[Objective]To assess the effectiveness of prepared strychnine in the treatment of bortezomib-induced peripheral neuropathy(BIPN)and explore the mechanism of intervention of BIPN based on long noncoding RNA(lncRNA)X inactivated specific transcript(XIST)/ZNFX1 antisense RNA 1(ZFAS1).[Methods]Twenty patients diagnosed as multiple myeloma who received bortezomib(BTZ)and developed BIPN and received strgchnine treatment were collected by prospective non-randomized controlled study method.The traditional Chinese medicine(TCM)symptom score,neurotoxicity score,peripheral neuropathy(PN)grade,and partial peripheral nerve conduction velocity were compared with patients who did not receive strychnine treatment.Using self-control,peripheral blood samples were collected from patients in the treatment group,and enzyme-linked immunosorbent assay(ELISA)was used to detect the expression of inflammation-related factors.DRG 50B11 cells were cultured and screened by cell counting kit-8(CCK-8)for the optimal acting concentration and time of strychnine and the optimal acting time of BTZ,and the cases were randomly divided into normal control group,BTZ group,and strychnine+BTZ group.Real-time quantitative polymerase chain reaction(Real-time qPCR)was used to detect the expression levels of inflammation-related factors and total RNA related indexes,and it analyzed the differences and correlations.[Results]The clinical study showed that compared with control group,PN,TCM syndrome scores and neurotoxicity score were decreased after treatment,while peripheral nerve conduction velocity was increased(P＜0.05),and there were no significant adverse effects.The experimental results showed that compared with those before treatment,the expression of interleukin-17(IL-17),tumor necrosis factor-α(TNF-α),IL-1β,IL-6,nerve growth factor(NGF)and brain-derived neurotrophic factor(BDNF)were reduced(P＜0.05),and there was a significant negative correlation with time(P＜0.01).Compared with BTZ group,the expression levels of IL-17,TNF-α,IL-1β,IL-6,NGF,BDNF,the lncRNA XIST,fibronectin 1(FN1)and phospho-focal adhesion kinase(p-FAK)were decreased in strychnine+BTZ group(P＜0.05),while the expressions of miR-96-5P and miR-1271-5P increased(P＜0.05),without significant difference in the expression of lncRNA ZFAS1(P＞0.05).lncRNA XIST expression levels were significantly positively correlated with the expressions of IL-17,TNF-α,IL-1β,IL-6,NGF,BDNF,FN1 and p-FAK(P＜0.01),but no moderate negative correlated with miR-96-5P(P＜0.05),or very weakly correlated or no correlated with miR-1271-5P(P＞0.05).[Conclusion]Prepared strychnine capsule can alleviate BIPN to a certain extent and is relatively safe,and its mechanism may be related to the regulation of lncRNA XIST for promoting the expression of miR-96-5P/FN1 and inhibit p-FAK-mediated neuroinflammation.

Objective To observe the activity of histone deacetylase and the mRNA expression level of HDAC1 and HDAC2 in human bone marrow mononuclear cells,which induced by hydroquinone and exposed to hydroquinone plus Trichostatin as a histone deacetylase inhibitor for 10 hours respectively.Methods Collect the bone marrow mononuclear cells suspension,divided into control group,HQ group (3 h,6 h,12 h,24 h),HQ+ TSA 10 h group and HQ 10 h group.Extract the nuclear proteins and RNA,test the activity of histone deacetylase with the colorimetric HDAC assay kit and detect the mRNA expression level of HDAC 1 and HDAC2 by real-time Polymerase Chain Reaction(PCR).Results The HDAC activity of HQ3 h group,HQ6 h group and HQ12 h group were 1.31 times,1.53 times and 1.148 times than that of control group respectively.And the difference was statistically significant (P＜0.05).Except the HQ24 h group (P＞0.05),the HDAC1 mRNAexpression of HQ3 h group,HQ6 h group and HQ12 h group were 1.173 times,1.901 times and 2.348 times than that of control group respectively.And the difference was statistically significant (P＜0.05).The HDAC2 mRNA expression of HQ6 h group and HQ12 h group were 1.426 times and 1.766 times than that of the control group respectively.And the difference was statistically significant (P＜0.05).No significant difference was observed between HQ3 h group,HQ24 h group and control group(P＞0.05).The cells were treated by hydroquinone plus TSA for 10 hours.The HDAC activity of HQ+TSA 10h group was reduced by 25.6％ than that of HQ 10 h group (P＜0.05) and rised 13.0％ compared to the control group (P＜0.05).And the difference was statistically significant between groups (P＜0.05).The cells were treated by hydroquinone plus TSA for 10 hours.The HDAC 1 mRNA expression of the HQ+TSA 10h group is reduced by 26.9％ than that of HQ10h group.The HDAC2 mRNA expression is reduced by 19.3％ compared to the HQ 10h group.And the difference was statistically significant between groups (P＜0.05).The HDAC1 and HDAC2 mRNA expression is obviously higher than the control group,the difference was statistically significant (P＜0.05).Conclusion Treatment of hydroquinone,the histone deacetylase activity and the mRNA expression of HDAC1 and HDAC2 were increased in a certain time range.The histone deacetylase inhibitor (TSA) can reduce the histone deacetylase activity and the mRNA expression level of HDAC 1 and HDAC2 in the bone marrow mononuclear cell induce by hydroquinone.It can be confirmed that hematopoietic damage induced by the benzene metabolites is related to the histone acetylation modification level.

Objective To observe the activity of histone deacetylase and the mRNA expression level of HDAC1 and HDAC2 in human bone marrow mononuclear cells,which induced by hydroquinone and exposed to hydroquinone plus Trichostatin as a histone deacetylase inhibitor for 10 hours respectively.Methods Collect the bone marrow mononuclear cells suspension,divided into control group,HQ group (3 h,6 h,12 h,24 h),HQ+ TSA 10 h group and HQ 10 h group.Extract the nuclear proteins and RNA,test the activity of histone deacetylase with the colorimetric HDAC assay kit and detect the mRNA expression level of HDAC 1 and HDAC2 by real-time Polymerase Chain Reaction(PCR).Results The HDAC activity of HQ3 h group,HQ6 h group and HQ12 h group were 1.31 times,1.53 times and 1.148 times than that of control group respectively.And the difference was statistically significant (P＜0.05).Except the HQ24 h group (P＞0.05),the HDAC1 mRNAexpression of HQ3 h group,HQ6 h group and HQ12 h group were 1.173 times,1.901 times and 2.348 times than that of control group respectively.And the difference was statistically significant (P＜0.05).The HDAC2 mRNA expression of HQ6 h group and HQ12 h group were 1.426 times and 1.766 times than that of the control group respectively.And the difference was statistically significant (P＜0.05).No significant difference was observed between HQ3 h group,HQ24 h group and control group(P＞0.05).The cells were treated by hydroquinone plus TSA for 10 hours.The HDAC activity of HQ+TSA 10h group was reduced by 25.6％ than that of HQ 10 h group (P＜0.05) and rised 13.0％ compared to the control group (P＜0.05).And the difference was statistically significant between groups (P＜0.05).The cells were treated by hydroquinone plus TSA for 10 hours.The HDAC 1 mRNA expression of the HQ+TSA 10h group is reduced by 26.9％ than that of HQ10h group.The HDAC2 mRNA expression is reduced by 19.3％ compared to the HQ 10h group.And the difference was statistically significant between groups (P＜0.05).The HDAC1 and HDAC2 mRNA expression is obviously higher than the control group,the difference was statistically significant (P＜0.05).Conclusion Treatment of hydroquinone,the histone deacetylase activity and the mRNA expression of HDAC1 and HDAC2 were increased in a certain time range.The histone deacetylase inhibitor (TSA) can reduce the histone deacetylase activity and the mRNA expression level of HDAC 1 and HDAC2 in the bone marrow mononuclear cell induce by hydroquinone.It can be confirmed that hematopoietic damage induced by the benzene metabolites is related to the histone acetylation modification level.

Objective:To explore the risk factors and outcomes of central nervous system(CNS)complications associated with hematopoietic stem cell transplantation(HSCT).Methods:A total of 550 recipient after HSCT in the department of hematology of Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 1 2019 to August 31 2021were enrolled.According to the occurrence of CNS complications, they were divided into the CNS group(24 cases)and the non CNS group(526 cases). The clinical information and prognosis were compared.We further analyzed the risk factors associated with CNS complications, and conducted multivariate logistic regression on statistically significant indicators.Cox regression analysis is conducted on prognostic factors such as age, gender and risk degree.Results:A total of 550 recipients were enrolled, of which 330 underwent allo-HSCT, and others received auto-HSCT.A total of 24 cases (4.36%)had CNS complications, of which 4 cases had 2 types of CNS complications.The type of CNS complications included intracranial infection(8 cases, 28.57%), transplantation-associated thrombotic microangiopathy(TA-TMA)(6 cases, 21.43%), central tumor invasion(4 cases, 14.29%), intracranial hemorrhage(4 cases, 14.29%), leucodystrophy(2 cases, 7.14%)and unexplained encephalopathy(4 cases, 14.29%). Logistic regression analysis of risk factors related to CNS complications showed that, Platelet implantation time( β=0.084, OR=1.088, P=0.048), CMV infection( β=1.295, OR=3.65, P=0.008)is positively correlated with the occurrence of CNS complications in HSCT recipients but age( β=-0.052, OR=0.949, P=0.004)is negatively correlated with it.Nine of the 24 cases(37.50%)who experienced CNS complications died, including 3 cases of intracranial infection, 3 cases of cerebral hemorrhage, 2 cases of TMA, and 1 case of unexplained encephalopathy.Platelet implantation time is an independent risk factor for poor prognosis of CNS complications in HSCT recipients. Conclusions:Our results indicated that, age, CMV infection and platelet implantation time were associated with the occurrence of CNS complications after HSCT.Platelet implantation time is an independent risk factor for poor prognosis of CNS complications in HSCT recipients.