[Experimental Study of Ginsenoside Rg1 Combined with Antibiotics in the Treatment of Acute Lung Injury in Mice with Sepsis].

OBJECTIVE: To observe the effect of ginsenoside Rg1 on the acute lung injury of sepsis in combination with the antibiotic imipenem in a mouse model of sepsis that induced by cecal puncture. METHODS: C57BL/6 mice were used to establish the model of sepsis. The model mice were randomly divided into model group, imipenem group, ginsenoside Rg1 group, and ginsenoside Rg1+imipenem group, 10 mice in each group. Another 10 mice were set as control group. Sham operation was performed in the mice of control group. Each mice was intraperitoneally injected the corresponding drug in 2 h, 26 h and 50 h after surgery for three times. They were 2 h after surgery, 26 h after surgery and 50 h after surgery. 2 h after the last administration, the oxygenation index of the arterial blood was measured, the lung tissue was taken to measure lung wet/dry ratio (W/D), and HE staining was used to observe the lung inflammation. The ELISA kits were used to detect the levels of interleukin (IL)- 1ß, IL-6, tumor necrosis factor (TNF)-α and nuclear factor-kappa B (NF-κB) inalveolar lavage fluid. Western blot and immunohistochemical staining were used to detect NF-κB p65 expression in lung tissues. RESULTS: The drug-administered groups significantly reduced the W/D of the lungs in the septic mice and increased the oxygenation index in the blood ( P<0.01), and decreased the inflammation in lung and the levels of IL-1ß, IL-6, TNF-α and NF-κB in the alveolar lavage fluid ( P<0.01), and decreased the expression of NF-κB p65 in lung tissue ( P<0.01). When ginsenoside Rg1 was combined with imipenem, the above indicators were closer to the control group than that in the ginsenoside Rg1 and imipenem groups. CONCLUSION: Rg1 can significantly inhibit lung inflammation in septic mice. It has a better therapeutic effect when combined with antibiotics.

Dietary patterns, BCMO1 polymorphisms, and primary lung cancer risk in a Han Chinese population: a case-control study in Southeast China.

BACKGROUND: We investigated whether BCMO1 variants and dietary patterns are associated with lung cancer risk. METHODS: Case-control study including 1166 lung cancer cases and 1179 frequency matched controls was conducted for three BCMO1 variants (rs6564851, rs12934922, and rs7501331) and four dietary patterns were investigated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: The rs6564851, rs12934922, and rs7501331 were not found to be associated with lung cancer risk (P > 0.05). In multivariable-adjusted models, compared to the lowest quartile of the score on the "fruits and vegetables" pattern, the highest quintile was associated with a 78.4% decreased risk (OR Q4 vs. Q1 = 0.216; 95% CI, 0.164-0.284; P for trend < 0.001). Other patterns were not found the association. The "fruits and vegetables" pattern was associated with a reduced risk of lung cancer with all 3 SNPs irrespective of genotypes (all P for trend< 0.001). The association for the "Frugal" pattern was associated with increased risk of lung cancer among smokers (P for interaction = 0.005). The protective effects of the "cereals/wheat and meat" pattern was more evident for squamous cell carcinoma and other histological type. CONCLUSIONS: We did not observe associations of BCMO1 variants and lung cancer. Diets rich in fruits and vegetables may be protective against lung cancer.

Role of autophagy in acute myeloid leukemia therapy.

Despite its dual role in determining cell fate in a wide array of solid cancer cell lines, autophagy has been robustly shown to suppress or kill acute myeloid leukemia cells via degradation of the oncogenic fusion protein that drives leukemogenesis. However, autophagy also induces the demise of acute leukemia cells that do not express the known fusion protein, though the molecular mechanism remains elusive. Nevertheless, since it can induce cooperation with apoptosis and differentiation in response to autophagic signals, autophagy can be manipulated for a better therapy on acute myeloid leukemia.

Soluble CD4 effectively prevents excessive TLR activation of resident macrophages in the onset of sepsis.

T lymphopenia, occurring in the early phase of sepsis in response to systemic inflammation, is commonly associated with morbidity and mortality of septic infections. We have previously shown that a sufficient number of T cells is required to constrain Toll-like receptors (TLRs) mediated hyperinflammation. However, the underlying mechanisms remains unsolved. Herein, we unveil that CD4+ T cells engage with MHC II of macrophages to downregulate TLR pro-inflammatory signaling. We show further that the direct contact between CD4 molecule of CD4+ T cells or the ectodomain of CD4 (soluble CD4, sCD4), and MHC II of resident macrophages is necessary and sufficient to prevent TLR4 overactivation in LPS and cecal ligation puncture (CLP) sepsis. sCD4 serum concentrations increase after the onset of LPS sepsis, suggesting its compensatory inhibitive effects on hyperinflammation. sCD4 engagement enables the cytoplasmic domain of MHC II to recruit and activate STING and SHP2, which inhibits IRAK1/Erk and TRAF6/NF-κB activation required for TLR4 inflammation. Furthermore, sCD4 subverts pro-inflammatory plasma membrane anchorage of TLR4 by disruption of MHC II-TLR4 raft domains that promotes MHC II endocytosis. Finally, sCD4/MHCII reversal signaling specifically interferes with TLR4 but not TNFR hyperinflammation, and independent of the inhibitive signaling of CD40 ligand of CD4+ cells on macrophages. Therefore, a sufficient amount of soluble CD4 protein can prevent excessive inflammatory activation of macrophages via alternation of MHC II-TLR signaling complex, that might benefit for a new paradigm of preventive treatment of sepsis.

Aquaporin-4 and traumatic brain edema.

Brain edema leading to an expansion of brain volume has a crucial impact on morbidity and mortality following traumatic brain injury as it increases intracranial pressure, impairs cerebral perfusion and oxygenation, and contributes to additional ischemic injuries. Classically, two major types of traumatic brain edema exist: "vasogenic" and "cytotoxic/cellular". However, the cellular and molecular mechanisms contributing to the development/resolution of traumatic brain edema are poorly understood and no effective drugs can be used now. Aquaporin-4 (AQP4) is a water-channel protein expressed strongly in the brain, predominantly in astrocyte foot processes at the borders between the brain parenchyma and major fluid compartments, including cerebrospinal fluid and blood. This distribution suggests that AQP4 controls water fluxes into and out of the brain parenchyma. In cytotoxic edema, AQP4 deletion slows the rate of water entry into brain, whereas in vasogenic edema, AQP4 deletion reduces the rate of water outflow from brain parenchyma. AQP4 has been proposed as a novel drug target in brain edema. These findings suggest that modulation of AQP4 expression or function may be beneficial in traumatic brain edema.

Effect of Xingnaojing injection on cerebral edema and blood-brain barrier in rats following traumatic brain injury.

OBJECTIVE: To explore the effects of Xingnaojing injection on cerebral edema and blood-brain barrier (BBB) in rats following traumatic brain injury (TBI). METHODS: A total of 108 adult male Sprague-Dawley rats were used as subjects and randomly assigned to three groups: sham-operation, TBI and Xingnaojing injection groups (10 ml/kg/d, intraperitoneal injection). TBI in rats was set up by the improved device of Feeney's weight-dropping model with the impact of 600 g.cm. Brain water content and BBB permeability expressed as Evans blue content were measured at 1, 3, 5 and 7 days after surgery. RESULTS: In sham-operation group, brain water content and Evans blue content in brain tissue were 78.97%+/-1.22% and 5.13 microgram+/-0.71 microgram. Following TBI, water content in brain tissue was increased significantly at 1, 3, 5 and 7 days (83.49%+/-0.54%, 82.74%+/-0.72%, 80.22%+/-0.68%, 79.21%+/-0.60%), being significantly higher than that in sham operation group (P less than 0.05). Evans blue content was increased in TBI group (16.54 microgram+/-0.60 microgram, 14.92 microgram+/-0.71 microgram, 12.44 microgram+/-0.92 microgram, 10.14 microgram+/-0.52 microgram) as compared with sham-operation group(P less than 0.05). After treatment with Xingnaojing injection, brain water content decreased as compared with TBI group (81.91%+/-1.04%, 80.38%+/-0.72%, 79.54%+/-0.58%, 78.60%+/-0.77%, P less than 0.05). Xingnaojing injection also reduced the leakage of BBB as compared with TBI group (15.11 microgram+/-0.63 microgram, 13.62 microgram+/-0.85 microgram, 10.06microgram+/-0.67 microgram, 9.54 microgram+/-0.41 microgram, P less than 0.05). CONCLUSION: Xingnaojing injection could alleviate cerebral edema following TBI via reducing permeability of BBB.

[Protective effect of Xingnaojing and Xuesaitong injections on cerebral ischemic reperfusion injury in rats].

OBJECTIVE: To investigate the mechanism of protective effect of Xingnaojing and Xuesaitong injections on cerebral ischemic reperfusion injury in rats. METHODS: The focal cerebral ischemia & reperfusion model was established by middle cerebral artery occlusion (MCAO). A total of 152 male SD rats were randomly assigned into 19 groups: sham operated group, Xingnaojing group, Xingnaojing plus Xuesaitong group and control group according to different reperfusion durations: 2, 4, 8, 24, 48, 72 h. Each group had 8 rats. Rats in Xingnaojing group received the ip injections of Xingnaojing (1 ml x 100 (-1) x d(-1)) until an onset of ischemia; Xingnaojing plus Xuesaitong group received the ip injections of Xingnaojing (1 ml x 100 g(-1) x d(-1)) and Xuesaitong (1 ml x 100 g(-1) x d(-1)) until an onset of ischemia; In the meantime, rats in control group received the same ip dose of saline. The levels of SOD and MDA were detected. The number of apoptotic neurons was detected by terminal-deoxynucleotidyl transferase medicated nick end labeling (TUNEL). RESULTS: During ischemic reperfusion, the MDA content of brain homogenate increased while the SOD activity decreased (P < 0.05). Xingnaojing could significantly inhibit the increase of MDA after cerebral ischemic reperfusion (P < 0.05) and the decrease of SOD activity in rats. The changes of SOD and MDA were smaller in the Xingnaojing plus Xuesaitong group than those in the Xinnaojing group (P < 0.01). The number of apoptotic neurons in the Xingnaojing group was significantly lower than that in control group (P < 0.05). And the number of apoptotic neurons in the Xingnaojing plus Xuesaitong group was even lower than that in the Xingnaojing group(4,8 h: P < 0.05, 24, 48, 72 h: P < 0.01). CONCLUSION: The Xingnaojing plus Xuesaitong injection has protective function after cerebral ischemic reperfusion.

Genome-wide DNA methylation and RNA expression profiles identified RIPK3 as a differentially methylated gene in Chlamydia pneumoniae infection lung carcinoma patients in China.

Aim: To explore the relationship between Chlamydia pneumonia (Cpn) infection and lung cancer using integrative methylome and transcriptome analyses. Methods: Twelve primary lung cancer patients who were positive for Cpn and twelve patients who were negative were selected for demographic, clinicopathological, and lifestyle matching. Genomic DNA and RNA were extracted and DNA methylation and mRNA levels were detected using the Infinium Human Methylation 450 Beadchip array and mRNA + lncRNA Human Gene Expression Microarray. We identified differentially expressed methylation and genes profiles. Results: Integrative analysis revealed an inverse correlation between differentially expressed genes and DNA methylation. Cpn-related lung cancer methylated genes (target genes) were introduced into the gene ontology and KEGG, PID, BioCarta, Reactome, BioCyc and PANTHER enrichment analyses using a q-value cutoff of 0.05 to identify potentially functional methylation of abnormal genes associated with Cpn infection. Gene sets enrichment analysis was evaluated according to MsigDB. Levels of differentially expressed methylated sites were quantitatively verified. The promoter methylation sites of 62 genes were inversely related to expression levels. According to the quantitative analysis of DNA methylation, the methylation level of the RIPK3 promoter region was significantly different between Cpn-positive cancerous and adjacent tissues, but not between Cpn-negative cancerous and adjacent tissues. Conclusion:  Hypomethylation of the RIPK3 promoter region increases RIPK3 expression, leading to regulated programmed necrosis and activation of NF-κB transcription factors, which may contribute to the development and progression of Cpn-related lung cancer.

Impact of invasive fungal infection on outcomes of severe sepsis: a multicenter matched cohort study in critically ill surgical patients.

INTRODUCTION: Fungal infection is increasingly common in critical illness with severe sepsis, but the influence of invasive fungal infection (IFI) on severe sepsis is not well understood. The aim of this study was to investigate the impact that IFI has on the outcomes of critically ill surgical patients with severe sepsis in China by means of matched cohort analysis; we also evaluated the epidemiologic characteristics of IFI in this population. METHODS: Records for all admissions to 10 university hospital surgical intensive care units (ICUs) from December 2004 to November 2005 were reviewed. Patients who met criteria for severe sepsis were included. IFI was identified using established criteria based on microbiologic or histological evidence. A matched cohort study was conducted to analyze the relationship between IFI and outcomes of severe sepsis. RESULTS: A total of 318 patients with severe sepsis were enrolled during the study period, of whom 90 (28.3%) were identified as having IFI. A total of 100 strains of fungi (58% Candida albicans) were isolated from these patients. Independent risk factors for IFI in patients with severe sepsis included mechanical ventilation (>3 days), Acute Physiology and Chronic Health Evaluation score, coexisting infection with both gram-positive and gram-negative bacteria, and urethral catheterization (>3 days). Compared with the control cohort, IFI was associated with increased hospital mortality (P < 0.001), high hospital costs (P = 0.038), and prolonged stay in the ICU (P < 0.001) and hospital (P = 0.020). CONCLUSION: IFI is frequent in patients with severe sepsis in surgical ICUs and is associated with excess risk for hospital mortality, longer ICU and hospital stays, and greater consumption of medical resources.

[Protective effects of edaravone on renal ischemia-reperfusion injury in rats].

OBJECTIVE: To investigate the effect of edaravone on renal ischemia-reperfusion injury in rats. METHODS: Fifty rats were randomly divided into five groups: sham operation group (Group A), renal ischemia-reperfusion group (Group B) and edaravone treated groups (Group C1, Group C2 and Group C3 with different drug dosages). Serum maleic dialdehyde (MDA) and superoxide dismutase (SOD), renal MDA and SOD, serum creatinine (Cr), blood urea nitrogen (BUN) were measured after the rat kidney was ischemia-reperfused for 24 hours. Renal ultrastructure was observed. RESULT: Compared with Group A, serum and renal MDA, serum Cr, BUN of Group B were significant increased (P <0.01), serum and renal SOD of Group B were significant decreased (P <0.01). After edaravone treatment, serum MDA, Cr and renal MDA of Group C were lower than those in Group B (P<0.01); Serum and renal SOD of group C were higher than those in Group B (P <0.01); Compared with Group B, BUN level of Group C had no significant change (P >0.05). The renal ultrastructure was greatly injured in Group B, meanwhile it was obviously ameliorated in Group C. CONCLUSION: Edaravone has protective effects on renal ischemia-reperfusion injury in rats.

[Double filtration plasmapheresis in treatment of hyperlipidemic acute pancreatitis].

OBJECTIVE: To investigate the therapeutic effects of double filtration plasmapheresis(DFPP) in treatment of hyperlipidemic acute pancreatitis. METHODS: Nine patients with acute hyperlipidemic pancreatitis were treated with DFPP in addition to the conventional therapeutic measures. The clinical symptoms,serum levels of triglyceride (TG) and APACHE II scores were observed before and after DFPP. RESULT: After DFPP the clinical symptoms of patients were improved greatly; serum levels of TG decreased from (83.48 +/-2.54)mmol/L to (4.09 +/-0.65)mmol/L(P<0.01) and APACHE II scores decreased from 12.2 +/- 2.3 to 6.2 +/- 1.3(P <0.05). There were no significant side effects during and after DFPP. CONCLUSION: DFPP can be effectively and safely applied in patients with acute hyperlipidemic pancreatitis.

Effect of AVP on brain edema following traumatic brain injury.

OBJECTIVE: To evaluate plasma arginine vasopressin (AVP) level in patients with traumatic brain injury and investigate the role of AVP in the process of brain edema. METHODS: A total of 30 patients with traumatic brain injury were involved in our study. They were divided into two groups by Glasgow Coma Scale: severe traumatic brain injury group (STBI, GCS less than or equal to 8) and moderate traumatic brain injury group (MTBI, GCS larger than 8). Samples of venous blood were collected in the morning at rest from 15 healthy volunteers (control group)and within 24 h after traumatic brain injury from these patients for AVP determinations by radioimmunoassay. The severity and duration of the brain edema were estimated by head CT scan. RESULTS: Plasma AVP levels (ng/L) were (mean+/-SD): control, 3.06+/-1.49; MTBI, 38.12+/-7.25; and STBI, 66.61+/-17.10. The plasma level of AVP was significantly increased within 24 h after traumatic brain injury and followed by the reduction of GCS, suggesting the deterioration of cerebral injury (P less than 0.01). And the AVP level was correlated with the severity (STBI r equal to 0.919, P less than 0.01; MTBI r equal to 0.724, P less than 0.01) and the duration of brain edema (STBI r equal to 0.790, P less than 0.01; MTBI r equal to 0.712, P less than 0.01). CONCLUSIONS: The plasma AVP level is closely associated with the severity of traumatic brain injury. AVP may play an important role in pathogenesis of brain edema after traumatic brain injury.

[Effect of salvianolic acid B on neural cells damage and neurogenesis after brain ischemia-reperfusion in rats].

This study is to observe the effect of salvianolic acid B (Sal B) on neural cells damage and neurogenesis in sub-granular zone (SGZ) and sub-ventricular zone (SVZ) after brain ischemia-reperfusion (I/R) in rats. A modified middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia-reperfusion was used. The rats were divided into four groups: sham control group, ischemia-reperfusion group, Sal B 1 and 10 mg x kg(-1) groups. Sal B was consecutively administrated once a day by ip injection after MCAO. The neurogenesis in SGZ and SVZ was investigated by BrdU method 7 days after MCAO. The Nissl staining for neurons in the hippocampal CA1 and cerebral cortex was performed 14 days after MCAO. A beam-walking test was used to monitor the motor function recovery. We found that brain ischemia resulted in an increase of BrdU positive cells both in ipsilateral SGZ and SVZ at 7th day after MCAO. Sal B (10 mg x kg(-1)) significantly increased further the number of BrdU positive cells both in SGZ and SVZ (P < 0.01). Ipsilateral hippocampal neuron damage occurred and CA1 almost lost 14 days after MCAO. Sal B (10 mg x kg(-1)) obviously attenuated the neuron damage and increased the number of neuron both in ipsilateral CA1 and cerebral cortex (P < 0.01). We also observed an obvious improvement of motor function recovery when Sal B (10 mg x kg(-1)) administrated. From the results above we concluded that Sal B stimulated neurogenesis process both in SGZ and SVZ after brain ischemia, and also alleviated neural cells loss and improved motor function recovery after brain ischemia in rats.

MicroRNA-302d downregulates TGFBR2 expression and promotes hepatocellular carcinoma growth and invasion.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-associated mortality in China and the third leading cause worldwide. A number of microRNAs (miRNAs) have been implicated in cell cycle progression, growth, apoptosis, angiogenesis and metastasis in HCC. In the present study, reverse transcription-quantitative polymerase chain reaction analysis was used to detect the levels of miR-302d expression in the tissues of 30 patients with HCC. Cell cycle, growth, apoptosis and migration were analyzed using a cell counting kit, flow cytometry and a Transwell migration assay. Dual-luciferase reporter assays and western blotting were also used to analyze the expression levels of transforming growth factor beta type II receptor (TGFBR2) in HCC cells. The present study evaluated the role of miR-302d in the development and progression of HCC. Abnormally high expression of miR-302d was observed in 80% of HCC specimens. Moreover, patients with lower levels of miR-302d expression experienced a longer survival time than those with higher levels of miR-302d expression. It was demonstrated that miR-302d promoted HCC cell growth and migration, suppressed cell apoptosis and affected cell cycle distribution in vitro, and augmented tumorigenicity in vivo. Furthermore, TGFBR2, which is a tumor suppressor, was confirmed as a target of miR-302d in HCC cells. Dual-luciferase reporter assays indicated that TGFBR2 expression was negatively regulated by miR-302d. Taken together, the results of the present study suggest that miR-302d may serve as a valuable tool for predicting the prognosis of patients with HCC.

The association between human papillomavirus infection and lung cancer: a system review and meta-analysis.

To estimate the global attributable fraction of human papillomavirus (HPV) in lung cancer, we provided updated information through a system review and meta-analysis. We did a literature search on PubMed, Ovid and Web of Science to identify case-control studies and cohort studies that detected HPV in lung carcinomas. We included studies that tested 30 or more cases and were published before Feb 28, 2017. We collected information about gender, smoking status, HPV detection methods, HPV types, materials and clinical features. If it was not possible to abstract the required information directly from the papers, we contacted the authors. A meta-analysis was performed to calculate the pooled effect sizes (OR/RR) with 95% confidence intervals (CI) including subgroup analysis and meta-regression to explore sources of heterogeneity, by Stata 13.0 software. 36 case-control studies, contributing data for 6,980 cases of lung cancer and 7,474 controls from 17 countries and one cohort study with 24,162 exposed and 1,026,986 unexposed from China were included. HPV infection was associated with cancer of lung, pooled OR was 3.64 (95% CI: 2.60-5.08), calculated with the random-effects model. Pooled OR for allogeneic case-control studies, self-matched case-control studies and nested case-control studies were 6.71 (95% CI: 4.07-11.07), 2.59 (95% CI: 1.43-4.69) and 0.92 (95% CI: 0.63-1.36), respectively. Pooled OR for HPV 16 and HPV 18 infection, were 3.14 (95% CI: 2.07-4.76) and 2.25 (95% CI: 1.49-3.40), respectively. We also found that HPV infection may be associated with squamous cell carcinoma, adenocarcinoma and small cell carcinoma. There is evidence that HPV infection, especially HPV 16 and HPV 18 infection, significantly increase the risk of lung cancer. Future research needs to focus attention toward whether an HPV vaccine can effectively reduce the incidence of lung cancer.

A case-control study of the association between self-reported occupational and recreational physical activity and lung cancer.

This case-control study with a Fujian population investigated whether self-reported occupational and recreational physical activity may be associated with lung cancer.The population comprised 1622 patients with newly diagnosed primary lung cancer and 1622 age- and gender-matched healthy controls.High-intensity occupational physical activity was associated with significantly higher risk of lung cancer (OR = 1.354, 95% CI: 1.068-1.717), especially nonsmall cell lung carcinoma (OR = 1.384, 95% CI: 1.087-1.762). Moderate or low intensity recreational physical activity was associated with reduced risk of lung cancer. The protective effect of recreational physical activity was observed in current or former smokers, but not never-smokers, and in subjects with normal or high BMI, but not low BMI, as well as people without a history of chronic lung disease. The frequency of recreational physical activity was associated with a linear reduction in the risk of lung cancer (P < .001), and also specifically nonsmall cell lung cancer (P < .001).Occupational and recreational physical activity was associated with different effects on the risk of lung cancer in a Fujian population. While recreational physical activity was associated with decreased risk of lung cancer, occupational physical activity was associated with increased risk of lung cancer.

The relationship of lung cancer with menstrual and reproductive factors may be influenced by passive smoking, cooking oil fumes, and tea intake: A case-control study in Chinese women.

The aim of this study was to investigate the association of menstrual and reproductive factors with risk of lung cancer in women. Potential etiological clues related to lung cancer in women are identified to inform preventive strategies.Case-control study of 477 newly diagnosed women with lung cancer and 479 age-matched (±2 years) controls. Data on menstrual and reproductive factors and history of oral contraceptive use were obtained on personal interviews using a structured questionnaire. Risk factors were analyzed by unconditional logistic regression analysis.Maternal age ≥25 years at first birth appeared to protect against female lung cancer [odds ratios (ORs): 0.511, 95% confidence interval (CI), 0.376-0.693]. Age at menopause > 50 years and use of contraceptives was associated with an increased risk of lung cancer in women (OR: 1.471, 95% CI, 1.021-2.119 and OR: 1.844, 95% CI: 1.111-3.061, respectively). Age ≥13 years at menarche was associated with a decreased risk of lung adenocarcinoma (OR: 0.563, 95% CI, 0.317-0.997). There was significant heterogeneity in the levels of cooking oil fume (COF) exposure (Pheterogeneity = .015). Higher levels of exposure to passive smoking, COF, and lack of tea intake were associated with an increased risk of lung cancer.Menstrual and reproductive factors are considered to play a role in the development of lung cancer in women. Exposure to passive smoking, COF, and lack of tea intake appeared to significantly modify the relationship.

Phase I clinical study of personalized peptide vaccination combined with radiotherapy for advanced hepatocellular carcinoma.

AIM: To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination (PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma (HCC). METHODS: A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases (the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL. RESULTS: Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response (PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade II bone marrow suppression and the remaining patients had no significant hematological side effects. CONCLUSION: Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective.

[Protective effect of 3,4-oxo-isopropylidene-shikimic acid on vascular endothelial cell injured by hydrogen peroxide].

AIM: To study the effect of 3,4-oxo-isopropylidene-shikimic acid (ISA) on H2O2 (200 mol.L-1, 4 h) injured human umbilical vein endothelial cells (HUVEC). METHODS: Morphological change was observed under microscop. Cell viability was assessed by MTT assay. The release of intracellular lactate dehydrogenase (LDH) and NO was assessed by colorimetry. Radioimmunoassay was used to assess 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). RESULTS: Pretreatment with ISA for 6 h alleviated the morphological damage of H2O2 induced HUVECs. At the concentration of 1-100 mumol.L-1, ISA prevented the inhibitory effect on cell viability induced by H2O2 in dose-dependent manner, but increased the ratio of cell viability from 60.4% to 84.3%. ISA reduced LDH release and increased the level of NO and 6-keto-PGF1 alpha in H2O2 induced HUVECs. CONCLUSION: ISA exerted protective effect on H2O2 injured HUVEC.

[Experimental studies on the anti-thrombosis effect of 3,4-oxo-isopropylidene-shikimic acid].

AIM: To study the effect of 3,4-oxo-isopropylidene-shikimic acid (ISA) against arteriovenous shunt and middle cerebral artery thrombosis (MCAT) in rats. METHODS: Arteriovenous shunt model was adopted to measure thrombus weight; The neurologic deficit (ND) and the infarct size (IS) of the middle cerebral thrombosis (MCAT) model induced by FeCl3 were observed; The effect of ISA on platelet aggregation rate of rat and rabbit by giving ISA in vivo and in vitro was studied. RESULTS: ISA 25, 50, 100 and 200 mg.kg-1 ig was shown to reduced the weight of thrombus in arteriovenous shunt model; ISA 50, 100 and 200 mg.kg-1 ig for 2 times in 24 hours, attenuated the ND of rats subjected to MCAT; ISA 100 and 200 mg.kg-1 reduced IS of rats after MCAT by 27.8% and 31.6%, respectively; ISA 50, 100 and 200 mg.kg-1 ig inhibited platelet aggregation of normal rats; ISA 10(-3)-10(-5) mol.L-1, inhibited rabbit platelet aggregation in vitro. CONCLUSION: ISA inhibited thrombosis by anti-platelet-aggregation.