Selective synthesis of 4-(sulfonyl)-methyl-1H-pyrazoles and (E)-4,5-dihydro-1H-pyrazoles from N-allenic sulfonylhydrazones.

Selective synthesis of 4-(sulfonyl)-methyl-1H-pyrazoles and (E)-4,5-dihydro-1H-pyrazoles from N-allenic sulfonylhydrazones with sulfonyl group migrations has been developed. A key feature of these reactions is that the migrations of the sulfonyl groups to different positions can be controlled by changing the Lewis acids.

Effects of clarithromycin on the pharmacokinetics of tacrolimus and expression of CYP3A4 and P-glycoprotein in rats.

The objective of this study was to investigate the effect of clarithromycin on the pharmacokinetics of tacrolimus in rats and better understand its mechanism. In the control group (n = 6), rats received a single oral dose of 1 mg tacrolimus on day 6. In the experimental group (n = 6), rats received 0.25 g of clarithromycin daily for five consecutive days and then a single oral dose of 1 mg tacrolimus on day 6. Orbital venous blood (250 µL) was collected at 0, 0.25, 0.50, 0.75, 1, 2, 4, 8, 12, and 24 h before and after tacrolimus administration. Blood drug concentrations were detected via mass spectrometry. Small intestine and liver tissue samples were collected after rats were euthanized via dislocation, and CYP3A4 and P-glycoprotein (P-gp) protein expression was determined using western blotting. Clarithromycin increased the blood tacrolimus concentration and affected its pharmacokinetic properties in rats. Compared with those in the control group, the AUC0-24 , AUC0-∞ , AUMC(0-t) , and AUMC(0-∞) of tacrolimus in the experimental group were significantly increased, whereas the CLz/F was significantly lower (P < 0.01). Simultaneously, clarithromycin significantly inhibited CYP3A4 and P-gp expression in the liver and intestine. Protein expression of CYP3A4 and P-gp in the liver and the intestinal tract was significantly downregulated in the intervention group compared with that in the control group. Clarithromycin significantly inhibited the protein expression of CYP3A4 and P-gp in the liver and intestine, thereby increasing the mean blood concentration and significantly increasing the AUC of tacrolimus.

Supramolecular chirality of coordination polymers of Ag+ with a chiral thiol ligand that bears a ß-turn structure.

We report coordination polymers forming from Ag+ and a chiral thiol ligand that bears a ß-turn structure, exhibiting supramolecular chirality showing both the majority rules effect (MRE) and the racemate rules effect (RRE).

Perioperative management of pregnant women combined with congenital fibrinogen deficiency: four cases report and literature review / 北京大学学报(医学版)

Congenital fibrinogen deficiency is an autosomal recessive or dominant disorder in which quantitative (afibrinogenaemia or hypofibrinogenaemia) or qualitative (dysfibrinogenaemia) defects in the fibrinogen Aa, Bb or c protein chains that lead to reduced functional fibrinogen. We now report the perioperative management of 4 pregnant women suffering from hypofibrinogenaemia scheduled for elective caesarean section from December 2012 to October 2016 in Peking University First Hospital and review this disease with reference to classification, symptom, replacement therapy, and selection of the modes of pregnancy termination and anesthesia. The four patients were all asymptomatic, whereas there existed recurrent pregnancy loss (case 3), family history (case 2), and offspring heredity (cases 3 and 4). Routine clotting studies revealed low fibrinogen levels and prolonged thrombin time (TT) during pregnancy and on admission. However, the platelet (PLT) count, prothrombin time (PT) and activated partial thromboplastin time (APTT) were normal. All the patients were administered fibrinogen concentrate perioperatively, and underwent uncomplicated combined spinal-epidural anesthesia and uneventful surgical procedure without postpartum hemorrhage. The replacement therapy of fibrinogen or fresh frozen plasma administration was essential to avoid anesthesia and obstetric complications. Regional blockade could safely be offered in the caesarean section, providing that their coagulation defect was corrected by availability of therapeutic products and adequate response to treatment. In addition, the point-of-care rotational thrombelastometry (ROTEM) or thrombelastogram (TEG) could play an important role in an optimal perioperative management for such patients. Management plans must be tailored to each individual, taking into consideration their bleeding risk as well as potential maternal and neonatal complications.

RAPD and ISSR analyses of genetic diversity of American ginseng germplasm from different habitats in China / 中草药

Objective: To analyze the genetic diversity of American ginseng (Panax quinquefolium) produced in 10 regions of China by usting RAPD and ISSR. Methods: Genomic DNA was extracted by CTAB and the following two kinds of ginseng were used as controls which are ginseng (P. ginseng) produced in China and American ginseng produced in Canada. Thirteen RAPD primers and 12 ISSR primers were selected to perform PCR amplification. According to the band number, NTSYS-pc2.10e software was applied to the cluster analysis using UPGMA. Results: Thirteen RAPD primers had amplified 97 clear bands, 81 polymorphic bands, and the percentage of polymorphism was 85.51%; Twelve ISSR primers had amplified 99 clear bands, 64 polymorphic bands, and the percentage of polymorphism was 64.65%; Through cluster analysis, the samples were clustered into four categories by RAPD and RAPD + ISSR and two categories by ISSR. Conclusion: RAPD and ISSR markers are used to construct a dendrogram of samples, which is slightly different in classification, but the overall trend is consistent. Ginseng and American ginseng are clear distinction. On the ISSR, American ginseng from Xingshen Town and Beigang Town in Jilin province are gathered for a major categories with ginseng. In the growing environment and planting conditions, the genetic diversity of American ginseng has been changed in the part of northeast China compared with Canada.

Research on genetic stability to American ginseng introduced into China for 30 years / 中国中药杂志

To study the genetic stability of Panax quinquefolium after introduced into China for 30 years, the samples of P. quinquefolium from 14 regions of China were studied. RAPD molecular marker technology was applied in this research, and POPGEN32 data analysis and NTSYS2. 10 cluster diagram were used to analyze the data. The results showed that there are abundant genetic diversity in the ginseng samples. There were 81 polymorphic bands based on the 13 random primers. The polymorphism was 83.51%, the effective number of alleles (N(e)) was 1.456 7; Nei's gene diversity index (H) was 0.274 8; Shannon's diversity index (H(o)) was 0.419 4. The clustering analyses indicated that P. quinquefolium and P. ginseng were classified into two obvious groups, especially, it was also found that the P. quinquefolium could be divided into two obvious groups based on whether the P. ginseng was cultivated in the same region or not, but it was thought that there was not genetically a qualitative difference. Thus it suggests that a good breeding field should be established in Jilin Province of China for the germplasm purification.

Effects of PreS2 synthetic peptides on infiltrating T lymphocyte subgroups expression in hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To explore whether PreS2 can change the percentage of T lymphocyte subgroups and the ration of CD4+/CD8+ in hepatocellular carcinoma (HCC) caused by HBV.</p><p><b>METHODS</b>The P120-146 region composed by the way of Merrifield, which was the most intensive antigen in PreS2 peptides, served as the antigen after dissolved in 0.01 mol/L PBS. 12 patients were chosed as the subjects, who were pathologically diagnosed as HCC after operation, were HBsAg-, HBeAg-, anti-HBc, and HBV DNA positive in serum, and expressed HBsAg in HCC tissue. The monocytes were isolated and cultured in 96 microplate with 1x 10(6) cells in every well, then the PreS2 synthetic peptides was added in at the doses of 1microg, 5microg, and 10microg, also IL-2 with 500 U was added in. Seven days later, the percentage of CD3+, CD4+, CD8+, and the ratio of CD4+/CD8+ were detected.</p><p><b>RESULTS</b>It was found that the percentage of CD4+ increased significantly (t = 3.508, P < 0.01), and the ratio of CD4+/CD8+ decreasedly obviously (t = 2.235, P < 0.05) in the 5microg PreS2 synthetic peptides group, compared with those in the control group. The percentage of CD3+ rised markedly in the IL-2 group, compared with that in the control group.</p><p><b>CONCLUSION</b>With proper doses, PreS2 is capable of changing the expression of T lymphocyte subgroups in HCC tissue, increasing the percentage of CD4+ obviously and changing the motionless state of CD8+, to make the carcinoma cell killed through the action of CD4+ and CD8+.</p>

Reduced neutralization of SARS-CoV-2 B.1.617 variant by inactivated and RBD-subunit vaccine

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Spike protein that mediates coronavirus entry into host cells is a major target for COVID-19 vaccines and antibody therapeutics. However, multiple variants of SARS-CoV-2 have emerged, which may potentially compromise vaccine effectiveness. Using a pseudovirus-based assay, we evaluated SARS-CoV-2 cell entry mediated by the viral Spike B.1.617 and B.1.1.7 variants. We also compared the neutralization ability of monoclonal antibodies from convalescent sera and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine) and ZF2001 (RBD-subunit vaccine) against B.1.617 and B.1.1.7 variants. Our results showed that, compared to D614G and B.1.1.7 variants, B.1.617 shows enhanced viral entry and membrane fusion, as well as more resistant to antibody neutralization. These findings have important implications for understanding viral infectivity and for immunization policy against SARS-CoV-2 variants.