Effects of Forsythia suspensa ethanol extract on the proliferation，migration and invasion of lung cancer cells NCI-H226 / 中国药房

OBJECTIVE To investigate the effects of Forsythia suspensa ethanol extract on the proliferation， migration and invasion of lung cancer cells NCI-H226. METHODS As research objects， lung cancer cells NCI-H226 were divided into control group， F. suspensa ethanol extract low-， medium- and high-concentration groups （5， 10， 20 mg/mL）， activator group [10 mg/mL F. suspensa ethanol extract+0.5 μmol/L nuclear factor kappa B （NF-κB） signaling pathway activator PMA]， inhibitor group （10 mg/mL F. suspensa ethanol extract+10 μmol/L NF-κB signaling pathway inhibitor BAY 11-7082） and positive control group （20 μg/mL cisplatin）. Except for the control group of cells without intervention， all other groups of cells were cultured with corresponding drugs for 24 hours； the proliferation， migration and invasion of cells were all detected， and the proliferation rate， migration rate， and the number of invading cells were also calculated； protein expressions of NF-κB p65， NF-κB inhibitory protein α （IκBα）， phosphorylated NF-κB p65 （p-NF-κB p65） and phosphorylated IκBα （p-IκBα） were determined. RESULTS Compared with control group， the proliferation rate， migration rate， and the number of invading cells as well as the protein expressions of p- IκBα and p-NF-κB p65 were decreased significantly in F. suspensa ethanol extract groups and positive control group （P＜0.05）. Compared with F. suspensa ethanol extract medium-concentration group， the proliferation rate， migration rate， and the number of invading cells as well as above protein expressions were all decreased significantly in inhibitor group （P＜0.05）， while those of activator group were increased significantly （P＜0.05）. CONCLUSIONS F. suspensa ethanol extract can inhibit the proliferation， migration and invasion of lung cancer cells NCI-H226， and the mechanism of which may be related to the inhibition of NF-κB signaling pathway.

Aerobic glycolysis in colon cancer is repressed by naringin via the HIF1Α pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Metabolic reprogramming is a common phenomenon in cancer, with aerobic glycolysis being one of its important characteristics. Hypoxia-inducible factor-1α (HIF1Α) is thought to play an important role in aerobic glycolysis. Meanwhile, naringin is a natural flavanone glycoside derived from grapefruits and many other citrus fruits. In this work, we identified glycolytic genes related to HIF1Α by analyzing the colon cancer database. The analysis of extracellular acidification rate and cell function verified the regulatory effects of HIF1Α overexpression on glycolysis, and the proliferation and migration of colon cancer cells. Moreover, naringin was used as an inhibitor of colon cancer cells to illustrate its effect on HIF1Α function. The results showed that the HIF1Α and enolase 2 (ENO2) levels in colon cancer tissues were highly correlated, and their high expression indicated a poor prognosis for colon cancer patients. Mechanistically, HIF1Α directly binds to the DNA promoter region and upregulates the transcription of ENO2; ectopic expression of ENO2 increased aerobic glycolysis in colon cancer cells. Most importantly, we found that the appropriate concentration of naringin inhibited the transcriptional activity of HIF1Α, which in turn decreased aerobic glycolysis in colon cancer cells. Generally, naringin reduces glycolysis in colon cancer cells by reducing the transcriptional activity of HIF1Α and the proliferation and invasion of colon cancer cells. This study helps to elucidate the relationship between colon cancer progression and glucose metabolism, and demonstrates the efficacy of naringin in the treatment of colon cancer.

Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 Protein Vaccine

Background COVID-19 vaccines with alternative strain compositions are needed to provide broad protection against newly emergent SARS-CoV-2 variants of concern. Methods We conducted a global Phase 3, multi-stage efficacy study (NCT04904549) among adults aged [≥]18 years. Participants were randomized 1:1 to receive two intramuscular injections 21 days apart of a bivalent SARS-CoV-2 recombinant protein vaccine with AS03-adjuvant (5 g of ancestral (D614) and 5 g of B.1.351 [beta] variant spike protein) or placebo. Symptomatic COVID-19 was defined as laboratory-confirmed COVID-19 with COVID-19-like illness (CLI) symptoms. The primary efficacy endpoint was the prevention of symptomatic COVID-19 [≥]14 days after the second injection. Results Between 19 Oct 2021 and 15 Feb 2022, 12,924 participants received [≥]1 study injection. 75% of participants were SARS-CoV-2 non-naive. 11,416 participants received both study injections (efficacy-evaluable population [vaccine, n=5,736; placebo, n=5,680]). Up to 15 March 2022, 121 symptomatic COVID-19 cases were reported (32 in the vaccine group and 89 in the placebo group) [≥]14 days after the second injection with a vaccine efficacy (VE) of 64.7% (95% confidence interval [CI] 46.6; 77.2%). VE was 75.1% (95% CI 56.3; 86.6%) in non-naive and 30.9% (95% CI -39.3; 66.7%) in naive participants. Viral genome sequencing identified the infecting strain in 68 cases (Omicron [BA.1 and BA.2 subvariants]: 63; Delta: 4; Omicron and Delta: 1). The vaccine was well-tolerated and had an acceptable safety profile. Conclusions A bivalent vaccine conferred heterologous protection against symptomatic infection with newly emergent Omicron (BA.1 and BA.2) in non-naive adults 18-59 years of age. ClinicalTrials.gov: NCT04904549

Safety and immunogenicity of a SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in healthy adults: interim findings from a phase 2, randomised, dose-finding, multi-centre study

BackgroundThis study evaluated the safety and immunogenicity of an AS03-adjuvanted SARS-CoV-2 recombinant protein candidate vaccine, CoV2 preS dTM. MethodsThis Phase 2, modified double-blind, parallel-group study (NCT04762680) was conducted in adults, including those at increased risk of severe COVID-19. Participants were randomised 1:1:1, stratified by age (18-59/[≥]60 years), rapid serodiagnostic test (positive/negative) and high-risk medical conditions (yes/no), to receive two injections (day [D]1 and D22) of 5g, 10g or 15g of CoV2 preS dTM antigen with fixed AS03 content. Interim safety and reactogenicity results (to D43) and neutralising antibodies (NAbs) against the D614G variant are presented (primary objectives). FindingsOf 722 participants enrolled and randomised between 24 February and 8 March 2021, 721 received [≥]1 injections (5g, n=240; 10g, n=239; 15g, n=242). Four participants reported unsolicited immediate adverse events (AEs), two were vaccine-related (investigator assessment). Five participants reported seven vaccine-related medically-attended AEs. No vaccine-related serious AEs and no AEs of special interest were reported. Solicited reactions (local and systemic) were reported at similar frequencies between study groups; these were mostly mild to moderate and transient, with higher frequency and intensity post-injection 2 than post-injection 1. In SARS-CoV-2 naive participants at D36, 96{middle dot}9%, 97.0% and 97{middle dot}6% of participants had [≥]4-fold-rise in NAb titres from baseline in the 5g-, 10g- and 15g-dose groups, respectively. NAb titres increased with antigen dose in younger (GMTs: 2954, 3951 and 5142 for 5g-, 10g- and 15g-dose groups) but not older adults (GMTs: 1628, 1393 and 1736, respectively). NAb titres in non-naive adults after one injection were higher than titres after two injections in naive adults. InterpretationTwo injections of CoV2 preS dTM-AS03 demonstrated acceptable safety and reactogenicity, and robust immunogenicity in SARS-CoV-2 naive and non-naive adults. These results informed antigen dose selection for progression to Phase 3 evaluation of primary and booster vaccination.

Pharmacokinetics and tissue distribution characteristics of sunitinib / 中国临床药理学与治疗学

AIM: To establish a HPLC-UV method to determine sunitinib in rat plasma and mouse tissues, and to study its pharmacokinetics in rats and tissue distribution characteristics in mice. METHODS: The biotic samples were prepared by protein precipitation followed by a stereoselective analysis of sunitinib was achieved on Waters XBridgeTM C18 (4.6 mm×250 mm, 5 μm) with a mobile phase composing of methanol-0.02 mol/L sodium dihydrogen phosphate (70:30) at a flow rate of 1.0 mL/min. The detection wavelength was 310 nm, and the column temperature was 25 ℃. RESULTS: The calibration curve for rat plasma sunitinib was linear in the range of 0.019 2-15.34 μg/mL. The linear ranges in mice brain and kidney were 0.038 3-11.50 and 0.038 3-69.00 μg/mL, respectively. After intragastric administration of sunitinib at a dose of 20 mg/kg to rats, the pharmacokinetic characteristics were Tmax=9.0 h, Cmax=0.194 mg/L, t1/2=18.4 h, AUC(0-∞)=6.8 mg•L-1•h. And the absolute bioavailablity was 47.1%. It was indicated that sunitinib could permeate the blood brain barrier, but the concentration was lower in brain and higher in kidney. CONCLUSION: A HPLC-UV method for the determination of sunitinib in rat plasma and mouse tissues was established. The method is simple, rapid, reliable, and provides a reference for the clinical application of sunitinib.

Genotyping and resistant mutants analysis of P gene in HBV fragment sequencing / 中华检验医学杂志

Objective To establish a method for efficient,accurate genotyping and nucleoside drug-resistant mutation analysis for hepatitis B virus ( HBV ).Methods The 48 HBV serum samples were collected from the Third People's Hospital of Taiyuan from July to August 2011,and HBV DNA were extracted using the commercial kit.The HBV whole genome and P gene were amplified and sequenced.Each HBV sample was genotyped by both constructing phylogenetic trees and genotyping software analysis.The results from two strategies were compared for every sample.Results A total of 48 HBV full genome sequences were identified into 12 B and 36 C genotype's by both constructing phylogenetic trees and genotyping software analysis,which was exactly the same as the analysis using P gene fragment sequencing.Seven forms of nucleoside drug-resistant mutation were found in the P gene for all the samples,with the ratio of 27.1％ ( 13/48 ),in which all the mutation forms were associated with lamivudine or adefovir,and no other nucleotide drugs-related resistance mutations existed.In addition,there were 11 B and 35 C genotype and 2 B/C hybrid type with the analysis using Real-time PCR genotyping for the 48 samples.Conclusion P gene sequencing can be used as a new clinical method for efficient,accurate HBV genotyping and resistant mutation analysis,which provides guidance for hepatitis B treatment.

Clinical research in continuous veno-venous hemofiltration of patients with multiple organ dys-function syndrome / 中国实用护理杂志

Objective To investigate the effect and monitoring point of continuous veno-venous hemofil-tration (CVVH) in patients with multiple organ dysfunction syndrome (MODS). Methods In 22 patients with MODS,a double lumen catheter was put into the central vein,and the CWH was performed with the BRAUN Diapact CRRT. The level of BUN,Scr,serum potassium and arterial blood gas were measured 30 minutes before and after CVVH. The plasma TNF-α、IL-1、IL-8 were measured by ELISA. Vital signs were monitored dur-hag treatment process. Results The vital signs of all patients` was stable, the levels of BUN,Scr and serum potassium decreased significantly after CVVH. The plasma concentrations of TNF-α,IL-1 and IL-8 gradually decreased. Conclusions CWH can improve the blood biochemical markers,remove inflammatory cytokines in plasma,stsblize the vital signs during treatment,which is suitable for patients with MODS.

HPLC Determination of Berberine Hydrochloride in GuZheNing Liniment / 浙江中医药大学学报

[Objective]To develop an HPLC method for the determination of berberine hydrochloride in GuZheNing liniment.[Methods]The chromatographic system consisted of Dimonsil C18 column and mobile phase of acetonitrile-50mmol?L-1 sodium dihydrogen phosphate(adjusted PH to 2.5 with H3PO4)(25:75).The flow rate was 1.0 mL?min-1,and the detective wavelength was at 348 nm.[Results]The calibration curve was linear in the range of 0.106～0.530 ?g(n=5).The method was proved to be repeatable with RSD 0.7%(n=6).4 batches of sample were analyzed and the Berberine Hydrochloride contents were 19.11,18.81,18.83,18.92mg/100mg,respectively.[Conclusion]The method is selective,simple and accurate,and could be used for the quality control of this preparation.

HPLC Determination of Berberine Hydrochloride in GuZhiNing Liniment / 浙江中医药大学学报

[Objective] To develop an HPLC method for the determination of berberine hydrochloride in GuZheNing liniment.[Methods]The chromatographic system consisted of Dimonsil C18 column and mobile phase of acetonitrile—50mmol?L-1 sodium dihydrogen phosphate(adjusted PH to 2.5 with H3PO4)(25∶75).The flow rate was 1.0 mL?min-1,and the detective wavelength was at 348 nm.[Results]The calibration curve was linear in the range of 0.106～0.530 ?g(n=5).The method was proved to be repeatable with RSD 0.7%(n=6).4 batches of sample were analyzed and the Berberine Hydrochloride contents were 19.11,18.81,18.83,18.92mg/100mg,respectively.[Conclusion]The method is selective,simple and accurate,and could be used for the quality control of this preparation.