As an internal environment of tumor occurrence, tumor microenvironment is composed of a variety of cells and extracellular matrix, and plays a crucial role in tumor formation, transfer and resistance to drugs. The regulation of tumor microenvironment will be a potential target to control the cancer. MicroRNAs (miRNAs) are a kind of 21 to 25 nucleotides single-stranded RNA, and are mainly involved in regulating gene expression. Recently, with the suggestion of cellular auton-omous tumor inhibition mechanism, the regulation of tumor microenvironment by miRNAs has received great attention. This review summarizes recent findings on the non-cell-autonomous mechanisms of miRNAs-mediated regulation of tumor micro-environments, which provides foundations and perspective on the design of therapeutic interventions.

Glioblastoma (GBM) is one of the WHO gradeⅣmalignancies, which is an acentral nervous system cancer with poor prognosis unless the lesion is in the brain stem. The incidence of GBM accounts for 80%of human primary malignant tumors in brain. Only 5%GBM can survive up to 5-years. Many researches showed that Sox2 is a pluripotent regulator, and muta?tion or abnormal function of Sox2 are closely related to the development of GBM. There are studies demonstrated the possibil?ity of using Sox2 gene as apotential target for GBM therapy. This paper reviewed recent progress in GBM.

BACKGROUND: An ideal repairing material characterizes by both great biocompatibility and osteogenesis ability. Any biomaterials should meet excellent biological security and biocompatibility prior to clinical application.OBJECTIVE: To evaluate the biocompatibility and the biological security of the TiO_2-Ag-nano-hydroxyapatite/polyamide66 (TiO_2-Ag-nHA/PA66) composite.DESIGN, TIME AND SETTING: A randomized controlled duplicated design was performed in Chongqing Medical University from July 2008 to July 2009.MATERIALS: A total of 40 Kunming mice aged 3 weeks and of clean grade and 32 healthy adult New Zealand rabbits were provided by Experimental Animal Center of Chongqing Medical University. TiO_2-Ag-nHA/PA66 composite powder (10 g),TiO_2-Ag-nHA/PA66 composites (n=32, 5 mm ×25 mm), and TiO_2-Ag-nHA/PA66 composites (n=32, 3 mm × 5 mm) were provided by Research Center of Nano-Biomaterials of Sichuan University.METHODS: General toxicity test: Forty mice were randomly divided into experimental and control groups. Composite powder was used to prepare leaching liquor which was treated on experimental mice by an intraperitoneal injection. While, an equal amount saline was inserted into the control mice. Intramuscular implanting test: The 16 rabbits were randomly divided into experimental and control groups. Two TiO_2-Ag-nHA/PA66 composite (5 mm × 25 mm) were implanted into left and right erector spinae, respectively. A similar surgery with the exception of implantation was performed on the control rabbits. Intrabony implanting test: The resting 16 rabbits were implanted one TiO_2-Ag-nHA/PA66 composite (3 mm × 5 mm) into left and right lateral epicondyle, respectively. Hemolytic test: A 8-mL anti-coagulation blood was obtained and added with composite powder (0.1,0.15, and 0.2 g).MAIN OUTCOME MEASURES: Biocompatibility and biological security of TiO_2-Ag-nHA/PA66 composite.RESULTS: General toxicity test demonstrated that mice in the two groups had good activity and eating, normal breathing, stable body mass, no paralysis, convulsion, and death. Intramuscular implanting test and intrabony implanting test showed that there was no significant difference in levels of alanine aminotransferase, aspartate transaminase, urea nitrogen, and creatinine and leukocyte numbers between the two groups before implantation and at day 4,1 week, and 2 weeks after implantation (P> 0.05).In particular, there was no significant difference in the experimental group at varying time points (P> 0.05). Intramuscular implanting test indicated that tissue sections in the experimental group displayed coated tissue of materials. The inflammatory variation in the experimental group was generally similar to that in the control group. Intrabony implanting test indicated that tissue sections in the experimental group displayed new bone formation. Hemolytic test suggested that hemolytic ratio of three varying concentrations of TiOrAg-nHA/PA66 composites was less than 5%, which met the normal criterion.CONCLUSION: TiO_2-Ag-nHA/PA66 composite has a good biocompatibility and biological security.

Objective:To investigate the expression of MKK 4 protein in the nasopharyngeal carcinoma and its clinical significance.Methods:Immunohistochemical methods were employed to analyze MKK 4 positive expression intensity and positive cells in freshly collected nasopharyngeal carcinoma of both 90nasopharyngeal carcinoma cases and 20 chronic nasopharyngitis control.The clinical pathological characteristic were analyzed.Results:The data obtained by MKK4 immunohistochemistry showed that the MKK 4 positive rate was higher in control group than in the NPC group (95.5%vs 75.6%,P<0.05).The expression of MKK4 was related to tumor differentiation and lymph node metastasis ( P<0.05 ) , but not to gender , age, tumor volum and TNM stage ( P>0.05 ) . Conclusion:Positive rate of MKK4 protein in nasopharyngeal carcinoma tissues is lower than in chronic nasopharyngitis.MKK4 protein expressions in nasopharyngeal carcinoma tissues negatively correlated with lymph node metastasis ,clincal stage ,invasive depth ,and TTP (Time to progression),but not with age,gender,location and tumor volume.

Objective:To study the feasibility, safety and technique for laparoscopic anatomical liver resection of segment 8.Methods:The clinical data of 9 patients who underwent laparoscopic anatomical liver resection of segment 8 from January 2015 to December 2019 at Hunan Provincial People's Hospital were retrospectively analyzed. There were 6 males and 3 females, with age ranging from 29 to 67 years (average 53.6 years). The operation time, intraoperative blood loss , postoperative hospital stay, postoperative complications, and long-term survival and recurrence rates on follow-up were analysed.Results:Laparoscopic anatomical liver resection of segment 8 was successfully carried out in these patients. The mean operative time was 188.9 min(range 140-240 min). The mean estimated intraoperative blood loss was 117.8 ml (range 20-300 ml). The postoperative hospital stay was 6.9 days (range 3-12 days). One patient developed pleural effusion after operation and responded to conservative treatment. Another patients developed ascites with delayed extubation. The patient was successfully treated with conservative treatment. No patients developed complications above Clavien Dindo Ⅲa. There were no perioperative deaths. The postoperative pathological results showed hepatocellular adenoma ( n=2), hepatocellular carcinoma ( n=4), cholangiocarcinoma ( n=1), and metastatic liver cancer ( n=2). On follow-up for 12-58 months (median 22 months) one patient with hepatocellular carcinoma developed recurrence at 18 months after operation and was treated with microwave ablation. The other patients were well on follow-up. Conclusions:With adequate preoperative evaluation, reasonable case selection, rigorous surgical planning, and skilled laparoscopic techniques, laparoscopic anatomical liver resection of segment 8 was safe and feasible, and the short-term efficacy was good in this study.

OBJECTIVEGas chromatography (GC) was used to investigate the cellular fatty acid (CFA) composition of 141 Acinetobacter baumannii and 32 A. calcoaceticus isolates from different locations in China and to find chemical markers to differentiate these two closely related bacteria.

METHODSWhole cell fatty acid methyl esters (FAMEs) were obtained by saponification, methylation, and extraction for GC analysis, followed by a standardized Microbial Identification System (MIS) analysis.

RESULTSAll A. baumannii and A. calcoaceticus strains contained some major fatty acids, namely, 18:1 ω9c, 16:0, Sum In Feature 3, 12:0, 17:1ω8c, 3-OH-12:0, 17:0, Sum In Feature 2, 2-OH-12:0, and 18:0 compounds. Although most of the total CFAs are similar between A. baumannii and A. calcoaceticus strains, the ratios of two pairs of CFAs, i.e., Sum In Feature 3/18:1 ω9c versus 16:0/18:1 ω9c and Sum In Feature 3/18:1 ω9c versus unknown 12.484/18:1 ω9c fatty acids, could differentiate these two closely related bacteria. A. baumannii could be easily classified into two subgroups by plotting some ratios such as Sum In Feature 3/16:0 versus 17:0 and Sum In Feature 3/2-OH-12:0 versus 17:0 fatty acids.

CONCLUSIONThe ratios of some CFAs could be used as chemical markers to distinguish A. baumannii from A. calcoaceticus.

Acinetobacter baumannii ; classification ; cytology ; metabolism ; Acinetobacter calcoaceticus ; classification ; cytology ; metabolism ; Biomarkers ; metabolism ; Fatty Acids ; metabolism ; Species Specificity

OBJECTIVETo observe the revascularization process and histological changes in the dermal substitutes after grafting.

METHODSTwenty-one SD rats were enrolled in the study and were randomly divided into swine acellular dermal matrix (sADM), human acellular dermal matrix (hADM), and artificial dermal equivalent (Integra) groups according to different dermal substitutes grafted underneath the skin of SD rats. The gross appearance of the grafts was observed, and the tissue biopsies were harvested at 2, 3, 4, 7, 10, 14, 21, 30, 60, 90, 120, 150, 180 post grafting day (PGD) for the observation of the revascularization process and their histological changes.

RESULTSGross observation: The incision in each group healed well without local swelling and inflammatory response after grafting. The grafts had a compact contact with the wounds. The texture of the grafted dermis in each group was soft and could not be felt from the surface of the body on 90 PGD. The presence of the grafts could be discerned on 180 PGD in all the groups, but some of them became smaller in size and thinner, even hard to identify in a few. Fibroblasts, neutrophils and lymphocytes migrated into the grafts from 2PGD on. New capillary sprouts from the receiving beds could be observed after 3PGD. Affluent capillary nets formed in the grafts during 30 to 60 PGD. The structure of the grafts became nearly unidentifiable from the native dermis after 150 PGDs. Absorption and degradation to various degrees occurred in some of the grafts after 180 PGD.

CONCLUSIONThe revascularization of the three dermal substitutes could begin shortly after grafting. The sponge-like structure of the substitutes was advantageous for the migration of the host fibroblast into the substitute and for the secretion of the new extra-cellular matrix. The dermal substitutes could last in the wound for a long time with partial absorption and degeneration.

Animals ; Dermis ; transplantation ; Female ; Humans ; Neovascularization, Physiologic ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reconstructive Surgical Procedures ; Skin ; blood supply ; Skin Transplantation ; methods ; Skin, Artificial ; Swine ; Transplants ; Wound Healing

It is unanimously accepted that stroke is a highly heterogeneous disorder.Different subtypes of ischemic stroke may have different risk factors,clinical features,and prognoses.The aim of this study was to evaluate the risk factors,clinical characteristics,and prognoses of different subtypes of ischemic stroke defined by the Trial of ORG10172 in Acute Stroke Treatment (TOAST) criteria.We prospectively analyzed the data from 530 consecutive patients who were admitted to our hospital with acute ischemic stroke within 7 days of stroke onset during the study period.Standardized data assessment was used and the cause of ischemic stroke was classified according to the TOAST criteria.Patients were followed up till 30 and 90 days after stroke onset.It was found that large-artery atherosclerosis was the most frequent etiology of stroke (37.4％),and showed the highest male preponderance,the highest prevalence of previous transient ischemic attack,and the longest hospital stay among all subtypes.Small artery disease (36.4％) was associated with higher body mass index,higher plasma triglycerides,and lower plasma high-density lipoprotein cholesterol than cardioembolism.Cardioembolism (7.7％),which was particularly common in the elderly (i.e.,individuals aged 65 years and older),showed the highest female preponderance,the highest prevalence of atrial fibrillation,the earliest presentation to hospital after stroke onset,the most severe symptoms on admission,the maximum complications associated with an adverse outcome,and the highest rate of stroke recurrence and mortality.Our results suggest that ischemic stroke should be regarded as a highly heterogeneous disorder.Studies involving risk factors,clinical features,and prognoses of ischemic stroke should differentiate between etiologic stroke subtypes.

A cDNA encoding novel type III polyketide synthase (PKS) was cloned and sequenced from young leaves of Chinese club moss Huperzia serrata (Thunb.) Trev. by RT-PCR using degenerated primers based on the conserved sequences of known CHSs, and named as H. serrata PKS2. The terminal sequences of cDNA were obtained by the 3'- and 5'-RACE method. The full-length cDNA of H. serrata PKS2 contained a 1212 bp open reading frame encoding a 46.4 kDa protein with 404 amino acids. The deduced amino acid sequence of H. serrata PKS2 showed 50%-66% identities to those of other chalcone synthase super family enzymes of plant origin. The recombinant H. serrata PKS2 was functionally expressed in Escherichia coli with an additional hexahistidine tag at the N-terminus and showed unusually versatile catalytic potency to produce various aromatic tetraketides, including chalcones, benzophenones, phloroglucinols, and acridones. In particular, the enzyme accepted bulky starter substrates N-methylanthraniloyl-CoA, and carried out three condensations with malonyl-CoA to produce 1, 3-dihydroxy-N-methylacridone. Interestingly, H. serrata PKS2 lacks most of the consensus active site sequences with acridone synthase from Ruta graveolens (Rutaceae).
Acyltransferases ; genetics ; isolation & purification ; metabolism ; Amino Acid Sequence ; Cloning, Molecular ; DNA, Complementary ; genetics ; DNA, Plant ; genetics ; Escherichia coli ; genetics ; metabolism ; Gene Expression Regulation, Plant ; Huperzia ; enzymology ; genetics ; Molecular Sequence Data ; Plant Leaves ; enzymology ; genetics ; Plants, Medicinal ; enzymology ; genetics ; Recombinant Proteins ; genetics ; metabolism ; Sequence Alignment ; Substrate Specificity

OBJECTIVETo investigate the effect of Compound Qingqin Liquid (CQL) on the expression level of angiotensin II (Ang II) and COX-2 mRNA transcription and protein expression in the renal tissue of rats with uric acid nephropathy.

METHODSSD rats were randomly divided into the blank control group, the model group, the positive drug group, the high, moderate, and low dose CQL group according to number randomization principle. The model was established by gastrogavage of adenine, accompanied with yeast feeding. Distilled water was given by gastrogavage to rats in the blank control group and the model group. Allopurinol at the daily dose of 9.33 mg/kg was given by gastrogavage to rats of the positive control group. CQL at the daily dose of 3.77 g/kg, 1.89 g/kg, and 0.09 g/kg was respectively given by gastrogavage to rats in the high, moderate, and low dose CQL groups. All treatment lasted for 6 weeks. Rats were randomly divided at week 4 (3 in the blank control group, and 6 in the rest groups), and the rest rats were killed at week 6. The renal tissue was extracted. The expression level of Ang II and COX-2 mRNA transcription were detected by RT-PCR. The expression level of Ang II was detected by ELISA. The expression level of COX-2 protein was detected by Western blot and immunohistochemical assay.

RESULTSCompared with the blank control group, except the mRNA expression of Ang II at week 4, the mRNA and protein expression of Ang II and COX-2 obviously increased at week 4 and 6 in the model group (P < 0.01, P < 0.05). The COX-2 protein expression at week 4 was obviously lower in the high and moderate dose CQL groups than in the model group and the low dose CQL group (P < 0.05); the average integral of optical density value was obviously lower in the positive control group than in the model group. Except the mRNA expression of Ang II in the high dose CQL group at week 6, the mRNA and protein expression of Ang II obviously decreased in the positive control group and each dose CQL group (P < 0.01, P < 0.05). Of them, the effects were better in the high and moderate dose CQL groups than in the positive control group and the low dose CQL group (P < 0.05, P < 0.01). Besides, the mRNA expression of COX-2, the average integral of optical density value were obviously lower in the positive control group and each dose CQL group than in the model group (P < 0.05). The protein expression of COX-2 was obviously lower in the high and moderate dose CQL groups than in the model group (P < 0.05). Of them, the mRNA expression of COX-2 was better in the moderate dose CQL group than in the positive control group (P < 0.05); the protein expression of COX-2 was better in the high dose CQL group than in the low dose CQL group (P < 0.05).

CONCLUSIONCQL was capable of lowering the expression level of Ang II, COX-2 mRNA transcription and protein expression, thus suppressing the inflammatory pathological injury of the renal tissue.

Angiotensin II ; metabolism ; Animals ; Cyclooxygenase 2 ; genetics ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; metabolism ; Kidney Diseases ; drug therapy ; metabolism ; Male ; RNA, Messenger ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Uric Acid