It has been widely accepted in modern pharmaceutical industry that quality cannot be tested into products , instead quality should be built-in by design . However , the implementation of Quality by Design ( QbD ) in development , manufacture and supervision of traditional Chinese medicine ( TCM ) still remains to be a challenge . The program of safety re-evaluation of TCM injections provides an opportunity to practice QbD approach in TCM industry . This paper discussed some potential ways that improve the quality of TCM injec-tions base on QbD related tools , including identification of critical quality attributes , critical process parameters and critical material attributes, development of design space and control strategy.

The morbidity of young non-small cell lung cancer(NSCLC)increases in the recent years.Young group patients should be defined as age under 40 years old.The risk factors of etiology in the young NSCLC may be related with smoking,genetic predisposition,Internal and external environment factors havoc and etc.There is no specific symptoms of young NSCLC,therefor,it happens misdiagnosis and harder to be confirmed.The morbidity in young female group of NSCLC patients is higher than aged patients.The most frequent histopathologic type is adenocarcinoma and the ratio of advanced stages with low differentiation has been found to be more common.The chances of surgery seems lower than others.EGFR gene mutation percentage in the young NSCLC maybe lower than that in the old patients,while the positive mutation of MEL4-ALK gene maybe more prevalent in the young patients.The prognosis of young NSCLC seems to be poor with lower tumor progression time of the first line therapy.Better prognosis of young NSCLC patients maybe achieved by early diagnosis and efficient therapy according to the accurate genotypes.

Objective To compare clinical effect and complications of micro-implant anchorage(MIA ) or self -driven titanium implant(SDIA) with headgear anchorage in treatment of maxillary dentoalveolar protrusion .Methods 50 patients with maxillary dentoalveolar protrusion were selected and divided into observation group and control group .Each group contained 25 patients .14 patients in observation group received MIA treatment while 11 patients received SDIA treatment .All patients in control group re-ceived headgear anchorage treatment .Comparison was made in respects of course of treatment ,clinical effect and complications .Re-sults The course of treatment in observation group was (19 .85 ± 2 .01) months while in control group was(23 .58 ± 1 .79) months . The treatment time in control group were longer than observation group (P < 0 .05) .U1-SN angle in observation group were de-creased(16 .8 ± 1 .9)° while the control group decreased(20 .2 ± 2 .1)° .In the vertical direction ,the observation group maxillary inci-sor and first molars were shorten (2 .0 ± 0 .8)mm and(1 .6 ± 1 .0)mm respectively ,while the control group were shorten (0 .7 ± 0 .5) mm and(0 .3 ± 0 .7)mm .In the sagittal direction ,the observation group maxillary first molars were moved (0 .6 ± 1 .1)mm while the control group were moved (1 .7 ± 0 .8)mm .The difference of U1-SN ,U1-X ,U6-Y ,U6-X between two group were statistically sig-nificant .The comparison of expulsion rate between MIA and SDIA had no statistical significance .But the rate inflammation symp-tom and hyperplasia of the gum in SDIA patients were higher than MIA patients .Conclusion MIA and SDIA had better ability in treatment of maxillary dentoalveolar protrusion in vertical direction than headgear and improve the curative effect of maxillary den -toalveolar protrusion and both of them had same fell off rate ,but SDIA had higher rate of inflammation .

In March,2009,novel influenza pandemic A(H1N1)virus emerged in Mexico and rapidly disseminated worldwide.Secondary pulmonary infection is a predominant contributor to the death of novel influenza A(H1N1),The most common causative pathogens of secondary pulmonary infection in novel influenza A(H1N1)include Streptococcus pneumoniae,Haemophilus influenzae and Staphylococcus aureus.The recognization of the pathogenesis of secondary pulmonary infection in novel influenza A(H1N1)is critically significant to the strategy in diagnosis and treatment of novel influenza A(H1N1).Therefore,we elaborate the current situation of secondary pulmonary infection in novel influenza A(H1N1)and provide insight into the clinical diagnosis and treatment of novel influenza A(H1N1).

Objective To investigate the clinical efficacy of splenectomy combined with coronary-caval shunt in treatment of portal hypertension (PHT).Methods The retrospective descriptive study was conducted.The clinical data of 21 patients with PHT who underwent splenectomy combined with coronary-caval shunt at the First Affiliated Hospital of Xi'an Jiaotong University from January 2001 to December 2015 were collected.Observation indicators included (1) operation situations,changes of pre-and post-operative portal hemodynamics including operation time and volume of intraoperative blood loss,diameter and blood flow velocity of portal vein (PV),gastric coronary vein and superior mesenteric vein (SMV).(2) Clinical indexes in perioperative period (before operation,at postoperative 1 week and 1 month):① blood routine test:the counts of red blood cell (RBC),white blood cell (WBC) and platelet (PLT),② liver function:Child-Pugh score,alanine transaminase (ALT),total bilirubin (TBil),albumin (Alb),extended time of prothrombin time (PT) and international normalized ratio (INR).(3) Follow-up:postoperative 1-,3-,5-year complications [upper gastrointestinal re-bleeding,peritoneal effusion,hepatic encephalopathy,hepatic failure,portal vein thrombosis (PVT) and anastomotic stoma thrombosis].The follow-up using outpatient examination and telephone interview was regularly conducted once every 3 months within postoperative 1 year and once every 6 months after postoperative 1 year up to March 2016 or end of follow-up (death).Measurement data with normal distribution were presented as x ± s.The comparison of different time-point was analyzed by the repeated measures ANOVA and Student t test.Measurement data with sknewed distribution were presented as M (range).Results (1) Operation situations and changes of pre-and post-operative portal hemodynamics:21 patients underwent successful splenectomy combined with coronary-caval shunt,including 19 receiving splenic vein bypass combined with anastomosis of gastric coronary vein and inferior vena cava and 2 receiving anastomosis of gastric coronary vein and inferior vena cava.Operation time,volume of intraoperative blood loss were (187 ± 33)minutes and (233 ± 114)mL.Diameter and blood flow velocity of PV,gastric coronary vein and SMV were (1.39±0.20)cm,(0.66±0.15)cm,(0.74±0.32)cm,(11.2±3.4)cm/s,(6.6± 1.3)cm/s,(7.0 ±2.2)cm/s before operation and (1.36 ±0.22)cm,(0.42 ±0.11)cm,(0.81 ±0.23)cm,(10.4 ± 2.5) cm/s,(8.2 ± 2.5) cm/s,(6.9 ± 2.4) cm/s after operation,respectively,showing no statistically significant difference in the diameter and blood flow velocity of PV and SMV before and after operation (t =0.46,-0.81,0.87,0.14,P ＞ 0.05)and with statistically significant differences in the diameter and blood flow velocity of gastric coronary vein before and after operation (t =5.9 1,-2.60,P ＜ 0.05).(2) Clinical indexes in perioperative period:① routine blood test:the counts of RBC,WBC and PLT were (2.70 ± 0.50) × 1012/L,(2.6 ±2.3) × 109/L,(55 ±28) × 109/L before operation and (3.10 ±0.60) × 1012/L,(2.8 ±2.0) × 109/L,(248 ± 182) × 109/L at postoperative 1 week and (3.70 ±0.20) × 1012/L,(6.2 ± 1.9) × 109/L,(457 ± 184) × 109/L at postoperative 1 month,respectively,with statistically significant differences (F =31.91,11.03,30.74,P ＜ 0.05).There were statistically significant differences in the counts of RBC and PLT between 1 week postoperatively and before operation (t =-2.35,-4.81,P ＜ 0.05) and between 1 month postoperatively and 1 week postoperatively (t =-4.35,-5.65,-3.71,P ＜ 0.05).② Liver function:Child-Pugh score,ALT,TBil,Alb,extended time of PT and INR were 6.3 ± 1.2,(23 ± 17) U/L,(28 ± 18) μmol/L,(31.1 ± 6.8) g/L,(4.8 ±2.1) s,1.40 ± 0.20 before operation and 6.2 ± 0.9,(44 ± 24) U/L,(26 ± 11) μmol/L,(35.0 ± 7.4) g/L,(3.4 ± 2.0) s,1.30 ± 0.20 at postoperative 1 week and 6.0 ± 0.6,(36 ± 22) U/L,(23 ± 8) μmol/L,(34.2 ± 2.2) g/L,(3.7 ± 3.0) s,1.50 ± 0.30 at postoperative 1 month,respectively,showing no statistically significant difference (F =1.97,2.60,1.18,1.45,P ＞0.05).There were statistically significant differences in the ALT and extended time of PT (F =7.97,4.37,P ＜ 0.05) and in the ALT and extended time of PT between 1 week postoperatively and before operation (t =3.23,2.21,P ＜ 0.05).(3) Follow-up:21 patients were followed up for 3-168 months with a median time of 37 months.During follow-up,3 patients were dead.One,1,2 patients were complicated with upper gastrointestinal re-bleeding at postoperative 1,3,5 years and received hemostatic therapy under endoscopy,and then 2 were dead.Three,2 and 2 patients had peritoneal effusion and were improved by symptomatic treatment.One patient had hepatic encephalopathy and hepatic failure at postoperative 5 years and was dead after conservative treatment.PVT and anastomotic stoma thrombosis at postoperative 1,3,5 years were detected in 2,2,1 and 2,1,1 patients,with anticoagulant therapy,and 1 patient received vascular recanalization.Conclusion Coronary-caval shunt is a highly selective portosystemic shunt,it can significantly down regulate the regional pressure while ensure the normal blood flow of liver and decrease the rate of rebleeding,hepatic encephalopathy and thrombosis,meanwhile,it might be a potential therapy in management of PHT.

MicroRNAs (miRNAs) negatively mediate the post transcriptional target genes by degrading mRNAs and inhibiting translation of protein.Deregulation of miRNAs are directly or indirectly correlated with tumorigenesis and development of cancer.Currently,the application of miRNAs as a non-invasive potential biomarker with high stability is under investigation.

Glial cell line-derived neurotrophic factor(GDNF) is a kind of protein factor which can regulate the enteric nervous system in survival,differentiation,colonization and injury repair.It has been confirmed in the disorders of the enteric nervous system,such as hirschsprung and anorectal malformations,but the specific mechanism in regulation of this factor is still unknown.Studies have found that GDNF/GFRa1/RET and GDNF/GFRa1 / NCAM pathway may be involved in the growth and maturation of the enteric nervous system,the disorders of those pathways above may lead to diseases by affecting the differentiation,proliferation and migration of intestinal neural stem cells,causing dysfunctions in the anatomical structure and function of the intestinal neurons.

Objective To investigate the status of iodine nutrition and variations of thyroid hormone levels in pregnant women in Foshan and to provide the science theory on the clinical diet supplement rational .Methods The samples were collected from 442 ca‐ses of pregnant women in Chancheng district center hospital from June 2013 to November 2014 .Free triiodothyronine(FT3) ,free thyroxine(FT4) and thyroid stimulating hormone(TSH) were determined by method of electrochemiluminescence .The urinary io‐dine content in pregnant women was measured by using cold digestion method according to iodine catalytic effect of Arsenic‐Ceri‐um .Results The median urinary iodine in 442 cases of pregnant women was 174μg/L .The percentage of midrange iodine deficien‐cy ,mild iodine deficiency ,iodine sufficiency and iodine overdose in 442 cases of pregnant women were respectively 4 .30% ,29 .86% , 39 .59% and 26 .24% .First trimester ,second trimester ,third trimester with abnormal level of urine iodine was respectively 72 .41% ,45 .89% ,62 .91% .The different gestational age with abnormal level of urine iodine and normal level of urine iodine was significant differences(P<0 .05) .The urine iodine sufficient group of FT3 ,TSH were lower than the urine iodine deficiency groups and the urine iodine excess group ,The FT4 of urine iodine sufficient group compare with iodine deficiency groups was significant differences(P<0 .05) .TSH in urine iodine sufficient group to compared urine iodine excess group ,with significant differences(P<0 .05) .Conclusion The abnormal rate of the level of iodine nutrition and the prevalence of thyroid diseases of pregnant women in FoShan are relatively high .The pregnant women should be screening and intervention in time to raise healthier .

Objective:Through animal experiments to observe the behavior and serum malondialdehyde(MDA)and total antioxidative capacity(T-AOC)content after electro-acupuncture "Baihui,Fengfu,Shenshu,Xuanzhong" Point of Alzheimer, s disease in rat.Method:Select forty Healthy adult Wistar rats,the Wistar rats were randomly divided into four groups,model group,electro-acupuncture group,western medicine group,electro-acupuncture and western medicine group.Abdominal cavity injection of D-galactose in order to prepare the Alzheimer, s disease model rats.Electro-acupuncture group:acupuncture Baihui,Shenshu, Fengfu,Xuanzhong.Western medicine group:Piracetan intragastric administration one times a day.Every other day give the fixed and crawl for ten minutes.Electro-acupuncture and western medicine group:Accupuncture treatment and drug treatment are above all.Model group:Every day give the same fixed and crawl as electro-acupuncture group.Behavior and serum MDA,T-AOC levels tested after treatment.Results:electro-acupuncture group,electro-acupuncture and western medicine group could extend the incubation period,reduce the number of errors(P

Objective To explore the mRNA expressions of NLRP1 (NOD-like receptor 1 ) and NLRP3 inflammasomescomponents and related pro-inflammation cytokines in peripheral blood mononuclear cells (PBMCs).Methods A total of 21 septic patients,20 non-infectious SIRS patients and 20 health subjects were enrolled in this study.The mRNA expressions of inflammasomes components and related proinflammation cytokines were measured by using RT-PCR,and serum levels of IL-1β and IL-18 were measured using ELISA.One-way ANOVA was usedd to compare the data of all three groups,and SNK-q was employed to compare thedata among different groups.Spearman correlation analysis was used to analyze the correlation between these biomarkers and the severity of septic patients.Results ①The mRNA expression of NLRP1 in PBMCs of septic patients in early stage and non-infectious SIRS patients was down-regulated in comparison with healthy subjects (P ＜0.01 ).The expression of NLRP3 in septic patients was not differentfrom that in healthy subjects ( P ＞ 0.05 ),but NLRP3 mRNA expression in non-infectious SIRS patients was significantly higher than that in septic patients and in healthy subjects ( P ＜ 0.01 ).ASC ( apoptosis associated speck like protein containing a CARD) and caspase-1 mRNA expressions in septic patients and non-infectious SIRS patients were higher than those in healthy subjects ( P ＜ 0.01 ).There was no difference in level of IL-1β found among all groups.IL-18 mRNA expression in septic patients and non-infectious SIRS patients was higher than that in healthy subjects ( P ＜ 0.01 ),and that in non-infectious SIRS patients was highest.②)Serum protein level of IL-1β in septic patients was lower than that in healthy subjects (P ＜0.05 ),and serum level of IL-18 in septic patients was significantly higher than that in non-infectious SIRS patients and in healthy subjects ( P ＜ 0.01 ).③NLRP1 was negatively related to SOFA ( sepsis-related organ failure assessment) score (r =-0.44,P ＜ 0.05 ) and negatively related to APACHE Ⅱ score as well ( r =- 0.52,P ＜ 0.05 ).Conclusions NLRP1 mRNA expression was down regulated in patients with early sepsis and its expression was negatively correlated to the severity of septic patients,indicating the lower NLRP1 mRNA expression the severer illness.