Bronchial asthma （asthma for short） is a common clinical respiratory disease mainly characterized by chronic airway inflammation， with complicated pathogenesis and a long treatment cycle. It is lingering and difficult to be cured， and lack specific drugs. Oxidative stress is a new focus in the research on the pathogenesis of asthma and a potential key target for the treatment. Under physiological conditions， the oxidative and antioxidative systems in the body are in a dynamic balance， and the two antagonize each other to maintain normal life activities. In the case of asthma attack， oxidation products such as reactive oxygen species （ROS）， malondialdehyde （MDA）， and nitric oxide （NO） are produced excessively， while the content of antioxidants such as superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） is reduced. As a result， the oxidation exceeds the removal of oxidation products， which aggravates oxidative stress. In addition， the overproduction of ROS activates oxidative stress-related signaling pathways to produce pro-inflammatory factors， exacerbating inflammation， which leads to lung and airway tissue damage. In recent years， traditional Chinese medicine has garnering increasing attention because of the unique advantages in the treatment of asthma， especially in regulating redox balance， alleviating oxidative stress in asthma patients， and reducing inflammation. On the one hand， by inhibiting the mitogen-activated protein kinase （MAPK） and transcription factor （NF）-κB signaling pathways， traditional Chinese medicine can reduce the content of oxidation products and pro-inflammatory factors from the source. On the other hand， by activating the nuclear factor-erythroid 2-related factor 2 （NrF2） signaling pathway， traditional Chinese medicine can elevate the levels of antioxidant enzymes and enhance the antioxidant system to neutralize the excessive accumulation of oxidation products. Therefore， the adjustment of redox balance state by traditional Chinese medicine may be a new means and a new direction for the prevention and treatment of asthma in the future. This paper summarizes the oxidative stress-related pathways in the pathogenesis of asthma and reviews the latest research progress in the regulation of oxidative stress-related pathways by Chinese medicine extracts and prescriptions in the treatment of asthma， with a view to providing a fuller， more solid， and more scientific theoretical basis for the clinical and basic research on the prevention and treatment of asthma by traditional Chinese medicine.

Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis. It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis. Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile. We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in HepG2 cells. Gavage administration of nitazoxanide inhibited high-fat diet (HFD)-induced increases of liver weight, blood and liver lipids, and ameliorated HFD-induced renal lipid accumulation in hamsters. Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers. In the hamsters with pre-existing hyperlipidemia and hepatic steatosis, nitazoxanide also showed therapeutic effect. Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet (WD)-induced hepatic steatosis in Apoe ^-/- mice. The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.

Objective: To detect the differences in the expression of Yes-associated protein(YAP) in non-cardia gastric cancer and normal gastric tissue and analyze the associations between single nucleotide polymorphisms(SNP) in the YAP gene andits protein expression,and to preliminarily discuss the correlationbetween YAP and the development of non-cardia gastric cancer,so as to provide new ideas for the prevention and treatment of non-cardia gastric cancer. Methods: 126 casesofnon-cardia gastric cancer tissues and 104 cases of paracancerous normal tissues were collected and set as case group and control group,respectively. Immunohistochemical SP assay was used to detect the expression of YAP in non-cardia gastric cancer tissues and adjacent normal tissues. Taqman method was used for genotyping. The unconditional logistic regression method was used to calculate the odds ratio(OR) and its 95%confidence interval(CI) to detect the associations between YAP SNPs and the expression of YAP protein under Codominant,Dominant,Overdominant,Recessive,and Log-additive genetic models. Results: The expression of YAP protein in non-cardia gastric cancer tissues was significantly higher than that in normal gastric tissues(P<0. 001).The expression level of YAP protein was negatively correlated with the degree of tumor differentiation(P<0. 05).There was no correlationbetween the expression level of YAP protein and gender,age,lymph node metastasis and tumor size respectively(P>0. 05). No associations were found between SNP rs11225163 and rs1820453 and the expression of YAP protein under Codominant,Dominant,Overdominant,Recessive and Log-additive genetic models.Haplotype was constructed by Haploview 4. 2 software,and the association between haplotype and YAP protein expression was analyzed. Conclusion YAP may be involved in the development of non-cardia gastric cancer.

Organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1/3) as important uptake transporters play a fundamental role in the transportation of exogenous drugs and endogenous substances into cells. Rat OATP1B2, encoded by the gene, is homologous to human OATP1B1/3. Although OATP1B1/3 is very important, few animal models can be used to study its properties. In this report, we successfully constructed the S knockout (KO) rat model using the CRISPR/Cas9 technology for the first time. The novel rat model showed the absence of OATP1B2 protein expression, with no off-target effects as well as compensatory regulation of other transporters. Further pharmacokinetic study of pitavastatin, a typical substrate of OATP1B2, confirmed the OATP1B2 function was absent. Since bilirubin and bile acids are the substrates of OATP1B2, the contents of total bilirubin, direct bilirubin, indirect bilirubin, and total bile acids in serum are significantly higher in KO rats than the data of wild-type rats. These results are consistent with the symptoms caused by the absence of OATP1B1/3 in Rotor syndrome. Therefore, this rat model is not only a powerful tool for the study of OATP1B2-mediated drug transportation, but also a good disease model to study hyperbilirubinemia-related diseases.

EGFR tyrosine kinase inhibitor (EGFR-TKI) has been used successfully in clinic for the treatment of solid tumors. In the present study, we reported the discovery of from our in-house diverse compound library, which was validated to be a potent and selective EGFR-TKI. showed excellent inhibitory activities against EGFR (IC = 0.81 nmol/L), EGFR (IC = 1.2 nmol/L) and EGFR (IC = 1.1 nmol/L), but was less effective or even inactive against other nine kinases. also displayed excellent antiproliferative activities against a panel of human cancer cell lines, and exhibited the ability to reduce colony formation and wound healing the same as gefitinib. We found that upon oral administration showed better anti-tumor activity in A431 bearing xenograft mouse models compared to gefitinib. In addition, showed better intestinal absorption than gefitinib and had favorable pharmacokinetic properties and microsomal metabolic stability in different species. These studies indicate that has strong antitumor activity and , and could be used for the development of anti-lung cancer agent targeting EGFR.

Objective To investigate the expressions of large tumor suppressor kinase 1 (LATS1) and large tumor suppressor kinase 2 (LATS2) proteins in gastric cancer tissues, and to explore the correlation between expressions of LATS1 and LATS2 proteins and the occurrence and development of gastric cancer. Methods A total of 93 gastric cancer paraffin tissues and the corresponding adjacent gastric normal mucosa in the Department of Pathology in Baotou Cancer Hospital from September 2008 to June 2010 were collected. The immunohistochemistry was used to detect the expressions of LATS1 and LATS2 proteins in gastric cancer and adjacent normal tissues. The differences of the expressions of LATS1 and LATS2 proteins in gastric cancer and adjacent normal tissues were compared by usingχ2 test. The relationship between the expressions of LATS1 and LATS2 proteins and the clinicopathological features was also analyzed. Results In gastric cancer tissues, LATS1 was negatively expressed in 54 cases (58.1％), weakly positive expressed in 15 cases (16.1％), moderately positive expressed in 16 cases (17.2％), and strongly positive expressed in 8 cases (8.6％);in adjacent normal tissues, LATS1 was negatively expressed in 17 cases (18.3％), weakly positive expressed in 16 cases (17.2％), moderately positive expressed in 31 cases (33.3％), and strongly positive expressed in 29 cases (31.2％). The positive expression rate of LATS1 in gastric cancer tissues was lower than that in adjacent normal tissues, and the difference was statistically significant (χ2=37.460, P<0.01). In gastric cancer tissues, LATS2 was negatively expressed in 28 cases (30.1％), weakly positive expressed in 17 cases (18.3％), moderately positive expressed in 33 cases (35.5％), strongly positive expressed in 15 cases (16.1％);in adjacent normal tissues, LATS2 was negatively expressed in 5 cases (5.4％), weakly positive expressed in 7 cases (7.5％), moderately positive expressed in 32 cases (34.4％), strongly positive expressed in 49 cases (52.7％). The positive expression rate of LATS2 in gastric cancer tissues was lower than that in adjacent normal tissues, and the difference was statistically significant (χ2=38.275, P<0.01). The expressions of LATS1 and LATS2 were not related to patients'age, gender, lymph node metastasis, degree of differentiation and tumor diameter (all P>0.05). Conclusion LATS1 and LATS2 proteins may be involved in the occurrence of gastric cancer and have the inhibiting effect on the occurrence and development of gastric cancer.

Objective To investigate the CT-guided percutaneous irreversible electroporation (IRE) in treating locally advanced pancreatic cancer (LAPC) and providing guidance for its prevention and treatment. Methods We retrospectively analyzed the clinical and imaging data of 17 patients (17 lesions) of LAPC treated with CT-guided IRE in our hospital from July 2015 to June 2016. Complications were documented and reviewed at day 7,30 and 90 follow up as well as during the procedure. The Clavien?Dindo was used for classification. The reasons that induced complications were summarized and to further discuss the prevention and treatment approaches. Results Of 17 patients, 2 patients suffered a transient tachycardia during the procedure. Eleven patients (65%) showed complications at day 7, of which gradeⅠcomplications occurred in 6 cases, including abdominal pain, nausea, vomiting, or a few of inflammatory exudations around the pancreas; four patients have grade Ⅱ complications, along with portal vein thrombosis;one patient showed grade Ⅲ a complications for retroperitoneal infection. With 30 days follow up, the grade Ⅰ complications disappeared, gradeⅡcomplications have not getting better, while grade Ⅲ a complications have been improved. With 90 days follow up,patients with grade Ⅲ a complications getting better; two patients with grade Ⅱ complications didn't show any changes;2 cases progressed to grade Ⅴ, and died of digestive tract bleeding at 82 days and 98 days after procedure. Conclusion CT-guided irreversible electroporation for treating LAPC is a safe ablation approach. Strict patient selection before procedure and make a reasonable prevention and treatment measures can reduce the complications.

Large tumor suppressor kinase 1 (LATS1) and LATS2 are the kinases found in recent years which can inhibit the tumor development. They are highly homologous and overlap in function. LATS1 and LATS2 proteins have been confirmed to be associated with the occurrence of multiple malignancies, including soft tissue sarcoma, leukemia, astrocytoma, breast cancer, prostate cancer, lung cancer, liver cancer, esophageal cancer, etc. Studies have shown that LATS has more extensive biological functions, such as regulating gene transcription and cell cycle checkpoint, inducing apoptosis, inhibiting cell migration, maintaining genetic stability and regulating organ size, and loss of any one can cause a variety of biological changes. So insighting into the structure and mechanism of LATS1 and LATS2 is the key to understanding the occurrence and development of tumors. The discovery of LATS gene and the structure, expression, target and function of LATS protein are summarized in this paper.

Objective To investigate the sleep quality of inland military officers and soldiers stationed and trained at plateau and its possible influence factors.Methods A total of 459 military officers and soldiers stationed and trained at plateau were performed the on site psychological assessment by adopting the psychological stress self-evaluation test (PSET),Pittsburgh Sleep Quality Index (PSQI),work related fatigue feelings (WRFFQ) and self compiled general data questionnaire.Results (1) The mean value of overall sleep quality in militaries stationed and trained at plateau was 5.61-±-3.48.40.5 ％ of respondents had good sleep quality,25.3％ had poor sleep quality and 34.2％ had general sleep quality.(2)The fatigue and psychological stress scores in the militaries with poor sleep quality were significantly higher than those in the militaries with good sleep quality (t1 =10.70,t2 =-9.68,P＜0.01).(3)The psychological stress,fatigue degree,confidence level of self-assessment health status had significantly positive correlation(r =0.517,0.488,0.259,0.352,P＜ 0.01).(4) The psychological stress,fatigue degree,confidence level of self-assessment health status entered the PSQI total score regression equation,moreover the predictive variation amount was 36.1％.Conclusion The psychological stress status and fatigue level in the militaries at plateau affect the sleep quality,and the confidence degree and health status assessment of officers and soldiers on exercise also produce the active influence on sleep.

Ranpirnase (onconase, ONC) is a new drug, with weak RNase activity and strong cytotoxicity to various tumor cells in vitro and in vivo. This study is to obtain recombination onconase (rONC) with high bioactivity. Based on the codon preference of Pichia pastoris, we designed and synthesized the gene according to cDNA sequences of ONC and the α mating factor's prepeptide. We screened positive clones after transforming the recombination plasmids into P. pastoris X-33, GSS115 and SMD1168. We screened the best combination of seven different vectors and host strains. Moreover, we optimized culture condition in shake flasks and 10 L bioreactor, and purified rONC from the supernatant after inducing it with 0.25% methanol by aqueous two-phase extraction coupling G50 molecular exclusion method. The highest rONC production was 13 mg/L in pPICZα-A/X-33/ONC combination under the condition of pH 5.5 and 23 degrees C in shake flasks for 7 d; and that the highest rONC production was 180 mg/L when the induction is performed in the lower basic salt medium with pH 5.5 in the 10 L bioreactor for 7 d. The yield of rONC is more than 90% at a purity of above 95%. rONC can kill various tumor cells in vitro. The expression and purification of rONC would be useful for further investigation of this new drug.
Antineoplastic Agents ; metabolism ; Bioreactors ; Cell Line, Tumor ; Codon ; DNA, Complementary ; Genetic Vectors ; Humans ; Pichia ; metabolism ; Recombinant Proteins ; biosynthesis ; Ribonucleases ; biosynthesis