BACKGROUND Centipedes have been used to treat tumors for hundreds of years in China. However, current studies focus on antimicrobial and anticoagulation agents rather than tumors. The molecular identities of antihepatoma bioactive components in centipedes have not yet been extensively investigated. It is a challenge to isolate and characterize the effective components of centipedes due to limited peptide purification technologies for animal-derived medicines. AIM To purify, characterize, and synthesize the bioactive components with the strongest antihepatoma activity from centipedes and determine the antihepatoma mechanism. METHODS An antihepatoma peptide (scolopentide) was isolated and identified from the centipede scolopendra subspinipes mutilans using a combination of enzymatic hydrolysis, a Sephadex G-25 column, and two steps of high-performance liquid chromatography (HPLC). Additionally, the CCK8 assay was used to select the extracted fraction with the strongest antihepatoma activity. The molecular weight of the extracted scolopentide was characterized by quadrupole time of flight mass spectrometry (QTOF MS), and the sequence was matched by using the Mascot search engine. Based on the sequence and molecular weight, scolopentide was synthesized using solid-phase peptide synthesis methods. The synthetic scolopentide was confirmed by MS and HPLC. The antineoplastic effect of extracted scolopentide was confirmed by CCK8 assay and morphological changes again in vitro. The antihepatoma effect of synthetic scolopentide was assessed by the CCK8 assay and Hoechst staining in vitro and tumor volume and tumor weight in vivo. In the tumor xenograft experiments, qualified model mice (male 5-week-old BALB/c nude mice) were randomly divided into 2 groups (n = 6): The scolopentide group (0.15 mL/d, via intraperitoneal injection of synthetic scolopentide, 500 mg/kg/d) and the vehicle group (0.15 mL/d, via intraperitoneal injection of normal saline). The mice were euthanized by cervical dislocation after 14 d of continuous treatment. Mechanistically, flow cytometry was conducted to evaluate the apoptosis rate of HepG2 cells after treatment with extracted scolopentide in vitro. A Hoechst staining assay was also used to observe apoptosis in HepG2 cells after treatment with synthetic scolopentide in vitro. CCK8 assays and morphological changes were used to compare the cytotoxicity of synthetic scolopentide to liver cancer cells and normal liver cells in vitro. Molecular docking was performed to clarify whether scolopentide tightly bound to death receptor 4 (DR4) and DR5. qRT-PCR was used to measure the mRNA expression of DR4, DR5, fas-associated death domain protein (FADD), Caspase-8, Caspase-3, cytochrome c (Cyto-C), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), x-chromosome linked inhibitor-of-apoptosis protein and Cellular fas-associated death domain-like interleukin-1 beta converting enzyme inhibitory protein in hepatocarcinoma subcutaneous xenograft tumors from mice. Western blot assays were used to measure the protein expression of DR4, DR5, FADD, Caspase-8, Caspase-3, and Cyto-C in the tumor tissues. The reactive oxygen species (ROS) of tumor tissues were tested. RESULTS In the process of purification, characterization and synthesis of scolopentide, the optimal enzymatic hydrolysis conditions (extract ratio: 5.86%, IC50: 0.310 mg/mL) were as follows: Trypsin at 0.1 g (300 U/g, centipede-trypsin ratio of 20: 1), enzymolysis temperature of 46 degrees C, and enzymolysis time of 4 h, which was superior to freeze-thawing with liquid nitrogen (IC50: 3.07 mg/mL). A peptide with the strongest antihepatoma activity (scolopentide) was further purified through a Sephadex G-25 column (obtained A2) and two steps of HPLC (obtained B5 and C3). The molecular weight of the extracted scolopentide was 1018.997 Da, and the peptide sequence was RAQNHYCK, as characterized by QTOF MS and Mascot. Scolopentide was synthesized in vitro with a qualified molecular weight (1018.8 Da) and purity (98.014%), which was characterized by MS and HPLC. Extracted scolopentide still had an antineoplastic effect in vitro, which inhibited the proliferation of Eca-109 (IC50: 76.27 mu g/mL), HepG2 (IC50: 22.06 mu g/mL), and A549 (IC50: 35.13 mu g/mL) cells, especially HepG2 cells. Synthetic scolopentide inhibited the proliferation of HepG2 cells (treated 6, 12, and 24 h) in a concentration-dependent manner in vitro, and the inhibitory effects were the strongest at 12 h (IC50: 208.11 mu g/ mL). Synthetic scolopentide also inhibited the tumor volume (Vehicle vs Scolopentide, P = 0.0003) and weight (Vehicle vs Scolopentide, P = 0.0022) in the tumor xenograft experiment. Mechanistically, flow cytometry suggested that the apoptosis ratios of HepG2 cells after treatment with extracted scolopentide were 5.01% (0 mu g/mL), 12.13% (10 mu g/mL), 16.52% (20 mu g/mL), and 23.20% (40 mu g/mL). Hoechst staining revealed apoptosis in HepG2 cells after treatment with synthetic scolopentide in vitro. The CCK8 assay and morphological changes indicated that synthetic scolopentide was cytotoxic and was significantly stronger in HepG2 cells than in L02 cells. Molecular docking suggested that scolopentide tightly bound to DR4 and DR5, and the binding free energies were-10.4 kcal/mol and-7.1 kcal/mol, respectively. In subcutaneous xenograft tumors from mice, quantitative real-time polymerase chain reaction and western blotting suggested that scolopentide activated DR4 and DR5 and induced apoptosis in SMMC-7721 Liver cancer cells by promoting the expression of FADD, caspase-8 and caspase-3 through a mitochondria-independent pathway. CONCLUSION Scolopentide, an antihepatoma peptide purified from centipedes, may inspire new antihepatoma agents. Scolopentide activates DR4 and DR5 and induces apoptosis in liver cancer cells through a mitochondria-independent pathway.

癌痛严重影响癌症患者的心身状态.基于治疗癌痛的临床实践,提出"卒病痼疾,荣亏瘀伤"的癌痛辨治理念,将癌痛病因病机归结于"卒病痼疾"与"荣亏瘀伤",将中医"卒病痼疾"理念与西医"急慢性癌痛综合征"相融合,认为"荣亏瘀伤"的癌痛病机特点为中州胃气不足、下元精血虚衰,导致气血乏源,阳气亏损,气血津液运行无力形成瘀血等有形之邪,邪气阻络而痛.治疗上首要辨清癌痛病因,根据"卒病痼疾"的缓急原则进行治疗,察胃气以衡攻补,建中填精以养荣,温阳活血以通瘀,佐以补肾平肝防转移,标本兼顾,通补相合,共奏止痛之功.

时辰给药是一种新的给药方法,在肿瘤治疗中的应用仅局限于化疗药物,鲜有肿瘤中医治疗的时辰给药研究.根据天地人的阳气生长规律以及肿瘤的增殖转移规律,探讨时辰给药在肿瘤中医治疗中的意义,提出平旦、日中、日西3个时间段内肿瘤治疗的理法方药.平旦之治,当益肾填精以扶阳气,轻可扶助人体阳气以抗癌,重可回阳救逆,挽救生命,根据阴阳亏损的程度给予方药.日中之治,当补益脾胃以蓄气血,既可借天地阳气鼓邪外出,又可防止日西阳衰,正不胜邪,根据补脾胃、畅六腑之法给予方药.日西之治,当温阳解毒以攻邪实.一则抑制肿瘤夜间转移,二则顾护阳气防止正伤,根据内、外治法给予方药.

总结尹周安从气血津液精"盈虚通滞"理论辨治垂体泌乳素腺瘤的经验,尹周安认为本病与肾精不足、肝失疏泄所致气血津液精"盈虚通滞"改变相关,"盈"与"通"难成此病,多由"阻滞""虚损"发病.阻滞病变责之气、血、津液不通,虚损病变咎于精、血、气不足,两者均可导致气郁、血瘀、津停的产生.阻滞病变,以通为补,首畅肝气;虚损病变,以补为通,首补精血.提出了调畅少阳三焦、解除筋膜挛急、疏通气血津液精阻滞的治疗方法,同时重调神、畅情志以缓解患者紧张恐慌的情绪,达到身心同治的目的.

恶性肿瘤的发病率连年升高,现已证明许多恶性肿瘤属于心身疾病范畴.心理因素在肿瘤的形成与发展阶段产生了不可忽视的作用,在肿瘤形成后亦导致了一系列心身症状,影响肿瘤的临床治疗效果.然而,临床医师对肿瘤患者的心身症状存在识别率较低,治疗方法不足的问题 [1],常将心理因素与躯体症状割裂开看待,使得临床疗效欠佳.心身症状是指与心理社会因素密切相关的症状,患者常因躯体症状就诊于非精神科室,但症状的严重程度与疾病并不相符.临床常见的肿瘤相关心身症状包括焦虑、抑郁、癌痛、失眠、疲乏、自主神经功能紊乱如恶心呕吐等 [2].焦虑、抑郁是最常见的肿瘤心身症状,虽然属于心理症状,但常作为其他躯体症状的伴见因素,治疗肿瘤心身症状多可以从识别、治疗焦虑、抑郁着手.本文将分享笔者对肿瘤心身症状中焦虑、抑郁的临床诊疗 体悟.

目的 系统评价他达拉非对良性前列腺增生(BPH)所致下尿路症状的临床疗效以及安全性.方法 通过计算机检索Pubmed、Embase、Cochrane Library数据库中关于他达拉非治疗BPH所致下尿路症状的随机双盲安慰剂对照试验.对符合纳入及排除标准的文献进行偏倚风险评价和数据提取,采用Revman 5.3软件进行Meta分析.结果 本研究共纳入11项随机对照试验,最终8项进入Meta分析.Meta分析结果显示,他达拉非5 mg能有效改善BPH所致下尿路症状.主要结局指标:国际前列腺症状评分(MD=-1.95,95％CI=-2.43～-1.48,P=0.000)、BPH影响指数(MD=-0.55,95％CI=-0.80～-0.30,P=0.000);次要结局指标:最大尿流率(MD=0.23,95％CI=-0.35～0.80,P=0.440).安全性评估:不良事件发生率的差异(OR=0.06,95％CI=0.03～0.09,P=0.000),主要为轻度不良反应,对他达拉非耐受性良好.结论 他达拉非5 mg用于治疗BPH所致下尿路症状有较好的临床疗效,且副作用发生率低,值得临床推广应用.

目的 探讨肋间神经阻滞联合局麻微创经皮肾镜碎石取石术(MPCNL)的可行性与安全性.方法 2018年10月至2019年11月,超声引导下于患侧第10、11、12肋骨下缘与脊柱交叉点处进行肋间神经阻滞,每个部位注射0.5%布比卡因5 ml(含1/1000肾上腺素),然后在选定的穿刺通道上进行局部浸润麻醉(2%利多卡因10 ml+生理盐水15 ml混合液约10 ml).采用超声引导下穿刺、一步扩张法MPCNL,分别在钬激光碎石开始10 min及术后2 h、6 h、24 h行视觉模拟评分(VAS)评估疼痛严重程度;术后2 h及术后第1天复查血常规评估术中出血量;术后4周复查腹部平片或超声评估结石清除率.结果 38例均顺利完成手术,无一例需改变麻醉方式,无严重并发症发生,无一例中转开放手术,术中及术后2 h、4 h、24 h的VAS均值分别为2.6、2.2、1.8和1.3分,术后4周结石总体清除率91.3%(21/23).结论 选择合适的病例,肋间神经阻滞联合局麻MPCNL操作简便,手术安全,疗效满意,值得临床推广.