藏药独一味药理作用及临床应用新进展

简要综述了独一味及其制剂的药理作用和临床应用研究的最新进展,并对其今后的研究方向提出了建议。认为独一味有良好地利用价值和开发潜力,对其研究开发的前景广阔;对其药效的物质基础及作用机理的研究有待深入,尤其应重点关注其疗效确切的镇痛活性。     

IL‐27 improves adoptive CD8+ T cells’ antitumor activity via enhancing cell survival and memory T cell differentiation

IL‐27 is an anti‐inflammatory cytokine that triggers enhanced antitumor immunity, particularly cytotoxic T lymphocyte responses. In the present study, we sought to develop IL‐27 into a therapeutic adjutant for adoptive T cell therapy using our well‐established models. We have found that IL‐27 directly improved the survival status and cytotoxicity of adoptive OT‐1 CD8⁺ T cells in vitro and in vivo. Meanwhile, IL‐27 treatment programs memory T cell differentiation in CD8⁺ T cells, characterized by upregulation of genes associated with T cell memory differentiation (T‐bet, Eomes, Blimp1, and Ly6C). Additionally, we engineered the adoptive OT‐1 CD8⁺ T cells to deliver IL‐27. In mice, the established tumors treated with OT‐1 CD8⁺ T‐IL‐27 were completely rejected, which demonstrated that IL‐27 delivered via tumor antigen–specific T cells enhances adoptive T cells’ cancer immunity. To our knowledge, this is the first application of CD8⁺ T cells as a vehicle to deliver IL‐27 to treat tumors. Thus, this study demonstrates IL‐27 is a feasible approach for enhancing CD8⁺ T cells’ antitumor immunity and can be used as a therapeutic adjutant for T cell adoptive transfer to treat cancer.     

Comparison of the safety and prognosis of sequential regorafenib after sorafenib and lenvatinib treatment failure in patients with unresectable hepatocellular carcinoma: a retrospective cohort study

BackgroundThere is lack of studies on sequential regorafenib after sorafenib and lenvatinib treatment failure in patients with unresectable hepatocellular carcinoma (HCC). This study was to explore the safety and prognosis of sequential regorafenib after sorafenib and lenvatinib failure in HCC patients.MethodsThis study was a retrospective, real-world study that included 50 HCC patients who received sequential regrafinib after sorafenib and lenvatinib failure. The safety and prognosis of two groups were compared.ResultsThe incidence of all grade and III/IV adverse events were 68% and 24%. According to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 and modified (m) RECIST standards, the objective response rates (ORRs) after receiving regorafenib were 14.0% and 22.0%, respectively. The disease control rates (DCRs) were 62.0% and 60.0%, respectively. Based on different first-line targeted drugs, 50 patients were divided into sorafenib (n=22) and lenvatinib group (n=28). There was no differences between two groups except age and bilirubin. And there was no differences in other treatments before or after regorafenib. The baseline between two groups was basically same and had good comparability. There was no difference in incidence of all grade and III/IV adverse events, ORR and DCR between two groups (P>0.05). On long-term prognosis, total overall survival (TOS) in sorafenib and lenvatinib group were 23.0 (95% CI: 15.1–30.9) vs. 29.7 (95% CI: 21.4–38.1) months. The difference was statistically significant (P=0.041). Besides, regorafenib overall survival (ROS) in sorafenib and lenvatinib group were 11.7 (95% CI: 7.1–16.3) vs. 15.9 (95% CI: 8.3–23.5) months. The difference was statistically significant ( P=0.045). The regorafenib progression-free survival (RPFS) was 5.6 (95% CI: 1.9–9.2) vs. 8.0 (95% CI: 5.1–10.9) months in sorafenib and lenvatinib group, respectively, and difference was not statistically significant (P=0.380).ConclusionsRegorafenib is an effective drug for second-line treatment of HCC, with fewer severe adverse events, ORR and DCR was 14–22% and 62–60%, respectively. Both TOS and ROS in lenvatinib group were better than those in sorafenib group. For HCC patients whose first-line targeted drug is lenvatinib, it is safe and effective to accept regorafenib after disease progresses.     

Clinical application of metagenomic next‐generation sequencing technology in the diagnosis and treatment of pulmonary infection pathogens: A prospective single‐center study of 138 patients

IntroductionRapid and accurate pathogen identification is essential for the treatment of pneumonia. Metagenomic next‐generation sequencing (mNGS) is a newly developed technology to obtain microbial nucleic acid sequence information quickly, efficiently, and without bias.MethodsWe performed shotgun metagenomic next‐generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) for pathogen identification in pneumonia in a prospective study with 138 patients from a single center. We compared the results of mNGS with standard methods including culture, staining, and targeted PCR and evaluated the clinical applicability of mNGS.ResultsMost of the patients (128/138, 92.75%) were cured or improved. One patient (1/138, 0.72%) died because of acute gastrointestinal bleeding, and 9 patients (9/138, 6.52%) showed no improvement. mNGS identified more bacteria (53 versus 27), fewer fungi (8 versus 31), and more viruses (16 versus 1) than standard methods. In total, treatment in 34 out of 138 cases (24.64%) was adjusted and optimized because of mNGS results. Positive mNGS results contributed to a definitive diagnosis in 23 cases (16.67%), which helped guide treatment decision by either adjusting the antibiotics without de‐escalation or continuing the empirical treatment. mNGS also confirmed no active infection in 11 cases (7.97%) allowed for antibiotic de‐escalation.ConclusionThis prospective clinical study evaluated the clinical utility of mNGS for the diagnosis of pneumonia and showed that mNGS of BALF provides valuable information for effective treatment.     

艾司西肽普兰联合利培酮对精神分裂症阴性症状疗效和安全性

目的 观察艾司西肽普兰辅助治疗精神分裂症患者阴性症状的疗效及安全性。方法 采用随机双盲对照研究方法。将我院86例住院精神分裂症患者分为两组,排除脱落人数后最终人数为：研究组利培酮联合艾司西肽普兰组39例;对照组利培酮联合安慰剂组41例。分别于基线及治疗第4、8、12周末采用阳性和阴性症状量表（PANSS）、阴性症状量表（SANS）、个人和社会功能量表（PSP）评估疗效,不良反应量表（TESS）评估安全性。结果 两组中PANSS总分、阴性因子总分、SANS总分于治疗第4周末开始均低于治疗前,两组中PSP总分于治疗第4周开始均高于治疗前（P<0.01）;在第8周末及第12周末利培酮联合艾司西酞普兰组PANSS阴性因子总分、SANS总分、分量表综合评价分均低于对照组（P<0.01）,PSP总分均高于对照组（P<0.01）;利培酮联合艾司西酞普兰组与利培酮联合安慰剂组PANSS阴性因子总分、SANS总分、PSP总分组间效应、时间主效应、交互效应均有统计学意义（P<0.01或P<0.05）。两组间不良反应差异无统计学意义（P>0.05）。结论 艾司西酞普兰对治...     

The bevacizumab plus oxaliplatin-based chemotherapy regimen is more suitable for metastatic colorectal cancer patients with a history of schistosomiasis: a clinical retrospective analysis

BackgroundThe basic platelet counts of schistosomiasis patients are low. If it does not meet the requirements for chemotherapy, the patient’s treatment will not be carried out, which directly affects their prognosis. Therefore the impact of treatment on platelet counts is critically important. The effects of bevacizumab plus oxaliplatin-based chemotherapy and bevacizumab plus irinotecan-based chemotherapy regimens on platelets are different but have not been determined. In order to find a more suitable plan for metastatic colorectal cancer (mCRC) patients with a history of schistosomiasis, we conducted a retrospective analysis of mCRC patients and evaluated the impact of bevacizumab on their platelets.MethodsThe medical records of all mCRC patients with a history of schistosomiasis who received oxaliplatin-based chemotherapy or irinotecan-based chemotherapy as first-line treatment for no less than 4 cycles, with or without bevacizumab from September 1, 2017, to June 30, 2019, in Kunshan Hospital were reviewed. Six-month cumulative incidence rates of splenomegaly and thrombocytopenia of chemotherapy with and without bevacizumab groups, oxaliplatin-based chemotherapy with and without bevacizumab groups, irinotecan-based chemotherapy with and without bevacizumab groups were compared from the first cycle until the completion of chemotherapy using Kaplan-Meier analysis and Log-rank test.ResultsEvaluable splenic enlargement and thrombocytopenia results were obtained from 153 mCRC patients. The 6-month cumulative incidence rates of splenomegaly (23.3% vs. 55%; P=0.01) and that of thrombocytopenia (43.8% vs. 57.5%; P=0.40) were lower in the bevacizumab group than the non-bevacizumab group, however there were no statistical differences for the rates of thrombocytopenia. For patients treated with oxaliplatin, the rates of splenomegaly (19.5% vs. 66.7%; P=0.01) and thrombocytopenia (31.7% vs. 77.2%; P=0.02) were lower in the bevacizumab-treated cohort than that in the non-bevacizumab cohort. When stratified for irinotecan, there were no statistical differences in the frequency of splenomegaly between the two groups. However, the rates of thrombocytopenia were higher in the bevacizumab-treated cohort than that in the non-bevacizumab cohort (59.4% vs. 8.7%; P=0.01).ConclusionsThe bevacizumab plus oxaliplatin-based chemotherapy regimen is safer for mCRC patients with a history of schistosomiasis, especially for patients with a lower platelet count.     

1例X连锁型视网膜色素变性家系的分子遗传学研究

目的 对1例来自云南省的X连锁型视网膜色素变性家系进行相关分子遗传学研究.方法 在本研究小组前期工作中对该家系已初步确定的X连锁型遗传位点--RP2和RP3处选取具有高信息量的9个微卫星位标进行精细单倍型分析.在定位的候选基因RP3基因即RPGR基因上,使用构象敏感凝胶电泳(conformation sensitive gel electrophoresis, CSGE)的方法对其1～14号外显子进行突变筛选的同时对已有报道的突变热点区--外显子ORF15进行直接测序以寻找致病突变.结果 通过精细定位扫描及相关单倍型分析,将该例家系的致病基因定位在RP3位点.RPGR基因1～14号外显子经CSGE的方法进行突变筛选,未发现有异常电泳条带;通过直接对突变热点区外显子ORF15的测序,在该例家系中检测到1个在国内外均有报道的热点突变:g.ORF15 483_484delGA.结论 g.ORF15 483_484delGA移码突变导致了该家系产生X连锁型视网膜色素变性.     

急性缺氧条件下氰化钠中毒对大鼠脑组织能量代谢的影响

目的探讨急性高原缺氧条件下氰化钠中毒对大鼠脑组织能量代谢的影响。方法雄性sD大鼠,分为平原组和高原组。平原组动物在本地常规实验室内处理。高原组动物放置于模拟4000m海拔高度的低压舱内3d后开始实验。为大鼠腹腔注射氰化钠（NaCN）3．6mg／kg染毒,于0、0．5、1、2、4、6h6个时相点麻醉后断头取脑。以干湿质量法测定脑组织含水量,伊文思蓝法检测脑组织血管通透性,高效液相色谱（high performance liquid chromatography,HPLC）法测定大鼠脑纹状体和海马组织腺苷三磷酸（adenosine triphosphate,ATP）、腺苷二磷酸（adenosine diphosphate,ADP）和腺苷-磷酸（adenosine monophosphate,AMP）含量。结果与平原组比较,高原缺氧环境氰化钠中毒大鼠脑组织含水量增加,纹状体和海马组织ATP和ADP含量减少,AMP含量增加。结论高原缺氧可导致大鼠脑组织腺苷酸能量代谢障碍,缺氧条件下氰化钠中毒可进一步加重脑组织能量代谢障碍,同时脑水肿也进一步加重。     

Network pharmacology-based pharmacological mechanism prediction on Eucommia ulmoides against rheumatoid arthritis

Rheumatoid arthritis (RA) is a common chronic autoimmune disease characterized by synovial inflammation and progressive joint destruction. Eucommia ulmoides (EU) is a kidney-tonifying Chinese medicine that has been applied to treat RA for decides. The present study aims to explore pharmacological mechanisms of EU against RA using network pharmacology approach. Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen active ingredients of EU, and their relative targets were fished from UniProt database. RA-related targets were screened from GeneCards database and DisGeNET database. The overlapping genes between EU and RA were identified by Venn diagram, and further analyzed for protein-protein interaction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG). Fifty active ingredients were identified in EU, and corresponded to 207 targets. Meanwhile, 499 targets were closely associated with RA development. A total of 50 overlapping genes between EU and RA were identified, which were regarded as therapeutically relevant. GO enrichment analysis indicated that EU exerted antiRA effects depending on regulating multiple biological processes including inflammatory response, oxidative stress, cell apoptosis and matrix catabolism. Several key pathways such as TNF pathway, IL-17 pathway, T cell receptor pathway, NOD-like receptor pathway and Toll-like receptor pathway, were involved in the above biological processes. Network pharmacology revealed that EU exerts therapeutic effects on RA through multi-ingredients, multi-targets and multi-pathways, which provides basis for its clinical application and promising directions for subsequent research.