium intake was associated with lower diabetes prevalence in participants with MDS <2 (PR, 0.92; 95% CI, 0.87 to 0.98) and those with MDS ≥2 (PR, 0.91; 95% CI, 0.84 to 0.98; pinteraction=0.030). CONCLUSIONS MDS is associated with diabetes, particularly among individuals with low magnesium intake. Adequate dietary magnesium intake may reduce diabetes risk, especially in those with high MDS.