Using machine learning for mortality prediction and risk stratification in atezolizumab-treated cancer patients: Integrative analysis of eight clinical trials.

BACKGROUND: Few models exist to predict mortality in cancer patients receiving immunotherapy. Our aim was to build a machine learning-based risk stratification model for predicting mortality in atezolizumab-treated cancer patients. METHODS: Data from 2538 patients in eight atezolizumab-treated cancer clinical trials across three cancer types (non-small-cell lung cancer, bladder transitional cell carcinoma, and renal cell carcinoma) were included. The whole cohort was randomly split into development and validation cohorts in a 7:3 ratio. Machine-learning algorithms (extreme gradient boosting, random forest, logistic regression with lasso regularization, support vector machine, and K-nearest neighbor) were applied to develop prediction models. Model performance was mainly assessed by area under the receiver operating characteristic curve (AUC) value, calibration plot, and decision curve analysis. The probability of death risk was then stratified. RESULTS: One thousand and three hundred and seventy-nine (54.33%) patients died. The random forest (RF) model was overall the best in terms of predictive performance, with the AUC of 0.844 (95% confidence interval [CI]: 0.826-0.862) in the development cohort and 0.786 (95% CI: 0.754-0.818) in the validation cohort for predicting mortality. Twelve baseline variables contributing to mortality prediction in the RF model were C-reactive protein, PD-L1 level, cancer type, prior liver metastasis, derived neutrophil-to-lymphocyte ratio, alkaline phosphatase, albumin, hemoglobin, white blood cell count, number of metastatic sites, pulse rate, and Eastern Cooperative Oncology Group (ECOG) performance status. A total of 1782 (70.2%) patients were separated into the high-risk and 756 (29.8%) low-risk groups. Patients in the high-risk group were significantly more likely to die, experience disease progression, discontinue study, and discontinue treatment than patients in the low-risk group (all p values < 0.001). Risk groups were not associated with immune-related adverse events and grades 3-5 treatment-related adverse events (all p values > 0.05). CONCLUSION: RF model has good performance in mortality prediction and risk stratification for cancer patients receiving atezolizumab monotherapy.

Promotion of Lung Cancer Metastasis by SIRT2-Mediated Extracellular Protein Deacetylation.

Acetylation of extracellular proteins has been observed in many independent studies where particular attention has been given to the dynamic change of the microenvironmental protein post-translational modifications. While extracellular proteins can be acetylated within the cells prior to their micro-environmental distribution, their deacetylation in a tumor microenvironment remains elusive. Here it is described that multiple acetyl-vWA domain-carrying proteins including integrin ß3 (ITGB3) and collagen 6A (COL6A) are deacetylated by Sirtuin family member SIRT2 in extracellular space. SIRT2 is secreted by macrophages following toll-like receptor (TLR) family member TLR4 or TLR2 activation. TLR-activated SIRT2 undergoes autophagosome translocation. TNF receptor associated factor 6 (TRAF6)-mediated autophagy flux in response to TLR2/4 activation can then pump SIRT2 into the microenvironment to function as extracellular SIRT2 (eSIRT2). In the extracellular space, eSIRT2 deacetylates ITGB3 on aK416 involved in cell attachment and migration, leading to a promotion of cancer cell metastasis. In lung cancer patients, significantly increased serum eSIRT2 level correlates with dramatically decreased ITGB3-K416 acetylation in cancer cells. Thus, the extracellular space is a subcellular organelle-like arena where eSIRT2 promotes cancer cell metastasis via catalyzing extracellular protein deacetylation.

Determination of deuterium incorporation of new drug donafenib tosilate by two methods of LC-MS with natural isotope abundance correction and 1H NMR relative quantitative method / 药学学报

An LC-MS method with natural isotope abundance correction and a 1H NMR relative quantitative method were established to determine the deuterium incorporation of donafenib tosilate, a new deuterated drug molecule. First, the peak areas of isotopic impurities (non-deuterated and incompletely deuterated impurities) and deuterated drug were recorded through the single ion monitoring (SIM) mode of the established LC-MS method and then corrected in terms of the natural isotope abundance offered by ChemDraw soft, removing the nature isotope interference from 13C, 37Cl, etc. The corrected areas were subsequently used to calculate mol% of isotopologues (D0, D1, D2, D3) and Atom% D, namely, deuterium incorporation. In addition, a 1H qNMR experiment was conducted with the aromatic proton at δ 8.63 and the residual proton of isotopic impurities at δ 2.79 as quantitative peaks. The mixture of DMSO-d6 and D2O (10∶1) was employed as the solvent to change the spin-coupling between the residual proton and active hydrogen so that the residual proton could be measured as the single peak, and the sensitivity was greatly improved. The acquisition parameters were also optimized, and Atom% 1H and the deuterium incorporation were then calculated. The two methods were applied to samples of three commercial batches, and the testing results were almost consistent. Both methods proved accurate, sensitive, fast and independent of standard substances and accurate weighing, which could be applied to the determination of the deuterium incorporation of donafenib tosilate and provide a reference for other deuterated drugs.

Neuroprotective Effect and Mechanisms of Notoginsenosides：A Review / 中国实验方剂学杂志

Notoginsenosides， the saponins extracted from Panax notoginseng， have many pharmacological effects， such as anti-inflammation， anti-oxidation， anti-tumor， nervous system and cardiovascular system protection， microcirculation improvement and calcium overload inhibition. At present， notoginsenosides are widely used clinically for treating many diseases with good efficacy， especially for nervous system diseases such as stroke， stroke sequelae and Alzheimer's disease. In recent years， the mechanism underlying their neuroprotective effect has been continuously explored. To advance the applied research on notoginsenosides in the prevention and treatment of central nervous system diseases， this paper， combined with the latest reports， summarizes their neuroprotective effect and mechanisms in terms of regulating voltage-gated ion channels， protecting nerve cells and neurovascular unit， inhibiting oxidative stress and inflammatory reaction， promoting angiogenesis and reducing excitatory neurotoxicity. Although the protective mechanism of notoginsenosides for the nervous system mainly involves the above several aspects， some of them still remain to be fully elucidated， which necessitates the further exploration of neuroprotective effect of notoginsenosides with molecular biology， metabolomics， proteomics and other technologies.

Prostate Cancer Risk and Prognostic Influence Among Users of 5-Alpha-Reductase Inhibitors and Alpha-Blockers: A Systematic Review and Meta-Analysis.

We systematically assessed the effect of 5-alpha-reductase inhibitors (5-ARIs) and/or alpha-blockers use on prostate cancer (CaP) incidence and outcomes, including CaP pathologic progression, CaP-specific mortality, and all-cause mortality. 5-ARIs but not alpha-blockers decreased risk of overall CaP, low grade CaP (Gleason < 7), and delayed CaP pathologic progression. Both 5-ARIs and alpha-blockers had no significant impact on risk of high grade CaP (Gleason ≥ 7), CaP-specific mortality, or all-cause mortality. Our result suggested that finasteride should be given for at least 4 years if used for preventing CaP.

Hematopoietic and lymphatic cancers in patients with periodontitis: a systematic review and meta-analysis

BACKGROUND: Numerous studies have explored the correlation of periodontal disease (PD) with risk of hematopoi-etic and lymphatic cancers, but the findings were inconsistent. Therefore, we did a meta-analysis to ascertain the correlation of PD with risk of incident hematopoietic and lymphatic cancers. MATERIAL AND METHODS: The authors searched relevant studies in databases (PubMed, Web of Science, and MED-LINE). The summary relative risk (RR) along with 95% confidence interval (CI) was calculated by use of random or fixed effects models. RESULTS: Six studies were included in qualitative synthesis. The pooled analysis revealed that PD was significantly associated with an increased risk of hematopoietic and lymphatic cancers (RR = 1.17; 95% CI = 1.07-1.27; P = 0). Stratified analysis showed the association of PD with hematopoietic and lymphatic cancers remained significant in the never smokers (RR = 1.28; 95% CI = 1.07-1.54; P = 0.007), and in the American population (RR = 1.17; 95% CI = 1.05-1.30; P = 0.003), respectively. CONCLUSION: Never smokers population and the American population with PD have a higher risk of developing hematopoietic and lymphatic cancers. PD might be considered as a risk factor for hematopoietic and lymphatic cancers

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Detoxification mechanism of Aconiti Lateralis Radix Praeparata combined with dried Rehmanniae Radix based on metabolic enzymes in liver / 中国中药杂志

The enzymes CYP1 A2 and CYP3 A4 were measured by building a "Cocktail" probe drug and the incubation system of liver microsomes. The compatibility of Aconiti Lateralis Radix Praeparata combined with dried Rehmanniae Radix on CYP450 enzyme protein and gene expression was explored from the level of protein and molecular biology. It explored the molecular mechanism of compatibility detoxication of Aconiti Lateralis Radix Praeparata to provide scientific support for clinical safe and effective application of Aconiti Lateralis Radix Praeparata. The CYP450 enzyme activity was determined by using "Cocktail" probe drugs. The content of CYP450 enzyme was measured by CO reduction of differential spectrum method. The mRNA expression of CYP1 A2 and CYP3 A4 enzyme was detected by RT-PCR technology. Compared with the blank group, the CYP1 A2 and CYP3 A4 enzyme activity and mRNA expression were increased in the dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata group with significant differences(P<0.05), while the CYP3 A4 enzyme activity and mRNA expression were no influence in the Aconiti Lateralis Radix Praeparata group. The CYP3 A4 enzyme activity and mRNA expression were increased in the dried Rehmanniae Radix and the dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata group, and there were significant differences(P<0.05). The content of CYP450 enzyme was decreased in the Aconiti Lateralis Radix Praeparata group, contributed to extremely significant difference(P<0.01). The content of CYP450 enzyme was increased in the dried Rehmanniae Radix and the dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata group, and there were significant differences(P<0.05). The CYP1 A2 and CYP3 A4 enzyme activity and gene expression were enhanced after dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata. The metabolism of toxic ingredients of Aconiti Lateralis Radix Praeparata was accelerated to reach an effect of detoxication. The detoxication mechanism of compatibility of Aconiti Lateralis Radix Praeparata was verified from the viewpoint of liver metabolic enzymes.

A nomogram for predicting survival and retroperitoneal lymph node dissection treatment in patients with resected testicular germ cell tumors.

BACKGROUND AND OBJECTIVES: To build nomogram incorporating potential prognostic factors for predicting survival outcomes of testicular germ cell tumors (TGCT) patients after resection of the primary tumor. METHODS: Data of TGCT patients from the Surveillance, Epidemiology, and End Results database (2010-2016) who underwent resection of the primary tumor were collected. Overall survival (OS) and cancer-specific survival (CSS) were analyzed by using Cox regression models, nomogram, Kaplan-Meier method, and log-rank test. RESULTS: We identified 7272 TGCT patients. Age at diagnosis, histology, tumor size, American Joint Committee on Cancer (AJCC) staging system, and number of metastases sites were independent prognostic factors and were integrated into nomograms. The nomograms had higher C-indexes for both OS and CSS compared with the AJCC 7th staging system (0.881 vs 0.831 and 0.895 vs 0.856, respectively). Moreover, the new stratification of risk groups based on the nomograms showed a more significant distinction between Kaplan-Meier curves for survival outcomes than the AJCC staging system. Retroperitoneal lymph node dissection was associated with statistically improved survival probability in the nomogram middle-risk group in resected TGCT patients. CONCLUSION: The novel nomogram-based staging system could provide satisfactory risk stratification and survival prediction ability beyond traditional AJCC staging systems.

Effect of phosphodiesterase type 5 inhibitors on prostate cancer risk and biochemical recurrence after prostate cancer treatment: A systematic review and meta-analysis.

Recent studies have examined the impact of phosphodiesterase type 5 inhibitors (PDE5-Is) use on the risk of prostate cancer, and biochemical recurrence (BCR) in prostate cancer patients, but the results were inconsistent. A meta-analysis was conducted to assess the associations with all published studies. Databases (PubMed, Web of Science and MEDLINE) were retrieved to identify relevant studies which explored the impact of PDE5-Is use on the risk of prostate cancer, and BCR in prostate cancer patients. The summary results along with 95% confidence intervals (CIs) were calculated. Nine articles were eligible for the inclusion criteria. The pooled analysis showed that PDE5-Is use was not related to the increased risk of prostate cancer (odds ratio (OR), 0.71; 95% CI, 0.40-1.29). Moreover, PDE5-Is use was not linked to BCR risk in prostate cancer patients with erectile dysfunction (ED) following radical prostatectomy or radiation therapy (relative risk (RR), 1.09; 95% CI, 0.89-1.34). The heterogeneity test suggested moderate heterogeneity across studies. PDE5-Is use does not influence the risk of prostate cancer, and BCR in prostate cancer patients. More well-designed studies are warranted to confirm the findings of our analyses.

Effects of intravenous lidocaine and dexmedetomidine on cough during extubation after endoscopic thyroidectomy / 实用医学杂志

Objective Comparation of the effects of intravenous lidocaine and dexmedetomidine on coughing during extubation after endoscopic thyroidectomy. Methods 60 patients who underwent endoscopic thyroidectomy were randomly divided into group L, group D and group C, each group included 20 cases. Group L were given a loading lidocaine 1.5 mg/kg over 10 minutes before anesthesia induction, followed by a continuous intravenous lidocaine 1.5 mg/ (kg·h) until 30 min before the end of surgery. Group D were given a loading dexmedetomidine 0.5μg/kg over 10 minutes before anesthesia induction, followed by a continuous intravenous dexmedetomidine 0.4 μg/ (kg · h) until 30 min before the end of surgery. Group C were given intravenous infusion of equal volume normal saline. The incidence and severity of coughing were recorded within 2 minutes after extubation. Hemodynamic variables were measured at T0 (before anaesthesia induction) , T1 (immediately after extubation) , and T2 (5 min after extubation). The volume of drainage was recorded within 24 hours after surgery. Results The incidence and grade of cough were significantly lower in group L and group D than in group C (P < 0.05). Compared with group L and group D, MAP and HR were significantly increased in group C at T1 and T2 (P < 0.05). Compared with group C, the volume of drainage was significantly reduced in group L and group D within 24 hours after surgery (P < 0.05).Conclusion Intravenous lidocaine and dexmedetomidine can effectively inhibit coughing during extubation period after endoscopic thyroidectomy, and there is no significant difference between the two treatments.

Effect of different pressure CO2pneumoperitoneum on postoperative gastroeuteric function in female pa-tients undergoing gynecological laparoscopic surgery / 临床麻醉学杂志

Objective To investigate the effect of different pressure CO2pneumoperitoneum on postoperative gastroeuteric function in female patients undergoing gynecological laparoscopic surgery. Methods A total of 120 female patients,aged 30-60 years,ASA physical status Ⅰ or Ⅱ,scheduled for elective gynecological laparoscopic surgery were randomly into three groups (n=40 in each).The pressure of CO2pneumoperitoneum were set at 6-8,9-11 and 12-14 mm Hg in group L,group M and group H,respectively.All patients were detected on an empty stomach of serum concentrations of D-lactic acid 6 hours before operation and after opration.In addition,pH,PaCO2and PaO2were recor-ded before anesthesia (T1),before pneumoperitoneum (T2),1 hour after pneumoperitoneum (T3)2 hours after pneumoperitoneum (T4)and 1 hour (T5)after stopping pneumoperitoneum.The time of pneumoperitoneum,the time of first flatus,intake and defecation,length of primary hospital stays after operation were recorded.Results Compared with 6 hours before operation,the serum concen-trations of D-lactic acid were obviously increased at postoperative 6 hours in all groups (P<0.05). Compared with group L,the serum concentrations of D-lactic acid at 6 hours after operation were ob-viously increased in group M and group H (P<0.05).PaO2in three groups was not different at T1-T5.Compared with group L,pH at T3,T4was significantly decreased in group M and group H (P<0.05).Compared with group L,PaCO2was significantly increased at T3-T5in group M and group H (P<0.05 ).Compared with group L,the time of first flatus,intake and defecation,length of primary hospital stays after operation were obviously delayed in group M and group H(P<0.05). Conclusion The low pressure of CO2pneumoperitoneum can reduce the damage of CO2pneumoper-itoneum on postoperative gastroeuteric function and avail the recovery of parents’postoperative gas-troeutericfunction in female patients undergoing gynecological laparoscopic surgery.

Safety and efficacy of Ofatumumab in chronic lymphocytic leukemia: a systematic review and meta-analysis.

OBJECTIVES: Increasing numbers of clinical studies have been carried out to investigate the therapeutic effect of Ofatumumab for patients with chronic lymphocytic leukemia (CLL) but no studies have yet reported a pooled estimate of the treatment effect. We performed a meta-analysis of evidence from 13 clinical trials to assess effectiveness and safety of Ofatumumab-based therapy in patients with CLL. METHODS: Relevant publications from PubMed, Web of Science, Embase, and ClinicalTrials.gov were searched. The primary efficacy outcomes were progression-free survival (PFS) and overall survival (OS). The second endpoint was the adverse events. RESULTS: The pooled efficacy analysis showed that there were no significant difference in PFS [hazard ratios (HR) = 0.88, 95% confidence interval (CI) = 0.47-1.63, p = 0.677, I2 = 94.9%] and OS (HR = 0.97, 95% CI = 0.70-1.36, p = 0.878, I2 = 58.7%) between Ofatumumab-based therapy and non-Ofatumumab therapy. The pooled toxicity analysis showed that Ofatumumab-based therapy was associated with an increased risk of infusion-related reaction but decreased risk of thrombocytopenia and anemia compared with non-Ofatumumab-based therapy. Moreover, infections, and infusion-related reaction occurred more frequently in participants with single Ofatumumab studies. DISCUSSION: Our analysis showed PFS was statistically significantly improved with Ofatumumab-based treatments (including Ofatumumab alone, Ofatumumab plus chemotherapy) for CLL compared with observation or chemotherapy-based regimen groups. Ofatumumab had no statistically significant improvement on the OS of patients with CLL. The Ofatumumab-based therapy could generally decrease the risk of adverse effects except infusion-related reaction and infections.

Chinese medicine as complementary therapy for female infertility.

Chinese medicine (CM) has been used in clinical treatment for thousands of years in China, Japan, Korea, and other countries. CM is at present attracting many attentions around the world for reproductive health care and disease prevention, including treatment of female infertility. This review focuses on the CM treatment for female infertility patients, and supplies a summary on the efficacy, safety, and mechanism of some Chinese herbal medicines, herbal medicine-derived active compounds, and acupuncture. A large number of researches have reported that CM could alleviate or even cure female infertility by regulating hormone, improving reproductive outcome of in vivo fertilization, affecting embryonic implantation, curing polycystic ovarian syndrome, endometriosis, pelvic inflammatory disease, relieving mental stress, and regulating immune system. Meanwhile, a few studies claimed that there was little adverse reaction of CM in randomized controlled trials. However, up to present there is a lack of adequate evidences with molecular mechanistic researches and randomized controlled trials to prove the CM as an effective and safe treatment for infertility. Thus, utility of CM as a complementary medicine will be a feasible method to improve the outcome of female infertility treatment.

Effect of different pressure CO2 pneumoperitoneum on early postoperative cognitive function in female ;patients undergoing gynecological laparoscopic surgery / 临床麻醉学杂志

Objective To investigate the effect of different pressure CO 2 pneumoperitoneum on early postoperative cognitive function in female patients undergoing gynecological laparoscopic sur-gery.Methods Ninety female patients,aged 40-60 years,ASA physical status Ⅰor Ⅱ,scheduled for elective gynecological laparoscopic surgery,were randomly divided into three groups (n = 30). The pressure of CO 2 pneumoperitoneum were set at 6-8,9-1 1 and 12-14 mm Hg in groups L,M and H,respectively.All of the patients were tested by the neuropsychology and questionnaire review to estimate whether the patient got cognitive decline at 24 h before the operation.The venous blood sam-ples 10 minutes before anesthesia (T1 ),at the end of surgery (T2 ),6 hours after surgery (T3 ),24 hours after surgery (T4 )and 72 hours after surgery (T5 )were collected for determination of serum concentrations of NSE and S100βprotein.The pH,PaCO 2 and PaO 2 were recorded before anesthesia (Ta ),before pneumoperitoneum (Tb ),1 hour after pneumoperitoneum (Tc ),2 hours after pneumo-peritoneum (Td )and 1 hour after stopping pneumoperitoneum (Te ).Results Scores of these tests in three groups were not different and there was no patient with cognitive decline after surgery.Com-pared with group H,the concentration of NSE at T2 and T3 was significantly lower in groups L and M (P <0.05).Compared with group H,the concentration of S100βprotein at T2 was significantly lower in groups L and M (P <0.05).Compared with group L,pH at Tc and Td was significantly decreased in groups M and H (P <0.05).Compared with group L,PaCO 2 was significantly increased at Tc-Te in groups M and H (P <0.05).Conclusion Different pressure of CO 2 pneumoperitoneum has no ob-vious effect on the early cognitive function,but low (6-8 mm Hg)CO 2 pneumoperitoneum can reduce the release of NSE and S100βprotein after operation.

Controversies regarding and perspectives on clinical utility of biomarkers in hepatocellular carcinoma.

The prevalence of hepatocellular carcinoma (HCC) worldwide parallels that of persistent infection with the hepatitis B virus (HBV) and/or hepatitis C virus (HCV). According to recommendations by the World Health Organization guidelines for HBV/HCV, alpha-fetoprotein (AFP) testing and abdominal ultrasound should be performed in routine surveillance of HCC every 6 mo for high-risk patients. These examinations have also been recommended worldwide by many other HCC guidelines over the past few decades. In recent years, however, the role of AFP in HCC surveillance and diagnosis has diminished due to advances in imaging modalities. AFP was excluded from the surveillance and/or diagnostic criteria in the HCC guidelines published by the American Association for the Study of Liver Diseases in 2010, the European Association for the Study of the Liver in 2012, and the National Comprehensive Cancer Network in 2014. Other biomarkers, including the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), des-γ-carboxyprothrombin, Dickkopf-1, midkine, and microRNA, are being studied in this regard. Furthermore, increasing attention has focused on the clinical utility of biomarkers as pre-treatment predictors for tumor recurrence and as post-treatment monitors. Serum and tissue-based biomarkers and genomics may aid in the diagnosis of HCC, determination of patient prognosis, and selection of appropriate treatment. However, further studies are needed to better characterize the accuracy and potential role of these approaches in clinical practice.

Sorafenib-based combined molecule targeting in treatment of hepatocellular carcinoma.

Sorafenib is the only and standard systematic chemotherapy drug for treatment of advanced hepatocellular carcinoma (HCC) at the current stage. Although sorafenib showed survival benefits in large randomized phase III studies, its clinical benefits remain modest and most often consist of temporary tumor stabilization, indicating that more effective first-line treatment regimens or second-line salvage therapies are required. The molecular pathogenesis of HCC is very complex, involving hyperactivated signal transduction pathways such as RAS/RAF/MEK/ERK and PI3K/AKT/mTOR and aberrant expression of molecules such as receptor tyrosine kinases and histone deacetylases. Simultaneous or sequential abrogation of these critical pathways or the functions of these key molecules involved in angiogenesis, proliferation, and apoptosis may yield major improvements in the management of HCC. In this review, we summarize the emerging sorafenib-based combined molecule targeting for HCC treatment and analyze the rationales of these combinations.

Effect of different pressure CO2 pneumoperitoneum on function of liver and kidney in patients undergoing laparoscopic gastrectomy / 临床麻醉学杂志

Objective To investigate the effect of different pressure CO2 pneumoperitoneum on function of liver and kidney in patients undergoing laparoscopic gastrectomy.Methods A total of sixty pa-tients,aged 40-65 years,scheduled for elective laparoscopic gastrectomy were randomly divided into three groups (n=20).The pressures of CO2 pneumoperitoneum were set at 6-8,9-11 and 12-14 mm Hg in group L,group M and group H respectively.The venous blood samples before pneumoperitoneum (T1 ),1 hour after pneumoperitoneum(T2 ),2 hour after pneumoperitoneum (T3 ),1 hour(T4 )and 24 hours(T5 )after stopping pneumoperitoneum were collected for determination of serum concentrations of NAG,Cys-C, ALT,AST,Cr,BUN and the amount of urine.pH,PaCO2 ,PaO2 were recorded at T1-T4 .Results ALT, AST,Cr and BUN were not different at T1-T5 in the three groups.Compared with group L,the concentra-tion of NAG and Cys-C at T2-T5 were significantly higher in the group M and H (P <0.05).Compared with group L,the amount of urine at T2-T5 was significantly lower in the group M and H (P <0.05 ), PaCO2 was significantly increased in the group H and M at T2-T4 (P <0.05).Conclusion The pressure of 6-8 mm Hg CO2 pneumoperitoneum can alleviate the damage of function of liver and kidney in patients un-dergoing laparoscopic gastrectomy.

Downregulation of p38 MAPK involved in inhibition of LDL-induced proliferation of mesangial cells and matrix by curcumin.

Curcumin, as a main pharmacological component in the traditional Chinese medicine-turmeric, has shown anti-inflammatory, anti-oxidation, anti-tumor and anti-fibrotic effects. This study aimed to investigate the possible underlying signaling pathway which was involved in the inhibition of LDL-induced proliferation of mesangial cells and matrix by curcumin. Rat mesangial cells in vitro were incubated with low-density lipoprotein (LDL) and different concentrations of curcumin (0, 6.25, 12.5, 25.0 µmol/L) or p38 MAPK inhibitor, SB203580 (10 µmol/L). Under LDL incubation, mesangial cells proliferated, the expression of MMP-2 mRNA and protein was decreased, the expression of COX-2 mRNA and protein was increased, reactive oxygen species (ROS) generation was increased and p38 MAPK was activated significantly (P<0.05). When LDL-induced cells were treated with curcumin in the concentration of 12.5 or 25.0 µmol/L, LDL-induced proliferation of mesangial cells was suppressed, the expression of MMP-2 mRNA and protein increased, the expression of COX-2 mRNA and protein downregulated, the production of ROS inhibited and p38 MAPK inactivated (P<0.05). In conclusion, curcumin can inhibit the LDL-induced proliferation of mesangial cells and up-regulate the expression of MMP-2, which may be related with the inhibitory effect of curcumin on COX-2 expression, ROS production and p38 MAPK.

Pharmacokinetic interaction between scutellarin and valsartan in rats / 药学学报

Scutellarin is the main effective constituent of breviscapine, a flavonoid mixture isolated from the dried whole plant of Erigeron breviscapus (Vant.) Hand-Mazz, and valsartan is used as an antihypertensive drug. These two drugs have already been clinically used together to treat diabetic nephropathy (DN) in China, and the combined medications showed some enhanced protection against DN. The aim of this study is to investigate the potential pharmacokinetic interaction between scutellarin and valsartan in rats. Breviscapine injection (20 mg x kg(-1), i.v.) and valsartan (15 mg x kg-, i.g.), either alone or together were given to 18 male Sprague-Dawley rats. Concentrations of scutellarin and valsartan were quantified by HPLC, and pharmacokinetic parameters were calculated by non-compartmental methods. We found that the pharmacokinetic parameters of scutellarin altered significantly after co-administration of oral valsartan. The plasma clearance (CL(p)) and the bile clearance (CL(b)) of scutellarin were reduced significantly in the presence of valsartan. After oral administration of valsartan with or without intravenous scutellarin, however, the pharmacokinetic parameters of valsartan were comparable. In conclusion, our data suggests that the concurrent use of valsartan reduces the biliary excretion of scutellarin, and this may be due to the inhibitory effect of valsartan on the biliary excretion of scutellarin mediated by Mrp2 (Multidrug resistance-associated protein 2).

Epidemic characteristics of hand, foot, and mouth disease in Shanghai from 2009 to 2010: Enterovirus 71 subgenotype C4 as the primary causative agent and a high incidence of mixed infections with coxsackievirus A16.

BACKGROUND: Enterovirus 71 (EV71) has been the main causative agent of hand, foot, and mouth disease (HFMD) outbreaks in recent years. A significant increase in the number of HFMD cases in China over the last 3 y has made the public prevention and therapy of this disease a critical issue. METHODS: A total of 3208 HFMD patients in Shanghai during the period 2009 to 2010 were analyzed; 437 clinical specimens were collected for the determination of causative pathogens. Eight of the isolated EV71 strains were sequenced and phylogenetically analyzed. RESULTS: The widespread outbreak of HFMD in Shanghai was caused predominantly by EV71 (86.5%), and in part by coxsackievirus A16 (CA16) (6.9%). The high incidence of mixed infections with EV71 and CA16 (17.6% of the total CA16-infected cases) has never before been observed in China. Most HFMD patients (76.9%) were aged 1-4 y. Boys showed a higher HFMD prevalence rate (65.3%) than girls (34.7%). Phylogenetic analysis on the basis of the VP1 gene and the complete genome sequences revealed that the EV71 strains that circulated in Shanghai belonged to the C4 subgenotype. CONCLUSIONS: EV71 subgenotype C4 was the major causative agent of the HFMD outbreak in Shanghai. A high incidence of mixed infections with EV71 and CA16 was also observed.