Objective To develop and validate a simple,rapid,sensitive,and reproducible HPLC method for determination of hyperoside in plasma of dogs and for the subsequent pharmacokinetic (PK) study.Methods An accurate and reproducible HPLC-UV method was developed and validated for the determination of hyperoside in plasma of dogs,using kaempferol as internal standard.The plasma samples of dogs following ig administration of hyperoside were analyzed for the detection of quercetin after enzymatic hydrolysis treatment with combined β-glucuronidase and sulphatase.The analytes were separated on a Diamonsil C18 column (250 mm × 4.6 mm,5 μm).The mobile phase consisted of methanol-buffer solution (0.1mol/L NH4Ac + 0.3 mmol/L EDTA-Na2)-acetic acid (60:40:1) and was delivered at a flow rate of 1mL/min.The UV detector was set at 370 nm and the column temperature was maintained at 35 ℃.The sample injection volume was 20 μL.Data were collected and analyzed using the ANASTAR software.PK parameters were calculated with DAS software (2.0).Results Linear relationships were validated over the range of 0.01-1μg/mL for hyperoside (r =0.9997).The intra-and inter-day precision values for all samples were within 10.0％,and the accuracies of intra-and inter-day assays were within the range of 92.4％-102.4％.The validated method was successfully used to determine the hyperoside concentration in plasma of dogs for up to 12 h,after a single ig administration (25 mg/kg).The mean PK parameters for male and female dogs were as follows:Cmax (0.18 ± 0.05) and (0.16 ± 0.05) μg/mL,AUC0-∞ (0.79 ± 0.34) and (0.86 ± 0.27) μg/(mL·h),t1/2(ka) (0.89 ± 0.41) and (0.88 ± 0.28) h,respectively.Statistical analysis on the PK of hyperoside in male and female groups showed that sex had no significant impact on the PK of hyperoside (P ＞ 0.05).Conclusion The method is able and sufficient to be used in drug PK studies of hyperoside.

brain and fatty. The accumulation excretion ratios within 96 h were 70.16% in urine and only 1.35% in feces after iv administration in rats, while within 24 h was 3.46% in bile. Conclusion The results of pharmacokinetics of novel r-hirudin in rats given by iv determined by RA are different from those determined by TCA-RA, but the trends indicated by the two methods are the same; urine excretion is the major excretion pathway.

Objective To establish the reference intervals of hemoglobin A 1c( HbA1c ) and fasting plasma glucose ( FPG ) in the first and second trimester of pregnancy in Chongqing , and to evaluate the viability of the combination of HbA 1c and FPG in screening gestational diabetes mellitus (GDM).Methods The study retrospectively selected the pregnant women seen at the Department of Obstetrics and Gynecology in Daping Hospital between September 2014 and August 2015.The results of FPG during 10-13 pregnant weeks and 75 g oral glucose tolerance test ( OGTT ) and HbA1c during 24-28 pregnant weeks were available.Totally 185 cases were assigned into GDM group , and 269 cases were assigned into normal group based on the American Diabetes Association ( ADA) guidelines.Reference intervals of HbA 1c and FPG in normal pregnant woman were developed .The difference of HbA 1c , FPG and OGTT results between two groups was analyzed.T-student test, NcMemar test,signed rank sum test, ROC curve were used for statistical analysis.Results The reference intervals of HbA 1c and FPG in first and second trimester were 4.58%-5.52%,4.21-5.49 mmol/L and 4.03-5.08 mmol/L.The FPG level in first and second trimester and HbA 1c level in GDM group vs normal group were(5.06 ±0.37) vs(4.85 ±0.32)mmol/L(t=6.569,P=0.000), 5.23(5.11,5.4) vs 4.74(4.54,4.91) mmol/L(z=-14.31,P=0.000)and 5.3(5.1,5.4)% vs 5.2(5.0, 5.3)%( z=-5.79,P=0.000) respectively.The area under receiver operating characteristic curve ( ROC) of HbA1c , and FPG in first and second trimester was 0.655, 0.659 and 0.890 respectively.When the cut-off value of HbA1c was 5.35%, the AUC of the combination of HbA 1c and FPG in second trimester was 0.898, the sensitivity was 0.838,and the specificity was 0.859.The kappa coefficient for identifying GDM between OGTT and the combined method was 0.692(P=0.000).Conclusion HbA1c combined with FPG is of some value in screening GDM.

Hepatitis B virus(HBV)-infected hepatitis is one of the most common infectious disease worldwide. To find novel effective anti-HBV agents, a series of Matijin-Su(MTS)derivatives with aromatic heterocycles were synthesized and evaluated for their anti- HBV activities in HepG2 2. 2. 15 cells. Among them, compounds 7a(IC50=2. 94 μmol/L)and 9a(IC50=2. 21 μmol/L)exhibited more potent inhibitory activity against the replication of HBV DNA in HepG2 2. 2. 15 cells than that of lead compound MTS(IC50=11. 16 μmol/L). Notably, both 7a and 9a displayed a high selective index(SI)of 146. 39 and > 250, respectively, which were also much higher than that of MTS(SI=10. 78). Therefore, compounds 7a and 9a may be promising anti-HBV agents with safety profile for HBV infection.

Qingyan Dropping Pills have the effects of relieving wind and heat, detoxifying, and promoting the pharynx. It is commonly used in traditional Chinese medicines to treat acute and chronic pharyngitis, as well as sore throats and dry throats caused by surgery. Recently, many studies have shown that Qingyan Dropping Pills have certain effects on bacteriostasis, anti-inflammatory, antioxidant, and antiviral activities. As the coronavirus disease 2019 (COVID-19) pandemic enters the post-epidemic era, the regular use of drugs for COVID-19 pandemic symptoms has become a new trend. Therefore, there is a good market prospect to explore and develop Chinese patent medicines with antiviral effects. A preliminary study on the herbal formula and material basis of Qingyan Dropping Pills revealed that they have potential for antiviral applications. In this paper, the research on the quality study and antiviral effect of Qingyan Dropping Pills was reviewed, and the research direction of its secondary development was discussed to provide ideas and references for the new use of old traditional Chinese medicines.

Traditional Chinese medicine (TCM) has played a pivotal role in maintaining the health of Chinese people and is now gaining increasing acceptance around the global scope. However, TCM is confronting more and more concerns with respect to its quality. The intrinsic "multicomponent and multitarget" feature of TCM necessitates the establishment of a unique quality and bioactivity evaluation system, which is different from that of the Western medicine. However, TCM is investigated essentially as "herbal medicine" or "natural product", and the pharmacopoeia quality monographs are actually chemical-markers-based, which can ensure the consistency only in the assigned chemical markers, but, to some extent, have deviated from the basic TCM theory. A concept of "quality marker" (Q-marker), following the "property-effect-component" theory, is proposed. The establishment of Q-marker integrates multidisciplinary technologies like natural products chemistry, analytical chemistry, bionics, chemometrics, pharmacology, systems biology, and pharmacodynamics, etc. Q-marker-based fingerprint and multicomponent determination conduce to the construction of more scientific quality control system of TCM. This review delineates the background, definition, and properties of Q-marker, and the associated technologies applied for its establishment. Strategies and approaches for establishing Q-marker-based TCM quality control system are presented and highlighted with a few TCM examples.

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example,