This study aims to investigate the optimal ratio of Astragali Radix-Curcumae Rhizoma(AC) for inhibiting the proliferation of 143B osteosarcoma cells, and to investigate the mechanism by which AC inhibits osteosarcoma growth and metastasis through angiogenesis and cell adhesion mediated by the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/hypoxia inducible factor-1α(HIF-1α) pathway. A subcutaneous 143B tumor-bearing nude mouse model was successfully established and randomly divided into the model group, and the AC 1∶1, 2∶1, and 4∶1 groups. Body weight, tumor volume, and tumor weight were recorded. Real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot were used to detect the mRNA and protein expression levels of PI3K, Akt, phosphorylated Akt(p-Akt), HIF-1α, vascular endothelial growth factor A(VEGFA), transforming growth factor-β1(TGF-β1), epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), vimentin, matrix metalloproteinase 2(MMP2), matrix metalloproteinase 9(MMP9), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3 in the hypoxic core region of the tumor tissue. A cell hypoxia model was established, and the effects of AC-medicated serum(model group, AC 1∶1, 2∶1, and 4∶1 groups) on angiogenesis, proliferation, adhesion, invasion, and migration of 143B osteosarcoma cells were examined through CCK-8, flow cytometry, Transwell assay, cell adhesion assay, and HUVEC tube formation assay. The results showed that compared with the model group, the tumor weight and volume were smallest in the 2∶1 group. The expression levels of PI3K, Akt, p-Akt, HIF-1α, VEGFA, and TGF-β1 were significantly decreased, and the protein expression of E-cadherin was significantly increased, while the protein expression of N-cadherin, vimentin, MMP2, and MMP9 was significantly decreased. Additionally, the protein expression of Bax and caspase-3 was significantly increased, and Bcl-2 protein expression was significantly decreased. In vitro experiments showed that after intervention with AC-medicated serum at a 2∶1 ratio, the cell activity, adhesion, invasion, and migration of 143B cells were significantly reduced, apoptosis was significantly increased, and HUVEC tube formation was significantly decreased. In conclusion, the 2∶1 ratio of AC showed the most effective inhibition of 143B cell growth. AC can inhibit the growth and metastasis of osteosarcoma 143B cells by regulating the PI3K/Akt/HIF-1α signaling pathway, inhibiting angiogenesis and reducing cell adhesion, invasion, and migration.
Osteosarcoma/pathology* ; Animals ; Proto-Oncogene Proteins c-akt/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Humans ; Mice ; Cell Adhesion/drug effects* ; Cell Proliferation/drug effects* ; Neovascularization, Pathologic/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Phosphatidylinositol 3-Kinases/genetics* ; Cell Line, Tumor ; Mice, Nude ; Signal Transduction/drug effects* ; Astragalus Plant/chemistry* ; Bone Neoplasms/physiopathology* ; Male ; Rhizome/chemistry* ; Mice, Inbred BALB C ; Angiogenesis

A novel pair of Z/E isomeric compounds with unprecedented carbon skeleton were isolated from an aqueous extract of Aspongopus chinensis Dallas by macroporous resin, silica gel, and semi-preparative high performance liquid chromatography (HPLC). Their structures were identified by nuclear magnetic resonance (NMR), Infrared spectroscopy (IR), Mass spectroscopy (MS) and other spectroscopic methods as (Z)-3-(but-1″-en-1″-yl)-1-(2ʹ-hydroxyethyl)-4-propylpyridin-1-ium, namely aspongopyridine A, and (E)-3-(but-1″-en-1″-yl)-1-(2ʹ-hydroxyethyl)-4-propylpyridin-1-ium, namely aspongopyridine B, respectively. Besides, the anti-inflammatory, anti-tumor, acetylcholinesterase inhibition and butyrylcholinesterase inhibition activities of the compounds 1 and 2 were evaluated. The results showed that compounds 1 and 2 have no anti-inflammatory, anti-tumor, and butyrylcholinesterase inhibition activities instead of weak acetylcholinesterase inhibition activity.

Aim To evaluate the effectiveness and safety of remimazolam tosylate for administering general anesthesia in morbidly obese patients.Methods This clinical trial was conducted at a single center from De-cember 2021 to October 2023.It assessed 108 morbid-ly obese patients(body mass index,BMI≥40)who underwent laparoscopic sleeve gastrectomy.Patients were randomly assigned to either the remimazaolam group(Group R)or the propofol group(Group P)for general anesthesia induction and maintenance.The primary outcome was to compare the incidence of ad-verse events and postoperative recovery characteristics between the two groups.Results During induction pe-riod,the incidence of adverse events was higher in group P,including hypotension(P＜0.01),hypox-emia(P＜0.05),bradycardia(P＜0.01),and in-creased vasopressor requirement(P＜0.05).The time to loss of consciousness and BIS falling to 60 was shor-ter in group P than in group R(P＜0.01).There were no statistically significant differences between the two groups in terms of postoperative quality of recovery(QoR-40 score),24-hour postoperative pain visual an-alogue scale(VAS)scores and morphine consump-tion.In conclusion,remimazolam tosylate,utilized for anesthesia induction in morbidly obese patients,signif-icantly reduced hypotension and hypoxemia compared to propofol,while it could also maintain similar postop-erative recovery quality.Conclusions Remimazolam is effective in reducing the incidence of hypotension and hypoxaemia during the induction period of general anaesthesia in morbidly obese patients and it is compa-rable to propofol in terms of quality of postoperative re-covery.

Objective: To explore the gene-lifestyle interaction on coronary heart disease (CHD) in adult twins of China. Methods: Participants were selected from twin pairs registered in the Chinese National Twin Registry (CNTR). Univariate interaction model was used to estimate the interaction, via exploring the moderation effect of lifestyle on the genetic variance of CHD. Results: A total of 20 477 same-sex twin pairs aged ≥25 years were recruited, including 395 CHD cases, and 66 twin pairs both had CHD. After adjustment for age and sex, no moderation effects of lifestyles, including current smoking, current drinking, physical activity, intake of vegetable and fruit, on the genetic variance of CHD were found (P>0.05), suggesting no significant interactions. Conclusion: There was no evidence suggesting statistically significant gene-lifestyle interaction on CHD in adult twins of China.
Adult ; China/epidemiology* ; Coronary Disease/genetics* ; Diseases in Twins/genetics* ; Humans ; Life Style ; Twins/genetics* ; Twins, Dizygotic ; Twins, Monozygotic

Objective:To investigate the predictors of the efficacy of extracorporeal shock wave lithotripsy (ESWL) in the treatment of ureteral calculi, and to evaluate the predictive value of the maximum ureteral wall thickness (UWT) in the treatment of ureteral calculi with ESWL.Methods:The clinical data of 138 patients with ureteral calculi treated with ESWL in the Second People's Hospital of Hefei from January 2020 to December 2020 were retrospectively analyzed. There were 91 males and 47 females. The age was (50.9±14.8) years old. The body mass index was (25.3±3.6) kg/m 2. The stones of 73 cases were located on the left side and 65 cases were on the right side. 70 cases had upper ureteral stones, 18 cases had middle ureteral stones, and 50 cases had lower ureteral stones. The median length of the stone was 8.5 (7.5, 10.5) mm. The CT value of the stone was 509 (343, 783) HU. The anteroposterior diameter of the renal pelvis was 12.0 (10.1, 16.0) mm, and UWT was (2.8 ± 0.8) mm. All patients underwent urinary non-contrast CT before lithotripsy, and the UWT of the stone bed was measured on the CT images. According to the stone removal situation 2 weeks after the operation, the patients were divided into a successful lithotripsy group and a failed lithotripsy group. Univariate analysis was used to compare the differences of various indicators between the two groups, and multivariate logistic regression was used to analyze the independent predictors of ESWL in the treatment of ureteral calculi for the indicators. The receiver operating characteristic (ROC) curve was used to calculate the area under the curve (AUC) of each independent predictor, and the cut-off value, sensitivity and specificity were analyzed. Results:All operations were successfully completed, and the success rate of the first-stage lithotripsy was 71.7% (99/138). The results of univariate analysis showed that the stone length diameter, stone CT value, anteroposterior diameter of renal pelvis, stone skin distance, and UWT were significantly different between the successful lithotripsy group and the failure group ( P<0.05). There was no significant difference in age, gender, body mass index, stone side and stone location ( P>0.05). The results of multivariate logistic analysis showed that stone length ( OR=1.393, P=0.015), stone CT value ( OR=1.002, P=0.043) and UWT ( OR=17.997, P<0.001) were all for the efficacy of ESWL in the treatment of ureteral stones. The ROC curve was used to compare the three independent predictors. The area under the UWT curve was the largest (AUC=0.898, P<0.001), followed by the length of the stone (AUC=0.744, P<0.001), and the CT value of the stone (AUC=0.672, P= 0.002). The cut-off value for UWT was 3.19 mm, which had a sensitivity of 91.9% and a specificity of 71.8% for predicting the success of ESWL lithotripsy. When dividing the patients into thin wall group (UWT ≤3.19 mm) and thick wall group (UWT>3.19 mm) according to the cut-off value, the success rates of one-stage lithotripsy in the two groups were 89.2% (91 / 102) and 22.2% (8/36), respectively ( P<0.05). Conclusions:UWT, calculus length and calculus CT value are independent predictors of the efficacy of ESWL in the treatment of ureteral calculi, and UWT has the best predictive value. When UWT≤3.19 mm, the success rate of ESWL in the treatment of ureteral calculi is higher.

OBJECTIVE: To estimate the univariate heritability of resting heart rate and common chronic disease such as hypertension, diabetes, and dyslipidemia based on extended pedigrees in Fujian Tulou area and to explore bivariate heritability to test for the genetic correlation between resting heart rate and other relative phenotypes. METHODS: The study was conducted in Tulou area of Nanjing County, Fujian Province from August 2015 to December 2017. The participants were residents with Zhang surname and their relatives from Taxia Village, Qujiang Village, and Nanou Village or residents with Chen surname and their relatives from Caoban Village, Tumei Village, and Beiling Village. The baseline survey recruited 1 563 family members from 452 extended pedigrees. The pedigree reconstruction was based on the family information registration and the genealogy booklet. Univariate and bivariate heritability was estimated using variance component models for continuous variables, and susceptibility-threshold model for binary variables. RESULTS: The pedigree reconstruction identified 1 seven-generation pedigree, 2 five-generation pedigrees, 23 four-generation pedigrees, 186 three-generation pedigrees, and 240 two-generation pedigrees. The mean age of the participants was 57.2 years and the males accounted for 39.4%. The prevalence of hypertension, diabetes, dyslipidemia in this population was 49.2%, 10.0%, and 45.2%, respectively. The univariate heritability estimation of resting heart rate, hypertension, and dyslipidemia was 0.263 (95%CI: 0.120－0.407), 0.404 (95%CI: 0.135－0.673), and 0.799 (95%CI: 0.590－1), respectively. The heritability of systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was 0.379, 0.306, 0.393, 0.452, 0.568, 0.852, and 0.387, respectively. In bivariate analysis, there were phenotypic correlations between resting heart rate with hypertension, diabetes, diastolic blood pressure, fasting glucose, and triglyceride. After taking resting heart rate into account, there were strong genetic correlations between resting heart rate with fasting glucose (genetic correlation 0.485, 95%CI: 0.120－1, P<0.05) and diabetes (genetic correlation 0.795, 95%CI: 0.181－0.788, P<0.05). CONCLUSION Resting heart rate was a heritable trait and correlated with several common chronic diseases and related traits. There was strong genetic correlation between resting heart rate with fasting glucose and diabetes, suggesting that they may share common genetic risk factors.
Blood Pressure ; Chronic Disease ; Female ; Heart Rate ; Humans ; Hypertension ; Male ; Middle Aged ; Pedigree

This study aimed to investigate the mechanisms of Yu-Ping-Feng-San (YPFS) on attenuating allergic inflammation in the initial stage of atopic dermatitis (AD). AD mouse model was established with fluorescein isothiocyanate (FITC) sensitization and elicitation. Epithelial barrier structure was observed with transmission electron microscope. The populations of dendritic cells (DCs) and group 2 innate lymphoid cells (ILC2s) were detected by flow cytometry. Human immortalized keratinocyte (HaCaT) cells were stimulated with Poly(I:C)/TNF-α in vitro to assessthymic stromal lymphopoietin (TSLP), interleukin (IL)-33 and nuclear factor-κB (NF-κB) levels or expressions by immunofluorescence, enzyme linked immunosorbent assay (ELISA) and western blot. In the initial stage of AD, ear swelling and infiltration of inflammatory cells in ear tissues were markedly attenuated with YPFS treatments. The damaged structures of ear epithelium and the increased levels of Th2-cytokines induced by FITC were significantly rescued in YPFS-treated mice. The production of pro-allergic cytokines, TSLP and IL-33, as well as the cell populations of their target cells DCs and ILC2s were decreased in AD model, respectively. Likewise, the levels of TSLP and IL-33 in Poly(I:C)/TNF-α-stimulated HaCaT cells showed the same results. Lower levels of p-NF-κB were detected with YPFS treatment, and the expressions of TSLP and IL-33 could be further decreased with inhibiting of NF-κB. Therefore, YPFS attenuates allergic inflammation in the initial stage of AD probably through regulating NF-κB-TSLP/IL-33 pathway, which may provide a novel effective target for the prevention and treatment of allergic diseases.

MSC transplantation has been explored as a new clinical approach to stem cell-based therapies for bone diseases in regenerative medicine due to their osteogenic capability. However, only a small population of implanted MSC could successfully reach the injured areas. Therefore, enhancing MSC migration could be a beneficial strategy to improve the therapeutic potential of cell transplantation. Catharmus tinctorius volatile oil (CTVO) was found to facilitate MSC migration. Further exploration of the underlying molecular mechanism participating in the pro-migratory ability may provide a novel strategy to improve MSC transplantation efficacy. This study indicated that CTVO promotes MSC migration through enhancing ROCK2 mRNA and protein expressions. MSC migration induced by CTVO was blunted by ROCK2 inhibitor, which also decreased myosin light chain (MLC) phosphorylation. Meanwhile, the siRNA for ROCK2 inhibited the effect of CTVO on MSC migration ability and attenuated MLC phosphorylation, suggesting that CTVO may promote BMSC migration via the ROCK2/MLC signaling. Taken together, this study indicates that C. tinctorius volatile oil could enhance MSC migration via ROCK2/MLC signaling in vitro. C. tinctorius volatile oil-targeted therapy could be a beneficial strategy to improve the therapeutic potential of cell transplantation for bone diseases in regenerative medicine.

Objective To understand the water quality of self-supply wells in four provinces of northern China (Heilongjiang, Beijing, Inner Mongolia and Tibet), so as to provide a reference for supervision and management of self-supply wells. Methods Water were sampled from 233 self-supply wells in four northern provinces of China according to standard examination methods for drinking water (GB/T 5750-2006). In total, The samples were tested for 27 kinds of water quality parameters involving sensory properties, chemistry, bacteriology and toxicology, and then evaluated. Results The total unqualified rate of water quality in self-supply well water in four northern provinces of China was 52.36%. The water quality varied greatly among provinces. As for Heilongjiang, the main unqualified indicators of self-supply wells water involved turbidity, visible to the naked eye, manganese, arsenic and nitrate. In relation to Beijing, these referred to the nitrate and microorganism. In case of Inner Mongolia province, these included sulfate and fluoride. With reference to Tibet, these were zinc and chloride. Conclusions To ensure the safety of drinking water for residents, the management, disinfection and purifying measures of self-supply wells should be strengthened basing on their regional differences and water quality characteristics.

Objective To find out about the sanitary conditions of drinking water along the border line of Inner Mongolia via safety evaluation of drinking water along the border line of Inner Mongolia.Methods 108 samples of drinking water along the border line of Inner Mongolia(70 samples of self-supply source water,21 ones of self-supply tap water and 17 ones of municipal tap water)were collected.Hygienic evaluation of sensory indexes, normal chemical indexes, toxicological indexes and microbiology indexes of water quality was performed according to hygienic standards for drinking water(GB 5749—2006).Results 58 samples were qualified with a total qualified rate of 53.7%.The unqualified rate of the total number of coliforms was the highest(20.4%),followed by fluoride(19.4%).As for deep wells, shallow wells and surface water,there was no statistically significant difference.Compared with municipal tap water,the unqualified rate of self-supply water(28.6%)was higher(17.7%).Conclusion The qualified rate along the border line of Inner Mongolia of drinking water is low.Treatment and disinfection facilities for drinking water,detection devices of water quality are needed.The cleaning and disinfection of storage tanks should be performed periodically in oder to prevent waterborne infectious diseases.