OBJECTIVE To evaluate the effectiveness and safety of sequential therapy with parathyroid hormone analogues and bisphosphonates for osteoporosis. METHODS PubMed， Embase， the Cochrane Library， Web of Science， China National Knowledge Infrastructure， VIP， Wanfang data， and SinoMed were searched in both English and Chinese databases from their inception to March 25， 2024. Two researchers independently conducted literature searches， screening， and data extraction. Review Manager 5.4 software was used for the meta-analysis. Subgroup analyses and sensitivity analyses were performed based on different medication sequences in the treatment group to account for potential sources of heterogeneity. RESULTS A total of 7 randomized controlled trials involving 2 461 participants were included， with 1 215 in the treatment group and 1 246 in the control group. The meta-analysis results showed that the treatment group using sequential therapy with parathyroid hormone analogues and bisphosphonates had superior effects on improving bone mineral density at the lumbar spine [SMD＝0.90， 95%CI （0.44， 1.35）， P＜0.001]， total hip [SMD=0.68， 95%CI （0.14， 1.21）， P＝0.01]， and femoral neck [SMD＝0.45， 95%CI （0.04， 0.86）， P＝0.03] compared to the control group. It also significantly outperformed the control group in reducing the incidence of fractures post- treatment [OR＝0.72， 95%CI （0.54， 0.97）， P＝0.03].significant difference was noted in the incidence of adverse reactions between the two groups [OR＝1.21， 95%CI （0.99， 1.46）， P＝0.06]. Subgroup analysis based on intervention measures in the treatment group showed that switching from bisphosphonates to parathyroid hormone analogues [SMD＝0.56， 95%CI （0.09， 1.03）， P＝0.02] or switching from parathyroid hormone analogues to bisphosphonates [SMD＝0.97， 95%CI （0.49， 1.46）， P＜0.001] both significantly potentiated lumbar spine bone mineral density compared to the control group. Switching from bisphosphonates to parathyroid hormone analogues also significantly promoted total hip bone mineral density compared to the control group [SMD＝0.66， 95%CI （0.18， 1.13）， P＝0.007]. Sensitivity analysis indicated that the results of this study were robust. CONCLUSIONS Sequential therapy with parathyroid hormone analogues and bisphosphonates can be recommended as an effective treatment for patients with osteoporosis， with good safety profiles. The medication sequences should be individually adjusted based on the patient’s particular situation and the different responses of various skeletal sites.

Objective To investigate the predictive value of white blood cell-to-hematocrit ratio (WBCHR) for in-hospital major adverse cardiovascular events (MACE) after reperfusion therapy in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods A case-control study was conducted to retrospectively select 319 patients with first-time diagnosis of STEMI who underwent percutaneous coronary intervention (PCI). Patients were divided into MACE group (69 cases) and non-MACE group (250 cases) based on the occurrence of MACE during hospitalization. Clinical data, including general information, laboratory test indicators, echocardiography, and coronary angiography results, were compared between the two groups. Univariate and multivariate Logistic regression analyses were performed to explore the risk factors for in-hospital MACE after reperfusion therapy in STEMI patients. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive value of WBCHR for in-hospital MACE after reperfusion therapy in STEMI patients. Results The levels of fasting blood glucose, uric acid, creatinine, white blood cell count, neutrophil count, high-sensitivity C-reactive protein (hs-CRP), D-dimer, and WBCHR were significantly higher in the MACE group than in the non-MACE group, while red blood cell count, hemoglobin, hematocrit, and left ventricular ejection fraction were lower (P < 0.05). No significant differences were observed in age, gender, smoking history, hypertension history, diabetes history, door-to-wire (D2W) time, total cholesterol, triglycerides, and the number of diseased vessels between the two groups (P>0.05). Multivariate Logistic regression analysis revealed that elevated uric acid levels (OR=1.005; 95%CI, 1.002 to 1.009; P=0.004), decreased hemoglobin concentration (OR=0.964; 95%CI, 0.941 to 0.988; P=0.003), increased hs-CRP levels (OR=1.032; 95%CI, 1.009 to 1.056; P=0.007), and increased WBCHR (OR=1.455; 95%CI, 1.295 to 1.635; P < 0.001) were independent risk factors for in-hospital MACE after reperfusion therapy in STEMI patients. ROC curve analysis showed that the area under the curve of WBCHR for predicting in-hospital MACE after reperfusion therapy in STEMI patients was 0.855 (95%CI, 0.796 to 0.914, P < 0.001), with a sensitivity of 63.8% and a specificity of 99.6%. Conclusion WBCHR is an independent influencing factors of in-hospital MACE after reperfusion therapy in STEMI patients and has a high predictive value for in-hospital MACE in these patients.

Objective To establish an efficient method for isolating migrasomes from RAW264.7 macrophages and identifying these isolated migrasomes. Methods Scanning electron microscopy was used to observe the morphological characteristics of migrasomes produced by RAW264.7 cells. A 0.45 μm filter was employed for reverse filtration and elution to isolate the migrasomes. The morphological characteristics of the migrasomes were then observed using transmission electron microscopy. Western blot analysis was performed to determine the expression of characteristic markers of the migrasomes. The RNA carried by the migrasomes was analysed by using LabChip bioanalyzer. Results Scanning electron microscopy revealed that the migrasomes, with membranous structures, were attached to the tip or bifurcation of the retraction fiber formed in the tail of RAW264.7 cells. Transmission electron microscopy showed that the isolated migrasomes had a typical oval vesicle-like structure with wrinkled membrane surfaces. Western blot analysis confirmed the expression of the characteristic markers phosphatidylinositol glycan anchor biosynthesis class K (PIGK), epidermal growth factor domain-specific O-linked N-acetylglucosamine transferase (EOGT) and tetraspanin 4 (TSPAN4) in the migrasomes, while the EV (extracellular vesicle) markers tumor susceptibility gene 101 (TSG101) and Arabidopsis homolog of apoptosis-linked gene 2-interacting protein X (ALIX) were not detected. Furthermore, the isolated migrasomes were found to be rich in small RNA, which were approximately 25-200 nt in length. Conclusion A method for the extraction of well-structured and high quality migrasomes from macrophages is established.
Extracellular Vesicles ; Microscopy, Electron, Transmission ; RNA ; Macrophages

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
Male ; Humans ; Middle Aged ; Atorvastatin/therapeutic use* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Hypercholesterolemia/drug therapy* ; Cholesterol, LDL/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome ; Triglycerides ; Apolipoproteins B/therapeutic use* ; Double-Blind Method ; Pyrroles/therapeutic use*

OBJECTIVES: Gastric cancer is a common cancer of the digestive system. Long non-coding RNA (lncRNA) plays an important role in the formation and development of gastric cancer. This study aims to investigate the effect of long non-coding lncRNA 114227 on biologic behaviors in gastric cancer cells. METHODS: The experiment was divided into 4 groups: a negative control (NC) group, a lncRNA 114227 small interference (si-lncRNA 114227) group, an empty vector (Vector) group, and an overexpression vector (OE-lncRNA 114227) group. The expressions of lncRNA 114227 in gastric mucosa and gastric cancer tissues, gastric mucosal epithelial cells and different gastric cancer strains were determined by real-time reverse transcription PCR (real-time RT-PCR).The proliferation were detected by CCK-8 assay in gastric cancer cells. The epithelial-mesenchymal transformation (EMT) was utilized by Transwell assay, scratch healing assay, and Western blotting in gastric cancer cells. The effect of lncRNA 114227 on proliferation of gastric cancer cells was detected by tumor bearing experiment in nude mice in vivo. RESULTS: The expression level of lncRNA 114227 in the gastric cancer tissues was significantly lower than that in the gastric mucosa tissues, and in 4 kinds of gastric cancer strains was all significantly lower than that in gastric mucosal epithelial cells (all P<0.01). In vitro, the proliferation and migration abilities of gastric cells were significantly reduced after overexpressing lncRNA 114227, and cell proliferation and migration were enhanced after silencing lncRNA 114227 (all P<0.05). The results of in vivo subcutaneous tumorigenesis in nude mice showed that the tumorigenic volume of the tumor-bearing mice in the OE-lncRNA 114227 group was significantly smaller than that of the Vector group, and the tumorigenic quality was lower than that of the Vector group (P<0.05), indicating that lncRNA 114227 inhibited tumorigenesis. CONCLUSIONS The expression of lncRNA 114227 is downregulated in gastric cancer gastric cancer tissues and cell lines. LncRNA 114227 may inhibit the proliferation and migration of gastric cancer cells through EMT process.
Animals ; Mice ; RNA, Long Noncoding/metabolism* ; Stomach Neoplasms/pathology* ; Mice, Nude ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Carcinogenesis/genetics* ; Cell Movement/genetics* ; Epithelial-Mesenchymal Transition/genetics* ; Gene Expression Regulation, Neoplastic ; Apoptosis/genetics*

Objective: To explore the effect of the comprehensive intervention on overweight and obesity among middle school students at the population level (health education lecture and official account push) and individual level (personalized dietary guidance), so as to provide a reference for preventing and controlling their overweight and obesity. Methods: Three junior high schools and three senior high schools were randomly selected in Guangzhou in 2018 by convenience sampling. Through physical examination, 1 457 overweight and obese students aged from 12 to 18 years old were screened. Intervention was administered through "Student Personalized Dietary Guidance" manual, health tweets on the official accounts, and health education lectures from September 2018 to December 2019. The Chi square test was used to compare the difference in overweight and obesity constituent ratio between the two groups before and after the intervention. And intervention effect was evaluated by analyzing the number needed to treated(NTT). Results: The proportion of overweight before the intervention was 66.71% (972/1 457), and decreased to 59.92% (873/1 457) after the intervention; the proportion of obesity before the intervention was 33.29% (485/1 457), which decreased to 26.63% (388/1 457) after the intervention. Among obese students, the smallest NNT was seen in the girl group aged 12-13 years (NNT=2.6, 95% CI =1.9-4.1), while the largest NNT in the boy group aged 14-18 years (NNT=5.9, 95% CI =4.7-8.1). The NNT of the girls aged 12-13 years was the smallest (NNT=2.7, 95% CI =2.2-3.5), and the NNT of the boys aged 14-18 years was the largest (NNT=7.4, 95% CI =6.0-9.7). Conclusion Health education at population level (health education lectures, official account push) with individual level (personalized dietary guidance) can effectively intervene overweight and obesity among middle school students in Guangzhou.

The implantation of biventricular assist device (BiVAD) is more challenging than that of left ventricular assist device for the interaction in the process of multiple input and output. Besides, ventricular assist device (VAD) often runs in constant speed (CS) mode in clinical use and thus BiVAD also faces the problems of low pulsation and imbalance of blood volume between systemic circulation and pulmonary circulation. In this paper, a delay assist mode for a VAD by shortening the support time of VAD was put forward. Then, the effect of the delay mode on cardiac output, pulsation and the function of the aortic valve was observed by numerical method and the rules of hemodynamics were revealed. The research showed that compared with VAD supported in CS mode, the VAD using delay mode in systolic and diastolic period proposed in this paper could meet the demand of cardiac output perfusion and restore the function of the arterial valves. The open ratio of aortic valve (AV) and pulmonary valve (PV) increased with the time set in delay mode, and the blood through the AV/PV helped to balance the left and the right cardiac volume. Besides, delay mode also improved the pulsation index of arterial blood flow, which is conducive to the recovery of the ventricular pulse function of patients.
Cardiovascular System ; Diastole ; Heart Failure ; Heart Rate ; Heart-Assist Devices ; Hemodynamics ; Humans ; Models, Cardiovascular

Objective: To explore the association between maternal pre pregnancy and pre delivery overweight with overweight and obesity among offspring during adolescence in Guangzhou, and to provide evidence for child obesity prevention. Methods: Based on the routine physical examination of primary and secondary school students in Guangzhou, random sampling was used to 6 middle schools and questionnaire survey was conducted among 3 384 students and their parents. Students with overweight and obesity were included in the case group, and the other students were included in the control group. Propensity Score Matching (PSM) was adopted to reduce selection bias. Logistic regression model and χ 2 test were used to analyze the data before and after PSM. Results: The result of univariate analysis showed that there were statistically significant differences between overweight/obese group and the control group by gender, schooling stage (middle and high schools), picky eater, family history of obesity, family monthly income, delivery mode, high birthweight, and gestational weight gain before PSM( χ 2=42.38, 10.64, 14.47, 26.85, 10.58, 13.59 , 15.53, 20.64, P <0.05). After PSM, results showed that there were no statistically significant differences between overweight/obese group and the control group in middle and high schools, and mother delivery mode( P >0.05). Logistic regression analysis showed that the risk of overweight and obesity of maternal pre pregnancy on adolescent offspring was 1.54 times higher than control group (95% CI =1.01-2.36) before PSM, and the overweight and obesity of maternal predelivery also increased the risk of overweight and obesity of adolescent offspring( OR=2.35, 95%CI =1.67-3.31). After PSM, maternal overweight and obesity pre pregnancy ( OR=2.17, 95%CI =1.41-3.34) and maternal overweight and obesity pre delivery( OR=2.99, 95%CI =2.08-4.31) significantly increased the risk of overweight and obesity in adolescent offspring. Conclusion Maternal overweight and obesity pre pregnancy and pre delivery are associated with increased risk of overweight and obesity in adolescent offspring.

Vascular calcification is an important pathophysiological basis of cardiovascular disease with its underlying mechanism unclear. In recent years, studies have shown that aging is one of the risk factors for vascular calcification. The purpose of this study was to investigate the microenvironmental characteristics of vascular calcification, identify aging/senescence-induced genes (ASIGs) closely related to calcified plaques, and explore the evolution trajectory of vascular calcification cell subsets. Based on the bioinformatics method, the single cell transcriptome sequencing data (Gene Expression Omnibus: GSE159677) of carotid artery samples from 3 patients undergoing carotid endarterectomy were grouped and annotated. Vascular calcification-related aging genes were identified by ASIGs data set. The pseudotime trend of ASIGs in cell subsets was analyzed by Monocle 3, and the evolution of vascular calcification cells was revealed. After quality control, all cells were divided into 8 cell types, including B cells, T cells, smooth muscle cells, macrophages, endothelial cells, fibroblasts, mast cells, and progenitor cells. Ten ASIGs related to vascular calcification were screened from the data set of ASIGs, which include genes encoding complement C1qA (C1QA), superoxide dismutase 3 (SOD3), lysozyme (LYZ), insulin-like growth factor binding protein-7 (IGFBP7), complement C1qB (C1QB), complement C1qC (C1QC), Caveolin 1 (CAV1), von Willebrand factor (vWF), clusterin (CLU), and αB-crystallin (CRYAB). Pseudotime analysis showed that all cell subsets were involved in the progression of vascular calcification, and these ASIGs may play an important role in cell evolution. In summary, AGIS plays an important role in the progression of vascular calcification, and these high expression genes may provide ideas for early diagnosis and treatment of vascular calcification.
Humans ; Endothelial Cells ; Muscle, Smooth, Vascular ; Aging ; Vascular Calcification/metabolism* ; Computational Biology ; Myocytes, Smooth Muscle/metabolism*

Objective: To understand the homology and resistance characteristics of Streptococcus pneumoniae (S. pneumoniae) in healthy preschool children, so as to provide basis for disease transmission prevention and rational use of antibiotics. Methods: Stratified cluster random sampling method was used to sample 1 829 healthy children from six kindergartens in Shunde District, Foshan City. Nasal swabs were taken and tested for S. pneumoniae. Multi locus sequence typing was used for homology analysis. The Chi squared test and random forest analysis were used to explore the resistance characteristics. Results: The nasal carriage rate of S. pneumoniae and multidrug resistant S. pneumoniae (MDRSP) in children were 22.5%(412/1 829) and 21.3%(390/1 829), respectively. Homology analysis in sequence types showed that the total homology rates of 6 kindergartens were 93.5%(87/93), 91.1% (72/79), 89.2%(58/65), 88.9%(64/72), 86.2%(50/58), 77.8%(35/45), respectively. It was found that the highest homology rate was 82.8% (48/58) within class and 93.1% (81/87) between classes. S. pneumoniae was mainly resistant to azithromycin (97.1%, 400/412), erythromycin (92.0%, 379/412) and tetracycline (91.5%, 377/412). The dominant multidrug resistance pattern of MDRSP isolates was not sensitive to azithromycin, erythromycin, cotrimoxazole, tetracycline and clindamycin. Random forest analysis indicated that the important phenotypic markers associated with MDRSP were resistance to azithromycin, cotrimoxazole, tetracycline, clindamycin and erythromycin(MDG=8.94, 6.92, 5.80, 4.84, 2.58). Conclusion The risk of cross transmission of S. pneumoniae among preschool children is high, and direct contact is the main way of transmission. Consequently, kindergartens and health departments should take effective measures to effectively prevent and block the spread of Streptococcus pneumoniae.