The new HIV-1 NNRTI drug Etravirine (TMC125) and a promising drug candidate Rilpivirine (TMC278) in phase III clinical trial are compounds belonging to the diarylpyrimidine (DAPY) family. They are extremely high potent against both wild-type and many drug-resistant HIV-1 strains, providing new hope for HIV-infected patients who fail to use current drugs due to the emergence of drug-resistant HIV mutants. The discovery and development of DAPY derivatives as next-generation NNRTI drugs depend on multidisciplinary coordination and their success has encouraged new researches to explore more next-generation NNRTIs with new scaffolds. This review described the story of discovery and development of DAPY derivatives as next-generation NNRTIs and related progress.
Anti-HIV Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Resistance, Viral ; HIV Infections ; drug therapy ; HIV-1 ; drug effects ; Humans ; Molecular Structure ; Nitriles ; chemical synthesis ; chemistry ; pharmacology ; Pyridazines ; chemical synthesis ; chemistry ; pharmacology ; Pyrimidines ; chemical synthesis ; chemistry ; pharmacology ; Reverse Transcriptase Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Rilpivirine

Objective To evaluate the efficiency and safety of exercise interventions on cancer related fatigue. Methods Cochrane Library, JBI Database of Systematic Reviews, MEDLINE, EMbase, CINAHL, Chinese Journal Full- text Database, Chinese Biomedical Literature Database, and Wanfang Databse were searched from the inception to November 2014 to screen the systematic review and Meta-analysis conforming to the inclusion criteria. Two authors independently appraised their methodological qualities with Overview Quality Assessment Questionnaire (OQAQ), and analyzed the data using descriptive analysis. The primary outcome included the scaling of cancer related fatigue, the secondary outcome included adherence to exercise intervention and the incidence of adverse events. Results Fourteen systematic review/Meta-analysis were identified, twelve of them had a high methodological quality (Scoring 5-7). Six systematic review/Meta-analysis found that aerobic exercise could effectively alleviate cancer related fatigue, especially for breast cancer patients;seven articles showed that exercise could modulate cancer related fatigue of patients under active treatments;seven articles reported the compliance to the exercise intervention, four articles reported adverse events occurring during the intervention, very few of them resulted directly from the exercise intervention. Conclusions Exercise intervention can modulate cancer related fatigue with good safety.

Rhynchosia volubilis Lour has been a major drug in a folk prescription for contraception in China, whereas its mechanism remains unknown. Its antifertility effects on male mice and antimicrobial activities on sexually transmitted infection (STI) pathogens were previously reported. This study was undertaken to develop the n-Butanol extract of Rhynchosia volubilis Lour (BERVL) as a spermicidal agent with STI prevention. The spermicidal activities of BERVL with different doses were assessed using selected high-motile sperms of normal human semen samples, and their inhibitory effects on Lactobacillus acidophilus were determined. The mechanism of the spermicidal activity was explored by aqueous Eosin Y and Hoechst 33342/PI staining. The results showed spermicidal activities and inhibitory effects of BERVL on Lactobacillus acidophilus were dose-dependent. Dose of 90 mg/mL BERVL terminated all progressive sperm motility within 2 min, and had slight inhibitory effect on Lactobacillus acidophilus, suggesting it was an effective and safe dose for contraception use. About 80% sperms exposed to BERVL displayed changes consistent with high permeability of head membrane. It is concluded that BERVL as spermicide has advantages over N-9 with strong ability to instantaneously kill human sperm and possesses light inhibitory effect on Lactobacillus acidophilus.

Objective To study the characteristics of dynamic susceptibility-contrast(DSC)MR perfusion curves,color images and perfusion values in pre-operative brain metastasis.Methods Twenty- eight brain metastases underwent DSC MR perfusion imaging by using a first-pass T_2~* echo-planar sequence. The patients' data were transferred to on-line workstation.Time-signal intensity curves,color perfusion maps and rCBV,rMTT values in both tumor parenchyma and peri-tumor edema were analyzed,and independent t- test was used and P0.05).Conclusion Different originated brain metastases have nearly same characteristics in DSC MR perfusion imaging.

Object To design a casualty sorting unit with chest integrated with table in the tent-form field medical system.Methods The unit was designed with virtual prototype simulation and CAD, which took considerations on the service orientation, the types and quantity of equipment and devices as well as the requirements for packaging box's size and dimensions of the tent-form field medical system.Results The unit had a size of 1795 mm ×600 mm ×600 mm when deployed, and could be used as the field diagnostic and treatment table; the size was 800 mm ×600 mm ×600 mm when withdrawn, when the module met the requirements of the tent-form field medical system for the packaging box and could be used to hold valuable devices such as color Doppler ultrasound and ECG machine. Finite element simulation and check verified that the module had shape and stress changes due to austere force satisfy the desired requirements.Conclusion The unit gains advantages in deployment and withdrawal, materials, mechanical structure and ergonomics-based operation, accords with the requirements for modularity and multi function integrated into one decice, and enhances the efficiency of casualty sorting in the tent-form field medical system.

OBJECTIVETo investigate the effect of Bushengzhuyang Fang (Yangjing Capsule, YJC) on penile erectile function and its action mechanisms in rats.

METHODSFifty-six male SD rats were randomly divided into seven groups of equal number: blank control, daidzein, daidzein + testosterone, daidzein + sildenafil, daidzein + low-dose YJC, daidzein + medium-dose YJC, and daidzein + high-dose YJC. The rats in the blank control group were treated intragastrically with normal saline and those in the other groups with daidzein at the dose of 100 mg per kg per day for 30 days. Then the last five groups received additionally testosterone (4 mg per kg per day), sildenafil (2.5 mg per kg per day), low-dose YJC, (0.315 mg per kg per day), medium-dose YJC (0.63 mg per kg per day), and high-dose YJC (1. 26 mg per kg per day), respectively. At 0, 30 and 60 days of treatment, we observed the apomorphine-induced spontaneous erectile response and pathological changes in the corpus cavernosum of the rats, recorded the number of penile erection and erectile incubation period, and determined the serum levels of testosterone (T) and luteinizing hormone (LH).

RESULTSAt 30 days of treatment, the number of apomorphine-induced erections was decreased, the erectile incubation period prolonged, and the serum levels of T and LH reduced remarkably in all groups of rats (P < 0.05). Compared with the findings at 30 days, the number of penile erections was significantly decreased at 60 days in the daidzein group (1.39 ± 0.42 vs 2.67 ± 0.33, P < 0.05) and daidzein + low-dose YJC group (1.33 ± 0.49 vs 2.83 ± 0.61, P < 0.05); the erectile incubation period was markedly ex- tended ([16.33 ± 3.11] vs [8.50 ± 0.93] min and [15.50 ± 3.21] vs [8.63 ± 1.54] min, P < 0.05); and the serum levels of T ([5.34 ± 0.89] vs [1.24 ± 0.30] ng/ml and [5.28 ± 1.12] vs [2.07 ± 0.76] ng/ml, P < 0.05) and LH ([3.62 ± 0.37] vs [2.09 ± 0.12] ng/ml and [3.79 ± 0.28] vs [2.17 ± 0.33] ng/ml, P < 0.05) were significantly reduced in the daidzein and daidzein + low-dose YJC groups, respectively. Pathological examination revealed slightly decreased cavernous sinuses and blood vessels in the corpus cavernosum of the rats in the daidzein + testosterone, daidzein + sildenafil, daidzein + medium-dose YJC, and daidzein + high-dose YJC groups as compared with those in the blank control group.

CONCLUSIONHigh-dose Yangjing Capsule is efficacious for the recovery of erectile function in rats, especially for phytoestrogen-induced erectile dysfunction.

Animals ; Apomorphine ; pharmacology ; Drugs, Chinese Herbal ; therapeutic use ; Erectile Dysfunction ; chemically induced ; drug therapy ; Humans ; Isoflavones ; pharmacology ; Luteinizing Hormone ; Male ; Penile Erection ; drug effects ; physiology ; Penis ; drug effects ; pathology ; Phytoestrogens ; Phytotherapy ; Piperazines ; therapeutic use ; Purines ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sildenafil Citrate ; Sulfonamides ; therapeutic use ; Testosterone ; therapeutic use ; Vasodilator Agents ; therapeutic use

OBJECTIVEThis review aimed to summarize the relationship between intestinal microbiota metabolism and cardiovascular disease (CVD) and to propose a novel CVD therapeutic target.

DATA SOURCESThis study was based on data obtained from PubMed and EMBASE up to June 30, 2015. Articles were selected using the following search terms: "Intestinal microbiota", "trimethylamine N-oxide (TMAO)", "trimethylamine (TMA)", "cardiovascular", and "atherosclerosis".

STUDY SELECTIONStudies were eligible if they present information on intestinal microbiota metabolism and atherosclerosis. Studies on TMA-containing nutrients were also included.

RESULTSA new CVD risk factor, TMAO, was recently identified. It has been observed that several TMA-containing compounds may be catabolized by specific intestinal microbiota, resulting in TMA release. TMA is subsequently converted to TMAO in the liver. Several preliminary studies have linked TMAO to CVD, particularly atherosclerosis; however, the details of this relationship remain unclear.

CONCLUSIONSIntestinal microbiota metabolism is associated with atherosclerosis and may represent a promising therapeutic target with respect to CVD management.

Atherosclerosis ; metabolism ; microbiology ; Gastrointestinal Microbiome ; physiology ; Humans ; Methylamines ; metabolism

OBJECTIVETo investigate the level and distribution characteristics of anemia of the minority ethnic group children in Yunnan.

METHODThe cases with anemia were surveyed from 13 336 samples of 15 minority ethnic groups and Han children in Yunnan by Taking the method of random cluster sampling.

RESULTThe prevalence of anemia among the children under 7 years of age of 15 ethnic groups of minority in Yunnan was 13.6%. There are differences among the different ethnic groups (χ(2) = 716.33, P < 0.01), the highest was 26.6% in Jingpo, the lowest was 3.5% in Bai. There were differences among the different regions, the prevalence of anemia was high in the border regions City, the highest was 23.8% in Dehong; the prevalence of anemia was low in inland cities, the lowest was 2.7% in Fugong, and was higher in border areas. The prevalence of anemia was higher in boys (13.6%) than in girls (12.1%). There were differences among the different age in the different ethnic groups (6 months to 1 years old: χ(2) = 70.52, P < 0.01; 1 - 2 years old:χ(2) = 185.86, P < 0.01; 2 - 5 years old: χ(2) = 296.12, P < 0.01; 5 - 6 years old:χ(2) = 107.11, P < 0.01; 6 - 7 years old:χ(2) = 185.02, P < 0.01), the highest was 59.0% of Deang in 1 to 2 years old children. The trend of change was that the highest prevalence was seen in 6 months to 1 year old children, the prevalence gradually declined among older children, but rose again in children 6 years of age or older.

CONCLUSIONThe prevalence of anemia was 13.6% among the children of 15 ethnic minority under 7 years of age in Yunnan. There were differences among different ethnic groups of minority in different prefectures. There were differences among different ethnic groups of different age groups, but it was highest in 6 months to 1 year old children, it declined among older children, and rose in children 6 years of age or older. The prevalence of anemia was related to the ethnic and geographic factors.

Age Distribution ; Altitude ; Anemia ; diagnosis ; epidemiology ; ethnology ; Biomarkers ; analysis ; Child ; Child, Preschool ; China ; epidemiology ; ethnology ; Ethnic Groups ; Female ; Hemoglobins ; analysis ; Humans ; Infant ; Infant, Newborn ; Male ; Minority Groups ; statistics & numerical data ; Prevalence ; Sampling Studies ; Sex Distribution

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

The purpose of this study is to find out anti-HIV-1 reverse transcriptase (RT)/protease (PR) activity and inhibition of virus replication in cell cultures of novel coumarin analogs and determine their structure-activity relationship. Coumarin derivatives have been demonstrated to inhibit the activity of HIV-1 RT/PR in cell free system. It also shows inhibition effects to HIV-1 replication in cell culture. Based on the Chinese traditional pharmacological characteristics and protein three dimension computer aided design, analogs of tetracyclic dipyranocoumarin were synthesized from natural leading compounds. We studied the relationship of antiviral effects and chemical structures via HIV-1 PR/RT enzyme models and cell culture model system. Seven compounds were designed and tested. Several compounds showed anti-HIV-1 activity in varying degrees, especially V0201 showed much higher anti-HIV-1 activity with 3.56 and 0.78 micromol x L(-1) of IC50 against HIV-1 PR/RT and 0.036 micromol x L(-1) against HIV-1 replication in PBMC cultures. V0201 with a novel structure may be a new leading compound. These new compounds are valuable for development of new anti-HIV drugs in the future.
Anti-HIV Agents ; chemical synthesis ; chemistry ; pharmacology ; Cells, Cultured ; HIV Core Protein p24 ; metabolism ; HIV Protease ; metabolism ; HIV Reverse Transcriptase ; metabolism ; HIV-1 ; physiology ; Humans ; Inhibitory Concentration 50 ; Leukocytes, Mononuclear ; cytology ; metabolism ; virology ; Pyranocoumarins ; chemical synthesis ; chemistry ; pharmacology ; Reverse Transcriptase Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship ; Virus Replication ; drug effects