A study of outcome in COVID-19 patients receiving casirivimab-imdevimab

Objectives: In December 2019, coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, as a respiratory tract infection causing symptoms, such as fever, chills, dry cough, fatigue, and shortness of breath. Despite the low mortality rate of COVID-19, patients with comorbidities such as hypertension, cardiovascular disease, and diabetes mellitus seem to be prone to more severe symptoms and to a higher mortality rate than others. Such patients are shown to benefit from usage of monoclonal antibodies. Casirivimab-imdevimab is a cocktail made up of two non-competing, neutralizing human immunoglobulin G1 antibodies that target the receptor binding domain of the severe acute respiratory syndrome coronavirus 2 spike protein and block viral entry into human cells. We assessed the clinical profile and outcome of 42 patients who received the antibody cocktail. Materials and Methods: Casirivimab-imdevimab was administered to COVID-positive patients with mild severity. Forty-two patients who satisfied the inclusion criteria received casirivimab-imdevimab and were included in the study. Demographic and clinical data were tabulated in Microsoft Excel and statistics were run in OpenEpi software. Results: No adverse reactions were seen in any of the patients. Among the 42 patients, there were no deaths. Twentytwo (52.3%) patients improved, while 20 (47.6%) worsened after receiving the antibody cocktail. Out of 21 (50%) patients who did not have any comorbidity, 13 (30.9%) worsened after receiving the drug and 8 (19%) improved, while among those with comorbidities, 7 (16.6%) worsened and 14 (33.3%) improved (P < 0.05). Thirteen (30.9%) unvaccinated patients improved, while 14 (33.3%) worsened, whereas 6 (14.2%) fully vaccinated patients improved while only 2 (4.7%) worsened. Among the patients who were administered the cocktail within 5 days of onset of symptoms, 12 (28.5%) improved and 10 (23.8%) worsened, whereas among those who received the drug between 6 and 10 days of symptom onset, ten improved, and ten worsened. There was no statistically significant association between vaccination status and outcome, and infusion interval and outcome in these patients. Conclusion: None of the 42 patients developed any reaction to casirivimab-imdevimab. There were no deaths in the study population. About 52.3% of the patients improved and 47.6% worsened after receiving the cocktail. About 33.3% of the comorbid patients improved. There was no statistically significant association between vaccination status and outcome, and infusion interval and outcome in these patients.

Neutralizing monoclonal antibodies present new prospects to treat SARS-CoV-2 infections / 医学前沿

The coronavirus disease 2019 (COVID-19) has caused global public health and economic crises. Thus, new therapeutic strategies and effective vaccines are urgently needed to cope with this severe pandemic. The development of a broadly neutralizing antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the attractive treatment strategies for COVID-19. Currently, the receptor-binding domain (RBD) of the spike (S) protein is the main target of neutralizing antibodies when SARS-CoV-2 enters human cells through an interaction between the S protein and the angiotensin-converting enzyme 2 expressed on various human cells. A single monoclonal antibody (mAb) treatment is prone to selective pressure due to increased possibility of targeted epitope mutation, leading to viral escape. In addition, the antibody-dependent enhancement effect is a potential risk of enhancing the viral infection. These risks can be reduced using multiple mAbs that target nonoverlapping epitopes. Thus, a cocktail therapy combining two or more antibodies that recognize different regions of the viral surface may be the most effective therapeutic strategy.

Research progress on action mechanism and preparation of monoclonal antibodies against 2019-nCoV / 中华临床感染病杂志

During the treatment of critically ill COVID-19 patients it has been revealed that the neutralizing monoclonal antibodies against 2019-nCoV have the advantages of high specificity, high purity, and can be prepared in a large scale, which are expected to be a effective preparation for clinical use. This article introduces the way of 2019-nCoV invasion into the host cells, the major variants of novel coronavirus, and the mechanism of action of anti-2019-nCoV monoclonal antibodies, as well as the progress of research and development of their preparation in major pharmaceutical companies, to provide reference for scientific research and clinical application.

Inhibitory Effects of Cajanonic Acid A on 5 Kinds of Common CYP 450 Enzyme in Human Liver Microsomes in vitro / 中国药房

OBJECTIVE：To study the inhibitor y effects of cajanonic acid A on 5 kinds of cytochrome P 450（CYP）enzyme，in human liver microsomes in vitro . METHODS ：By Cocktail probe substrate method ，50.0，15.0，5.0，1.5，0.5，0.15，0.05 μmol/L cajanonic acid A were added into liver microsomes ， and incubated with mixed probe substrates [including phenacetin ， dextromethorphan，omeprazole，testosterone and toluenesulfonbutylurea （probe substrates of CYP 1A2，CYP2D6，CYP2C19， CYP3A4，CYP2C9，respectively）]. On the basis of setting up blank group and positive control group [ α-naphthalene brass ， quinidine，（+）-N-3-benzyl vanillin ，ketoconazole and sulfabendazole （specific inhibitors of CYP 1A2，CYP2D6，CYP2C19， CYP3A4，CYP2C9，respectively）]，using puerarin as internal standard ，UPLC-MS/MS method was adopted to determine the contents of corresponding metabolites （acetaminophen， dextrophane， 5-hydroxy omeprazole ， 6 β-hydroxytestosterone， hydroxytolbutamide）. The determination was performed on ACQUITY UPLC ® BEH C 18 column，with mobile phase consisted of 0.01％ formic acid aqueous solution- 0.01％ acetonitrile formic acid （gradient elution ）at the flow rate of 0.4 mL/min. The column temperature was 40 ℃，and the sample size was 2 μL. An electrospray ionization source was used to conduct positive and negative ion scanning in the multiple reaction monitoring mode. The data acquisition range was m/z 100-1 200，the collision gas was argon ， the atomized gas was nitrogen ，the gas flow rate of the cone hole was 50 L/h，the desorption gas flow rate was 800 L/h，the capillary voltage under positive and negative mode was 2.0， 1.5 kV，and the ion source temperature was 120 ℃，110 ℃， respectively. The desolvent temperature were 400 ℃ and 450 ℃ ， respectively. Non linear regression analysis was performed by using Graphpad Prism 5.0 software and IC 50 wascalculated. RESULTS ：The linear ranges of above metabolifes were 0.26-8.35，0.36-34.56，0.10-3.09, 3.67-117.37，0.15-4.88 μmol/L（R2＞0.99）. The limits of quantitation were 0.26，0.36， 0.10，3.67，0.15 μmol/L，respectively. The IC 50 values of specific inhibitors in positive control group to CYP 1A2，CYP2D6， CYP2C19，CYP3A4 and CYP 2C9 in human liver microsomes were all within the acceptable range reported in the literature. The IC50 values of cajanonic acid A to CYP 1A2，CYP2D6 and CYP 3A4 in human liver microsomes were all more than 50 μmol/L，and the IC 50 values of CYP 2C9 and CYP 2C19 were 4.94 and 18.00 μmol/L，respectively. CONCLUSIONS ：Cajanonic acid A has no inhibitory effect on CYP 1A2，CYP2D6 and CYP 3A4，but has a certain inhibitory effect on CYP 2C9 and CYP 2C19.

Research progress on Streptococcus mutans phages in the prevention of dental caries / 口腔疾病防治

@#The Streptococcus mutans (S. mutans) phage, as one of the principal pathogenic bacteria of dental caries, is a main cause of the formation and development of dental caries due to its overproliferation in dental plaque biofilms. Bacterial viruses, also known as bacteriophages, have the capability of specifically infecting bacteria and effectively degrading bacterial biofilms. S. mutans phages, therefore, may prevent and control caries. Therapy based on phages has been applied in many fields, but the application of S. mutans phages in caries remains exploratory. This article will review the research progress of S. mutans phages in clinical caries prevention, aiming to provide a new idea for the clinical prevention of caries. The results of the literature review show that the living bacteriophage system has the advantages of high specificity, high affinity and good safety. However, due to its unstable structure, it can be processed into a more stable formulation by freeze-drying, spray drying, adding stability enhancers, or incorporating bacteriophages into ointments, biodegradable polymer matrices or particles to a certain extent to improve stability. The lysozyme produced by phages can digest the bacterial cell wall and release the assembled phage particles, which effectively cleave biofilms. In addition, the antigen binding fragment library for cariogenic pathogens was screened by phage display technology, and the purpose of caries prevention and treatment was achieved by passive immunization of antigen binding fragments. However, the host range of bacteriophages is narrow, so this kind of problem can be overcome by phage combined with traditional therapy or other drug use or cocktail therapy with multiple phages in clinical caries prevention and control.

Analgesic effect of cocktail therapy combined with femoral nerve block on total knee arthroplasty / 中国组织工程研究

BACKGROUND: Total knee arthroplasty is an important measure to save the function of knee joint, but the postoperative pain caused great pain to patients. On the background of multimodal analgesia, cocktail therapy and femoral nerve block are widely used in clinic, and the analgesic effect is exact; however, the analgesic effect and safety of the two methods used together are unknown, so more clinical evidence is needed. OBJECTIVE: To study the effect and safety of analgesic and functional recovery of cocktail therapy combined with femoral nerve block after total knee arthroplasty. METHODS: Totally 100 patients undergoing primary unilateral total knee arthroplasty were enrolled. One hundred patients were randomly divided into two groups (n=50 per group) according to the table of random numbers. Group A was given cocktail therapy combined with femoral nerve block; group B received the injection of same volume of normal saline surrounding the knee joint combined with femoral nerve block. The postoperative resting-state visual analogue scale score, knee joint range of motion, global pain scale, and incidences of adverse reactions were compared between groups. The time and frequency of analgesic drugs were recorded. RESULTS AND CONCLUSION: (1) The postoperative visual analogue scale score at rest in the group A was significantly lower than that in the group B at 24, 36 and 48 hours postoperatively (P < 0.05). The scores at 12 and 72 hours did not differ significantly between groups (P < 0.05). (2) The knee joint range of motion on postoperative 1 and 3 days in the group A was significantly higher than that in the group B (P < 0.05), and no significant difference was detected at 14 days, 1 and 3 months postoperatively (P < 0.05). (3) At 3 months after operation, there was no significant difference in the Global Pain Scale between the two groups (P < 0.05). (4) There was no significant difference in incidences of adverse reactions and additional analgesics between the two groups (P < 0.05). (5) In summary, cocktail therapy combined with femoral nerve block can relieve the early resting pain after total knee arthroplasty, and improve the activity of knee joint in the early stage, which is safe and effective.

Efficacy of different ways of cocktail analgesic mixture injection on total knee arthroplasty / 中南大学学报(医学版)

OBJECTIVES@#To evaluate the efficacy of different ways of cocktail analgesic mixture injection on total knee arthroplasty (TKA).@*METHODS@#A total of 50 patients with knee osteoarthritis treated by TKA from July to September 2018 were randomly divided into two groups (=25). The Group 1 underwent anterior intra-articular injection before prosthesis implanted while the Group 2 underwent posterior intra-articular injection before prosthesis implanted. Visual Analogue Scale (VAS) of all patients for pain during activity and at rest, maximal flexion degree of the knee at the 48th h and the 72th h after surgery, the time of raise leg, usage rate of patient-controlled analgesia (PCA), and complications were evaluated and analyzed.@*RESULTS@#VAS for pain at rest of patients in the Group 1 was significantly less than that in the Group 2 at the 6th, 12th, and 24th h after surgery (all <0.05). Maximal flexion degree of the knee at the 48th h and the 72th h after surgery in the Group 1 was better than that in the Group 2 (both <0.05). The Group 1 costed less time than the Group 2 on the ability to perform an active straight leg raise (=0.027).@*CONCLUSIONS@#The anterior intra-articular cocktail analgesic mixture injection can strongly relieve the pain early after TKA, which can improve knee function and achieve painless rehabilitation in most patients, with safety.

Application of intravenous injection of tranexamic acid combined with local use of tranexamic acid cocktail in intertrochanteric fracture fixation / 中国修复重建外科杂志

Objective: To explore the efficacy and safety of intravenous injection of tranexamic acid (TXA) combined with local use of TXA cocktail in intertrochanteric fracture fixation with proximal femoral nail antirotation (PFNA). Methods: Patients with intertrochanteric fractures who underwent close reduction and internal fixation with PFNA between February 2018 and March 2019 were enrolled in the study. Among them, 45 patients who met the selection criteria were included in the study and randomly allocated into 3 groups ( n=15). The patients in group A were not received TXA during perioperative period. The patients were intravenously injected of 1.0 g TXA before operation in group B and combined with local use of TXA cocktail during operation in group C. There was no significant difference in the age, gender, body mass index, fracture classification, disease duration, and complications between groups ( P>0.05). The perioperative blood loss and blood transfusion rate, the visual analogue scale (VAS) score before operation and at 12, 24, and 48 hours after operation, the levels of prostaglandin E2 (PGE2) and bradykinin (BK) before operation and at 1 and 3 days after operation, postoperative complications, and the maximum amplitude (MA) of thromboelastogram were recorded and compared between groups. Results: The total blood loss, hidden blood loss, and visible blood loss were significantly lower in groups B and C than those in group A ( P0.05). The postoperative VAS scores and the levels of PGE2 and BK were significantly lower in group C than in groups A and B ( P0.05). The incidences of postoperative complications were 33.33% (5/15), 20.00% (3/15), and 13.33% (2/15) in groups A, B, and C, respectively, with no significant difference between groups ( χ2=1.721, P=0.550). Conclusion: For intertrochanteric fractures, application of intravenous injection of TXA combined with local use of TXA cocktail in PFNA fixation can reduce perioperative blood loss, relieve pain after operation, and do not increase the risk of complications.

Evaluation of the effects of resveratrol on the activity human cytochrome P450 through combined probe method / 中国临床药理学与治疗学

AIM: To evaluate the effects of resveratrol on five human cytochrome enzyme P450 subtypes, i.e. CYP1A2, CYP2D6, CYP2C9, CYP3A4, and CYP2C19, through a combined probe method. METHODS: We conducted a randomized controlled study in which 26 healthy male volunteers were recruited and were randomized into the resveratrol group and the placebo group. Volunteers were given oral placebo /resveratrol at a dose of 1 g each time, once daily for 14 days. Then, they took five oral probe drugs, caffeine (for CYP1A2), losartan (for CYP2D6), omeprazole (for CYP2C19), dextromethorphan (for CYP2C9), and midazolam (for CYP3A4). Blood samples at different times were collected to detect the concentration of the three probes, i.e. midazolam, caffeine and omeprazole; 0-8 h urine samples were collected to measure the metabolic rate of losartan and dextromethorphan. RESULTS:Compared with the placebo group, the AUC0-12, AUC0-∞, Cmax of caffeine in the resveratrol group was increased by 32.10% (P0.05) as compared with the placebo group. The 8 h urinary DTM/DT ratio was increased by 79.91% (P=0.003) and 8 h urinary losartan/E-3174 ratio was increased by 531.34% (P<0.001).CONCLUSION: Resveratrol significantly inhibited the enzymatic activities of CYP1A2, CYP2D6 and CYP2C9 after repeated administration, but did not significantly change the enzymatic activities of CYP3A4 and CYP2C19.

Safety of steroid-containing cocktail periarticular injection after knee arthroplasty: A meta-analysis / 中国组织工程研究

BACKGROUND: Steroids have strong anti-inflammatory, anti-emetic and analgesic effects and are widely used in perioperative analgesia. Studies have shown that periarticular injection of steroid-containing cocktail analgesic therapy in knee arthroplasty can relieve postoperative pain, improve knee activity, and reduce complications. However, the other studies show that steroids can increase the risk of postoperative infection, and tendon rupture. Therefore, the safety and efficacy of steroid-containing cocktail periarticular injection in knee arthroplasty is still controversial. OBJECTIVE: To evaluate the safety and efficacy of steroid-containing cocktail periarticular injection after knee arthroplasty by meta-analysis. METHODS: The published literatures were searched on the databases of PubMed/Medline, Cochrane Central Register of Controlled Trials, and EMBASE until April 2019. All randomized controlled trials of topical steroid analgesia after knee arthroplasty were collected and eligible articles were screened. Two researchers independently assessed the risk of bias and methodological quality of included studies by the Cochrane 5.0. The outcome data were extracted and a meta-analysis was conducted by Review Manager 5.2 software. RESULTS AND CONCLUSION: (1) A total of 10 randomized controlled articles involving 820 patients were included. (2) The meta-analysis showed that visual analogue scale score was lower in the steroid group than in the control group at postoperative 1 day [MD=-1.52, 95%C/(-2.94, -0.10), P=0.04]. Motion range was higher in the steroid group than in the control group at postoperative 1, 2, 3,4 and 5 days [MD=11.57, 95%C/(9.85, 13.30), P < 0.000 01; MD=9.03, 95%C/(B.67, 11.38), P < 0.000 01; MD=5.73, 95%C/(0.85, 10.60), P=0.02; MD=5.53, 95%C/(0.68, 10.38), P=0.03); MD=5.90, 95%C/(0.87, 10.93), P=0.02j. Morphine use was less in the steroid group than in the control group [MD=-7.94, 95%C/(-14.35, -1.53), P=0.02j. Hospital stay was shorter in the steroid group than in the control group [AfD=-0.98, 95%C/(-1.25, -0.71), P < 0.000 01]. Straight leg raising took less time in the steroid group than in the control group [MD=0.65, 95%C/(-0.86, 0.44), P < 0.000 01]. Postoperative C-reactive protein level was lower in the steroid group than in the control group [WMD=-4.82, 95%C/(7.41, 2.23), P=0.000 3]. Knee society score and complication rate were not significantly different between the two groups. (3) To conclude, the periarticular injection of steroid-containing cocktails after knee arthroplasty is safe and effective.

Adding hormone in cocktail promotes rapid recovery after unicompartmental knee arthroplasty / 中国组织工程研究

BACKGROUND: Postoperative pain is a common clinical problem in unicompartmental knee arthroplasty, and severe pain can affect postoperative efficacy. Hormone is a common and effective anti-inflammatory drug, and there is some controversy over whether to add hormone to the local injection of cocktail in unicompartmental knee arthroplasty. OBJECTIVE: To evaluate the effectiveness of adding hormones to the cocktail to promote rapid recovery after unicompartmental knee arthroplasty. METHODS: Osteoarthritis patients receiving unilateral unicompartmental knee arthroplasty from October 2017 to March 2019 were randomly divided into a hormone group (local injection of cocktail + 40 mg triamcinolone acetonide) and a control group (local injection of cocktail + equivalent normal saline). Visual analogue scale score, fentanyl consumption, knee function, inflammatory indicators, adverse reactions and complications were observed in both groups after surgery. RESULTS AND CONCLUSION: (1) Finally, 80 patients were included in the study (n=40 in each group). There was comparability between the two groups (P > 0.05). (2) The static and dynamic visual analogue scale scores of patients in the hormone group at 1, 2 and 3 days after surgery were significantly lower than those in the control group (P 0.05). (6) C-reactive protein levels at 3 days and interleukin-6 levels at 24 hours after surgery in the hormone group were significantly lower than those in the control group (P < 0.05). (7) The incidence of complications in the hormone group was significantly lower than that in the control group (P < 0.05). (8) Addition of hormones in the cocktail can effectively promote the rapid recovery after unicompartmental knee arthroplasty..

Effects of Valeriana amurensis Roots and Rhizomes Extract and Its Active Constituents on Activities of Drug Metabolism Enzymes in Liver / 中国实验方剂学杂志

Objective::To evaluate the effects of Valeriana amurensis roots and rhizomes extract and its active constituents on the activities of six major cytochrome P450 (CYP450) enzymes in human liver microsomes. Method::Coumarin, bupropion, tolbutamide, omeprazole, dextromethorphan and testosterone were used as probe substrates for CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, respectively. Taking their specific metabolites of hydroxylation or demethylation (7-hydroxycoumarin, hydroxybupropion, 4-hydroxytolbutamide, 5-hydroxyomeprazole, dextromethorphan, 6β-hydroxytestosterone) as indicators of enzyme activities. The analytical indexes were used to establish an in vitro model of human liver microsomes of Cocktail probe substrates. This method was applied to evaluate the effects of V. amurensis roots and rhizomes extract and its active constituents on human liver microsomal enzymes. Result::The V. amurensis roots and rhizomes extract had different inhibitory effects on CYP2B6, CYP2C9, CYP2D6 and CYP3A4, their half-inhibitory concentration (IC50) values were 87.49, 1.73, 68.29, 2.80 mg·L-1, respectively. Among the 9 lignans, (-)-massoniresinol-3α-O-β-D-glucopyranoside had a moderate inhibitory effect on CYP2A6 with an IC50 value of 8.51 μmol·L-1, 8, 8′-dihydroxypinoresinol-4, 4′-di-O-β-D-glucopyranoside had a moderate inhibitory effect on CYP2D6 with an IC50 value of 8.73 μmol·L-1, (+)-medioresinol-4, 4′-O-di-β-D-glucopyranoside had a moderate inhibitory effect on CYP2B6 and CYP2C9 with IC50 values of 5.41 μmol·L-1 and 8.20 μmol·L-1. Conclusion::The V. amurensis roots and rhizomes extract and its active constituents have inhibitory effects on liver CYP450 enzymes. Therefore, in the clinical study of new drugs, it is necessary to fully evaluate the risk of drug interactions caused by combination therapy.

Comparison of different stains in exfoliated oral mucosal cell micronucleus of potentially malignant disorders of oral cavity

Background: Micronucleus (MN) has been proved to be an important biomarker of genomic damage. Leishman Giemsa (LG) cocktail, being a relatively new staining technique, has not been used in exfoliative cytology. The aim of this study is to observe and compare the micronuclei (MN) frequency in potentially malignant disorders (PMDs) and also to compare the staining efficacy of May-Grünwald Giemsa (MGG), LG cocktail, and Papanicolaou (PAP) for micronuclei in exfoliated oral mucosal cells. Materials and Methods: Three smears were prepared from each 30 controls (buccal mucosa) and 120 patients (40 oral submucous fibrosis, 40 lichen planus, and 40 leukoplakia) clinically diagnosed with having one of the PMDs of the oral cavity stained with PAP, MGG, and LG cocktail stains. MN frequency (No. of MN/1000 cells) was evaluated and compared between the cases and the controls. Comparison between the three different stained smears was also made to determine the clarity and efficacy of the stains. Results: LG cocktail gave comparatively better results followed by PAP and MGG. Statistically significant results (P < 0.05) were obtained, using Mann–Whitney test for comparison of MN frequency between cases and controls. Conclusion: LG cocktail is an easy, cost- effective, and one step technique comparable to PAP staining; however, it warrants further study in its potential application in screening of oral cancer.

Effect of Honey Cocktail on Macular Thickness, Retinal Nerve Fiber Layer Thickness and Optic Nerve Head Parameters in Post-Menopausal Women

@#Introduction: Honey postulated may have an estrogenic effect on the retinal estrogenic receptors. The aim of the study is to compare the mean macular thickness, retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) parameters with and without honey cocktail supplement in post-menopausal women. Methods: A randomised interventional study was conducted from March 2014 to July 2015. A total of 60 post-menopausal women were selected and randomised into 2 groups: honey cocktail (20 mg/day) and control. Macular thickness, RNFL thickness and ONH parameters were measured using optical coherence tomography at baseline and at 3 months post honey cocktail supplementation. Results: The mean global macular thickness and RNFL thickness were significantly thicker in post-menopausal women with honey cocktail at 3 months post supplement (p = 0.002 and 0.033 respectively). There was a significant increase in the mean change of global macular thickness and RNFL thickness in honey cocktail group at 3 months post supplement (p < 0.001 and < 0.001 respectively). Although there was no significant difference in the ONH parameters at 3 months post supplement between the two groups but there was significant increase in the mean change of rim area (p = 0.003), and significant reduce in the mean change of cup area (p = 0.001) and cup-disc-ratio (p <0.001) in honey cocktail group at 3 months post supplement. Conclusion: Honey cocktail supplement showed structural changes in the macular thickness, RNFL thickness and OHN parameters of post-menopausal women.

Effect of Inula cappa on CYP450 Enzyme in Rats by Cocktail Probe Drugs / 中国实验方剂学杂志

Objective:To study on the effect of Inula cappa extract on the activities of six cytochrome P450(CYP450) enzymes in rats by Cocktail probe method. Method:Rats in the I. cappa high and low dose groups were given oral administration of active fractions of I. cappa at a dose of 8.127,2.709 g·kg-1·d-1 of the material for 7,14 d,repectively.Probe drugs(caffeine,midazolam,tolbutamide,omeprazole,metoprolol,chlorzoxazone) were simultaneously injected to rats after administration.Plasma was collected at different time after the administration of probe drugs.The plasma concentrations of these six probes were measured by UPLC-MS and their corresponding pharmacokinetic parameters were calculated with DAS 2.0. Result:Compared with the control group,only the apparent volume of distribution(V) of midazolam was increased;area under the curve(AUC0-t and AUC0-∞)and half-life period(T1/2) of caffeine,midazolam,tolbutamide and omeprazole were increased and the clearance rate(CL) of them was decreased in rats of I. cappa groups.But there were no differences in pharmacokinetic parameters of chlorzoxazone and metoprolol. Conclusion:I. cappa can reduce the enzymatic activities of CYP3A,CYP1A2,CYP2C9 and CYP2C19 in rats at different degree,among which CYP3A is the strongest.

Role of Ad36 in inducing browning of 3T3-L1 cells / 中华内分泌代谢杂志

Objective@#To investigate the role of adenovirus type 36 (Ad36) in the browning of 3T3-L1 cells.@*Methods@#BODIPY staining was performed on the 0, 2nd, 4th, 6th and 8th days of the cocktail induction (control) group and the cocktail plus Ad36 induction (experimental) group to observe the adipogenesis of 3T3-L1 cells.The mRNA and protein expressions of uncoupling protein-1(Ucp1), ATP synthase, H+ transporting, mitochondrial F1 complex, O subunit (Atp5o), cytochrome c oxidase subunit 5B(Cox5b), and perilipin were detected by real-time PCR and Western-blot.@*Results@#The results of BODIPY staining showed that the lipid droplets in the control group gradually became larger with the differentiation of the cells, while the lipid droplets in the experimental group firstly became larger, and then appeared smaller after Ad36 was added on the fourth day. Compared with the control group, the mRNA and protein expression levels of Ucp1, Atp5o, and Cox5b in the experimental group were significantly increased while the expression level of perilipin was significantly decreased (all P<0.05).@*Conclusion@#During the differentiation of 3T3-L1 cells, Ad36 promotes its browning via increasing the expressions of Ucp1, Atp5o, and Cox5b.

Role of ad36 in inducing browning of 3T3-L1 cells / 中华内分泌代谢杂志

Objective To investigate the role of adenovirus type 36 ( Ad36) in the browning of 3T3-L1 cells. Methods BODIPY staining was performed on the 0, 2nd, 4th, 6th and 8th days of the cocktail induction (control) group and the cocktail plus Ad36 induction ( experimental) group to observe the adipogenesis of 3T3-L1 cells. The mRNA and protein expressions of uncoupling protein-1 ( Ucp1 ), ATP synthase, H+ transporting, mitochondrial F1 complex, O subunit ( Atp5o), cytochrome c oxidase subunit 5B ( Cox5b), and perilipin were detected by real-time PCR and Western-blot. Results The results of BODIPY staining showed that the lipid droplets in the control group gradually became larger with the differentiation of the cells, while the lipid droplets in the experimental group firstly became larger, and then appeared smaller after Ad36 was added on the fourth day. Compared with the control group, the mRNA and protein expression levels of Ucp1, Atp5o, and Cox5b in the experimental group were significantly increased while the expression level of perilipin was significantly decreased ( all P＜0. 05 ). Conclusion During the differentiation of 3T3-L1 cells, Ad36 promotes its browning via increasing the expressions of Ucp1, Atp5o, and Cox5b.

Application of D2-40/CD34-CK cocktail antibodies for colorectal cancer with insufficient lymph node harvest / 临床与实验病理学杂志

Purpose To investigate the value of application of D2-40/CD34-CK cocktail antibodies by double immunohistochemical staining for assessment of lymphovascular invasion (LVI) and to determine its prognostic significance in colorectal cancer with insufficient lymph node harvest. Methods Specimens from 133 cases of colorectal cancer with less than 12 lymph nodes were selected. HE staining and double immunohistochemical staining of the cocktail antibodies were performed to compare the difference of the two methods in screening for LVI. The The relationship between LVI confirmed by cocktail antibody immunohistochemical staining and clinicopathological characteristics and overall survival (OS) of patients was analyzed. Results (1) The detection rates of cocktail antibody double immunohistochemical staining and HE staining for LVI were 42.9％ (57/133) and 21.8％ (29/133) with statistically significant difference (P < 0.001). (2) The presence of LVI confirmed by double staining was significantly associated with Dukes staging, depth of invasion, clinical stages, lymph node metastasis and tumor budding (P < 0.05). (3) The presence of LVI, the location and extent of LVI, and the number of tumor cells in thrombus ≥5.5 for cases with LVI ≤2 clusters, were significantly associated with OS (P < 0.05). Conclusion D2-40/CD34-CK cocktail antibodies double staining is superior to routine HE staining in assessing LVI. LVI is intimately associated with tumor stage, lymph nodes metastasis and tumor budding, and it is an independent prognostic factor for CRC patients. It should be a supplementary examination for these patients with insufficient lymph node harvest.

Application of tranexamic acid combined with intra-articular cocktail and TXA mixture perfusion in pri-mary total knee arthroplasty / 实用医学杂志

Objective To investigate the efficacy and safety of intravenous tranexamic acid(TXA)admin-istration combined with intra-articular"cocktail"+TXA infusion in primary total knee arthroplasty(TKA). Meth-ods 90 patients were randomly divided to experimental group A,control group B and control group C,30 cases in each group.There was no significant difference(P>0.05) in the preoperative general informations,such as age, sex,body mass index,hemoglobin,hematocrit,D-dimer,preoperative KSS score,knee activity ROM,VAS scores,operation time,time of using tourniquet. All the patients were intravenously injected with TXA 1g before using the tourniquet. After suturing the capsule,for the group A,100 ml of TXA and cocktail mixture(TXA 1g, ropivacaine 40 mg,epinephrine 0.1 mg,methylprednisolone 40 mg) were perfused into the articular cavity through the drainage which then be clamped.By the same ways,group B patients infused with tranexamic acid solution 100 mL(TXA 1g),group C patients infused with saline 100 mL.The total blood loss volume,drainage volume,intraop-erative blood loss,hidden blood loss,the change of hemoglobin and hematocrit in postoperative 3 days,blood trans-fusion,adverse reactions,the VAS scores at 6,12,24,72 h in the postoporative quiescent condition and the VAS scores at 12,24,72 h in the postoporative activity condition were measured and compared.Results The volume of total blood loss,hidden blood loss,drainage,were(685.7 ± 120.6)mL、(259.9 ± 162.0)mL、(151.5 ± 48.9)mL in group A,the decrease of hemoglobin and hematocrit at postoperative 3 d were(18.6 ± 3.2)g/L、(3.1 ± 1.3)% in group A,there was statistically significant(P<0.05) comparing with the control groups.The VAS scores of experi-mental group in the resting and the active state were lower than that in control groups(P < 0.05). Conclusion The application of intravenous tranexamic acid administration combined with intra-articular"cocktail"+TXA infu-sion can reduce the volume of postoperative total blood loss,drainage and hidden blood loss.Simultaneously,it can significantly alleviate the early postoperative pain,which is conducive to early rapid recovery,while not increasing the risk of thrombosis,and no adverse reactions.

Role of LncRNA ROR in Ad36-induced browning of human adipose-derived stem cells / 中华内分泌代谢杂志

Objective To investigate the role of LncRNA ROR in Ad36-induced browning of human adipose-derived stem cells(hADSC). Methods After hADSC was induced by cocktail and Ad36 for 2,4,6,and 8 days,Oil red O staining was performed for observing the adipogenic status. The mRNA expressions of LncRNA ROR, uncoupling protein 1(UCP1),and PRDM16 were detected by real-time PCR and the protein expressions of UCP1 and PRDM16 were detected by Western-blot. After LncRNA ROR was knocked down by siRNA, UCP1 and PRDM16 mRNA and protein expression levels in the process of Ad36-induced adipocyte differentiation were detected by real-time PCR and Western-blot. Results Oil red O staining showed that fat droplets in the cocktail-induced group were larger than those in the Ad36-induced group. Compared with the cocktail group,the mRNA expressions of LncRNA ROR, UCP1 and PRDM16, and the protein expressions of UCP1 and PRDM16 in Ad36 group were significantly increased(P<0.05). The mRNA and protein expressions of UCP1 and PRDM16 in LncRNA ROR knockdown group were significantly lower than those in control group(P<0.05). Conclusion In the process of Ad36-induced hADSC differentiation,the up-regulation of LncRNA ROR may stimulate UCP1 and PRDM16 expression,and thus promote the browning of hADSC.