丹参酮提取物物理化学质量属性相关性分析

目的：探寻丹参酮提取物化学成分的含量与物理性质之间的相关性。方法：HPLC测定50批丹参酮提取物中隐丹参酮、丹参酮IIA的含量,经典方法测定物理性质,将成分含量与物理性质进行相关性分析。结果：两变量组组内的隐丹参酮与丹参酮IIA含量,D10、D50、D90 之间,松装密度与振实密度,豪斯纳比率与压缩度指数均具有较强的相关性,休止角与均齐度、豪斯纳比率、压缩度指数具有一定的相关性,但相关性不强。两变量组的原始变量组间相关性系数最大不超过0.400,相关性不强。经过典型相关分析,3对典型变量的相关性显著,相关系数分别为0.851,0.674,0.565。结论：对于丹参酮提取物的化学、物理质量属性,原始变量组内具有较好的相关性,但组间相关性较差。相比原始变量,典型变量呈现出了较好的组间相关性,表明丹参酮提取物的物理化学属性之间具有一定的相关性。     

Plasma exchange treats severe intrahepatic cholestasis caused by dacomitinib: A case report

Rationale:Dacomitinib-induced liver injury is often manifested by mild elevations of transaminases and bilirubin, and severe intrahepatic cholestasis caused by dacomitinib for simultaneous taking orally cytochrome P450 2D6 (CYP2D6) competitive substrates has been rarely reported.Patient concerns:The patient was a 69-year-old woman with non–small cell lung cancer (NSCLC) who was prescribed oral dacomitinib for a month; she was given oral loratadine due to “allergic rhinitis” and metoprolol extended action tablets due to “tachycardia” separately for a few days during the course of dacomitinib treatment. The patient developed liver damage, increased fatigue, yellow urine, and pruritus, with significantly elevated serum levels of bilirubin and glutamyltranspetidase.Diagnosis:Intrahepatic cholestasis, drug-induced liver injury, and NSCLC.Interventions:After admission, the patient was prescribed adenosylmethionine, acetylcysteine, ursodeoxycholic acid capsule, methylprednisolone and fenofibrate for a month, with progressive elevation of liver biochemical parameters. Through drug enzyme gene assays in the liver tissue after percutaneous liver biopsy, we found both CYP2D6*10/*10 and ATP-binding cassette subfamily B member 1 GG variants (rs1045642) positive. After the poor response to the conventional medication, the patient underwent plasma exchange.Outcomes:The patient was discharged after her liver parameters improved; the parameters remained normal at several follow-up visits, and she renewed the NSCLC regimens without dacomitinib after being evaluated by oncologists.Lessons:Dacomitinib can induce severe intrahepatic cholestasis. It is considered that patients with intermediate metabolic CYP2D6 are susceptible to drug-induced liver injury caused by dacomitinib; plasma exchange may be an effective treatment.     

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.     

Balsalazine decreases intestinal mucosal permeability of dextran sulfate sodium-induced colitis in mice

Aim： To investigate the effect of balsalazine treatment on intestinal mucosal permeability in dextran sulfate sodium （DSS）-induced colitis and to determine the mechanism of the balsalazine-induced changes.
Methods： Experimental colitis was induced in C57BL/6J mice by the administration of 5% DSS. Balsalazine was administered intragastrically at doses of 42, 141, and 423 mg/kg. The disease activity index （DAI） score was evaluated and colon tissue was collected for the assessment of histological changes. The amount of malondialdehyde （MDA） in the colon was determined, along with the activity of myeloperoxidase （MPO）, superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px）. Mucosa from the small intestine was collected to determine the levels of tumor necrosis factor （TNF）-α and interferon （IFN）-γ. The mucosa was ultrastructurally examined with transmission electron microscopy and intestinal permeability was assayed using Evans blue.
Results： Balsalazine was found to reduce the DAI score and the histological index （HI） score, decrease the MDA content and the activity of MPO, and increase the activity of SOD and GSH-Px in colitis mice. At the same time, balsalazine ameliorated microvillus and tight junction structure, resulting in a decrease in the amount of Evans blue permeating into the intestinal wall and the levels of TNF-α and IFN-γ in colitis mice.
Conclusion： In colitis mice, the anti-colitis effect of balsalazine results in a decrease in intestinal mucosal permeability. The mechanism of this effect is partly associated with balsalazine＇s antioxidative and anti-inflammatory effects.     

Comparison of the effects of perineural or intravenous dexamethasone on thoracic paravertebral block in Ivor‐Lewis esophagectomy: A double‐blind randomized trial

Efforts to prolong thoracic paravertebral block (TPVB) analgesia include local anesthetic adjuvants, such as dexamethasone (Dex). Previous studies showed that both perineural (PN) and intravenous (i.v.) routes could prolong analgesia. As PN Dex is an off‐label use, anesthesiologists should be fully informed of the clinical differences, if any, on block duration. This study was designed to evaluate the two administration routes of Dex for duration of analgesia in TPVB. Ninety‐five patients scheduled for Ivor‐Lewis esophagectomy were randomized to receive TPVB (0.5% ropivacaine 15 ml), PN or i.v. Dex 8 mg. The primary end point was the duration of analgesia. The secondary end points included pain scores, analgesic consumption, adverse effects rate, and incidence of chronic pain at 3 months postoperatively. The PN‐Dex group showed better analgesic effects than the i.v.‐Dex group (p < 0.05). Similarly, the visual analogue scale scores in patients at 2, 4, 8, and 12 h postoperatively were lower in the PN‐Dex group than the i.v.‐Dex group (p < 0.05). The analgesic consumption in both the PN‐Dex and i.v.‐Dex groups was significantly lower than that in the control group (p < 0.05). Regarding the incidence of chronic pain, regardless of route, Dex decreased the incidence of chronic postsurgical pain and neuropathic pain at 3 months after surgery (p < 0.05), but there were no clinical differences between the i.v.‐Dex and PN‐Dex groups. Perineural dexamethasone improved the magnitude and duration of analgesia compared to that of the i.v.‐Dex group in TPVB in Ivor‐Lewis esophagectomy. However, there were no clinically significant differences between the two groups in the incidence of chronic pain.

Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Both perineural (PN) and intravenous (i.v.) dexamethasone (Dex) could prolong the duration of a nerve block, but the superiority of either route is still inconclusive. WHAT QUESTION DID THIS STUDY ADDRESS? The study investigated the effects of the two routes of Dex added to ropivacaine on analgesic effects of thoracic paravertebral block in patients undergoing Ivor‐Lewis esophagectomy. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? These results extend the knowledge of the superior analgesic effect of Dex for the management of perioperative pain in the setting of Ivor‐Lewis Esophagectomy. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? Because PN Dex is an off‐label use, our study conformed the safety of Dex as PN adjuvants and extended its application field in clinical work.     

The clinical analysis of poor ovarian response in in-vitro-fertilization embryo-transfer among Chinese couples

Purpose To explore the prevalence, predictor of clinical pregnancy and possible aetiology of poor ovarian response (POR) in in vitro fertilization–embryo transfer (IVF–ET) in Chinese. Methods A total of 4,600 retrieval oocyte cycles were finished between July 1, 2004 and April 30, 2006. Poor ovarian responses were observed in 426 patients of 472 cycles undergoing IVF, which were selected on the same retrieve oocyte day as the control group. The outcome of IVF–ET and the common markers of ovarian reserve were compared. Results The patients had previous ovarian surgery in 64 cycles of 472 poor ovarian response cycles. The group with poor ovarian response has significant differences in comparison with the control group in age (36.6 ± 4.2 vs 33.3 ± 4.04), ovarian surgeries (13.6 vs 2.8%), dose of gonadotrophin (58.5 ± 15.8 vs 40.6 ± 17.0), fertilization rate (71.5 vs 86%) and pregnancy rate (14.8 vs 36.7%). In the group with poor ovarian responses, clinical pregnancy rate declined significantly in women aged >40 years than in those aged ≤40 years (2.8 vs 18.5%, P < 0.001). The age, basal serum follicle stimulating hormone (FSH), basal serum luteinizing hormone (LH), basal oestradiol (E2) concentrations, FSH to LH ratio and the antral follicle count (AFC) are the common markers of ovarian reserve in our center. We found that there were significant differences in age, basal FSH, FSH-to-LH ratio and the antral follicle count. But no statistical significant differences were observed in basal oestradiol concentration and basal serum LH when comparing the two groups. Binary logistic regression analysis was used to study the relation among age, FSH, LH, E2, AFC and clinical pregnancy, and the age (odds ratio, 0.863; 95% confidence interval, 0.805–0.925; p = 0.000) was the only variable selected. Conclusion Our data show that the prevalence of poor ovarian response in Chinese is 11.9%. Previous ovarian surgery is associated with poor ovarian responses. The pregnancy rate of women with poor ovarian response is low in IVF–ET, especially the decline in clinical pregnancy rate of women aged >40 years became accelerated. Correct identification of those who are at risk for POR prior to stimulation is helpful in tailoring the best stimulation protocol to individual patients. Chronological age significantly improved the prediction of clinical pregnancy of poor ovarian responders.     

Analysis of meiotic segregation patterns and interchromosomal effects in sperm from six males with Robertsonian translocations

Purpose To provide more genetic information about meiotic segregation behavior and the possibility of interchromosomal effects (ICE) in spermatozoa from carriers of Robertsonian (Rob) translocations. Materials and methods Meiotic segregation behavior in spermatozoa from six carriers of Rob translocations, four t(13;14), one t(14;22) and one t(13;21), was investigated by dual fluorescence in-situ hybridization (FISH). Aneuploidy for chromosomes 18, X and Y was studied by triple FISH. Results The rate of normal/balanced spermatozoa resulting from alternate segregation ranged from 78.14 to 86.88%. The frequency of unbalanced spermatozoa resulting from adjacent segregation varied between 11.70 and 19.53%. The higher frequencies of aneuploidy for sex chromosome were observed in three Rob translocation carriers. In addition, the increased rates of diploid were found in two t(13;14) carriers. Conclusions Alternate segregation is dominant in the different types of Rob translocations. Some carriers may be at an increased risk for ICE. Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users. An increased aneuploidy for sex chromosome observed in three Robertsonian translocation carriers suggests that an interchromosomal effect is likely in some carriers.     

经肛门内镜显微手术前预防性应用抗生素的临床价值

目的  探讨术前预防性使用抗生素在经肛门内镜显微手术（TEM）中的临床价值。方法 选取30例于该院行TEM手术治疗直肠肿瘤的患者作为研究对象,随机分为抗生素组和对照组,抗生素组为术前和术后均应用抗生素,对照组为仅术后应用抗生素。评估患者术前和术后血沉（ESR）、C-反应蛋白（CRP）、降钙素原（PCT）、白细胞计数（WBC）、中性粒细胞（NE%）和体温（T）等指标的变化。结果  抗生素组患者术后第1天和第3天ESR、CRP、WBC、NE%和T均明显低于对照组（P <0.05）,并且WBC、NE%和T在术后第3天较术后第1天有明显的下降趋势。对于PCT,在术后第1天两组比较差异有统计学意义,抗生素组低于对照组（P <0.05）,但在术后第3天,两者之间差异无统计学意义（P >0.05）。结论  术前预防性应用抗生素对TEM微创手术引起的炎症减轻和感染预防可能有一定的临床价值,但最终结论仍需要扩大病例数进一步研究。

     

RNA Interference-Mediated Knockdown of Bombyx mori Haemocyte-Specific Cathepsin L (Cat L)-Like Cysteine Protease Gene Increases Bacillus thuringiensis kurstaki Toxicity and Reproduction in Insect Cadavers

The silkworm’s Cat L-like gene, which encodes a lysosomal cathepsin L-like cysteine protease, is thought to be part of the insect’s innate immunity via an as-yet-undetermined mechanism. Assuming that the primary function of Cat L-like is microbial degradation in mature phagosomes, we hypothesise that the suppression of the Cat L-like gene expression would increase Bacillus thuringiensis (Bt) bacteraemia and toxicity in knockdown insects. Here, we performed a functional analysis of Cat L-like in larvae that were fed mulberry leaves contaminated with a commercial biopesticide formulation based on Bt kurstaki (Btk) (i.e., Dipel) to investigate its role in insect defence against a known entomopathogen. Exposure to sublethal doses of Dipel resulted in overexpression of the Cat L-like gene in insect haemolymph 24 and 48 h after exposure. RNA interference (RNAi)-mediated suppression of Cat L-like expression significantly increased the toxicity of Dipel to exposed larvae. Moreover, Btk replication was higher in RNAi insects, suggesting that Cat L-like cathepsin may be involved in a bacterial killing mechanism of haemocytes. Finally, our results confirm that Cat L-like protease is part of the antimicrobial defence of insects and suggest that it could be used as a target to increase the insecticidal efficacy of Bt-based biopesticides.