[Clinical analysis of long-term survival and influencing factors of chimeric antigen receptor T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia].

Objective: To analyze the survival and influencing factors of chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia (R/R B-ALL) . Methods: Clinical information of patients who received CAR-T-cell therapy and achieved complete remission of R/R B-ALL between May 2015 and June 2018 at the Shaanxi Provincial People's Hospital was obtained. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and leukemia-free survival (LFS) times of patients, and Cox regression analysis was performed to analyze the prognostic factors that affect patient survival after CAR-T therapy. Results: Among the 38 patients with R/R B-ALL, 21 were men, with a median age of 25 (6-59) years and a median OS time of 18 (95% CI 3-33) months. Multivariate Cox regression analysis showed that positive MLL-AF4 fusion gene expression was an independent risk factor for OS and LFS (OS: HR=4.888, 95% CI 1.375-17.374, P=0.014; LFS: HR=6.683, 95% CI 1.815-24.608, P=0.004). Maintenance therapy was a protective factor for OS and LFS (OS: HR=0.153, 95% CI 0.054-0.432, P<0.001; LFS: HR=0.138, 95% CI 0.050-0.382, P<0.001). In patients with MRD negative conversion, LFS benefit (HR=0.209, 95% CI 0.055-0.797, P=0.022) and OS difference was statistically insignificant (P=0.111). Moreover, patients with high tumor burden were risk factors for OS and LFS at the level of 0.1 (OS: HR=2.662, 95% CI 0.987-7.184, P=0.053; LFS: HR=2.452, 95% CI 0.949-6.339, P=0.064) . Conclusion: High tumor burden and high-risk genetics may affect the long-term survival rate of patients with R/R B-ALL receiving CAR-T, and lenalidomide-based maintenance therapy may improve their prognosis.

[The 479th case: cognitive impairment, respiratory failure, colon mass].

A 78-year-old man was admitted to Peking Union Medical College Hospital with fever, weakness of lower extremities, less speech, loss of memory. Fever was relieved after antibiotic treatment, while cognitive impairment and disorder of consciousness progressed rapidly, followed by critical pulmonary infections, respiratory failure, and septic shock. Lab tests showed negative occult blood, normal serum CEA level and positive Anti-nuclear-antibody. PET-CT suggested that strong FDG uptake signals were seen at sigmoid, while bilateral frontal lobe, temporal lobe, parietal lobe, posterior cingulate gyrus showed lower metabolic activity. Colonoscopy biopsy revealed differentiated adenocarcinoma of sigmoid colon. Therefore, paraneoplastic syndrome of nervous system secondary to colon cancer was considered. Rapid and proper diagnosis and treatment were completed by multidisciplinary team including departments of neurology, gastroenterology, general surgery, ICU, rheumatology, clinical nutrition. The laparoscopic sigmoid colectomy was performed under general anesthesia. The patient finally presented with significant improvement of cognition and consciousness. Respiratory function was totally recovered.

Efficacy of orally toxic sugar baits against contact-insecticide resistant culex quinquefasciatus.

In recent years, attractive toxic sugar bait has been used in the mosquito control in nature, and achieved good control effects. However, the current researches about toxic sugar bait did not focus on whether the wild mosquito population used for control is resistant or not. The purpose of this study was to evaluate the effectiveness of the toxic sugar bait against mosquito resistant populations to test the effects of bait on the control of mosquitoes with different levels of resistance. Boric acid, dinotefuran and deltamethrin were separately formulated into toxic sugar bait to test their anti-mosquito activity against Culex quinquefasciatus. Using the sugar baits formulated with boric acid and dinotefuran, the mortality of Cx. quinquefasciatus resistant populations was significantly higher than that of sensitive populations at the same concentration. Conversely, with the use of sugar baits formulated with deltamethrin, the mortality of Cx. quinquefasciatus resistant populations was significantly lower than that of sensitive populations at the same concentration. The results suggested that toxic sugar baits might have a good application prospect in high resistant mosquito management.

[Experts consensus on the management of the right heart function in critically ill patients].

To establish the experts consensus on the right heart function management in critically ill patients. The panel of consensus was composed of 30 experts in critical care medicine who are all members of Critical Hemodynamic Therapy Collaboration Group (CHTC Group). Each statement was assessed based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) principle. Then the Delphi method was adopted by 52 experts to reassess all the statements. (1) Right heart function is prone to be affected in critically illness, which will result in a auto-exaggerated vicious cycle. (2) Right heart function management is a key step of the hemodynamic therapy in critically ill patients. (3) Fluid resuscitation means the process of fluid therapy through rapid adjustment of intravascular volume aiming to improve tissue perfusion. Reversed fluid resuscitation means reducing volume. (4) The right ventricle afterload should be taken into consideration when using stroke volume variation (SVV) or pulse pressure variation (PPV) to assess fluid responsiveness.(5)Volume overload alone could lead to septal displacement and damage the diastolic function of the left ventricle. (6) The Starling curve of the right ventricle is not the same as the one applied to the left ventricle,the judgement of the different states for the right ventricle is the key of volume management. (7) The alteration of right heart function has its own characteristics, volume assessment and adjustment is an important part of the treatment of right ventricular dysfunction (8) Right ventricular enlargement is the prerequisite for increased cardiac output during reversed fluid resuscitation; Nonetheless, right heart enlargement does not mandate reversed fluid resuscitation.(9)Increased pulmonary vascular resistance induced by a variety of factors could affect right heart function by obstructing the blood flow. (10) When pulmonary hypertension was detected in clinical scenario, the differentiation of critical care-related pulmonary hypertension should be a priority. (11) Attention should be paid to the change of right heart function before and after implementation of mechanical ventilation and adjustment of ventilator parameter. (12) The pulmonary arterial pressure should be monitored timingly when dealing with critical care-related pulmonary hypertension accompanied with circulatory failure.(13) The elevation of pulmonary aterial pressure should be taken into account in critical patients with acute right heart dysfunction. (14) Prone position ventilation is an important measure to reduce pulmonary vascular resistance when treating acute respiratory distress syndrome patients accompanied with acute cor pulmonale. (15) Attention should be paid to right ventricle-pulmonary artery coupling during the management of right heart function. (16) Right ventricular diastolic function is more prone to be affected in critically ill patients, the application of critical ultrasound is more conducive to quantitative assessment of right ventricular diastolic function. (17) As one of the parameters to assess the filling pressure of right heart, central venous pressure can be used to assess right heart diastolic function. (18). The early and prominent manifestation of non-focal cardiac tamponade is right ventricular diastolic involvement, the elevated right atrial pressure should be noticed. (19) The effect of increased intrathoracic pressure on right heart diastolic function should be valued. (20) Ttricuspid annular plane systolic excursion (TAPSE) is an important parameter that reflects right ventricular systolic function, and it is recommended as a general indicator of critically ill patient. (21) Circulation management with right heart protection as the core strategy is the key point of the treatment of acute respiratory distress syndrome. (22) Right heart function involvement after cardiac surgery is very common and should be highly valued. (23) Right ventricular dysfunction should not be considered as a routine excuse for maintaining higher central venous pressure. (24) When left ventricular dilation, attention should be paid to the effect of left ventricle on right ventricular diastolic function. (25) The impact of left ventricular function should be excluded when the contractility of the right ventricle is decreased. (26) When the right heart load increases acutely, the shunt between the left and right heart should be monitored. (27) Attention should be paid to the increase of central venous pressure caused by right ventricular dysfunction and its influence on microcirculation blood flow. (28) When the vasoactive drugs was used to reduce the pressure of pulmonary circulation, different effects on pulmonary and systemic circulation should be evaluated. (29) Right atrial pressure is an important factor affecting venous return. Attention should be paid to the influence of the pressure composition of the right atrium on the venous return. (30) Attention should be paid to the role of the right ventricle in the acute pulmonary edema. (31) Monitoring the difference between the mean systemic filling pressure and the right atrial pressure is helpful to determine whether the infusion increases the venous return. (32) Venous return resistance is often considered to be a insignificant factor that affects venous return, but attention should be paid to the effect of the specific pathophysiological status, such as intrathoracic hypertension, intra-abdominal hypertension and so on. Consensus can promote right heart function management in critically ill patients, optimize hemodynamic therapy, and even affect prognosis.

Role of TIM-3 in ovarian cancer

Evidences have suggested that immunotherapy for ovarian cancer is effective. Immune checkpoints have emerged in the field of cancer immunotherapy. Multiple studies have shown negative regulation of TIM-3 expression on CD4+ and CD8+ T cells and other immunocytes. Overexpression of TIM-3 in innate immune cells has been found in certain types of tumor. The blockade of TIM-3 leads to sustained anti-tumor reactions. TIM-3 plays an inhibitive role for immunity in ovarian cancer. TIM-3 is involved in the development of various subtypes of ovarian cancer and thus has the potential to be a therapeutic target for treatment of ovarian cancer (AU)

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Role of TIM-3 in ovarian cancer.

Evidences have suggested that immunotherapy for ovarian cancer is effective. Immune checkpoints have emerged in the field of cancer immunotherapy. Multiple studies have shown negative regulation of TIM-3 expression on CD4+ and CD8+ T cells and other immunocytes. Overexpression of TIM-3 in innate immune cells has been found in certain types of tumor. The blockade of TIM-3 leads to sustained anti-tumor reactions. TIM-3 plays an inhibitive role for immunity in ovarian cancer. TIM-3 is involved in the development of various subtypes of ovarian cancer and thus has the potential to be a therapeutic target for treatment of ovarian cancer.

High hydrostatic pressure upon the vasa vasorum of the greater saphenous and splenic vein walls: a comparative study.

AIMS: Hypoxia and high hydrostatic pressure can induce an increase in the thickness of the tunica media and intima; secondary vasa vasorum (VV) increase to fit the remodeling of the vessel wall. We aimed to investigate the impact of high hydrostatic pressure on VV in the varicose greater saphenous veins (VGSVs) and diseased splenic veins (DSVs). METHODS: We collected 34 VGSVs and DSVs. Thirty-four normal greater saphenous veins (GSVs) and splenic veins (SVs) were also collected (control group). Samples were cut into slices, and observed under both light and electron microscopy. The mean density and cross-sectional areas of the VV in the adventitia were measured. RESULTS: In both VGSVs and DSVs, VV density increased, in the adventitia and exterior tunica media, offering an intensive linear distribution. However, sporadic distribution of the interior tunica media and intima were seen on light microscopy. The integrated structure of the cell nucleus of endothelial cells in VV, normal morphology and distribution of chromatin, partially hyperchromatic mitochondria matrix, fuzzy or fractured mitochondria cristae, and medullary cristae changes were observed by electron microscopy. Mean density and cross-sectional areas of VV in the adventitia of GSVs and SVs were significantly different. CONCLUSION: Under high hydrostatic pressure conditions, the number of VV were increased in the wall of VGSVs and DSVs. There was heterogeneity between both types of veins. The splenic vein has a higher number of VV, but the greater saphenous vein has a higher average cross-sectional area. The same ultrastructural changes are seen in the endothelial cells of the VV in both vessels.

Oral ridaforolimus plus trastuzumab for patients with HER2+ trastuzumab-refractory metastatic breast cancer.

BACKGROUND: Although trastuzumab-containing therapies prolong survival in patients with metastatic breast cancer (MBC), most tumors develop trastuzumab resistance, potentially mediated by aberrant phosphatidylinositide 3-kinase (PI3K)/AKT signaling. Ridaforolimus (a mammalian target of rapamycin [mTOR] inhibitor) may overcome trastuzumab resistance by inhibiting PI3K signaling. METHODS: A single-arm, phase IIb trial was conducted to evaluate the efficacy and safety of ridaforolimus-trastuzumab in human epidermal growth factor receptor 2-positive (HER2(+)) trastuzumab-refractory MBC (NCT00736970). Ridaforolimus was administered orally (40 mg daily) for 5 d/wk plus weekly trastuzumab. The primary end point was objective response (OR). RESULTS: Thirty-four patients were enrolled (91% had received 1 or 2 previous trastuzumab-based therapies, whereas 9% had received 3 previous therapies). The most common reasons for discontinuation were disease progression (62%) and adverse events (AEs; 24%). Three patients died; 1 because of bowel perforation, which was possibly ridaforolimus related. Partial response was observed in 5 patients (15%). Median duration of response was 19.1 weeks (range, 15.9-80.1 weeks). Fourteen patients (41%) achieved stable disease (SD); 7 patients (21%) maintained SD for ≥ 24 weeks. The clinical benefit response (CBR) rate was 34.3%. Median progression-free survival (PFS) and overall survival (OS) were 5.4 months (range, 0-20.3 months; 95% confidence interval [CI], 2.0-7.4) and 17.7 months (range, 0-25.9 months; 95% CI, 8.8-20.8), respectively. PFS rate at 6 months was 37%. The most common treatment-related AEs were stomatitis (59%), diarrhea (27%), and rash (27%). CONCLUSION: Ridaforolimus-trastuzumab was well tolerated and demonstrated antitumor activity in trastuzumab-resistant HER2(+) MBC.

Therapeutic potential of furin inhibitors for the chronic infection of hepatitis B virus.

BACKGROUND & AIMS: Hepatitis B e antigen (HBeAg) is essential for the development of chronic hepatitis B virus (HBV) infection. Furin, a proprotein convertase, plays a key role in processing of HBeAg precursor into maturated HBeAg. For these reasons, the therapeutic potential of furin inhibition for chronic HBV infection was studied. METHODS: The effects of furin inhibitor I (decanoyl-RVKR-chloromethylketone, CMK) and furin inhibitor II (hexa-D-arginine, D6R) on HBeAg secretion, the destination of unprocessed precursor and cellular secretory functions were comparatively investigated. RESULTS: CMK and D6R significantly decreased the supernatant level of HBeAg and increased the intracellular level of HBeAg precursor in HepG2.2.15 cells in vitro. The accumulated HBeAg precursor was not found to be retro-transported into the cytosol to inhibit HBV replication as expected, but was found to be expressed on the cell surface, where it may be more convenient to mediate host immune responses. Furthermore, these inhibitors at effective concentrations were not found to interfere with the maturations of albumin and prothrombin. Compared with CMK, D6R was suboptimal in effectiveness; however, D6R neither enhanced HBV replication through the accumulation of cytosolic HBcAg nor did it cause severe cell damage in an elongated safety analyses. CONCLUSION: Furin inhibitors CMK and D6R reduce HBeAg secretion and increase cell surface expression of the HBeAg precursor in HepG2.2.15 cells. Novel furin inhibitors or modified forms of D6R may promote the reduction of immune tolerance and the elimination of infected hepatocytes in patients with chronic HBV infection.

Inhibition of matrix metalloproteinase-9 attenuates acute small-for-size liver graft injury in rats.

Ischemia/reperfusion (I/R) and portal hypertension have been implicated in small-for-size liver graft dysfunction. Matrix metalloproteinases-2 and -9 (MMP-2/9) are critically proposed to involve in hepatic I/R injury and activated by hemodynamic force. We hypothesized that MMP-2/9 overexpression played a crucial role in acute graft injury following small-for-size liver transplantation (LT). Rats were randomly assigned into four groups: 75% partial hepatectomy (PH); 100% LT; 25% LT and 25% LT treated with CTT peptide (MMP-2/9 inhibitor). ELISA, real-time PCR, gelatin zymography and immunohistochemistry were used to determine the expression pattern of MMP-2/9 in liver tissue. MMP-9 expression was significantly increased 6 h after reperfusion and reached a peak 12 h in the 25% LT group, whereas MMP-2 was expressed in all groups invariably. Compared with the 25% LT group, rats from CTT-treated group exhibited markedly decreased alanine aminotransferase and total bilirubin values, downregulated proinflammatory cytokines, attenuated malondialdehyde (MDA) and myeloperoxidase (MPO) activities, and improved liver histology. Likewise, MMP-9 inhibition significantly reduced number of TUNEL-positive cells and caspase-3 activity, along with decreased protein levels of Fas and Fas-L. Specifically, rat survival was also improved in the CTT-treated group. These results support critical function of MMP-9 involved in acute small-for-size livergraft injury.

Celecoxib reduces symptoms in men with difficult chronic pelvic pain syndrome (Category IIIA)

We investigated the effectiveness of celecoxib in reducing symptoms in patients with difficult chronic pelvic pain syndrome (CPPS), NIH category IIIA. Sixty-four patients with category IIIA CPPS were randomized into two groups of 32 subjects each. One group was treated with celecoxib (200 mg daily) and the other with placebo. All patients underwent treatment for 6 weeks and were evaluated clinically before (baseline) and after 1, 2, 4, 6, and 8 weeks of treatment. The evaluation included the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and a subjective global assessment (SGA). Repeated measures analysis of variance was used to evaluate treatment and time effects and their interaction. A decrease (means ± SD) in total NIH-CPSI score from 23.91 ± 5.27 to 15.88 ± 2.51 in the celecoxib group and from 24.25 ± 5.09 to 19.50 ± 2.50 in the placebo group was observed during treatment (0 to 6 weeks). A statistically significant decrease was observed in pain subscore (P < 0.006), quality of life subscore (P < 0.032) and total NIH-CPSI score (P < 0.015) after 2, 4 and 6 weeks, but not in urinary subscore. In addition, 38 percent of the celecoxib and 13 percent of the placebo subjects had at least a moderate improvement in SGA. The trend was similar for the NIH-CPSI scores. However, the response to treatment in terms of total NIH-CPSI score or subscore was not significantly different from placebo after interruption of treatment for 2 weeks. Our results show that celecoxib provides significant symptomatic improvement limited to the duration of the therapy in patients with difficult category IIIA CPPS compared to placebo.

Celecoxib reduces symptoms in men with difficult chronic pelvic pain syndrome (Category IIIA).

We investigated the effectiveness of celecoxib in reducing symptoms in patients with difficult chronic pelvic pain syndrome (CPPS), NIH category IIIA. Sixty-four patients with category IIIA CPPS were randomized into two groups of 32 subjects each. One group was treated with celecoxib (200 mg daily) and the other with placebo. All patients underwent treatment for 6 weeks and were evaluated clinically before (baseline) and after 1, 2, 4, 6, and 8 weeks of treatment. The evaluation included the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and a subjective global assessment (SGA). Repeated measures analysis of variance was used to evaluate treatment and time effects and their interaction. A decrease (means +/- SD) in total NIH-CPSI score from 23.91 +/- 5.27 to 15.88 +/- 2.51 in the celecoxib group and from 24.25 +/- 5.09 to 19.50 +/- 2.50 in the placebo group was observed during treatment (0 to 6 weeks). A statistically significant decrease was observed in pain subscore (P < 0.006), quality of life subscore (P < 0.032) and total NIH-CPSI score (P < 0.015) after 2, 4 and 6 weeks, but not in urinary subscore. In addition, 38% of the celecoxib and 13% of the placebo subjects had at least a moderate improvement in SGA. The trend was similar for the NIH-CPSI scores. However, the response to treatment in terms of total NIH-CPSI score or subscore was not significantly different from placebo after interruption of treatment for 2 weeks. Our results show that celecoxib provides significant symptomatic improvement limited to the duration of the therapy in patients with difficult category IIIA CPPS compared to placebo.

Transurethral prostatectomy using Vista bipolar radiofrequency system: comparison with conventional transurethral resection of the prostate.

To assess the efficacy and safety of transurethral prostatectomy using Vista system, between 2002 and 2004, patients with symptomatic BPH without suspected cancer were treated using the Vista device. The therapeutic effect was retrospective studied compared with patients who were received by TURP. Bipolar resection using the Vista device exhibits a statistically difference in maximum urinary flow rate, RUV, IPSS and QOL(P < .05) 3 and 6 months after operation, and no transurethral resection syndrome occurred. TURP also exhibits a statistically difference in maximum urinary flow rate, RUV, IPSS and QOL(P < .05), but TURS occurred in 2 patients. Compared with TURP, the Vista device shows a statistically less blood loss (P < .05), and longer operation time in prostate enlarged III(0)(P < .05). The Vista system seems to be effective and safe, and especially fit the patients who have a bigger prostate and high risk factors. It appears to be an effective treatment for BPH. Long-term results should be evaluated.

Efficient pyruvate production by a multi-vitamin auxotroph of Torulopsis glabrata: key role and optimization of vitamin levels.

A multi-vitamin auxotroph, Torulopsis glabrata strain WSH-IP303, which can use ammonium chloride as a sole nitrogen source for pyruvate production, was selected. To optimize pyruvate yield and productivity, a simple but useful, orthogonal design method, was used to investigate the relationship between thiamine, nicotinic acid, pyridoxine, biotin, and riboflavin. Thiamine was confirmed to be the most important factor affecting pyruvate production. When the concentration of thiamine was 0.01 mg/l or 0.015 mg/l, glucose consumption was improved by increasing the nicotinic acid concentration. When the concentrations of nicotinic acid, thiamine, pyridoxine, biotin, and riboflavin were 8.0, 0.015, 0.4, 0.04, and 0.1 mg/l, respectively, pyruvate concentration and yield reached 52 g/l and 0.52 g/g, respectively, in a 48-h flask culture. By employing a combination of the optimum vitamin concentrations, a batch culture was conducted in a 2.5-l fermentor with an initial glucose concentration of 112 g/l; and the pyruvate concentration reached 69 g/l after 56 h (yielding 0.62 g/g).

[Effect of nutritional conditions on the fermentative production of pyruvic acid by Torulopsis glabrata].

The effects of some nutritional conditions, such as peptone concentration, feeding glucose as well as oxygen supply manner and ratio of C/N in batch culture, on the fermentative production of pyruvic acid by Torulopsis glabrata WSH-IP12 were investigated. In shaking-flask culture: (1) peptone of more than 20 g/L inhibited the accumulation of pyruvic acid; (2) production of pyruvic acid was increased from 23.5 g/L to 30.2 g/L by simply feeding glucose. In 5 L jar-fermentor batch culture: (1) high level of dissolved oxygen and (2) increasing the concentration of glucose and peptone proportionally with constant C/N ratio(26:1) improved the production of pyruvic acid. It was also found that, glucose consumption and pyruvic acid production almost stopped under the condition of nitrogen difficiency while recovered by adding peptone and (NH4)2SO4. By using ammonia water instead of potassium hydroxide for the control of pH, the cells kept stronger ability for synthesizing pyruvic acid within the whole process, 57.3 g/L pyruvic acid with the yield of 0.498 g/g was achieved at 55 h of fermentation.

Human colorectal cancers express a constitutively active cholecystokinin-B/gastrin receptor that stimulates cell growth.

Although ectopic expression of the cholecystokinin B/gastrin receptor (CCK-BR) is widely reported in human colorectal cancers, its role in mediating the proliferative effects of gastrin1-17 (G-17) on these cancers is unknown. Here we report the isolation of a novel splice variant of CCK-BR that exhibits constitutive (ligand-independent) activation of pathways regulating intracellular free Ca(2+) ([Ca(2+)](i)) and cell growth. The splice variant (designated CCK-BRi4sv for intron 4-containing splice variant) is expressed in colorectal cancers but not in normal colonic mucosa adjacent to the cancer. Balb3T3 cells expressing CCK-BRi4sv exhibited spontaneous, ligand-independent, oscillatory increases in [Ca(2+)](i), whereas cells expressing wild-type CCK-BR did not. Primary cultures of cells isolated from resected colorectal cancers also exhibited a similar pattern of spontaneous [Ca(2+)](i) oscillations. For both Balb3T3 and primary tumor cells, application of G-17 (10 and 200 nm, respectively) caused an increase in [Ca(2+)](i). Selective CCK-BR antagonists blocked the G-17-stimulated Ca(2+) responses but not the spontaneous [Ca(2+)](i) oscillations. Cells expressing CCK-BRi4sv exhibited an increased growth rate ( approximately 2.5-fold), in the absence of G-17, compared with cells expressing wild-type CCK-BR. The selective pattern of expression, constitutive activity, and trophic action associated with CCK-BRi4sv suggest that this variant may regulate colorectal cancer cell proliferation though a gastrin-independent mechanism.

[Protective effect of Ginaton on rat liver microcirculation disturbance following liver xenotransplantation].

OBJECTIVE: To study the effect of Ginaton on liver microcirculation disturbance following liver xenotransplantation in rats. METHODS: Ginaton was injected intravenously to recipients at a dosage of 14 mg/kg before graftng liver of guinea pigs. The portal blood flow (PBF) was measured by Doppler ultrasound at 0, 30 and 60 minutes after transplantation, and the pathologic changes of liver and heart were observed. RESULTS: The reperfusion status of control group was poor and leukocyte infiltration appeared in the center of lobute following transplantation and myocardial cells were impaired. Significant reduction in PBF was found in rats following transplantation. Ginaton pretreatment distinctly ameliorated PBF. The speed of PBF was closely correlated with the pathologic changes following transplantation. CONCLUSION: In the process of liver transplantation, ischemia reperfusion damage may lead to xenoheptic microcirculaton disturbance. Ginaton could improve the xenoheptic microcirculation and reduce ischemic reperfusion damage.

[The important role of vitamins in the over-production of pyruvic acid].

The effect of nicotinic acid, thiamine, pyridoxine, biotin and riboflavin on the production of pyruvic acid by Torulopsis glabrata WSH-IP303 with glucose as carbon source and NH4Cl as sole nitrogen source was investigated. By using orthogonal experiment method, thiamine was confirmed to be the most important factor affecting the production of pyruvic acid. Based on a certain concentration range of thiamine (0.01-0.015 mg/L), glucose consumption rate can be enhanced by increasing the concentration of nicotinic acid. When the concentration of nicotinic acid, thiamine, pyridoxine, biotin and riboflavin were 8, 0.015, 0.4, 0.04 and 0.1 mg/L, respectively, the concentration and yield to glucose of pyruvic acid reached 52.4 g/L and 0.525 g/g at 48 h in flask culture, respectively. Batch culture was conducted in a 2.5 L fermentor with initial glucose concentration of 120 g/L. By adopting the optimal concentration combination of vitamins, the concentration and yield to glucose of pyruvic acid reached 69.4 g/L and 0.593 g/g at 57.5 h, which were increased by 32.4% and 13% than the best results in flask culture, respectively.