Aim To explore the protective effect of icariin on the damage of tight junctional function of Sertoli cells in naturally aging mice and the related mechanism.Methods 15-month-old C57BL/6J male mice were randomly divided into three groups:aging model group,low-dose and high-dose icariin treatment group(5 and 20 mg·kg-1).Another 1-month-old C57BL/6J male mice were considered as adult control group(n=10).The mice in adult control group and aging model group were given the vehicle(0.5％sodi-um carboxymethyl cellulose solution)by intragastric administration,while the mice in icariin-treated groups were given different concentrations of icariin,respec-tively.After continuous administration of icariin for three months,the testes and epididymis were immedi-ately removed,weighed,and the organ index was calcu-lated.Sperm viability and sperm concentration in epi-didymis were measured.The morphological changes of testes were observed by HE staining.The ultrastructur-al changes of tight junctions of Sertoli cells were ob-served by transmission electron microscopy.The ex-pression levels of tight junction-related proteins ZO-1,Occludin,and Claudin11 of testicular Sertoli cells were detected by Western blot.The expression and localiza-tion of ZO-1,Occludin,Raptor,Rictor,p-70S6K,and p-rps6 were detected by immunofluorescence.Results Compared with the aging model group,icariin signifi-cantly increased testicular weight and its index,and ep-ididymal index,improved sperm viability and increased sperm concentration in naturally aging mice.In addi-tion,icariin improved the degeneration of testicular morphology and the damage of ultrastructure of Sertoli cell tight junction with aging.Furthermore,Western blot results showed that icariin up-regulated the expres-sion of ZO-1 and Occludin,but had no significant effect on the expression of Claudin 11.Immunofluorescence assay showed that icariin up-regulated the expression of Rictor,and down-regulated the expression of p-70S6K,p-rps6 and Raptor.Conclusions Icariin improves the tight junction damage of Sertoli cells in naturally aging mice,and its mechanism may be related to restoring the balance between mTORC1 and mTORC2.

BACKGROUND: As an essential part of health services, rehabilitation is of great significance to improve the health and quality of life of the whole population. Accelerating aging calls for a significant expansion of rehabilitation services in China, but rehabilitation needs remain unclear. We conducted the study to explore the rehabilitation needs in China and project the trend of rehabilitation needs from 2020 to 2034. METHODS: The data of health conditions that might potentially benefit from rehabilitation were obtained from Global Burden of Disease (GBD) study. Estimated annual percentage changes (EAPCs) were calculated to quantify the trends of the age-standardized rates. Projections of rehabilitation needs were made until 2034 using Bayesian age-period-cohort analysis (BAPC). RESULTS: Approximately 460 million persons (33.3% of the total population) need rehabilitation in China, contributing to 63 million years lived with disabilities (YLDs) in 2019. The number of prevalent cases that need rehabilitation increased from around 268 (95% uncertainty interval [UI]: 257-282) million in 1990 to almost 460 (95% UI: 443-479) million in 2019, representing an increase of 71.3%. The highest contribution to the need for rehabilitation was musculoskeletal disorders with about 322 (95% UI: 302-343) million persons in seven aggregate disease and injury categories, and hearing loss with over 95 (95% UI: 84-107) million people among 25 health conditions. Based on the projection results, there will be almost 636 million people (45% of the total population) needing rehabilitation services in China by 2034, representing an increase of 38.3%. The rehabilitation needs of neoplasms, cardiovascular diseases, and neurological disorders are expected to increase significantly from 2019 to 2034, with increases of 102.3%, 88.8% and 73.2%, respectively. CONCLUSIONS The need for rehabilitation in China substantially increased over the last 30 years. It is predicted that over two in five people will require rehabilitation by 2034, thus suggesting the need to develop rehabilitation services that meet individuals' rehabilitation needs.
Humans ; China/epidemiology* ; Global Burden of Disease ; Female ; Male ; Musculoskeletal Diseases/epidemiology* ; Rehabilitation/trends* ; Quality of Life ; Middle Aged ; Aged ; Bayes Theorem

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*

Aim To explore the protective effect of icariin on the damage of tight junctional function of Sertoli cells in naturally aging mice and the related mechanism.Methods 15-month-old C57BL/6J male mice were randomly divided into three groups:aging model group,low-dose and high-dose icariin treatment group(5 and 20 mg·kg-1).Another 1-month-old C57BL/6J male mice were considered as adult control group(n=10).The mice in adult control group and aging model group were given the vehicle(0.5％sodi-um carboxymethyl cellulose solution)by intragastric administration,while the mice in icariin-treated groups were given different concentrations of icariin,respec-tively.After continuous administration of icariin for three months,the testes and epididymis were immedi-ately removed,weighed,and the organ index was calcu-lated.Sperm viability and sperm concentration in epi-didymis were measured.The morphological changes of testes were observed by HE staining.The ultrastructur-al changes of tight junctions of Sertoli cells were ob-served by transmission electron microscopy.The ex-pression levels of tight junction-related proteins ZO-1,Occludin,and Claudin11 of testicular Sertoli cells were detected by Western blot.The expression and localiza-tion of ZO-1,Occludin,Raptor,Rictor,p-70S6K,and p-rps6 were detected by immunofluorescence.Results Compared with the aging model group,icariin signifi-cantly increased testicular weight and its index,and ep-ididymal index,improved sperm viability and increased sperm concentration in naturally aging mice.In addi-tion,icariin improved the degeneration of testicular morphology and the damage of ultrastructure of Sertoli cell tight junction with aging.Furthermore,Western blot results showed that icariin up-regulated the expres-sion of ZO-1 and Occludin,but had no significant effect on the expression of Claudin 11.Immunofluorescence assay showed that icariin up-regulated the expression of Rictor,and down-regulated the expression of p-70S6K,p-rps6 and Raptor.Conclusions Icariin improves the tight junction damage of Sertoli cells in naturally aging mice,and its mechanism may be related to restoring the balance between mTORC1 and mTORC2.

Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective To observe the effect of parecoxib sodium combined with dexmedetomidine preemptive analgesia on postoperative analgesia in patients with modified radical mastectomy for breast cancer.Methods Patients who underwent modified radical mastectomy for breast cancer were randomly divided into control group and treatment group based on simple binary randomization by random number table method.In the control group,"0.05 mg·kg-1 midazolam+1.0-1.5 mg·kg-1 propofol+0.4 μg·kg-1sufentanil citrate+0.15 mg·kg-1 phenylsulfonyl cisatracurium"was used for induction and maintenance of anesthesia.In the treatment group,the induction and maintenance of anesthesia was performed with the protocol of"parecoxib sodium 40 mg+dexmedetomidine 0.5 μg·kg-1·h-1)continuous pumping"on the basis of control group,and mechanical ventilation was performed by tracheal intubation 5 min after induction.The effect of pre-analgesia,postoperative sedation,hemodynamic indexes,surgical improvement indexes and application safety were observed by groups.Results There were 46 patients in each group.Pain visual analogue scores at 6,12 and 24 h in treatment group were 2.09±0.72,4.17±1.07 and 4.07±1.05,lower than those in control group,which were 2.61±1.03,4.76±1.27 and 4.65±1.11,the differences were statistically significant(all P＜0.05).The Ramsay sedation scores of the treatment group and the control group at 6 h after surgery were(2.85±0.62)and(2.11±0.73)points,respectively;the sedation scores of Ramsay at 12 h were 1.41±0.28 and 1.06±0.15,respectively.At 24 h,the sedation scores of Ramsay were 1.15±0.18 and 0.64±0.13,respectively,and the difference was statistically significant(P＜0.05).HR and MAP of treatment group and control group at T2 and T3 were significantly lower than those at T1 and T0(P＜0.05),there were no difference in HR and MAP between treatment group and control group at T2 and T3(P＜0.05).Operation time,recovery time after operation and intraoperative blood loss in treatment group were significantly lower than those in control group,and the differences were statistically significant(all P＜0.05).The success rate of 12-hour postoperative analgesia in test group and control group was 82.61％(38 cases/46 cases)and 63.04％(29 cases/46 cases),respectively,and the difference was statistically significant(P＜0.05).The adverse drug reactions in treament group and control group mainly included bradycardia,headache,dizziness and nausea,and the incidence of adverse drug reactions in treatment group and control group were 13.04％(6 cases/46 cases)and 8.70％(4 cases/46 cases),respectively,the difference was no statistically significant(P＜0.05).Conclusion Parecoxib sodium combined with dexmedetomidine preemptive analgesia has significantly improved analgesia and sedative effects in modified radical mastectomy for breast cancer,can prolong sedation and analgesia time,and stably control the perioperative hemodynamics of patients.

Objective To develop the functions and optimize the automatic monitoring module for arrhythmias of the adverse drug event active surveillance and assessment system-Ⅱ,in order to continuously improve the performance,enhance the monitoring efficiency,and explore the ways to optimize the module.Methods Expand and optimize the functions of the module,increase the customized configuration,and determine the optimal setting conditions;compare the optimized test data with the results of the evaluation studies on the automatic monitoring of drug-induced arrhythmias in large samples of medicated population previously,and verify the optimization extent as well as the accuracy of the module.Results In the new module optimized according to the characteristics of the monitoring population,the function of"mandatory medical order keywords"was added,and it was determined that the inclusion of 6 electrocardiogram examination-related medical order keywords with a frequency of not less than 2 occurrences was the optimal configuration condition for the optimization of the module;combining the results of the previous automatic monitoring and evaluation researches,the system functions were verified and compared under the conditions of using the whole drugs and 2 kinds of single drug.While there was no loss of true positive cases,the number of cases with system alarms decreased by 30.75％,80.13％and 90.82％,respectively,compared with that before the optimization of the module,and the positive predictive value was significantly improved.Conclusion After the function expansion and optimization,the automatic monitoring module of drug-induced arrhythmias significantly reduces the labor cost of case evaluation and keeps the accuracy of monitoring results constant;the new module can better adapt to the demands of different automatic monitoring modes and operates stably,which is more generalizable and flexible,and provides a new way of considering for the research and development of automatic monitoring modules.

Objective:To investigate the risk factors for severe hyperbilirubinemia complicated by acute bilirubin encephalopathy (ABE), and the value of total serum bilirubin (TSB) and bilirubin (B)/albumin (A) ratio in predicting ABE.Methods:Clinical data of children with severe hyperbilirubinemia admitted to the Affiliated Hospital of Inner Mongolia Medical University, Ordos Central Hospital, People's Hospital of Inner Mongolia Autonomous Region, the Fourth Hospital of Baotou, Tongliao Hospital, Maternal and Child Health Hospital of Hohhot, the Affiliated Hospital of Chifeng University, Manzhouli People's Hospital, and Chifeng Hospital from January 1, 2020, to December 31, 2021, were retrospectively collected. The subjects were divided into ABE and non-ABE groups based on the occurrence of ABE. Multivariate logistic regression analysis was used to identify high-risk factors for ABE. Statistical analysis was performed using t-test, Wilcoxon signed-rank test, or Chi-square tests. Indicators with statistically significant differences were included in the multivariate logistic regression model, and stepwise regression was used to analyze the influencing factors of ABE. Results:(1) A total of 543 children were included in this study, accounting for 3.7% (543/14 831) of the total admissions during the same period. Among the 543 children, 81 (14.9%) had ABE, and 462 (85.1%) did not. The age at admission was (7.2±2.1) d, and the length of hospital stay was (5.2±2.2) d. The breastfeeding initiation time was 2 d (1-4 d) after birth. The peak TSB of the 543 cases was (385.98±51.22) μmol/L, and the age at peak TSB was (4.4±2.1) d. Fourteen cases (2.5%) gradually reached the peak TSB after admission [(392.01±61.24) μmol/L], while 529 cases (97.5%) had already reached the peak TSB at admission [(386.42±50.22) μmol/L]. Among the 543 cases, 356 had a clear etiology (65.6%, with 278 cases having a single cause and 78 cases having more than two causes), and 187 cases (34.4%) had an unknown etiology. (2) Compared with the non-ABE group, the breastfeeding initiation in the ABE group was later [6 h (2-6 h) vs. 2 h (1-3 h), Z=－6.87] and the length of hospital stay was longer [(6.5±1.9) d vs. (5.0±2.1) d, t=0.55]. The proportions of breastfeeding, delayed meconium passage, isoimmune hemolysis, and maternal gestational diabetes, as well as peak TSB and B/A ratio at peak TSB, were higher in the ABE group than in the non-ABE group [64.2% (52/81) vs. 36.8% (170/462), χ2=21.96; 16.0% (13/81) vs. 2.4% (11/462), χ2=27.32; 27.2% (22/81) vs. 10.6% (40/462), χ2=16.61; 24.7% (20/81) vs. 13.6% (63/462), χ2=6.50; (442±68) vs. (375±39) μmol/L, t=－8.55; (11.9±1.6) vs. (9.8±1.2), t=－11.61; all P<0.05]. The admission weight, proportion of transfer from the hospital's obstetrics department, unknown etiology, and breast milk jaundice were lower in the ABE group than in the non-ABE group [(3 098±482) vs. (3 278±493) g, t=3.04; 12.3% (10/81) vs. 42.4% (196/462), χ2=30.48; 3.7% (3/81) vs. 39.8% (184/462), χ2=39.83; 0.0% (0/81) vs. 5.8% (27/462), χ2=3.81; all P<0.05]. (3) Isoimmune hemolysis, peak TSB, and B/A ratio at peak TSB were independent risk factors for ABE [ OR(95% CI) were 2.924 (1.209-7.073), 1.006 (0.997-1.014), and 2.647 (1.841-3.805), respectively]. When the peak TSB was 380.05 μmol/L and the B/A ratio at peak TSB was 10.45, the sensitivity for predicting ABE was 0.963, the specificity was 0.789, and the area under the receiver operating characteristic curve was 0.752. Conclusions:Isoimmune hemolysis, peak TSB, and B/A ratio at peak TSB are independent risk factors for ABE. The B/A ratio at peak TSB and peak TSB can effectively predict ABE.

Objective:To investigate the significance and value of peripheral blood lymphocyte subset characteristics in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for distinguishing cytomegalovirus (CMV) infection.Methods:This retrospective study gathered data from allo-HSCT patients treated at Beijing Ludaopei Hospital between May 2021 and January 2023. This study included 50 patients in the CMV infection group and 47 patients in the non-CMV infection group. Flow cytometry was used to detect peripheral blood lymphocyte subsets 1 month after the allo-HSCT. The absolute lymphocyte count and their subsets were analyzed to assess their predictive significance in the occurrence of CMV infection. Mamn-whiney U test and χ 2 test were used. Indicators with statistical significance in univariate analysis were further subjected to binary logistic regression analysis and receiver operating characteristic (ROC) curves construction. The generation of survival curves for different outcomes was conducted using the Kaplan-Meier method, and the Log-rank test was applied. A two-sided P-value of<0.05 was considered statistically significant. Results:1. Among patients in the CMV infection group, 22% (11/50) were diagnosed with CMV viremia combined with CMV disease. The maximum CMV viral load in peripheral whole blood in these patients was 1 600 (1 400, 5 800) copies/ml, which was significantly higher than that in patients without confirmed CMV disease 970 (670, 2 300) copies/ml, with a statistically significant difference ( Z=-2.281, P=0.029). 2. The overall survival (OS) at the follow-up endpoint was 80% (40/50) in the CMV infection group and 87.2% (41/47) in the non-CMV infection group. There was no statistically significant difference in OS between the two groups at the follow-up endpoint ( χ2=0.231, P=0.630). 3. In the binary logistic regression model, the number of CD34 cells transfused into the patient, the percentage of CD3+CD38+T cells in CD3+T cells, and the percentage of CD4+CD38+T cells in CD4+lymphocytes were identified as important independent risk factors for infection. The ROC curve analysis demonstrated that the area under the curve (AUC) for these independent risk factors of CMV infection was 0.914 (>0.7, P<0.001), with a decision value of 0.702, a sensitivity of 0.857, and a specificity of 0.844. Conclusion:Followingallo-HSCT, the immune subsets in the CMV infection group exhibited a diminished proportion of T cells and CD4+T cells in comparison to the non-CMV infection group. In terms of T cell differentiation, there was an increase in TEM cells and a decrease in Naive T cells. Additionally, the expression level of the activation marker CD38 on T cells exhibited a high degree of predictive value for the occurrence of CMV infection. Understanding the immune characteristics of post-transplant CMV-infected patients is beneficial for the analysis of their immune reconstitution status, providing valuable insights for clinicians in the diagnosis and treatment of CMV infection after transplantation.