Tumor cells leads to enhanced glucose uptake and the conversion of a larger fraction of pyruvate into lactate even under the circumstance of abundant oxygen. This phenomenon of aerobic glycolysis is known as the Warburg effect. Lactic acid, as an important tool for tumor cells to modify the tumor microenvironment, promotes the process of tumor invasion and metastasis, and contributes to tumor development by inducing and recruiting immunosuppression-related cells and molecules. Lactic acid could efflux out of the cancer cells via the monocarboxylate transporters to prevent intracellular acidification. Lactate can inhibit the cytolytic activity of T cells and natural killer (NK) cells, promoting the differentiation of tolerogenic interleukin 10 (IL-10)-producing dendritic cells. Moreover, the lactate-derived lactylation of histone lysine residues can promote macrophage polarization toward the M2-like phenotype, suppressing the immune response within the tumor microenvironment. In this review, we discuss the role of lactate as an immunosuppressor molecule that contributes to tumor evasion from the aspects of lactic acid metabolism and its effect on immune cells. And we explore the possibility of targeting potential targets in lactate metabolism for tumor treatment. At last, we proposed a tumor immunotherapy strategy by inhibiting the pathway of aerobic glycolysis and proteins associated with the production and transport of lactic acid.

OBJECTIVE:To prepare dexibuprofen sustained-release pellets,and to analyze the drug release behavior in vitro. METHODS:Centrifugal granulation powder layering-eudragit dispersion coating method was used to prepare dexibuprofen sus-tained-release pellets using 3%HPMC as adhesive agent. The formula of the pellets was optimized by orthogonal test with weight ra-tio of sucrose to dexibuprofen,weight ratio of HPMC to Eudragit NE30D and coating weight as factors,using 1,4 and 10 h accu-mulated release rate (Q) as index. The release of the drug from the pellets was analyzed. RESULTS:The optimized formulation was that the proportion of sucrose to drug was 1:10,the weight ratio of HPMC to Eudragit NE30D was 1.5:1,the increased weight of coating material was 8%. Q1 h,Q4 h and Q10 h of prepared pellets were 21%,57% and 89%,respectively(n=3). The co-rrelation coefficient of zero-order,one-order and Higuchi equation release model were 0.956 6,0.989 9,0.996 5. CONCLUSIONS:Prepared pellets show good sustained-release effect in vitro. Drug release of pellets is more in accordance with Higuchi equation.

Objective To investigate the effects of different tidal volume mechanical ventilation on pulmonary function and inflammatory factors in gynecologic laparoscopic surgery.Methods 45 patients undergoing gynecological laparoscopic surgery without lung disease,ASA Ⅰ-Ⅱ,aged 20-45 years old,weight 45-65 kg,operation time 2-3 hours,were randomly divided into A,B,C three groups,15 cases in each group.Mechanical ventilation with different tidal volume of the three groups,A group,B group and C group were 8mL/kg,9mL/kg,10mL/kg.Blood gas analysis was performed before anesthesia (T0),30 minutes (T1),(T2),PA-aDO2 (60 minutes) (T3),and 120 min (T4),respectively,and the peak airway pressure and mean pressure were recorded.IL-6,TNF-α and IL-10 levels in plasma by radial artery blood sampling were simnultaneously determined.Results Comnpared with A group,the concentrations of Ppeak and Pmean were increased in B group at T1-T4 (t =5.13,4.78,6.54,5.32 and t =7.54,4.88,5.37,4.95;all P ＜ 0.05),the concentration of Ppeak and Pmean in C group at T1-T4 increased (t =7.76,8.87,7.23,8.99 and t =6.42,7.38,7.62,9.86;all P ＜ 0.05).Compared with B group,the concentrations of Ppeak and Pmean were increased in C group at T1-T4 (t =4.76,5.87,4.23,3.99 and t =4.76,3.99,6.06,4.52;all P ＜ 0.05).Compared with A group,the A-aDO2 values of B group and C group were increased at T1,T2,T3 and T4 (t =5.32,5.48,4.88,5.69 and t =7.85,7.32,8.45,6.67;all P ＜ 0.05).Compared with B group at the same time point,the A-aDO2 value of C group increased at four times of T1-T4 (t =5.62,4.38,6.94,4.22,P ＜0.05).Compared with group A,the concentration of A-aDO2 in C group was higher than that in B group at the same time point (t =4.45,4.87,5.32,4.79 and t =7.68,7.59,7.44,8.38;all P ＜ 0.05).The levels of IL-6 and TNF-α in C group were significantly higher than those in the control group (t =4.78,5.56,7.62,8.03 and t =3.98,4.52,5.46,6.23;all P ＜ 0.05).Compared with T0,IL-6 and TNF-α concentrations AT T2-T4 in A group had no statistically significant differences (all P ＞ 0.05).Compared with B group,the levels of IL-6 and TNF-α in C group were significantly higher (t =4.58,4.99,6.53,4.77 and t =5.62,7.89,6.43,4.52;all P ＜ 0.05).Compared with T0,IL-6 and TNF-α concentrations at T2-T4 in A group had no statistically significant differences (all P ＞0.05).There was no significant difference in IL-10 concentration among the thrce groups.Conclusion Laparoscopic surgery according to the end tidal carbon dioxide partial pressure (PetCO2) ventilation frequency,8 mL/kg tidal volume mechanical ventilation has no effect on the IL-6,TNF-alpha,IL-10 and other inflammatory factors,mechanical ventilation tidal volume is more appropriate.

A novel raw-starch-digesting glucoamylase producer,Rhizopus sp.W-08,was used in a novel fermentation system of solid-state followed by submerged,and high enzyme activity of 72 IU/mL was obtained.In the following simultaneous saccharification and fermentation process, Saccharomyces cerevisiae Z-06 directly converted raw corn flour to ethanol with the concentration of 21 % (V/V) at 30℃ after 48h.The conversion efficiency of raw corn flour to ethanol was 94.5 % of the theoretical ethanol yield.

ObjectiveThe efficacy and safety of nitrous oxide-sedated transnasal gastroscopy for high-risk patients of intravenous anesthesia were evaluated. MethodsA total of 157 patients were randomly assigned to the nitrous oxide group ( n =80) and the oxygen group ( n =77). Heart rate, blood oxygen saturation, blood pressure and electrocardiogram were monitored. Complications in both groups were recorded.Satisfaction degrees of patients and endoscopy physicians were evaluated with a questionnaire and visual analog scale (VAS) score. The questionnaire questions for physicians included the procedure evaluation ( steady, ok, unsteady). Patients' questionnaire questions included discomfort (light, moderate, severe), the patients' tolerance ( fine, moderate, weak) and the patients' willingness to undergo a second procedure. Statistical analysis was performed between the two groups. ResultsSix of the toal 157 patients were removed because of the operation failure (difficulty in access to nasal cavity in 5 patients and nose bleeding in one patient), 151 patients underwent the transnasal gastroscopy successfully and completed the questionnaires. In experimental group, there were 37 males and 41 females (mean age was 67.7 years, ranging 16-88 years, 7 patients were grade 1 of ASA, 61 were grade 2, and 11 were grade 3). In the control group, there were 36 males and 37 females (mean age was 67.9 years, ranging 17-86 years, 6 patients were grade 1 of ASA, 57 were grade 2, and 9 were grade 3). There was no differences in sex, average age and ASA grade between the two groups (P ＞ 0. 05 ). There was no difference in the mean operation time between the two groups, either (200. 1 s vs 200. 3 s) ( P ＞ 0. 05 ). There were no significant differences between the two groups in changes of blood oxygen saturation, blood pressure, electrocardiogram and complication rates ( P ＞ 0. 05 ).Both physicians' and patients' positive evaluations of the experimental group were more than that of the control (P ＜ 0. 05 ), while physicians' and patients' negative evaluations of the experimental group were less than the control (P ＜0. 05). VAS of physicians' satisfaction in the experimental group was higher than that of the control group (84 vs 70, t =14. 67, P ＜ 0. 05), and VAS of patients' satisfaction in the experimental group was superior to the control group (82 vs 71, t =11.56, P ＜ 0. 05). The number of patients wiring to undergo a second procedure in the experimental group was higher than that of the control (89. 7％ vs 69. 9％, P ＜ 0. 05). ConclusionNitrous oxide-sedated transnasal endoscopy is an effective and safe procedure for high risk patients of intravenous anesthesia.

ObjectiveTo assess the diagnostic value of EUS for pancreatic neuroendocrine tumors.MethodsClinical data of 26 patients with final diagnosis of pancreatic neuroendocrine tumors,who had underwent EUS and EUS-FNA,were retrospectively analyzed.Results On EUS,pancreatic neuroendocrine tumors presented as hypoechoic masses with clear margins and rich blood flow.Of the 26 pancreatic lesions,3 were in the head,2 in unicate process,2 in neck,11 in body and 8 in tail.The tumors presented with function in 16 ( mean size 9 mm),and on function in 10 ( mean size 29 mm).EUS-FNA yeilded positive results in 22 patients and negative in 4.The accuracy rate of EUS for preoperative localization was 100％ in 23 patients who underwent surgery.ConclusionEUS can provide accurate preoperative localization and pathologic evidence for pancreatic neuroendocrine tumors.

This study is to investigate effects of genistein on rat femoral bone metabolic in vitro. Rat femoral tissues was isolated and randomly divided into two groups including control group and genistein (1 x 10(-5) mol x(-1)) group. Determinations of alkaline phosphatase (ALP) activity, calcium content and osteoprotegerin (OPG), type I-collagen (Collagen-I), RANKL, Runx-2 and bone morphogenetic protein (BMP-2) mRNA expression were done by real-time PCR. The results showed that 1 x 10(-5) mol x L(-1) genistein could increase the activity of ALP and contents of Ca, regulate bone metabolism activity of OPG, RANKL, BMP-2, Collagen-I and Runx-2 mRNA expression level. Genistein can significantly modulate bone metabolism related gene expression level of rat femoral tissue in vitro, and can increase calcium content and the activity of ALP.

AIM: To explore the molecular mechanisms about fibrosis and transforming growth factor (TGF) - β1 as well as inflammation in rats heart after acute myocardial infarction (AMI). METHODS: AMI model in rats was produced by left coronary artery ligation. Samples of rat cardiac tissue were collected at the end of 1 week, 4 weeks and 8 weeks. Hemodynamics had been performed before rats were sacrificed. Reverse transcription polymerase chain reaction (RT- PCR) and immunohistochemical methods were used to analyze mRNA expression and protein production of TGF- β1, respectively. Hydroxyproline was determined by chloramines T method. HE staining was resorted to analyze pathological myocardium after AMI. RESULTS: There were remarkable differences in hemodynamics between AMI groups and sham group (P＜0.01). Compared with sham group, TGF-β1mRNA expression and protein production and hydroxyproline quantification were enhanced greatly. Among them, the levels of TGF -β1 and hydroxyproline at 1 week were higher than those at 4 weeks or 8 weeks. A positive correlation between TGF- β1 protein and hydroxyproline was presented (r=0.75 - 0.99, P＜0.05). In microscope, leucocytes infiltrated significantly in the infarcted and border myocardium at 1 week after AMI, and were rarely seen at 4 weeks and 8 weeks. TGF - β1 protein were detected in cytoplasm of cardiac myocyte and leucocytes at 1 week, and at 4 and 8 weeks in myofibroblast and interstitial. CONCLUSIONS:TGF- β1 is upregulated and found in cytoplasm of cardiac myocyte and leucocytes as well as myofibroblast in heart after AMI,which is associated with dynamic changes of hydroxyproline content and inflammation. TGF - β1 is showed to play an important role in myocardial inflammatory repair and ventricular remodeling after AMI.

Objective To evaluate the efficacy of endoscopic metal stent implantation for afferent limb obstruction after pancreaticoduodenectomy(PD). Methods A retrospective analysis of 5 patients with afferent limb obstruction after PD treated by endoscopic metal stent implantation was performed.Data of each patient was reviewed including the records of the endoscopic procedure,the complications and the clinical outcomes. Results All the metal stents were implanted successfully in the 5 patients. The abdominal disten-sion and cholangeitis were well relieved in all the patients. The liver function improved in all the patients in 3 to 5 days.No abdominal discomfort,bleeding,perforation,or stent dislocation occurred.CT scan showed that all stents were well expanded.The survival time of the 5 patients were 3 to 8 months,and 4. 6 months on av-erage. There was no recurrence of afferent limb obstruction. Conclusion For afferent limb obstruction after PD,endoscopic metal stent implantation is effective in relieving obstruction,the symptoms,and improving the quality of life.

Objective To investigate the optimal time for double balloon enteroscopy (DBE) in patients with obscure gastrointestinal bleeding (OGIB).Methods Data of 78 patients with OGIB who underwent DBE from January 2009 to November 2013 were retrospectively analyzed.They were classified into two groups:emergency DBE and non-emergency DBE.The demographic and clinical features and outcomes of DBE,the time of examination and complications were compared.Results The overall diagnostic yield of DBE was 48 lesions (61.54 ％).The overall diagnostic yield of emergency DBE group was 77.14％,which was significantly higher than that in non-emergency DBE group (48.83％) (P =0.019).The time of examination in emergency group was shorter than that of non-emergency group with significant difference (P =0.031).Conclusion Emergency DBE takes less time and yields a higher rate of detection.Patients withOGIB should receive DBE as soon as possible.