Beclin-1 is the firstly-identified mammalian protein of the autophagy machinery, which functions as a molecular scaffold for the assembly of PI3KC3 (class III phosphatidylinositol 3 kinase) complex, thus controlling autophagy induction and other cellular trafficking events. Notably, there is mounting evidence establishing the implications of Beclin-1 in diverse tumorigenesis processes, including tumor suppression and progression as well as resistance to cancer therapeutics and CSC (cancer stem-like cell) maintenance. More importantly, Beclin-1 has been confirmed as a potential target for the treatment of multiple cancers. In this review, we provide a comprehensive survey of the structure, functions, and regulations of Beclin-1, and we discuss recent advances in understanding the controversial roles of Beclin-1 in oncology. Moreover, we focus on summarizing the targeted Beclin-1-regulating strategies in cancer therapy, providing novel insights into a promising strategy for regulating Beclin-1 to improve cancer therapeutics in the future.

Aortic Valve ; Aortic Valve Stenosis/surgery* ; Heart Valve Prosthesis ; Humans ; Length of Stay ; Patient Discharge ; Risk Factors ; Transcatheter Aortic Valve Replacement ; Treatment Outcome

Platycodonis Radix, which was first recorded in the Agriculture God's Canon of Materia Medica. It is a multi-functional drug with a wide range of applications. The processing of Platycodonis Radix has been recorded as early as in the Jin dynasty, and has a long history of processing. Today, in addition to the washing, cutting and stir-frying with honey, there have also been more than 20 kinds of processing methods, such as stir-frying with wine, stir-frying with bran, stir-frying with Lilii Bulbus juice and so on. The ancients believed that Platycodonis Radix could enhance the effect of diffusing the lung, promoting pharynx and relieving cough by processing. In terms of the chemical compositions in Platycodonis Radix, more than 100 compositions, like triterpenoid saponins, flavonoids, phenols, sterols, polysaccharides and polyacetylenes, have been isolated and identified from it. Among them, triterpenoid saponins are the essential compositions. In addition, Platycodonis Radix has the pharmacological effects of expectorant, antitussive, anti-inflammatory, anti-tumor, etc. The medicinal ingredients of Platycodonis Radix are mainly triterpenoid saponins and polysaccharides. Among them, triterpenoid saponins have diverse biological activities, which lead it to be one of the hotspots of current researches. Platycodonis Radix has a good role in promoting lung and removing phlegm. After being processed, its medicinal effects are enhanced. It is complex and diverse in compositions of Platycodonis Radix so that has rich pharmacological activities. On the basis of sorting out the literature, this paper discusses the processing history, chemical composition and pharmacological effect of Platycodonis Radix, in order to provide reference for the special processing and modern research of Platycodonis Radix. Furtherly, it provides a theoretical basis for the research of its processing mechanism and quality control.

Coronavirus disease-2019 (COVID-19) is highly contagious. In the early stages of the disease, the symptoms of coldness, dampness and depression in the lungs often appear, including fever, fatigue, soreness, dry cough, poor appetite, and white greasy tongue coating. During the development of the disease, the damp toxin epidemic often enters the inner and generates heat, and the damp heat epidemic toxin blocks pleurodiaphragmatic sites, the triple energizer and lungs, with manifestations of chest tightness, shortness of breath, exacerbation after exercise, or high fever without bringing down, poor appetite, bitterness in mouth, fatigue, diarrhea, loose stools, and yellow and thick tongue fur. As the pathogen can go outward or enter more deeply inside to cause death at the moment, it is the crucial time to treat the disease. In this study, Haoqin Qingdantang was used to clear dampness and heat, reconcile Shaoyang channel and recover the triple energizer, detoxify the dampness fever epidemic toxin, and block the toxin inside, with a good efficacy. This prescription focuses on smoothing the Shaoyang gallbladder channel and the triple energizer, and regards the spleen and stomach as the acquired essence. In the prescription, Erchentang reconciles the spleen and stomach, elevates clear Qi and lower turbid Qi. Bupleuri Radix is added to increase its detoxification function, and Paeoniae Rubra Radix is added to circulate the blood and prevent pathogen from the blood. When the condition improves, Sweet Wormwood Herb and talc are often withdrawn, and Codonopsis is added to nourish the spleen and stomach, to strengthening vital qi to eliminate pathogenic factor. Based on the cases of COVID-19 treated in Wuhan Jinyintan Hospital, this paper summarized some experience of applying Haoqin Qingdantang.

Objective To provide the basis for influenza epidemic prevention and control by monitoring the antibody level of influenza among the general population in Dapeng New District of Shenzhen City. Methods A total of 1 350 serum samples of people were collected ten times from 2014 to 2018, and the antibody level was tested by hemagglutination-inhibition test. Results During 2014-2018 years, only the positive rate of antibody to H3N2 was above 60%.The positive rates of H1N1, H3N2, BV and BY were 50.0%, 85.6%, 35.4% and 45.6%, respectively, and the geometric mean titers (GMT) of antibody were 8.2, 81.5, 3.9 and 6.4, respectively.Influenza antibody titers of 1 : 160 and 1 : 320 were mainly distributed in influenza H3N2.The antibody level of BV and BY in age group 0~4 years was 29.0% and 30.4% separately. Conclusion It is imperative to enhance the surveillance of antibody level of influenza among general population in Dapeng New District, to investigate the epidemic development trend of influenza constantly, and to prevent and control the outbreak of influenza epidemics.

Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.

OBJECTIVETo investgate the effects of rapamycin(RPM)and RPM-loaded poly(lactic-co-glycolic)acid(PLGA)nanoparticles(NPs)on the apoptosis of human umbilical arterial vascular smooth muscle cells(HUASMCs)in vitro and expression of bcl-2 and p27(kip1) protein.

METHODSHUASMCs were cultured in vitro and divided to RPM and RPM-PLGA-NPs groups treated at 3 different concentration by 12 and 24 hours,with M231-smooth muscle growth supplements medium and null-PLGA-NPs treated groups as controlled. The apoptosis of HUASMCs was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining and flow cytometry. The expressions of bcl-2 and p27(kip1) were detected by streptacidin/peroxidase immunohistochemical method. The effect on cellular proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidecolorimetry.

RESULTSThe proliferation of HUASMCs was inhibited by RPM and RPM-PLGA-NPs in a dose-dependent manner. DNA electrophoresis showed DNA ladder in RPM and RPM-PLGA-NPs groups and classical scalar strips in control groups. The apoptotic indexes of RPM 100 ng/ml group and RPM-PLGA-NPs 500 ng/ml group detected by flow cytometry were(45.45<2.36)% and(35.04<5.64)%,respectively,which were significantly higher than that of M231-smooth muscle growth supplements control group [(2.60<0.95)%,all P<0.01]. The apoptotic indexes of groups incubated with RPM and RPM-PLGA-NPs for 24 hours were significantly higher than those of groups which incubated for 12 hours(P<0.05,P<0.01). The positive expression indexes(PEI)of p27(kip1) and bcl-2 protein were higher in RPM and RPM-PLGA-NPs groups than that of control groups. The Spearman's rank correlation coefficient test showed that there was no significant correlation between the PEI of p27(kip1) and the apoptotic indexes in the RPM group and RPM-PLGA-NPs group(P>0.05).

CONCLUSIONSRapamycin-loaded PLGA nanoparticles and rapamycin have similar effects in inhibiting proliferation and inducing apoptosis;meanwhile,they upregulate the expression of p27(kip1) protein without downregulating the expression of bcl-2 protein in HUASMCs in vitro. RPM-PLGA-NPs has more potent pro-apoptotic effect than equivalent dose of RPM but is not linearly correlated with the p27(kip1) expression level.

Apoptosis ; Cell Proliferation ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p27 ; Humans ; In Situ Nick-End Labeling ; Lactic Acid ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle ; Nanoparticles ; Polyglycolic Acid ; Sirolimus ; Umbilical Arteries

To investigate the epidemiology of hand, foot, and mouth disease (HFMD) and the genetic characteristics of enterovirus A71 (EV-A71) in Linyi of Shandong Province, China during 2007-2012. The number of reported HFMD cases were obtained from the National Notifiable Disease Reporting System (NNDRS) were analyzed by descriptive epidemiology method; the VP1 region of EV-A71 isolated from HFMD patients in Linyi was amplified and sequenced. Finally, the genetic variability and phylogenecity of VP1 sequences of EV-A71 were analyzed by MEGA 5.0. The results showed that HFMD incidence was reported in each year from 2007 to 2012 in Linyi, and the highest incidence and mortality were reported in 2009, when there were total 14697 cases and 9 of death. The reported incidence was 140.28/100000, and the mortality was 0.086/100000. The peak incidence usually occurred between April and July, and the summit occurred in May. Scattered children accounted for 77.37%-92.00% of all cases. The peak age was 2.5 years during 2007-2009 and 1.5 years during 2010-2012. A total of 1365 laboratory-confirmed HFMD cases were reported in the 6 consecutive years, accounting for 2.98% of the gross number. Among these reports, the ratio of EV-A71 was 44.18%, and the ratio of coxsackievirus A16 (CVA16) was 46.59%. All EV-A71 strains isolated in Linyi during 2007-2012 belonged to the C4a evolutionary branch of C4 genotype. In conclusion, HFMD outbreaks occurred every year in Linyi during 2007-2012. Incidence varied significantly among different counties. The peak incidence in each year lasted from April to July. Most of the patients were children under 3 years of age, and scattered children took the highest proportion. Co-circulation of EV-A71 and CVA16 was the major cause of HFMD in each year. Since the first report of HFMD prevalence caused by EV-A71 (C4a) in 2007, the virus has been prevalent continuously in Linyi for 6 years.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; epidemiology ; Enterovirus ; classification ; genetics ; isolation & purification ; Female ; Hand, Foot and Mouth Disease ; epidemiology ; virology ; Humans ; Infant ; Male ; Middle Aged ; Molecular Sequence Data ; Phylogeny ; Young Adult

The development history, education, legislation, charge and institutes of acupuncture and moxibustion in Singapore are introduced in this article. Acupuncture and moxibustion has been developed in Singapore since 1840. Nowadays there are three universities that set up standard Chinese medicine courses and two acupuncture-moxibustion associations. Legislation of acupuncture and moxibustion is published in 2000. The acupuncture and moxibustion is applied for approximately 50 kinds of diseases. The acupuncture and moxibustion is at one's own expense in public or private institutions, but cheap or completely free in charity.
Acupuncture ; education ; history ; manpower ; trends ; Acupuncture Therapy ; economics ; history ; trends ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Hospitals ; Humans ; Moxibustion ; economics ; history ; trends ; Singapore