Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Objective To investigate the genetic polymorphisms of Plasmodium falciparum multidrug resistance protein 1 (PfMDR1), chloroquine resistance transporter (PfCRT) and Kelch 13 (PfK13) genes in Bioko Island, Equatorial Guinea, so as to provide insights into the development of the malaria control strategy in local areas. Methods A total of 85 peripheral blood samples were collected from patients with Plasmodium falciparum infections in Bioko Island, Equatorial Guinea in 2018 and 2019, and genomic DNA was extracted. The PfMDR1, PfCRT and PfK13 genes were amplified using a nested PCR assay. The amplification products were sequenced, and the gene sequences were aligned. Results There were no mutations associated with artemisinin resistance in PfK13 gene in Bioko Island, Equatorial Guinea, while drug-resistant mutations were detected in PfMDR1 and PfCRT genes, and the proportions of PfMDR1_N86Y, PfMDR1_Y184F and PfCRT_K76T mutations were 35.29% (30/85), 72.94% (62/85) and 24.71% (21/85), respectively. Conclusion There are mutations in PfMDR1, PfCRT and PfK13 genes in P. falciparum isolates from Bioko Island, Equatorial Guinea.

With the growth of number of Chinese patent medicines and clinical use, the rational use of Chinese medicine is becoming more and more serious. Due to the complexity of Chinese medicine theory and the uncertainty of clinical application, the prescription review of Chinese patent medicine always relied on experience in their respective, leading to the uncontrolled of clinical rational use. According to the traditional Chinese medicine (TCM) theory and characteristics of the unique clinical therapeutics, based on the practice experience and expertise comments, our paper formed the expert consensus on the prescription review of Chinese traditional patent medicine for promoting the rational use of drugs in Beijing. The objective, methods and key points of prescription review of Chinese patent medicine, were included in this expert consensus, in order to regulate the behavior of prescription and promote rational drug use.

Objective To explore the clinical effect of non-invasive positive pressure ventilation(NPPV)for treatment of acute left heart failure after mitral valve replacement. Methods Sixty patients with acute left heart failure after mitral valve replacement in Xinxiang Central Hospital from April 2009 to August 2017 were selected. The patients were divided into control group and NPPV group,with 30 patients in each group. The patients in the control group were treated with double oxygen ab-sorption (mask and nasal catheter),strong heart,diuresis and dilated blood vessels. Based on the treatment of control group, the patients in NPPV group were treated with NPPV therapy. The plasma N-terminal pro-B-type natriuretic peptide(NT-proB-NP)level of patients in the two groups was monitored by rapid determination of immunofluorescence before treatment and 6,24 hours after treatment. The respiratory frequency,blood oxygen saturation,heart rate and oxygen partial pressure monitoring of patients in the two groups was monitored before treatment and 2,6 and 24 hours after treatment. Results The total effective rate of patients in the control group and NPPV group was 92. 4％(26 / 28)and 96. 6％(28 / 29)respectively;there was no sig-nificant difference in the total effective rate between the two groups(χ2 = 1. 25,P > 0. 05). There was no significant difference in the plasma NT-proBNP level between the two groups before treatment (P > 0. 05);the level of NT-proBNP at 6,24 h after treatment was significantly lower than that before treatment in the two groups (P < 0. 05);the level of NT-proBNP of patients in the NPPV group was significantly lower than that in the control group at 6,24 h after treatment (P < 0. 05). There was no significant difference in the respiratory frequency,blood oxygen saturation,heart rate and oxygen partial pressure between the two groups before treatment(P > 0. 05). Compared with before treatment,the respiratory frequency and heart rate of patients were decreased and the blood oxygen saturation,oxygen partial pressure were increased at 2,6,24 h after treatment in the two groups (P < 0. 05). There was no significant difference in the oxygen partial pressure between the two groups at 2 h after treat-ment(P > 0. 05);the oxygen partial pressure of patients in the NPPV group was significantly higher than that in the control group at 6,24 h after treatment(P < 0. 05);there was no significant difference in the respiratory frequency,blood oxygen satu-ration and heart rate between the two groups at each time piont after treatment(P > 0. 05). Conclusion NPPV is an effective treatment for acute left heart failure after mitral valve replacement.

Objective:To investigate the effect of PTEN on proliferation of cardiac fibroblasts and its mechanism. Methods:Stimulation of cardiac fibroblasts by high glucose, the levels of PTEN in cells were detected by qRT-PCR and Western blot. Cell transfection of PTEN over expression vector,the levels of PTEN in transfected cells were detected by qRT-PCR and Western blot. High glucose stimulated transfection of PTEN overexpression vector into cardiac fibroblasts,cell proliferation was detected by MTT,the levels of p-STAT3 and STAT3 in cells were detected by Western blot,STAT3 pathway blocker AG490 was added into the cell culture medium to treat the cells, cell proliferation was detected by MTT, the levels of p-STAT3 and STAT3 in cells were detected by Western blot. Results:The levels of PTEN mRNA and protein in cardiac fibroblasts after high glucose treatment were significantly lower than those in normal culture ( P＜0. 05 ) . The expression of PTEN mRNA and protein in transfected PTEN overexpressing cells was significantly higher than that in non transfected cells( P＜0. 05) . The cell proliferation activity and p-STAT3 level were significantly higher than those of normal cells after high glucose(P＜0. 05). The expression of PTEN was increased after high glucose induction,the cell proliferation activity and p-STAT3 level were decreased, the proliferation of the cells treated with AG490 decreased further. Conclusion:PTEN slows down the proliferation of cardiac fibroblasts induced by high glucose by inhibiting STAT3 signaling pathway.

AIM To investigate the effect and mechanism of methanolic extract of Eupatorium (MEOE) to model rats with chronic soft tissue injury.METHODS The model rats were established by mechanical injury and a subsequent two-week normal feeding for respective administration of high,medium and small dosage of MEOE once a day successively for 14 days.An array of indices,the level of superoxide dismutase (SOD),malondialdehyde (MDA),prostaglandin E2 (PGE2),nitric oxide (NO),interleukin-6 (IL-6) and histamine,the expression of tumor necrosis factor-alpha (TNF-α),nitric oxide (NO) and Collagen-Ⅰ/Ⅲ,and the activity of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were measured to analyze the effect of MEOE to model rats with chronic muscle injury.RESULTS MEOE resulted in apparent reduction of contents of MDA,PGE2 and NO,and the levels of TNF-α and IL-6 in muscular tissue (P ＜ 0.05),significantly increased of the SOD in muscular tissue (P ＜ 0.01),a remarkably inhibited expression of the tissue Collagen-Ⅰ/Ⅲ protein (P ＜ 0.01),and significantly improved activity of tissue VEGF and bFGF (P ＜ 0.01).CONCLUSION The certain therapeutic effects of MEOE to rats with chronic muscle injury may correlate with its influence to the levels of inflammatory factors inhibition,the oxidative stress relief,the overexpression of collagen-Ⅰ/Ⅲ inhibition,the VEGF and bFGF activity improvement,and the time spare from the repairing.

This paper discusses variations of laparoscopic transgastric cystogastrostomy in management of retrogastric pancreatic pseudocysts for 8 patients with symptom or pseudocysts (larger than 6 cm) companied with clinical manifestations.Using a Harmonic scalpel,two 3-5-cm incisions were made in the anterior and posterior gastric wall respectively.In the last step,the anterior gastrotomy was closed with an Endo-GIA stapler.All cases were successfully treated without large blood loss and without conversion to open surgery.The mean operative time was 114.29±19.24 min,blood loss was 157.14±78.70 mL,and mean hospital stay was 8.29±2.98 days,Gastric fistula occurred in one case on the postoperative day 7,and closed 1 month later.No bleeding was seen in all patients during the perioperative follow-up period.CT scans,given one month after the surgeries,displayed that the pancreatic pseudocysts disappeared or decreased in size,and ultrasounds showed no fluid or food residue in stomas at the third and fifth month following surgery.No patient experienced a recurrence during the follow-up period.Transgastric laparoscopic cystogastrostomy is a minimally invasive surgical procedure with a high rate of success and a low rate of recurrence,accompanied by rapid recovery.It is easy to master,safe to perform and may be the preferred option to treat retrogastric pancreatic pseudocysts.

Adult ; Humans ; Kidney Neoplasms ; surgery ; Laparoscopy ; methods ; Male ; Nephrectomy ; methods ; Retroperitoneal Space ; surgery

BACKGROUNDAt present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone.

METHODSThis study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment.

RESULTSAt week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 μU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 μU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups.

CONCLUSIONSCompared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated.

REGISTRATION NUMBERChiCTR-TRC-13003776.

Adult ; Blood Glucose ; drug effects ; C-Reactive Protein ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Drug Combinations ; Drug Therapy, Combination ; Female ; Humans ; Hypoglycemic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Metformin ; administration & dosage ; adverse effects ; therapeutic use ; Middle Aged ; Thiazoles ; administration & dosage ; adverse effects ; therapeutic use