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*

Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Objective To investigate the relationship between ferroptosis-related genes[heme oxygenase-1(HO-1),solute carrier family 7 member 11(SLC7A11),and long-chain acyl-coenzyme A synthetase 4(ACSL4)]expression and cardiovascular events in patients with chronic renal failure(CRF),aiming to pro-vide clinical insights for risk assessment of cardiovascular complications.Methods A total of 124 CRF pa-tients(CRF group)admitted to the hospital from January 2020 to January 2023 and 124 healthy people(con-trol group)who underwent physical examination in the hospital during the same period were selected as the research objects.The levels of ferroptosis-related gene HO-1,SLC7A11 and ACSL4 were detected and com-pared between the two groups.CRF patients were followed up for 12 months after discharge,and they were di-vided into concurrent group(n=56)and non-concurrent group(n=66)according to the occurrence of cardio-vascular events.Spearman correlation analysis was used to investigate the correlation between iron death relat-ed genes HO-1,SLC7A11,ACSL4 and cardiovascular events in CRF patients.Univariate and multivariate Lo-gistic regression analysis were used to investigate the influencing factors of cardiovascular events in CRF pa-tients.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of iron death re-lated genes HO-1,SLC7A11,and ACSL4 for cardiovascular events in CRF patients.Results Serum HO-1 and SLC7A11 levels in CRF group were lower than those in control group(P＜0.05),and the ACSL4 level was higher than that in control group(P＜0.05).The serum HO-1 and SLC7A11 levels in concurrent group were lower than those in non-concurrent group(all P＜0.05),and the serum ACSL4 level was higher than that in non-concurrent group(P＜0.05).Ferroptosis-related genes HO-1 and SLC7A11 were negatively correlated with cardiovascular events(r=-0.708,—0.721,P＜0.05),while ACSL4 was positively correlated with car-diovascular events(r=0.699,P＜0.05).High serum ACSL4 expression and high cTnT level were risk fac-tors for cardiovascular events in CRF patients(P＜0.05),and high hemoglobin level and high serum HO-1 and SLC7A11 expression were protective factors for cardiovascular events in CRF patients(P＜0.05).ROC curve analysis results showed that the area under the curve(AUC)of serum HO-1,SLC7A11,ACSL4,hemo-globin and cTnT alone for predicting cardiovascular events in CRF patients were 0.787,0.735,0.773,0.651 and 0.782,respectively.The AUC of the combined prediction of ferroptosis-related genes was 0.837,and the AUC of the combined application of five factors was 0.880.According to Delong's test,the AUC of both com-bined application models was significantly higher than those of individual application(P＜0.05).The nomo-gram model showed that all ferroptosis-related genes were positively expressed(HO-1＜1.5,SLC7A11＜1.15,ACSL4≥2.75),and the risk of developing concurrent cardiovascular events in CRF patients could reach over 75％.Conclusion The expression of serum HO-1 and SLC7A11 in CRF patients is decreased,and the ACSL4 expression is increased,which is closely related to cardiovascular events,and the combined detection of three indexes has high value in predicting cardiovascular events in CRF patients.

Objective To establish a 13C isotope-labeled hyperinsulinemic-euglycemic clamp model for the assessment of insulin sensitivity in mice.Methods The mouse model of insulin resistance was established by high-fat diet feeding.The phosphorylation level of downstream insulin signaling protein,Protein Kinase,also known as Akt was assessed.Glucose metabolism was evaluated using glucose tolerance test,insulin tolerance test,and pyruvate tol-erance tests and the area under the curve of the respective testes over 2 hours was calculated to quantify overall blood glucose level.Mice underwent jugular vein catheterization surgery,and a 13C isotope-labeled hyperinsulinemic-eugly-cemic clamp experiment was conducted to monitor blood glucose levels and to calculate the glucose infusion rate(GIR).Tail vein serum was collected for liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis to determine glucose disposal rate(GDR)and hepatic gluconeogenesis rate(HGP).Following the inhibition of glycog-enolysis in mice,Akt phosphorylation level was measured to evaluate insulin signaling.The clamp test was repeated to calculate GIR,and tail vein blood serum was analyzed by LC-MS/MS to determine GDR and HGP.Results After one week of high-fat diet feeding,mice exhibited significantly elevated blood glucose level(P＜0.001)accompanied by reduced p-Akt level in liver and muscle.Glucose tolerance tests,insulin tolerance tests and pyruvate tolerance test demonstrated a significant increase in blood glucose level(P＜0.05)and a higher area under curves(AUC)(P＜0.001)in high-fat-fed mice.During the 13C-labeled hyperinsulinemic-euglycemic clamp experiment,after the blood glucose levels were stable,the GIR of high-fat-fed mice was significantly reduced(P＜0.001),GDR was de-creased(P＜0.0001)and hepatic gluconeogenesis rate was increased(P＜0.01).After pharmacological inhibition of glycogenolysis,mice showed elevated blood glucose level(P＜0.001)and further reductions in p-Akt level in liver and muscle.The 13C-labeled clamp experiment revealed that in the treated group,the GIR decreased(P＜0.01)while GDR was reduced(P＜0.000 1)and HGP increased(P＜0.01).Conclusions An improved hyperinsulinemic-eugly-cemic clamp model was developed to assess insulin sensitivity in mice.

Objective:To compare the antiplatelet effects of vicagrel and clopidogrel in patients with different cytochrome P450 (CYP) 2C19 genotypes.Methods:This is a post-hoc analysis of a phase Ⅱ clinical trial of vicagrel, which included patients with coronary heart disease who underwent percutaneous coronary intervention from August 2018 to June 2019 in 18 centers. Patients were categorized based on the presence of CYP 2C19 *2 or *3 loss-of-function (LOF) alleles into LOF carrier group ( n=111) and non-LOF carrier group ( n=90). Each group included patients received vicagrel 5 mg, 6 mg, 7.5 mg, or clopidogrel 75 mg for 28 days per study protocol. P2Y 12 reaction units (PRU) were measured using VerifyNow at baseline, 6 to 8 hours after loading dose, 7 to 10 days after randomization, and 28 days after randomization and the percentage inhibition of platelet aggregation (%IPA) was calculated. The primary endpoint was %IPA on day 28. Within the patients from the General Hospital of Northern Theater Command, 8 to 12 patients in each study arms were enrolled in a prespecified pharmacokinetic sub-study, measuring the time to reach maximum plasma concentration (T max), peak plasma concentration (C max), and area under the plasma concentration-time curve (AUC). Results:Among 201 patients, the age was (58.8±8.5) years, and 139 (69.2%) were male. In non-LOF carriers, there was no significant differences in PRU values and %IPA between the vicagrel 5 mg, 6 mg, 7 mg, and clopidogrel groups at all time points (all P>0.05). In LOF carriers, %IPA was significantly higher in the vicagrel-treated groups than in the clopidogrel group at 6-8 hours after loading dose (22.9 (14.2, 31.5)% vs. 19.8 (11.0, 28.6)% vs. 29.5 (20.9, 38.0)% vs. 12.9 (3.9, 21.9)%, P=0.038) and 7-10 days after randomization (22.4 (14.2, 30.5)% vs. 34.4 (26.1, 42.6)% vs. 39.8 (31.8, 47.9)% vs. 24.7 (16.3, 33.2)%, P=0.001), with a trend towards higher %IPA in the vicagrel-treated groups at day 28 (30.4 (21.3, 39.6)% vs. 36.5 (27.2, 45.7)% vs. 40.8 (31.8, 49.8)% vs. 30.7(21.2, 40.2)%, P=0.056). Pharmacokinetic results of 35 patients showed that the C max and AUC of the active metabolite M15-2 of vicagrel was similar to that of clopidogrel in non-LOF carriers, but AUC between vicagrel 5 mg, 6 mg, 7 mg and clopidogrel were significantly different in LOF carriers ((5.6±0.6) h·μg -1·L -1 vs. (6.8±2.7) h·μg -1·L -1 vs. (9.2±3.3) h·μg -1·L -1 vs. (4.2±1.9) h·μg -1·ml -1, P=0.020). Conclusion:Vicagrel and clopidogrel have similar antiplatelet effects in non-LOF carriers, but vicagrel exhibits superior antiplatelet effects in LOF carriers.

OBJECTIVES: Several countries have successfully eliminated measles, and China is making significant strides toward achieving this goal. This study focused on investigating the patterns of measles infections in Zhejiang Province, China, as well as control measures. The objective was to provide valuable insights that could contribute to the development of nationwide elimination strategies. METHODS: We analyzed measles surveillance data from 2005 to 2022 in Zhejiang Province. We utilized a joinpoint regression model to examine trends in measles. Additionally, we employed SaTScan version 9.5 to identify spatial-temporal clusters. Finally, we used an age-period-cohort model to assess the effects of age, period, and cohort. RESULTS: The age-standardized incidence rate (ASIR) of measles infection in Zhejiang Province from 2005 to 2022 was 5.24 per 100,000, showing a consistent and significant downward trend with an annual percentage change of -24.93% (p<0.05). After 2020, the ASIR for measles infection fell to below 0.1 per 100,000. The majority of measles cases occurred in individuals either without an immunization history or with an unknown immunization status, representing 41.06% and 41.40% of the cases from 2010 to 2022, respectively. According to data from the National Measles Surveillance System, the annual rate of discarded measles cases from 2009 to 2014, and the annual rate of discarded measles and rubella cases from 2015 to 2022, were both above 2 per 100,000, indicating the high sensitivity of the measles surveillance system. CONCLUSIONS The significant reduction in measles incidence from 2005 to 2022 demonstrates substantial progress in Zhejiang Province towards the elimination of measles.

OBJECTIVES: Several countries have successfully eliminated measles, and China is making significant strides toward achieving this goal. This study focused on investigating the patterns of measles infections in Zhejiang Province, China, as well as control measures. The objective was to provide valuable insights that could contribute to the development of nationwide elimination strategies. METHODS: We analyzed measles surveillance data from 2005 to 2022 in Zhejiang Province. We utilized a joinpoint regression model to examine trends in measles. Additionally, we employed SaTScan version 9.5 to identify spatial-temporal clusters. Finally, we used an age-period-cohort model to assess the effects of age, period, and cohort. RESULTS: The age-standardized incidence rate (ASIR) of measles infection in Zhejiang Province from 2005 to 2022 was 5.24 per 100,000, showing a consistent and significant downward trend with an annual percentage change of -24.93% (p<0.05). After 2020, the ASIR for measles infection fell to below 0.1 per 100,000. The majority of measles cases occurred in individuals either without an immunization history or with an unknown immunization status, representing 41.06% and 41.40% of the cases from 2010 to 2022, respectively. According to data from the National Measles Surveillance System, the annual rate of discarded measles cases from 2009 to 2014, and the annual rate of discarded measles and rubella cases from 2015 to 2022, were both above 2 per 100,000, indicating the high sensitivity of the measles surveillance system. CONCLUSIONS The significant reduction in measles incidence from 2005 to 2022 demonstrates substantial progress in Zhejiang Province towards the elimination of measles.

OBJECTIVES: Several countries have successfully eliminated measles, and China is making significant strides toward achieving this goal. This study focused on investigating the patterns of measles infections in Zhejiang Province, China, as well as control measures. The objective was to provide valuable insights that could contribute to the development of nationwide elimination strategies. METHODS: We analyzed measles surveillance data from 2005 to 2022 in Zhejiang Province. We utilized a joinpoint regression model to examine trends in measles. Additionally, we employed SaTScan version 9.5 to identify spatial-temporal clusters. Finally, we used an age-period-cohort model to assess the effects of age, period, and cohort. RESULTS: The age-standardized incidence rate (ASIR) of measles infection in Zhejiang Province from 2005 to 2022 was 5.24 per 100,000, showing a consistent and significant downward trend with an annual percentage change of -24.93% (p<0.05). After 2020, the ASIR for measles infection fell to below 0.1 per 100,000. The majority of measles cases occurred in individuals either without an immunization history or with an unknown immunization status, representing 41.06% and 41.40% of the cases from 2010 to 2022, respectively. According to data from the National Measles Surveillance System, the annual rate of discarded measles cases from 2009 to 2014, and the annual rate of discarded measles and rubella cases from 2015 to 2022, were both above 2 per 100,000, indicating the high sensitivity of the measles surveillance system. CONCLUSIONS The significant reduction in measles incidence from 2005 to 2022 demonstrates substantial progress in Zhejiang Province towards the elimination of measles.

OBJECTIVES: Several countries have successfully eliminated measles, and China is making significant strides toward achieving this goal. This study focused on investigating the patterns of measles infections in Zhejiang Province, China, as well as control measures. The objective was to provide valuable insights that could contribute to the development of nationwide elimination strategies. METHODS: We analyzed measles surveillance data from 2005 to 2022 in Zhejiang Province. We utilized a joinpoint regression model to examine trends in measles. Additionally, we employed SaTScan version 9.5 to identify spatial-temporal clusters. Finally, we used an age-period-cohort model to assess the effects of age, period, and cohort. RESULTS: The age-standardized incidence rate (ASIR) of measles infection in Zhejiang Province from 2005 to 2022 was 5.24 per 100,000, showing a consistent and significant downward trend with an annual percentage change of -24.93% (p<0.05). After 2020, the ASIR for measles infection fell to below 0.1 per 100,000. The majority of measles cases occurred in individuals either without an immunization history or with an unknown immunization status, representing 41.06% and 41.40% of the cases from 2010 to 2022, respectively. According to data from the National Measles Surveillance System, the annual rate of discarded measles cases from 2009 to 2014, and the annual rate of discarded measles and rubella cases from 2015 to 2022, were both above 2 per 100,000, indicating the high sensitivity of the measles surveillance system. CONCLUSIONS The significant reduction in measles incidence from 2005 to 2022 demonstrates substantial progress in Zhejiang Province towards the elimination of measles.

Objective To explore the safety and effectiveness of the comprehensive therapy of "Five-in-One" of traditional Chinese medicine combined with low concentration of atropine in the prevention and control of myopia in adolescents. Methods Eighty adolescents diagnosed with mild myopia were included in the study. According to the wishes of the subjects and their guardians, they were divided into control group with 40 cases and traditional Chinese medicine intervention group with 40 cases. The control group received 0.01% atropine sulfate eye drops in both eyes once before bedtime every night, the traditional Chinese medicine intervention group underwent twice-weekly comprehensive therapy of "Five-in-One" of traditional Chinese medicine on the basis of local application of medication in the control group. Both groups received a 12-month intervention course. Follow-up visits were conducted before intervention and at 3, 6, and 12 months after treatment. The international standard visual acuity chart was used to examine the changes in unaided distance visual acuity before and after treatment in both groups. The changes of distant visual acuity of naked eye before and after treatment were measured in two groups. The changes in equivalent spherical lens power before and after treatment in both groups were measured by mydriatic refraction combined with a computer optometer. The changes in axial length before and after treatment were measured using an optical biometer. The adverse reactions after treatment in both groups were compared. Results In the control group, the uncorrected distance visual acuity decreased compared with that before intervention as the treatment time prolonged, while was gradually increased in the traditional Chinese medicine intervention group compared with that before intervention (P < 0.05). At 12 months after treatment, the uncorrected distance visual acuity in the traditional Chinese medicine intervention group was higher than that in the control group (P < 0.05). With the prolongation of treatment time, the equivalent spherical lens power gradually increased in both groups (P < 0.05).At 12 months after treatment, the equivalent spherical lens power in the traditional Chinese medicine intervention group was lower than that in the control group (P < 0.05). The axial length gradually increased with the prolongation of treatment time in both groups (P < 0.05). At 6 and 12 months after treatment, the axial length in the traditional Chinese medicine intervention group was shorter than that in the control group (P < 0.05). After using 0.01% atropine, 8 children in the control group developed outdoor photophobia symptoms; after treatment with the comprehensive therapy of "Five-in-One" of traditional Chinese medicine combined with 0.01% atropine sulfate eye drops in the traditional Chinese medicine intervention group, 4 children developed outdoor photophobia symptoms, but the symptoms disappeared after 2 weeks of medication. Conclusion The comprehensive therapy of "Five-in-One" in traditional Chinese medicine combined with low-concentration atropine is significantly more effective than low-concentration atropine alone in effectively controlling the progression of refractive myopia and reducing its adverse reactions.