Objective To explore relationships of expression of hypoxia?inducible factor?1α(HIF?1α), vascular endothelial growth factor(VEGF)and protein kinase B(P?Akt)with angiopoiesis and cell apoptosis. Methods Biopsy specimens were collected from skin lesions of 32 patients with lichen planus and normal skin of 20 patients with lipomyoma, and subjected to paraffin embedding. Immunohistochemical staining was performed to measure expression of HIF?1α, VEGF and P?Akt, and TUNEL technique was used to detect apoptosis of keratinocytes in these paraffin?embedded tissue sections. Microvessel density (MVD)was assessed by counting CD34?labeled vascular endothelial cells. Results HIF?1α, VEGF and P?Akt were moderately or strongly expressed in lichen planus lesions, but absent or weakly expressed in normal skin of controls, and the expression of HIF?1α, VEGF and P?Akt was significantly higher in the lichen planus group than in the control group (all P < 0.01). HIF?1α was mainly expressed in nuclei of keratinocytes, while VEGF and P?Akt were expressed in the cytoplasm of keratinocytes. In addition, the lichen planus group showed significantly increased MVD(21.27 ± 6.54 vs. 10.26 ± 1.10 microvessels/high?power(200 ×)field, t = 5.607, P < 0.01)and apoptosis rate of keratinocytes(72.81% ± 9.234% vs. 28.16% ± 3.464%, t = 8.431, P < 0.01) compared with the control group. Pearson correlation analysis showed that there were positive correlations between HIF?1αand VEGF expression, between VEGF and P?Akt expression, and between P?Akt and HIF?1αexpression in the lichen planus group(r=0.625, 0.453, 0.455, respectively, all P<0.01), and expression of HIF?1α, VEGF and P?Akt was all positively correlated with MVD(r=0.721, 0.646, 0.671, respectively, all P<0.01). Conclusion HIF?1αand its downstream target genes VEGF and P?Akt may play a certain role in the occurrence of lichen planus.

BACKGROUND:Studies have reported that taurine has a certain therapeutic effect on the disease of various systems, such as nervous system, cardiovascular system, immune system and digestive system. The liver is the main place, also the important target organ, of taurine metabolism. Therefore, the relationship between taurine and hepatopathy has become a hot topic in recent years. OBJECTIVE:To investigate the influence of taurine on superoxide dismutase and malondialdehyde expression in the liver tissue of rat models of liver fibrosis induced by carbon tetrachloride. METHODS:Thirty male C57B/L rats of SPF grade were randomly and evenly divided into blank control, model and taurine groups. Rats in the blank control group were intraperitonealy injected with 100% peanut oil of 1 mL/kg, twice a week, in total 10 weeks. Rats in the model group were intraperitonealy injected with peanut oil of 1 mL/kg containing 20% carbon tetrachloride, twice a week, in total 10 weeks. Rats in the taurine group were intraperitonealy injected with peanut oil of 1mL/kg containing 20% carbon tetrachloride, twice a week, in total 10 weeks, and were intragastricaly administered taurine of 500 mg/kg per day starting from the 3rd week til the 10th week. RESULTS AND CONCLUSION:Compared with the blank control group, the serum levels of hyaluronic acid, laminin, typeⅢ procolagen, typeⅣ colagen, alanine aminotransferase, aspartate aminotransferase were significantly increased (P < 0.05), the level of superoxide dismutase in the liver tissue was lowered (P < 0.05), the level of malondialdehyde in liver tissue was significantly increased (P < 0.05), and liver index was increased (P < 0.05) in the model group. Pathological examination showed that there were necrosis of liver cels, fat vacuoles, fibrous tissue hyperplasia and inflammatory cel infiltration in the rats of the model group. Compared with the model group, the serum levels of hyaluronic acid, laminin, typeⅢ procolagen, typeⅣ colagen, alanine aminotransferase, aspartate aminotransferase were significantly lowered (P < 0.05), the level of superoxide dismutase in the liver tissue was significantly increased (P < 0.05), the level of malondialdehyde in the liver tissue was significantly lowered (P < 0.05), and liver index was significantly decreased (P < 0.05) in the taurine group. Pathological examination showed that there were no inflammatory cel infiltration, fat vacuoles, and fibrous tissue deposition in the liver tissue. The results indicate that taurine can decrease the contents of superoxide dismutase and malondialdehyde, and relieve the degree of liver fibrosis induced by carbon tetrachloridevia exerting its antioxidative effects.

Objective:To predict the gastrointestinal side effects of chemotherapeutic drugs using healthy murine colon organoids.It aimed to identify safer alternative treatments for patients intolerant to certain chemotherapy regimens and demonstrate the potential clinical ap-plications of organoids in predicting gastrointestinal side effects.Methods:Healthy mouse colonic crypt cells were cultured in 3D.Paraffin sections of colon tissues and organoids were subsequently prepared,followed by haematoxylin and eosinand immunohistochemical staining(CDX2,Ki67,and CK19).The colonic organoids were treated with five chemotherapeutic drugs,and cell activity was assessed to determine their intestinal toxicity.The consistency of the incidence of gastrointestinal side effects observed in this study and in clinical practice were analyzed by comparing the results to the published literature.Results:The histological characteristics of the colon organoids were highly consistent with those of the original colon tissues.The tolerance of normal colon organoids to different chemotherapeutic drugs was vari-able.Capecitabine had the least cytotoxic effect on mouse colon organoids,whereas paclitaxel liposomes showed the strongest cytotoxic ef-fect when IC50 was the only consideration.Considering clinical drug concentrations,a significant difference was observed in the organoid in-hibition rates between albumin paclitaxel and liposomal paclitaxel.Statistical analysis of clinical trial data showed that the incidence of gradeⅢ/Ⅳ diarrhea caused by albumin paclitaxel,epirubicin,capecitabine,and cyclophosphamide was consistent with the corresponding or-ganoid inhibition rates.Conclusions:Combining clinical drug doses,we recommend prioritizing albumin paclitaxel and avoiding the use of liposomal paclitaxel to improve chemotherapy tolerance.This study demonstrates that normal colon organoids can effectively predict the occurrence of severe diarrhea associated with most chemotherapeutic drugs.

Objective To design a new integrated portable biliary internal-external drainage catheter carrying125 I seeds used for the treatment of malignant biliary obstruction lesions so as to achieve the dual curative effects of biliary drainage and brachytherapy. Methods A total of 15 patients with malignant obstructive jaundice, who were admitted to the First Affiliated Hospital of Zhengzhou University, China, during the period from September 2016 to January 2018, were enrolled in this study. Biliary stent implantation was performed in all patients, which was followed by insertion of a new integrated portable biliary internal-external drainage catheter carrying125 I seeds. The technical success rate, clinical success rate, complications, stent patency time and patient survival rate were evaluated. Results The placement of the drainage tube was simple and smooth, and the technical procedure was successful in all patients. One month after treatment, the bilirubin level was decreased significantly when compared with preoperative one (P<0.01), while the blood indexes and immunological indicators showed no obvious changes (P>0.05) . After treatment, 2 patients (13.3％) developed cholangitis and 2 patients (13.3％) had small amount of biliary bleeding, which returned to normal after symptomatic treatment. No severe complications such as perforation of bile duct, massive bleeding, radiation enteritis and radioactive source leakage, etc., occurred. The patients were followed up for 55-402 days, 6 patients (40.0％) developed biliary re-obstruction. The median patency time of stent was 255 days, and 6-month stent patency rate was 64.5％. Five patients died and 10 patients survived, the 9-month survival rate was 64.3％, the median survival time was 368 days. Conclusion By using the new integrated portable biliary internal-external drainage catheter carrying125 I seeds, the effects of bile drainage and brachytherapy can be simultaneously achieved. Preliminary clinical practice indicates that this new drainage catheter is feasible, safe and effective, although its long-term efficacy needs to be clarified with further follow-up observations and controlled studies.

Objective To analyze the changes of serum hypoxia-inducible factor-1α(HIF-1α),vas-cular endothelial growth factor ( VEGF) and endothelin-1 ( ET-1) levels in neonates with hypoxia-induced pulmonary hypertension(HPH),and to explore the roles of three factors in the pathogenesis of HPH in neo-nates. Methods A total of 50 neonates with HPH in the neonatal intensive care unit as HPH group and an-other 25 non-HPH hospitalized neonates with similar clinical data in the same period as control group were enrolled from January 2014 to December 2017. The levels of serum HIF-1α,VEGF and ET-1 were deter-mined by enzyme linked immunosorbent assay when neonates were diagnosed as HPH and their pulmonary artery systolic blood pressure(PASP) decreased to 35 mmHg below respectively. The changes of three factors levels were analyzed and compared with those of control group at the same time point. Results (1) The levels of serum HIF-1α,VEGF and ET-1 of HPH group were significantly higher than those of the control group (F value were 151. 97,43. 31,and 129. 56 respectively,all P<0. 01). Furthermore,the more serious the grade of HPH,the higher the levels of three factors. The differences were statistically significant (all P<0. 01). (2) After PASP of neonates in HPH group decreased to 35 mmHg or below,the levels of serum HIF-1α,VEGF and ET-1 also significantly decreased,and the differences were statistically significant ( all P <0. 01). However,there were no statistically significant differences compared with those of the control group for the levels of serum HIF-1α and VEGF(both P>0. 05) in addition to serum ET-1 levels (F＝14. 98,P<0. 05). Conclusion High levels of HIF-1α,VEGF and ET-1 caused by hypoxia may play an important role in neonatal HPH.

OBJECTIVE：To observe the ef fectiveness and safety of bosentan in the treatment of hypoxic pulmonary hypertension（HPH）in neonates. METHODS ：From Jan. 2014 to Mar. 2019，a total of 82 HPH neonates hospitalized in the department of neonatology of our hospital were selected as research subjects. According to whether or not receiving bosentan therapy，50 cases were included into bosentan group and 32 cases into non-bosentan group. Meanwhile ，another 25 non-HPH neonates with serum sample retention time and general information such as gestational age at birth and day age matching the HPH group were selected as the control group. All neonates with HPH were given continuous intravenous infusion of Dopamine hydrochloride injection 5 mg/（kg·min）until PASP was normal. On this basis, neonates in the bosentan group were additionally given Bosentan tablets 1 mg/kg（fed after dissolving with appropriate amount of water for injection ）for q 12 h，72 h. The relationship between serum ET- 1 levels of neonates with HPH and PASP was analyzed ，as well as PASP before and after treatment and therapeutic efficacy between bosentan and non-bosentan groups ，the changes of arterial blood gas indexes and ADR in 3 groups were compared. RESULTS ：Before treatment ，the serum ET- 1 levels of bosentan group was （164.3±115.3）pg/mL，which was significantly higher than （41.9±3.7）pg/mL of control group and positively correlated with PASP level （r＝0.864，P＜0.001）. Total response rate of bosentan group was 90.00％，which was significantly higher than 71.88％ of non-bosentan group （P＜0.05）. After 72 h of treatment ，PASP of 2 groups was decreased significantly ，compared with before treatment （P＜0.001），and the bosentan group was significantly lower than the non-bosentan group （P＜0.05）. The PaO 2，SaO2，PaCO2 and OI in 3 groups was significantly improved compared with that before treatment （P＜0.001），and the PaO 2，SaO2 and OI in the bosentan group was significantly higher than that in the non-bosentan group （P＜0.05）. During the treatment period of bosentan and within one week after drug withdrawal，there was no significant change in serum LDH ，AST，ALT and Scr levels in neonates. There was no statistically significant difference in the incidence of feeding intolerance ，anemia，reduced WBC and reduced PLT in 3 groups（P＞0.05）. CONCLUSIONS： Bosentan can improve the oxygenation status of neonates with HPH, reduce PA SP，and short-termmedication is safe. com