Objective:To investigate the effect of sorafenib on the proliferation of human oral cancer TCA8113 cells and to explore the underlying mechanisms.Methods:Mter treated with sorafenib at 2.5,5,10,20 μg/ml respectively for48 h,TCA8113 cell proliferation was examined by MTT and colony formation assay.Western blotting was employed to examine the p38MAPK expression in the cells.TCA8113 cells were pretreated with 10 μmol/L of SB203580 (a specific inhibitor of p38MAPK) for 30 min,and then by different concentrations of sorafenib for 48 h,cell proliferation was tested by MTT assay.Results:Sorafenib significantly inhibited the proliferation of TCA8113 cells in a concentration dependent fashion.Sorafenib also remarkably promoted the activation of p38MAPK of the cells.SB203580 significantly alleviated soiafenib induced TCA8113 cell viability decrease.Conclusion:Sorafenib can inhibit the proliferation of TCA8113 cells,which may be related to the activation of p38MAPK.

Objective To investigate the effects of growth hormone on illness severity and prognosis of septic patients. Methods Thirty septic shock patients were randomized into control group (10 cases) and growth hormone treatment group (20 cases) , to receive 8 U recombinant human growth hormone every day for 7 consecutive days, control group received NS. Serum concentration of procalcitonin ( PCT) , C-reactive protein ( CRP) , tumor necrosis factor-? ( TNF-?) and interleukin-6 ( IL-6 ) were measured on the 1st,4th,and 7th day. The severity of illness was assessed daily with the Acute Physiology and Chronic Health Evaluation-Ⅱ (APACHE-Ⅱ ) scoring system and the Elebute & Stoner's Sepsis scoring system. The efficacy also were evaluated on day 15 postoperation. Results The serum concentration of PCT, CRP, TNF-?, IL-6 decreased gradurally in both group after study starting. PCT, TNF-? and IL-6 were significantly different on the 7th day in both group (P

AIM:To investigate the effect of genistein on the proliferation of human oral cancer TCA 8113 cells and to explore the underlying mechanisms .METHODS:The cell proliferation was examined by MTT assay , cell counting and colony formation assay .Western blotting was employed to examine the protein levels of vascular endothelial growth fac -tor (VEGF), extracellular signal-regulated kinase (ERK) and p-ERK.RESULTS: Genistein significantly inhibited the proliferation of TCA8113 cells in a concentration-dependent fashion .Moreover , genistein dose-dependently decreased the protein levels of VEGF, ERK and p-ERK.The expression of VEGF was also blunted by U 0126, a specific inhibitor of ERK.U0126 and axitinib, a VEGF receptor antagonist , both significantly inhibited the proliferation of TCA 8113 cells. CONCLUSION:Genistein inhibits the proliferation of TCA8113 cells, which may be related to its inhibitory effect on ERK expression and activation , thus subsequently decreasing the expression of VEGF .

Objective:To investigate the mechanism of programmed death 1(PD-1)/ programmed death ligand 1(PD-L1) signaling pathway and its feasibility as a potential therapeutic target and prognostic predictor by detecting the expressions, of PD-1 and PD-L1 in bone marrow mononuclear cells of children with acute lymphoblastic leukemia (ALL), and to provide new ideas for the diagnosis and treatment of ALL as well.Methods:Bone marrow samples were collected from 59 children with ALL in the First Affiliated Hospital of Zhengzhou University from September 2018 to July 2019.Flow cytometry was applied to detect the expression of PD-1 and PD-L1 in bone marrow mononuclear cells in 59 ALL patients, including 47 newly-diagnosed ALL patients and 12 relapsed ALL patients, respectively, at initial diagnosis, after induction therapy and early intensive treatment.Their relevant clinical data were collected and compared with the bone marrow specimens of 12 children suffering from non-malignant blood diseases as the control group of the same hospital during the same period.Results:There was no significant difference in the expression of PD-1 in the bone marrow mononuclear cells of the primary diagnosis group, recurrence group and control group ( H=2.402, P>0.05). The expression of PD-L1 in the relapsed and refractory group [(7.32±3.60)%] and the newly diagnosed group [(3.18±2.37)%] was higher than that in the control group [(0.84±0.39)%], and the differences were statistically significant ( H= 28.048, P<0.05). In the initial treatment group, the expression of PD-L1 in the bone marrow mononuclear cells was the strongest expression before treatment ( B=1.293), followed by after induction treatment ( B=0.036) and after early intensive treatment ( B=0.000), suggesting that there was a downward trend as the continued treatment.The expression of PD-L1 was the weakest expression in the low-risk group ( B=-3.912) than in the medium-risk group ( B=-3.595) and high-risk group ( B=0.000), revealing that the expression of PD-L1 is related to the risk grades of ALL.The higher the risk rating is, the higher the PD-L1 protein expression is. Conclusions:The high expression of PD-L1 may be involved in the pathogenesis and be used as an adverse predictor of ALL childhood and an evaluation index of chemotherapy efficacy.PD-1 / PD-L1 signaling pathway may be a potential therapeutic target of ALL childhood.

Objective: : The facial nerve trace on the ipsilateral side of the vestibular schwannoma was reconstructed by diffusion tensor imaging tractography to identify the adjacent relationship between the facial nerve and the tumor, and to improve the level of intraoperative facial nerve protection. Methods: : The clinical data of 30 cases of unilateral vestibular schwannoma who underwent tumor resection via retrosigmoid approach were collected between January 2019 and December 2020. All cases underwent magnetic resonance imaging examination before operation. Diffusion tensor imaging and anatomical images were used to reconstruct the facial nerve track of the affected side, so as to predict the course of the nerve and its adjacent relationship with the tumor, to compare the actual trace of the facial nerve during operation, verify the degree of coincidence, and evaluate the nerve function (House-Brackmann grade) after surgery. Results: : The facial nerve of 27 out of 30 cases could be displayed by diffusion tensor imaging tractography, and the tracking rate was 90% (27/30). The intraoperative locations of facial nerve shown in 25 cases were consistent with the preoperative reconstruction results. The coincidence rate was 92.6% (25/27). The facial nerves were located on the anterior middle part of the tumor in 14 cases, anterior upper part in eight cases, anterior lower part in seven cases, and superior polar in one case. Intraoperative facial nerve anatomy was preserved in 30 cases. Among the 30 patients, total resection was performed in 28 cases and subtotal resection in two cases. The facial nerve function was evaluated 2 weeks after operation, and the results showed grade I in 12 cases, grade II in 16 cases and grade III in two cases. Conclusion : Preoperative diffusion tensor imaging tractography can clearly show the trajectory and adjacent position of the facial nerve on the side of vestibular schwannoma, which is beneficial to accurately identify and effectively protect the facial nerve during the operation, and is worthy of clinical application and promotion.

Objective:To determine the concentration of hydroxychloroquine (HCQ) and its active metabolite deethylhydroxychloroquine (DHCQ) in breast milk of lactating patients with autoimmune disease. To observe the safety of hydroxychloroquine in lactation period, and to explore the factors that may affect HCQ and DHCQ concentration in the milk.Methods:Lactating patients with autoimmune disease who have taken HCQ for at least 6 months were included in our study. A new high performance liquid chromatography (HPLC) method was established to detect HCQ and DHCQ levels in breast milk. Milk samples were collected at different time points: before taking the drug (0 hours), and 2 hours, 4 hours, 6 hours after taking the drug. In addition, the genotype of cytochrome CYP3A4*1G, CYP3A5*3 and CYP2D6*10 which were related to HCQ metabolism were tested by dideoxy chain termination method. Visual acuity, hearing and growth status of the patients' infants were followed up on a regular basis. T-test, one-way ANOVA and Pearson's test were used for data analysis. Results:In 15 patients, the average concentration of HCQ and DHCQ in the milk of patients taking 200 mg/d were (520±261) ng/ml and (177±112) ng/ml, respectively. While the average concentration of HCQ and DHCQ in the milk of patients taking 400 mg/d were (1 036±374) ng/ml and (397±271) ng/ml, respectively. The peak of HCQ level for 11 patients was at 4 hour after taking the drug, while the others' were at 2 hour. The breast-fed infants did not show any abnormal symptoms of hearing, vision and growth. However, cytochrome gene polymorphism did not affect the peak of HCQ and DHCQ.Conclusion:The concentration of HCQ and DHCQ in breast milk is positively correlated to the dosage. The peak level of HCQ milk is 4 hours after taking the drug. The levels of HCQ and DHCQ at 6 hours are similar as those in the whole blood. It is suggested that patients who take HCQ can feed 4 hours after taking the drug to reduce the HCQ and its active metabolites being absorbed by infants. However, the impact of HCQ on infant safety and gene polymorphism of CYP on milk concentration among individuals needs to be further verified in large sample studies and long-term follow-up.

OBJECTIVETo evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for gastrointestinal disorders.

METHODSRetrospective analysis of the clinical data of 406 patients who underwent FMT from May 2014 to April 2016 in the Intestinal Microenvironment Treatment Centre of Nanjing General Hospital was performed, including patients with constipation(276 cases), recurrent Clostridium Difficile infection (RCDI, 61 cases), ulcerative colitis(44 cases), irritable bowel syndrome (15 cases) and Crohn's disease(10 cases). Donors were completely unrelated, 18- to 50-year-old non-pregnant healthy adult, with healthy lifestyle and habits, without taking antibiotics, probiotics and other probiotics history within 3 months. There were three routes of FMT administration: patients received 6 days of frozen FMT by nasointestinal tube placed in the proximal jejunum under gastroscope (319 cases); patients received capsules FMT per day for 6 consecutive days (46 cases) or once 600 ml of treated fecal liquid infusion into colon and terminal ileum by colonoscopy(41 cases).

RESULTSClinical cure rate and improvement rate of different diseases receiving FMT were respectively as follows: RCDI was 85.2% (52/61) and 95.1%(58/61); constipation was 40.2%(111/276) and 67.4%(186/276); ulcerative colitis was 34.1%(15/44) and 68.2% (30/44); irritable bowel syndrome was 46.7% (7/15) and 73.3% (11/15) and Crohn disease was 30.0%(3/10) and 60.0%(6/10). RCDI had the best efficacy among these diseases(P<0.01). There was no significant difference between the three routes of FMT administration(P=0.829). The clinical cure rate and improvement rate of different routes were 43.3%(138/319) and 58.6% (187/319) respectively in nasogastric transplantation group, 41.5%(17/41) and 61.0%(25/41) in colonoscopy group, 37.0%(17/46) and 63.0% (29/46) in the capsule transplantation group. There was no serious adverse event during the follow-up. The most common side effects were respiratory discomfort (27.3%, 87/319) and increased venting (51.7%, 165/319) in nasogastric transplantation group. Diarrhea was the most common complication in colonoscopy group (36.6%, 15/41). The main symptoms were increased venting (50.0%, 23/46) and nausea(34.8%, 16/46) in oral capsule group. Side effect symptoms disappeared after the withdraw of nasogastric tube, or at the end of treatment, or during hospitalization for 1-3 days.

CONCLUSIONSFMT is effective for many gastrointestinal disorders. No significant adverse event is found, while the associated mechanism should be further explored.

Adult ; Clostridium Infections ; drug therapy ; Clostridium difficile ; drug effects ; Colitis, Ulcerative ; drug therapy ; Colonoscopy ; adverse effects ; methods ; Constipation ; drug therapy ; Crohn Disease ; drug therapy ; Diarrhea ; chemically induced ; Fecal Microbiota Transplantation ; methods ; statistics & numerical data ; Female ; Flatulence ; chemically induced ; Gastrointestinal Diseases ; drug therapy ; Gastroscopy ; methods ; Humans ; Intubation, Gastrointestinal ; adverse effects ; methods ; Irritable Bowel Syndrome ; drug therapy ; Male ; Middle Aged ; Nausea ; chemically induced ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo evaluate the efficacy and safety of fecal microbiota transplantation (FMT) combined with soluble dietary fiber and probiotics for slow transit constipation(STC).

METHODSTwenty-three patients with STC from Jinling Hospital, Medical School of Nanjing University were prospectively enrolled between April 2015 and January 2016. STC patients received FMT combined with soluble dietary fiber and probiotics. Fresh stool(100 g) was immediately mixed in a blender with 500 ml of 0.9% sterile saline for several seconds, which was then filtered through a gauze pad and a decreasing number of gauze screen (2.0 to 0.5 mm). The fecal bacteria suspension was stored frozen at -20centi-degree. The preparation time of FMT material was less than 1 hour. Total time of treatment was 9 days. An initial oral antibiotics(vancomycin 500 mg orally twice per day) was given for 3 consecutive days. Then the fecal microbiota(100 ml) was infused slowly(5 min) through nasojejunal tube for 6 consecutive days. After FMT, patients were recommended to receive soluble dietary fiber (pectin, 8 g/d) and probiotics (bifid triple viable capsules, twice per day) for 4 weeks. Rates of clinical improvement and remission, adverse events, constipation-related symptoms (PAC-SYM scores), bowel movements per week and gastrointestinal quality-of-life index (GIQLI) were recorded during the 12-week follow-up. This study was registered in the Clinical Trials.gov (NCT02016469).

RESULTSAmong 23 patients, 7 were male, 16 were female, the mean age was (49.6±14.7) years, the body mass index was (21.2±2.2) kg/m, the duration of constipation was (8.3±5.9) years, and the defecation frequency was 1.8±0.7 per week. Compared with pre-treatment, PAC-SYM scores decreased significantly from 2.3±0.5 to 1.3±0.4 at week 12 (P<0.01), defecation frequency increased from 1.8±0.7 per week to 4.8±2.0 per week at week 12 (P<0.01), and patients felt satisfied with improved GIQLI score (from 78.5±15.5 to 120.8±21.3, P<0.01). During the follow-up, the clinical improvement and remission of STC patients reached 69.6%(16/23) and 52.2%(12/23), respectively. No serious adverse events were observed.

CONCLUSIONFMT combined with soluble dietary fiber and probiotics is safe and effective in treating slow transit constipation, which can improve the symptom and quality of life significantly.

Objective:To evaluate component separation technique (CST)for the managetment of abdominal wall defect after resection of abdominal wall tumor.Methods:Clinical data of 12 patients treated by CST form Jan 2016 to Jan 2019 at our two Hospitals were retrospectively analyzed. The abdominal wall defect after tumor radical resection were reconstructed with synthetic mesh.Results:The most common pathological type was dermatofibrosarcoma protuberans (4 cases), followed by desmoid fibroma (2 cases) and abdominal metastasis of colon cancer (2 cases). The maximum diameter of tumor was (5.3±1.5) cm by CT preoperatively.The largest transverse diameter of abdominal wall defect after tumor resection was (9.4±1.4) cm.7 patients were treated with CST. 10 patients used synthetic mesh. Incision-related complications occurred in 3 patients, abdominal hypertension and atelectasis in 1 case and acute myocardial infarction in 1 case. All patients were helped and discharged.One patient died of liver metastasis of colon cancer 17 months after operation, and the other 11 patients had no recurrence of tumor or incisional hernia.Conclusion:Using CST in patients with abdominal wall tumor can effectively close the defect, reconstruct the function of abdominal wall and prevent the occurrence of incisional hernia.

Objective To observe the expressions of brain derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) in rats with early brain injury (EBI) after subarachnoid hemorrhage,and study the neuroprotective effects of BDNF and TrkB on EBI.Methods Male Sprague-Dawley rats (n=56),weighing 280-320 g,were randomly divided into sham-operated group and SAH group;SAH models were established by endovascular perforation ofinternal carotid artery.At 24 and 72 h after modeling,neurological scale scores were recorded;brain water content was measured;immunohistochemical staining and ELISA were used to observe the dynamical expressions of BDNF and TrkB in the brain.Results At 24 and 72 h after modeling,the neurological function scores and brain water content of SAH rats were higher than those of sham-operated group.The expression scores of BDNF in the SAH rats were 1.33±0.52 and 1.67±0.52,and the expression levels were (12.11±0.44) mg/mL and (15.82±0.89) mg/mL;the expression scores of TrkB were 1.17±0.75 and 2.00±0.00,and the expression levels were (18.89±0.38) mg/mL and (25.18±0.68) mg/mL.The expression scores of BDNF in the sham-operated group were 0.33±0.52 and 0.17±0.41,and the expression levels of BDNF in the sham-operated group was (4.92±0.16) mg/mL and (4.93±0.20) mg/mL;the expression scores of TrkB were 0.17±0.41 and 0.33±0.52,and the expression levels were (8.52±0.41) mg/mL and (8.08±0.34) mg/mL.There were significant differences in BDNF and TrkB expressions between the two groups at 24 and 72 h after modeling (P＜0.05).Conclusion The expressions of BDNF and TrkB increase significantly after SAH,and BDNF and TrkB play protective effect on EBI after SAH.