Objective Herbal medicines containing toxic herbs or minerals such as Compound Danshen Tablet (CDT), Angong Niuhuang Pill (ANP), and Lidan Paishi Tablet (LPT) are avoided or used with caution for pregnant women because of potential teratogenicity. To understand their mechanism, they were chosen as model subjects for the research. Methods Zebrafish embryos were used to evaluate their potential teratogenic risk in vitro. Results All of them showed teratogenic and lethal effects in zebrafish embryos, with the EC50 values at 351, 793, and 220 μg/mL, and LC50 values at 417, 596, and 380 μg/mL, respectively. CDT and LPT, displaying week potential teratogenicity as their teratogenicity indexes were greater than 1, induced tail malformation and cardiac edema mainly in zebrafish embryos, respectively. Conclusion The results provide the significant guidance of clinical safety of medication.

OBJECTIVETo further explore the effect of Jiangu Erxian Pill (JGEXP) on proliferation and cell cycle of human osteoblast on the basis of previous clinical and experimental studies.

METHODSHuman primary osteoblast were isolated and cultured. The cell proliferation was tested by 3H-thymine incorporation and methyl thiazolyl tetrazolium (MMT) method and the cell cycle was determined by flow cytometry technique.

RESULTSIn the medium and high dosage JGEXP groups, the cell proliferation rate and index, and percentage of diploid synthesis phase (S phase) cells were significantly higher than those in the blank control group (P < 0.01 or P < 0.05), and similar to those in the estrogen group; and the cell apoptosis rate and percentage of G0-G1 stage cells were lower than those in the blank control group (P < 0.01 and P < 0.05).

CONCLUSIONJGEXP could effectively promote the cell proliferation and differentiation, and prevent the cell apoptosis of osteoblast in vitro.

Animals ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Division ; drug effects ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; Osteoblasts ; cytology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

【Objective】 To study the differentiate expression genes and regulation signaling pathways related to the occurrence and development of dilated cardiomyopathy with heart failure, we used bioinformatics methods to explore gene chip in gene expression omnibus(GEO) and genes related to dilated cardiomyopathy in online mendelian inheritance in man(OMIM) . 【Methods】 GSE21610 and GSE29919 chip gene sets sequenced by Herz- &Diabeteszentrum NRW laboratory of the University of Bochum, Germany with myocardial biopsy specimens from clinical cases under the platform GPL570 and uploaded to GEO public database were selected to perform our study. Myocardial biopsy specimens from dilated cardiomyopathy with heart failure and normal cardiac function were regarded as the experimental group(14 and 21 cases, respectively) and the control group(12 and 8 cases, respectively). Up-regulated expression genes with the criteria: P < 0.05, were screened in GEO2R with the selected samples of two chips, which were then used to perform kyoto encyclopedia of genes and genomes(KEGG) pathways analysis, gene ontology(GO) function analysis, and protein-protein interaction(PPI) analysis, and the results were displayed through Volcano map, Venn map, Heat map, and Bubble charts with enrichment pathways drawn by R language packages. Meanwhile, KEGG pathways with the criteria: NOM. P < 0.05, and core genes relating to dilated cardiomyopathy with heart failure were performed through gene set enrichment analysis (GSEA). All candidate genes were then intersected with the reported genes in the OMIM, respectively, and clinical significance of these candidate genes was explored in relevant literatures. 【Results】 A total of 173 up-regulated expression genes with P < 0.05, were obtained by GEO2R, which are mainly related to inflammatory signals, cell proliferation and differentiation regulating, and classical apoptotic signaling pathways. These genes were intersected with the 754 reported genes in OMIM, and three reported up-regulated expression genes were obtained: NPPA for diagnosis of heart failure, APOA1 that associates with cytokine action, and COL6A1 that regulates lateral tubular remodeling. 158 and 46 core genes from KEGG pathways with NOM. P < 0.05 were obtained by GSEA, respectively, which were then intersected with the 754 reported genes in OMIM, and two core genes were obtained: PRKCA, enhancing myocardial contractility, and BMP2, promoting the development of heart failure. 【Conclusions】 Based on bioinformatics analysis, we found that the candidate genes PRKCA, BMP2, NPPA, and COL6A1 are likely to be closely related to the occurrence and development of dilated cardiomyopathy with heart failure, which can be used to reveal meaningful therapeutic clues and directions for the clinical treatment of dilated cardiomyopathy with advanced cardiac dysfunction.

Progresses in the studies on chemical constituents of Clematis L. (belonging to the family Ranunculaceae) were systematiically reviewed in this article. The plants in this genus have a wide spectrum of constituents as follows: triterpenes, flavonoids, lignans, coumarins, alkaloids, volatile oils, steroids, organic acids, macrocyclic compounds and phenols, etc., among which triterpenoid saponins, flavonoids and lignans are the main components. The triterpenoid saponins are mainly oleanolic type and hederagenin type, most of which are bidesmosidic saponins, substituted with oligosaccharide chains at both C-3 and C-28, and some are substituted with acetyl, caffeoyl, isoferuloyl, p-methoxy cinnamyl and 3,4-dimethoxy cinnamyl groups in the oligosaccharide chains. The flavonoids from Clematis species are mainly flavones, flavonols, flavanones, isoflavones, xanthones and their glucosides (sugar moieties are connected to the aglycone through either the oxygen or the carbon atoms), the aglycones of which are mainly apigenin, kaempferol, luteolin and quercetin. The lignans from Clematis are mainly eupomatene lignans, cyclolignans, monoepoxylignans, bisepoxylignans and lignanolides. Clematis spp. are rich in resources, however, studies on their chemical constituents have only been carried out on twenty or so spp. As a result, it is necessary to expand our study on other spp. from this genus for better utilization of medicinal resources.
Clematis ; chemistry ; Drugs, Chinese Herbal ; chemistry

ObjectiveTo analyze the risk factors for in-hospital mortality in patients with Takotsubo Syndrome （TTS）. MethodsHospitalization data of consecutive patients with TTS from February 2009 to January 2022 were retrospectively collected and analyzed. Patients were divided into survival group and death group according to outcomes. The basic clinical information， triggering factors， laboratory examinations， electrocardiogram， echocardiography， complications and treatments of the two groups were compared. Univariable logistic regression analysis was used to screen the possible risk factors for in-hospital mortality in TTS patients， and multivariable logistic regression analysis was used to determine the independent risk factors for in-hospital mortality in TTS patients. ResultsA total of 62 TTS patients were included in our study， including 21 males （33.9%）， 41 females （66.1%） and 26 postmenopausal women （41.9%）， with the mean age of （55.6±16.2） years， and physical triggers were found in 50 patients （80.6%）. 17 patients （27.4%） died while 45 patients （72.6%） survived during hospitalization. The death group had lower systolic blood pressure and left ventricular ejection fraction （LVEF）， higher incidence rate of syncope， higher level of N-terminal pro-B natriuretic peptide （NT-proBNP） and hypersensitive troponin T （hs TnT） when compared with survival group （all P value <0.05）. As for the triggering factors， the proportion of TTS induced by neurologic disorders in the death group was higher than that in the survival group （P<0.05）. The death group had higher rates of cardiogenic shock， malignant ventricular arrhythmia， atrial fibrillation， and respiratory failure （all P value <0.05）. Compared with the survival group， therapeutic dopamine， therapeutic norepinephrine， hemodialysis and mechanical ventilation were higher in the death group （all P value <0.05）. Univariable logistic regression analysis suggested that syncope， NT-proBNP， LVEF， neurologic disorders， cardiogenic shock， malignant ventricular arrhythmia， atrial fibrillation， respiratory failure， therapeutic dopamine， therapeutic norepinephrine， hemodialysis and mechanical ventilation were potential risk factors for in-hospital mortality in TTS patients （all P value <0.05）. Multivariable logistic regression analysis indicated that neurologic disorders ［OR（95%CI）=5.651（1.195，26.715），P=0.029］， atrial fibrillation ［OR（95%CI）=6.217（1.276，30.298）， P=0.024）］ and therapeutic norepinephrin ［OR（95%CI）=8.847（1.912，40.949）， P=0.005］ were independent risk factors for in-hospital mortality in TTS patients. ConclusionsNeurologic disorders， atrial fibrillation and therapeutic norepinephrin are independent risk factors for in-hospital mortality in patients with Takotsubo Syndrome. Clinically， attention should be paid to the prevention and treatment of neurologic disorders and atrial fibrillation； norepinephrine should be carefully used in patients with diagnosed TTS complicated with hemodynamic instability.

【Objective】Serum gamma-glutamyltransferase（GGT）has recently been implicated in the pathogenesis of atherosclerosis and coronary heart disease（CHD）. We aimed to evaluate the association between the serum GGT level and the 10-year risk score for CHD（Framingham Risk Score，FRS）in a Chinese population.【Methods】We conducted a population-based cross-sectional study in 9，544 Guangzhou residents aged 40 years and older. Participants were divided into four quartiles according to their GGT levels：Quartile 1 <15 U/L（n=2 407），Quartile 2 15~19.9 U/L（n=2 302）， Quartile 3 20~28.9 U/L（n=2 442），and Quartile 4 ≥29 U/L（n=2 393）. The multivariate logistic regression analysis was used to assess the incidence of intermediate and high risk of developing CHD at 10 years（FRS≥10%）in relation to each quartile increase of serum GGT level.【Results】The incidence of FRS≥10% increased with elevating serum GGT levels（P for trend<0.001）. Compared with the lowest quartile of serum GGT level ，the adjusted odds ratio in the highest quartile was 1.72（95% confidence interval 1.28 to 2.29）.【Conclusion】Serum GGT level is associated with the FRS for CHD ，and might be used as an adjuvant marker for identifying patients at increased risk of cardiovascular events and early intervention.

【Objective】 To explore the clinical value of urinary aldosterone concentration(UAC) in primary aldosteronism(PA) screening and to evaluate the consistency of the two methods, liquid chromatography tandem mass spectrometry(LC-MS/MS) and chemiluminescence immunosorbent assay(CLIA), for determining UAC. 【Methods】 Among the 133 patients with suspected PA enrolled from October 2018 to August 2019, 55 were diagnosed with PA(30 with aldosteroneproducing adenoma and 25 with bilateral idiopathic hyperplasia) and 78 with essential hypertension(EH). Parallel determination of UAC was done with LC-MS/MS and CLIA assays on all subjects, then we compared the two methods and evaluated their correlation and consistency. Reciever operating characteristic(ROC) analysis was applied to assess the diagnostic accuracies, area under the curve(AUC) and cutoff values of UAC, plasma aldosterone concentration(PAC), random aldosterone to renin ratio(ARR) and urine aldosterone to renin ratio(UARR). Furthermore, ROC analysis of high urine sodium subgroup(urine sodium≥130 mmol/24h) was performed to evaluate the impact of sodium intake on PA screening. 【Results】 ①UACCLIA and UACLC-MS/MS were positively correlated(r=0.69, P < 0.001). Bland-Altman analysis showed poor consistency between CLIA and LC-MS/MS. ②The diagnostic efficiency of UAC and PAC in PA screening was equivalent (P > 0.05), while ARR was more efficient than UAC and PAC(P < 0.0001). AUC of UACCLIA, UACLC-MS/MS, PAC and ARR was 0.739, 0.659, 0.723, 0.943, respectively. The cutoff values for them were 5.1 μg/24 h, 11.6 μg/24 h, 27.6 ng/dL and 23.2 ng·dL^-1(/ μg·L^-1·h^-1), respectively. ③Both UARRCLIA and UARRLC-MS/MS performed as well as ARR in PA screening. AUC of UARRCLIA was 0.924 at the cutoff value of 1.75 μg·24h^-1(/ μg·L^-1·h^-1). While AUC of UARRLC-MS/MS was 0.906 at the cutoff value of 4.63 μg·24h^-1(/ μg·L^-1·h^-1). AUC of UACLC-MS/MS in high urine sodium subgroup was 0.708 at the cutoff of 14.9 μg/ 24 h. ④The diagnostic efficiency of UAC made no difference after sodium intake increased to 130 mmol/24 h or higher. 【Conclusion】 UAC alone is of little clinical value compared to ARR in PA screening and can serve as a supplementary indicator currently. But UARR, a combintion of UAC and plasma renin activity(PRA), is as valuable as ARR for screening PA. The optimal cutoff values of UACLC-MS/MS and UACCLIA are 11.6 μg/24 h, 5.1 μg/24 h, respectively. The optimal cutoff values of UARRLC-MS/MS and UARRCLIA are 4.63 μg·24 h^-1/(μg·L^-1·h^-1) and 1.75 μg·24 h^-1/(μg·L^-1·h^-1), respectively. Besides, significant bias of UAC observed in CLIA and LC-MS/MS results indicates that appropriate definition of cutoff value and reference range for each method are mandatory.

Keratin (K) is the main component of the epithelial cell mesenchymal cytoskeleton, which protects the integrity of epithelial cells and maintains the function of normal epithelial cells. The expression of keratin affects epidermal proliferation and differentiation, and so as to be used as a marker for proliferation, differentiation and migration of keratinocytes. Middle ear cholesteatoma is one of the common ear diseases. In the middle ear cholesteatoma, keratinocytes over-proliferate and keratin debris accumulates. In this paper, we reviewed the recent studies on middle ear cholesteatoma and explained the possible mechanisms of keratin in the pathogenesis of middle ear cholesteatoma from the aspects of "proliferation" and " bone resorption ". At the same time, the existing problems as well as the prospect of the future research were discussed.

ObjectiveTo investigate the clinical efficacy of oral dydrogesterone alone for luteal phase support in natural cycle frozen-thawed embryo transfer （NC-FET）. MethodsThe clinical data of 1 530 NC-FET cycles enrolled in our Reproductive Center from January 2019 to September 2021 were retrospectively analyzed. According to different luteal support protocols， the patients were divided into oral dydrogesterone alone （group A， n=524）， vaginal progesterone soft capsules （group B， n=401） and vaginal progesterone soft capsules combined with dydrogesterone （group C， n=605）. The clinical outcomes and cost-effectiveness ratio were compared among the three groups. The primary outcome was live birth rate. ResultsThe live birth rate was 43.13% （226/524） in group A， 39.15% （157/401） in group B， and 42.64% （258/605） in group C. There was no statistical difference among the three groups （P > 0.05）. No statistical difference was observed in the HCG positive rate， implantation rate， biochemical pregnancy rate， clinical pregnancy rate， spontaneous miscarriage rate， ectopic pregnancy rate， twin delivery rate， premature delivery rate and newborn weight among the three groups （P>0.05）. Logistic regression analysis revealed that the three luteal support regimens did not affect live birth rate. Pharmacoeconomic analysis showed that taking group B as a reference， the cost increased by 19 227.30 yuan for every 1% increase in live birth rate in group A. ConclusionsIn NC-FET cycle， oral dydrogesterone alone can achieve the same clinical outcomes as vaginal progesterone soft capsules and vaginal progesterone soft capsules combined with dydrogesterone. Compared with that of progesterone soft capsules， the cost of oral dydrogesterone alone is increased， a large sample and multicenter prospective study is needed to further confirm our results.

Administration, Oral ; Anticoagulants/adverse effects* ; Atrial Fibrillation/drug therapy* ; Humans ; Stroke ; Vascular Calcification/drug therapy* ; Warfarin