Objective To evaluate the clinical value and efficacy of prophylactic pancreatic duct stenting for biliary-type stenosis of Oddi sphincter with difficulty cannulation.Methods The present study was a retrospective study of 63 patients with biliary-type stenosis of Oddi sphincter and difficult cannulation.The stent group consisted 30 patients who underwent prophylactic pancreatic duct stenting from February 2010 to February 2011 and the control group included 33 patients who underwent only ERCP without prophylactic pancreatic duct stenting from January 2009 to January 2010.The incidence of postoperative pancreatitis were compared between the two groups.Results The incidence of postoperative pancreatitis of the control group was significantly higher than that of the stent group (P ＜ 0.05).Conclusion For patients with definite diagnosis of biliary-type stenosis of Oddi sphincter and difficult cannulation,prophylactic pancreatic duct stent placement is safe and effective.

Objective To study multimodal analgesia in patients who underwent transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Methods 60 patients who underwent TACE for HCC from Aug.2016 to Nov.2016 were randomized into two groups:the multimodal analgesia group and the control group.The pain scores of these two groups of patient during the procedure and at different posttreatment time points,and the rates of adverse effect and pharmacoeconomic differences were recorded.Results When compared to the control group,the pain scores at 0 h,2 h,4 h,6 h,12 h after treatment in the multimodal analgesia group were significantly lower (P ＜ 0.05),and the satisfactory scores for the patients were significantly improved (96.6％ vs.66.7％).The multimodal group of patients also had significandy lower adverse effect rates of nausea and vomiting,and it was more cost-effective.Conclusions Patients who required multimodal analgesia had better pain relieve,patient satisfaction and less adverse reactions after TACE than patients in the control group.Multimodal analgesia was a safe,effective and economic way to control TACE pain and it was worth recommended in clinical practice.

Objective To explore the value of controlling nutritional status(CONUT)score and related inflammatory indicators in predicting the prognosis of clear cell renal cell carcinoma(ccRCC)patients,to provide a reference for better clinical assessment and individualized treatment plan.Methods A retrospective study was conducted on 132 patients with ccRCC admitted to four comprehensive hospitals in Yibin during 2010 and 2018.Patients'medical and follow-up records were collected,and receiver operating characteristic(ROC)curve was drawn to analyze the area under the curve(AUC)and optimal cut-off value of CONUT score and related indicators.Survival curve was plotted with Kaplan-Meier method,and the influencing factors of prognosis were analyzed with Log-rank test and Cox regression.Results During the follow-up of 62(53,71)months,37(28.03％)deaths occurred.The disease-specific survival(DSS)and progression-free survival(PFS)were 51(41,58)and 46(35,56)months,respectively.The 3-year and 5-year DSS and PFS were 84.09％and 71.97％,and 75.00％and 71.97％,respectively.The AUC of CONUT score,neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),and lymphocyte to monocyte ratio(LMR)were 0.980,0.905,0.899 and 0.884,respectively,with the optimal cut-off values of 3.50,3.19,89.07 and 3.56,respectively.Cox regression showed that CONUT score(HR=0.042,95％CI:0.013-0.140)and PLR(HR=0.182,95％CI:0.045-0.744)were associated with DSS;CONUT score(HR=0.029,95％CI:0.010-0.086)and LMR(HR=2.984,95％CI:1.227-7.258)were associated with PFS.Conclusion The prognosis of ccRCC patients is related to their nutritional,immune,and inflammatory status.CONUT score and inflammatory factors(PLR,LMR)may be important predictors of DSS and PFS.

Objective To investigate the role of lipopolysaccharide(LPS)in regulating the inflammatory response of neutrophil through the leucine-rich α-2 glycoprotein 1(LRG1)/Rho-associated protein kinase(ROCK1)signaling.Methods HL-60 cells were treated with 1 μmol/L all-trans retinoic acid(ATRA)and 12.5 μL/mL dimethyl sulfoxide(DMSO)for 72 h and 96 h,and the morphological changes were observed by Wright-Giemsa staining.The expression of CD11b was detected by flow cytometry.LPS induced the activation of dHL-60 and human peripheral blood neutrophils.The transcription and secretion levels of LRG1,ROCK1 and inflammatory cytokines were detected by qPCR and ELISA,respectively.The expression levels of LRG1 and ROCK1 after the activation of dHL-60 were detected by Western blotting.Furthermore,dHL-60 was treated with the recombinant protein LRG1 and ROCK1 inhibitor Y-27632;the transcription levels of inflammatory cytokines were detected by qPCR.Results Neutrophils were activated by LPS.The expression levels of LRG1 and ROCK1 were significantly increased,and the transcription levels of inflammatory cytokines were significantly increased.The recombinant protein LRG1 activated dHL-60 in vitro,and the transcription levels of ROCK1 and inflammatory cytokines were significantly increased.Using the ROCK1 inhibitor Y-27632,the production levels of inflammatory cytokines were significantly reduced.Conclusion LPS can regulate the production levels of neutrophil inflammatory cytokines through activating the LRG1/ROCK1 signaling,thus exacerbating the inflammatory response.

Objective:To explore the effects and mechanisms of bortezomib on the proliferation and apoptosis of acute T lymphocyte leukemia cell line Jurkat.Methods:MTT assay was used to test the influence of bortezomib on the proliferation of Jurkat cells.Flow cytometry was used to detect the influence of bortezomib on apoptosis of Jurkat cells.Real-time quantitative polymerase reaction(RT-PCR) was used to detect the effects of bortezomib on the expression of Bax, Bcl-2 and Cox-2 genes in Jurkat cells.Results:The inhibition rates of 5ng/mL, 10ng/mL, 20ng/mL and 40ng/mL bortezomib on Jurkat cells at 24h were (13.23±0.71)%, (39.53±0.95)%, (53.07±1.12)%, (60.43±0.75)%, respectively, and the inhibition rates at 48h were (25.20±0.96)%, (52.80±1.30)%, (60.67±0.64)%, (75.10±1.35)%, respectively.The inhibitory rates of proliferation of Jurkat cells at 72h were (38.37±0.93)%, (60.94±0.85)%, (73.83±5.08)%, (88.37±1.55)%, respectively.The inhibitory rates of proliferation of Jurkat cells increased with the increase of drug concentration and the prolongation of action time, and the differences were statistically significant( F=1 602.202, 1 085.089, 181.034, all P<0.05). Bortezomib (5ng/mL, 10ng/mL, 20ng/mL and 40ng/mL) treatment for 24h, 48h and 72h, the apoptosis rate of Jurkat cells increased with the increase of drug concentration and the prolongation of action time, the differences were statistically significant( F=1 288.571, 223.378, 251.175, all P<0.05). The expression of Bax mRNA in Jurkat cells increased with the increase of drug concentration and time( F=258.446, 518.929, 276.764, all P<0.05). The Bcl-2 mRNA and Cox-2 mRNA expression levels decreased with the increase of drug concentration and the prolongation of action time( FBcl-2 mRNA=236.848, 264.849, 343.968, FCox-2 mRNA=679.404, 1288.681, 1541.850, all P<0.05). Conclusion:Bortezomib can inhibit the proliferation and induce apoptosis of Jurkat cells.Bortezomib can increase the expression of Bax mRNA and decrease the expression of Bcl-2 and Cox-2 mRNA, which may be the molecular mechanism of bortezomib to promote apoptosis.

Objective To evaluate the effect of dezocine on cognitive function after sevoflurane anesthesia in a rat model of physiological stress.Methods Physiological stress was induced by applying repeated foot shock stimulation and confirmed by open field test.Thirty Spragne-Dawley rats with physiological stress,weighing 180-220 g,were divided into 3 groups (n=10 each) using a random number table:control group (group C),sevoflurane group (group S) and dezocine plus sevoflurane group (group D+S).Normal saline 0.5 ml was intraperitoneally injected at 6 h of oxygen inhalation in group C.Normal saline 0.5 ml was intraperitoneally injected at 6 h of 3.0％ sevoflurane inhalation in group S.Dezocine 3 mg/kg was intraperitoneally injected at 6 h of 3.0％ sevoflurane inhalation in group D+S.At 1,12,24 and 48 h after the end of intraperitoneal injection (T1-4),Morris water maze test was performed,and the time of staying at the original platform quadrant and frequency of crossing the original platform were recorded.The rats were sacrificed after the end of Morris water maze test,brains were removed and hippocampi were isolated for determination of nitric oxide synthase-1 (nNOS) expression (by Western blot) and nNOS positive cells (by immunohistochemistry).Results Compared with group C,the time of staying at the original platform quadrant was significantly shortened at T1,2,the frequency of crossing the original platform was reduced at T1,the expression of nNOS in hippocampus was down-regulated,and the number of nNOS positive cells in hippocampal CA1 region was reduced in group S (P＜0.05),and no significant change was found in the parameters mentioned above in group D+S (P＞0.05).Compared with group S,the time of staying at the original platform quadrant was significantly prolonged at T1,the frequency of crossing the original platform was increased at T1,2,the expression of nNOS in hippocampus was up-regulated,and the number of nNOS positive cells in hippocampal CA1 region was increased in group D+S (P＜0.05).Conclusion Dezocine can improve cognitive function after sevoflurane anesthesia in a rat model of physiological stress,and the mechanism may be related to up-regulating nNOS expression in hippocampi.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Currently, hepatectomy, radiofrequency ablation, interventional therapy, and so on are widely used in the treatment of liver cancer; however the 5-year survival rate of patients is still very poor. The onset of liver cancer is insidious, and most patients do not have the opportunity to undergo surgery when they are initially diagnosed. In addition, patients with advanced liver cancer lack effective treatment, which is mainly due to chronic inflammation of the liver. Immunotherapy has great potential advantages in the treatment of liver cancer, so it has attracted more and more researchers' attention. Importantly, with the development of biomedical science into the era of precision medicine, more precise and effective immunotherapy strategies for HCC treatment have been explored, thus bringing new hope to HCC patients. This article reviews the research status and progress of liver cancer immunotherapy in the context of precision medicine.

The comprehensive detection and identification of active ingredients in complex matrices is a crucial challenge.Liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS)is the most prominent analytical platform for the exploration of novel active compounds from complex matrices.However,the LC-HRMS-based analysis workflow suffers from several bottleneck issues,such as trace content of target compounds,limited acquisition for fragment information,and uncertainty in interpreting relevant MS2 spectra.Lycibarbarspermidines are vital antioxidant active ingredients in Lycii Fructus,while the reported structures are merely focused on dicaffeoylspermidines due to their low content.To comprehensively detect the new structures of lycibarbarspermidine derivatives,a"depict"strategy was developed in this study.First,potential new lycibarbarspermidine derivatives were designed according to the biosynthetic pathway,and a comprehensive database was established,which enlarged the coverage of lycibarbarspermidine derivatives.Second,the polarity-oriented sample prep-aration of potential new compounds increased the concentration of the target compounds.Third,the construction of the molecular network based on the fragmentation pathway of lycibarbarspermidine derivatives broadened the comprehensiveness of identification.Finally,the weak response signals were captured by data-dependent scanning(DDA)followed by parallel reaction monitoring(PRM),and the efficiency of acquiring MS2 fragment ions of target compounds was significantly improved.Based on the integrated strategy above,210 lycibarbarspermidine derivatives were detected and identified from Lycii Fructus,and in particular,170 potential new compounds were structurally characterized.The integrated strategy improved the sensitivity of detection and the coverage of low-response components,and it is expected to be a promising pipeline for discovering new compounds.

The stimulator of interferon genes(STING),an integral adaptor protein in the DNA-sensing pathway,plays a pivotal role in the innate immune response against infections.Additionally,it presents a valuable therapeutic target for infectious diseases and cancer.We observed that fangchinoline(Fan),a bis-benzylisoquinoline alkaloid(BBA),effectively impedes the replication of vesicular stomatitis virus(VSV),encephalomyocarditis virus(EMCV),influenza A virus(H1 N1),and herpes simplex virus-1(HSV-1)in vitro.Fan treatment significantly reduced the viral load,attenuated tissue inflammation,and improved survival in a viral sepsis mouse model.Mechanistically,Fan activates the antiviral response in a STING-dependent manner,leading to increased expression of interferon(1FN)and interferon-stimulated genes(ISGs)for potent antiviral effects in vivo and in vitro.Notably,Fan interacts with STING,preventing its degradation and thereby extending the activation of IFN-based antiviral responses.Collectively,our findings highlight the potential of Fan,which elicits antiviral immunity by suppressing STING degra-dation,as a promising candidate for antiviral therapy.

Obesity, which underlies various metabolic and cardiovascular diseases, is a growing public health challenge for which established therapies are inadequate. Given the current obesity epidemic, there is a pressing need for more novel therapeutic strategies that will help adult individuals to manage their weight. One promising therapeutic intervention for reducing obesity is to enhance energy expenditure. Investigations into human brown fat and the recently discovered beige/brite fat have galvanized intense research efforts during the past decade because of their pivotal roles in energy dissipation. In this review, we summarize the evolution of human brown adipose tissue (hBAT) research and discuss new in vivo methodologies for evaluating energy expenditure in patients. We highlight the differences between human and mouse BAT by integrating and comparing their cellular morphology, function, and gene expression profiles. Although great advances in hBAT biology have been achieved in the past decade, more cellular models are needed to acquire a better understanding of adipose-specific processes and molecular mechanisms. Thus, this review also describes the development of a human brown fat cell line, which could provide promising mechanistic insights into hBAT function, signal transduction, and development. Finally, we focus on the therapeutic potential and current limitations of hBAT as an anti-glycemic, anti-lipidemic, and weight loss-inducing 'metabolic panacea'.
Adipose Tissue, Beige ; metabolism ; pathology ; Adipose Tissue, Brown ; metabolism ; pathology ; Animals ; Cell Line ; Energy Metabolism ; Humans ; Mice ; Obesity ; metabolism ; pathology ; therapy