Eight new diaryltriazine derivatives containing 4-allylamino and 4-azido substitutes guided by molecular docking have been designed and synthesized based on our previous work. The evaluation of HIV inhibitory activity demonstrated that all compounds were potent against HIV-1 replication. The most active compound 7c exhibited activity against HIV-1 (IC50 = 0.034 micromol x L(-1), SI = 6,475) and the double mutant strain (IC50 = 9.39 micromol x L(-1)) in the micromolar range, which was more potent than nevirapine.
Anti-HIV Agents ; chemical synthesis ; chemistry ; pharmacology ; Catalytic Domain ; HIV-1 ; drug effects ; Inhibitory Concentration 50 ; Molecular Structure ; Reverse Transcriptase Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Triazines ; chemical synthesis ; chemistry ; pharmacology

OBJECTIVETo observe the effect of acupoint injection by astragalus injection on local SIgA and pathomorphologial changes in rats with chronic pelvic inflammatory disease (CPID).

METHOD50 female Wistar rats were randomly devided into 6 groups, in which CPID model was made except the normal group and sham operation group. The astragalus injection group and the 0.9% NaCl injection group were treated by acupoint injection in Guanyuan (RN4) and Zusanli (ST36). The group was fed Qianjinpian solution into stomach. The histopathologic changes of rats' uterus of each group were observed and SIgA in vagina flushing was detected.

RESULTThe model group showed inflammatory changes, and astragalus injection group and Qianjinpian group showed little histopathologic changes. The levels of SIgA in astragalus injection group were significantly higher than those in other groups, but that in the model group was the lowest.

CONCLUSIONThe deficiency of local SIgA lead to repeatedly attack of CPID. The treatment of acupoint injection by astragalus injection can improve the excretion of SIgA, reinforce the local immunity, and prevent the repeatedly attack.

Acupuncture Points ; Animals ; Astragalus membranaceus ; chemistry ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Female ; Immunoglobulin A, Secretory ; blood ; Injections ; Pelvic Inflammatory Disease ; blood ; pathology ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Wistar ; Uterus ; pathology

OBJECTIVETo investigative vacA, cagA and iceA genes dominant genotypes of Helicobacter pylori (Hp) isolated from children suffering from gastric and duodenal diseases in Guangzhou area.

METHODSTotally 105 children who underwent gastroscopy in Guangzhou Children's Hospital were enrolled into this study. From each patient, 3 biopsy specimens from the gastric antrum were taken, one was used for rapid urease test, one for histological examination, and one for polymerase chain reaction (PCR) for detecting ureA, vacA, cagA, and iceA genes. DNA was prepared directly from the biopsy specimens from the gastric antrum using a QIAamp DNA mini kit (Qiagen, Germany) according to the manufacturer's instructions. Then 11 primers were used for detecting the genotypes including ureas, (s1, s1a, s1b, s1c, s2) and m (m1, m1T, m2) region of vacA, cagA and iceA (iceA1 and iceA2) genotypes in the 105 children. The distribution of the genotypes of Hp was analyzed.

RESULTAmong the 105 children, only 52 children were positive by the three methods, among these 52 children, 26 were boys and 26 girls. Hp vacA s1as1c/m2 was detected in 43 out of 52 children (82.7%), s1as1c/m1T in 9.6% (5/52), m region that could not betyped was 7.7% (4/52). No strains presented genotypes vacA s1b, s2, m1. The comparison of the positive ratio of vacA s1as1 c/m2 detected in the children infected with Hp and that of the other combination of signal region and middle region was statistically significantly different (P < 0.01). With regard to cagA gene, cagA(+) gene and cagA(-) gene were found in 90.4% (47/52) and 9.6% (5/52) of the children, respectively. The cagA(+) gene was more frequent in the children infected with Hp. Single iceA1 was detected in 78.8% (41/52) children, and single iceA2 was detected to be 1.9% (1/52), multiple strains infection of iceA1 and iceA2 were detected in 3.8% (2/52) children, iceA1 and iceA2 were not detected in 15.4% (8/52), the comparison of the positive ratio of iceA1 detected in the children infected with Hp and that of the other genotypes was statistically significantly different (P < 0.01).

CONCLUSIONThe s1as1c/m2, cagA and iceA1 were the dominant genotypes of Hp in the children in Guangzhou area and s1as1c/m2, cagA and iceA1 were the dominant genotypes combination of Hp in the children in this area.

Antigens, Bacterial ; genetics ; therapeutic use ; Bacterial Outer Membrane Proteins ; genetics ; Bacterial Proteins ; genetics ; Child ; China ; epidemiology ; Female ; Genes, Bacterial ; drug effects ; genetics ; Genotype ; Helicobacter Infections ; drug therapy ; genetics ; Helicobacter pylori ; genetics ; Humans ; Male ; Polymerase Chain Reaction ; Pyloric Antrum ; microbiology

A simple, sensitive and reliable method was developed for simultaneous determination of ten banned drugs residues including zeranols(ZALs),chloroamphenicol,pentachlorophenol,etc. in swine urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The urine samples were pretreated using lyophilization and QuEChERS procedures, respectively. Acetonitrile and ammonium acetate (5 mmol/L) were chosen as mobile phases. Target compounds were separated well in ZorbaxSB-C18by following the optimized gradient elution program and determined by LC-MS/MS in negative electrospray ionization mode. The linearity of the matrix-matched standard curve of ten analytes in two methods was good in the range of the experimental concentration with correlation coefficients more than 0.99. The recoveries of ten drugs were in the range of 80.7%-107.7% and 73.5%-103.3% at the spiked levels of 5,10 and 20 μg/L by lyophilization and QuEChERS methods,respectively. The coefficients of variation were less than 15%. The limits of detection (LOD) and the limits of quantification (LOQ) from lyophilization and QuEChERS method were 0.1 to 2.0 μg/L and 0.2 to 5.0 μg/L,respectively.

We established the rapid response system for non-hospitalized patients from 2012 in order to improve the effectiveness of emergent critical care for non-hospitalized patients when emergency happened.From January 2013 to December 2016,there were 122 cases with RRS activation for non-hospitalized patients.The time to arrive was 3.16±0.41 min,and 107 cases(86.89％)were sent to the emergency department.Fifteen patients(14.02％)were classified as level 1,26(24.03％)as level Ⅱ,48(16.82％)as level Ⅲ,and 18(16.82％) as level ⅣV,and 83％ were critical patients.Rapid response system is important to cope with emergency in non-hospitalized patients.

Cyclooxygenases play a vital role in inflammation and are responsible for the production of prostaglandins. Two cyclooxygenases are described, the constitutive cyclooxygenase-1 and the inducible cyclooxygenase-2, for which the target inhibitors are the non-steroidal anti-inflammatory drugs (NSAIDs). Prostaglandins are a class of lipid compounds that mediate acute and chronic inflammation. NSAIDs are the most frequent choices for treatment of inflammation. Nevertheless, currently used anti-inflammatory drugs have become associated with a variety of adverse effects which lead to diminished output even market withdrawal. Recently, more studies have been carried out on searching novel selective COX-2 inhibitors with safety profiles. In this review, we highlight the various structural classes of organic and natural scaffolds with efficient COX-2 inhibitory activity reported during 2011-2021. It will be valuable for pharmaceutical scientists to read up on the current chemicals to pave the way for subsequent research.

Considering the undesirable metabolic stability of our recently identified NNRTI 5 (t_1/2 = 96 min) in human liver microsomes, we directed our efforts to improve its metabolic stability by introducing a new favorable hydroxymethyl side chain to the C-5 position of pyrimidine. This strategy provided a series of novel methylol-biphenyl-diarylpyrimidines with excellent anti-HIV-1 activity. The best compound 9g was endowed with remarkably improved metabolic stability in human liver microsomes (t_1/2 = 2754 min), which was about 29-fold longer than that of 5 (t_1/2 = 96 min). This compound conferred picomolar inhibition of WT HIV-1 (EC₅₀ = 0.9 nmol/L) and low nanomolar activity against five clinically drug-resistant mutant strains. It maintained particularly low cytotoxicity (CC₅₀ = 264 μmol/L) and good selectivity (SI = 256,438). Molecular docking studies revealed that compound 9g exhibited a more stable conformation than 5 due to the newly constructed hydrogen bond of the hydroxymethyl group with E138. Also, compound 9g was characterized by good safety profiles. It displayed no apparent inhibition of CYP enzymes and hERG. The acute toxicity assay did not cause death and pathological damage in mice at a single dose of 2 g/kg. These findings paved the way for the discovery and development of new-generation anti-HIV-1 drugs.

Following on our recently developed biphenyl-ATDP non-nucleoside reverse transcriptase inhibitor ZLM-66 (SI = 2019.80, S = 1.9 μg/mL), a series of novel heterocycle-substituted ATDP derivatives with significantly improved selectivity and solubility were identified by replacement of the biphenyl moiety of ZLM-66 with heterocyclic group with lower lipophilicity. Evidently, the representative analog 7w in this series exhibited dramatically enhanced selectivity and solubility (SI = 12,497.73, S = 4472 μg/mL) in comparison with ZLM-66 (SI = 2019.80, S = 1.9 μg/mL). This new NNRTI conferred low nanomolar inhibition of wild-type HIV-1 strain and tested mutant strains (K103N, L100I, Y181C, E138K, and K103N + Y181C). The analog also demonstrated favorable safety and pharmacokinetic profiles, as evidenced by its insensitivity to CYP and hERG, lack of mortality and pathological damage, and good oral bioavailability in rats (F = 27.1%). Further development of 7w for HIV therapy will be facilitated by this valuable information.