As many as 80 % of pancreatic cancer patients might suffer from cancer cachexia, a distressing condition characterized by involuntary weight loss and muscle wasting. Regrettably, there remains an insufficiency of efficacious pharmacological interventions for the management of cancer cachexia. The effectiveness of corylifol A (CYA) in treating pancreatic cancer-associated cachexia was assessed, and its underlying mechanisms were examined in the present study. Cultured C2C12 myotubes induced with conditioned medium from MiaPaCa-2 pancreatic cancer cells (MIA CM) were utilized as an in vitro model to investigate the impact of CYA on muscle atrophy associated with cancer cachexia. The MIA cachexia mice model was utilized to evaluate the in vivo impact of CYA on cancer cachexia. CYA (2.5, 5, and 10 μM) dose-dependently mitigated MIA CM-induced myotube atrophy through targeting the thousand and one amino acid protein kinase 1 (TAOK1) and blocking protein degradation via the ubiquitin-proteasome system (UPS) and the autophagic-lysosomal pathway (ALP). Importantly, CYA (10 mg/kg/d, i.p.) not only significantly ameliorated weight loss and muscle atrophy but also inhibited the tumor growth in MIA cancer cachexia mice. In pancreatic cancer cells, CYA directly targets the thousand and one amino acid kinase 3 (TAOK3). Both knockdown and overexpression of TAOK3 could alleviate the cytotoxicity of CYA on pancreatic cancer cells. Collectively, CYA ameliorated pancreatic cancer-associated cachexia by targeting TAOK1 in skeletal muscle cells as well as targeting TAOK3 in pancreatic cancer cells.

Introduction: Carnosol exhibited ameliorating effects on muscle atrophy of mice developed cancer cachexia in our previous research.Method: Here, the ameliorating effects of carnosol on the C2C12 myotube atrophy result from simulated cancer cachexia injury, the conditioned medium of the C26 tumor cells or the LLC tumor cells, were observed. To clarify the mechanisms of carnosol, the possible direct target proteins of carnosol were searched using DARTS (drug affinity responsive target stability) assay and then confirmed using CETSA (cellular thermal shift assay). Furthermore, proteomic analysis was used to search its possible indirect target proteins by comparing the protein expression profiles of C2C12 myotubes under treatment of C26 medium, with or without the presence of carnosol. The signal network between the direct and indirect target proteins of carnosol was then constructed.Results: Our results showed that, Delta-1-pyrroline-5-carboxylate synthase (P5CS) might be the direct target protein of carnosol in myotubes. The influence of carnosol on amino acid metabolism downstream of P5CS was confirmed. Carnosol could upregulate the expression of proteins related to glutathione metabolism, anti-oxidant system, and heat shock response. Knockdown of P5CS could also ameliorate myotube atrophy and further enhance the ameliorating effects of carnosol.Discussion: These results suggested that carnosol might ameliorate cancer cachexia-associated myotube atrophy by targeting P5CS and its downstream pathways.

Aim: Our study focuses on the microbial and metabolomic profile changes during the adenoma stage, as adenomas can be considered potential precursors to colorectal cancer through the adenoma-carcinoma sequence. Identifying possible intervention targets at this stage may aid in preventing the progression of colorectal adenoma (CRA) to malignant lesions. Furthermore, we evaluate the efficacy of combined microbial and metabolite biomarkers in detecting CRA. Methods: Fecal metagenomic and serum metabolomic analyses were performed for the discovery of alterations of gut microbiome and metabolites in CRA patients (n = 26), Colorectal cancer (CRC) patients (n = 19), Familial Adenomatous Polyposis (FAP) patients (n = 10), and healthy controls (n = 20). Finally, analyzing the associations between gut microbes and metabolites was performed by a Receiver Operating Characteristic (ROC) curve. Results: Our analysis present that CRA patients differ significantly in gut microflora and serum metabolites compared with healthy controls, especially for Lachnospiraceae and Parasutterella. Its main metabolite, butyric acid, concentrations were raised in CRA patients compared with the healthy controls, indicating its role as a promoter of colorectal tumorigenesis. alpha-Linolenic acid and lysophosphatidylcholine represented the other healthy metabolite for CRA. Combining five microbial and five metabolite biomarkers, we differentiated CRA from CRC with an Area Under the Curve (AUC) of 0.85 out of this performance vastly superior to the specificity recorded by traditional markers CEA and CA199 in such differentiation of these conditions. Conclusions: The study underlines significant microbial and metabolic alterations in CRA with a novel insight into screening and early intervention of its tumorigenesis.

In our previous study, we found that corylifol A (CYA), an active component derived from Psoralea corylifolia L, exhibited ameliorating effects on cancer cachexia. Anamorelin (AML), a ghrelin receptor agonist, is the only approved drug for the clinical treatment of cancer cachexia. Here, we checked the combination of CYA and AML on muscle atrophy and fat lipolysis in cancer cachexia mice to explore the possible clinic therapeutic potency of the combination on cancer cachexia. C26 colon tumor-bearing mice, a well-established animal model of cancer cachexia, were used to evaluate the effects of combined therapy involving CYA and AML on cancer cachexia and compared with those of CYA or AML alone. Histological analysis was performed to assess the changes in gastrocnemius (GAS) muscle tissue and epididymal adipose tissue (eWAT) and the possible involved molecular pathways were explored using western blotting and ELISA. Treatments of CYA, AML, or CYA+AML all significantly ameliorated the body weight decrease, muscle atrophy as well as fat loss in the tumor-bearing mice. Notably, the ameliorating effects of CYA+AML on fat loss were more significant than CYA or AML alone. The eWAT weight of mice in healthy control, C26 model, C26 +CYA, C26 +AML or C26 +CYA +AML group was 0.48 ± 0.07, 0.21 ± 0.10, 0.26 ± 0.10, 0.37 ± 0.10 and 0.48 ± 0.18 g, respectively. CYA+AML could increase food intake, significantly decrease the serum levels of inflammatory cytokines (TNF-α and IL-6) and inhibit the activation (phosphorylation) of hormone-sensitive lipase (HSL) in the eWAT tissues of the C26 tumor-bearing mice. Treatment of CYA along could significantly decrease the serum TNF-α level of the C26 tumor-bearing mice. Treatment of AML alone could increase food intake but could not decrease the serum levels of inflammatory cytokines of the C26 tumor-bearing mice. These results suggested that the effects of CYA+AML include both the appetite-stimulating effects of AML and the anti-inflammatory effects of CYA. CYA+AML was better than CYA or AML alone in ameliorating cancer cachexia, especially fat loss, of C26 tumor-bearing mice and might be a novel and beneficial therapeutic option for cancer cachexia.

By analyzing the classical and modern studies related to pancreatic cancer,we realize that the pancreatic cancer is located in the spleen,which is related to the liver.The pathogenesis is summarized as deficiency of the original.The specific interpretation is based on spleen deficiency,coupled with Qi stagnation,endogenous dampness-heat phlegm and blood stasis,and repeatedly invasion by cancer poison.Based on the understanding of etiology and pathogenesis,the basic treatment of pancreatic cancer should be based on supplementing the deficiency and strengthening the spleen,regulating Qi,dampness removal,heat clear,phlegm dissolve,stasis disperse,and external cancer toxin,while not forgetting to regulate the liver.We also summarize the modern TCM treatment of pancreatic cancer in terms of modern Chinese medicine formulas,Chinese medicine injections,acupoint dressing,acupuncture,electroacupuncture,percutaneous nerve stimulation,ear pressure pills,and moxibustion,and realize that in modern Chinese medicine treatment,the principles of prescription medicine and acupoint selection are mostly based on strengthening the spleen and regulate the liver,which is consistent with the basic treatment principles.Further studies have found that modern traditional Chinese medicine treatment can inhibit the growth of pancreatic cancer cells,prolong the survival of patients,reduce tumor indicators,alleviate the adverse reactions of radiotherapy and chemotherapy,and improve the general conditions of patients such as cancer pain,hiccups,nausea and vomiting,postoperative gastric paralysis,depression,insomnia.

目的 观察揿针联合阿片类镇痛药物治疗中重度癌性疼痛的临床疗效及对血清β-内啡肽、P物质水平的影响.方法 将76例中重度癌性疼痛患者随机分为治疗组、对照组,每组38例.对照组给予常规治疗(包括积极治疗原发病、营养支持、阿片类镇痛药物止痛治疗等),治疗组在常规治疗的基础上加用揿针疗法,连续治疗14 d.观察不良反应的发生情况,比较治疗前后两组患者疼痛数字评分(NRS)、简明疼痛量表(BPI)、卡氏功能状态评分(KPS),以及血清β-内啡肽、P物质水平的变化情况.结果 ①试验期间,治疗组脱落4例,对照组脱落3例,最终完成试验者69例,其中治疗组34例、对照组35例.②治疗前后组内比较,治疗组疼痛NRS评分降低、KPS评分升高(P<0.05),对照组疼痛NRS、KPS评分差异无统计学意义(P>0.05);组间治疗后比较,治疗组疼痛NRS评分低于对照组、KPS评分高于对照组(P<0.05).③治疗前后组内比较,治疗组BPI中24 h最剧烈疼痛、24 h平均疼痛、目前疼痛、对日常生活影响、对情绪影响、对日常工作影响、对睡眠影响及疼痛影响程度总评分降低(P<0.05),对行走能力影响评分升高(P<0.05),对照组上述指标差异无统计学意义(P>0.05);组间治疗后比较,上述指标差异无统计学意义(P>0.05).④治疗前后组内比较,两组血清β-内啡肽水平升高、P物质水平降低(P<0.05);组间治疗后比较,治疗组血清P物质水平低于对照组(P<0.05).⑤治疗组便秘、恶心呕吐发生率及不良反应总发生率低于对照组(P<0.05).结论 加用揿针对癌性疼痛患者具有更好的临床疗效,可缓解疼痛、改善患者生活质量、降低阿片类镇痛药物的不良反应发生率,其机制可能与调节血清β-内啡肽、P物质表达水平有关.

目的 通过观察晚期胰腺癌患者生存情况,评价健脾散结方对晚期胰腺癌生存期的影响.方法 采用非随机同期对照临床研究,以是否接受健脾散结方治疗分为中药组和非中药组,并进一步以有无接受化疗进行分层分析.在基线均衡的条件下比较接受健脾散结方联合化疗的中药组和仅接受化疗的同期非中药组的生存期.单因素以及多因素回归模型分析影响晚期胰腺癌预后的独立因素,Kaplan-Meier法和Log-rank检验估算中位总生存时间(Overall survival time,OS).结果 共纳入晚期胰腺癌患者165例,其中中药组109例,非中药组56例,全组中91例患者出现终点事件,占55.2％.健脾散结方、化疗、Karnofsky(KPS)功能状态评分、性别为影响晚期胰腺癌预后的独立性因素.以是否行姑息化疗分层:化疗亚组中,中药组的中位OS为16.0个月,较非中药组的10.7个月延长,差异有统计学意义(P=0.005,Log-rank检验).非化疗亚组中,中药组的中位OS为9.7个月,较非中药组的4.1个月延长,差异有统计学意义(P=0.007,Log-rank检验).结论 健脾散结方中药是影响晚期胰腺癌预后的独立性保护因素,单独应用或联合化疗均可改善晚期胰腺癌患者的生存期.

目的:探讨骨痛灵(Gutongling,GTL)方治疗肺癌骨转移疼痛的潜在作用机制.方法:将50只C57BL/6雄性小鼠随机分为5组(n=10):假手术组(Sham组)、模型组(Model组)、唑来膦酸组(ZA组)、骨痛灵组(GTL组)、骨痛灵+唑来膦酸组(GTL+ZA组).除Sham组给予接种PBS溶液外,其余各组均予鼠源肺腺癌细胞Lewis-LUC悬液造模.采用von Frey纤维丝测痛仪检测小鼠足底的机械痛阈值,共聚焦显微镜观察破骨细胞伪足小体F-actin环,实时荧光定量PCR法与免疫组化法检测各组小鼠左后肢胫骨骨组织中整合素αvβ3、富含脯氨酸的酪氨酸激酶2(PyK2)、酪氨酸激酶Src、Casitas B细胞淋巴瘤家族蛋白(Cb1)mRNA及蛋白表达水平.结果:与Sham组比较,Model组小鼠造模后机械痛阈值下降(P<0.05).造模后第14天:各给药干预组机械痛阈值较Model组升高(P<0.05);ZA组与GTL组机械痛阈值相当;造模后第21天:GTL+ZA组机械痛阈值较各给药组明显升高(P<0.05).与Sham组比较,Model组F-actin环结构完整、αvβ3、PyK2、Scr、Cbl mRNA表达及蛋白染色强度升高(P<0.05);GTL+ZA组F-actin环较各给药组破坏程度明显、αvβ3、PyK2、Scr、Cbl mRNA表达及蛋白染色强度明显下降(P<0.05).结论:骨痛灵方可能通过调控骨组织中αvβ3/PyK2/Src/Cbl通路抑制F-actin环形成起到骨保护作用,从而治疗肺癌骨转移疼痛.

Background Community-based intervention is an important part of palliative care for advanced cancer patients. However, its role in the health management of advanced cancer patients remains to be supported by medical evidence. Objective To evaluate the efficacy of community-involved hospice care for patients with advanced cancer. Methods Wanfang Data Knowledge Service Platform, CNKI, VIP were searched by using Chinese keywords such as "community" "medical model" and "advanced cancer", Cochrane Library, PubMed and Web of Science were searched by using English keywords such as "Community-based" "Model of Palliative Care" "Advanced Cancer" "Quality of Life", to obtain randomized controlled trials (RCTs) related to the efficacy of community-involved hospice care from 2007-01-01 to 2022-05-10 by using Cochrane system evaluation method on 2022-05-22. The quality of RCTs meeting the inclusion criteria was evaluated, and the valid information was extracted for meta-analysis. Results A total of 11 RCTs in English and 9 RCTs in Chinese were included in the study, involving 2 356 and 1 238 patients, respectively. Meta-analysis showed that compared with routine cancer care, community-involved hospice care could improve quality of life and symptom severity in patients with advanced cancer, demonstrated by increasing Functional Assessment of Chronic Illness Therapy-Palliative Care scale socre〔MD (95%CI) =3.77 (0.83, 6.71) , P=0.01〕and Quality of Life Instruments for Cancer Patients scale total score〔MD (95%CI) =12.53 (2.36, 22.69) , P=0.02〕, reducing Functional Assessment of Cancer Therapy scale total score〔MD (95%CI) =-2.61 (-3.53, -1.70) , P<0.01〕 and Edmonton Symptom Assessment System score〔MD (95%CI) =-2.45 (-4.70, -0.20) , P=0.03〕. However, the improvement of community-involved hospice care on depressive symptoms and overall survival rates of patients remains controversial, and its effect on economic indicators such as admission rates, hospitalization days/numbers needs to be further explored. Conclusion Community-involved hospice care can improve the quality of life and symptom severity of patients with advanced cancer, however, its improvement in hospice care in the depressive symptoms and overall survival rates of the patients remains controversial, and its improvement in economic indicators such as admission rate and hospital stay/inpatients admissions remains to be further explored.

大黄素抑制胰腺癌作用机制的研究主要集中于促进细胞凋亡、抑制细胞增殖、抑制血管生成、抑制肿瘤转移方面,抑癌基因、非编码RNA等微观层面以及糖酵解代谢方面亦有所涉及.大黄素治疗胰腺癌的多种机制涉及的信号通路间多有重叠,主要有核因子 κB(nuclear factor-κB,NF-κB)、Hippo、Wnt、转化生长因子-β(transforming growth factor-p,TGF-β)/Smads和血管生成素(angiopoietin,Ang)/酪氨酸激酶受体(tyrosine kinase receptor,Tie)等.但目前针对大黄素抑制胰腺癌的作用机制不明确,仅局限于作用于肿瘤细胞的表型研究,且多为临床前研究,体外实验较多,后期临床应用尚需探索,临床用量及体内代谢情况的研究需要进一步完善.

目的:探讨慢性乙型肝炎病毒(hepatitis B virus,HBV)感染伴脂肪肝患者的中医证候要素特征.方法:采用隐结构模型方法,构建690例HBV慢性感染伴脂肪肝患者的隐结构模型,采用隐类概率、条件概率、互信息及累积信息覆盖率量化症状及证候数据,同时辅以人工判读的方式诠释该人群的主要证候要素特征.结果:以累积信息覆盖率达到95％为主要证候要素的判定标准,HBV慢性感染伴脂肪肝患者中医证候要素常见的有气滞、脾虚、湿热、寒湿、瘀血、阴虚、阳虚,证候要素涉及脏腑为肝、脾、肾.对同类别相关证素进行综合聚类分析得到6种常见中医证型,即肝郁气滞证、湿热蕴结证、脾虚证、瘀血阻络证、气阴两虚证、脾肾阳虚证,各证候出现概率分别为30％、25％、23％、22％、16％、9％.结论:基于隐结构模型的证候要素评价方法可量化各变量的关联程度及发生概率,HBV慢性感染伴脂肪肝患者以肝郁气滞、湿热蕴结、脾虚证更为多见.

目的:观察三阶梯镇痛疗法联合揿针治疗癌痛的有效性、安全性,探讨揿针联合三阶梯镇痛疗法改善癌痛的潜在途径.方法:纳入70例中重度癌痛患者,随机分为治疗组和对照组,每组35例,入组后两组病例即采用三阶梯镇痛疗法进行阿片类药物滴定,NRS评分稳定至0~3分后,对照组继续三阶梯镇痛治疗;治疗组在对照组的基础上加用揿针治疗,疗程为2周,疗程结束,继续观察2周.记录两组患者NRS评分、EORTC QLQ-C30生活质量量表评分、不良反应发生情况.同时观察揿针联合三阶梯镇痛疗法治疗组治疗前后血清中内源性致痛因子降钙素基因相关肽(CGRP)及前列腺素E2(PGE2)水平的差异.结果:两组患者治疗后,NRS评分均有下降(P＜0.05),且治疗组下降趋势较对照组明显(P＜0.05);治疗组不良反应发生率54%(18/33)明显低于对照组84%(28/33)(P＜0.01),治疗组EORTC-QLQ-C30生活质量量表评分在恶心与呕吐、疼痛、食欲丧失、便秘症状改善方面优于对照组(P＜0.05).揿针联合三阶梯镇痛疗法治疗后血清PGE2、CGRP水平低于治疗前(P＜0.01).结论:三阶梯镇痛疗法联合揿针治疗癌痛疗效确切,且能减少阿片类药物不良反应,改善患者生活质量.揿针联合三阶梯镇痛疗法治疗癌痛可能与血清中PGE2和CGRP水平降低有关.

AbstractBackgroundAtractylenolide I (AI) is a natural sesquiterpene lactone isolated from Atractylodes macrocephala Koidz, known as Baizhu in traditional Chinese medicine. AI has been found to ameliorate cancer cachexia in clinic cancer patients and in tumour‐bearing mice. Here, we checked the influence of AI on biogenesis of IL‐6 and extracellular vesicles (EVs) in cancer cachexia mice and then focused on studying mechanisms of AI in inhibiting the production of tumour‐derived EVs, which contribute to the ameliorating effects of AI on cancer cachexia.MethodsC26 tumour‐bearing BALB/c mice were applied as animal model to examine the effects of AI (25 mg/kg) in attenuating cachexia symptoms, serum IL‐6 and EVs levels. IL‐6 and EVs secretion of C26 tumour cells treated with AI (0.31–5 μM) was further observed in vitro. The in vitro cultured C2C12 myotubes and 3T3‐L1 mature adipocytes were used to check the potency of conditioned medium of C26 cells treated with AI (0.625–5 μM) in inducing muscle atrophy and lipolysis. The glycolysis potency of C26 cells under AI (0.31–5 μM) treatment was evaluated by measuring the extracellular acidification rate using Seahorse XFe96 Analyser. Levels of related signal proteins in both in vitro and in vivo experiments were examined using western blotting to study the possible mechanisms. STAT3 overexpression or knockout C26 cells were also used to confirm the effects of AI (5 μM).ResultsAI ameliorated cancer cachexia symptoms (P < 0.05), improved grip strength (P < 0.05) and decreased serum EVs (P < 0.05) and IL‐6 (P < 0.05) levels of C26 tumour‐bearing mice. AI directly inhibited EVs biogenesis (P < 0.001) and IL‐6 secretion (P < 0.01) of cultured C26 cells. The potency of C26 medium in inducing C2C12 myotube atrophy (+59.54%, P < 0.001) and 3T3‐L1 adipocyte lipolysis (+20.73%, P < 0.05) was significantly attenuated when C26 cells were treated with AI. AI treatment inhibited aerobic glycolysis and the pathway of STAT3/PKM2/SNAP23 in C26 cells. Furthermore, overexpression of STAT3 partly antagonized the effects of AI in suppressing STAT3/PKM2/SNAP23 pathway, EVs secretion, glycolysis and the potency of C26 medium in inducing muscle atrophy and lipolysis, whereas knockout of STAT3 enhanced the inhibitory effect of AI on these values. The inhibition of AI on STAT3/PKM2/SNAP23 pathway was also observed in C26 tumour tissues.ConclusionsAI ameliorates cancer cachexia by decreasing the production of IL‐6 and EVs of tumour cells. The decreasing effects of AI on EVs biogenesis are based on its inhibition on STAT3/PKM2/SNAP23 pathway.

e16305 Background: Pancreatic cancer is a malignancy with poor prognosis and high mortality ranking 7th worldwide and with a 5-year survival rate of 10.8%. More than 50% pts are diagnosed at the late stage. The monoclonal antibodies of immune checkpoint inhibitors are also being investigated but has very limit progression free survival (PFS) and overall survival (OS) benefit. KN046, a novel recombinant humanized bispecific antibody, can simultaneously block PD-1/PD-L1 and CTLA-4 pathways and restore T-cell immune response to tumor. KN046 plus nab-paclitaxel/gemcitabine as first-line treatment for unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) in a phase 2 study arm 2 (NCT04324307) was reported before. Here, we report the efficacy and safety of KN046 as a monotherapy in the 2nd line and above setting (arm1). Methods: This ongoing phase 2 trial in China enrolled pts with histologically or cytologically confirmed unresectable locally advanced or metastatic PDAC who have ECOG PS of 0-1 and failed to at least one systemic anti-tumor treatment in arm 1. Single agent of KN046 (5mpk, Q2W) were administered until disease progression or intolerable toxicity. Tumor response was assessed according to RECIST 1.1 every 8 weeks. The primary endpoint is investigator-assessed objective response rate (ORR). Secondary endpoints including disease control rate (DCR), PFS, OS and safety, etc. Results: As of Jan 10, 2022, 21pts were enrolled, median (range) age was 57 (51-64) years, 14 (66.7%) pts ECOG 1, 16 (76.2%) pts had distant metastases, and 11 (52,4%) pts had received ≥2 lines systemic treatment. Median KN046 exposure time was 4.1(2.1,6,4) wks. 9 pts were included in the efficacy analysis with 1 PR and 3 SD. 21 pts in the safety analysis. Confirmed ORR was 11.1% (95% CI: 0.28,48.25), and DCR was 44.4% (95% CI: 13.7,78.8). Median PFS was 2.1 months (95% CI:1.61̃7.29), PFS rate in 6 and 9 months were 31.4% and 21%, respectively. Median OS was 7.5months (95% CI:3.02-NR), OS rate in 6 and 9 months were 61.3% and 49.5%, respectively. The incidence of KN046 related treatment-emergent adverse events (TRAE) was 71.4% (15/21), with 14.3% (3/21) ≥grade 3 TRAEs. Two pts experienced TRAE leading to discontinuation. The most common TRAEs (≥10%) were rash (n=6, 28.6%), alanine aminotransferase increased, chills, γ-glutamyl transferase increased and platelet count decreased (n = 3, 14.3%, respectively). No TRAE leading to death occurred. Conclusions: KN046, a bispecific antibody as 2nd line and above monotherapy for unresectable locally advanced or metastatic PDAC patients demonstrated a good PFS and OS benefit as well as acceptable safety profile, supporting KN046 in combination of chemotherapy as first line treatment. Clinical trial information: NCT04324307.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumour with a poor prognosis and a high mortality rate. It is of great significance to explore sensitive or specific biomarkers for early diagnosis and prognosis. We first examined the metabolome and gut microbiota of resectable and unresectable PDAC patients to comprehensively investigate the characteristics of PDAC at different stages of progression. At the genus level, we found that the relative abundances of Alistipes, Anaerostipes, Faecalibacterium and Parvimonas were reduced in unresectable PDAC patients, whereas Pseudonocardia, Cloacibacterium, Mucispirillum, and Anaerotruncus were increased. Metabolomics analysis showed that the main changed metabolites were amino acids, carnitine derivatives, lipids and fatty acids. ROC analysis showed that Oleic acid, Linoleic acid, Palmitic acid, Linoelaidyl carnitine, 2-Octenedioic acid, 3R, 7R-1,3,7-Octanetriol, LysoPE (P-16:0/0:0) and 3-Hydroxyanthranilic acid had high AUC values (>0.9). Function and network analyses showed that these altered metabolites correlated with NF-kappa B signalling, the FXR/RXR pathway, mitochondrial dysfunction, mTOR signalling and IL-6 signalling. In particular, the abundance of Palmitic acid, Oleic acid, Linoelaidyl carnitine and 2-Octenedioic acid positively correlated with g_Anaerostipes, g_Alistipes, s_indistinctus, s_catus and s_formicigenerans but negatively correlated with g_Cloacibacterium, s_reuteri and s_hathewayi. Meanwhile,We also found that s_catus, s_ formicigenerans, s_ hathewayi, g_ Alistipes, g_ Anaerostipes, PE (22:6 (4Z, 7z, 10z, 13z, 16Z, 19Z)/p-18:1 (11z)), (3R, 7R) - 1,3,7-octanetriol and linoelaidyl carnitine were positively correlated with the survival time of patients.These findings may be helpful for the differentiation of resectable and unresectable PDAC based on changes in intestinal flora and metabolites at different stages of PDAC. This study also provides a strategy for preventing the deterioration of PDAC by regulating the gut microbiota and metabolism.

疼痛作为大多数疾病常见的并发症之一,其调节机制涉及多种生物分子.降钙素基因相关肽(calcitonin gene-related peptide,CGRP)广泛分布于人体外周和中枢神经系统伤害性通路中,其受体也在疼痛通路中表达.CGRP及其受体通过激活谷氨酸受体和第二信使系统参与中枢敏化,且CGRP本身作为促炎神经肽,还与其他炎症介质相互作用参与外周神经系统敏化,进而传递伤害性疼痛信息.目前较多研究表明CGRP参与疼痛发生,而阻断CGRP受体及抑制CGRP表达与疼痛缓解存在一定联系,本文将综述CGRP通过参与神经系统敏化诱导疼痛发生的相关机制及抑制其表达后对疼痛缓解的影响,为今后寻找新的疼痛靶向治疗方法提供新的思路.

Abstract Background Vascular calcification associated with chronic kidney disease (CKD) can increase the risk of mortality. Elevated serum levels of high mobility group box 1 (HMGB1) promotes vascular calcification in CKD via the Wnt/β-catenin pathway. Sirtuin 6 (SIRT6) prevents fibrosis in CKD by blocking the expression of β-catenin target genes through deacetylation. This study aimed to investigate whether the inhibition of vascular calcification by bone marrow mesenchymal stem cell (BMSC)-derived exosomes is related to SIRT6 activity and assess the regulatory relationship between HMGB1 and SIRT6. Methods CKD characteristics, osteogenic markers, calcium deposition, and the differential expression of HMGB1 and SIRT6 have been measured in a 5/6 nephrectomized mouse CKD model fed a high-phosphate diet to induce aortic calcification. In vitro assays were also performed to validate the in vivo findings. Results High phosphate promotes the translocation of HMGB1 from the nucleus to the cytosol and induces the expression of Runx2, osteopontin, and Msx2. However, BMSC-derived exosomes were found to alleviate CKD-related fibrosis and the induction of osteogenic genes although less significantly when SIRT6 expression is suppressed. SIRT6 was found to modulate the cytosol translocation of HMGB1 by deacetylation in vascular smooth muscle cells. Conclusion Our results indicate that BMSC-derived exosomes inhibit high phosphate-induced aortic calcification and ameliorate renal function via the SIRT6–HMGB1 deacetylation pathway.

目的:观察健脾散结方对Ⅱ-Ⅲ期胃癌术后且完成辅助化疗患者无病生存期生活质量的影响.方法:采用前瞻性同期对照研究,纳入Ⅱ-Ⅲ期胃癌根治术后患者,以是否自愿接受基于健脾散结为主的辨证治疗方案将其分为健脾散结方组和对照组,两组患者均需完成术后辅助化疗.COX多因素回归分析、Kaplan-Meier生存分析对健脾散结方组和对照组的无病生存率进行比较,同时采用癌症患者生命质量测定量表对胃癌患者生活质量改善状况进行评估.结果:健脾散结方组与对照组1年、2年无病生存率分别为87.0％、73.9％及58.5％,43.9％,差异均有统计学意义(P＜0.05);无病生存期(disease-free survival,DFS)分别为29个月和18个月,差异有统计学意义(P =0.004);生活质量改善方面,健脾散结方组在疲倦、恶心与呕吐、失眠、食欲丧失、便秘方面改善优于对照组(P＜0.05).结论:与对照组相比,健脾散结方可提高Ⅱ-Ⅲ期胃癌患者1年、2年的无病生存率,延长无病生存期,改善胃癌患者生活质量.

目的 探讨腹腔灌注顺铂联合紫杉醇?替吉奥(TS-1)多途径化疗方案对晚期腹膜转移性胃癌患者的疗效.方法 收集了2012 年3 月至2018 年10 月在岳阳中西医结合医院肿瘤科采用顺铂(40 mg/ m2腹腔灌注)?紫杉醇(50 mg/m2静滴)?TS-1(50 mg/ m2口服)联合化疗方案治疗的胃癌腹膜转移患者的临床资料,评价患者的疗效和毒副反应,Kaplan-Meier 法绘制生存曲线.结果 77 例患者至少完成2 个周期化疗,均可评价疗效,客观缓解率为54.5%(42/77).77 例患者1年生存率为52%,2 年生存率为25%,3 年生存率为5%,中位OS 为12.0 个月(95% CI:8.2~15.8 个月).27 例伴肝转移患者的中位OS 为8.0 个月(95% CI:4.9~11.1 个月).伴腹水患者中位OS 为9 个月(95% CI:4.1~13.9 个月),无腹水患者中位OS达14 个月(95% CI:10.5~17.5 个月),差异有统计学意义(P =0.05).常见不良反应主要为1~2 级的胃肠道毒性?血液学毒性及脱发.结论 顺铂(腹腔灌注)?紫杉醇(静脉注射)和TS-1(口服)三药联合多途径给药方案治疗腹膜转移性胃癌有效且安全性较好.