[Objective] To explore the bone histomorphology effect of QiangGuYin on neck of femur of ovariectomized rats.[Methods]Ninety femal SD rats,weight 230～280 gram,were rangdonmized into three groups:QiangGuYin group(treatment group),Miacalcic group(contrast group)and control group.All rats were variectomized.After 10 weeks,the osteoporosis model succeed,the treatment group,contrast group were given QiangGuYin,Miacalcic respectively.The treatment group used QiangGuYin everyday,1ml/g.The contrast group used Miacalcic 0.72u/kg,everyday hyodermic.And 3,4.5,6 months after the treatment,kill 10 rats to explore.The neck of femur were cut and stined with Masson Golder Trichrome for bone histomorphomemetric contrast group analysis.[Result]The treatment group ovariectomized rats' in 3m,BV/TV compared with statistical significance;compared with control group in Tb.sp,BV/TV,Tb.Th with statistical significance.After 4.5m treatment group Tb.Th compared with contrast group have statistical significance.Give the medicine 6m,Tb.sp,Tb.Th compared with contrast group all have statistical significance.[Conclusion]Giangguyin can effectively improve the histomorphometry index.The mechanism probably is stimulating osteogenesis and supperssing the cytoactive of osteoclast and trend of the high bone transform.

Objective To investigate the changes in serum level of vascular endothelial growth factor (VEGF), nitric oxide (NO), erythropoietin (EPO) and plasma level of carbon monoxide (CO) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and their clinical significance. Methods Sixty-four patients diagnosed as OSAHS by polysomnography (PSG), were divided into two groups according to apnea-hypopnea index (AHI), 20 in mild group [5/h≤AHI≤20/h, with a mean of (12± 5)/hi and 44 in moderate-severe group[AHI > 20/h, with a mean of (63±23)/h]. Blood samples were obtained from all the patients after PSG for measurement of levels of serum VEGF, NO and EPO and plasma CO. Results Levels of serum VEGF [(101±91) ng/L], NO [(10.3±3.3) μmol/L]and plasma CO [(0.56±0. 35) mg/L]in moderate-severe OSAHS group were significantly higher than those in mild group (all P <0.05). There was no significantly difference in serum level of EPO between the two groups (P> 0.05). Levels of serum VEGF, NO and plasma CO in OSAHS patients positively correlated with AHI and percentage of time with percutaneous arterial blood oxygen saturation lower than 0. 9 (SLT90) of all sleep time (all P < 0. 05), but reversely correlated with the lowest arterial blood oxygen saturation (LSaO2) at night (P>0.05). No correlation between EPO and all the indicators was found (P>0.05). Multiple linear regression analysis showed that LSaO2 was an independent risk factor to affect levels of serum VEGF and plasma CO (R2=0.198, P=0.001, and R2=0.210, P=0.000, respectively) and SLT90 was an independent risk factor to affect serum level of NO (R2= 0. 148, P=0.004) in OSAHS patients. Conclusion Hypoxia at night is a main cause leading to increased level of serum VEGF, NO and plasma CO in OSAHS patients.

[Objective]To study whether Cervus and Cucumis Polypeptide(CCP ,Lugua polypeptide) can treat osteoporosis or not. [Methods]Forty 4-month-old female SD rats were randomized into four groups(10 in each group) ,including SHAM,0VX, OVX+CCP1 and OVX+CCP2 groups. Male rats in OVX groups take the ovariectomized surgery. Since the 13th week, rats in groups A and B got 0.9% physiological saline injection once in a day, group C was treated with CCP 0.4mL/(kg·d)injection and group D treated with CCP0.8mL/(kg·d) injection once one day. Twelve weeks later, al rats were sacrificed for obtaining specimen. Took right femurs, measured the bone biomechanical properties. [Results ]After 12 weeks since injection, the biomechanical property of right femurs in group OVX was significantly lower than that of the SHAM group( P<0.01); parameters such as maximum load and elastic load in group OVX+CCP1 and OVX+CCP2 were higher than that of group OVX(P<0.05), but lower than that of group SHAM(P<0.05). The distinction of the above parameters was significant( P<0.05)between group OVX+CCP1 and OVX+CCP2. [Conclusion]1.CCP can significantly im-prove the bone internal biomechanical properties in ovariectomized(OVX) rats, so it has function to treat osteoporosis caused by drop in estrogen level. There are differences of bone biomechanical properties aspects when treated with different dosage of CCP, which shows the tendency of dose-dependent effect. So we can conclude that CCP may have dose-dependent effect.

OBJECTIVE:To establish a method for simultaneous determination of methadone,venlafaxine and their metabolites in rat plasma,and to use it for the study of pharmacokinetic in rats. METHODS:UPLC-MS/MS method was adopted to determine plasma after precipitated with acetonitrile using diazepam as internal standard. The determination was performed on Waters Acquity UPLC BEH C18 column with mobile phase consisted of acetonitrile-0.1％ formic acid (gradient elution) at the flow rate of 0.4 mL/min. The column temperature was set at 40 ℃,and sample size was 2 μL. ESI was used for positive ion scanning by multiple reaction monitoring (MRM) mode. The ion pairs for quantitative analysis were m/z 310.4→265.4(methadone),m/z 278.2→234.1 (EDDP),m/z 278.1→57.8(venlafaxine),m/z 263.9→57.9(O-desvenlafaxine),m/z 285.1→193.1(internal standard). Eight SD rats were given methadone hydrochloride 6 mg/kg and venlafaxine hydrochloride 10 mg/kg intragastrically(4 rats for each drug);blood samples (0.3 mL) were collected from the tail vein before and 0.083,0.167,0.25,0.5,0.75,1,1.5,2,3,4,6,8,10,12, and 24 h after medication. Pharmacokinetic parameters were calculated by using DAS 3.0 software. RESULTS:The linear ranges of methadone,EDDP,venlafaxine and O-desvenlafaxine were 0.5-250 ng/mL(r=0.9997),0.5-250 ng/mL(r=0.9992),0.4-200 ng/mL(r=0.9999),0.4-200 ng/mL(r=0.9999),respectively. The limits of quantitation were 0.5,0.5,0.4,0.4 ng/mL. RSDs of intra-day and inter-day were all lower than 9.0％(n=6). The method recoveries were 94.20％-102.87％,90.93％- 102.94％, 92.95％-101.61％,90.33％-101.97％(RSD≤5.5％,n=6). The extraction recoveries were 85.90％-94.45％,85.97％- 91.66％, 87.97％ -93.58％ , 88.53％ -94.54％(RSD≤5.9％ ,n=6). The matrix effects were 95.96％ -97.78％ , 92.33％ -97.40％ , 95.28％-97.71％,95.33％-95.74％(RSD≤4.9％,n=3). The pharmacokinetic parameters included that t1/2 were (1.42 ± 1.02),(2.59 ± 0.76),(0.63 ± 0.08),(1.29 ± 0.14) h;cmax were (52.21 ± 5.42),(25.68 ± 3.45),(45.68 ± 2.29),(47.63 ± 13.09) μg/L;MRT0-24 h were (3.55 ± 0.21),(3.98 ± 0.41),(1.44 ± 0.21),(2.01 ± 0.17) h;AUC0-24 h were (201.95 ± 51.14),(86.092 ± 15.95),(75.38 ± 23.95),(82.90 ± 23.44)μg·h/L. CONCLUSIONS:The method is specific, absolute separated, rapid and sensitive, and can be used for the simultaneous determination of methadone,venlafaxine and their metabolites in plasma and pharmacokinetics research.

A resurging interest in targeted covalent inhibitors (TCIs) focus on compounds capable of irreversibly reacting with nucleophilic amino acids in a druggable target. p97 is an emerging protein target for cancer therapy, viral infections and neurodegenerative diseases. Extensive efforts were devoted to the development of p97 inhibitors. The most promising inhibitor of p97 was in phase 1 clinical trials, but failed due to the off-target-induced toxicity, suggesting the selective inhibitors of p97 are highly needed. We report herein a new type of TCIs (i.e., FL-18) that showed proteome-wide selectivity towards p97. Equipped with a Michael acceptor and a basic imidazole, FL-18 showed potent inhibition towards U87MG tumor cells, and in proteome-wide profiling, selectively modified endogenous p97 as confirmed by in situ fluorescence scanning, label-free quantitative proteomics and functional validations. FL-18 selectively modified cysteine residues located within the D2 ATP site of p97. This covalent labeling of cysteine residue in p97 was verified by LC‒MS/MS-based site-mapping and site-directed mutagenesis. Further structure-activity relationship (SAR) studies with FL-18 analogs were established. Collectively, FL-18 is the first known small-molecule TCI capable of covalent engagement of p97 with proteome-wide selectivity, thus providing a promising scaffold for cancer therapy.

Tuberculosis （TB） and human immunodeficiency virus infection / acquired immune deficiency syndrome （HIV/AIDS） are both serious global public health threats. Early detection of infected persons and/or patients through TB/HIV bi-directional screening is crucial for prevention and control strategy in China and globally. In recent years， with the promotion and application of new TB and HIV detection technologies worldwide， TB/HIV bi-directional screening technologies and strategies have made remarkable changes. This expert consensus introduces the significance and challenges of TB/HIV bi-directional screening， summarizes important progress of research and applications， and makes recommendations on screening measures and procedures to further strengthen TB/HIV bi-directional screening in China.

Surgical innovation is an important part of surgical research and practice. The evaluation of surgical innovation through the stages is similar to those for drug development, but with important differences. The Idea, Development, Exploration, Assessment, and Long-term follow-up (IDEAL) Framework and Recommendations represent a new paradigm for the evaluation of surgical intervention and devices which was developed in 2009. The IDEAL is a five-stage framework involving the nature stages of surgical innovation, together with recommendations for surgical research pathway. The Framework and Recommendations were updated and published in 2019, which added a pre-IDEAL stage if necessary. The updated IDEAL also underlines the purpose, key question and ethical issues for each stage. In the first paper of IDEAL Framework and Recommendations series, we conducted a comprehensive introduction of IDEAL (e.g. the development, updates and application of IDEAL) to promote the dissemination and application of IDEAL in China.