Liver fibrosis is a pathological process for the liver to repair various chronic liver injuries and may eventually progress to liver cirrhosis,liver failure,or even liver cancer.Therefore,early intervention arid treatment of liver fibrosis is of particular importance.This article summarizes the latest research advances in the roles of TGF-β/Smad signaling pathway,Notch signaling pathway,Wnt signaling pathway,Hedgehog signaling pathway,and integrin signaling pathway in the pathogenesis of liver fibrosis and points out that these signaling pathways play an extremely important role in the development and progression of liver fibrosis and may provide new directions for the treatment of liver fibrosis.

Objective To compare the clinical outcome of intramedullary nail with locking plate in the treatment of two-part proximal humerus fractures.Methods PubMed,SpringerLink,EMBASE,The Cochrane Library,Medline,Science Direct,CNKI,Wanfang Data and VIP database were searched for relevant studies comparing intramedullary nailing and locking plate fixation of two-part proximal humerus fractures.A meta-analysis of the two methods was conducted using the RevMan 5.0.Differences between the two methods were compared with respect to operation time,intraoperative bleeding,bone union time,Constant score and postoperative complication incidence.Results Seven studies were included in the meta-analysis,with 136 patients treated with intramedullary nail and 159 patients treated with locking plate.Intramedullary nailing showed advantages over locking plate fixation with regards to operation time (WMD =-27.71,95％ CI-36.07--19.35,P ＜ 0.05),intraoperative blood loss (WMD =-114.18,95％ CI-169.91--58.45,P ＜ 0.01) and bone union time (WMD =-2.91,95％ CI-5.80--0.01,P ＜ 0.05).While the two methods showed no significant differences in Constant score (WMD =-2.84,95 ％ CI-5.90--0.22,P ＞ 0.05) and postoperative complication incidence (OR =0.89,95％ CI 0.43-1.84,P ＞ 0.05).Conclusion Intramedullary nail is superior to locking plate in operation time,intraoperative blood loss and bone union time for the treatment of two-part proximal humerus fractures,but the two methods are similar in Constant score and postoperative complications rate.

Objective To introduce the operation skills of tail vein injection in conscious rats , and improve the success rate of ingection .Methods The rat was fixed by the operator with a self-made binding clothes , one person assists to fix the rat tail, one person performs puncture , and one person performs injection .During the injection process , we should minimize the injury to the rat tail and the stress caused by operation , strictly limit the needle point , the number of puncture , the maximum dose and injection speed , and to make the needle position away from the injection site to avoid contamination and waste of the drug solution .Results The operation method was successfully established and it was fast , stable, with good repeatability and high degree of coordination .Conclusion This operation is rapid, reliable and stable, worthy of recommendation , especially for the intravenous injection of expensive drugs .

Objective To study the clinical features of patients with scrub typhus and provide scientific basis for clinical diagnosis and treatment. Methods Clinical data of patients with scrub typhus in the First Affiliated Hospital of Kunming Medical University from January 2016 to December 2016 were collected. Epidemiological data, clinical manifestations, laboratory findings, image examination results, treatment and outcome were retrospectively analyzed. Results The clinical manifestations included 59 cases (100.0％) with fever, 44 cases (74.6％) with headache, 39 cases (66.1％) with chills, 34 cases (57.6％) with muscle and joint pain, 29 cases (49.2％) with prostration, 49 cases (83.1％) with eschar or ulcer, 42 cases (71.2％) with lymphadenectasis, 23 cases (39.0％) with hepatosplenomegaly. Laboratory test results: 51 cases (86.4％) had normal or elevated white blood cell count, 50 cases of eosinophil reduced (84.7％), 27 cases of blood platelet (PLT) reduced (45.8％), 33 cases of albumin reduced (55.9％), 50 cases of alanine aminotransferase (ALT) increased (84.7％), 48 cases of aspartate aminotransferase (AST) increased (81.4％), and 56.1％ (23/41) of the patients with triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3) and free thyroxine (FT4) levels significantly lowered, with predominantly free FT3 reduction (82.6％,19/23); C reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR) and ferritin were increased in 93.9％(46/49), 35.4％ (17/48), 64.9％ (24/37), and 83.8％ (31/37) of the patients, and 95.6％(43/45) was accompanied with chest radiographic abnormalities. Tetracycline, doxycycline and azithromycin treatment were all effective. Conclusions The clinical manifestations of patients with scrub typhus, involving multisystem, are diverse and thyroid hormones decrease is observed. Early diagnosis and treatment is the key to improve the prognosis of patients with scrub typhus.

Depression is a major cause of disability and has adverse effects.Despite the many types of anti-depressants,clinical treatments of depression remain poor.Therefore,novel anti-depressant mechanisms need to be explored.The beneficial effects of irisin on the nervous system are gradually being elucidated,and studies have found that irisin has an anti-depressant effect,which may become a new treatment for depression.This study explored the mechanism of irisin and its upstream and downstream anti-depressants by reviewing the existing studies explaining the link between irisin and depression,and proposes that SIRT1/PGC-1α may mediate FNDC5/irisin to regulate BDNF to promote neurogenesis and improve depression,which provides a new idea to study irisin and its upstream and downstream anti-depressants.

Objective To compare the pharmacodynamics between different batches of recombinant decoy receptor innovative drug RC28-E1 and RC28-E2 in retinal angiogenesis and neovascularization,and analyze its mechanism.Methods Sixty postnatal Day 4 (P4) C57BL/6J mice were randomly divided into normal control group,vascular endothelial growth factor (VEGF)+fibroblast growth factor 2 (FGF2) group,VEGF+FGF2+RC28-E1 group,VEGF+FGF2+RC28-E2 group,VEGF+FGF2+conbercept group and VEGF+FGF2+FGF trap group by using a random number table,with 10 mice in each group.The mouse retinal explant culture system was established,and stimulated with the corresponding factors and drugs prepared in the starving culture media.The normal controls were treated with the starving media.Then the retinal explants were stained with Isolectin B4 and imaged.The number of filopodia per vascular length was quantified.In addition,ninety-six P7 C57BL/6J mice were randomly divided into normal control group,oxygen-induced retinopathy (OIR) model control group,OIR + RC28-E1 group,OIR + RC28-E2 group,OIR+conbercept group and OIR+FGF trap group by using a random number table,with 16 mice in each group.The normal controls were raised under normoxia for 10 days,and the rest of the groups were raised under hyperoxia for 5 days,then returned to normoxia for another 5 days.On P17,the retinas were isolated and stained with Isolectin B4.The stained retinas were mountedon the slides and photographed.The relative vessel obliteration and neovascularization in retina were analyzed with computer software.Then the protein levels of VEGF and FGF2 were examined by Western blot in the retinas of each group in the OIR experiment.Finally,in the RF/6A cells stimulated with VEGF and FGF2,the activities of the signaling pathways,including MEK-extracellular regulated protein kinases (Erk),protein kinase C (PKC) and protein kinase B (Akt) pathways,were examined by Western blot.All experimental procedures were evaluated and approved by the Institutional Animal Care and Use Committee of Tianjin Medical University (SYXK 2009-0001),and were in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.Results The results of retinal explant cultures showed that the numbers of filopodia per vascular length in VEGF + FGF2 + RC28-E1,VEGF + FGF2 + RC28-E2,VEGF + FGF2 + conbcrcept,and VEGF+FGF2+FGF trap groups were all significantly less than that in the VEGF+FGF2 group (all at P ＜ 0.001).The filopodia number in retinal vascular front in RC28-E1 group was similar to that in the RC28-E2 group (P =0.15),whereas the filopodia numbers in both groups were significantly decreased as compared to those in VEGF+ FGF2+conbercept group and VEGF+FGF2+FGF trap group (all at P＜0.001).The results from the OIR mouse model showed that the relative vessel obliteration area in OIR model control group was dramatically higher than those in the drug intervention groups (all at P＜0.05).There was no statistical significance in the relative vessel obliteration area between OIR+RC28-E1 group and OIR+RC28-E2 group (P =0.17),while the obliteration areas in both RC28-E-intervened groups were significantly lower than those in the OIR+conbercept group and OIR+FGF trap group (all at P＜0.05).The relative neovascular pixels in the intervention groups were significantly lower than those in the OIR model control group (all at P＜0.001).The neovascular pixels in OIR+RC28-E1 group were significantly lower than those in VEGF+FGF2+conbercept group and VEGF + FGF2 + FGF trap group (both at P ＜ 0.05),but comparable to those in OIR+RC28-E2 group (P =0.39).Western blot result showed that,the protein expression of VEGF and FGF2 in the OIR mouse retinas were significantly upregulated compared to those in the normal ones (both at P＜0.001).The upregulation of both genes were normalized by both RC28-E1 and RC28-E2.In addition,the stimulation of VEGF and FGF2 induced an enhanced activity in MEK-Erk pathway in RF/6A cells,whereas RC28-E1 inhibited the overactivation.Conclusions RC28-E1 and RC28-E2 both can inhibit angiogenesis in the retinal explants isolated from neonatal mice;they also reduce vessel obliteration and mitigate neovascularization in the OIR mouse model.Therefore,the pharmacology batch and pilot test batch of RC28-E have similar efficacies and reliable stability,and are superior in the anti-angiogenic and anti-neovascular efficacy to the currently clinically available drugs conbercept and FGF trap.RC28-E1 may suppress pathological neovascularization through inhibiting the overactivation of MEK-Erk pathway in retinal vascular endothelial cells.

Irritable bowel syndrome （IBS） is a functional gastrointestinal disease， but it often causes extreme gastrointestinal discomfort and prolonged illness， which seriously affects the quality of life of patients. The global incidence rate is increasing year by year. Clinically， western medicine mainly uses oral antispasmodics， secretagogues， and antidepressants， but there are many disadvantages such as adverse reactions and poor long-term efficacy. Therefore， finding an efficient and safe treatment method is an urgent problem to be solved. A large number of studies have shown that traditional Chinese medicine has definite curative and long-lasting effects on the treatment of IBS， which has become a hot research direction in recent years. By searching Chinese and foreign literature， it is found that electroacupuncture， moxibustion， Chinese medicine monomers， and compound decoctions are the main methods in the mechanism research of traditional Chinese medicine in the treatment of IBS-related pathways， and their signaling pathways involve nuclear transcription factor kappa B （NF-κB）， transient receptor potential vanillin subfamily 1 （TRPV1）， 5-hydroxytryptamine （5-HT）， mitogen-activated protein kinase （MAPK）， and so on. Traditional Chinese medicine can repair intestinal inflammation， reduce visceral sensitivity， enhance intestinal mucosal barrier， and regulate intestinal motility by regulating this series of signaling pathways， thereby playing an important role in the treatment of IBS with multi-level， multi-link and multi-target characteristics. Based on the cell signaling pathways， this paper reviewed the research progress on the mechanism of traditional Chinese medicine in the treatment of IBS， hoping to provide theoretical support and diagnosis and treatment ideas for the clinical treatment of IBS with traditional Chinese medicine.