Objective To study the inhibition of berberine on organ anion transporters (OATs) and its bidirectional trans-membrane transport.Method The transgene cell lines of the organ anion transporters including OAT1,OAT2,OAT3,OAT4,OAT7,and URAT1 were constructed and selected by animal cell transgenic method mediated by transporter Lipo 3000.Wild type (WT) cells were used as control group,and activity of OATs was verified by adding their radiolabeled substrates and inhibitors.The inhibition of 100 μmol/L berberine on the transporters was investigated in vitro.The IC50 of berberine on URAT1 was also determined.The bidirectional transport of berberine was studied through the Caco-2 model.Result The results showed that 100 μmol/L berberine inhibited the activity of OAT1,OAT2,OAT3,OAT4,OAT7 and URAT1 to (70.48±4.23)％,(69.13±1.28)％,(72.12±3.28)％,(79.77±6.49)％,(69.51 ±5.99)％ and (38.4 ± 2.67)％ respectively,the IC50 of berberine to URAT 1 was 13.19 μmol/L,the Papp (A-B) of 50 μmol/L and 100 μmol/L berberine were separately 0.28 × 10-6 and 0.40 × 10-6 cm/s,and the effiux rates were separately 3.18 and 3.15.Conclusion Berberine shows a stronger inhibition to URAT1 compared to OAT1,OAT2,OAT3,OAT4 and OAT7.Berberine may be the substrate of some effiux transporters.This study provides theoretical basis for explaining the low bioavailability ofberberine and forecasting the possible drug-drug interaction.

Objective To study the inhibitory effects ofberberine on human organic cation transporter (OCTs) including OCT1,OCT2,OCT3,OCTN1 and OCTN2.Methods Using animal cell transgenic method mediated by transporter Lipo 3000,the drug transporters over expression cell lines S2-OCT1,S2-OCT2,S2-OCT3,S2-OCTN1 and S2-OCTN2 were obtained by selective medium culture.The OCTs evaluation model was established by detecting the trans-membrane transport of radioactive substrate in vitro.Wild type (WT) cells were used as control group,activity of OCTs was verified by adding its inhibitor.The inhibition of berberine on the transporters was investigated in vitro.The IC50 of inhibitory effect of berberine on various drug transporters was also calculated.Result The transport activity of transporter cell lines was increased by more than 5 times compared to the WT cell line respectively,what's more,their transport activity decreased significantly by their corresponding inhibitor.The ICs0 of berberine to OCT1,OCT2,OCT3,OCTN1 and OCTN2 were respectively 7.63,6.80,2.25,4.66 and 210.34 μmol/L.Conclusion Berberine significant inhibition to OCT1,OCT2,OCT3,OCTN1 and OCTN2.The inhibition on OCT1,OCT2,OCT3,OCTN1 is stronger compared to OCTN2.

Objective: To investigate the role of PRDM1 gene inactivaion in the regulation of C-MYC in diffuse large B-cell lymphoma (DLBCL), and to explore the correlation of its immunophenotype and prognosis. Methods: 100 cases paraffin-embedded DLBCL tissues were collected from January 2009 to December 2015 at the First Affiliated Hospital of Xinjiang Medical University along with 20 cases of reactive proliferative lymph nodes as control. Immunohistochemical methods were used to detect the expression of CD20, CD10, MUM1, Ki-67, bcl-6, PRDM1/Blimp1, C-MYC and PAX5 protein. The tumors were classified into two subtypes according to Hans classification.The expression of PRDM1 and C-MYC gene in tumor group and control group was detected by reverse transcription PCR (RT-PCR) and the relationship between PRDM1 and C-MYC gene was analyzed.OCI-LY1 (GCB subtype) and OCI-LY3 (non-GCB subtype) cell lines were transfected with small interfering RNA by cationic liposome reagent transfection, and the expression of C-MYC in the transfected cell lines was detected by RT-PCR and Western blot. The Kaplan-Meier method was used to analyze the prognostic significance of PRDM1/Blimp1 and C-MYC at protein and mRNA levels. Results: There were 27 cases of GCB subtype and 73 cases of non-GCB subtype according to Hans classification. The positive expression of Blimp1 in DLBCL group and proliferative lymph nodes in control group was seen in 26(26.0%) and 20 cases(100%), respectively. There were 58 cases with high expression of PRDM1 at mRNA level, including 22 cases of GCB subtype and 36 cases non-GCB subtype, and the difference was statistically significant (P=0.004). There were differences in PRDM1 gene expression between the two immunological subtypes, serum lactate dehydrogenase (serum LDH) level, presence of B symptoms, tumor primary sites and other clinical pathological parameters, while C-MYC expression was different in gender, IPI score, and serum LDH levels. Upon PRDM1/Blimp1 gene silencing in the two cell lines, C-MYC protein and gene expression were up-regulated in the transfection group, compared with the blank control group and negative control group by reverse transcription PCR and Western blot analyses. Moreover, PRDM1 expression was significantly associated with C-MYC(χ²=7.648, P=0.006) at mRNA level. Conclusion The up-regulation of C-MYC gene expression induced by PRDM1 inactivation in DLBCL may play an important role for the development of DLBCL.PRDM1 protein and mRNA are associated with immunophenotyping and PRDM1 mRNA is a marker of poor prognosis.

Gait deficits and balance disturbances are prevalent clinical features in Parkinson′s disease (PD). There is an increasing body of evidence pointing towards the degeneration of central cholinergic neurons as a crucial factor leading to these disturbances in PD. This paper presents a comprehensive review of the relevant research on the involvement of the central cholinergic system in the mechanisms underlying gait deficits and balance disturbance in PD. The aim is to provide new perspectives and insights for the treatment of gait deficits and balance disturbances in PD.

Objective:To clarify the evolutionary characteristics and key site variations of the GII.6[P7] genome of norovirus disease outbreak in China.Methods:Genome amplification and sequencing of 46 GII.6[P7] positive samples monitored from CaliciNet China from 2018 to 2021. Simultaneous integration of all ORF1 (GII. P7) and ORF2 (GII.6) sequences for Bayesian evolutionary analysis. And the use of Simplot for restructuring analysis.Results:According to Bayesian evolution analysis, GII. P7 polymerase has temporal evolutionary characteristics, with an average base replacement rate of 2.067× 10 -3 nucleotide substitution/site/year, and recombination with 4 different VP1 genotypes (GII.6, GII.7, GII.14, GII.20). In the capsid region, GII.6 noroviruses can be further divided into GII.6a, GII.6b and GII.6c subtypes. The 46 strains in this study belong to the GII.6a subtype, which are divided into the same cluster as the virus strain NHBGR59 circulating in China in 2015. Simplot analysis determined that the recombination site of the GII.6[P7] strain in this study was at the ORF1-2 junction. The amino acid site variation of VP1 mainly occurred at the end of P1.1 and the P2 region. Compared with the reference strain of GII.6a subtype, there was no variation in the receptor binding site. Conclusions:The GII.6[P7] recombinant strains of the norovirus outbreak from 2018 to 2021 in China all belong to the GII.6a[P7] subtype.