This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals ; Osteoblasts/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Glucosides/administration & dosage* ; Cell Differentiation/drug effects* ; Phenols/administration & dosage* ; Mice ; Osteoclasts/metabolism* ; RANK Ligand/genetics* ; Rhodiola/chemistry* ; Osteogenesis/drug effects* ; Signal Transduction/drug effects* ; Interleukin-6/genetics* ; Male ; RAW 264.7 Cells ; Osteolysis/genetics* ; Humans ; Mice, Inbred C57BL

Objective:To analyze the death cases in Beijing municipal hospitals, identify possible medical quality issues in unexpected death cases, so as to provide a basis for medical quality management in medical institutions.Methods:A total of 432 death cases from Beijing municipal hospitals were included, and their acute physiology and chronic health status were evaluated. Based on the evaluation results and the death risk level determined by the diagnosis-related groups, an average of 10 cases were selected from each hospital. A total of 186 cases from 20 hospitals were selected for clinical diagnosis and treatment process evaluation, those cases with problems in the diagnosis and treatment process were defined as unexpected deaths.Results:According to expert judgment, 19.89% (37/186) of the examined deaths had medical quality issues. The main medical quality issues included delayed diagnosis and treatment of patient condition changes (15 cases), inadequate preoperative evaluation (12 cases), failure to consult as required(11 cases), and inadequate prevention of venous thromboembolism (7 cases).Conclusions:Medical institutions should attach importance to the analysis of death cases, address the medical quality issues in the diagnosis and treatment of unexpected death cases, continuously improve medical quality management.

Objective:To analyze the death cases in Beijing municipal hospitals, identify possible medical quality issues in unexpected death cases, so as to provide a basis for medical quality management in medical institutions.Methods:A total of 432 death cases from Beijing municipal hospitals were included, and their acute physiology and chronic health status were evaluated. Based on the evaluation results and the death risk level determined by the diagnosis-related groups, an average of 10 cases were selected from each hospital. A total of 186 cases from 20 hospitals were selected for clinical diagnosis and treatment process evaluation, those cases with problems in the diagnosis and treatment process were defined as unexpected deaths.Results:According to expert judgment, 19.89% (37/186) of the examined deaths had medical quality issues. The main medical quality issues included delayed diagnosis and treatment of patient condition changes (15 cases), inadequate preoperative evaluation (12 cases), failure to consult as required(11 cases), and inadequate prevention of venous thromboembolism (7 cases).Conclusions:Medical institutions should attach importance to the analysis of death cases, address the medical quality issues in the diagnosis and treatment of unexpected death cases, continuously improve medical quality management.

Background: The incidence density of metabolic dysfunction-associated fatty liver disease (MAFLD) and the effect of a healthy lifestyle on the risk of MAFLD remain unknown. We evaluated the prevalence and incidence density of MAFLD and investigated the association between healthy lifestyle and the risk of MAFLD. Methods: A cross-sectional analysis was conducted on 37,422 participants to explore the prevalence of MAFLD. A cohort analysis of 18,964 individuals was conducted to identify the incidence of MAFLD, as well as the association between healthy lifestyle and MAFLD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustments for confounding factors. Results: The prevalence of MAFLD, non-alcoholic fatty liver disease, and their comorbidities were 30.38%, 28.09%, and 26.13%, respectively. After approximately 70 thousand person-years of follow-up, the incidence densities of the three conditions were 61.03, 55.49, and 51.64 per 1,000 person-years, respectively. Adherence to an overall healthy lifestyle was associated with a 19% decreased risk of MAFLD (HR, 0.81; 95% CI, 0.72 to 0.92), and the effects were modified by baseline age, sex, and body mass index (BMI). Subgroup analyses revealed that younger participants, men, and those with a lower BMI experienced more significant beneficial effects from healthy lifestyle. Conclusion Our results highlight the beneficial effect of adherence to a healthy lifestyle on the prevention of MAFLD. Health management for improving dietary intake, physical activity, and smoking and drinking habits are critical to improving MAFLD.

Objective:To study the effects of Zuogui Pills on the expressions of miR-133b-3p and RhoA in osteoclasts of postmenopausal osteoporosis rats; To discuss its potential mechanism.Methods:SD female rats were randomly divided into normal group, model group, sham-operation group, and Zuogui Pills group using a random number table method, with 6 rats in each group. The model group and Zuogui Pills group were treated with oophorectomy to construct a rat model of osteoporosis. Zuogui Pills group was orally administered with Zuogui Pills decoction at a concentration of 10 g/kg for 12 consecutive weeks. Colorimetric method was used to measure the serum calcium and phosphorus levels of rats, and ELISA method was used to detect ALP levels. Bone density meter was used to measure the bone density of the femurs of rats in each group. The osteoclast of each group were cultured, and the expressions of RANKL and RUNX2 protein were detected by Western blot. MiRNA sequencing and differential expression analysis were performed on bone tissues of rats. Osteoclasts were treated with miR-133b-3p mimic and its negative control. The cell proliferation activity of osteoclasts was detected by cell counting kit-8 (CCK-8). The osteoclast differentiation activity was detected by the tartrate-resistant acid phosphatase staining. The dual-luciferase reporter assay was used to detect the relationship between miR-133b-3p and RhoA. The "rescue" experiment of miR-133b-3p mimic and RhoA co-expression were used to study the molecular regulatory mechanism of Zuogui Pills on osteoclast activity.Results:Compared with the model group, the bone mineral density of Zuogui Pills group significantly increased ( P<0.05, P<0.01), the levels of calcium and phosphorus in serum increased, the level of alkaline phosphatase ALP decreased ( P<0.05), the expression of RANKL protein decreased, and the expression of RUNX2 protein increased. Sequencing results showed that rno-miR-133b-3p was down-regulated in osteoclasts of postmenopausa osteoporosis rats treated with Zuogui Pills with the maximum difference ( P<0.01). Q-PCR results showed that the expression of miR-133b-3p in osteoclasts of Zuogui Pills group was significantly lower than that of the model group. The upregulation of miR-133b-3p could significantly promote the cell proliferation and differentiation of osteoclasts. RhoA overexpression could reverse the excessive proliferation and differentiation of osteoclasts caused by miR-133b-3p overexpression. Conclusions:RhoA is the target gene regulated by miR-133b-3p. Zuogui Pills can inhibit the activity of osteoclasts by regulating miR-133b-3p/RhoA axis, relieving the symptoms of osteoporosis.

Objective:To explore the effect of closed-loop nursing on self-efficacy and nursing satisfaction in children with nephrotic syndrome (NS) .Methods:From March 2019 to January 2021, convenience sampling was used to select 104 children with NS and their accompanying parents in Henan Provincial People's Hospital as the research object. The children were divided into the control group and the observation group by random number table method, 52 cases in each group. The control group received routine nursing, and the observation group carried out closed-loop nursing on the basis of the control group. The scores of the General Self-efficacy Scale and Satisfaction Scale were compared between the two groups.Results:After three months of intervention, the children's self-efficacy score in the observation group was higher than that in the control group, and the parents' satisfaction with nursing was 94.23% (49/52) , which was higher than 78.85% (41/52) in the control group. The differences were all statistically significant ( P<0.05) . Conclusions:The closed-loop nursing can improve the self-efficacy of children with NS and the satisfaction of their parents, which is worthy of clinical promotion.

Objective:To establish a candidate reference procedure for the enumeration of cell particles in urine and applied to the multi-center performance evaluation of an automated urine formed elements analyzer.Methods:According to the standardized mannual microscopic examination of fresh non-centrifuged urine samples and the recommended reference method for enumeration of cell particles in urine published by ISLH, we established a candidate reference procedure for the enumeration of cell particles in urine. From four class A tertiary hospitals′ clinical laboratories, three rigorous trained technicians per hospital tested the same specimen respectively using the reference procedure. Each specimen was repeatedly counted 5 times, obtaining the quantitative results of cell particles were obtained in urine. Four hospitals used the established candidate reference measurement procedure and the automated urine formed elements analyzer to detect 40 to 60 urine specimens from September 2020 to January 2021, and evaluate the established reference method, meanwhile evaluate the accuracy and consistency of the each count from automated urinalysis analyzer.Results:Using the candidate reference measurement procedures, the coefficient of variation of results derived from three trained technicians per hospital was less than 6.98% (red blood cells), 6.99% (white blood cells), 13.94% (epithelial cells) and met the quality requirements. The performance evaluation results of automated urine formed elements analyzer showed that the accuracy of red blood cells, white blood cells and epithelial cells met the requirements (bias≤4.98%) and was well consistent with the reference measurement procedure ( R2≥0.989). Conclusions:A candidate reference measurement procedure for the enumeration of urine cell particles was successfully established with satisfactory precision and accuracy. This procedure was applied to multicenter performance evaluation of an automated urine formed elements analyzer with good accuracy and consistency.

P-glycoprotein (P-gp) highly expressed in cancer cells can lead to multidrug resistance (MDR) and the combination of anti-cancer drugs with P-gp inhibitor has been a promising strategy to reverse MDR in cancer treatment. In this study, we established a label-free and detergent-free system combining surface plasmon resonance (SPR) biosensor with styrene maleic acid (SMA) polymer membrane proteins (MPs) stabilization technology to screen potential P-gp inhibitors. First, P-gp was extracted from MCF-7/ADR cells using SMA polymer to form SMA liposomes (SMALPs). Following that, SMALPs were immobilized on an SPR biosensor chip to establish a P-gp inhibitor screening system, and the affinity between P-gp and small molecule ligand was determined. The methodological investigation proved that the screening system had good specificity and stability. Nine P-gp ligands were screened out from 50 natural products, and their affinity constants with P-gp were also determined. The in vitro cell verification experiments demonstrated that tetrandrine, fangchinoline, praeruptorin B, neobaicalein, and icariin could significantly increase the sensitivity of MCF-7/ADR cells to Adriamycin (Adr). Moreover, tetrandrine, praeruptorin B, and neobaicalein could reverse MDR in MCF-7/ADR cells by inhibiting the function of P-gp. This is the first time that SMALPs-based stabilization strategy was applied to SPR analysis system. SMA polymer can retain P-gp in the environment of natural lipid bilayer and thus maintain the correct conformation and physiological functions of P-gp. The developed system can quickly and accurately screen small molecule ligands of complex MPs and obtain affinity between complex MPs and small molecule ligands without protein purification.

A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
Humans ; Pulse Wave Analysis ; Albuminuria ; Ankle Brachial Index ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Vascular Stiffness ; Prospective Studies ; Risk Factors ; China/epidemiology*

Systemic treatment is the first choice for patients with advanced hepatocellular carcinoma. Atezolizumab combined with bevacizumab can bring better survival for patients with advanced hepatocellular carcinoma. The authors introduce the efficacy and safety management of a hepatocellular carcinoma case with postoperative recurrence who received treatment of atezoli-zumab combined with bevacizumab. The patient had a probability of pseudoprogression during treatment, and had a good result of a continuous partial response over 2 years.