Modulating dendritic cells (DCs; inhibiting maturation and antigen-presenting capacity) potentially promote immune tolerance to the benefit of allografts. In this study, we aimed to elucidate the impact of miR-155 on DC maturation and allograft rejection. Donor monkey bone marrow-derived dendritic cells (BMDCs) were transduced with anti-miR-155 lentivirus to inhibit miR-155 expression, and the T cell phenotype and function of DCanti-155 upon lipopolysaccharide (LPS) stimulation were evaluated. In vivo, imDC, imDCanti-NC, and imDCanti-155 were injected into recipient monkeys before skin transplantation. The survival times of skin allografts were recorded and the proportions of T cell subsets in spleen and secretion levels of cytokines in serum were measured. SOCS1/JAK/STAT pathway expression was also examined. miR-155 level increased during the maturation of dendritic cells. Inhibition of miR-155 significantly attenuated LPS-induced DC maturation. imDCanti-155 promoted the differentiation of regulatory T cells (Tregs) and augmented the secretion of immunosuppressive cytokines. In vivo, subcutaneous injection of imDCanti-155 prolonged recipient monkey skin allograft survival times and attenuated immune rejection. An increase in the proportion of Treg cells and their secreted cytokines in serum was observed in the imDCanti-155 group. Mechanistic insights suggest that miR-155 likely regulates the SOCS1-JAK/STAT pathway. Suppression of miR-155 has the potential to inhibit DC maturation, affects the differentiation of T cell subsets, and prolongs skin allograft survival, which could serve as a promising therapeutic strategy for managing allograft rejection.

Background:: Uncontrolled inflammation plays an important role in the initiation and progression of tumors. The repeated circulation and continuous stimulation of gallbladder epithelium caused by gallstones is an important risk factor for gallbladder cancer. Methods:: To study pathogenesis, samples were collected for chronic cholecystitis caused by gallstones and early and advanced gallbladder cancer with gallstones and subjected to RNA-seq analysis. Gene Ontology and Kyoto Gene and Genome Encyclopedia analyses were used to elucidate the protein–protein interaction network and identify differentially expressed genes. Results:: Nine potential molecular markers, VTN, CHAD, AKR1C4, ABCC2, AOX1, ADH1A, ADH1C, PLA2G2A, and CYP4F3, with elevated expression gradients in cholecystitis and early and advanced gallbladder cancer, were identified. Using qPCR and immunohistochemistry on clinical tissues, we confirmed three factors, VTN, CYP4F3, and AOX1, to be worthy of further research. To demonstrate that these three genes are potential molecular markers for gallbladder cancer, their cellular biological functions were confirmed in gallbladder cancer cell lines through siRNA transfection. Conclusion:: The potential molecular markers CYP4F3, VTN, and AOX1 for cholecystitis and different stages of gallbladder cancer were identified. Further studies on differentially expressed genes vital in gallbladder cancer progression can help provide potential targets for the early diagnosis and treatment of gallbladder cancer.

Spontaneous splenic rupture (SSR) is an uncommon but life-threatening surgical emergency. When it occurs as a complication of systemic lupus erythematosus (SLE), the diagnostic and therapeutic strategy becomes particularly complex. Published literature on SSR in the setting of SLE is sparse, and there is no clear consensus on the optimal management of such a surgical catastrophe. What is the optimal treatment strategy for patients with SSR complicated by SLE? This paper addresses these questions by providing an in-depth analysis of a representative case of SLE complicated by SSR that we successfully diagnosed and treated. Our case study details the patient's entire clinical course, from the initial presentation with non-specific abdominal pain, through confirmation via imaging diagnostics, to the final recovery achieved through a personalized treatment plan developed by a multidisciplinary team (MDT). A key finding of our research is the emphasis that, for patients with known autoimmune diseases such as SLE, the acute onset of abdominal pain, hemodynamic instability, or any signs of intra-abdominal bleeding should prompt clinicians to maintain a high index of suspicion and include SSR in the differential diagnosis. Rapid identification, multidisciplinary collaboration (involving close coordination among rheumatology, critical care, surgery, and radiology), and individualized treatment decisions based on the patient's specific condition are the cornerstones of successfully managing this severe complication and improving patient outcomes. We believe the significance of our findings lies in their potential to greatly enhance clinicians' understanding of this rare yet fatal complication of SLE. The detailed diagnostic and therapeutic pathway and the decision-making rationale provided in this report can serve as a valuable reference guide for colleagues worldwide when faced with similar challenging cases, potentially saving more patients' lives.

The development of liver fibrosis is associated with inflammatory responses resulting from chronic liver disease. Immature dendritic cells (imDCs) play an important role in modulating the inflammatory environment of the liver. This study investigated the effects of imDCs on the regulation of hepatic stellate cells (HSCs) during liver fibrosis. We isolated and induced imDCs from monocytes of healthy volunteers, activated LX-2 cells with TGF-β to establish in vivo liver fibrosis HSCs model, and then set up a cell co-culture system with transwell membranes. imDC surface markers and apoptosis rates of LX-2 cells were detected by flow cytometry. The concentration of IL-10 secreted by imDC was measured through ELISA. The expression of α-SMA in LX-2 after co-culture was examined by qRT‑PCR. Proliferation of LX-2 cells were detected by CCK-8. The western blot was used to illustrate the LX-2 activation-related proteins such as Smad3/7 and TGF-β1. The imDCs co-culture group and the interleukin-10 (IL-10) treatment group had similar results, as they were both able to increase apoptosis, inhibit proliferation, downregulate α-SMA mRNA, and reduce TGF-β1 and Smad3 protein expression in LX-2 cells. Additionally, the Smad7 protein level was increased after treatment with imDC and IL-10. However, the results in the IL-10 antagonist group showed the opposite trend to that of imDCs and IL-10 groups. Thus, these results suggest that imDC secretion of IL-10 negatively regulates activated LX-2 cells, probably via inhibition of the TGF-β1/Smad3 pathway and increased expression of Smad7 protein. This may be a potential therapeutic target for liver fibrosis.

糖皮质激素（Glucocorticoid，GC）是一类由肾上腺皮质束状带分泌的一类甾体激素，由于其具有强大的抗炎作用及抑制免疫的作用，在减少术后并发症方面有较好的效果，被广泛运用于临床各科室，已逐渐成为快速康复外科中的重要组成部分。但其在肝胆外科围手术期的运用尚未达成共识。本文就GC在肝胆外科术后并发症方面的应用及不良反应作一简单综述。

Immature dendritic cells (imDCs) are activated and mature to initiate an adaptive immune response, resulting in allograft rejection and transplantation failure. Myeloid differentiation factor 88 (Myd88) is a key factor in the Toll-like receptor (TLR) signaling pathway. Here, we investigated the effect of Myd88 silencing on DC function and immune response. CD34 + cells were isolated from the bone marrow of rhesus monkeys by the immunomagnetic bead method and then infected with an adenovirus expressing Myd88-specific short hairpin RNA (sh-Myd88). sh-NC (nontargeting negative control)- or sh-Myd88-infected DCs were treated with lipopolysaccharide (LPS) for another 48 h to induce DCS maturation. The maturation of DCs was identified by immunofluorescence staining for MHCII, CD80, and CD86. DC apoptosis was examined using Annexin V/PI staining. DC-related cytokine levels (IFN-γ and IL-12) were assessed by ELISA. A mixed lymphocyte reaction (MLR) was performed to test the effect of Myd88-silenced DCs on T lymphocytes in vitro. The results showed that compared with control or sh-NC-infected DCs, Myd88-silenced DCs had lower MHCII, CD80, CD86, and DC-related cytokine (IFN-γ and IL-12) levels. Myd88 did not affect the apoptosis of DCs. MLR demonstrated that Myd88 silencing could effectively block LPS-activated T cell proliferation in vitro. These data were consistent with the characteristics of tolerogenic DCs. In conclusion, our data indicated that Myd88 silencing could inhibit the maturation of imDCs and alleviate immune rejection, which provides a reference for immune tolerance in clinical liver transplantation.

Dendritic cells (DC) initiate the immune response in the body. They can stimulate T cell activation, proliferation, and differentiation and ultimately participate in the immune response and the immune tolerance response. The purpose of this study was to coculture DCs and T cells and subcutaneously inject DCs transfected with miR-let-7i into rhesus monkey transplantations to verify the role of miR-let-7i in allograft immune tolerance. In vitro studies found that the expression of miR-let-7i was upregulated after inducing the maturation of DCs. The low expression of miR-let-7i inhibited the maturation of DCs, promoted the differentiation of T cells into T helper T cells 2 (Th2), and inhibited T helper T cell 1- (Th1-) driven rejection. In vivo studies also obtained similar results, and subcutaneous injection of DCs transfected with miR-let-7i inhibitor prolonged the survival time of allogeneic skin transplantation. Therefore, we conclude that inhibition of miR-let-7i inhibits DC maturation and improves the tolerance of grafted skin.

肝脏是人体重要的代谢器官,在受到感染、损伤以及手术切除后,会表现出强大的再生能力,能够在短期内恢复原有的质量和体积,从而使得生理功能正常运转.白细胞介素-6(IL-6)是一种具有多种活性的细胞因子,可与其特异性受体结合发挥生物学功能.IL-6与膜式受体IL-6R(mIL-6R)结合介导经典的IL-6/STAT3通路使IL-6/mIL-6R发生了构型改变,再与gp130(信号转导蛋白)结合,使得两个亚单位的gp130活化形成同源二聚体,然后激活JAK/STAT3通路.活化的STAT3经历核易位,诱导肝急性期和某些早期基因的表达,最终促进了肝细胞的增殖,在肝脏的再生中起到重要作用.本文就IL-6对肝细胞增殖方面的研究进展进行综述,以期为临床肝移植提供帮助.

Objective:To probe the effectiveness of laparoscopic sleeve gastrectomy in treating obesity and metabolic syndrome and analysis its safety.Methods:Fifty LSG patients from 18 cases of hepatobiliary surgery in Xiantao First People's Hospital Affiliated to Yangtze University and 32 cases of gastrointestinal surgery in the Second Hospital Affiliated to Kunming Medical University from November 2014 to January 2018 were collected for retrospective analysis. Through follow-up, part of the time was extended to 48 months. Patients' weight, laboratory indexes, remission and treatment of complications were recorded, and the preoperative and postoperative metabolic indexes, changes of trace elements, remission of complications and treatment results of complications were statistically analyzed.Results:Laparoscopic sleeve gastrectomy was successfully performed in all 50 obese patients and none of them was transferred to laparotomy. Postoperative weight, body mass index (BMI), percentage of excess weight loss (%EWL) et al of the patients decreased significantly at 3 months after surgery (P<0.05), and tended to be stable at 24, 36 and 48 months after surgery (P>0.05). The laboratory indexes of triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were significantly changed at 6 months after the operation (P<0.05), and tended to be stable after 12 months after the operation (P>0.05). Fe and VitB12 had a decreasing trend 3 months after surgery (P<0.05), and became stable after 3 months after surgery though dieting and supplement (P>0.05). Complications: fasting plasma glucose (FPG), 2-hour postprandial blood glucose (2hPG) and glycosylated hemoglobin A1c (HbA1c) decreased gradually within 6 months after the operation (P<0.05), In this period, 27 patients had complete remission (90.0%) and 3 patients had partial remission (10.0%), and they tended to be stable in 48 months after the operation (P>0.05).Hypertension, obstructive sleep apnea (OSA) and polycystic ovary syndrome were relieved to varying degrees within 2 years after surgery. There were 3 cases of short-term serious complications and 9 cases of long-term complications after surgery were achieved clinic crue after relevant treatment.Conclusions:Laparoscopic sleeve gastrectomy has a significant effect on obesity and metabolic syndrome, and the surgical operation is not complicated with fewer complications. Therefore, it is worthy of promotion in clinical practice.

Hepatocellular carcinoma (HCC) is a severe solid tumor threatening human health worldwide. In the discovery of novel therapies for HCC, phytochemicals play a crucial role. In our program to search bioactive compounds for the treatment of HCC, we have evaluated melohenine B using human HCC HepG2 cells. The results showed melohenine B reduced the proliferation of HepG2 cells via inducing apoptosis. At the same time, melohenine B inhibited caspase-3 activity, disrupted mitochondrial membrane potential, down-regulated Bcl-2, and up-regulated Bax, which indicated the apoptosis underwent intrinsic pathway. Further investigations revealed inactivation of PI3K/Akt pathway was involved in the apoptosis induced by melohenine B. These findings can provide evidences for the discovery of new therapy for the treatment of HCC.

目的 系统评价肝胰十二指肠切除术治疗胆囊癌的疗效.方法 检索中国知网、万方数据、PubMed、Embase等数据库关于肝胰十二指肠切除治疗胆囊癌的随机对照试验(RCT)、非随机对照研究、非随机实验性研究、病例对照研究、队列研究、案例系列研究等,各数据库检索时间均由建库至2019年12月.由两位学者按照纳入与排除标准筛选文献和提取资料,采用Stata软件进行Me-ta分析.结果 最终纳入16篇文献,包括205例病人.结果显示:(1)1、2、3、5年生存合并率分别为56.3％、26.4％、9.3％、6.6％.(2)R0亚组分析:通过合并率来看R0切除与非R0切除1、2年生存率基本相同,但R0切除的5年生存率比非R0切除高出很多.(3)病理Ⅳ、Ⅴ亚组分析,差异无统计学意义.(4)总的复发率分析,手术复发合并率为71.2％;亚组分析示复发率差异无统计学意义.(5)围手术期并发症发生率及死亡率均较高,并发症多为胰瘘、腹腔感染、肝衰竭等,而发生围手术期死亡的原因不尽相同.结论 肝胰十二指肠切除术治疗胆囊癌总体有一定价值,上述结论尚需进一步开展RCT研究来进一步验证.

Abstract Chemotherapy remains the mainstream treatment option for invasive and metastatic breast cancer. Adriamycin (ADR) is one of the most frequently used and an effective chemotherapeutic agent for treating patients with breast cancer. However, the resistance towards ADR becomes a major obstacle to achieve efficacy and favorable outcomes in breast cancer patients with chemotherapy. We recently developed a serial oridonalogs that may possess the ability to overcome chemoresistance in cancer cells, whereas whether these novel anti-cancer agents reverse ADR resistance in resistant breast cancer cells are not adequately explored and further the mechanism of action has not been studied. In this study, oridonalogs, YD0514, CYD0618, and CYD0686, were used to determine their effects on the proliferation of the ADR-resistant breast cancer cells. We found significant inhibition of proliferation of wild-type breast cancer cell line MCF-7 and ADR-resistant MCF-7/ADR cells, time- and dose-dependently. Among the tested compounds, CYD0618 and CYD0686 were more effective in inducing apoptosis in wild-type and resistant breast cancer cells than YD0514, in comparison to the natural product and lead compound oridonin. In addition, total STAT3 level was found higher in ADR-resistant breast cancer cells, while phospho-STAT3 was higher in resistant cells. CYD0618 inhibited STAT3 activation in ADR-resistant cells. Our findings suggest that STAT3 activation may be critically involved in the development of acquired resistance to ADR, while oridonalogs such as CYD0618 may open the avenue to reverse and overcome ADR resistance in breast cancer by targeting STAT3. Further mechanistic explorations are currently underway. Citation Format: Xi Liu, Yefei Wen, Hyejin Kim, Pingyuan Wang, Haiying Chen, Mingdao Hu, Ye Ding, Jia Zhou, Qiang Shen. Oridonalogs reverse chemoresistance in breast cancer cells by targeting STAT3 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-03-19.

Drug‐induced liver injury (DILI) can lead to acute liver failure, a lethal condition which may require liver transplantation. Hepatotoxicity associated with nonsteroidal anti‐inflammatory drugs (NSAIDs) accounts for ~ 10% of all DILI. In the current study, we determined whether indomethacin, one of the most commonly used NSAIDS, induced apoptosis in hepatocytes and investigated the underlying mechanism. Meanwhile, we investigated the protective effect of S‐allyl‐L‐cysteine (SAC), an active garlic derivative, on indomethacin‐induced hepatocyte apoptosis, and its implication on endoplasmic reticulum (ER) stress. We found that indomethacin triggered ER stress, as indicated by the elevated expression of phosphorylated eukaryotic translation initiation factor 2α (eIF2α), C/EBP homologous protein (CHOP) and spliced XBP1 in a rat liver BRL‐3A cell line. Following indomethacin treatment, caspase 3 activation and hepatocyte apoptosis were also observed. Inhibition of ER stress by chemical chaperone 4‐phenyl butyric acid alleviated cell apoptosis caused by indomethacin, indicating that ER stress is involved in indomethacin‐induced hepatocyte apoptosis. Moreover, SAC abated indomethacin‐induced eIF2α phosphorylation, inhibited CHOP upregulation and its nuclear translocation, abrogated the activation of caspase 3 and finally, protected hepatocytes from apoptosis. In conclusion, SAC protects indomethacin‐induced hepatocyte apoptosis through mitigating ER stress and may be suitable for development into a potential new therapeutic agent for the treatment of DILI.

耐受性树突状细胞(tolerogenic dendritic cell,tolDC)在器官移植和自体免疫性疾病中对免疫耐受调节至关重要.与免疫抑制剂相比,tolDC用于治疗移植后排斥反应的副作用较低.此外,tolDC可通过多种途径培养生成,且不同的培养方式具有独特功效.目前,tolDC作为一种诱导器官移植耐受的辅助治疗已在临床试验中广泛应用.本文就tolDC诱导免疫耐受、tolDC的体外诱导培养及其miRNA调控机制和应用进行综述并提出相关展望,以期为应用tolDC治疗减轻移植后排斥反应的研究提供新思路.

目的 探讨选择性入肝血流阻断在肝叶切除术中的临床运用价值.方法 收集2012年1月至2019年9月间长江大学附属仙桃市第一人民医院行肝叶切除的136例病例进行回顾性研究,按术中血流阻断方式分为两组,对照组采用第一肝门阻断(Pringle法)66例,研究组采用选择性入肝血流阻断法70例,将两组的术前资料(性别、年龄、BMI、肝功能分级、肝硬化、AFP、HbsAg),术中情况(手术时间、血流总阻断时间、术中出血量、术中输血量、输血率),术后生化指标(术后第1、3、5天血清ALT、AST、TBIL、ALB的变化),术后凝血时间、术后并发症(感染、胆漏、胸腔积液、腹腔积液、出血)等数据应用SPSS软件进行统计学分析.结果 两组术前资料无统计学差异(P>0.05),两组手术时间、术中出血量、术中输血量、输血率及血流阻断总时间比较无统计学差异(P>0.05).术后第1、3、5天血清ALT、AST、TBIL、ALB对照组明显高于研究组(P<0.05),术后凝血时间及术后并发症两组比较无统计学差异(P>0.05).结论 在肝叶切除术中选择性入肝血流阻断并不增加患者手术时间、术中出血和术后并发症,术中能有效地保护肝脏,有利于术后肝功能的恢复,是一种比较安全、可行的肝血流阻断方式.

胰腺癌预后极差,5年总体生存率仅为7％左右.由于胰腺癌发病隐匿,进展快,早期诊断困难,多数患者失去手术机会,并且胰腺癌对放化疗均不敏感,因此需要探索一种新的有效治疗方式.近年来针对肿瘤微环境代谢特点及相关免疫检查点靶向治疗联合传统药物化疗成为胰腺癌治疗的新思路.本文对胰腺癌微环境的特点、相关免疫及微环境代谢中的治疗进展进行综述,为进一步提高胰腺癌患者的生存率提供新思路.

目的 探讨非解剖性肝切除与经皮射频消融治疗单发小肝癌的临床疗效.方法 回顾性分析昆明医科大学第二附属医院2014年1月至2016年8月收治的51例单发小肝癌病人的临床资料.根据治疗方法的不同分为对照组和研究组,对照组23例行非解剖性肝切除术,研究组28例行经皮射频消融术,并记录两组病人的术后住院时间,术后3d肝功能变化,术后3d凝血功能指标,术后并发症情况以及随访术后1、2、3年的无瘤生存率及总体生存率等.结果 研究组与对照组比较,病人术后3 d的血清丙氨酸转氨酶(ALT)与天冬氨酸转氨酶(AST)水平更低,凝血酶原时间(PT)和活化部分凝血酶原时间(APTT)波动更小,术后住院时间更短,术后并发症发生率更低,差异均有统计学意义(均P<0.05).两组病人术后1、2、3年无瘤生存率:对照组为86.96％、69.57％、56.52％;研究组为85.71％、71.43％、60.71％.两组病人术后1、2、3年总体生存率:对照组为100％、91.30％、78.26％;研究组为100％、85.71％、75.00％,差异均无统计学意义(均P>0.05).结论对于单发的小肝癌,经皮射频消融可以和非解剖性肝切除达到一样的效果,它具有更小的创伤性,对病人肝功能损伤及凝血功能影响更小,能有效降低术后并发症的发生,减少病人的住院时间,其远期的无瘤生存率及总体生存率对比无明显差异,值得临床推广.

肝血管瘤作为最常见的肝脏良性肿瘤,随着影像学检查设备和技术的逐步发展,近年来,肝血管瘤的诊断率也逐步的提高.本文回顾了目前肝血管瘤的临床表现、诊断、手术治疗.本文主要对近段时间来肝血管瘤的外科手术治疗作一综述.

目的 研究探讨普外科使用三种不同的手术方式来治疗胆囊结石合并胆总管结石的临床疗效.方法 使用回顾性研究的方法分析自2015年10月至2018年10月,昆明医科大学第二附属医院收治的97例胆囊结石合并胆总管结石患者的临床资料.分为腹腔镜下胆囊切除(laparoscopic cholecystectomy,LC)+腹腔镜下胆总管切开探查取石(Laparoscopic Common Bile Duct Exploration,LCBDE)+一期缝合(A组),腹腔镜下胆囊切除(LC)+腹腔镜下胆总管切开探查取石(LCBDE)+T管引流(B组),腹腔镜下胆囊切除(LC)+内镜下乳头括约肌切开术(Endoscopic sphincterotomy,EST)取石(C组),其中A组,37例;B组,39例;C组,21例.监测与比较三组患者一般情况、总胆红素,以及手术时间、治疗费用等情况.结果 三组患者胆总管内径、总胆红素水平、胆总管结石数量、胆总管结石直径比较差异无统计学意义(P＞0.05),有可比性;A组与B组手术时间、总住院费用均低于C组(P＜0.05),B组总住院时间以及恢复正常生活时间(指患者手术切口创伤、肝肾功能、电解质及饮食情况恢复至正常状态所需要的时间)高于A组与C组(P＜0.05).三个对照组在术后出现并发症的情况差异无统计学意义(P＞0.05).结论 三种不同手术方式各有其优缺点,且适应症不同,综合而言,胆总管切开探查+一期缝合疗效最优.