Objective:To investigate the effects of Acanthopanax Senticosus polysaccharides (ASPS) on TLR4 signaling pathway in Lewis tumor-bearing mice,and to explore the immunomodulatory mechanism of ASPS.Methods:Lewis lung carcinoma cells and C57BL/6 mice were used to establish the animal model for solid tumor.The tumor-bearing mice were divided into five groups:normal saline (NS) group,Adriamycin (ADM) group,ASPS low-dose group,ASPS middle-dose group and ASPS high-dose group.Mter 25 d treatment,the weight of tumor,tumor inhibition rate and immune organ index were measured.ELISA were applied to detected the cytokines in peripheral blood of tumor-bearing mice.Quantitative real-time PCR (Q-PCR) and Western blot were selectively used to detect the gene and protein expression of TLR4 signaling pathway in splenocytes.Results:The tumor inhibition rate,immune organ index and the secretion of TNF-α,IL-1β and IL-6 were increased by ASPS,compared with NS group (P＜0.05).The gene and protein expression of TLR4,MyD88,TRAF6,NF-κB p65 and AP-1 were also induced by ASPS (P＜0.05).Meanwhile,ASPS had no obvious effects on the secretion of IL-12p70 and the expression of TRAM (P＞0.05).Conclusion:TLR4 signaling pathway may be involved in the immunomodulatory effects of ASPS on Lewis tumor-bearing mice.

Aim The current study was conducted to investigate the effect of GSTP1 codon 105 polymorphism, alone and in combination with GSTM1-deletion polymorphism, on erythrocyte GST activity in 196 Han Chinese. Methods GST activity was measured in healthy Chinese by a spectrophotometric method (n=196;101 males and 95 females; age range 21～81 years; median 43.5 years). GSTM1 polymorphisms were analyzed by a PCR-Multiplex procedure, whereas GSTP1 polymorphism was analyzed by PCR-RFLP. Results The frequency of GSTM1 null genotype was 56.1% and the frequency of I/I, I/V, and V/V genotypes was 60.7%, 35.2% and 4.1%, respectively, in Han Chinese. The mean erythrocyte GST enzyme activity for I/V genotype group(3.53?0.63 U?g -1Hb) was significantly lower than that for I/I genotypes (4.25?1.07 U?g -1Hb, P=0.000), while significantly higher than that for V/V genotypes (2.44?0.67 U?g -1Hb, P=0.004). In GSTM1(-) group, the GST activity of carriers of GSTM1(-)/GSTP1- I/I is significantly higher than that of GSTM1(-)/GSTP1- I/V or-V/V, however, in GSTM1(+) group, there is no difference between different subgroups. There was no significant difference in the mean GST activity among different age groups. Erythrocyte GST activities were significantly higher in females than in males, but not significantly. Conclusion The GST activity measured by CDNB-based assay is probably strongly correlated with the GSTP1 105Val genotype, although other GST enzymes would tend to dilute the GSTP1 genotype effect.

Objective:To detect the effects of polysaccharopeptide(PSP) on MyD88-dependent signaling pathway in EAC tumor-bearing mice,and explore the immunomodulatory mechanism of PSP.Methods: Ehrlich′s ascites carcinoma(EAC) C57BL/6 mice were used to establish the animal model for solid tumor.Mice were divided into two groups:WT group and MyD88-/-group.After 22 days of treatment,quantitative real-time PCR( Q-PCR) ,Western blot and were used to detect the related gene and protein expression of TLR4 pathway in spleens,ELISA were used to detect the terminal effect factors secretion eyeball blood from each group.Results:Related genes and proteins of TLR4 pathway in spleen were up-regulated significantly from two groups.Compared with WT group, related genes and proteins in MyD88-dependent pathway(MyD88,TRAF6,NF-κB,AP-1)was down-regulated in MyD88-/-group(P<0.05).Meanwhile,There was no significant change of the related genes and proteins of MyD88-independent pathway(TRAM,TRIF)in MyD88-/-group( P>0.05 ) .The terminal effect factors secretion of IL-2, IL-6, IL-10, TNF-αand IFN-γin MyD88-/-group were decreased significantly compared with WT group(P<0.05).Conclusion:The immunoregulatory effect of PSP on EAC tumor-bearing mice may be implement through the regulation of MyD88-dependent signaling pathway.

OBJECTIVETo explore the inhibitory effects of highly toxic organophosphorus compound and its substitute (methamidophos and acephate) on acetylcholinesterase (AChE) and their toxic mechanisms.

METHODSEllman method was used to measure AChE activity in vitro and vivo.

RESULTSAcephate and methamidophos could directly inhibit AChE activities in human erythrocyte membrane and rat brain synatosomal membrane in dose- and time-dependent manners in vitro, and this effect was irreversible. The IC50 of acephate and methamidophos affecting human erythrocyte membrane and rat synatosomal membrane were approximately 10(-4) mol/L and 10(-5) mol/L respectively and the Ki were 10(2) mol.L-1.min-1 and 10(3) mol.L-1.min-1 respectively. In vivo, after rats being administered with them for 5 d, the inhibitory rate of AChE activities in blood were increased to 68.24% and 54.80% respectively. When rats being administrated with acephate, there was 31.68% of inhibition on the brain stem, but no significant inhibition in other brain region was noticed, while methamidophos had a strong inhibitory effect on the activity of AChE in all brain regions, especially the cerebellum and brain-stem(71.51% and 61.85% respectively).

CONCLUSIONAcephate and methamidophos could directly inhibit the AChE activities in vitro, but the inhibition degree was different. In vivo, both could also inhibit AChE activities in blood. The difference in inhibition on brain regions may be one of the reason of various toxic effect of them.

Animals ; Cholinesterase Inhibitors ; toxicity ; Erythrocyte Membrane ; enzymology ; Humans ; Insecticides ; toxicity ; Organothiophosphorus Compounds ; toxicity ; Phosphoramides ; Rats ; Synaptosomes ; enzymology

Objective To observe the effect of Huoluojiangu Capsule(HJC) on anti-inflammatory experiment.Methods The anti-inflammatory experimental models were established in three kinds of rats with pleuritis,the swellen sole of the foot and the PGE_2 content in inflammatory tissues,respectively.Results The swollen reaction in the sole of foot in rats induced by egg white was lessoned with the treatment of low,middle and high dosage of HJC.Compared with the blank control group,the treatment is effective in low dosage group and evidently effective in groups of middle and high dosage after 30 min(P0.05),respectively.Compared with the blank control group,the effect of HJC on the PGE_2 content in the inflammatory tissues of middle and high dosage groups was significant(P

Objective To assess the reliability and validity of the Chinese version of Driving Anger Scale (DAS) in professional drivers in China and provide a scientific basis for the application of the scale in drivers in China. Methods Professional drivers, including taxi drivers, bus drivers, truck drivers and school bus drivers, were selected to complete the questionnaire. Cronbach's α and split-half reliability were calculated to evaluate the reliability of DAS, and content, contract, discriminant and convergent validity were performed to measure the validity of the scale. Results The overall Cronbach'sα of DAS was 0.934 and the split-half reliability was 0.874. The correlation coefficient of each subscale with the total scale was 0.639-0.922. The simplified version of DAS supported a presupposed six-factor structure, explaining 56.371% of the total variance revealed by exploratory factor analysis. The DAS had good convergent and discriminant validity, with the success rate of calibration experiment of 100%. Conclusion DAS has a good reliability and validity in professional drivers in China, and the use of DAS is worth promoting in divers.

Objective Based on the process theory of stress effect,the structural equation model of the influencing factors of self-regulatory fatigue in maintenance hemodialysis patients is constructed,which provides theoretical bases and references for the formulation of intervention programs to relieve self-regulatory fatigue in patients.Method A total of 420 maintenance hemodialysis patients were surveyed using General Information Questionnaire,Self-Regulatory Fatigue Scale,Dialysis Symptom Index,Life Orientation Test-Revised,Perceived Social Support Scale,Brief Illness Perception Questionnaire and Medical Coping Styles Questionnaire.Results Total score of self-regulatory fatigue in maintenance hemodialysis patients was(49.52±10.93),and self-regulatory fatigue showed significant positive correlation with symptom distress,the illness perception,avoidance coping style,yieldly coping(r=0.476,0.428,0.303,0.611,all P＜0.01);self-regulatory fatigue showed significant negative correlation with perceived social support and dispositional optimism(r=-0.410,-0.652,all P＜0.01);it showed no significant correlation with facing coping(r=-0.032,P＞0.05).The Bootstrap analysis revealed that the mediation effect of yielding coping,dispositional optimism,perceived social support,and illness perception between symptom distress and self-regulatory fatigue was significant(95％CI:0.027～0.203).The overall effect of symptom distress on self-regulatory fatigue was(P＜0.001,95％CI:0.576～0.751);the direct effect was(P＜0.001,95％CI:0.170～0.357);the indirect effect was(P＜0.001,95％CI:0.332～0.485);the mediation effect accounted for 61.1％of the total effect value.Conclusion Maintenance hemodialysis patients have a high degree of self-regulatory fatigue,which needs to be further improved.Medical staff should timely identify and evaluate the symptom distress of patients,focus on guiding patients to adjust optimistic disease,provide patients with psychological guidance and stress coping strategies,reduce the negative coping behavior tendency,guide the patients correctly perceive support and care in social relations,help patients set up the correct disease cognition,thus reducing the patient's self-regulatory fatigue.

Objective:To evaluate the safety and efficacy of bortezomib plus highdose melphalan (L-phenylalanine nitrogen mustard) (Bor-HDM) pretreatment regimen for multiple myeloma (MM) with autologous hematopoietic stem cell transplantation (ASCT).Methods:From August 2008 to December 2021, the relevant clinical data were retrospectively reviewed for 58 MM patients undergoing MM transplantation.The conditioning regimens were Bor-HDM (n=36) and HDM (n=22). Non-hematopoietic adverse reactions, hematopoietic reconstruction time, remission rate post-ASCT and minimal negative rate of residual disease (MRD) on flow cytometry within 3 months post-ASCT and survivals were analyzed.Results:In Bor-HDM and HDM groups, median time of neutrophil engraftment was 12(8-30) and 11(8-29) day and median time of platelet reconstitution 16(8-33) and 16(7-32) day respectively.There was no significant inter-group difference ( P=0.890, P=0.638). In Bor-HDM group, the most common non-hematological adverse reactions were nausea (n=21, 58.0%) and diarrhea (n=11, 30.6%). There was no transplant-related death.Complete remission (CR) rate was (25/36, 69.4%) versus (9/22, 40.9%). The inter-group difference was statistically significant ( P=0.032). Median follow-up period was 29.0(2.0-91.0) vs. 20.5(5.0-114.0) month, 3-year progression-free survival(PFS)62.1% vs. 39.7% and 3-year overall survival(OS) 83.8% vs. 62.5%.There were relapse (n=10 vs.10) and death (n=6 vs. 7). Median PFS in Bor-HDM and HDM groups was non-attained and 27 months( P=0.047) and median OS time non-attained and 40 months respectively ( P=0.282). Multivariate analysis revealed that CR was an independent risk factor for PFS ( HR=28.896, 95% CI: 6.130-136.198, P<0.001). Non-CR was an independent risk factor for OS ( HR=3.843, 95% CI: 1.334-11.071, P=0.013; HR=28.595, 95% CI: 6.273-130.355, P<0.001). Conclusions:Bor-HDM pretreatment regimen of ASCT is both safe and efficacious for MM patients.

Objective:To explore the clinical efficacy and risk factors of umbilical cord mesenchymal stem cells (UCMSCs) infusion at an early stage (i.e.gross hematuria) for hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The relevant clinical data were retrospectively reviewed for 300 patients undergoing allo-HSCT from January 2016 to July 2021.According to the presence or absence of HC, they were assigned into two groups of HC (n=89) and non-HC (control, n=211). According to whether or not receiving an infusion of UCMSCs, 51 patients of HC degree Ⅱ-Ⅳ were divided into two groups of UCMSC infusion and non-infusion.The risk factors of HC after allo-HSCT were analyzed by χ2 test.Logistic regression was employed for multivariate analysis of P<0.05.Mann-Whitney U test was utilized for statistically analyzing the duration of gross hematuria and urinary tract irritation symptoms and evaluating the clinical efficacy of UCMSCs infusion for HC. Results:Among them, 89 (29.67%) developed HC post-allo-HSCT.Clinical grades were Ⅰ (n=38, 42.70%), Ⅱ (n=36, 40.45%), Ⅲ (n=13, 14.61%) and Ⅳ (n=2, 2.25%). The median occurrence time was 29 (21.5-35.0) days post-allo-HSCT.In univariate analysis, age ≤30 years, haploid transplantation, antithymocyte globulin (ATG), acute graft-versus-host disease (aGVHD), CMV-DNA positive pretreatment significantly boosted the risk of HC ( P<0.05). In multivariate analysis, aGVHD was an independent risk factor for HC ( OR=10.281, 95% CI: 1.606-65.813, P=0.014). Among 89 HC patients, 38 grade Ⅰ patients were complete remission(CR). Among 51 patients of grade Ⅱ-Ⅳ HC, the outcomes were CR (n=48) and non-remission(NR)(n=3). And 24/51 of them received UCMSCs plus conventional treatment.The duration of gross hematuria was shorter in UCMSCs infusion group than that in UCMSCs non-infusion group [12(9-17) vs 17(12.0-26.5) day] and the difference was statistically significant ( P=0.045). And the duration of urinary tract irritation symptoms was shorter in UCMSCs infusion group than that in UCMSCs non-infusion group [18(11-30) vs 27(18.0-35.5) days] and the difference was statistically significant ( P=0.048). Conclusions:Indicated for post-ALLO-HSCT HC, infusion of UCMSCs may significantly shorten the course of disease.Age ≤30 years, haploid transplantation and preconditioning with positive ATG, aGVHD and CMV-DNA may boost the risks of HC post-allo-HSCT.And aGVHD is an independent risk factor for HC after allo-HSCT.

Colorectal cancer (CRC) has a high incidence and mortality rate worldwide. Its lesions are associated to gene mutation, epigenetic changes and activation of related signaling pathways. microRNAs (miRNAs) are a class of non-coding RNAs of 20-24 nt in length that can regulate the expression of target mRNAs and control various cellular mechanisms. As a novel marker for the treatment and prognosis of colorectal cancer, miRNAs are closely related to the occurrence and progression of colorectal cancer. In this review, we summarize the miRNAs dysregulated in CRC tissues, analyze the relationship between specific miRNAs and CRC proliferation, metastasis, apoptosis, and chemotherapy, and present the clinical applications of miRNAs in CRC treatment and prognosis.