半枝莲抗肿瘤药理研究进展

肿瘤恶性程度高,近年来研究显示,中药半枝莲具有多方面治疗肿瘤的作用,兹就半枝莲抗肿瘤作用作一概述,为半枝莲抗癌的靶向治疗奠定基础。     

扶正消癌方对乳腺癌患者癌细胞增殖、侵袭及凋亡的影响

目的:探讨扶正消癌方对乳腺癌患者癌细胞增殖、侵袭和凋亡的影响,并研究凋亡分子机制。方法:66例乳腺癌患者随机分为对照组30例和治疗组36例,对照组患者接受化疗药物表阿霉素和环磷酰胺治疗,治疗组患者在对照组基础上加用扶正消癌方,日1剂,连服9周;2组患者治疗结束后接受手术,术中留取瘤体组织。用免疫组化法检测乳腺癌组织中Ki67、MMP2、Fas基因的表达水平,Western blotting分析凋亡分子Bax、Bcl-2的蛋白表达情况。结果:治疗组乳腺癌组织Fas阳性率明显高于对照组(P0.05);治疗组乳腺癌组织Ki67、MMP2的阳性表达率明显低于对照组;Western blotting结果显示治疗组乳腺癌细胞Bax蛋白表达显著多于对照组,而Bcl-2蛋白表达明显少于对照组,差异比较均有统计学意义(P0.05)。结论:扶正消癌方可抑制乳腺癌细胞的增殖和侵袭转移,促进癌细胞凋亡,这可能是扶正消癌方治疗乳腺癌的作用机制。     

The role of costotransverse radical debridement,fusion and postural drainage in the surgical treatment of multisegmental thoracic spinal tuberculosis: a minimum 5-year follow-up

Purpose

We present a retrospective study of patients with multilevel contiguous tuberculous spondylitis of thoracic region that underwent single-stage posterolateral debridement and fusion and following posterior instrumentation.

Methods

From June 2000 to March 2009, 870 consecutive spinal tubercular patients including 36 patients who were diagnosed and treated as multilevel contiguous thoracic spinal tuberculosis in our institution. Apart from five patients being treated conservatively, the 31 cases received surgery by single-stage posterolateral debridement, fusion, following posterior instrumentation and postural drainage. The patients were evaluated based on the Frankel scoring system, kyphotic Cobb angle, and visual analog scale (VAS) pain score.

Results

The mean duration of postoperative follow-up was 79.2 ± 9.9 months (range 62–98 months). Neither mortalities nor any major complications were found. Solid bony fusion was achieved in all patients. No patients with neurological deficit deteriorated postoperatively. According to Frankel scoring system, 7 cases were rated as Grade D, 24 cases as Grade E at last follow-up. The average preoperative Cobb’s angle was 32° (range 21°–39°). The average early postoperative Cobb’s angle was 23° (range 15°–32°). The mean latest postoperative Cobb’s angle was 26° (range 20°–32°), with a small loss of correction at last follow-up. Pre-op VAS was 8.8 ± 0.7 (range 7–10) and final follow-up was 1.8 ± 1.1. There was a significant difference of VAS between preoperation and the final follow-up.

Conclusions

One-stage surgical treatment for multilevel contiguous spinal tuberculosis by posterolateral debridement, fusion, posterior instrumentation can be an effective and feasible treatment method.

     

Relationship between donor sperm parameters and pregnancy outcome after intrauterine insemination: analysis of 2821 cycles in 1355 couples

The aim of this study was to investigate whether sperm parameters can affect the pregnancy outcome of artificial intrauterine insemination with cryopreserved donor spermatozoon (AID). A total of 1355 couples received 2821 AID treatment cycles in the Reproductive Medicine Center of the Tongji Medical College between January 2010 and December 2013, and the data were collected and retrospectively analysed. The relationship between pre‐freezing, post‐thawing as well as optimised sperm parameters and AID pregnancy outcome was investigated. Clinical pregnancy rate and cumulated pregnancy rate were also calculated. A total of 728 cycles from 2821 treatment cycles achieved pregnancies, and cumulated pregnancy rate was 25.81%. Pre‐freezing progressive sperm motility in pregnant cycles was higher than that in nonpregnant cycles (P = 0.001); logistic regression analysis also indicated that pre‐freezing progressive sperm motility was the only parameter affecting pregnancy outcome (P = 0.0001). Our study also showed that the cumulated pregnancy rate increased progressively and reached a plateau after the fifth cycle. In conclusion, pre‐freezing progressive sperm motility should be a valuable predictor for AID pregnancy outcome. Female fertility factors should be considered, or IVF/ICSI should be recommended when couples received more than 5 AID cycles without pregnancy.     

Protective effect of Bu-zhong-yi-qi decoction,the water extract of Chinese traditional herbal medicine,on 5-fluorouracil-induced renal injury in mice

Background: Drug-induced renal injury is a serious toxic side effect of 5-fluorouracil (5-FU) treatment. Bu-zhong-yi-qi decoction (BZYQD), a water extract of Chinese traditional herbal medicine, is widely used in Asia as an alternative treatment to reduce the side effects of chemotherapy and also improve cancer survival. However, the mechanism is unknown. This study is designed to investigate the protective effect of BZYQD on 5-FU-induced renal injury in mice.

Methods: Mice were divided into four groups: the control, 5-FU, 5-FU?+?low, and high BZYQD group. Mice in the three latter groups were administered 5-FU (100?mg/kg/day, intraperitoneally) for six days, and in the 5-FU?+?low and high BZYQD groups were given BZYQD (1 or 2?g raw herb/kg/day, intragastrically) beginning four days before 5-FU and continuing until the termination of the experiment. The right kidney fixed in formalin for histological examination and the left was homogenized to measure the levels of apoptosis-related proteins and activities of oxidative stress-related biomarkers. Blood samples were collected for measuring renal function-related biochemical indices.

Results: Renal morphology injury, increased urea nitrogen and creatinine concentration, and decreased SOD, CAT, and GSH-Px were all observed in 5-FU-administrated mice. However, BZYQD almost reversed the morphological injury as well as renal function-related indices and antioxidant enzyme activity.

Conclusion: These results suggest that BZYQD inhibits 5-FU-induced renal injury, possibly through the reduction of apoptosis and necrosis in renal tubular epithelial cells via the antioxidant mechanism. Henceforth, BZYQD may be a potential antioxidant against drug-induced oxidative stress.     

Increased Expression of Aldehyde Dehydrogenase 2 Reduces Renal Cell Apoptosis During Ischemia/Reperfusion Injury After Hypothermic Machine Perfusion

Hypothermic machine perfusion (MP) can reduce graft's injury after kidney transplantation; however, the mechanism has not been elucidated. In the past decade, many studies showed that aldehyde dehydrogenase 2 (ALDH2) is a protease which can inhibit cell apoptosis. Therefore, this study aims to explore whether ALDH2 takes part in reducing organ damage after MP. Eighteen healthy male New Zealand rabbits (12 weeks old, weight 3.0 ± 0.3 kg) were randomly divided into three groups: normal group, MP group, and cold storage (CS) group (n = 6). The left kidney of rabbits underwent warm ischemia for 35 min through clamping the left renal pedicle and then reperfusion for 1 h. Left kidneys were preserved by MP or CS (4°C for 4 h) in vivo followed by the right nephrectomy and 24‐h reperfusion, and then the specimens and blood were collected. Finally, concentration of urine creatinine (Cr), blood urea nitrogen (BUN), and 4‐HNE were tested. Renal apoptosis was detected by TUNEL staining, and the expression of ALDH2, cleaved‐caspase 3, bcl‐2/ bax, MAPK in renal tissue was detected by immunohistochemistry or Western blot; 24 h after surgery, the concentration of Cr in MP group was 355 ± 71μmol/L, in CS group was 511 ± 44 μmol/L (P < 0.05), while the BUN was 15.02 ± 2.34 mmol/L in MP group, 22.64 ± 3.58 mmol/L in CS group (P < 0.05). The rate of apoptosis and expression of cleaved caspase‐3, p‐P38, p‐ERK, and p‐JNK in MP group was significantly lower than that in CS group (P < 0.05), while expression of ALDH2 and bcl‐2/bax in MP group was significantly higher than that in CS group (P < 0.05); expression of cleaved caspase‐3 in both MP and CS group significantly increased as compared with that in normal group (P < 0.05). In conclusion, increased expression of ALDH2 can reduce the renal cell apoptosis through inhibiting MAPK pathway during ischemia/reperfusion injury (IRI) after hypothermic MP.     

Endoscopic decompression of the optic canal for traumatic optic neuropathy

Purpose: Traumatic optic neuropathy (TON) is a serious complication of head trauma with the incidence rate of 0.5%e5%. The aim of this study was to investigate the therapeutic efficacy of endoscopic decompression of the optic canal for optic nerve injuries. Methods: In this study, 11 patients treated in our hospital from January 2009 to January 2015 with the visual loss resulting from TON were retrospectively reviewed for preoperative vision, visual evoked potential (VEP) scan, surgical approach, postoperative visual acuity, complications, and follow-up results. Results: All these patients received endoscopic decompression of the optic canal. At the 3-month followup, the visual acuity improvement rate of the 11 patients was 45.5%. The vision acuity of 2 cases improved from hand movement to 0.08 and 0.3 after operation. Another patient''s vision acuity returned to 0.05 compared to light sensation preoperatively. Two cases had finger counting before surgery but they had a vision acuity of 0.4 and light sensation respectively after surgery. However, the other 6 cases'' vision did not improve after surgery. Conclusion: Endoscopic decompression of the optic canal is an effective way to cure TON. VEP could be used as an important reference for preoperative and prognosis evaluation. Operative time after trauma is only a relative condition that may affect the therapeutic effect of optic canal decompression. Poor results of this procedure may be related to the severity of the optic nerve injury.     

三维斑点追踪技术评价系统性硬化病患者左心室收缩功能

目的 应用三维超声斑点追踪成像技术(3D-STI)评价系统性硬化病(SSc)患者左心室整体收缩功能,并探讨各整体应变指标诊断SSc心脏损害的应用价值.方法 选取临床确诊SSc患者34例,其中弥漫性皮肤型(dcSSc)18例,局限性皮肤型(lcSSc) 16例,正常健康对照组22例.采集标准心尖四腔心三维全容积图像,运用3D-STI软件脱机分析得出左心室整体面积收缩期峰值应变(GAS)、整体圆周收缩期峰值应变(GCS)、整体纵向收缩期峰值应变(GLS)、整体径向收缩期峰值应变(GRS)及左心室射血分数(LVEF)等指标.结果 SSc组左心室GAS、GCS、GLS及GRS较对照组减低,差异有统计学意义(P＜0.05);dcSSc组左心室GAS、GCS、GLS及GRS较lcSSc组减低,其中GAS和GLS差异有统计学意义(P＜0.05).ROC曲线显示,GAS诊断SSc左心室损害的AUC最大,为0.877,当GAS截断值为-29.34％时,其灵敏度为88.2％,特异度为77.3％.结论 SSc患者左心室纵向、环向及径向收缩功能均已存在不同程度的受损,3D-STI可早期评价SSc患者的左心室整体收缩功能,在各项应变指标中,以GAS诊断SSc心脏损害的准确度最高.     

Tris(2‐chloroethyl)phosphate‐induced cell growth arrest via attenuation of SIRT1‐independent PI3K/Akt/mTOR pathway

Tris(2‐chloroethyl)phosphate (TCEP) as an organophosphorus flame retardant and plasticizer has been widely used in industrial and household products. It not only was detected in residential indoor air and dust, surface and drinking water, but also in human plasma and breast milk, and tissue samples of liver, kidneys and brain from rodents. TCEP is classified as carcinogenic category 2 and toxic for reproduction category 1B. Sufficient evidence from experimental animals indicated carcinogenicity of TCEP in the liver, and kidneys as well as cell loss in the brain. However, the underlying mechanisms of TCEP‐induced hepatotoxicity are mostly unknown. We investigated the in vitro effects of TCEP as well as TCEP‐induced cell growth in the L02 and HepG2 cells through the PI3K/Akt/mTOR pathway. We found that TCEP reduced cell viability of these cell lines, induced the cell growth arrest, upregulated mRNA and protein levels of SIRT1, and attenuated the PI3K/Akt/mTOR pathway. However, growth arrest of the L02 and HepG2 cells were aggravated after inhibiting the SIRT1 expression with EX‐527. The findings above suggested that TCEP induced the cell growth arrest of L02 and HepG2 cells via attenuation of the SIRT1‐independent PI3K/Akt/mTOR pathway. Copyright © 2015 John Wiley & Sons, Ltd.