BACKGROUND:The mechanism of programmed death receptor-1(PD-1)effect on osteogenic differentiation of bone marrow mesenchymal stem cells in high glucose environment remains unclear. OBJECTIVE:To explore the effect of PD-1 on osteogenic differentiation of rat bone marrow mesenchymal stem cells in high glucose environment and its regulatory mechanism. METHODS:Rat bone marrow mesenchymal stem cells were randomly divided into normal glucose group(5.6 mmol/L),high glucose group(30 mmol/L),PD-1 overexpression group,PD-1 overexpression no-load group,PD-1 knockdown group,PD-1 knockdown no-load group,and PI3K/AKT pathway inhibitor group(PD-1 knockdown+5 μmol/L LY294002).Rat bone marrow mesenchymal stem cells were cultured in high glucose to simulate the diabetic environment in vitro.The mRNA expression of PD-1 and ligand PD-L1 and the mRNA expression of osteogenic markers Runx2 and OSX in rat bone marrow mesenchymal stem cells were detected by qRT-PCR.The osteogenic differentiation ability was observed by alkaline phosphatase staining and alizarin red staining.Cell proliferation was detected by CCK-8 assay.The protein expressions of PD-1,PD-L1,p-PI3K,and p-AKT were detected by western blot assay. RESULTS AND CONCLUSION:(1)The levels of PD-1 and PD-L1 were significantly increased in the high glucose environment in vitro,and the osteogenic differentiation ability of bone marrow mesenchymal stem cells was inhibited in the high glucose environment.(2)Knockdown of PD-1 expression could promote osteogenic differentiation of bone marrow mesenchymal stem cells,increase cell proliferation activity,and activate the PI3K/AKT pathway.(3)After addition of PI3K/AKT pathway inhibitor LY294002,the ability of bone marrow mesenchymal stem cells to differentiate into osteoblasts decreased.The results show that PD-1 is dependent on the PI3K/AKT signaling pathway to inhibit osteogenic differentiation of rat bone marrow mesenchymal stem cells under high glucose environment.

BACKGROUND:Programmed cell death protein 1 belongs to the immunoglobulin gene superfamily and can regulate the differentiation of osteoblasts and affect bone homeostasis.However,there are few studies on the regulatory role and mechanism of programmed cell death protein 1 in diabetic osteoporosis.OBJECTIVE:To investigate the regulatory role and mechanism of programmed cell death protein 1 on osteogenic differentiation of rat bone marrow mesenchymal stem cells under high-glucose environment.METHODS:(1)Animal experiment:A total of 12 Sprageu-Dawley rats were randomized into a control group(n=6)and a model group(n=6).The control group was fed routinely,whereas the model group was injected intraperitoneally with streptozotocin to establish a model of type 1 diabetes mellitus,and the high-fat feed was fed for 8 weeks to establish a model of type 1 diabetic osteoporosis.After 8 weeks of feeding,the femurs of rats in the two groups were taken and subjected to hematoxylin-eosin staining and micro-CT assay.The mRNA expression of programmed cell death protein 1 and programmed death ligand 1 was detected.(2)Cell experiment:Passage 3 rat bone marrow mesenchymal stem cells were randomly divided into four groups:normal control group,high-glucose model group cultured in low glucose medium,programmed cell death protein 1-silenced group transfected with programmed cell death protein 1 siRNA,and programmed cell death protein 1-silenced null group transfected with siRNA-NC.After 48 hours of transfection,the normal control group was cultured in a new low-glucose medium,and the other three groups were cultured in a high-glucose medium for another 48 hours of culture followed by osteogenic induction.After 21 days of osteogenic induction,alizarin red staining,and qRT-PCR(programmed cell death protein 1 and RUNX2 mRNA expression)and western blot(β-catenin,GSK-3β,p-GSK-3β and Axin2 protein expression)were performed.RESULTS AND CONCLUSION:In the animal experiment,hematoxylin-eosin staining and micro-CT assay showed successful modeling of type 1 diabetic osteoporosis in the model group.qRT-PCR assay showed that the mRNA expression of programmed cell death protein 1 and programmed cell death ligand 1 was higher in the model group than the control group(P<0.05).In the cell experiment,the results of alizarin red staining showed that the ability of mineralized nodule formation was lower in the high-glucose model group and the programmed cell death protein 1-silenced null group than in the control group and the programmed cell death protein 1-silenced group.Compared with the normal control group,the programmed cell death protein 1 mRNA expression and GSK3β and Axin2 protein expression were elevated in the high-glucose model group and the programmed cell death protein 1-silenced null group(P<0.05),and the RUNX2 mRNA expression and p-GSK3β and β-catenin protein expression were decreased(P<0.05).Compared with the high-glucose model group and the programmed cell death protein 1-silenced null group,programmed cell death protein 1 mRNA expression and GSK3β and Axin2 protein expression were decreased in the programmed cell death protein 1-silenced group(P<0.05),and RUNX2 mRNA expression and p-GSK3β and β-catenin protein expression were elevated(P<0.05).To conclude,programmed cell death protein 1 silencing can activate the Wnt/β-catenin and improve the osteogenic differentiation of rat bone marrow mesenchymal stem cells under high-glucose conditions.

Objective To investigate the relationship between the serum FMS-like tyrosine kinase 3 ligand(Flt3L),progranulin(PGRN)levels and the disease risk and disease outcome of patients with acute lympho-blastic leukemia(ALL).Methods A total of 104 patients with ALL admitted to the hospital from September 2019 to September 2021 were selected as the research subjects.ALL patients were divided into the low-risk group(n=34),the medium-risk group(n=39),and the high-risk group(n=31)according to the disease risk.The levels of serum Flt3L and PGRN of the patients at admission were detected by enzyme-linked immu-nosorbent assay.Pearson correlation analysis was used to analyze the relationship between serum Flt3L,PGRN in ALL patients and the risk of ALL disease.According to the follow-up results of ALL patients,they were divided into the good prognosis group(n=81)and the poor prognosis group(n=23).The receiver oper-ating characteristic curve and the area under the curve(AUC)were used to analyze the evaluation value of se-rum Flt3L and PGRN for the prognosis of ALL patients,and multivariate Cox regression was used to analyze the prognostic risk factors of ALL patients.Results The serum Flt3L levels in the low-risk group and the medium-risk group were higher than those in the high-risk group,and the difference was statistically signifi-cant(P＜0.05).The serum PGRN levels in the low-risk group and the medium-risk group were lower than those in the high-risk group,and the difference was statistically significant(P＜0.05).Serum Flt3L in ALL patients was negatively correlated with the risk of ALL disease(r=-0.461,0.593,P＜0.05).Serum PGRN in ALL patients was positively correlated with the risk of ALL disease(r=0.593,P＜0.05).The proportions of white blood cell count ≥50 × 109/L,hemoglobin＜90 g/L,and serum PGRN level in the poor prognosis group were higher than those in the good prognosis group,while the serum Flt3L level was lower than that in the good prognosis group,and the differences were statistically significant(P＜0.05).The AUC of serum Flt3L and PGRN in evaluating the prognosis of ALL patients were 0.762(95％CI:0.717-0.816),0.815(95％CI:0.764-0.863),and 0.915(95％CI:0.866-0.964),respectively.White blood cell count ≥50 × 109/L,hemoglobin＜90 g/L,Flt3L＜92.07 pg/mL,and PGRN≥335.14 pg/mL were risk factors affecting the prognosis of ALL patients(P＜0.05).Conclusion The levels of serum Flt3L and PGRN in ALL patients are related to the disease risk and disease outcome of ALL.The combined detection of the two has a good eval-uation value for the prognosis of adult ALL patients.

Objective:To analyze the trend of the health literacy level of Chinese residents from 2012 to 2023 and predict the health literacy level from 2024 to 2027.Methods:The study collected data on the health literacy surveillance of Chinese residents from 2012 to 2023. The Joinpoint regression model was used to calculate the average annual percent change (AAPC) and analyze the trend. The interrupted time series analysis with Prais-Winsten transformed generalized least squares estimation was employed to investigate the impact of the"Healthy China 2030" policy on residents′ health literacy levels. Joinpoint regression, autoregressive integrated moving average model and grey forecasting models were established to select the optimal model for forecasting health literacy levels from 2024 to 2027.Results:The results showed that the health literacy level of Chinese residents increased from 8.80% in 2012 to 29.70% in 2023 (AAPC=11.65%, P<0.05). The health literacy level of urban and rural residents increased from 11.79% and 7.13% in 2012 to 33.25% and 26.23% in 2023, respectively (AAPC=9.57% and 12.60%, both P<0.05). Rural (1.59% per year) saw a lower average annual increase than urban (1.79% per year), widening the urban-rural health literacy gap. All aspects of health literacy, including basic knowledge and concepts, healthy lifestyles and behaviors, and health skills, showed an upward trend. The literacy level of six health issues—safety and first aid, scientific health views, health information, infectious disease prevention, chronic disease prevention, and basic medical care—also exhibited rising trends. Interrupted time series analysis indicated a significant further increase in the health literacy level of Chinese residents after the implementation of the "Healthy China 2030" policy, with the growth rate increasing from 0.615% per year before implementation to 2.655% per year afterwards. The Joinpoint regression model showed superior predictive performance compared to autoregressive integrated moving average model and grey forecasting models. The prediction results suggested a continued upward trend in the health literacy level from 2024 to 2027, reaching 32.68%, 35.62%, 38.84%, and 42.34%, respectively. Conclusion:From 2012 to 2023, the overall and various aspects of health literacy among Chinese residents show a continuous upward trend. This study predicts that the level of residents′ health literacy will continue to rise by 2027.

Objective:To understand the development status of maternal and child health care institutions in China from 2012 to 2022, identify the challenges they face, and provide references for further promoting the high-quality development of these institutions.Methods:Data from the China Health Statistics Yearbook (2013—2015), China Health and Family Planning Statistics Yearbook (2016—2017), and China Health and Wellness Statistics Yearbook (2018—2023) were used. Descriptive analysis was conducted on the data related to resource allocation and utilization efficiency, service provision, income and expenditure structure, and operational status of maternal and child health care institutions in China from 2012 to 2022, using methods such as fixed-base growth rate, year-on-year growth rate, and average annual growth rate. Results:From 2012 to 2022, the number of maternal and child health care institutions in China decreased from 3 044 to 3 031. In terms of resource allocation, the average annual growth rates of bed numbers and business-use floor area were 5.404% and 10.923%, respectively, while the average annual growth rate of health professionals was 7.183%. Regarding service provision, the average annual growth rates of outpatient visits and inpatient admissions were 3.954% and 1.572%, respectively. In terms of service efficiency, the bed occupancy rate decreased from 76.9% to 53.9%, and the average number of patients seen per physician per day decreased from 8.85 to 7.30. In terms of income and expenditure and operations, the income-expenditure surplus rate decreased from 9.16% to 5.41%, and the debt-to-asset ratio increased from 27.88% to 33.60%. During the same period, the average annual growth rates of bed numbers and business-use floor area in grassroots maternal and child health care institutions were 4.545% and 10.091%, respectively, lower than the national average. The number of outpatient visits increased from 89.03 million to 126.93 million, with an average annual growth rate of 3.610%, while the number of inpatient admissions decreased from 4.19 million to 3.91 million, with an average annual decline of 0.689%. The income-expenditure surplus rate of grassroots institutions decreased from 7.76% to 4.05%, 1.36 percentage points lower than the national level, and the debt-to-asset ratio increased from 27.53% to 36.37%, higher than the overall level.Conclusions:From 2012 to 2022, maternal and child health care institutions in China achieved certain developments in resource allocation and service scale. However, several challenges remain, including unbalanced resource allocation, decreased utilization efficiency, slowed growth in medical service volume, imbalanced income and expenditure structure, increased asset operation risks, and restricted development of grassroots institutions. It is recommended that relevant management departments and maternal and child health care institutions optimize resource allocation, plan for service transformation and upgrading, expand income sources, strengthen internal financial control, and reinforce the construction of high-quality and efficient maternal and child health care systems to promote the high-quality development of maternal and child health care institutions in China.

Objective:This study utilizes data from the 2021 Chinese Longitudinal Healthy Longevity and Happy Family Survey(CLHLS-HF)to examine the current status of Long-Term Care Insurance(LTCI)implementation and to identify the factors influencing whether disabled elderly individuals receive formal care services.The study aims to provide policy recommendations to enhance the effectiveness and equity of the system.Methods:In this cross-sectional study, a sample of 1 447 older participants with dependency, residing in LTCI pilot areas and meeting the inclusion criteria from the 2021 CLHLS-HF, was selected.Chi-square tests and binary logistic regression analyses were employed to explore the factors influencing the receipt of formal care by dependent older individuals.Results:Among the 1 447 participants, there were 496 males with an average age of 92 years(SD 9)and 951 females with an average age of 95 years(SD 9). Of these, 701 received formal care.The logistic regression analysis revealed that factors influencing the receipt of formal care included urban residence( OR=2.237, 95% CI: 1.675-2.987, P<0.001), residing in the eastern region( OR=2.907, 95% CI: 1.747-4.837, P<0.001), living in the western region( OR=3.132, 95% CI: 1.816-5.501, P<0.001), having no children( OR=2.478, 95% CI: 1.108-5.540, P=0.027), and the degree of disability, with severe disability being more likely to receive care compared to mild( OR=0.497, 95% CI: 0.388-0.637, P<0.001)and moderate disabilities( OR=0.589, 95% CI: 0.433-0.801, P=0.001). Conclusions:Dependent older individuals in the eastern and western regions, particularly those without children or with severe disabilities, are more likely to receive formal care through the LTCI system.However, there are substantial inequities in LTCI coverage among individuals with varying degrees of disability.To enhance the effectiveness of the LTCI system, greater efforts should be directed towards economically disadvantaged regions and older individuals with mild to moderate disabilities, thereby ensuring better protection for the disabled population.

Objective: To analyze the association between each regional fat mass and total body bone mineral density (BMD) in children and adolescents aged 7-17 years in Beijing, so as to provide theoretical basis and practical guidance for implementing interventions. Methods: From September to December 2020, a stratified cluster random sampling method was used to select 1 423 children and adolescents aged 7-17 years in Tongzhou District, Beijing. Dual energy X-ray absorptiometry (DXA) was employed to measure regional body composition and total body BMD. Multiple linear regression was used to analyze the association between regional fat mass and total body BMD. Results: The median (interquartile range) fat mass values for total body, upper limbs, abdomen, hips, and thighs were 13.51(8.84, 19.21), 1.59(1.08, 2.23), 0.73(0.39, 1.29), 2.32(1.46, 3.26), 5.29(3.59, 7.21)kg, respectively. After adjusting for covariates, the results of multiple linear regression analysis showed that total body fat mass (β=0.010), abdominal fat mass (β=-0.100), and hip fat mass (β=0.104) were significant associations with total body BMD (all P<0.01). Sexstratified analysis revealed that in boys, total body fat mass (β=0.008) and hip fat mass (β=0.058) were positively associated with BMD, while thigh fat mass (β=-0.038) showed a negative association with total body BMD (all P<0.05). In girls, total body fat mass (β=0.013), hip fat mass (β=0.163), and thigh fat mass (β=0.023) were positively associated with total body BMD, whereas abdominal fat mass (β=-0.196) showed a negative association with total body BMD (all P<0.05). Among children and adolescents with body fat percentage below the standard range, within the standard range and above the standard range, total body fat masses were positively associated with total body BMD (β=0.021, 0.016, 0.015); among children and adolescents with body fat percentage within the standard range while upper limb (β=-0.042), abdominal (β=-0.067), and thigh fat mass (β=-0.018) showed negative associations with total body BMD, and hip fat mass demonstrated a positive association with total body BMD (β=0.082) (all P<0.05). Conclusion Regional fat distribution is associated with total body BMD in children and adolescents, with the nature of these associations varying by sex and body fat percentage.

Objective:To investigate the application value of intraoperative electrocochleography（ECochG） monitoring technique and insertion techniques in cochlear implant（CI） and analyze its relationship with postoperative residual hearing（RH） preservation. Methods:Thirty-one patients（35 ears） who received CI in our hospital from June 2022 to July 2024 were enrolled. The Advanced Bionics Active Insertion Monitoring（AIM） system was used for real-time ECochG monitoring during surgery. Intraoperative cochlear microphonics （CM） waveform changes were recorded and analyzed in relation to postoperative RH preservation. Results:①ECochG recordings were successfully obtained in 34 of 35 ears （97.1%）. ②According to Harris classification, there were 7 ears（20.6%） of Type A（rising）, 7 ears（20.6%） of Type C（declining）, 8 ears（23.5%） of Type CC（fluctuating）, and 12 ears（35.3%） of Type D（no response）. ③The total CM amplitude decrease was significantly moderately correlated with postoperative low-mid frequency hearing loss（r=0.67, P=0.017）. The total CM amplitude decrease was significantly moderately correlated with postoperative low frequency hearing loss（r=0.65, P=0.023）. ④For the mean amplitude variation, the Amax was 30.70 μV, the Amin was 8.64 μV, and the Aend was 18.27 μV. ⑤Sixteen cases completed postoperative follow-up, with an average low-mid frequency（125-1 000 Hz） residual hearing loss of 15.25 dB HL and a RH preservation rate of 87.5%. Conclusion:Intraoperative ECochG monitoring can effectively predict postoperative residual hearing changes, effectively guide surgical manipulation, and improve residual hearing preservation rate.
Humans ; Cochlear Implantation/methods* ; Audiometry, Evoked Response ; Cochlear Implants ; Male ; Female ; Adult ; Middle Aged ; Monitoring, Intraoperative ; Adolescent ; Young Adult ; Minimally Invasive Surgical Procedures ; Child ; Aged ; Postoperative Period

The diagnosis of hematological disorders is currently established from the combined results of different tests, including those assessing morphology (M), immunophenotype (I), cytogenetics (C), and molecular biology (M) (collectively known as the MICM classification). In this workflow, most of the results are interpreted manually (i.e., by a human, without automation), which is expertise-dependent, labor-intensive, time-consuming, and with inherent interobserver variability. Also, with advances in instruments and technologies, the data is gaining higher dimensionality and throughput, making additional challenges for manual analysis. Recently, artificial intelligence (AI) has emerged as a promising tool in clinical hematology to ensure timely diagnosis, precise risk stratification, and treatment success. In this review, we summarize the current advances, limitations, and challenges of AI models and raise potential strategies for improving their performance in each sector of the MICM pipeline. Finally, we share perspectives, highlight future directions, and call for extensive interdisciplinary cooperation to perfect AI with wise human-level strategies and promote its integration into the clinical workflow.