The methord of using pretreatment fitration and adsorption-prirrary ultafiltration-ion exchange-secondary ultrafiltration techogical.process to prepare water for injection fromtap water,river water,well water, fish pond water was studied. Through the examnination of pharmacopeia prescribed items,the examination of bactriology,spectrum analysis,the quality of water product prep-ared by using this technological process accorded with the stipulations of water for injection of Chinese pharmarcopeia edition No.21.It has been proved to be an efficient technological process for preparing water for injection.

Objective:To analyze the expression of CD27 on T lymphocytes in the microenvironment of multiple myeloma (MM), and explore whether CD27 level or the CD27-/CD27+ ratio of T-cell affect the prognosis of MM patients.Methods:A total number of 103 newly-diagnosed MM patients from January 2016 to June 2019 were enrolled in the Affiliated Cancer Hospital of Harbin Medical University. All patients received bortezomib-based three-drugs combination regimen. The expression of CD27 on T lymphocytes in bone marrow aspirate samples was detected by flow cytometry before any treatment. MM patients were divided into two groups according to the CD27 level: CD27-high expression group (CD27 expression on T-cells ≥20%) and CD27-low expression group (CD27 expression on T-cells <20%). The clinical characteristics, treatment response and prognosis of patients between the two groups were analyzed using χ 2-test. The survival and clinical information of patients were compared using Kaplan-Meier method, and the related factors related to the survival of MM were analyzed using Cox proportional risk model. Results:Among 103 MM patients, 68 cases (66.0%) were included in CD27 high expression group, and 35 cases (34.0%) were included in low expression group. The percentage of bone marrow plasma cells and β2-MG level in CD27 high expression group were higher than those in CD27 low expression group significantly (54.4% [37/68] vs 22.9% [8/35], χ2=9.352, P=0.002;58.8% [40/68] vs 37.1% [13/35], χ2=4.348, P=0.037), and the proportion of ISS stage Ⅱ-Ⅲ in CD27 high expression group was higher than the counterpart (79.4% [54/68] vs 60% [21/35], χ2=4.399, P=0.036). After 4 cycles of three-drug combination therapy, the overall response rate ( ORR=stringent complete response+complete response+very good partial response+partial response) of the low CD27 expression group was higher than the high expression group (82.9% [29/35] vs 38.2% [26/68], χ2=18.489, P<0.01). The deep response rate to treatment (stringent complete response+complete response+very good partial response) was higher (48.6% [17/35] vs 27.9% [19/68], χ2=4.326, P=0.038), and the progression, free surviva (PFS) was longer (21months vs.14.1months, t=18.655, P<0.001) in the low expression group compared with CD27-high group. Univariate analysis showed that CD27-/CD27+T lymphocyte ratio, ISS stage Ⅱ-Ⅲ, age ≥65 years, β2-Mg ≥3.5 mg/L, and plasma cell proportion ≥30% were associated with the poor prognosis of MM patients, and the differences were significant statistically ( P<0.05). Multivariate analysis showed that CD27-/CD27+T lymphocyte ratio was an independent prognostic factor for 2-year overall survival (OS)( HR=2.425, 95% CI 1.216-4.835, P=0.012) and 2-year PFS ( HR=1.881, 95% CI 1.085-3.260, P=0.024) in MM patients. Conclusions:The expression of CD27 in T lymphocytes is correlated with the prognosis, treatment response and progression-free survival of MM. The ratio of CD27-/CD27+T lymphocytes is an independent prognostic indicator.

The central nervous system is susceptible to the modulation of various neurophysiological processes by the cytochrome P450 enzyme(CYP),which plays a crucial role in the metabolism of neurosteroids.The antiepileptic drug phenytoin(PHT)has been observed to induce neuronal side effects in patients,which could be attributed to its induction of CYP expression and testosterone(TES)metabolism in the hip-pocampus.While pregnane X receptor(PXR)is widely known for its regulatory function of CYPs in the liver,we have discovered that the treatment of mice with pregnenolone 16α-carbonitrile(PCN),a PXR agonist,has differential effects on CYP expression in the liver and hippocampus.Specifically,the PCN treatment resulted in the induction of cytochrome P450,family 3,subfamily a,polypeptide 11(CYP3A11),and CYP2B10 expression in the liver,while suppressing their expression in the hippocampus.Func-tionally,the PCN treatment protected mice from PHT-induced hippocampal nerve injury,which was accompanied by the inhibition of TES metabolism in the hippocampus.Mechanistically,we found that the inhibition of hippocampal CYP expression and attenuation of PHT-induced neurotoxicity by PCN were glucocorticoid receptor dependent,rather than PXR independent,as demonstrated by genetic and pharmacological models.In conclusion,our study provides evidence that PCN can negatively regulate hippocampal CYP expression and attenuate PHT-induced hippocampal neurotoxicity independently of PXR.Our findings suggest that glucocorticoids may be a potential therapeutic strategy for managing the neuronal side effects of PHT.