Deinagkistrodon acutus(also known as the five-paced viper and the traditional Chinese medicine ingredient is called Agkistrodon) venom is a viscous liquid from the venom glands of the Deinagkistrodon acutus. It contains a variety of protein and peptide components such as phospholipase A2, serine protease, metalloproteinase, C-type lectin, L-amino acid oxidase, and has a variety of biological activities, playing an important role in anti-tumour, anti-thrombotic, anti-inflammatory and anti-bacterial activities. In recent years, snake venom research has become increasingly widespread, but there is still a lack of comprehensive and systematic studies on snake venom from Deinagkistrodon acutus. In this paper, the source, identification, active ingredients, toxicity studies and quality researches of Deinagkistrodon acutus venom are summarized and analysed by searching the related research progress, in order to provide reference for further development and utilization of Deinagkistrodon acutus venom.

ObjectiveTo investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells （T-bet） and GATA binding protein 3 （GATA3）. MethodA total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled. With the prospective， double-blind and randomized control methods， the patients were randomized into three groups： kidney deficiency group， Qi and blood deficiency group， and control group. The three groups were respectively treated with Bushen Shengxue prescription granule， Yiqi Yangxue prescription granule， and Placebo （half the dose of Bushen Shengxue formula granules）. In addition， all of them were given oral cyclosporin and androgen. The treatment lasted 6 months， with 3 months as a course. The blood routine indexes， T cell subsets， and fusion genes T-bet and GATA3 before and after treatment were analyzed， and the safety indexes were monitored. ResultDuring the observation， a total of 75 cases dropped out and 18 were rejected. Finally， 161 cases in the kidney deficiency group， 164 in the Qi and blood deficiency group， and 167 in the control group were included. After 6 months of treatment， the total effective rate was 98.8% （159/161） in the kidney deficiency group， which was higher than the 79.9% （131/164） in the Qi and blood deficiency group （χ²=30.135， P<0.01） and the 61.7% （103/167） in the control group （χ²=70.126， P<0.01）. The total effective rate was higher in the Qi and blood deficiency group than in the control group （χ²=13.232， P<0.01）. After treatment， the hemoglobin （HGB） content increased significantly in three groups （P<0.05） as compared with that before treatment， particularly the kidney deficiency group （P<0.01）. After treatment， the white blood cell （WBC） count and platelet （PLT） count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group （P<0.01）. There was no specific difference in neutrophils （ANC） after treatment among the three groups. At the same time point， the level of T helper type 1 （Th1） cells， Th1/Th2 ratio （P<0.05）， level of CD4⁺， and CD4⁺/CD8⁺ ratio （P<0.05） were significantly low in the kidney deficiency group among three groups. There was no significant difference in CD19^-， HLA/DR⁺， and CD25⁺ between the kidney deficiency group and the other two groups， but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group （P<0.05）. ConclusionBushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism， inhibiting the activity of immune system， modulating T cell subsets， suppressing Th1 and CD4⁺， and promoting bone marrow hematopoiesis. Moreover， it is safe with little side effects， which is worthy of further promotion.

Objective To investigate the clinicopathological characteristics and prognosis of patients with Borrmann type Ⅳ gastric cancer. Methods A cohort retrospective analysis of 2386 patients with gastric cancer who underwent radical surgery was used to screen out Borrmann type Ⅳ patients, and analyze their clinical features and prognostic factors. Results Among 2386 patients with gastric cancer, 363 cases (15.21%) were Borrmann type Ⅳ. Compared with non-Borrmann type Ⅳ gastric cancer patients, Borrmann type Ⅳ patients had higher rates of simultaneous liver metastasis, metachronous liver metastasis, lymph node metastasis and vascular infiltration. Moreover, the age of onset tended to be younger and the pathological type tended to be poorly differentiated-undifferentiated (all P < 0.05). The 5-year OS of the entire group was 49.32% and the 5-year DFS was 44.61%. There were significant differences in 5-year OS and DFS between Borrmann type Ⅳ and non-Borrmann type Ⅳpatients (all P < 0.001). The subgroup analyses showed that there were statistically significant differences in 5-year OS and DFS of gastric cancer patients between Borrmann type Ⅳ and non-Borrmann type Ⅳ in pT2-pT4a and pN0-pN3a stages (all P < 0.005). Multivariate analysis showed that the poorly differentiated-undifferentiated tumor, the T4a-pT4b stage of tumor invasion depth, lymph node metastasis, the ⅢA-ⅢC pTNM stage of the tumor, postoperative liver metastasis and peritoneal metastasis were independent risk factors affecting the prognosis of Borrmann type Ⅳ gastric cancer patients (all P < 0.05). Conclusion Borrmann type Ⅳ gastric cancer is prone to liver metastasis, lymph node metastasis, peritoneal metastasis and poor prognosis, and it's prognosis is affected by a variety of independent risk factors.

Objective To investigate the value of Cells Free Ferrous Protoporphyrin (FH) detection in cervical cancer screening.Methods Retrospective analysis of December 2013 to 2014 year in December to accept the clinical data of 368 cases of female cervical cancer screening in Ningxia People's Hospital of Zhongwei Prefecture, divided into normal group (n=210), cervical precancerous lesions group (n=130) and cervical carcinoma group (n=28).The liquid based thin-layer cell detection (TCT) and FH detection were carried out, and the detection effects of the 2 detection methods were observed and compared.Results The statistics and comparison, in the detection of normal cervix, the false positive rate of FH detection was 19.05%, significantly higher than the detection of TCT 4.76% (P< 0.05);in the detection of cervical precancerous lesions, FH positive detection rate was 86.15%, lower than the detection of TCT 86.92%, and with the degree of cervical lesions continuously improve the positive rate of the 2 detection methods are showing a rising situation;in the detection of cervical cancer, the positive rate of FH detection was 96.43%, higher than the detection of TCT 92.86%, but the difference was not significant.Conclusion With ThinPrep cytology test (TCT), FH in the detection of relative detection effect of normal cervix of the poor, but in precancerous lesions and cervical cancer detection and detection of TCT are basically the same, therefore, FH still has a certain application value in screening of cervical cancer.

Objective To detect mRNA expressions of STING and type Ⅰ interferons(IFN-α and IFN-β) in peripheral blood mononuclear ceils (PBMCs) of patients with chronic hepatitis C(CHC).Methods 113 patients with CHC and 94 healthy controls were collected from Renmin Hospital of Wuhan University during January 2015 and January 2016.Expressions of mRNA of STING,RIG-1,IFN-α and IFN-β were detected by real-time quantitative PCR,and their relative expression values were obtained by 2-△△Ct method and the results were statistically analyzed.Results The expression of mRNA of STING,RIG-1,IFN-α and IFN-β in CHC were 0.018,0.361,0.578 and 0.573 times than its in healthy controls respectively and the differences were statistically significant (t-8.28,4.26,2.18 and 2.07,all P ＜ 0.05).Pearson correlation analysis showed that mRNA expressions of STING in healthy controls were positively correlated with that of IFN-α mRNA and IFN-β mRNA (r=0.487 and 0.207,all P＜0.05),which had no correlation in CHC (r=0.174 and 0.091,all P＞0.05).The expressions of STING mRNA was positively correlated with that of RIG-1 mRNA in healthycontrols (r=0.222,P＜0.05),but there was no correlation of expression in CHC between STING mRNA and RIG-1 mRNA (r=-0.029,P＞0.05).Conclusion Compared with healthy controls,the expression of STING,RIG-1,IFN-α and IFN-β mRNA were all reduced.There was positive correlation between STING and RIG-1,IFN-α and IFN-β in healthy controls,but no correlation in CHC.

High mobility group box 1 protein,a kind of damage-associated molecular patterns,is a group of nonhistone DNA-binding protein in the nuclear.It not only involves in DNA replication,recombination,repair,regulation of gene transcription,but also induces activation of innate immunity and T cell generation and activates the adaptive immune response through Toll-like receptor.It is also more closely related to autoimmune diseases,inflammatory diseases,tumors and so on.Currently there are many researches on the role of TLR-mediated HMGB1 signaling pathway in diseases,which is involved in a variety of pathological processes and has a broad clinical outlook.

Objective To explore risk factors of recurrence in papillary thyroid microcarcinomas ( PTMC ) and papillary thyroid carcinomas with 1-2 cm diameter. Methods From January, 2008 to December, 2010 in PLA General Hospital, 323 eligible patients received first surgery and diagnosed pathologically with papillary thyroid cancer≤2 cm were analyzed retrospectively. According to rumor size, patients were divided into PTMC and PTC of 1-2 cm, which were investigated recurrence factors. Results Finally we indentified 320 PTC≤2 cm, including 218 (68.1%)PTMCand102(31.9%)PTCof1-2cmwithamedianfollow-uptimeof72.5(55-90)months.32cases (10%)of patients relapse, includig 22 cases(10%)in PTMC and 10 cases(9. 8%)in PTC of 1-2 cm. In the clinical characteristics analyses of PTC≤2 cm, the PTC of 1-2 cm was different from PTMC in age, lymph node metastasis and TNM stage. The univariate analysis showed that tumor location and lymph node metastasis influenced recurrence of PTMC and PTC of 1-2 cm,while tumor foci and extrathytoidal extension were risk factors of recurrence in PTMC but not in PTC of 1-2 cm. Lymph node metastasis was independent factor which influenced the recurrence of PTMC and PT C of 1-2 cm according to COX multivariate analysis. Conclusion Disease recurrence did not differ significantly between the PTMC and PTC of 1-2 cm and lymph node metastasis was an independent recurrence factor.

Objective To investigate the relationship between renal sympathetic nerve activity and the severity of heart failure in dogs with chronic heart failure ( CHF) .Methods CHF were induced by ab-dominal aorta constriction.Plasma renin activity ( PRA) , adrenaline ( E) , and noradrenaline ( NE) were determined in 9 dogs with CHF (CHF group) and 3 sham-operated dogs (control group).Results E, NE, PRA, and B-type natriuretic peptide ( BNP) were significantly higher in CHF group than those in con-trol group (all P <0.01).Compared to 10-week post-operation, PRA [(2.08 ±0.08)ng/(ml? h) vs (2.26 ±0.16)ng/(ml? h)], NE [(184.01 ±11.76)pg/ml vs (202.99 ±16.54)pg/ml] and BNP [(85.87 ±11.41)μg/ml vs (100.41 ±9.24)μg/ml] were significantly increased in the 12-week post-op-eration (all P <0.01).PRA [10 weeks post-operation:(2.13 ±0.08)ng/(ml? h) vs (2.02 ±0.05)ng/(ml? h);12 weeks post-operation:(2.38 ±0.09)ng/(ml? h) vs (2.11 ±0.07)ng/(ml? h)] and NE [10 weeks post-operation: (191.75 ±8.40) pg/ml vs (174.33 ±7.08) pg/ml;12 weeks post-operation:(215.69 ±6.26)pg/ml vs (186.36 ±7.98)pg/ml] were higher in high BNP group than those in low BNP group both in 10 and 12 weeks post-operation ( P =0.013, P =0.013, P =0.002, respectively).Con-clusions PRA was increased in dogs with CHF and associated with the severity of CHF.

Objective:To study immunosuppression mediated by the porcine FcγRⅢ in porcine reproductive and respiratory syndrome virus ( PRRSV ) infection to pulmonary alveolar macrophages ( PAMS ).Methods: In this study pulmonary alveolar macrophages cells were treated with containing 200 TCID50 PRRSV,lipopolysaccharide (LPS) (100 ng/ml) and purified mouse anti-pig FcγRⅢIgG (550 μg/ml) separately,simultaneously,PAM cells treated with purified mouse anti-pig FcγRⅢIgG (550 μg/ml) was infected by 200 TCID50 PRRSV ,untreated PAM cells as the control group.Each group were post-cultured 12,24,36,48,60,72 h, the cells and the supernatant were collected.The dynamic variation of PRRSV RNA copies in inoculation group were detected by using real-time fluorescence quantitative PCR method.mRNA level of IFN-αand TNF-αin each group were detected by using relative fluorescence quantitative PCR.Results:The result showed that mRNA level of IFN-αwas improved during PRRSV infection to PAMS 12-24 h,and mRNA level of IFN-αwas inhibited during 36-72 h,then mRNA level of IFN-αrecovered normally; mRNA level of TNF-αwas increased slightly post-infection 12-72 h.IFN-αand TNF-αmRNA levels of PAM cells treated with LPS were both up-regu-lated,using the purified mouse anti-pig FcγRⅢ IgG to treat the PAM cells,selective activation of porcine FcγRⅢ in the PAM cells down-regulated significantly mRNA levels of IFN-αand TNF-α.PRRSV infection assay mediated by selective activation FcγRⅢof the PAM cells inhibited antiviral cytokine ( IFN-αand TNF-α) mRNA levels.Conclusion:The results show selective activation of FcγRⅢinhibited significantly mRNA levels of the antiviral cytokine IFN-αand TNF-αof host cells,and innate antiviral immune response to PRRSV infection.

Objective To investigate the expression of NKG2D and related signaling molecules adaptor protein(DAP10) and extracellular signal-regulated kinase(ERK) in the inflammatory cells of gastric adenocarcinoma and para-carcinoma tissues,the effects of vasoactive intestinal peptide(VIP) on the expression of NKG2D,DAP10 and ERK in natural killer(NK) cells of healthy volunteers.Methods The expression of NKG2D,DAP10 and ERK in the inflammatory cells of 36 gastric adenocarcinoma and para-carcinoma tissues were detected by immunohistochemistry.The peripheral blood NK cells of healthy volunteers were isolated and purified with CDC method.The expressions of NKG2D,DAP10 and ERK in NK cells were determined by immunocytochemistry and reverse transcription-polymerase chain reaction(RT-PCR) methods before and after VIP intervention.The ttest was used for comparison between two groups and rank transformation nonparametric test (Kruskal-Wallis H test) for count data analysis.Results The expression levels of NKG2D,DAP10 and ERK in the inflammatory cells of gastric adenocarcinoma were significantly lower than those of para-carcinoma tissues (H=30.640,24.910,20.320,all P＜0.01).The expression levels of NKG2D,DAP10 and ERK were much lower in poorly differentiated gastric adenocarcinoma (H =4.049,11.830,8.118),at stage Ⅲ-Ⅳ (H=4.275,11.560,7.686),and the expression levels of NKG2D,ERK were lower with lymph nodes metastasis (H=6.513,6.064,all P＜0.05).The expression levels of NKG2D,DAP10 and ERK in gastric adenocarcinoma tissues and inflammatory cells were not correlated with gender,age and the location of lesions (all P＞0.05).The expression levels of NKG2D,DAP10 and ERK in NK cells was decreased after VIP intervention (protein:H=12.438,4.798,13.745,mRNA:F=337.640,638.579,1055.015,all P＜0.05).Conclusion Gastric adenocarcinoma may downregulate the expression of NKG2D,DAP10 and ERK in NK cells through VIP secretion,which may be involved in the immune escape of gastric cancer.