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 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.

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.

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.

Despite growing prevalence and incidence, the management of gout remains suboptimal. The intermittent nature of the gout makes the long-term urate-lowering therapy (ULT) particularly important for gout management. However, patients are reluctant to take medication day after day to manage incurable occasional gout flares, and suffer from possible long-term toxicity. Therefore, a safe and easy-to-operate drug delivery system with simple preparation for the long-term management of gout is very necessary. Here, a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal. This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention. Furthermore, its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models. Besides, the drug co-delivery system could help avoid long-term daily oral colchicine, a drug with a narrow therapeutic index. This system also avoids mass injection of uricase by improving its stability, enhancing the clinical application value of uricase. In general, this two-drug system reduces the dosage of uricase and colchicine and improves the patient's compliance, which has a strong clinical translation.

Objective To investigate the impact of usnic acid on neuronal necroptosis in rats with cerebral infarction by regulating the receptor-interacting protein kinase 1(RIPK1)/receptor-interacting protein kinase 3(RIPK3)/mixed lineage kinase domain-like protein(MLKL)signaling pathway.Methods The rat model of cerebral infarction was established by middle cerebral artery occlusion and reperfusion(MCAO/R).The successfully modeled rats were divided into model group,NEC-1(RIP1 inhibitor)group,low-,medium-,and high-dose of usnic acid groups,with 20 rats in each group.Another 20 rats were selected as a sham-operation group.After 3 days of drug intervention,the modified Neurological Severity Scale(mNSS)was applied to evaluate the degree of neurological damage of rats in each group.TTC staining was applied to detect the volume of cerebral infarction.HE staining was selected to observe pathological damage in brain tissue.PI/NeuN staining was selected to observe neuronal necrosis.RT-qPCR was used to detect mRNA levels of RIPK1,RIPK3 and MLKL in rat ischemic brain tissue.Western Blot was used to determine the expressions of RIPK1/RIPK3/MLKL signaling pathway related proteins in rat ischemic brain tissue.Results Compared with the sham-operation group,the neural cells in the model group showed structural damage,cell disrupted,deformation,and nuclear pyknosis,furthermore,the mNSS score,the cerebral infarction volume,proportion of PI-positive neurons were significantly increased(P＜0.05).The mRNA levels of RIPK1,RIPK3,MLKL in brain tissue,ratio of p-RIPK1/RIPK1,and the levels of RIPK3 and MLKL proteins were obviously increased(P＜0.05).Compared with the model group,the damage degree of neurocyte morphology in the low-,medium-,and high-dose of usnic acid groups was gradually alleviated,the nuclear membrane was gradually became clear,and the cell body was gradually returned to normal.The neurocyte morphology in the NEC-1 group was basically intact,and the nuclear membrane was basically clear.The mNSS score,cerebral infarction volume and proportion of PI-positive neurons in NEC-1 group and usnic acid groups were significantly decreased(P＜0.05).The mRNA levels of RIPK1,RIPK3,MLKL,ratio of p-RIPK1/RIPK1,and levels of RIPK3 and MLKL proteins in brain tissue were obviously reduced in usnic acid groups and NEC-1 group.Also,there was dose-dependent decrease in usnic acid groups(P＜0.05).No statistically obvious difference was found between the high-dose usnic acid group and the NEC-1 group(P＞0.05).Conclusion Usnic acid inhibits neuronal necroptosis in rats with cerebral infarction by inhibiting the RIPK1/RIPK3/MLKL signaling pathway,thereby alleviating brain injury in rats with cerebral infarction.

OBJECTIVE To provide reference and suggestions for dynamic adjustment of classification management lists for clinical use of antibiotics and the promotion of rational use of antibiotics. METHODS The latest version of provincial classification management lists for clinical use of antibiotics were aggregated into the “national list”， which was compared with 2021 WHO AWaRe classification list of antibiotics （hereinafter referred as to “AWaRe classification list”） to make a descriptive statistical analysis about the number of different classes of antibiotics in the two lists and their differences. RESULTS Based on the different classification principles， 262 kinds of antibiotic preparations in the national list were classified into non-restricted （84）， restricted （83） and highly-restricted classes （95）， and 258 kinds in the AWaRe classification list were classified into access （87）， watch （142） and reserve classes （29）； 182 kinds of antibiotic preparations were both included in the two lists. In the national list， among the non-restricted antibiotic preparations， 36 kinds belonged to access class， 30 belonged to watch class and 1 belonged to reserve class； among restricted antibiotic preparations， 7 belonged to access class， 46 kinds belonged to watch class and 3 belonged to reserve class； among highly-restricted antibiotic 82805019。E-mail：yyy211anne@163.com preparations， 9 belonged to access class， 35 belonged to watch class and 15 kinds belonged to reserve class. Among them， 91 kinds of antibiotic preparations were not recommended by WHO （20 kinds） or not included in the AWaRe classification list （71 kinds）. CONCLUSIONS The classification methods of two lists are different in classification principles and grading of some similar drugs. The classification management list of antibiotics is one of the key points of antibiotics management， more research is needed in the future to provide sufficient evidence for optimizing antibiotics classification management.