This study was amid to construct the pharmacophore model of L-type calcium channel antagonist in the application of screening Drugbank and TCMD. This paper repositions the approved drugs resulting from virtual screening and discusses the relocation-based drug discovery methods, screening antihypertensive drugs with L-type calcium channel function from TCMD. Qualitative hypotheses wre generated by HipHop separately on the basis of 12 compounds with antagonistic action on L-type calcium channel expressed in rabbit cardiac muscle. Datebase searching method was used to evaluate the generated hypotheses. The optimum hypothesis was used to search Drugbank and TCMD. This paper repositions the approved drugs and evaluates the antihypertensive effect of the chemical constituent of traditional Chinese medicine resulting from virtual screening by the matching score and literature. The results showed that optimum qualitative hypothesis is with six features, which were two hydrogen-bond acceptors, four hydrophobic groups, and the CAI value of 2.78. Screening Drugbank achieves 93 approved drugs. Screening TCMD achieves 285 chemical constituents of traditional Chinese medicine. It was concluded that the hypothesis is reliable and can be used to screen datebase. The approved drugs resulting from virtual screening, such as pravastatin, are potentially L-type calcium channels inhibitors. The chemical constituents of traditional Chinese medicine, such as Arctigenin III and Arctigenin are potentially antihypertensive drugs. It indicates that Drug Repositioning based on hypothesis is possible.
Animals ; Antihypertensive Agents ; chemistry ; pharmacology ; Calcium Channel Blockers ; chemistry ; pharmacology ; Calcium Channels, L-Type ; genetics ; metabolism ; Drug Repositioning ; methods ; Molecular Structure ; Myocardium ; metabolism ; Rabbits

To investigate 1alpha,25-(OH)2D3 regulation of matrix metalloproteinase-9 (MMP-9) protein expression during osteoclast formation and differentiation, receptor activator of nuclear factor kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) were administered to induce the differentiation of RAW264.7 cells into osteoclasts. The cells were incubated with different concentrations of 1alpha,25-(OH)2D3 during culturing, and cell proliferation was measured using the methylthiazol tetrazolium method. Osteoclast formation was confirmed using tartrate-resistant acid phosphatase (TRAP) staining and assessing bone lacunar resorption. MMP-9 protein expression levels were measured with Western blotting. We showed that 1alpha,25-(OH)2D3 inhibited RAW264.7 cell proliferation induced by RANKL and M-CSF, increased the numbers of TRAP-positive osteoclasts and their nuclei, enhanced osteoclast bone resorption, and promoted MMP-9 protein expression in a concentration-dependent manner. These findings indicate that 1alpha,25-(OH)2D3 administered at a physiological relevant concentration promoted osteoclast formation and could regulate osteoclast bone metabolism by increasing MMP-9 protein expression during osteoclast differentiation.
Acid Phosphatase/metabolism ; Animals ; Blotting, Western ; Calcitriol/*pharmacology ; Calcium Channel Agonists/pharmacology ; *Cell Differentiation ; Cell Line ; Cell Proliferation ; Gene Expression Regulation, Enzymologic/*drug effects ; Isoenzymes/metabolism ; Matrix Metalloproteinase 9/*genetics/metabolism ; Mice ; Osteoclasts/*cytology/*enzymology ; Tetrazolium Salts ; Thiazoles

BACKGROUNDSmoking is known to be a strong risk factor for premature atherosclerosis, acute myocardial infarction (AMI) and sudden cardiac death. According to a cross-sectional survey conducted in 2000 - 2001 in China, the prevalence of smoking among the Chinese men was 60.2%, the highest prevalence in the world. Up to date, the relationship between smoking and AMI in Chinese male smokers is still unclear. This study analyzed the baseline characteristics for male smokers hospitalized with AMI and investigated the effect of cigarette smoking on their clinical outcomes.

METHODSA total of 890 men aged 18 years or over with AMI were prospectively recruited from 1 January 2007 to 31 December 2009 from Shanxi Provincial People's Hospital. Patients were grouped into smokers and nonsmokers. The relationships between baseline characteristics and clinical outcomes were tested using either the chi-square test for trend for discrete variables or analysis of variance for continuous variables.

RESULTSSmokers accounted for 66.7% (594), more than twice of nonsmokers (296 (33.3%)), and were averaged 7 years younger ((56.61 ± 11.44) vs. (63.61 ± 11.62) years, P < 0.001). Smokers had the higher rate of TIMI flow grade 2 or 3 after thrombolytic therapy (42.4% vs. 24.5%, P = 0.002), 1 vessel disease (25.5% vs. 14.5%, P = 0.003) than nonsmokers. Smokers had better in-hospital outcome with lower in-hospital mortality rate than nonsmokers (6.2% vs. 10.8%, P = 0.023).

CONCLUSIONSMale smokers suffered from AMI in this study presented an average of 7 years earlier than nonsmokers and were more than twice as likely to have AMI as nonsmokers in China. Smoking appeared to result in earlier infarction, especially ST elevated myocardial infarction in otherwise healthier patients who are likely to survive.

Acute Disease ; Adult ; Aged ; China ; Hospital Mortality ; Hospitalization ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; mortality ; Smoking ; adverse effects

BACKGROUND: A correct thyroid function reference range is important for the accurate diagnosis of thyroid disease during pregnancy. However, there is no consensus on whether thyroid function reference ranges in Chinese population should follow the America Thyroid Association (ATA) guidelines. This study aimed to establish a thyroid function reference range more suited to the Chinese population by evaluating the current thyroid function reference range in pregnant Chinese women and comparing it to the ATA guidelines. METHODS: A total of 52,027 pregnant women were enrolled from January 2013 to December 2016. Thyroid stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) levels were tested during the first and third trimesters of pregnancy. Reference ranges of TSH and FT4 were established from the 2.5th and 97.5th percentiles of the TPOAb-negative population of women. The Mann-Whitney U test was used to compare thyroid hormones between the TPOAb-positive and TPOAb-negative groups. RESULTS: We obtained that the TSH reference ranges were 0.03 to 3.52 mU/L and 0.39 to 3.67 mU/L, and the FT4 reference ranges were 11.7 to 19.7 pmol/L and 9.1 to 14.4 pmol/L, in the first and third trimester, respectively. If we used the 2011 ATA criteria about 7.0% and 4.0% pregnant women would be over diagnosed in first and third trimester, respectively, compared with local population thyroid hormone reference. When we compared our local criteria with the new 2017 ATA criteria, about 1.2% and 0.8% pregnant women would have a missed diagnosis in first and third trimester, respectively. CONCLUSIONS: Based on our data, which is in line with the current ATA guidelines, a population-based thyroid function reference range would be the first choice for diagnosis of thyroid disease during pregnancy in China. In case such population-based thyroid function reference ranges are unavailable in the east of China, our reference ranges can be adopted, if the same assay is used. TRIAL REGISTRATION www.chictr.org.cn (No. ChiCTR1800014394).
Adult ; Asian Continental Ancestry Group ; Female ; Humans ; Iodide Peroxidase ; metabolism ; Pregnancy ; Thyroid Gland ; metabolism ; physiopathology ; Thyrotropin ; metabolism ; Thyroxine ; metabolism ; Young Adult

The purpose of this study was to determine whether osteoprotegerin (OPG) could affect osteoclat differentiation and activation under serum-free conditions. Both duck embryo bone marrow cells and RAW264.7 cells were incubated with macrophage colony stimulatory factor (M-CSF) and receptor activator for nuclear factor kappaB ligand (RANKL) in serum-free medium to promote osteoclastogenesis. During cultivation, 0, 10, 20, 50, and 100 ng/mL OPG were added to various groups of cells. Osteoclast differentiation and activation were monitored via tartrate-resistant acid phosphatase (TRAP) staining, filamentous-actin rings analysis, and a bone resorption assay. Furthermore, the expression osteoclast-related genes, such as TRAP and receptor activator for nuclear factor kappaB (RANK), that was influenced by OPG in RAW264.7 cells was examined using real-time polymerase chain reaction. In summary, findings from the present study suggested that M-CSF with RANKL can promote osteoclast differentiation and activation, and enhance the expression of TRAP and RANK mRNA in osteoclasts. In contrast, OPG inhibited these activities under serum-free conditions.
Acid Phosphatase/genetics/metabolism ; Animals ; Avian Proteins/*pharmacology ; Bone Marrow Cells/drug effects/*metabolism ; Cells, Cultured ; Ducks ; Embryo, Nonmammalian/drug effects/metabolism ; Isoenzymes/genetics/metabolism ; Macrophage Colony-Stimulating Factor/metabolism ; Osteoclasts/cytology/*drug effects/*metabolism ; Osteoprotegerin/*pharmacology ; RANK Ligand/metabolism ; Real-Time Polymerase Chain Reaction ; Receptor Activator of Nuclear Factor-kappa B/genetics/metabolism

Objective: To isolate and purify a bacteriophage against methicillin-resistant Staphylococcus aureus (MRSA), and to analyze its genomic information and biological characteristics. Methods: The experimental research methods were adopted. MRSA (hereinafter referred to as host bacteria) solution was collected from the wound of a 63-year-old female patient with the median sternum incision infection admitted to the Second Affiliated Hospital of Army Medical University (the Third Military Medical University). The bacteriophage, named bacteriophage SAP23 was isolated and purified from the sewage of the Hospital by sewage co-culture method and double-layer agar plate method, and the plaque morphology was observed. The morphology of bacteriophage SAP23 was observed by transmission electron microscope after phosphotungstic acid negative staining. The whole genome of bacteriophage SAP23 was sequenced with NovaSeq PE15 platform after its DNA was prepared by sodium dodecyl sulfonate/protease cleavage scheme, and genomic analysis including sequence assembly, annotation, and phylogenetic tree were completed. The bacteriophage SAP23 solution was co-incubated with the host bacterial solution for 4 h at the multiplicity of infection (MOI) of 10.000 0, 1.000 0, 0.100 0, 0.010 0, 0.001 0, and 0.000 1, respectively, and then the bacteriophage titer was measured by the drip plate method to select the optimal MOI, with here and the following sample numbers of 3. The bacteriophage SAP23 solution was co-incubated with the host bacterial solution at the optimal MOI for 5, 10, and 15 min, respectively, and the bacteriophage titer was measured by the same method as mentioned above to select the optimal adsorption time. After the bacteriophage SAP23 solution was co-incubated with the host bacterial solution at the optimal MOI for the optimal adsorption time, the bacteriophage titers were measured by the same method as mentioned above at 0 (immediately), 5, 10, 15, 20, 30, 40, 50, 60, 80, 100, and 120 min after culture, respectively, and a one-step growth curve was drawn. The bacteriophage SAP23 solution was incubated at 4, 37, 50, 60, 70, and 80 ℃ and pH 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 for 1 h, respectively, to determine its stability. A total of 41 MRSA strains stored in the Department of Microbiology of Army Medical University (the Third Military Medical University) were used to determine the host spectrum of bacteriophage SAP23. Results: The bacteriophage SAP23 could form a transparent plaque on the host bacteria double-layer agar plate. The bacteriophage SAP23 has a polyhedral head with (88±4) nm in diameter and a tail with (279±21) nm in length and (22.6±2.6) nm in width. The bacteriophage SAP23 has a linear, double-stranded DNA with a full length of 151 618 bp and 11 681 bp long terminal repeats sequence in the sequence ends. There were 220 open reading frames predicted and the bacteriophage could encode 4 transfer RNAs, while no resistance genes or virulence factors were found. The annotation function of bacteriophage SAP23 genes could be divided into 5 groups. The GenBank accession number was MZ427930. According to the genomic collinearity analysis, there were 5 local collinear blocks in the whole genome between the bacteriophage SAP23 and the chosen 6 Staphylococcus bacteriophages, while within or outside the local collinear region, there were still some differences. The bacteriophage SAP23 belonged to the Herelleviridae family, Twortvirinae subfamily, and Kayvirus genus. The optimal MOI of bacteriophage SAP23 was 0.010 0, and the optimal adsorption time was 10 min. The bacteriophage SAP23 had a latent period of 20 min, and a growth phase of 80 min. The bacteriophage SAP23 was able to remain stable at the temperature between 4 and 37 ℃ and at the pH values between 4 and 9. The bacteriophage SAP23 could lyse 3 of the 41 tested MRSA strains. Conclusions: The bacteriophage SAP23 is a member of the Herelleviridae family, Twortvirinae subfamily, and Kayvirus genus. The bacteriophage SAP23 has a good tolerance for temperature and acid-base and a short latent period, and can lyse MRSA effectively. The bacteriophage SAP23 is a new type of potent narrow-spectrum bacteriophage without virulence factors and resistance genes.
Bacteriophages/genetics* ; Genomics ; Humans ; Methicillin-Resistant Staphylococcus aureus/genetics* ; Middle Aged ; Phylogeny ; Sternum

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.
Humans ; Aged ; Middle Aged ; COVID-19/prevention & control* ; SARS-CoV-2 ; Pandemics/prevention & control* ; China/epidemiology* ; Disease Outbreaks/prevention & control* ; Vaccination