目的:探讨单孔和四孔腹腔镜胆囊切除术的疗效差异.方法:回顾性分析上海交通大学医学院附属仁济医院胆胰外科2018年6月至2019年8月期间施行单孔(单孔组)和四孔腹腔镜胆囊切除术(四孔组)的临床资料,包括手术时间、腹腔引流管留置率、手术方案转变率、手术出血量、术后并发症率(胆漏、出血、伤口感染)、住院时间、住院费用、术后24 h镇痛药物使用率和术后满意度等.结果:单孔组手术时间显著长于四孔组[(42.48±6.66)min Vs(32.18±7.08)min],单孔组腹腔引流管留置率显著低于四孔组(1.67％Vs21.67％),差异均有统计学意义(P＜0.05);单孔组的住院时间短于四孔组[(2.22±0.65)天Vs(2.71±0.57)天],单孔组住院费用高于四孔组[(2.19±0.17)万元Vs(1.81±0.14)万元],单孔组术后24 h镇痛药物使用率低于四孔组(4.17％Vs 16.67％),术后满意度评分单孔组较四孔组更高[(4.68±0.64)分Vs(4.47±0.68)分],差异均有统计学意义(P＜0.05);单孔组的手术出血量、手术方案转变率以及术后并发症与四孔组比较没有差异(P＞0.05).结论:单孔腹腔镜胆囊切除术的术后疼痛轻,恢复快,手术安全性与传统四孔腹腔镜胆囊切除术相比无明显差异,同时单孔腹腔镜胆囊切除术满意度更高,值得临床推广.

Cholangiocarcinoma (CCA) is a type of solid tumor derived from the bile duct epithelium that features universal gemcitabine resistance. Here, we utilized a gene-encoded ROS biosensor probe (HyPer3 probe) to sort subpopulations with different redox statuses from CCA cells. The isolated HyPer-low subpopulation CCA cells, which exhibited relatively lower cellular ROS levels, exhibited higher chemoresistance to gemcitabine than HyPer-high subpopulation CCA cells in vitro and in vivo. Mechanistically, increased expression of MTHFD1 was found in HyPer-low cells. Knocking down MTHFD1 in HyPer-low cells enhanced cellular ROS and restored sensitivity to gemcitabine. Furthermore, the MTHFD1 inhibitor antifolate compound methotrexate (MTX) increased cellular ROS, and combining gemcitabine with MTX effectively suppressed cholangiocarcinoma cell growth. In summary, the MTHFD1 level mediated the heterogeneous cellular redox status in CCA, which resulted in chemoresistance to gemcitabine. Our data suggest a novel strategy for CCA chemotherapy.

目的 总结单中心同一术者317例日间单孔腹腔镜胆囊切除术(single-incision laparoscopic cho-lecystectomy,SILC)的经验与体会.方法 回顾性分析上海交通大学医学院附属仁济医院同一术者于2017年4月至2020年9月间连续完成的日间病房317例SILC的临床资料,统计中转开腹率、术中出血量、术后疼痛评分、手术时间、住院时间、住院费用、手术并发症等指标,与同期同一术者完成的323例传统四孔法LC患者数据进行比较.结果 SILC组317例患者中313例成功施行SILC,传统四孔法LC组组323例患者中316例成功施行LC,两组中转开腹率无统计学差异[4例(1.3％)vs 7例(2.2％),χ2=0.82,P=0.362].SILC组的术后疼痛评分、住院时间方面明显低于传统四孔法LC组(P<0.001);但传统四孔法LC组的平均手术时间短于SILC组,住院费用明显低于SILC组(P<0.001).两组在术中出血量、术后并发症发生率方面无统计学差异(P>0.05).尽管总体上SILC组平均手术时间长于传统四孔法LC,但同一术者完成110例SILC手术后,SILC的平均手术时间与传统四孔法LC比较差异无统计学意义(P>0.05).结论 SILC是安全可行的,相比于传统四孔法LC具有改善患者术后疼痛与满足美观切口需求的优势.完成学习曲线后的持续实践能够有效缩短SILC的手术时间,推荐在严格把握适应证的情况下积极开展SILC.

目的 探讨中国胆囊癌病人的外科治疗模式、病理学特征和预后.方法 收集中国13个省市的26家医院自2010年1月至2017年12月收治的4345例胆囊癌病人临床资料,分析中国胆囊癌病人的地区、性别、年龄分布;基于病人的诊疗记录与检查结果对手术病人肿瘤的可切除性进行评估,分析可切除性肿瘤病人的外科治疗模式,参照术前检查、手术记录和术后病理学检查结果评估可切除性肿瘤手术治疗是否达到根治标准,分析行根治性手术胆囊癌病人的病理学特征.结果 4345例胆囊癌病人中,男性1664例(38.23％),女性2681例(61.77％).行外科手术治疗的病人3129例(71.01％),其中可切除性肿瘤2074例(66.28％).在可切除性肿瘤2074例病人中,仅1133例(54.63％)在术前即诊断为胆囊恶性肿瘤,1002例(48.31％)行根治性切除,1072例(51.69％)未达根治标准.胆囊癌根治性切除病人的病理学检查结果中,736例(73.45％)为腺癌,348例(34.73％)为低分化癌,376例(37.52％)伴肝侵犯,152例(15.17％)伴神经浸润,96例(9.58％)伴血管内癌栓,78例(7.78％)伴周围脂肪组织浸润,89例(8.88％)伴周围器官受累,328例(32.73％)活体组织病理学检查淋巴结阳性.获得生存随访资料的2357例手术治疗病人术后中位生存期为16.17个月,多因素Cox回归生存分析结果显示肿瘤TNM分期(P＜O.001)、肿瘤分化程度(P＜0.001)、肝脏侵犯(P＜0.001)、RO切除(P=0.003)均为术后生存期的独立预后因素.结论 中国胆囊癌术前诊断率有待提高;胆囊癌外科治疗模式亟待规范;病理学检查报告中反映的多个因素与胆囊癌病人预后密切相关,其描述的规范化对指导胆囊癌病人的精准治疗有重要意义.

Cholestasis is common in multiple clinical circumstances. The NOD-like receptor protein 3 (NLRP3) inflammasome pathway has been demonstrated to play an important role in liver injury and fibrosis induced by cholestasis. We previously proved that MCC950, a selective NLRP3 inhibitor, alleviates liver fibrosis and injury in experimental liver cholestasis induced by bile-duct ligation (BDL) in mice. Herein, we investigate the role of calcipotriol, a potent vitamin D receptor agonist, in experimental liver cholestasis, test its therapeutic efficacy, and explore its potential protective mechanism. C57BL/6 mice were made to undergo BDL or fed the 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet to establish two classic cholestatic models. Calcipotriol was administered intraperitoneally to these mice daily. Serum makers of liver damage and integrity, liver histological changes, levels of liver pro-fibrotic markers, bile acid synthetases and transporters were measured in vivo. The underlying mechanism by which calcipotriol alleviates cholestatic liver injury and fibrosis was further investigated. The results of the current study demonstrated that calcipotriol supplement significantly alleviate cholestatic liver injury and fibrosis. Moreover, calcipotriol supplement markedly inhibited NLRP3 inflammasome pathway activation to alleviate liver injury and fibrosis in vivo and inhibit hepatic stellate cell (HSC) activation in vitro. In addition, VDR agonist calcipotriol exert inhibitory effect on NLRP3 inflammasome activation through activating yes-associated protein 1 (YAP1). In conclusion, our findings proved that calcipotriol suppressed the NLRP3 signal by activating YAP1 to alleviate liver injury and retard fibrogenesis in cholestasis.

BACKGROUND:Single-incision laparoscopic surgery has emerged as an alternative to conventional laparoscopic cholecystectomy (LC) in the clinical setting. Limited information is available on the possibility of performing single-incision laparoscopic surgery as an ambulatory procedure. This study aimed to determine the feasibility and safety of single-incision laparoscopic cholecystectomy (SILC) versus conventional LC in an ambulatory setting. METHODS:Ninety-one patients were randomized to SILC (n = 49) or LC (n = 42). The success rate, operative duration, blood loss, hospital stay, gallbladder perforation, drainage, delayed discharge, readmission, total cost, complications, pain score, vomiting, and cosmetic satisfaction of the two groups were then compared. RESULTS:There were significant differences in the operative time (46.89 ± 10.03 min in SILC vs. 37.24 ± 10.23 min in LC; P < 0.001). As compared with LC, SILC was associated with lower total costs (8012.28 ± 752.67 RMB vs. 10258.91 ± 1087.63 RMB; P < 0.001) and better cosmetic satisfaction (4.94 ± 0.24 vs. 4.74 ± 0.54; P = 0.031). There were no significant differences between-group in terms of general data, success rate, blood loss, hospital stay, gallbladder perforation, drainage, delayed discharge, readmission, complications, pain score, and vomiting (P > 0.05). CONCLUSIONS:Ambulatory SILC is safe and feasible for selected patients. The advantages of SILC as compared with LC are improved cosmetic satisfaction and lower total costs.

Cholestasis occurs in many clinical circumstances and leads to severe liver disorders. MCC950, a small-molecule NLRP3 inhibitor, was previously shown to have anti-inflammatory effects. However, these effects have not yet been examined in cholestatic liver injury. This study aimed to investigate the role of NLRP3 inflammasome and test the therapeutic efficacy and molecular mechanisms of MCC950 in cholestatic liver injury through the common bile duct ligation (BDL) model in mice. The influence of MCC950 on histological changes, levels of liver damage, neutrophil infiltration, liver cell death, inflammatory cytokine levels, and NLRP3 inflammasome expression were examined. The results of the current study confirmed that NLRP3 components were up-regulated during bile duct obstruction. MCC950 treatment significantly alleviated BDL-induced liver injury by reducing production of the pro-inflammatory cytokines IL-1β and IL-18 and inhibiting neutrophil infiltration and hepatic cell death. Moreover, MCC950 significantly inhibited NLRP3 activation during cholestatic liver injury. In addition, transcriptome analysis indicated that Toll-like receptor signaling may be involved in the protective effects of MCC950 in cholestatic liver injury. In conclusion, experimental findings demonstrate that MCC950 exerted protective effects in cholestatic liver injury and liver fibrosis by blocking NLRP3 inflammasome activation and the mechanism was partially attributed to inhibition of Toll-like receptor signaling. The present study indicates MCC950 could potentially be an effective therapeutic strategy for the treatment of cholestatic liver injury.

Aims: Vitamin A and its metabolites has been found to be protective against cholestatic liver injury, but the exact underlying mechanisms involved in cholestatic liver injury remain unclear. The objective of this study was to determine the function and mechanisms of 9-cis-retinoic acid, the metabolite of vitamin A, in cholestatic liver injury. Methods: The bile duct ligated (BDL) mice were treated with 9-cis-retinoic acid by intravenous injection through the tail for 10 days. The liver function and histology were assessed in the matched group and experimental group. The expression of MRP3 in liver tissue was tested by qRT-PCR, Western blotting, and IHC. Effect of RXR alpha sumoylation on MRP3 expression was investigated at a cellular level. Influence of 9-cis-retinoic acid on RXR alpha sumoylation was also tested in cells. Results: Our findings showed that 9-cis-retinoic acid significantly decreases the serum ALT and AST level, alleviates hepatic necrosis of the BDL-mice. We also identified MRP3, an important protective hepatobiliary transporter in cholestasis, was elevated by 9-cis-retinoic acid in vivo and in vitro. 9-cis-retinoic acid weakened the sumoylation of RXR alpha, which promotes the cytoplasmic location of RXR alpha and lightens the interaction of RXR alpha and RAR alpha. Inhibition of RXR alpha and RAR alpha interaction increased MRP3 expression. Conclusions: 9-cis-retinoic acid alleviates cholestatic liver injury by elevating MRP3 expression through its mechanism of inhibiting sumoylation of RXR alpha. (C) 2018 Elsevier Inc. All rights reserved.

Clip migration into the common bile duct (CBD) is a rare but well-established phenomenon of laparoscopic biliary surgery. The mechanism and exact incidence of clip migration are both poorly understood. Clip migration into the common bile duct can cause recurrent cholangitis and serve as a nidus for stone formation. We present a case, a 54-year-old woman, of clip-induced cholangitis resulting from surgical clip migration 12 months after laparoscopic cholecystectomy and laparoscopic common bile duct exploration (LC+LCBDE) with primary closure.

Aim . To investigate the role of vitamin A in liver damage induced by bile duct ligation (BDL) in rats. Methods . Thirty male Wistar rats were randomly divided into three groups: SHAM group, BDL group, and BDL + VitA group . The concentrations of retinol and retinyl palmitate in the liver were analyzed using HPLC, and liver function was evaluated by the level of TBIL, ALT, AST, and ALP in serum. Hepatic oxidative status was estimated by measuring T-SOD, CAT, GSH, MDA, and AOPP. Nrf2 expression was assessed using immunohistochemistry and western blotting, and EMSA was performed to determine Nrf2 DNA-binding activity. The expression of the downstream factors such as Ho1 and Nqo1 was also examined using immunohistochemistry and western blotting assays. Results . Vitamin A treatment restored levels of retinoids in liver, improved liver function, alleviated oxidative stress, and facilitated the translocation of Nrf2 to the nucleus in the experimental obstructive jaundice. Vitamin A was also found to increase the expression of Nrf2 downstream proteins such as Ho1 and Nqo1. Conclusion . Vitamin A was here found to ameliorate cholestatic liver injury. This effect may be related to the activation of Nrf2/ARE pathway in bile duct ligation rats.

PURPOSE To observe the effect of cholecystectomy on the changes of motion pattern of Beagle dogs' sphincter of Oddi (SO), and investigate the modulatory role of nitric oxide (NO) and cholecystokinin (CCK) in the regulation of SO. METHODS Pressure of common bile duct, SO motility, response to bolus injections of cholecystokinin (CCK, 20 ng/kg and 100 ng/kg), basal pressure (BP) and phasic contraction amplitude (PCA) were measured respectively by manometry in six Beagle dogs before and after cholecystectomy. RESULTS After cholecystectomy, the pressure and diameter of common bile ducts (CBD) was significantly increased (p<0.01); BP and phasic contraction frequency (PCF) were also increased, however, no significant differences were found between the two groups; the SO motilities was not significantly changed. The relaxation responded to physiological dose of CCK (20ng/kg) was decreased, while bolus-dose of CCK (100ng/kg) induced rapid contractions and decreased PCA after cholecystectomy. The regulation pattern of SO pressure modulated by NO and its inhibitor had changed after cholecystectomy. CONCLUSION After cholecystectomy in Beagle dogs, no obviously change of motion pattern of SO was observed through self-compensation, but these compensations may lead to some changes of regulation pattern of CCK and NO on SO.

Objective To observe curative effect and analyse the influence of drug treatment on skin.Methods To divide 160 patients who suffered from Scabies tubercle into three groups named A,B,C randomly,and use three different treatment means which is triamcinolone acetonide cream,strapping and Subcutaneous closed in addition to taking orally Loratadine.Result The effective rate of triamcinolone acetonide cream and Subcutaneous closed is 100%,the effective rate of strapping is 66.1%,the three groups had very obvious difference on cross table(Sig=0.000).Conclusion The curative effect of treatment over Scabies tubercle with Triamcinolone acetonide cream and Subcutaneous closed is perfect and obviously better than using triamcinolone externally.

To study extraction and separation technology of pulchinenoside, pulsatillae was extracted by different abstraction technologyies. Pulchinenoside B4 content and yield were detected by HPLC and HPTLC. The results showed that technology Ⅱ is better than technology 1. Pulchinenoside B4 with high yield can be obtained by this technology Ⅱ and Pulchinenoside B4 was concentrated in n -butanol part. This research provides a test basis for B4 separation and purification.

ObjectiveTo establish HPLC and HPTLC methods for identification and determination of Schisandra.MethodsChromatographic conditions were as follows: deoxyschizandrin,γ-Schisandrin,Schisandrin,Schisantherin as control samples;band application on GF254 plate;developer solvent system: ligarine(30～60℃)-ethyl formate-methanoic acid(15∶5∶1);distance from lower edge of plate 8 mm and observing the fluorescent chromatogram in a UV cabinet at 254 nm.The sample solution was analyzed by HPLC.The assay was performed on a Zorbax SB-C18 column(4.6 mm×250 mm,5 μm).The mobile phase was: methanol:H2O=(65∶35),the flow rate was 1.0 ml·min-1,the detection wavelength was 254nm and column temperature was room temperature.ResultsHPTLC method could quickly and accurately identify different sources of Schisandra and three kinds of herbs were different in the content of schisandrin.ConclusionThe methods are simple,accurate and reproducible,which can evaluate the quality of Schisandra qualitatively and quantitatively.