Objective:To investigate the role of RNA m6A methylation in mediating cerebellar dysplasia through analyzing the phenotypes of the mouse cerebella and the expression of several key m6A regulators upon hypobaric hypoxia treatment.Methods:Five-day old C57/BL6 mice were exposed to hypobaric hypoxia for 9 days. The status of mouse cerebellar development was analyzed by comparing the body weights, brain weights and histological features. Immunostaining of cell-type-specific markers was performed to analyze the cerebellar morphology. Real-time PCR, Western blot and immunohistochemical staining were performed to detect the expression of key m6A regulators in the mouse cerebella.Results:Compared with the control, the body weights, brain weights and cerebellar volumes of hypobaric hypoxic mice were significantly reduced ( P<0.01). The expression of specific markers in different cells, including NeuN (mature neuron), Calbindin-D28K (Purkinje cell) and GFAP (astrocyte), was decreased in hypobaric hypoxic mouse cerebella ( P<0.01), accompanied with disorganized cellular structure. The expression of methyltransferase METTL3 was significantly down-regulated in the cerebella of hypobaric hypoxic mice ( P<0.05). Conclusions:Hypobaric hypoxia stimulation causes mouse cerebellar dysplasia, with structural abnormalities in mature granular neurons, Purkinje cells and astrocytes. Expression of METTL3 is decreased in hypobaric hypoxic mice cerebellum compared with that of normobaric normoxic mice, suggesting that its mediated RNA m6A methylation may play an important role in hypobaric hypoxia-induced mouse cerebellar dysplasia.

AIM: To evaluate the bioequivalence of cinacalcet hydrochloride tablets in healthy Chinese volunteers. METHODS: A randomized, open, double-period and crossover trial was conducted, 48 healthy volunteers were administered a single dose of cinacalcet test tablets or reference tablets orally under each fasting and fed condition. The concentration of cinacalcet was determined by validated LC-MS/MS method. Pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 to study its bioequivalence. RESULTS: The main pharmacokinetic parameters of test tablets and reference tablets under fasting condition were as follows: C

OBJECTIVE: To explore the mechanisms of large-conductance calcium-activated potassium channel (BKCa) involved in inflammatory response in sepsis. METHODS: The serum levels of BKCa were measured by enzyme-linked immunosorbent assay (ELISA) in patients with sepsis (28 cases), patients with common infection (25 cases) and healthy people (25 cases). The relationship between levels of BKCa and acute physiology and chronic health evaluation II (APACHE II) were analyzed. Cultured RAW 264.7 cells were stimulated by lipopolysaccharide (LPS). In some experiments, a cell model of sepsis was constructed using Nigericin as the second stimulus signal. The mRNA and protein expressions of BKCa in RAW 264.7 cells stimulated with LPS (0, 50, 100, 1 000 μg/L) were measured by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting. RAW 264.7 cells were transfected with small interfering RNA of BKCa (siRNA-BKCa), and the levels of caspase-1 precursor (pro-caspase-1), interleukin-1β precursor (pro-IL-1β) in cell, and the levels of caspase-1 p20, IL-1β p17 of cell culture medium, and NOD-like receptor protein 3 (NLRP3), nuclear factor-κB (NF-κB) were measured by Western blotting. The apoptosis were detected by staining with propidium iodide (PI), the release rate of lactate dehydrogenase (LDH) were measured, and the expression of apoptotic protein Gasdermin D (GSDMD) was measured by Western blotting to evaluate the effect of silencing BKCa on cell pyrosis. RESULTS: The level of serum BKCa in patients with sepsis was significantly higher than that in patients with common infection and health peoples (ng/L: 165.2±25.9 vs. 102.5±25.9, 98.8±20.0, both P < 0.05). In addition, the level of serum BKCa in patients with sepsis was significantly positively correlated with APACHE II score (r = 0.453, P = 0.013). LPS could construct a sepsis cell model by which LPS could promote BKCa expression in mRNA and protein with a concentration-dependent manner. The mRNA and protein expressions of BKCa in the cells stimulated by 1 000 μg/L LPS were significantly higher than that in the blank group (0 μg/L) [BKCa mRNA (2^-ΔΔCt): 3.00±0.36 vs. 1.00±0.16, BKCa/β-actin: 1.30±0.16 vs. 0.37±0.09, both P < 0.05]. Compared with the control group, the ratios of caspase-1 p20/pro-caspase-1 and IL-1β p17/pro-IL-1β in the model group were significantly increased (caspase-1 p20/pro-caspase-1: 0.83±0.12 vs. 0.27±0.05, IL-1β p17/pro-IL-1β: 0.77±0.12 vs. 0.23±0.12, both P < 0.05), however, transfection of siRNA-BKCa induced the decrease both of them (caspase-1 p20/pro-capase-1: 0.23±0.12 vs. 0.83±0.12, IL-1β p17/pro-IL-1β: 0.13±0.05 vs. 0.77±0.12, both P < 0.05). Compared with the control group, the number of apoptotic cells, LDH release rate and GSDMD expression in the model group were significantly increased [LDH release rate: (30.60±8.40)% vs. (15.20±7.10)%, GSDMD-N/GSDMD-FL: 2.10±0.16 vs. 1.00±0.16, both P < 0.05], however, transfection of siRNA-BKCa induced the decrease both of them [LDH release rate: (15.60±7.30)% vs. (30.60±8.40)%, GSDMD-N/GSDMD-FL: 1.13±0.17 vs. 2.10±0.16, both P < 0.05]. The mRNA and protein expressions of NLRP3 in sepsis cells were significantly higher than those in the control group [NLRP3 mRNA (2^-ΔΔCt): 2.06±0.17 vs. 1.00±0.24, NLRP3/GAPDH: 0.46±0.05 vs. 0.15±0.04, both P < 0.05]. However, the expression of NLRP3 after siRNA-BKCa transfection was significantly lower than that in model group [NLRP3 mRNA (2^-ΔΔCt): 1.57±0.09 vs. 2.06±0.17, NLRP3/GAPDH: 0.19±0.02 vs. 0.46±0.05, both P < 0.05]. Compared with the control group, the NF-κB p65 nuclear transfer of sepsis cell were significantly increased (NF-κB p65/Histone: 0.73±0.12 vs. 0.23±0.09, P < 0.05). However, the NF-κB p65 expression in the nucleus were decreased after siRNA-BKCa transfection (NF-κB p65/Histone: 0.20±0.03 vs. 0.73±0.12, P < 0.05). CONCLUSIONS BKCa is involved in the pathogenesis of sepsis, and its possible mechanism is to activate NF-κB/NLRP3/caspase-1 signaling pathway to induce inflammatory factor production and cell death.
Humans ; Histones ; Caspase 1 ; Large-Conductance Calcium-Activated Potassium Channels ; Lipopolysaccharides ; NF-kappa B ; NLR Family, Pyrin Domain-Containing 3 Protein ; L-Lactate Dehydrogenase ; Sepsis ; RNA, Small Interfering ; Caspases

Objective: To systematically evaluate the factors affecting diabetic retinopathy (DR) among Chinese adult patients with type 2 diabetes mellitus (T2DM), so as to provide insights into establishment of personalized risk prediction models for DR. Methods: Case-control studies pertaining to factors affecting DR among Chinese adults were retrieved from international and national databases, including CNKI, Wanfang Data, SinoMed, PubMed, Web of Science, Embase and CINAHL from inception to March 31, 2023. A meta-analysis was performed using the software Stata 17.0, and subgroup analysis was performed to explore the source of heterogeneity. Sensitivity analysis was performed using the leave-one-out method, and the publication bias was evaluated using the Egger's test and trim-and-fill method. Results: Totally 4 969 publications were retrieved, and 35 case-control studies were finally enrolled, including 32 high-quality publications (91.43%). The included studies involved 29 228 participants and 10 568 DR patients, and the prevalence of DR was 36.16%. Meta-analysis revealed that age (OR=1.06, 95%CI: 1.00-1.13), duration of T2DM (OR=1.09, 95%CI: 1.08-1.11), systolic blood pressure (OR=1.02, 95%CI: 1.01-1.03), glycated hemoglobin A1c (OR=1.38, 95%CI: 1.26-1.50), fasting blood glucose (OR=1.57, 95%CI: 1.07-2.31), urinary albumin to creatinine ratio (OR=1.50, 95%CI: 1.10-2.04), serum uric acid (OR=1.01, 95%CI: 1.00-1.01), urine microprotein (OR=2.01, 95%CI: 1.96-2.07), triglyceride (OR=1.77, 95%CI: 1.42-2.21), and total cholesterol (OR=1.82, 95%CI: 1.50-2.21) were risk factors for DR, and glomerular filtration rate (OR=0.98, 95%CI: 0.97-0.98) and C-peptide (OR=0.79, 95%CI: 0.68-0.93) were protective factors for DR. Sensitivity analysis of age effects was not robust. Following adjustment for glomerular filtration rate with the trim-and-fill method, there was still a publication bias, and the publication bias of other influencing factors had no impact on pooled effects. Conclusions Age, course of T2DM, systolic blood pressure, glycated hemoglobin A1c, fasting blood glucose, urinary albumin to creatinine ratio, serum uric acid, urine microprotein, triglyceride and total cholesterol were risk factors, and glomerular filtration rate and C-peptide were protective factors for DR among Chinese adults.

Objective:To collect data on urinary flow rate in the elderly female population across the country and to analyze the range of reference values.Methods:This study enrolled 333 subjects from July 2020 to June 2022.The study implementation process was divided into two steps.In the first step, subjects completed an electronic questionnaire, which included basic information about the subject, a short form for urinary incontinence, and a scoring form for the symptoms of overactive bladder syndrome.In the second step, the staff introduced the use of a mobile uroflowmetric device and distributed the instrument and materials.Uroflow rate data were automatically uploaded to a cloud database via the mobile phone.Subsequently, two or more physicians specializing in urinary control performed Uroflow rate-qualifying screenings and conducted statistical analyses.Results:A total of 333 subjects were enrolled in the study, and the researchers collected 1375 qualified urine flow rate records using a mobile urine flow rate instrument.The age of the subjects ranged from 60 to 84 years, with a mean age of 69 years.The reference ranges for urinary flow rate were found to be 24.8-26.2 s, with a mean urinary flow rate of 12.2-12.9 ml/s, a maximum urinary flow rate of 22.2-23.4 ml/s, and a time to peak of 8.5-9.7 s. The study observed a tendency for both maximal and mean urinary flow rates to decrease in older women as their age increased(Pearson correlation coefficient: -0.1, P<0.001). Conclusions:The uroflow rate of older women decreases with aging.Specifically, the average uroflow rate of women over 80 years old is lower than that of other age groups.This study aims to establish normal uroflow parameters for uroflowmetry in healthy older women in China.

Objective:To investigate the status of post-traumatic growth and its afffecting factors in middle-aged and young patients with type 2 diabetes, in order to carry out clinical intervention for reference.Methods:A general data questionnaire, Posttraumatic Growth Inventory, Perceived Social Support Scale, and Connor-Davidson Resilience Scale were used to survey 222 middle-aged and young patients with type 2 diabetes hospitalized from December 2020 to March 2021 in Shandong First Medical University Affiliated Center Hospital, Shandong Provincial Qianfoshan Hospital, Liaocheng People′s Hospital.Results:The total score of Posttraumatic Growth Inventory, Perceived Social Support Scale, and Connor-Davidson Resilience Scale was (45.20 ± 12.90), (42.73 ± 10.16),(51.41 ± 10.60) points in middle-aged and young patients with type 2 diabetes. Regression showed that treatment mode, medical payment mode, social support, and psychological resilience were the main influencing factors of post-traumatic growth levels in middle-aged and young patients with type 2 diabetes ( P<0.05), which could explain 42.3% of the variation. Conclusions:Middle-aged and young patients with type 2 diabetes have grown at low level. Medical staff should concentrate on the positive psychology of patients and improve their level of social support and resilience to promote the production of post-traumatic growth.

Objective:To construct an evaluation index system for quality of use of insulin pumps in hospitals, in order to provide a reference for evaluating quality of use of insulin pumps in hospitals in clinical work.Methods:Based on the three-dimensional quality evaluation model of "structure-process-result", the first draft was determined through literature review and group discussion from January to February 2022. Using the Delphi expert correspondence method, 26 experts from 13 provinces/municipalities in China were consulted in two rounds to determine the quality evaluation index system for the use of insulin pumps in the hospital.Results:The recovery rate of the two rounds of expert questionnaire was 100%, and the expert authority coefficient was 0.971. The mean value of the second round of index importance assignment was 4.500-5.000 and the coefficient of variation was 0-0.22. The final construction of quality evaluation index system of insulin pump use in the hospital included 3 first-level indicators, 15 second-level indicators and 37 third-level indicators.Conclusions:The constructed quality evaluation index system of insulin pump use in the hospital is scientific, reasonable and practical, which has guiding significance for evaluating the quality of insulin pump use in the hospital.

Dental hard tissues lack the ability to self-heal. In dentin and cementum, hydroxyapatite (HA) can exist outside and/or inside collagen fibers. It is difficult to repair or regenerate HA with a highly ordered orientation in the presence of collagen fibers. At present, the biomimetic mineralization of dentin and cementum, mainly carried out by imitating its biological formation process and its physiological structure, can be divided into those originating from the fiber mineralization mechanism and those with HA as the main component. The materials used include natural materials such as demineralized dentin matrix (DDM) and calcined bovine hydroxyapatite (BHA), and synthetic materials such as polymer-induced liquid precursor (PILP) and synthetic HA. In the future, natural materials and synthetic materials should be combined for the restoration and regeneration of dentin and cementum by means of biomimetic mineralization of calcium phosphate released by remineralization solution-HA.

Objective: To understand junior high school students’ sexual knowledge, sexual attitudes, sexual behaviors,as well as acess to sexual knowledge and related influencing factors, so as to provide reference for the practice of sexuality education. Methods: Using stratified cluster sampling method, 7 341 junior high school students were selected from Anhui, Fujian, Gansu, Guangxi, Henan, Xinjiang, Yunnan, Zhejiang and Beijing, and self-compiled questionnaires were used. Results: Junior high school students scored (61.71±18.79) in sexual knowledge, with pass rate and excellent rate being 59.02% and 18.53%. The attitudes towards LGBT was (65.44±20.01), the attitudes towards sexual and healthy behaviors was (67.04±49.23), and the attitudes towards sexual relations and behaviors was (70.75±10.46). Students had intimacy needs and sexual behaviors (18.70%), and some had such behaviors as kissing (13.80%), touching sensitive parts (6.70%) and sexual intercourse (2.20%). The results of multivariate Logistic regression analysis showed that students’ sexual knowledge was related to region, grade and school-based sexuality education (OR=2.11,P<0.05). Conclusion Junior high school students have sexual needs and behaviors, but their sexual knowledge is not sufficient; there are differences in sexual knowledge and attitudes of junior high school students across region,grade and gender; schools should promote school-based sexuality education for junior high school students’ sexual health.

Schisandra is a widely used herb in traditional Chinese medicine. It can maintain the balance of bone reconstruction and play an important role in promoting osteoblast differentiation, regulating osteoclast activity and protecting cartilage tissue. It provides a broad prospect for the treatment of osteoporosis, osteoarthritis and some other diseases. In this paper, the action mechanism of schisandra chinensis and its active components in bone reconstruction was reviewed in order to provide theoretical basis for its product development and application in bone tissue engineering.