In the last decade,many molecular targeted drugs,such as epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI),have been successively applied in clinical use,and they have brought about a substantial prolongation of survival life and improvement in life quality of those patients with lung adenocarcinoma,but that is not real in squamous cell lung cancer.Immunotherapy clinical trials for programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) pathway in non-small cell lung cancer (NSCLC) have been started since 2012.In 2015,an anti-PD-1 antibody,nivolumab,was proved by FDA to treat advanced squamous NSCLC with progression on or after platinum-based chemotherapy.This article reviews the recent advantages in the treatment of advanced lung squamous cell carcinoma.

OBJECTIVE:To optimize the technology of separation and purification of active constituents from Morus alba L. METHODS:With the adsorption rate and desorption rate as the indexes,static and dynamic macroporous resin adsorption-desorp-tion methods were adopted to optimize the type of macroporous resin,the loading amount of fluid,the volume fraction and amount of eluent in the separation and purification technology of total flavonids. With the yield and content of polysaccharide as the index-es,water extraction and alcohol precipitation method was used to optimize the volume fraction of alcohol for polysaccharide precipi-tation in the separation and purification technology of total polysaccharides. With the absorbance of total alkaloids as the index,ion exchange method was employed to optimize the loading amount of fluid and the amount of eluent in the separation and purification technology of total alkaloids. Then the verification was conducted. RESULTS:The optimal technology of total flavonids from Morus alba L. was with D101 macroporous resin as the adsorbent,loading fluid mass concentration of 0.1 g(material medicinal)/ml,loading fluid amount 9 times as the column volume(BV),70% alcohol of 5 BV for elution. The optimal volume fraction of alcohol for polysaccharide precipitation in the technology of total polysaccharides was 80%. The optimal technology of total alka-loids was with loading fluid amount of 3 BV,0.5 mol/L ammonia water of 8 BV for elution. After separation and purification,the purities of total flavonids,total polysaccharides and total alkaloids from Morus alba L. were 35.68%,47.14% and 55.79%,and the RSDs were 1.28%,1.61% and 1.14%(n=3). CONCLUSIONS:The optimal technology is stable and suitable for the separa-tion and purification of active constituents from M. alba L.

Objective To evaluate the role of Sonic hedgehog (Shh) signaling pathway in the spinal cord in neuropathic pain (NP) in the rats.Methods Seventy-two male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were randomly divided into 2 groups (n=36 each) using a random number table:sham operation group (S group) and NP group.Spared nerve injury was produced by exposing the sciatic nerve and its branches and ligation and transection of tibial nerve and common fibular nerve in anesthetized rats.The mechanical paw withdrawal threshold (MWT) was measured before operation and at 1,4,7,14 and 21 days after operation.After measurement of the pain threshold at 1,4,7,14 and 21 days after operation,the animals were then sacrificed,and the lumbar segment (L46) of the spinal cord was obtained for determination of Shh,Patched (Ptch),Gli1 and glial fibrillary acidic protein (GFAP)expression (by Western blot),Shh,Ptch and Gli1 mRNA expression (by fluorescent quantitative real-time reverse transcriptase-polymerase chain reaction),and Shh and GFAP expression (by immunohistochemistry).Results Compared with group S,the MWT was significantly decreased,and the expression of Shh,Ptch and Gli1 protein and mRNA and GFAP in spinal cord tissues was up-regulated in group NP (P＜ 0.05).Shh was mainly expressed in the cytoplasm of spinal dorsal horn neurons and in the gap around glial cells.Conclusion Shh signaling pathway in spinal cord is involved in the development and maintenance of NP in the rats.

Objective:To understand the drug purchase behaviors and prescription flows of outpatients and their influencing factors. Methods: After selecting and investigating tertiary hospitals, secondary hospitals, community health service centers ( one per each level) in Beijing, Zhengzhou, Guangzhou, this paper uses structured question-naire method to analyze 3,155 valid questionnaires. A logistic regression analysis is performed to understand the fac-tors influencing the drug purchase behaviors. Results:The factors influencing the drug purchase behaviors of outpa-tients mainly include the region where the patient is, level of the hospital, type of health insurance that the patient has, frequency of drug purchase, etc. Conclusions: This paper suggests hospital administrators to take measures to improve prescription flows, such as reforming the health care insurance to make payment system more suitable for pharmacies standardizing supply channels in order to make varieties consistent between hospitals and pharmacies, strengthening education and publicity to raise the outpatients’ awareness for drug purchase outside of hospitals, etc.

Objective To explore the effect on ultrasound localization method with radial artery cannulation in infants.Methods Sixty infants (1 month-1year old)undergoing elective surgical proce-dures required artery pressure,were randomly divided into two groups:ultrasound localization group (group B):the infants were used of portable B ultrasound probe in the wrist with two dimensional ul-trasound image to determine the body position of the radial artery;control group (group C):tradi-tional palpation determine the radial artery puncture position.One puncture success rate,total punc-ture success rate,the period of puncture time and incidence of complications were recorded;MAP, the radial artery diameter,the vertical distance from the ultrasound probe to the skin and the length from the puncture spot to the radial artery were also measured.Results The success rate of first puncture in group B was higher than that of group C (P <0.05),the times of puncture and procedure time were significantly less than those of group C (P <0.05),the incidence of hematoma was lower than that in group C (P <0.05).Conclusion The application of ultrasound-guided method for radial artery cannulation is safe and reliable with accurate localization,highly successful rate of puncture at first time,lower complication and shorter time for placement.

Electrochemiluminescence was used to determine thyroid function and thyroid autoantibodies in 140 pregnant women,who were then divided into normal group (n =117) and subclinical hypothyroidism group (n =23) based on the thyroid function.The urine iodine level in the pregnant women was detected by arsenic cerium catalytic spectrophotometric method.The awareness of past history of thyroid disease among the subjects with thyroid dysfunctions were investigated.The results showed that the prevalences of iodine deficiency were 50％ and 57％ in the normal group and the subclinical hypothyroidism group,respectively.The state of iodine level was not related to thyroid function.The levels of serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody were markedly related to serum TSH(P＜0.01),so was the level of serum TPOAb related to serum FT4 (P＜0.05).Among the subclinical hypothyroidism women,70％ did not undergo thyroid function and thyroid autoantibodies screening before pregnancy,8.7％ denied past history of thyroid disease,and 21.7％ suffered from hypothyroidism before pregnancy.Therefore,we advocate the screening of urine iodine and thyroid autoantibodies before or during the first trimester of pregnancy,aiming to correct iodine deficiency,avoid supplementing too much iodine,improve the outcome of perinatal stage,and reduce all the negative effects on the offsprings.

Objective To investigate the effects of keratinocyte growth factor on peritoneal adhesion formation in rats. Methods Thirty Sprague-Dawley( SD) female rats were randomly assigned to 3 groups, KGF group( n = 10), positive control group (n = 10) , and negative control group (n = 10). Seven days after surgery, rats were killed and the adhesion degree was evaluated by Leach scale. Immunohistochemical technique was used to identify the expression of tPA and PAI-1. Stained with HE,the histomorphology changes of the adhesion tissue were observed by light microscope. Picrosirius-polarization method was used to observe the expression of type Ⅰ or Ⅲ collagens in two groups. Results In the KGF group,lower collagen fibers were noted and the gross adhesion scores was significantly lower than that in positive control group (4. 8 ± 1. 0 vs 7. 6 ± 1. 0; t = 5.422; P ＜ 0. 01). The expression level of type Ⅰ collagens was significantly lower in the KGF group than in positive control group (69 ±11 versus 55 ±9;t = 3. 214 ;P ＜0. 01) ,but there was no significant difference in the expression of type Ⅲ collagens among the two groups (48 ± 7 versus 50 ± 10; t = 0. 481; P ＞ 0. 05). The immunohistochemistry showed that the expression of tPA significantly increased in the KGF group than in positive control group and negative control group(88 ±4.0 versus 112 ±4.0, 101 ±2.0;F = 109. l,P＜0. 01) , However, no statistically significant difference for the expression of PAI-1 was noted among the three groups ( F = 1. 391, P ＞ 0. 05). Conclusions Keratinocyte growth factor promotes mesothelium repair, increases mesothelial fibrinolytic activity, inhibits the deposition of collagen and reduces the intensity of postoperative adhesions.

Objective To explore the role of hypoxia inducible factor 1α(HIF-1α)-mediated signaling pathway in angiotensin Ⅱ(Ang Ⅱ)induced renal interstitial fibrosis. Methods Renal tubular epithelial cells were cultured and treated with different concentrations (10-9-10-6 mol/L)of Ang Ⅱ for 24 h and 48 h.Real-time quantitative PCR and Western blotting were preformed to detect the mRNA and protein expressions of HIF-1α,prolyl hydroxylase 2 (PHD2)and tissue inhibitor of metalloproteinase 1 (TIMP-1)in renal tubular epithelial cells. Results HIF-1αmRNA level was increased with Ang Ⅱ treatment in a concentration dependent manner.When cells were treated with Ang Ⅱ concentration at 10-7mol/L for 24 h,the mRNA level was markedly increased by 166%.Furthermore,by real-time quantitative PCR and Western blotting,compared with the control group,Ang Ⅱincreased the mRNA and protein levels of HIF-1α and TIMP-1 (P<0.05,respectively),while the mRNA and protein levels of PHD2 were decreased markedly (P<0.05,respectively)in renal tubular epithelial cells.Conclusion Ang Ⅱ reduces HIF-1αdegradation in renal tubular epithelial cells probably by reducing the expression of PHD2,which increases the expressions of HIF-1α and TIMP-1 involved in renal interstitial fibrosis.

Objective:To investigate the pharmacokinetics of mycophenolic acid( MPA)and its metabolites in different stages af-ter the administration of enteric-coated mycophenolate sodium( EC-MPS)tablets in Chinese liver transplant recipients. Methods:The blood samples of 24 patients were collected in 0-12h of the 1st and 3rd week after the administration of EC-MPS. The concentrations of MPA,AcMPAG and MPAG in plasma were measured by LC-MS/MS developed in our lab. The pharmacokinetic parameters of MPA and its metabolites were estimated by non-compartmental method. Results:After 1-and 3-week therapy with EC-MPS,Cmax ,AUC0-12 and t1/2 was(18. 1 ± 8. 75)and(20. 7 ± 16. 0)μg ml-1 ,(42. 7 ± 17. 5)and(47. 1 ± 23. 9)μg·h·ml-1 ,(3. 33 ± 2. 81)and (3.30 ±1.89)h for MPA;(2.50 ±1.86)and(1.78 ±1.72)μg·ml-1,(14.5 ±11.7)and(6.97 ±6.57)μg·h·ml-1, (4. 48 ± 2. 53)and(3. 76 ± 1. 8)h for AcMPAG;(171. 6 ± 135. 4)and(152. 2 ± 115. 9)μg·ml-1 ,(1299 ± 1 204)and(1 051 ± 561)μg·h·ml-1 ,(8. 73 ± 4. 25)and(7. 75 ± 2. 87)h for MPAG,respectively. There was no significant difference in the PK parameters of MPA after the 1-and 3-week therapy. The Cmax ,Tmax and t1/2 of MPA in the patients received EC-MPS were significantly higher than those in the patients received MMF(P<0. 05). Cmax and AUC0-12 of MPAG in the patients received EC-MPS were signifi-cantly higher than those in the patients received MMF after the 3-week therapy(P<0. 05). Conclusion:There is no significant accu-mulation of MPA after the therapy with EC-MPS at different stages. The absorption of MPA is delayed after the therapy with EC-MPS compared with that with MMF. There is no difference in MPA exposure between EC-MPS and MMF in Chinese liver transplant patients.

Objective: To investigate the inhibitory effects and induction of apoptosis on human gastric adenocarcinoma cells (SGC 7901) by genistein. Methods: MTT、 colony forming experiment、 electon microscope and FCM were used to study the effects of genistein on SGC 7901.Results: MTT and colony forming experiment showed that the genistein inhibited SGC 7901 growth. Electron microscope and FCM showed that genistein could induce apoptosis. [WT5HZ]Conclusion: [WT5BZ]Genistein inhibits SGC 7901 cells growth via apoptosis induction.