AIM To investigate the pharmacokinetic behaviors of total flavonoids from Epimedii Folium in osteoporotic rats in vivo.METHODS Twelve rats were divided into model group and sham group,after which the osteoporotic rat model was established by removing bilateral ovaries.After intragastric administration with total flavonoids (500 mg/kg),HPLC-DAD was applied to detecting the plasma concentrations of total flavonoids' prototype glycosides (epimedin A,epimedin B,epimedin C,icariin) and their metabolites (sagittatoside A,sagittatoside B,2-O-rhamnosylicariside Ⅱ,baohuoside Ⅰ,icaritin) at thirteen time points (0.083,0.25,0.5,0.75,1,2,3,4,6,8,12,24 and 48 h),then the plasma concentration-time curves were drawn,followed by the calculation of pharmacokinetic parameters.RESULTS Doubled peaks were observed in the plasma concentration-time curves of total flavonoids' prototype glycosides and their metabolites in both groups.Compared with the sham group,the integrated AUC and Cmax in the model group were significantly decreased (P ＜ 0.01),as well as the prolonged t1/2 (P ＜ 0.01).CONCLUSION The in vivo absorption and metabolism of total flavonoids from Epimedii Folium are much slower in the state of osteoporosis,thus affects the efficacy.

Objective To examine the expression levels of cyclin Dl in the patients with chronic myelogenous leukemia (CML), and evaluate the pathogenesis and clinical significance of cyclin Dl in CML Methods The real-time quantitative polymerase chain reaction (RQ-PCR) was performed to detect the expression levels of cyclin Dl in the bone marrow samples of 18 patients with CML, and 16 samples of benign hemopoietic patients. The relationship between the expression levels of cyclin Dl and the progression and prognosis of patients with CML were analyzed. Results The level of cyclin Dl was higher expressed in 18 patients with CML than the control group (P <0.001). The levels of cyclin Dl was apparently higher expressed in accelerated phase /blast crisis phase than in chronic phase (P <0.05). And the RQ-PCR method showed the tendency that a significant increase was observed in the levels of cyclin Dl from 0.1980 in control group to 1.4002 in chronic phase and 5.4540 in accelerated phase /blast crisis phase. Conclusion The cyclin Dl overexpressed in CML, the roles of cyclin Dl in CML might be an oncogene expressed. The expression level is correlated with the progression and prognosis of patients with CML.

Objective To observe any short-term analgesic effect of using heat stimulation at acupoints for treating migraine headaches without aura.Methods Totally 120 migraine patients were randomly divided into an observation group and a control group,each of 60.Both groups was given 5mg of Sibelium orally each night for 4 weeks.The observation group additionally received heat and pain stimulation at the Feng Chi,Shuai Gu,Yang Ling Quan,Wai Guan,Tai Yang and Yin Tang acupoints.The heat was in 0.3 s pulses at 54.5° with an inter-pulse interval of 10 s.Each acupuncture point was stimulated 5 times in rotation for a total of 20 min daily for 4 weeks.The frequency of headache attacks,their duration,their intensity rated using a visual analogue scale (VAS),accompanying symptoms and responses to a migraine-specific quality of life questionnaire (MSQ) were recorded before and after the treatment.Results After the treatment there was significantly greater improvement in the observation group compared to the control group in terms of headache frequency,headache duration,VAS ratings,and accompanying symptoms.The observation group also improved significantly more in terms of the average limitation dysfunction score,dysfunction score and emotion score on the MSQ.Moreover,the total effectiveness rate of the observation group (95.0％) was significantly higher than that of the control group (80.0％).During the treatment,no adverse reactions were found in terms of heart rate or blood pressure,and no abnormal manifestations such as infection,redness or swelling were observed at the stimulation sites.Conclusion Heat and pain stimulation at acupoints has a significant short-term analgesic effect on migraine without aura.Such treatment is safe and reliable,with few side effects.It provides a new treatment method for migraine patients and is worthy of clinical promotion and application.

Objective To summarize the medication law of TCM in the treatment of chronic bronchitis;To provide reference for clinical medication.Methods Medical records of patients with chronic bronchitis who were hospitalized in the Respiratory Department of the First Affiliated Hospital of Henan University of Chinese Medicine from January 1,2016 to December 31,2021 were extracted based on HIS electronic medical record data.After screening,the TCM prescriptions used by patients with chronic bronchitis were input into Excel 2019 to establish a database.Based on the software Lantern 5.0,the latent structure model was learned,hidden variables and explicit variables were obtained,and the model was interpreted.SPSS Modeler 18.0 was used to establish model points with Apriori algorithm for Chinese materia medica with a frequency greater than 6%,to obtain the association rules between drugs,and to analyze the medication law of TCM in treating chronic bronchitis.Results A total of 3 410 cases were included,involving 423 kinds of Chinese materia medica,with a cumulative frequency of 82 766 times.Among them,109 kinds of Chinese materia medica with a frequency of>6 % had a cumulative frequency of 69 845 times.The top five commonly used medicines were Fritillariae Cirrhosae Bulbus,Poria,Atractyodis Macrocephalae Rhizoma,Asteris Radix et Rhizoma,Citri Reticulatae Pericarpium,mainly with medicines of reducing cough and phlegm,antiasthmatic medicine,tonifying deficiency,clearing heat,relieving superficies,promoting blood circulation and removing blood stasis.The medicinal properties were warming,cold and mild,and the main tastes were bitter,sweet and pungent,and the meridians were mainly lung,spleen,liver and stomach meridians.Through analysis of latent structure,49 hidden variables and 149 hidden classes were obtained.Combined with professional knowledge,10 comprehensive clustering models and 21 core formulas were deduced,such as Sangbaipi Decoction,Xuefu Zhuyu Decoction,Xiaoqinglong Decoction,Erchen Decoction,Shashen Maidong Decoction,Liuwei Dihuang Pills,Yinqiao Powder,Zhisou Powder,Yupingfeng Powder,Xuefu Zhuyu Decoction combined with Daotan Decoction,etc.It was concluded that the chronic bronchitis syndrome included phlegm-heat stagnation lung syndrome,qi stagnation blood stasis syndrome,cold fluid attacking lung syndrome,phlegm-dampness accumulation lung syndrome,lung qi and yin deficiency syndrome,kidney yin deficiency syndrome,wind heat attacking lung syndrome,wind cold attacking lung syndrome,lung qi and spleen deficiency syndrome,phlegm stasis interjunction syndrome.A total of 41 strong association rules were screened in the analysis of association rules,including 5 strong association rules for two and 36 strong association rules for three.The high confidence rules were Saposheikovize Radix + Angelicae Sinensis Radix →Atractyodis Macrocephalae Rhizoma,Saposheikovize Radix + Codonopsis Radix → Atractyodis Macrocephalae Rhizoma,Codonopsis Radix + Citri Reticulatae Pericarpium → Atractyodis Macrocephalae Rhizoma;the higher degree of improvement were Bupleuri Radix + Mori Cortex → Scutellariae Radix,Perillae Fructus + Belamcandae Rhizoma → Fritillariae Cirrhosae Bulbus,Armeniacae Semen Amarum + Pinelliae Rhizoma → Citri Reticulatae Pericarpium,etc.Conclusion In the treatment of chronic bronchitis,TCM is mainly used to reduce phlegm,relieve cough and asthma,and the method of promoting blood circulation and removing blood stasis is commonly used to help eliminate phlegm.In addition,TCM pays attention to the application of methods such as tonifying lung and securing the exterior,invigorating spleen and benefiting qi.

This study was aimed to prepare tripterine-coix seed component microemulsions (TCC-MEs) with coix seed oil and coix seed polysaccharide as bimodal excipients and evaluate its activity on anti-lung cancer in vivo.Coix seed oil was extracted by supercritical extraction methods and coix seed polysaccharide was obtained through hot water extraction and alcohol precipitation from coix seed.Then,coix seed oil was used as the oil phase,and coix seed polysaccharide aqueous solution was used as the aqueous phase.RH40 was used as the surfactant.PEG400 was used as cosurfactant to prepare microemulsion.TCC-MEs were made by water titration method and characterized by size,polymer dispersity index (PDI),zeta potential,encapsulation efficiency and drug loading capacity.And then,anti-tumor activity of TCC-MEs was evaluated on the xenograft Lewis tumor mouse models.The liver and kidney toxicity was evaluated by HE staining and biochemical indicators.The results showed that the optimized prescription for TCC-MEs was coix seed oil 400 mg,RH40 300 mg,PEG 400 100 mg,coix seed polysaccharide 50 mg,tripterine 10 mg;and the tripterine encapsulation efficiency was (90.72 ± 0.28)％;the drug loading capacity was (1.08 ± 0.17)％;the mean diameter of microemulsion was (43.86 ± 0.22) nm;PDI was 0.10 ± 0.01;the zeta potential was (-13.14 ± 1.35) mV.The activity of anti-lung cancer in TCC-MEs was significantly better than that of the control group,with no significant liver and kidney toxicity after treatment with TCC-MEs.It was concluded that the prepared TCC-MEs had advantages of small amount of conventional auxiliary materials,small particle size and high stability.This study showed that the combination of triptolide and coix seed to microemulsion system has synergistic and attenuated effect.

Integrase inhibitors (INSTIs) are the newest class of antiretroviral drug which are available to people living with the human immunodeficiency virus (HIV). Since 2007, five types of INSTIs have been marketed: Raltegravir, Elvitegravir, Dolutegravir, Bictegravir and Cabotegravir, all of which were approved by the US Food and Drug Administration (FDA) for use in the initiation of antiretroviral therapy (ART) in treatment-na?ve individuals. Compared with other types of antiretroviral drugs, INSTIs have better efficacy and tolerability, so many countries around the world have listed INSTIs-containing regimens as the preferred regimen for HIV ART. In recent years, with the widespread use of INSTIs, some research data suggest that INSTIs may have some adverse effects (AEs), such as central nervous system symptoms, abnormal lipid metabolism, weight gain, abnormal liver and kidney function, etc. This review summarizes the current use of INSTIs in people living with the HIV, and highlights the clinical efficacy and their AEs among the five types of INSTIs in China.

Background::To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19.Methods::This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable.Results::A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%-48.1%; P = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151-3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350-67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. Conclusions::SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events.Trial registration::Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term= NCT04260594&draw=2&rank=1

UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a key role in detoxification of many potentially harmful compounds and drugs. UGT1A1 inhibition may bring risks of drug-drug interactions (DDIs), hyperbilirubinemia and drug-induced liver injury. This study aimed to investigate and compare the inhibitory effects of icotinib and erlotinib against UGT1A1, as well as to evaluate their potential DDI risksUGT1A1 inhibition. The results demonstrated that both icotinib and erlotinib are UGT1A1 inhibitors, but the inhibitory effect of icotinib on UGT1A1 is weaker than that of erlotinib. The ICvalues of icotinib and erlotinib against UGT1A1-mediated NCHN--glucuronidation in human liver microsomes (HLMs) were 5.15 and 0.68 μmol/L, respectively. Inhibition kinetic analyses demonstrated that both icotinib and erlotinib were non-competitive inhibitors against UGT1A1-mediated glucuronidation of NCHN in HLMs, with thevalues of 8.55 and 1.23 μmol/L, respectively. Furthermore, their potential DDI risksUGT1A1 inhibition were quantitatively predicted by the ratio of the areas under the concentration-time curve (AUC) of NCHN. These findings are helpful for the medicinal chemists to design and develop next generation tyrosine kinase inhibitors with improved safety, as well as to guide reasonable applications of icotinib and erlotinib in clinic, especially for avoiding their potential DDI risksUGT1A1 inhibition.