Nicorandil-Pretreated Mesenchymal Stem Cell-Derived Exosomes Facilitate Cardiac Repair After Myocardial Infarction via Promoting Macrophage M2 Polarization by Targeting miR-125a-5p/TRAF6/IRF5 Signaling Pathway.

Background: Exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) have been considered as a promising cell-free therapeutic strategy for ischemic heart disease. Cardioprotective drug pretreatment could be an effective approach to improve the efficacy of MSC-exo. Nicorandil has long been used in clinical practice for cardioprotection. This study aimed to investigate whether the effects of exosomes derived from nicorandil pretreated MSC (MSCNIC-exo) could be enhanced in facilitating cardiac repair after acute myocardial infarction (AMI). Methods: MSCNIC-exo and MSC-exo were collected and injected into the border zone of infarcted hearts 30 minutes after coronary ligation in rats. Macrophage polarization was detected 3 days post-infarction, cardiac function as well as histological pathology were measured on the 28th day after AMI. Macrophages were separated from the bone marrow of rats for in vitro model. Exosomal miRNA sequencing was conducted to identify differentially expressed miRNAs between MSCNIC-exo and MSC-exo. MiRNA mimics and inhibitors were transfected to MSCs or macrophages to explore the specific mechanism. Results: Compared to MSC-exo, MSCNIC-exo showed superior therapeutic effects on cardiac functional and structural recovery after AMI and markedly elevated the ratio of CD68+ CD206+/ CD68+cells in infarcted hearts 3 days post-infarction. The notable ability of MSCNIC-exo to promote macrophage M2 polarization was also confirmed in vitro. Exosomal miRNA sequencing and both in vivo and in vitro experiments identified and verified that miR-125a-5p was an effector of the roles of MSCNIC-exo in vivo and in vitro. Furthermore, we found miR-125a-5p promoted macrophage M2 polarization by inhibiting TRAF6/IRF5 signaling pathway. Conclusion: This study suggested that MSCNIC-exo could markedly facilitate cardiac repair post-infarction by promoting macrophage M2 polarization by upregulating miR-125a-5p targeting TRAF6/IRF5 signaling pathway, which has great potential for clinical translation.

Mendelian randomization study of causal link from gut microbiota to colorectal cancer.

Recent studies have shown the relevance of gut microbiota in the occurrence and development of colorectal cancer (CRC), but the causal relationship remains unclear in the human population. The present study aims to assess the causal relationship from the gut microbiota to CRC and to identify specific causal microbe taxa via genome-wide association study (GWAS) summary statistics based two-sample Mendelian randomization (MR) analyses. Microbiome GWAS (MGWAS) in the TwinsUK 1,126 twin pairs was used as discovery exposure sample, and MGWAS in 1,812 northern German participants was used as replication exposure sample. GWAS of CRC in 387,156 participants from the UK Biobank (UKB) was used as the outcome sample. Bacteria were grouped into taxa features at both family and genus levels. In the discovery sample, a total of 30 bacteria features including 15 families and 15 genera were analyzed. Five features, including 2 families (Verrucomicrobiaceae and Enterobacteriaceae) and 3 genera (Akkermansia, Blautia, and Ruminococcus), were nominally significant. In the replication sample, the genus Blautia (discovery beta=-0.01, P = 0.04) was successfully replicated (replication beta=-0.18, P = 0.01) with consistent effect direction. Our findings identified genus Blautia that was causally associated with CRC, thus offering novel insights into the microbiota-mediated CRC development mechanism.

Pramipexole attenuates neuronal injury in Parkinson's disease by targeting miR-96 to activate BNIP3-mediated mitophagy.

BACKGROUND: Parkinson's disease is a common neurodegenerative problem. Pramipexole (PPX) plays protective role in Parkinson's disease. Nevertheless, the mechanism of PPX in Parkinson's disease-like neuronal injury is largely uncertain. METHODS: 1-methyl-4-phenylpyridinium (MPP+)-stimulated neuronal cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice were used as the model of Parkinson's disease. MPP+-induced neuronal injury was assessed via cell viability, lactic dehydrogenase (LDH) release and apoptosis. microRNA-96 (miR-96) and BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) abundances were examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or Western blotting. Mitophagy was tested by Western blotting and immunofluorescence staining. MPTP-induced neuronal injury in mice was investigated via behavioral tests and TUNEL. RESULTS: PPX alleviated MPP+-induced neuronal injury via increasing cell viability and decreasing LDH release and apoptosis. PPX reversed MPP+-induced miR-96 expression and inhibition of mitophagy. miR-96 overexpression or BNIP3 interference weakened the suppressive role of PPX in MPP+-induced neuronal injury. miR-96 targeted BNIP3 to inhibit PTEN-induced putative kinase 1 (PINK1)/Parkin signals-mediated mitophagy. miR-96 overexpression promoted MPP+-induced neuronal injury via decreasing BNIP3. PPX weakened MPTP-induced neuronal injury in mice via regulating miR-96/BNIP3-mediated mitophagy. CONCLUSION: PPX mitigated neuronal injury in MPP+-induced cells and MPTP-induced mice by activating BNIP3-mediated mitophagy via directly decreasing miR-96.

Prognostic value of programmed cell death ligand 1 (PD-L1) for hepatocellular carcinoma: a meta-analysis.

The prognostic role of programmed death ligand-1 (PD-L1) expression in hepatocellular carcinoma (HCC) has been widely studied but the results are controversial. In this comprehensive meta-analysis, we elucidated the clinical value of PD-L1 in HCC. Relevant studies were systematically searched in the Cochrane Library, EMBASE, and PubMed until June 27, 2019. Eligible studies were validated for the prognostic effect of PD-L1 on the overall survival (OS), disease-free survival (DFS), and relapse-free survival (RFS) in HCC using a hazard ratio (HR) and its 95% confidence interval (95% CI). Twenty-three studies with 3529 patients were involved in this meta-analysis. The pooled results revealed that high membrane-bound PD-L1 (mPD-L1) expression was associated with poor OS (HR: 1.42; 95% CI: 1.12-1.80; P = 0.004) and had no significant correlation with RFS (HR: 1.14; 95% CI: 0.85-1.54; P = 0.39), and DFS (HR: 1.36; 95% CI: 0.81-2.28; P = 0.25). The results also indicated that high soluble PD-L1 (sPD-L1) levels were associated with worse OS (HR: 2.93; 95% CI: 2.20-3.91; P < 0.00001). In addition, high mPD-L1 expression was associated with high alpha-fetoprotein levels (AFP; OR = 1.46; 95% CI: 1.16-1.84; P = 0.001), hepatitis (OR = 0.72; 95% CI: 0.54-0.98; P = 0.03), poor tumor differentiation (OR = 0.68; 95% CI: 0.55-0.84; P = 0.03), and tumor-infiltrating lymphocytes (OR = 3.39; 95% CI: 1.06-10.91; P = 0.04). The mPD-L1 expression had no significant correlation with age, number of tumors, gender, tumor size, liver cirrhosis, vascular invasion, tumor encapsulation, or TNM stage. The study revealed that high mPD-L1 expression in the tumor tissue and high sPD-L1 levels were associated with shorter OS in HCC. Moreover, overexpression of mPD-L1 was significantly associated with poor tumor differentiation, hepatitis, AFP elevation, and tumor-infiltrating lymphocytes.

[Missing Data Replacement Methods in Different Scenarios].

OBJECTIVE: To compare the effect of different approaches of missing data replacement on the regression coefficient estimates r of "length of stay" on "hospital expenditure". METHODS: Data were extracted from the medical records of patients with head and neck neoplasms who were admitted to Sichuan Cancer Hospital. R 3.4.1 was used for generating and processing simulated datasets. Various scenarios were established by setting up different proportions of missing data and missing mechanisms using Monte Carlo method. Three strategies were tested for replacing missing data: Complete Case method,Expectation Maximization (EM),and Markov Chain Monte Carlo method (MCMC). The regression coefficient estimates r of standardized "length of stay" on standardized logarithmic "hospital expenditure" were calculated using these strategies and compared with that of the original complete dataset,in terms of their accuracy (magnitude of differences in r) and precision (differences in the standard error of r). RESULTS: The three replacement methods were all acceptable (within the limit rc±0.5 sc) when missing data were generated using MAR (2∶1) mechanism,or less than 30% data were simulated as missing using the MCAR and MAR (1∶2) mechanism. The EM method had the best estimation precision. CONCLUSION: Missing data replacement should consider the proportion of missing data and potential mechanisms involved.

Kallikrein-related peptidase 7 is a potential target for the treatment of pancreatic cancer.

Pancreatic cancer is one of the deadliest cancers with very poor prognosis, and the five-year survival rate of the patients is less than 5% after diagnosis. Kallikrein-related peptidases (KLKs) belong to a serine protease family with 15 members that play important roles in cellular physiological behavior and diseases. The high expression level of KLK7 in pancreatic cancer tissues is considered to be a marker for the poor prognosis of this disease. In this work, we set out to investigate whether KLK7 could be a target for the treatment of pancreatic cancer. Short hairpin RNAs (shRNAs) were designed and constructed in lentivirus to knock down KLK7 in pancreatic cancer cell line PANC-1, and the real time cellular analysis (RTCA) was used to evaluate cell proliferation, migration and invasion abilities. Small molecules inhibiting KLK7 were discovered by computer-aided drug screening and used to inhibit PANC-1 cells. Our results confirmed that KLK7 is significantly up-regulated in pancreatic cancer tissue, and knocking down or inhibiting KLK7 efficiently inhibited the proliferation, migration and invasion of pancreatic cancer cells. This study suggested that KLK7 could be a potential chemotherapy target for treatment of pancreatic cancer, which would provide us a novel strategy for the treatment of this disease.

Prognostic value from integrative analysis of transcription factors c-Jun and Fra-1 in oral squamous cell carcinoma: a multicenter cohort study.

Transcription factors c-Jun and Fra-1 have been reported to play a role during the initiation and progression in oral squamous cell carcinoma (OSCC). However, cohort studies are rarely reported. Here is an integrative analysis of their prognostic value in OSCC through a multicenter cohort study.313 OSCC patients were included in this study and received regular follow-up. The survival rate and hazard ratios(HR) were generated by survival analysis. The concordance probability and receiver operating characteristic curve area were chosen to measure the model discrimination. High expressions of c-Jun or Fra-1 were associated with poor prognosis, meanwhile the high expression of Fra-1 meant worse prognosis of patients than the high expression of c-Jun. Besides, the interaction effect of c-Jun and Fra-1 was antagonism, when the expression of c-Jun and Fra-1 was both high, the HR was lower than the hazard ratio when only the Fra-1 was at high expression. c-Jun and Fra-1 were both proved to be high risky predictors of death in OSCC, the antagonistic effect suggested that these biomarkers' activities could be influenced by each other. It may provide a new sight for the studies of OSCC prognosis and treatment.

A comparative study on postoperative mortality prediction of SFLI scoring system and Child-Pugh classification in patients with hepatocellular carcinoma.

PURPOSE: In our previous study, we have established the clinical significance of the SFLI (scoring formula of liver injury), the purpose of this study was to compare the SFLI system and the Child-Pugh grading system in the prediction of postoperative mortality in patients with hepatocellular carcinoma (HCC). METHODS: 114 patients with HCC who underwent surgical treatment were enrolled. According to the requirement of the indicators for the Child-Pugh classification, various indices (including albumin [ALB], total bilirubin [TBIL], prothrombin time [PT], ascites, and hepatic encephalopathy) were considered in these patients before surgery, and then Child-Pugh grading was performed. Similarly, the serum biochemical markers including ALB, pre-albumin (PA), TBIL, serum creatining (SCR), international normalized ratio (INR), alanine transminase (ALT), aspartate transaminase (AST), γ-glutamyl transpeptidase (ggr;-GT), alkaline phosphatase (ALP), PT, activated partial thromboplastin time (APTT), and thrombine time (TT) were collected before surgery for SFLI analysis. The predicted postoperative mortality rates of these two scoring models and their diagnostic efficacy were analyzed and compared. RESULTS: According to the Child-Pugh grading system, in level A, B and C were 75, 35, and 4 cases respectively, and the corresponding mortality rates were 1.3% (1/75), 17.1% (6/35) and 75% (3/4). Meanwhile, according to the SLFI classification, the number of patients in the grade I, I+, II, and III were 36, 29, 28, and 21, respectively, and the corresponding mortality rates were 0, 0, 14.3% (4/28), and 28.6% (6/21), respectively. The patient mortality rate increased significantly with increasing grading (p<0.01). These two classification methods were further compared using ROC analysis, in which the area under the curve (AUC) for the Child-Pugh method was 10.2% with a 95% confidence interval (95% CI) 17-18, and the AUC of SFLI was 88.2% with a 95% CI 80-96. CONCLUSION: The SFLI scoring system is very useful in the assessment of liver function and postoperative mortality, and its grading standard is much better than the traditional Child-Pugh classification in many aspects.

Dinitrophenyl hapten with laser immunotherapy for advanced malignant melanoma: A clinical study.

The present study aimed to evaluate the efficacy and safety of in situ immunotherapy with dinitrophenyl (DNP) hapten in combination with laser therapy for patients with malignant melanoma (MM). Between February 2008 and March 2012, 72 patients with stage III or IV MM were enrolled. Patients received in situ DNP alone (n=32) or in combination with laser therapy (n=32), and each group received dacarbazine chemotherapy. The levels of peripheral cluster of differentiation (CD)4+CD25+ regulatory T cells (Tregs), interleukin (IL)-10 and tumor growth factor (TGF)-ß were detected by ELISA. The association between delayed-type hypersensitivity (DTH) and survival time was evaluated. Although peripheral Treg levels significantly decreased over time in the two groups (P<0.001), there was no significant difference between the treatment groups (P=0.098). Patients receiving the combination treatment exhibited significantly higher interferon-γ production by CD8+ and CD4+ T cells (both P<0.001), as well as significantly reduced levels of IL-10, TGF-ß1 and TGF-ß2. In addition, patients in the combination treatment group experienced significantly longer overall survival (OS; P=0.024) and disease-free survival (DFS; P=0.007) times; a DTH response of ≥15 mm was also associated with increased OS time and DFS time (P≤0.001). Finally, no severe adverse events were observed in either treatment group. Overall, in situ immunization with DNP in combination with laser immunotherapy may activate focal T cells, producing a regional antitumor immune response that increases cell-mediated immunity and improves survival in MM patients. Thus, this may represent a novel therapeutic strategy for patients with unresectable, advanced MM.

Neoadjuvant Therapy of DOF Regimen Plus Bevacizumab Can Increase Surgical Resection Ratein Locally Advanced Gastric Cancer: A Randomized, Controlled Study.

Locally advanced gastric cancer (LAGC) is best treated with surgical resection. Bevacizumab in combination with chemotherapy has shown promising results in treating advanced gastric cancer. This study aimed to investigate the efficacy of neoadjuvant chemotherapy using the docetaxel/oxaliplatin/5-FU (DOF) regimen and bevacizumab in LAGC patients.Eighty LAGC patients were randomized to receive DOF alone (n = 40) or DOF plus bevacizumab (n = 40) as neoadjuvant therapy before surgery. The lesions were evaluated at baseline and during treatment. Circulating tumor cells (CTCs) were counted using the FISH test. Patients were followed up for 3 years to analyze the disease-free survival (DFS) and overall survival (OS).The total response rate was significantly higher in the DOF plus bevacizumab group than the DOF group (65% vs 42.5%, P = 0.0436). The addition of bevacizumab significantly increased the surgical resection rate and the R0 resection rate (P < 0.05). The DOF plus bevacizumab group showed significantly greater reduction in CTC counts after neoadjuvant therapy in comparison with the DOF group (P = 0.0335). Although the DOF plus bevacizumab group had significantly improved DFS than the DOF group (15.2 months vs 12.3 months, P = 0.013), the 2 groups did not differ significantly in OS (17.6 ± 1.8 months vs 16.4 ± 1.9 months, P = 0.776. Cox proportional model analysis showed that number of metastatic lymph nodes, CTC reduction, R0 resection, and neoadjuvant therapy are independent prognostic factors for patients with LAGC.Neoadjuvant of DOF regimen plus bevacizumab can improve the R0 resection rate and DFS in LAGC. These beneficial effects might be associated with the reduction in CTC counts.

Novel pH-sensitive nanoformulated docetaxel as a potential therapeutic strategy for the treatment of cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CC) is one of the fatal malignant neoplasms with poor prognosis. The traditional chemotherapy has been resistant to CC and does not improve the quality of life. The aim of the present study is to investigate the potential of chondroitin sulphate (CS)-histamine (HS) block copolymer micelles to improve the chemotherapeutic efficacy of docetaxel (DTX). RESULTS: pH-responsive property of CS-HS micelles was utilized to achieve maximum therapeutic efficacy in CC. In the present study, docetaxel-loaded CS-HS micelles (CSH-DTX) controlled the release of drug in the basic pH while rapidly released its cargo in the tumor pH (pH 5 and 6.8) possibly due to the breakdown of polymeric micelles. A nanosize of <150 nm will allow its accumulation in the tumor interstitial spaces via EPR effect. CSH-DTX effectively killed the cancer kills in a time- and concentration-dependent manner and showed pronounced therapeutic action than that of free drug at all-time points. CSH-DTX resulted in higher apoptosis of cancer cells with ~30% and ~50 of cells in early apoptosis quadrant when treated with 100 and 1000 ng/ml of equivalent drug. The micellar formulations showed remarkable effect in controlling the tumor growth and reduced the overall tumor volume to 1/5(th) to that of control and half to that of free drug treated group with no sign of drug-related adverse effects. Immunohistochemical analysis of tumor sections showed that fewer number of Ki-67 cells were present in CSH-DTX treated group comparing to that of free DTX treated group. CONCLUSION: Our data suggests that nanoformulation of DTX could potentially improve the chemotherapy treatment in cholangiocarcinoma as well as in other malignancies.

Expression of HSPA2 in human hepatocellular carcinoma and its clinical significance.

Hepatocellular carcinoma (HCC) remains one of the most common cancers worldwide. HSPA2 has been highlighted as an important marker in many types of cancers. However, little is known about the role of HSPA2 in HCC. The objective of the current study was to investigate the expression pattern and clinicopathological significance of HSPA2 in patients with HCC. Quantitative reverse-transcriptase ploymerase chain reaction (qRT-PCR) was applied to examine HSPA2 messenger RNA (mRNA) expression in 52 pairs of HCC tissues and adjacent noncancerous tissues. Immunohistochemistry (IHC) was performed to examine HSPA2 protein expression in paraffin-embedded tissues from 119 HCC patients. Statistical analyses were applied to evaluate the diagnostic value and associations of HSPA2 expression with clinicopathological characteristics. We identified abnormally elevated mRNA expression of HSPA2 in HCC tissues compared to paired adjacent noncancerous tissues (P < 0.001). Clinicopathological analysis showed that HSPA2 expression was significantly correlated with tumor size (P = 0.013), histological differentiation (P = 0.04), and tumor stage (P = 0.001). Patients with higher HSPA2 expression had shorter overall survival time, whereas those with lower HSPA2 expression had longer survival time. Furthermore, Cox regression analyses showed that HSPA2 expression was an independent predictor of overall survival. In conclusion, our findings provide evidences that positive expression of HSPA2 in HCC may be important in the acquisition of an aggressive phenotype and it is an independent biomarker for poor prognosis of patients with HCC.

Cyclin D2 plays a regulatory role in HBV replication.

Hepatitis B virus (HBV) infection is the leading cause of liver diseases. However, the molecular mechanisms of HBV infection and carcinogenesis have not been fully elucidated. In this study, we found that cyclin D2 was upregualted in HBV-expressing cells and liver tissues of HBV-transgenic mice. Gene silencing of cyclin D2 inhibited HBV DNA replicative intermediates, 3.5 kb mRNA, core protein level, as well as the secretions of HBsAg and HBeAg. On the contrary, overexpression of cyclin D2 promoted HBV replication. Furthermore, cyclin D2 regulated HBV replication by enhancing the activity of HBV core and Sp1 promoters by targeting transcription factor CREB2. Silencing of CREB2 abolished enhancement of HBV replication induced by cyclin D2. Together, our study has uncovered a positive role of cyclin D2 in HBV replication. It is conceivable that therapeutic application of cyclin D2 inhibitor in HBV infection therapy.

[Parental smoking and adolescent smoking: the intergenerational transmission of heath-risk behaviors].

OBJECTIVE: To determine the impact of parental smoking on adolescent smoking. METHODS: Data were retrieved from the China Health and Nutrition Surveys. Both Logistic regression and Tobit regression analyses were performed to estimate the intergenerational effects. RESULTS: The prevalence of adolescent smoking was 2.35%. The Logistic regression results showed that parental smoking was a risk factor for adolescent smoking. Estimations from Tobit regression showed that father smoking was also correlated with the numbers of cigarettes adolescent smoked. CONCLUSION: An intergenerational effect was observed between parental smoking and adolescent smoking. In order to reduce adolescent smoking, parental smoking control should be targeted.

Enhanced effect of water vapor on complete oxidation of formaldehyde in air with ozone over MnOx catalysts at room temperature.

At room temperature, the enhanced effect of water vapor on ozone catalytic oxidation (OZCO) of formaldehyde to CO2 over MnOx catalysts and the reaction stability was reported. In a dry air stream, only below 20% of formaldehyde could be oxidized into CO2 by O3. In humid air streams (RH≥55%), ∼100% of formaldehyde were oxidized into CO2 by O3 and the reaction stability was significantly enhanced. Meanwhile, in situ Diffuse Reflectance Infrared Fourier Transform (DRIFT) spectra of OZCO of HCHO demonstrate that the amount of both monodentate and bidentate carbonate species on MnOx, in the dry stream, increased gradually with time on stream (TOS). However, in the humid stream, almost no accumulation of carbonate species on the catalysts was observed. To clarify the enhanced mechanism, formaldehyde surface reactions and CO2 adsorption/desorption on the fresh, O3 and O3+H2O treated MnOx catalysts were examined comparatively.

Mda-9/syntenin promotes human brain glioma migration through focal adhesion kinase (FAK)-JNK and FAK-AKT signaling.

Invasion is usually recognized as the main reason for the high recurrence and death rates of glioma and restricts the efficacy of surgery and other therapies. Therefore, we aimed to investigate the mechanism involved in promotion effects of mda-9/syntenin on human glioma cell migration. The wound healing method was used to test the migration ability of human glioma cells CHG-5 and CHG-hS, stably overexpressing mda-9/syntenin. Western blotting was performed to determine the expression and phosphorylation of focal adhesion kinase (FAK) and JNK in CHG-5 and CHG-hS cells. The migration ability of CHG-hS cells was significantly higher than that of CHG-5 cells in fibronectin (FN)-coated culture plates. Phosphorylation of FAK on tyrosine 397, 576, and 925 sites was increased with time elapsed in CHG-hS cells. However, phosphorylated FAK on the tyrosine 861 site was not changed. Phosphorylated Src, JNK and Akt levels in CHG-hS cells were also significantly upregulated. Phosphorylation of JNK and Akt were abolished by the specific inhibitors SP600125 and LY294002, respectively. and the migration ability of CHG-hS cells was decreased, indicating that the JNK and PI3K/Akt pathways play important roles in regulating mda-9/syntenin-induced human brain glioma migration. Our results indicate Mda- 9/syntenin overexpression could activate FAK-JNK and FAK-Akt signaling and then enhance the migration capacity of human brain glioma cells.

[Inhibitory effect of lentiviral-mediated RNA on the expression of Foxp3 protein in melanoma cells].

AIM: To explore the feasibility of RNA interference in the treatment of melanoma by inhibiting the Foxp3 gene expression in mouse B16 melanoma cells using RNA interference (RNAi) in vitro. METHODS: Small interfering RNA (siRNA) was designed according to Foxp3 gene. A short hairpin RNA (shRNA) lentivirus expression vector was constructed and transfected into mouse B16 cells, and RNA interference was induced in vitro. Western blot and real-time RT-PCR were performed to detect the expression of Foxp3 gene. ELISA was applied to detect the changes of TGF-ß(1);, TGF-ß(2);, IL-10 and other cytokines. The B16 cells after interference were co-cultured with CD4(+);CD25(-);T lymphocytes. CCK8 assay was used to monitor the proliferation of CD4(+);CD25(-);T lymphocytes. RESULTS: shRNA could suppress the expression level of Foxp3, down-regulate the inhibitory ability of tumor cells on the proliferation of CD4(+);CD25(-);T lymphocytes, and reduce the secretion of TGF-ß(1);, TGF-ß(2);, IL-10 and other cytokines, in particular the expression of TGF-ß(2);. CONCLUSION: RNA interference can inhibit the expression of target gene Foxp3 in mice melanoma cells and the proliferation of tumor cells. It can also reduce the inhibition on the proliferation of CD4(+);CD25(-);T lymphocytes, and the secretion of inhibitory cytokines.

[Prognostic role of vascular endothelial growth factor in oral carcinoma: a meta analysis].

OBJECTIVE: To perform a Meta analysis of prognostic cohort studies for evaluating the use of vascular endothelial growth factor (VEGF) as a predictor of survival in patients with oral carcinoma. METHODS: A search of OVIDMEDLINE, EMBASE database and two Chinese database (CNKI and VIP) was conducted using common text words combined with medical subject headings to capture the related cohort studies. Data were collected comparing disease-free and overall survival in patients with high VEGF levels as compared to those with low levels. Studies were pooled and summary hazard ratios (HR) were calculated. RESULTS: 14 texts were included in this study. High tissue VEGF levels predicted poor overall survival (HR: 2.95, 95% CI: 2.14-4.08) and disease-free survival (HR: 2.28, 95%CI: 1.61-3.21). Similarly, high VEGF levels predicted poor overall survival (HR: 2.60, 95% CI: 1.82-3.73) and disease-free survival (HR: 2.58, 95% CI: 1.73-3.84) in patients with oral squamous cell carcinoma. CONCLUSION: VEGF may be useful for defining prognosis in oral carcinoma.

[Muscle atrophy of hand as an initial sign in a patient with protoplasmic astrocytoma: a case report and literature review].

We reported a rare case of protoplasmic astrocytoma presenting small muscle atrophy of the right hand as an initial sign. A 39-year-old male was admitted to hospital complaining of chronic muscle atrophy and subtle headache. Electromyography (EMG) showed brief small denervation and no signs of sensory-motor conduction impairment. CT and MRI revealed multiply expansive intracranial lesion in left hemisphere, which was highly suspected of cerebral echinococcus or Balo disease. The patient underwent surgical excision and pathological report was protoplasmic astrocytoma, with glial fibrillary acidic protein (GFAP, +++) of immunohistochemical method. We reviewed clinical features, radiological manifestations and pathology of protoplasmic astrocytoma with medical literature documents.

[Monitoring of photodynamic therapy of port wine stain by fluorescence spectroscopy].

The blood drug level and the formation of photoproduct were monitored during photodynamic therapy (PDT) of port wine stain (PWS) by fluorescence spectroscopy. The irradiation was implemented by a 532 nm double-frequency Nd:YAG laser, and the collection of fluorescence spectra was completed with the use of spectrograph and ICCD. In the experiment for validation of the system, the fluorescence basis spectra of hematoporphyrin monomethyl ether (HMME)-sensitized mouse normal skin were constructed, and, by least-square fitting, HMME fluorescence (624 nm) could be discriminated from that of photoproduct (652 nm). The fitting of fluorescence spectra measured from PWS patients skin containing PSD-007 was performed with the same basis spectra as those from the mouse skin. The curves of blood drug level of different patients with significant variance, as well as those of formation and bleaching of photoproduct were obtained. Fluorescence spectroscopy monitoring system and fitting method presented here can provide technical means for rigorous quantitative PDT dosimetry method, and the results obtained here will make for the individual scheme of PDT.