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To investigate the influences of adiponectin (APN) on the liver injury in sepsis rats and to explore whether it exerts a therapeutic effect through the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway.A rat model of sepsis was established through cecal ligation and puncture (CLP) (CLP group), and APN treatment group (APN group) and control group were also set. The changes in the liver function-related indicators, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were determined by automatic biochemistry analyzer, and the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1, and IL-6 were measured via enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was employed to detect liver tissue injury, and the hepatocyte apoptosis and necrosis after intervention with APN were evaluated using in situ fluorescence staining. Moreover, the mRNA expression of APN in liver tissues was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), and the expression levels of phosphorylated AMPK and mTOR proteins in liver tissue samples were determined using Western blotting.In terms of changes in liver function-related indicators, the concentrations of ALT and AST were substantially raised in the CLP group, and compared with those in the control group, the concentrations of the two indicators significantly declined in the APN group, showing statistically significant differences (p0.05). CLP and APN group had evidently higher levels of inflammatory factors than the control group, but their levels in APN group were notably lower than those in the CLP group (p0.05). It was found through the HE staining that the sepsis rats in CLP group had massive inflammatory cell infiltration, and that the inflammatory cells were remarkably decreased in the APN group after APN treatment. According to the in-situ fluorescence staining detection results, CLP group exhibited a notable increase in the cell apoptosis rate, and APN group had substantially reduced apoptotic cells (p0.05). The determination results of APN expression revealed that CLP group had a lowered level of APN, and that the level of APN in APN group was markedly higher than that in the control group. Based on the results of Western blotting, the level of phosphorylated AMPK was remarkably elevated, and that of phosphorylated mTOR was lowered in the CLP group compared with those in the control group, while in comparison with CLP group, APN group showed a considerable elevation of phosphorylated AMPK level and a distinct decline in the phosphorylated mTOR level.APN can activate the AMPK/mTOR pathway and reduce hepatocyte apoptosis to alleviate liver injury in sepsis rats.

The aim of this study was to investigate the effect of micro-ribonucleic acid-195 (miR-195) on myocardial fibrosis in hypertensive rats through the transforming growth factor beta 1 (TGFβ1)-Smad3 signaling pathway.Spontaneously hypertensive rats (SHRs) were selected in this study to establish the animal model. The content of miR-195 in the model group and control group was measured, respectively. Arterial blood pressure, liver function and myocardial function in the two groups were detected and examined. Pathological changes in rat myocardial tissues were detected via hematoxylin-eosin (HE) staining. After that, myocardial fibroblasts were collected and added with miRNA inhibitors and mimics to suppress and overexpress miR-195. Thereafter, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting were employed to detect the mRNA and protein expression levels of checkpoint kinase 1 (Chek1) and alpha-smooth muscle actin (α-SMA) (important molecules for proliferation and differentiation of myocardial fibroblasts), as well as the related pathway TGFβ1-Smad3. Furthermore, the effects of miR-195 on myocardial fibrosis in hypertensive rats via the TGFβ1-Smad3 signaling pathway were comprehensively observed.Serum alkaline phosphatase (ALP), glutamic pyruvic aminotransferase (ALT) and creatine kinase (CK) levels in the SHR group were significantly higher than those of the normal group. Cardiac function examination showed that SHR group had significantly reduced fractional shortening (FS, %) and ejection fraction (EF, %) in comparison with the normal group. However, systolic blood pressure, diastolic blood pressure, left ventricular end-diastolic dimension (LVEDd) and left ventricular end-systolic dimension (LVESd) were markedly elevated in the SHR group. In addition, the miR-195 expression level was remarkably reduced in hypertensive rats. Histopathological changes in rat myocardial tissues were detected through HE staining. The results showed that the normal group had orderly arranged myocardial cells. However, SHR group showed disorderly arranged myocardial cells, thickened myocardial fibers and myocardial fibrosis. RT-PCR assay results revealed that the mRNA levels of Collagen, Chek1, α-SMA, TGFβ1 and Smad3 in rat myocardial fibroblasts were significantly reduced in Mimics group (p0.05) and increased in Inhibitors group (p0.05). Western blotting results demonstrated that, compared with the control group, the protein levels of α-SMA, TGFβ1 and Smad3 in rat myocardial cells decreased significantly in Mimics group (p0.05). Opposite results were observed in Inhibitors group (p0.05). The above results suggested that overexpression of miR-195 inhibited the expressions of TGFβ1-Smad3 signaling pathway and related molecules, further repressing myocardial fibrosis.MiR-195 participates in the development and progression of myocardial fibrosis in hypertensive rats through the TGFβ1-Smad3 signaling pathway. Furthermore, this can inhibit the development of myocardial fibrosis in hypertensive rats and prevent myocardial diseases.

To explore the sensitivity ofThe resistance ofThe resistance indexes ofAfter decades of chemical control

Glioma is a common aggressive cancer and a major public health problem worldwide, with high incidence, recurrence, and mortality. Circular RNA (circRNA) has been reported to be involved in glioma, but the role of circ_0079593 in glioma is still unclear.The real-time quantitative polymerase chain reaction (RT-qPCR) was performed to quantify the expression levels of circ_0079593, miR-499a-5p, and karyopherin alpha 2 (KPNA2) in glioma tissues or cells. The protein expression level of KPNA2 was assessed by Western blot. 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT), flow cytometry, and transwell assays were conducted to evaluate proliferation, apoptosis, migration and invasion of glioma cells, respectively. The relationship between miR-499a-5p and circ_0079593 or KPNA2 was analyzed by bioinformatics database and confirmed by Dual-Luciferase reporter analyses, respectively. The effects of circ_0079593 silencing in vivo were measured by a xenograft experiment.Circ_0079593 and KPNA2 were elevated in glioma tissues and cells. Loss-of functional experiments revealed that knockdown of circ_0079593 hampered the progression of glioma by repressing proliferation, motility and inducing apoptosis in vitro and declining tumor growth in vivo. Similarly, suppression of KPNA2 impeded the process of glioma by inhibiting proliferation, motility and increasing apoptosis. MiR-499a-5p, interacting with KPNA2, was a target gene of circ_0079593. In addition, overexpression of KPNA2 could reverse the effects of circ_0079593 knockdown on proliferation, apoptosis, migration and invasion of glioma cells. Mechanistically, circ_0079593 mediated proliferation, motility and apoptosis of glioma cells by regulating KPNA2 expression via sponging miR-499a-5p.Circ_0079593 stimulated the pathological process of glioma via acting as competing endogenous RNA to sponge miR-499a-5p.

To examine the effect of low temperature on trehalose and trehalase levels inThe fourth instar larvae and female adult mosquitoes ofThe contents of trehalose and trehalase significantly increased in the larval and female adult mosquitoes post-exposure to low temperature. The changing trend of trehalose levels was consistent in the larval and female adult mosquitoes, and the highest levels were (2.458 8 ± 0.379 2) mg/g and (2.825 7 ± 0.211 1) mg/g 3 h post-exposure to low temperature, respectively. The trehalose and trehalase levels fluctuated greatly within the first 6 h post-exposure to low temperature. Following adaptation for a period of time, the trehalose and trehalase levels remained at a relatively high level.Low temperature may induce the production of trehalose and trehalase in

目的 通过剂量递增的Ⅰ期临床试验，评价重组人-鼠嵌合抗CD20单克隆抗体注射液IBI301单次给药在经治疗达客观缓解的CD20+ B细胞非霍奇金淋巴瘤患者中的耐受性、安全性及药效学特征。 方法 纳入9例受试者，按剂量递增原则设125、375和500 mg/m2三个剂量组，每组3例逐组完成试验。3组受试者均接受单次IBI301静脉输注，125、375、500 mg/m2组IBI301的中位暴露量分别为243、690、980 mg。观察IBI301给药后不良事件（AE）发生情况。采用流式细胞术检测外周血CD19+、CD20+ B细胞比例，采用速率散射比浊法检测血清IgG、IgM水平，进行药效学评价。 结果 9例受试者发生52例次AE，包括：125 mg/m2组18例次，375 mg/m2组14例次，500 mg/m2组20例次。其中不良反应共26例次，22例次与试验药物可能有关，4例次可能无关；对症处理后均消失或恢复至基线水平。常见的AE包括WBC降低、上呼吸感染、ANC降低、消化不良、高尿酸血症、感觉异常、口腔黏膜炎和头晕。研究中未出现AE导致的用药暂停、受试者退出或试验提前中止，未发生严重AE（SAE）及剂量限制性毒性（DLT）事件。所有受试者CD20+、CD19+ B细胞比例均有不同程度下降，而IgG和IgM水平无明显变化。 结论 IBI301耐受性良好，受试者出现的不良反应均恢复，未发生SAE及DLT事件。IBI301对CD20+ B细胞有较好的清除作用。

Munc13-1 may be a key factor in regulating insulin exocytosis, but its exact expression and role have not been clarified yet, especially during pancreatic development. We attempted to investigate the expression and function of Munc13-1 during embryonic pancreatic development in rats and determine the effects on insulin secretion. In the present study, pancreata of rats at embryonic day 12.5 (E12.5), E15.5, E18.5, new-born, 21 after birth (P21), and adult stage were dissected under microscope. The rat model of intrauterine growth retardation (IUGR) was made by 50% calorie restriction in pregnant rats from gestational day 15 until term. The expression of Munc13-1 and insulin secretion was studied by the techniques of RTPCR, real-time PCR, Western blot, and enzyme-linked immunosorbent assay. Immunohistochemistry and immunofluorescence were used to define the location of Munc13- 1. We found that Munc13-1 was located at islet along with insulin. Insulin- and Munc13-1-specific mRNA were not detected until E12.5 and E15.5, respectively, and increased with the development of the fetus. Western blot showed that Munc13-1 was low at E15.5 and E18.5 and increased later. The blood insulin level and Munc13-1 were reduced simultaneously in IUGR newborn rats compared with normal ones. These results suggest that Munc13-1 exists in pancreas islets during fetus development and its deficiency in the pancreas, as occurs in IUGR, was in accordance with decreased blood insulin level. Munc13-1 may play an essential role in insulin exocytosis.

To study the protective effects of Schwann cell derived neurotrophic factor (SDNF) on motoneurons of spinal anterior horn from spinal root avulsion induced cell death.Twenty SD rats were made the animal model of C6.7 spinal root avulsion induced motoneuron degeneration, and SDNF was applied at the lesion site of spinal cord once a week. After three weeks, the C6.7 spinal region was dissected out for motoneuron count, morphological analysis and nitric oxide synthase (NOS) enzyme histochemistry.68.6% motoneurons of spinal anterior horn death were occurred after 3 weeks following surgery, the size of survivors was significantly atrophy and NOS positive neurons increased. However, in animals which received SDNF treatment, the death of motoneurons was significantly decreased, the atrophy of surviving motoneurons was prevented, and expression of NOS was inhibited.SDNF can prevent the death of motoneurons following spinal root avulsion. Nitric oxide may play a role in these injury induced motoneuron death.

SUMMARYThe efficacy of DNA-based immunization in conferring protective immunity against certain microbial pathogens including human immunodeficiency virus type 1 (HIV-1) has been described. The potential advantage of DNA-based immunization over the traditional vaccines largely results from its capacity to efficiently induce Th1-biased immune responses against an encoded antigen. We describe how Th1-biased immune responses are induced by DNA-based immunization, using a DNA vaccine construct encoding HIV-1 gp160 cDNA and an eukaryotic expression plasmid carrying murine IFN-γ cDNA. Transfection of an eukaryotic expression plasmid carrying immunostimulatory sequences (ISS) as well as a gene of interest (DNA vaccine) into professional antigen presenting cells (APC) induced transactivation of IL-12 mRNA, which resulted in antigen-specific Th1-biased immune responses against the encoded antigen. Th1-biased immune responses induced by DNA-based immunization were substantially upregulated by a codelivery of an ectopic IFN-γ expression system, and this augmentation was mediated via action on professional antigen presenting cells to upregulate IL-12 production. Taken together, it appears likely that Th1-biased immune responses induced by DNA-based immunization are mediated via action on professional antigen-presenting cells to produce IL-12. Interestingly, the model provided strikingly resembles that previously described in infection with Listeria monocytogenes, an intracellular Gram-positive bacterium that induces strong Th1-biased immune responses. The result suggests that DNA-based immunization mimics certain aspects of natural infection with microbial organisms like attenuated vaccines, which in turn provides a rationale to the question of why DNA-based immunization so efficiently induces protective immunity against these microbial pathogens.

This experiment mainly describes the effects of acupuncture on immunologic function and histopathology of transplanted mammary cancer in mice. The results were as follows: in acupuncture group, NK cell activity and T-lymphocyte positive rate of acid alpha-naphthyl acetate esterase (ANAE) and lymphocyte transformation rate were all increased. Compared with the control group, there was a significant difference (P0.01). The difference was insignificant, when compared with normal group (P0.05). Comparing the pathology grading of acupuncture group with control group, it showed marked difference in pathological section (P0.01). Adenoid structure and the degree of lymphocytic infiltration also have marked difference between acupuncture and control group (P0.05). Less tumour volume in acupuncture than control group were observed (P0.01). This indicated that acupuncture might increase the immunologic function of transplanted mammary cancer in mice and inhibit the growth of mammary cancer and enhance both differentiation level of mammary cancer cells and lymphocytic infiltration. Possibly acupuncture mightt reduce the malignancy of mammary cancer cells.

In isolated guinea pig sinus node and crista terminalis cells, berberine, (Ber) 10 mumol.L-1 shortened the S-C and C-H intervals; increased the membrane responsiveness accompanying in the dose dependent inhibition of action potentials of these cells. The sinus cells were more sensitive to the depressive effect of Ber than crista terminalis cells. Similarly, after iv Ber (10 mg.kg-1), the intervals of A-H and H-V were decreased; whereas AERP and AVNFRP prolonged on His bundle electrogram in anesthetized rabbits. The above results indicate that Ber possessed a positive dromotropic effects on both intra-atrial and atrioventricular conductions, which were independent to increase of Vmax and APA. Thus the actions of Ber might be relevant to its effects on myocardial cell membrane by decreasing impedence and increasing electric coupling. Furthermore, Ber 15 mg.kg-1 iv in rabbits caused a severe myocardial inhibition.

Berberine (Ber) 0.1-30 mumol/L decreased the APA, Vmax, maximal depolarization potentials (MDP) and rate of spontaneous impulse initiation in sinoatrial node (SAN) and atrioventricular node (AVN) cells with prolongation of APD50, APD95 and ERP in a dose-dependent manner. The depression of SAN function was shown by increasing sinus cycle length (SCL), sinus recovery time (SRT) as well as corrected sinus recovery time (CSRT). In atria (crista terminalis, CT) higher concentrations of Ber were needed to prolong APD50, APD95, and ERP as compared with SAN and AVN. The effects of Ber on SAN were not antagonized or reversed by atropine (1 mumol/L), alpha 2-receptor agonist BHT-920 (10 mumol/L) or alpha 1-receptor agonist phenylephrine (10 mumol/L), but those effects of Ber on SCL, APA and Vmax could be reversed by norepinephrine (0.1 mumol/L). In calcium free Tyrode's solution, the inhibitory effects of Ber still revealed on SAN but on atria only prolongations of APD50 and APD95 were observed.