Study on long-acting analgesic lappaconitine hydrobromide lyotropic liquid crystal injection / 药学学报

Long-acting analgesia is a common clinical treatment method after surgery. The slow-release injection with long-acting analgesia has the advantages of less medication frequency and stable effect. In this study, the analgesic drug lappaconitine hydrobromide lyotropic liquid crystal injection was prepared, and its sustained release mechanism, drug release and pharmacodynamic characteristics were evaluated. The results of polarizing microscope and freeze-transmission electron microscope showed that the lyotropic liquid crystal injection of the liquid crystal precursor preparation of lappaconitine hydrobromide could be obtained by the combination of glycerol monooleate (GMO) and soybean lecithin (SPC) in different proportions. The results of dissolution study in vitro showed that the drug release rate of different forms of liquid crystal preparations was layered liquid crystal > cubic liquid crystal > hexagonal liquid crystal. The mathematical model fitting results of the release data showed that the external release of layered liquid crystal, cubic liquid crystal and hexagonal liquid crystal conforms to the Ritger-Peppas model, and the release mechanism was Fick diffusion. The results of pharmacodynamics study in vivo showed that the analgesic effect of lappaconitine hydrobromide lyotropic liquid crystal injection lasted for 3 days, and there was no abnormality in the incision and local tissue, showing good safety and tolerance. The study on drug release and elimination process of the in vivo gel repository showed that lappaconitine hydrobromide could be completely released from the lyotropic liquid crystal 3 days after administration, and the sustained-release materials could be gradually eliminated locally. All animal experiments were approved by the Experimental Animal Ethics Committee of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences (No. 2021-08-GY-61) and the experiments were conducted in accordance with the relevant guiding principles and regulations. The lyotropic liquid crystal injection of lappaconitine hydrobromide prepared in this study presented a solution state at room temperature, and underwent phase transition in contact with the body fluid at the administration site, formed a drug depot and exerted a slow drug release effect. This preparation can reduce systemic toxicity, prolong the duration of analgesia, reduce the number of administrations, improve the compliance of postoperative patients, and provide a reference for the design of long-term sustained release analgesic preparations.

CD7 expression and its prognostic significance in acute myeloid leukemia patients with wild-type or mutant CEBPA / 中华血液学杂志

Objective: To analyze the prognostic value of CD7 expression in newly diagnosed acute myeloid leukemia (AML) patients, and to further explore the correlation between CD7 expression and CEBPA mutation, and to clarify the prognostic value of CD7(+) in AML patients with wild-type (WT) or mutant-type (MT) CEBPA. Methods: The clinical data of 298 newly diagnosed non-M(3) AML patients between January 2010 and December 2016 were analyzed retrospectively. The clinical characteristics and prognosis of CD7(+) and CD7(-) patients were respectively compared in all patients, and in patients with WT and MT CEBPA. The relationship between CD7 expression and CEBPA mutation was determined by chi-square, and the effects of CEBPA mutation on survival and prognosis in CD7(+) group by Kaplan-Meier method. Results: In CD7(+) group, the frequencies of CEBPA mutation were 10.1% (single site) and 33.9% (double site) , significantly higher than those of the CD7(-) group (5.3% and 4.2%) (P=0.000) . Subgroup prognostic analysis showed a lower CR rate (P=0.001) and a higher RR (P=0.023) in CD7(+) group comparing to those of CD7(-) group in AML patients with wild type CEBPA. There were no statistical difference between CD7(+) group and CD7(-) group in overall survival (OS) and disease free survival (P>0.05) , while in the CEBPA mutant group the CD7(+) group has higher OS (P=0.019) and DFS (P=0.010) . Based on the CD7 expression and CEBPA mutation, 298 cases were divided into 3 subgroups, named as CD7(+)-CEBPA MT group, CD7(-) and CD7(+)-CEBPA WT group. The 3-year OS of the 3 groups were 80.2%, 48.0% and 30.6%, respectively (P<0.001) , and the 3-year DFS were 74.1%, 37.4% and 22.2%, respectively (P<0.001) . Conclusion: The CEBPA mutation rate was higher in CD7(+) AML patients then that of CD7(-) patients. CD7 expression has opposite prognostic significance in AML patients carrying the wild-type or mutant-type CEBPA. Based on CD7 expression and CEBPA mutation, a new risk stratification model can be established, which is helpful to guide the clinical individualized treatment for AML patients.

Autophagy in fibrotic and postoperative remnant liver in rat / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the characteristics of autophagy in fibrotic and postoperative remnant liver.</p><p><b>METHODS</b>Male Wistar rats were randomly divided into three groups: control group; fibrosis group, which received the solution of CCl4 in oil twice a week for 5 weeks; and hepatectomy group, which underwent 70% hepatectomy. Liver tissues and plasma were harvested 18 hours after the surgery. The rats' general conditions and plasma liver function were observed. Histopathological characteristics and regeneration were observed with microscope and transmission electron microscope. Qualitative analysis of autophagosome was made base on the data from transmission electron microscope.</p><p><b>RESULTS</b>Compared with the control group, plasma total protein and albumin level significantly decreased in the fibrosis group (P < 0.01). Proliferating cell nuclear antigen (PCNA) index was 85%-95% in the fibrosis group. Plasma alanine aminotransferase and aspartate aminotransferase levels significantly increased in the hepatectomy group compared with the control group (P < 0.01), while the autophagical index significantly decreased in both the fibrosis group and hepatectomy group compared with the control group (-95%, P < 0.01; -19%, P < 0.05, respectively). PCNA index was 20%-30% in the hepatectomy group.</p><p><b>CONCLUSIONS</b>Autophagy is weakened after fibrosis and hepatectomy, although it differs between these two processes. Proper regulation of autophagy may help facilitate the recovery of the residual liver function after hepatectomy.</p>

Expression of melanoma antigen-1, 3 genes in human intrahepatic cholangiocarcinoma and its clinical significance / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the possibility of using melanoma antigen (MAGE)-1 and MAGE-3 gene encoding proteins as an index of potential target for immunotherapy in intrahepatic cholangiocarcinoma (IHCC) patients.</p><p><b>METHODS</b>The expressions of MAGE-1 and MAGE-3 genes in tumor tissues and tumor adjacent non-IHCC liver tissues were examined by RT-PCR method. The relationship between positive expression rates of MAGE-1 and MAGE-3 genes and clinical data including sex, age, tumor diameters, tumor envelope, tumor nodules number, and hepatitis B virus surface antigen were determined.</p><p><b>RESULTS</b>The positive expression rates of MAGE-1 (35%) and MAGE-3 genes (45%) were significantly higher in the tumor tissues than in tumor adjacent tissues (0) (P<0.01). The positive expression rates of MAGE-1 and MAGE-3 genes had no relationship with the clinical data (P >0.05), except the morphology of tumor (P <0.05).</p><p><b>CONCLUSION</b>The high expression rates of MAGE-1 and MAGE-3 genes in IHCC suggests the MAGE-1 and MAGE-3 gene may be a target for immunotherapy in IHCC patients.</p>