4-氨甲酰基-4′-叠氮-1,2,3-三氮唑核苷的合成研究

目的 合成4-氨甲酰基-4′-叠氮-1,2,3-三氮唑核苷,以期发现具有高抗病毒活性的核苷类药物。方法 以商业易得的二丙酮叉-D-葡萄糖为起始原料,经9步反应得到重要糖基叠氮化合物,再与炔丙酸甲酯进行[3+2]偶极环加成反应以构建三氮唑环以及自由基脱羧叠氮化反应和脱保护得到4-氨甲酰基-4′-叠氮-1,2,3-三氮唑核苷。结果　以最长线性步骤5步反应,30%的总收率合成了4-氨甲酰基-4′-叠氮-1,2,3-三氮唑,这为后期的抗病毒活性测试奠定了基础。     

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.     

Decreased expression of claudin-18.2 in alpha-fetoprotein-producing gastric cancer compared to conventional gastric cancer

BackgroundAlpha-fetoprotein-producing gastric cancer (AFPGC) is a subtype of gastric cancer (GC) with more aggressive biological behavior. As a highly specific tight junction component exclusively present in gastric mucosa and gastric adenocarcinomas, claudin-18.2 (CLDN18.2) has become an emerging target in GC. In this study, we aimed to provide insight into AFPGC and investigate the expression and the clinical implications of CLDN18.2 in AFPGC.MethodsWe retrospectively collected 98 cases of AFPGC and reviewed their clinical, morphological, and immunohistochemical features. Another 356 patients with stage-matched conventional GC (cGC) were enrolled as a control group. We further surveyed CLDN18.2 expression by immunohistochemistry (IHC) in 51 AFPGC tissues and explained its association with the clinicopathological parameters of AFPGC.ResultsOur results showed that AFPGC was a unique GC type with elevated serum alpha-fetoprotein (AFP), which was a predictor of a worse prognosis. AFPGC showed typical morphological features and positive staining of at least 1 hepatocytic or enteroblastic marker. The expression rate of CLDN18.2 was low, with a positivity rate of 21.6%, which was much lower than that observed in cGC tissues (38.5%). A significant correlation was found between CLDN18.2 expression and the differentiation of AFPGC. CLDN18.2 expression was negatively correlated with the serum AFP level of AFPGC. We also found that AFPGC with a hepatoid type (HPT) component showed a significantly lower CLDN18.2 expression than those without.ConclusionsThis study demonstrated that CLDN18.2 was significantly decreased in AFPGC and was negatively correlated with the patient’s preoperative serum AFP level. The negative correlation between AFP and CLDN18.2 could be explained by retro-differentiation of AFPGC. Special treatment strategies might be needed for this unique tumor type.     

UBE2C promotes the progression of pancreatic cancer and glycolytic activity via EGFR stabilization-mediated PI3K-Akt pathway activation

BackgroundPancreatic cancer (PC) is among the most prevalent and deadliest endocrine tumors, yet the mechanisms governing its pathogenesis remain to be fully clarified. While ubiquitin-conjugating enzyme E2C (UBE2C) has been identified as an important oncogene in several cancers, its importance in PC has yet to be established.MethodsUBE2C expression in PC tumor samples and cell lines was examined via quantitative real-time polymerase chain reaction (qRT-PCR), while appropriate commercial kits were used to assess lactate production, ATP generation, and the uptake of glucose.ResultsUBE2C was found to be upregulated in PC patient tumors and correlated with poorer survival outcomes. In PC cell lines, the silencing of this gene suppressed the malignant activity of cells, thus supporting its identification as an oncogene in this cancer type. Mechanistically, UBE2C was found to promote enhanced matrix metalloproteinase (MMP) protein expression via activating the PI3K-Akt pathway. Moreover, it was found to bind to the epidermal growth factor receptor (EGFR), stabilizing it and driving additional PI3K-Akt pathway activation. UBE2C knockdown in PC cells impaired their uptake of glucose and their ability to produce lactate and ATP.ConclusionsIn conclusion, the results of this study support a role for UBE2C as a driver of metastatic PC progression owing to its ability to bind to EGFR and to induce signaling via the PI3K-Akt pathway.     

腹腔镜肝切除联合脾动脉结扎术治疗肝癌合并门脉高压症的疗效分析

目的 探讨腹腔镜肝切除联合脾动脉结扎术治疗肝癌合并门脉高压症患者的安全性及有效性.方法 2018年2月至2020年2月我院共手术治疗的28例原发性肝细胞肝癌合并肝炎后肝硬化、门脉高压症及脾功能亢进患者,在腹腔镜下先行脾动脉主干结扎、然后再行肝癌的切除,其中局部不规则切除19例、左肝外叶切除9例.回顾性分析患者的一般资料...     

抗生素西索米星发酵过程中次要组分的调控

在西索米星产生菌橄榄星孢小单孢菌Ｍ－４１的发酵代谢与产物合成的研究中,发现通过控制种子期菌丝的生长形态、培养基中磷酸盐含量,并在发酵过程中添加合适的抑制剂,可有效地减少发酵液中次要组分ｖｅｒｄａｍｉｃｉｎ的生物合成,增加主要组分西索米星的含量。     

薄层扫描法测定元胡止痛片中延胡索乙素的含量

目的：制定元胡止痛片中延胡索乙素含量测定方法。方法：双波长薄层扫描法,以苯－石油醚（９０～１２０℃）－甲醇－三氯甲烷（３：３：０．５：１０）为展开剂,检测波长３４０ｎｍ,参比波长３６５ｎｍ。结果：回收率平均为９７．６％（ＲＳＤ＝１．７９％,ｎ＝５）。标准曲线ｒ＝０．９９９８,线性范围０．２～１．２ｕｇｊ。结论：本方法简便,准确,可作为元胡止痛片的质量标准。     

Tunable Boc modification of lignin and its impact on microbial degradation rate

A new type of modified lignin, lignin-p-Boc, was obtained through reaction with di-tert-butyl dicarbonate (Boc₂O) in aqueous media catalyzed by 4-dimethylaminopyridine (DMAP). Boc modification occurred regardless of type of lignin, was tunable, and proceeded well in recovering lignin at high purity from sodium lignosulfonate (a common byproduct from pulping industry; lignin content: 60%). Lignin-p-BOC was demonstrated as a potential reactive filler in green plastic and as a potential crosslinker in design of bioresorbable composite polymeric implants. Furthermore, the effect of the modification on breakdown rate of alkali lignin by microbes was investigated, and results showed that the modification substantially decreases the breakdown rate. The tunable Boc modification process was designed via a system thinking, including availability of raw lignin, economical/green modification, potentiality of drop-in-change to current thermoplastic processing, modification impact on microbial degradability/disposed environment at the end of use life; hence the holistic consideration makes this alternative method for upgrade of technical lignins very practical for future industrial application. Via “in-situ” forming “easily breakable covalent bonds” with existing thermopolymers inside, Lignin-p-BOCs are also promising to play an important role as both excellent binders via “random match” and reductants in transforming linear plastic waste into circular plastics.     

参乌益智胶囊治疗血管性痴呆的临床研究

目的 观察参乌益智胶囊治疗血管性痴呆的临床疗效.方法 将80例血管性痴呆患者数字表法随机分为对照组和治疗组,每组40例.在常规治疗基础上,对照组予吡拉西坦片口服,治疗组予以参乌益智胶囊口服.60d为1个疗程.比较治疗前后简单智力状况检查(MMSE)量表积分、Blessed行为量表积分变化.结果 两组治疗前后MMSE积分、Bcessed行为量表积分均明显改善(均P＜0.05);治疗后治疗组MMSE积分、Bcessed行为量表积分分别为(19.83±5.24)分、(7.18±4.21)分,均优于对照组的(20.01±4.89)分、(7.23±3.99)分(t=4.148,2.141,均P＜0.05).结论 参乌益智胶囊能改善轻、中度血管性痴呆患者认知功能,提高患者记忆力、计算力、定向力,增强患者行为能力,减轻痴呆症状,取得较好近期疗效.     

耳蜗电图在梅尼埃病诊断中的价值

迄今尚缺乏诊断梅尼埃病的敏感且特异的客观试验，７０年代以来，若干研究探讨了耳蜗电图（Ｅｌｅｃｔｒｏｃｏｃｈｌｅｏｇｒａｍ，ＥＣｏｃｈＧ）在梅尼埃病诊断中的价值，认为典型的改变是－ＳＰ异常增大，导致－ＳＰ／ＡＰ比值增高，以及－ＳＰ－ＡＰ复合波形异常增宽。各家报告－ＳＰ／ＡＰ诊断梅尼埃病阳性率从３２％至８７％．本文报告了９７例１００耳梅尼埃病鼓室内法检测的耳蜗电图结果，４９例－ＳＰ／ＡＰ比值异常增高，阳性率４９％；波型异常增宽１７耳，总阳性率６６％．眼震电图检测的阳性率６１％．耳蜗电图和眼震电图改变一致的４３耳，二者总阳性率为８４％。对各家阳性率不一致的原因作了分析。认为耳蜗电图－ＳＰ／ＡＰ比值诊断梅尼埃病的敏感性不如文献报告的那么乐观，在目前尚无更敏感更特异的诊断手段的情况下，耳蜗电图和眼震电图在梅尼埃病的诊断中起着相互印证和相互补充的作用。