患者 男,62 岁.便秘 6 个月,加重伴肛周坠胀 1 d入院. 5 个月前因冠心病行经皮冠状动脉介入治疗(percutaneous cor-onary intervention,PCI).术后坚持口服"阿司匹林、瑞舒伐他汀"等药物治疗.入院后遵医嘱行结肠运输试验.常规进行胸部 X线检查,双肺未见明显异常.嘱患者吞服 20 粒医用钢珠,吞服过程及吞服完毕患者无呛咳等不适.

Tumor-associated macrophages (TAMs) are the major immunosuppressive components infiltrating the tumor microenvironment (TME). Targeting TAMs has emerged as a promising strategy to remodel immunosuppressive TME and enhance T-cell mediated anti-tumor immunity for cancer therapy. In this study, we investigate the effect and mechanism of total tannin fraction of Terminalia bellirica (Gaertn.) Roxb. (TB-TF) against hepatocellular carcinoma (HCC) using established Hepa1–6 orthotopic mouse model and murine bone marrow derived macrophage polarization model. Here we showed that TB-TF significantly inhibited orthotopic tumor growth and promoted the polarization of M2-TAMs toward the anti-tumor M1 phenotype in vivo. Further studies showed that TB-TF reversed tumor-conditioned medium induced M2 polarization of macrophages as indicated by increased expression of TNF-α, IL-1β, and iNOS, and decreased expression of Arg-1, thereby re-educating macrophages co-cultured with tumor-conditioned medium into M1 phenotype. In addition, we found that TB-TF also promoted T cell infiltration mediated by chemokines such as CCL5 and CXCL10, and restored the cytotoxic function of CD8+T cells as evidenced by upregulated expression of Granzyme B, Perforin, and IFN-γ. Our data suggest TB-TF as a promising anti-cancer agent, mediates its anti-tumor effects via remodeling the tumor immunosuppressive microenvironment, indicating its potential in the immunotherapy for hepatocellular carcinoma.

目的 对余甘子药材质量标准进行改进和修订.方法 建立紫外-可见分光光度法测定余甘子果实和果肉中总鞣质含量的方法,建立HPLC测定果实和果肉中没食子酸和鞣花酸含量的方法;采用建立的方法对15批余甘子果实和果肉样品进行测定并建立相应质量标准.结果 总鞣质、没食子酸和鞣花酸分别在(0.001023～0.01023)mg·mL-1、(0.02128 ～0.5320)μg、(0.02124～0.5310)μg范围内线性良好,平均加样回收率在97.33％～99.29％范围内,方法学验证均符合要求.根据15批余甘子果实和果肉样品测定结果,建议修订药材含量测定项,按在干燥品计算,含鞣质不得少于6.0％,含没食子酸、鞣花酸的总量不得少于2.0％.增加余甘子去核饮片为冬季至次春果实成熟时采收,剖开除去果核,干燥,并规定饮片含量测定项,按在干燥品计算,含鞣质不得少于8.5％,含没食子酸、鞣花酸的总量不得少于2.7％.结论 本研究建立的标准具有较好的专属性和稳定性,可为余甘子标准的修订提供依据.

Ethnopharmacological relevance: Inflammatory responses are associated wieh the pathophysiology of depression. Ginsenoside Rb1 (Rb1) exerts antidepressant effect, but the relationship between its activity and inflammation remains unclear. Aim of the study: In this study, the antidepressant-like effect and underlying mechanisms of Rb1 were been investigated. Materials and methods: The neuroinflammatory mouse model of lipopolysaccharide (LPS)-induced acute depression-like behavior was employed to detect the action of Rb1. An integrative strategy combining the identification of prototype (Rb1) and its metabolites in vivo with network pharmacology analysis was used to explore therapeutic mechanisms of these ingredients. The putative targets and signalings were experimentally validated. The antidepressant-like effect of F2, the metabolite of Rb1, was firstly evaluated. Results: Rb1 significantly ameliorated LPS-induced depressive-like behavior. Rb1 and its metabolites (Rd, F2, compound K, Rh2, Rg3, PPD) were identified and then a disease-component-target network was established. Experimental validation showed that Rb1 inhibited peripheral and hippocampal inflammation via MAPK/NF-Kappa B signaling. In inflammatory-mediated depression state, Rb1 improved impaired glucocorticoid receptor, suppressed indoleamine 2,3-dioxygenase activity, increased 5-HT level and 5-HT1A receptor expression. Additionally, F2 was firstly discovered to exert antidepressant-like effect, and it existed higher activity than Rb1 against depression. Conclusion: The study highlighted the potential of Rb1 and F2 as healthy supplement or agent for inflammationinduced depression.

目的 利用UPLC-Q-Orbitrap-MS技术系统研究藏药复方大三果主要化学成分并结合网络药理学探讨发挥药效的主要作用机制.方法 采用UPLC-Q-Orbitrap-MS对大三果主要化学成分进行分析,根据化合物的一级、二级质谱信息,结合相关文献和对照品,对化学信息进行快速识别.采用网络药理学的方法对大三果的成分靶点构建化合物-靶点网络,通过蛋白相互作用(PPI)网络筛选出核心靶点,对靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析.结果 从大三果醇提物中共鉴别出85个学成分,主要包括酚酸类、鞣质类、黄酮类成分.根据ADME过筛标准获得12个主要活性成分,包括Quercetin,Kaempferol,Luteolin,Morin和Ellagic acid等作用于10个关键靶点,包括CXCL8、APP、CHRM2、CXCL2、CXCL10、ADCY2、CXCR1、CXCL11、PTGER3、ADORA1等,富集的信号通路主要集中在对炎症、癌症、免疫等方面.结论 本研究从网络药理学角度阐明大三果多成分、多靶点、多途径的整体调节特点,初步揭示了抗炎、抗癌、免疫调节的物质基础和作用机制,为大三果进一步的临床应用和深入研究提供了思路和线索.

Phyllanthus emblica L. is widely used in traditional Tibetan medicine for its therapeutic effects on treating liver, kidney, and bladder problems. We have reported that the tannin fraction has a good anti-hepatocellular carcinoma effect, but its active ingredients are not clear. This study was to find the active ingredients of the tannin fraction using UPLC-MSn and network pharmacology. First of all, the UPLC-MSn method was employed to obtain high-resolution mass spectra of different components, and 110 compounds were obtained. Then a network pharmacology method was used to find biomarkers for quality control. Network pharmacology results showed that gallic acid, punicalagin A, punicalagin B, methyl gallate, geraniin, corilagin, chebulinic acid, chebulagic acid, and ellagic acid should be the biomarkers of the tannin fraction. Furthermore, 9 components were detected in the serum, which also proved that they could be biomarkers, because we generally believe that the ingredients which are absorbed into the blood are effective. In the end, a simple method for simultaneously determining the contents of the 9 compounds was constructed by HPLC-DAD. This research established a new method to find biomarkers of traditional Chinese medicine. This is of great significance to improving the quality standards of Tibetan medicine.

辣木Moringa oleifera为辣木科辣木属多年生热带落叶乔木,广泛种植于亚洲、非洲的热带和亚热带地区.辣木叶中主要含有黄酮类、多酚类、苯丙素类、萜类、甾体类、生物碱类、异硫氰酸酯类以及多种有机酸类等化学成分,且这些成分表现出良好的降血糖、降尿酸、抗肿瘤、调血脂、抗氧化以及保肝等药理活性.主要对辣木叶化学成分和药理活性的研究进展进行综述,以期为进一步研究和开发利用辣木叶提供参考.

Ginseng, the root and rhizome of Panax ginseng C. A. Mey., is a famous herbal medicine, and its major ginsenosides exert beneficial effects on nonalcoholic fatty liver disease (NAFLD). Due to the multicomponent and multitarget features of ginsenosides, their detailed mechanisms remain unclear. This study aimed to explore the role of ginsenosides on NAFLD and the potential mechanisms mediated by the gut microbiota and related molecular processes. C57BL/6J mice were fed a high-fat diet (HFD) supplemented or not supplemented with ginsenoside extract (GE) for 12 weeks. A strategy that integrates bacterial gene sequencing, serum pharmacochemistry and network pharmacology was applied. The results showed that GE significantly alleviated HFD-induced NAFLD symptoms in a dose-dependent manner. Furthermore, GE treatment modulated the HFD-induced imbalance in the gut microbiota and alleviated dysbiosis-mediated gut leakage and metabolic endotoxemia. Additionally, 20 components were identified in the mouse plasma after the oral administration of GE, and they interacted with 82 NAFLD-related targets. A network analysis revealed that anti-inflammatory effects and regulation of the metabolic balance might be responsible for the effects of GE on NAFLD. A validation experiment was then conducted, and the results suggested that GE suppressed NF-κB/IκB signaling activation and decreased the release and mRNA levels of proinflammatory factors (TNF-α, IL-1β and IL-6). Additionally, GE promoted hepatic lipolytic genes (CPT-1a), inhibited lipogenic genes (SREBP-1c, FAS, ACC-1) and improved leptin resistance. These findings imply that the benefits of GE are involved in modulating the gut microbiota, enhancing the gut barrier function, restoring the energy balance, and alleviating metabolic inflammation. Moreover, GE might serve as a potential agent for the prevention of NAFLD through the integration of prebiotic, anti-inflammatory and energy-regulatory effects.

The fruits of Terminalia bellirica (Gaertn.) Roxb. (TB) are used as a multi-use therapeutic herbal product in the Tibetan medicinal system and are prescribed as a general health tonic in the traditional Ayurvedic medicinal system. It has been demonstrated that these fruits have a variety of pharmacological activities, including anti-tumor, anti-oxidative, anti-inflammatory, hepatoprotective and immunoregulatory effects, etc. However, the therapeutic effects of tannins in TB on HCC and the underlying mechanisms remain uncharacterized. In the current study, we aimed to identify the anti-tumor effect of tannins in TB by employing a H22 xenograft mouse model and by performing cell-based in vitro studies with the assistance of the network pharmacology analysis. The crude extract of TB was purified to yield total tannin fraction (TB-TF), and our results found that TB-TF significantly inhibited the tumor growth of H22 xenografts in mice by inducing apoptosis and reducing angiogenesis. A total of 90 compounds were then identified in TB-TF by UPLC-MS/MS, and 27 were found in serum after oral administration of TB-TF in mice. The network pharmacology analysis based on these absorbed components was performed and, along with experimental evidence, it revealed that the ERBB, PI3K-Akt, and MAPK signaling pathways may be involved in the anti-tumor effect of TB-TF on HCC. Furthermore, we suggested that TB-TF effectively modulated the immunosuppressive tumor microenvironment in H22 xenograft mice. In summary, our study demonstrated that TB-TF could be developed as a functional food, which is not only a promising anti-cancer reagent but also a potential candidate with bright prospects for the emerging trends of immunotherapy for HCC.

采用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱联用技术(UPLC-Q-Exactive Orbitrap-MS),在电喷雾负离子模式下对使君子科(Combretaceae)榄仁树属(Terminalia Linn.)成分相近的藏药诃子与毛诃子的化学成分进行快速识别和鉴定.采用Acquity UPLC HSS T3色谱柱(2.1 m×100 mm×1.8μm),以含0.1％乙酸的甲醇-0.1％乙酸水溶液为流动相进行梯度洗脱.通过高分辨质谱给出的分子离子峰和碎片离子数据,结合相关文献和对照品,从诃子中鉴定出94个成分,包括28个特有成分,从毛诃子中鉴定出96个成分,包括30个特有成分,二者共有成分66个,其中12个鞣质类成分为首次从榄仁树属内发现.本研究可为诃子与毛诃子的快速鉴定,质量控制及阐明其药效基础提供参考.

患者男,27岁,间断右侧胸痛3年余入院.患者于3年前无明显诱因出现右侧胸痛,为间断性闷胀痛,未引起重视.近期疼痛频发,遂就诊.胸部CT检查示:右侧第7前肋膨胀性骨质破坏,其内似见液-液分层现象(图1,2).门诊以“右侧肋骨肿瘤”收入院.既往体健,无特殊病史.体格检查:T 36.3℃,P 76次/min,R 20次/min,Bp 125 mmHg/78 mmHg(1 mmHg=0.133 kPa).专科查体:胸廓无畸形,右侧胸壁略压痛(第7肋腋中线处),余未及异常.入院后积极术前准备,在全麻下行“胸腔闭式引流术+肋骨病损切除术”.术中在右侧第7肋骨腋中线处见一长约5.0 cm骨质破坏,内可见黄色分泌物,胸腔未见明显积液.术后病理巨检:骨组织1块,大小10.0 cm×3.0 cm×1.5 cm,切面灰红,可见空腔,质脆.病理镜下见:骨组织及软骨组织,巢状软骨细胞可见异型性,增生纤维组织中见新生不规则骨组织伴骨母细胞增生,易见破骨巨细胞,部分区出血、血管增生充血、囊性变.

Objectives. Tannins with complex structures are important plant resources, which are abundant in the genus Terminalia. Various Terminalia species have been playing an important role in traditional medicine system. A systematic scoping review of Terminalia Linn. research literature for tannins was conducted to summarize the structures of tannins and analysis fragmentation pathway characteristics, which could provide references for the structural analysis of tannins from Terminalia Linn. Methods. After an update of the literature search up to September 2018, the terms of Terminalia in all publications were analyzed. Electronic searches were conducted in scifinder and PubMed, and the information from 197 articles in all with regard to the tannin structure study was extracted. Results. The compounds of 82 tannins from the genus Terminalia were reviewed. According to the structural differences, they can be divided into three categories, hydrolysable tannins, condensed tannins, and complex tannins, respectively. The fragmentation pathways of 46 identified tannins were analyzed, and the fragmentation rules of tannins were speculated according to different types. Conclusion. This review has attracted attention to the active substances in this species such as the tannins summarized in further study. How to improve the extraction and purification technology of tannins from genus Terminalia is an urgent problem to be solved.

临床资料 患者,女,43 岁. "咳嗽1 月余,加重半月"入院. 患者1月前无明显诱因出现咳痰不适,无发热,无心慌、胸闷及呼吸困难. 近半月以来,患者咳嗽、咳痰症状加重,无痰中带血,无发热不适. 外院行输液抗感染治疗四天后,咳嗽较前好转,未愈. 外院胸片提示:"右肺占位性病变". 病后体力、体重未见明显变化. 既往体健,病史无特殊. 体格检查:T 36. 8℃ P 78次/分R 20次/分Bp 134/86 mmHg. 专科检查未及异常.

患者 男,25岁."右足疼痛1年,加重1周"入院.患者于1年前无明显诱因出现右足背疼痛,为持续性酸胀疼痛,夜间疼痛较明显.患病以来未诊治,一周前因扭伤右踝致右足疼痛加重入院.当地X线片诊断右足第三跖骨慢性骨髓炎.入院查体:右足背2～4跖骨区压痛、叩击痛,软组织稍肿胀,局部皮肤完整、未见色素沉着,皮温正常.实验室检查均阴性.

患者 女,79 岁. "双下肢疼痛麻木9h"入院. 患者于9h前无明显诱因双下肢疼痛麻木,以双足部明显,无发热等其它异常. 外院CT诊断"腰椎间盘突出症"收治入院. 既往有高血压病史,自服高血压药物治疗尚可;冠心病病史多年. 检查:T36. 4℃, BP120/80mmHg. 专科检查:L4 ～S1 棘突间压痛明显,双膝反射、踝反射未引出. 右下肢足下垂,踇背伸,胫前肌、踇屈肌肌力约0～1级. 左下肢踇伸肌、踇屈肌,胫前肌、小腿三头肌肌力3级,双侧踝关节以下感觉麻木. 双髋关节以下至踝关节以上肌力3 级. 肌张力无明显异常,其它病理反射未引出.

患者 男,76岁. "间断性左鼻出血2 月余,鼻塞半月余"入院. 患者2月前无明显诱因出现左鼻出血,呈间断性,时有鼻部痒感,无流脓性鼻涕. 半月前出现鼻塞,自觉左侧鼻腔通气不畅,遂就诊. CT检查示双侧上颌窦、筛窦及蝶窦腔内见软组织密度影,左侧鼻道及鼻前庭内见软组织影充填,最大范围约2.1cm ×2.7cm,密度不均匀,其中心区CT值约40HU(图1). 门诊检查后以"左鼻腔新生物"收入院. 病后除上述症状外无其他异常. 既往史无特殊. 入院专科体检:外鼻无明显畸形,鼻中隔无明显偏曲,左侧鼻腔可见新生物堵塞,新生物表面可见较多血痂,右侧下鼻甲肥大,鼻腔见粘脓性分泌物,未见新生物. 入院后积极准备,在气管内插管全麻静脉复合麻醉下行"鼻内窥镜下鼻内病损切除术+鼻甲射频消融术".

患者女，47岁。“发现右侧乳房肿胀、疼痛10天余”入院。患者于10天前发现右侧乳房肿胀，伴胀痛，无明显局部红肿，无乳头溢液，无局部皮肤破溃，无胸痛，咳嗽、咳痰，在外院就诊考虑为“乳腺炎”，给予抗炎治疗，病情未好转，乳房渐肿胀，疼痛渐加重。患者既往2001年在我院行双侧隆乳术，术后自本次发病前无任何不适。我院门诊乳腺彩超示：右乳后方囊性包块，双侧假体植入术后，右胸壁低回声区。遂以“1）乳腺炎；2）双侧隆乳术后”收住入院。入院体格检查：T 36．5℃，P 72bpm，R 20bpm，BP 120／80mmHg。专科体检：右侧乳腺较左侧乳腺明显增大，肿胀明显，无明显发红，无橘皮样改变，无皮肤破溃，触痛明显，挤压乳头无血性溢液。双侧腋窝未及明显异常。入院后积极行抗炎、对症支持治疗。患者入院后第2天夜间出现发热，最高体温40.0℃，遂行胸部CT检查（图1，2）：右侧乳腺区见直径15 cm半圆形低密度区，CT值为18 HU，其内可见液气平面，与周围软组织似可见分隔。周围脂肪间隙内可见少许气体影。左乳腺区未见明显异常。双肺及纵隔未见异常。 CT诊断：结合临床考虑右侧隆乳术后感染并脓肿形成。血常规检查示白细胞计数升高（13．29109／L，4～10），中性粒细胞百分数升高（85．0％，50～75），中性粒细胞绝对值升高（11．29109／L，2～7．5），淋巴细胞百分数降低（7．6％，20～40）。入院积极准备在全麻下行乳房植入物取出术＋皮肤和皮下组织脓肿抽吸术＋皮肤及皮下组织清创术。术中所见：左乳后间隙与大小肌间可见玉米粥样液体约1000 ml，右乳后间隙与大小肌间可见脓性样液体约1300ml，呈恶臭味。双侧胸大、小肌肌肉坏死并感染，呈条索样。术后标本患者家属过目后送病理检查，病理诊断：（乳腺包块）异物巨细胞肉芽肿。术后积极引流、抗炎及对症治疗，患者康复出院。

目的 探讨MSCT增强联合CT血管成像(CTA)技术在腹腔镜下肾肿瘤切除术中的临床应用价值.方法 回顾性分析29例经腹腔镜切除的肾肿瘤患者术前行MSCT联合CTA检查资料,采用多平面重组(MPR)、最大密度投影(MIP)、容积再现(VR)等计算机重建技术按照PADUA评分系统评估肾脏肿瘤的位置、血供、肿瘤与集合系统的关系以及肾脏血管系统,分析肾肿瘤解剖结构与腹腔镜下肾肿瘤切除术式之间的关系.结果 按照PAD-UA评分系统显示,肿瘤的纵向位置位于上/下极20例,中部9例;肿瘤位于肾脏外侧缘23例,内侧缘6例;肿瘤外凸率≥50％ 14例,＜50％ 12例,完全内陷3例;与肾窦有关9例,与肾窦无关20例;与集合系统有关20例,与集合系统无关9例;肿瘤最大径≤4 cm 11例,4.1～7 cm 10例,＞7 cm8例.结果行后腹腔镜肾根治切除术(LRN)18例,评分显示≥9分;行后腹腔镜下肾部分切除术(LPN)11例,评分显示为≤8分.同时发现双支肾动脉5例,肾动脉走行变异1例;肾静脉瘤栓形成1例,淋巴结转移2例,1例肾静脉胡桃夹征.结论 MSCT增强检查特别是肾动脉CTA能够清晰显示肾血管的起源、走行、变异及发现副肾动脉,清楚显示肿瘤与肾脏血管系统、集合系统的关系以及肿瘤的载瘤动脉,对腹腔镜下肾肿瘤切除术式的选择以及减少术后并发症具有重要的临床指导价值.