Objective To isolate E.scherichia coli-specific bacteriophages from hospital waste water,analyze their biological character-istics and detect their cleavage effects on bacterial biofilms.Methods The phages were isolated and purified by double-layer agar plate method and their morphology was observed by transmission electron microscopy.Their one-step growth curve,in vitro lysis curve,tem-perature and acid-base stability were determined.Whole genome sequencing was used to analyze the genome composition and character-istics of bacteriophages.The crystal violet staining was used to evaluate the scavenging effects of phage on host biofilms.Results A novel Escherichia coli-specific bacteriophage named vB_EcoP-R1 was isolated from hospital sewage.Transmission electron microscopy revealed that the morphology of vB_EcoP-R1 was similar to that of Podoviridae,a member of Caudovirales,and it could survive stably in the temperature range of-20 ℃ to 50 ℃ and pH 5.0 to 11.0.The total length of the vB_EcoP-R1 genome was 40 875 bp and the GC content was 49.94％.There were no virulence genes and drug resistance genes in the phage genome.vB_EcoP-R1 was capable of lysing clinically isolated Escherichia coli and showed high species and genus specificity.After the phage acted on the host bacteria preformed biofilm for 4 h,the clearance rate of the biofilm reached 80.16％.Conclusion vB_EcoP-R1 should be a novel Escherichia coli-specif-ic bacteriophage with strong lysis and high specificity for species and genus.The bacteriophage could lyse the biofilm formed by the host bacteria,and is expected to be used as an alternative treatment for Escherichia coli infection.

The incidence of depression after myocardial infarction (DAMI) is high, causing significant harm to the patients' physical and mental health, but the pathogenesis is unknown. Establishing animal models which simulate the pathogenesis of DAMI in humans is an effective way to explore the mechanism of the disease. In this paper, problems existing in the modeling process, such as animal selection, model selection, model preparation and behavioral evaluation, are summarized and considered in order to provide reference for DAMI model research.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Objective:To investigate the effect of total ginsenoside ginseng root on the learning and memory impairment and anxiety of hindlimb suspension rats by detecting the performance of rats in the water maze， elevated plus maze， and the expression of hypothalamic-pituitary-adrenal （HPA） axis， inflammatory factors and tryptophan pathway related factors through the intervention of ginsenosides in hindlimb suspension rats. Method:The Wistar male rats were divided into normal group， hindlimb suspension model group， Huperzine A group （0.1 mg·kg^-1）， and total ginsenoside ginseng root low and high dose groups （100， 200 mg·kg^-1）， with 8 rats in each group. Except for the normal group， the rats in the other groups maintained a -30° hindlimb suspension state for 24 h. The normal group and the model group received intragastric administration of 10 mL·kg^-1 pure water . After 28 days of continuous administration， the water maze and elevated plus maze behavioral tests were performed. After the tests， blood was taken from the abdominal aorta， and the rat brain cortex was peeled off on ice， quenched with liquid nitrogen， and stored at -80 ℃ for later use. LC-MS/MS was used to detect neurotransmitter levels of dopamine， acetylcholine， glutamate， γ-aminobutyric acid and tryptophan pathway metabolites （tryptophan， 5-hydroxytryptamine， 5-hydroxyindoleacetic acid， kynurenine， 3-hydroxykynurenine， and kynurenine） in rat brain cortex. An enzyme-linked immunosorbent assay （ELISA） kit was used to detect the levels of inflammatory factors interleukin-6 （IL-6）， interleukin-10 （IL-10， the HPA axis-related hormone corticotropin （ACTH）， and the level of corticosterone （CORT）. Result:Compared with the normal group， the escape latency in the water maze significantly increased， the number of crossings was significantly reduced， and the number of open-arm entry and the percentage of open-arm entry were significantly reduced in the elevated plus maze in model group （P<0.05， P<0.01）， the content of dopamine， acetylcholine， glutamic acid， and γ-aminobutyric acid in the cortex decreased， kynurenine and kynurenic acid showed an upward trend， 3-hydroxykynurenine， 5-hydroxytryptamine， 5-hydroxyindole acetic acid showed a downward trend， and the levels of IL-6， IL-10， ACTH， and CORT in the serum significantly increased （P<0.05， P<0.01）. Compared with the model group of rats， total ginsenoside ginseng root low and high dose groups group reduced the avoidance latency in the water maze， and increased the number of crossings and the number of open arms of the elevated plus maze， dopamine， acetylcholine， glutamate， and γ-aminobutyl content increased， while kynurenine and kynurenic acid showed a downward trend， 3-hydroxykynurenine， serotonin， and 5-hydroxyindole acetic acid showed an upward trend， and IL-6， IL-10， ACTH， and CORT factor levels were down-regulated（P<0.05， P<0.01）. Conclusion:Hindlimb suspension for 28 days in simulated microgravity can impair the learning and memory ability of rats and cause anxiety-like behaviors. Total ginsenoside ginseng root can improve their learning and memory impairment and anxiety-like behaviors. The mechanism may be mainly related to inhibiting body inflammation and regulating HPA axis imbalance.

Objective:To evaluate the clinical efficacy of kidney-invigorating and asthma-relieving granules in treating kidney deficiency type of bronchial asthma patients in persistent.Methods:A total of 100 patients with bronchial asthma admitted to Shanghai Municipal Hospital of TCM from March 2020 to August 2020 were selected as the research subjects. The patients were divided into control group and treatment group by random and double blind method, 50 in each group. Both groups were treated by routine basic treatment. The control group was treated with Kidney-invigorating and asthma-relieving Placebo, while the observation group was treated with kidney-invigorating and asthma-relieving granules. All the treatment lasted for 6 weeks. The TCM syndromes scores, Asthma Control Test (ACT) scores, Peak expiratory flow/predicted value (PEF%) and eosinophil in peripheral blood before and after treatment were observed.Results:A total of 91 patients completed the clinical study. There were 45 patients in the control group and 46 in the treatment group. The total effective rate in the treatment group was 93.5% (43/46), while that in the control group was 77.8% (35/45), and the difference was statistically significant ( χ2=4.579, P=0.032). After the treatment, the scores of integral efficacy on syndromes in Chinese medicine, ACT and PEF% in the treatment group were significantly higher than those in the control group ( t values were 2.802, 3.420 and 8.938, respectively, all Ps<0.01). The eosinophil in peripheral blood of patients in the treatment group was significantly lower than that of the control group ( t=3.481, P=0.001). Conclusion:On the basis of conventional treatment of western medicine, kidney-invigorating and asthma-relieving granules can relieve the clinical symptoms of asthma, improve the control level of asthma, enhance the level of PEF, reduce airway inflammation.

Objective: To explore the relationship between the ideal cardiovascular health behaviors and factors and newonset heart failure. Methods: It was a prospective cohort study. People who attended the 2006-2007 physical examination of Kailuan Group Company and with complete data of cardiovascular behaviors and related factors were eligible for this study. A total of 95 167 participants who were free of valvular heart diseases, congenital heart diseases and a prior history of heart failure were included. Basic cardiovascular health score (CHS) of each participant was calculated. Participants were divided into 3 groups according to CHS. Group 1:CHS<8 (n=26 640), Group 2:8≤CHS<10 (n=35 230), Group3:CHS≥10 (n=33 297). The general clinical data and laboratory test results were collected. The outcome was defined as the first occurrence of heart failure at the end of followup(December 31, 2016). Cox regression model was used to determine the association between baseline CHS and the risk of newonset heart failure. Results: After a median followup of 10.3 years, the incidence of newonset heart failure in the group of CHS<8,8≤CHS<10,CHS≥10 were 2.7%(729/26 640), 1.8%(651/35 230) and 1.1%(360/33 297),respectively. After adjustment for age, sex, history of myocardial infarction, history of atrial fibrillation, income, alcohol consumption, education and the use of antihypertensive, cholesterol-lowering, glucose-lowering medications, compared with the group of CHS<8, the Cox regression model showed that HRs of the group of 8≤CHS<10 and CHS≥10 were 0.68 (95%CI 0.61-0.75), 0.49 (95%CI 0.43-0.55), respectively. Cox regression analysis after removing each single cardiovascular behavior or factor showed that the HR value range ability was as follows:systolic blood pressure(HR=0.78,95%CI 0.74-0.82), body mass index(HR=0.78,95%CI 0.74-0.82), fasting blood glucose (HR=0.77,95%CI 0.73-0.81), total cholesterol(HR=0.76,95%CI 0.72-0.80), physical exercise(HR=0.72,95%CI 0.69-0.76), smoking(HR=0.75,95%CI 0.71-0.79) and salt intake(HR=0.73,95%CI 0.69-0.77). Conclusion: CHS is negatively associated with the risk of newonset heart failure, and there is a dose-response relationship between the two indexes.
Blood Pressure ; Cardiovascular Diseases/epidemiology* ; Health Behavior ; Heart Failure/epidemiology* ; Humans ; Prospective Studies ; Risk Factors

Objective:To construct a multi-stage dynamic prevention and control model, establish a system of intervention points and prevention and control measures for the prevention and control of workplace violence in hospitals, so as to provide guidance for hospitals and medical staffs to effectively prevent and respond to such incidents.Methods:Based on the crisis management theory, a model for the prevention and control of workplace violence in hospitals was constructed, the intervention points and prevention and control measures were screened by the Delphi method.Results:A multi-stage dynamic prevention and control model of workplace violence in hospitals was constructed, and a system of intervention points and prevention and control measures for workplace violence in hospitals were established according to the model. The system was divided into three stages: the pre-event stage contained 10 intervention points and 48 countermeasures, the in-event stage contained 6 intervention points and 17 countermeasures, and the post-event stage contained 3 intervention points and 12 countermeasures.Conclusions:It is an effective way to avoid violence and reduce the damage degree of violent incidents by selecting different countermeasures for different intervention points and carrying out multi-stage dynamic prevention and control of workplace violence in hospitals.

As a new type of cell death, necroptosis is initiated by tumor necrosis factor receptor 1(TNFR1), and then activated receptor-interacting protein kinase 1(RIP1) and receptor-interacting protein kinase 3 (RIP3), following by the activation of mixed lineage kinase domain-like protein(MLKL) to deliver cell death signal. When necroptosis happens, damage associated molecular patterns (DAMPs) enter into extracellular area through the ruptured cytomembrane, followed by the disordered tissue hemeostasis. In recent years, many researches showed that necroptosis playimportant roles in a few bone related diseases, such as osteoporosis, osteonecrosis, osteosarcoma, etc. Thus, we try to briefly review the researches in this field.
Apoptosis ; Necroptosis ; Protein Kinases

OBJECTIVE: To investigate the effect of 2-methoxyestradiol (2-ME2) to lymphoma Raji cells and its mechanism. METHODS: Different concentrations of 2-ME2 were used to treat lymphoma Raji cells. CCK8 method was used to detect the effect of 2-ME2 to proliferation of Raji cells. Flow cytometry FITC/PI double labeling method was used to detect early apoptosis of the cells. Western blotting was used to detect the effect of 2-ME2 to the expression of BCL-2, Bax, Caspase-3 and C-myc proteins in Raji cells. RESULTS: 2-ME2 significantly inhibited the proliferation of Raji cells. The inhibition rate increased with the increasing of drug concentration, and increased significantly with the prolongation of drug treatment time (r=0.9215). Flow cytometry FITC/PI double staining showed that the apoptotic rate of 2.5 μmol/L 2-ME2 treatment group was (33.79±1.63) %, while the apoptosis rate of the 48 h group was (51.90±2.72) %, and that of the control group was (7.08±0.36) %. After treated with 2.5 μmol/L 2-ME2 for 12 h, the expression of Bax protein was up-regulated, BCL-2 protein was down-regulated, caspase-3 protein expression was up-regulated, and C-myc protein expression was down-regulated, all of them showed a time-dependent relationship. CONCLUSION 2-ME2 shows obvious inhibitory effect on lymphoma Raji cells in a dose- and time-dependent manner. Its mechanism of treatment on lymphoma Raji cells may be related to up-regulation of Bax/BCL-2 ratio and activation of Caspase-3 to induce apoptosis in cancer cells. Down-regulation of C-myc protein expression also participates in the apoptotic process.
2-Methoxyestradiol ; Apoptosis ; Caspase 3/metabolism* ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Lymphoma ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Up-Regulation ; bcl-2-Associated X Protein

Objective: To investigate the impact of change of ideal cardiovascular behavior and related factors on healthy vascular aging(HVA). Methods: This study was a multi-center cross-sectional survey. Six thousand three hundred and sixteen participants who underwent at least 2 healthy examinations from 2006 to 2015 at 11 hospitals, including Kailuan Hospital and so on, and examined brachial-ankle pulse wave velocity (baPWV) during 2010 and 2016, with available information about cardiovascular behavior and factors were included. The cardiovascular health score (CHS) was calculated. Basic CHS was collected from the first examination. The second CHS derived from the healthy examination in the same year of baPWV examination. Change of cardiovascular health score (ΔCHS) was calculated. Participants were defined into 5 groups according to ΔCHS, namely ΔCHS≤-2 (n=2 166), ΔCHS=-1 (n=1 284), ΔCHS=0 (n=1 187), ΔCHS=1 (n=860), and ΔCHS≥2 (n=819). Participants' characteristics, value of baPWV and proportion of HVA were compared among different groups. Multiple logistic regression analysis was used to investigate the association between ΔCHS and HVA. The ΔCHS was recalculated and included in multiple logistic regression analysis model again after each component of the cardiovascular health metrics was removed separately in order to investigate effects of removal factors on HVA by observing changes in effect values. Results: The percentage of the participants with HVA in the group of ΔCHS≤-2, ΔCHS=-1, ΔCHS=0, ΔCHS=1 and ΔCHS≥2 were 23.3%(505/2 166), 27.8%(357/1 284), 28.7%(341/1 187),31.9%(274/860) and 33.9%(278/819), respectively. After adjustment for age, sex, income, education, alcohol consumption and the basic CHS, a significant positive association between ΔCHS and proportion of participants with HVA was observed (OR=1.50, 95%CI 1.44-1.56). Multiple regression analysis after removing each single cardiovascular behavior or factor showed that the OR value decreased as follow systolic blood pressure (OR=1.04, 95%CI 1.00-1.09), fasting blood glucose (OR=1.14, 95%CI 1.09-1.18), physical exercise (OR=1.16, 95%CI 1.11-1.21), salt intake (OR=1.17, 95%CI 1.12-1.22), body mass index (OR=1.18, 95%CI 1.13-1.23), smoking(OR=1.18, 95%CI 1.13-1.23) and total cholesterol (OR=1.20, 95%CI 1.16-1.24). Conclusion: The improvement of every ideal cardiovascular behavior and factor is associated with the increase of the proportion of HVA population.
Aging ; Ankle Brachial Index ; Blood Pressure ; Body Mass Index ; Cardiovascular Diseases ; Cardiovascular Physiological Phenomena ; Cross-Sectional Studies ; Humans ; Pulse Wave Analysis ; Risk Factors