Melatonin Ameliorates Liver Fibrosis Induced by Carbon Tetrachloride in Rats via Inhibiting TGF-β1/Smad Signaling Pathway / 华中科技大学学报（医学）（英德文版）

Melatonin has been reported to inhibit hepatic fibrosis and the mechanism may be correlated to its anti-oxidant effect.Nevertheless,the mechanism is not completely identified.This study was conducted to investigate the effects of melatonin on TGF-β1/Smad signaling pathway in liver fibrosis in rats.The liver fibrosis model was made by the subcutaneous injection of CCl4.The liver pathology changes were detected using hematoxylin and eosin (H&E) staining and Van Gieson (VG) staining.Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured with an autoanalyzer.Glutathione peroxidase (GPx) activities and levels of malondialdehyde (MDA) and hydroxyproline (Hyp) in liver were evaluated by spectrophotometry.Expression levels of TGF-β1,Smad2/3,phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in liver were detected by immunohistochemistry and Western blot analysis.Results showed that melatonin suppressed CC14-induced liver fibrosis,along with an improvement in histological changes,significant decreases in pathologic grading sores and obvious decreases in Hyp levels in liver.Melatonin improved liver function indicated by decreased serum ALT and AST activities.In addition,melatonin exerted its anti-oxidant effects,as supported by decreased MDA levels and increased GPx activities in liver.Furthermore,melatonin inhibited TGF-β1/Smad pathway,as evidenced by decreased TGF-β1,Smad2/3 and p-Smad2/3 expression and increased Smad7 expression in liver.In conclusion,melatonin may suppress CCl4-induced hepatic fibrosis in rats via inhibiting TGF-β1/Smad pathway.It is possible for melatonin to be a potential reagent to treat and cure liver fibrosis.

Melatonin Ameliorates Liver Fibrosis Induced by Carbon Tetrachloride in Rats via Inhibiting TGF-β1/Smad Signaling Pathway / 华中科技大学学报（医学）（英德文版）

Melatonin has been reported to inhibit hepatic fibrosis and the mechanism may be correlated to its anti-oxidant effect.Nevertheless,the mechanism is not completely identified.This study was conducted to investigate the effects of melatonin on TGF-β1/Smad signaling pathway in liver fibrosis in rats.The liver fibrosis model was made by the subcutaneous injection of CCl4.The liver pathology changes were detected using hematoxylin and eosin (H&E) staining and Van Gieson (VG) staining.Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured with an autoanalyzer.Glutathione peroxidase (GPx) activities and levels of malondialdehyde (MDA) and hydroxyproline (Hyp) in liver were evaluated by spectrophotometry.Expression levels of TGF-β1,Smad2/3,phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in liver were detected by immunohistochemistry and Western blot analysis.Results showed that melatonin suppressed CC14-induced liver fibrosis,along with an improvement in histological changes,significant decreases in pathologic grading sores and obvious decreases in Hyp levels in liver.Melatonin improved liver function indicated by decreased serum ALT and AST activities.In addition,melatonin exerted its anti-oxidant effects,as supported by decreased MDA levels and increased GPx activities in liver.Furthermore,melatonin inhibited TGF-β1/Smad pathway,as evidenced by decreased TGF-β1,Smad2/3 and p-Smad2/3 expression and increased Smad7 expression in liver.In conclusion,melatonin may suppress CCl4-induced hepatic fibrosis in rats via inhibiting TGF-β1/Smad pathway.It is possible for melatonin to be a potential reagent to treat and cure liver fibrosis.

Superficial peroneal neurocutaneous vascular axial adipofascial-cutaneous flap pedicled with lateral supramalleolar perforator for coverage of donor site defects at foot dorsum / 中华整形外科杂志

<p><b>OBJECTIVE</b>To report the operative techniques and clinical results of modified superficial peroneal neurocutaneous propeller adipofascial-cutaneous flap for reconstruction of donor site defects at foot dorsum.</p><p><b>METHODS</b>A propeller adipofascial flap with a skin pedicle (4-6 cm in width) based on the lateral superamalleolar perforating artery which vascularized the flap through the nutrient vessel chain of the superficial peroneal nerve was designed to repair defects after harvesting of foot pedicled dorsal flap. The defects at donor site of the leg was closed directly and split-thickness skin grafting was performed on the adipofascial surface of the flap primarily or secondarily.</p><p><b>RESULTS</b>From May 2007 to Oct. 2011, 7 cases were treated. All flaps were transplanted successfully with satisfactory cosmetic and functional results. The flaps size ranged from 19 cm x 8 cm to 30 cm x 11 cm.</p><p><b>CONCLUSIONS</b>The flap has reliable blood supply with a relatively large vascularized area, long rotation are and minimum donor-site cosmetic morbidity. It' s a simple and safe procedure which is suitable for covering donor sites defects after harvesting foot pedicled dorsal flap.</p>

Dominant perforator neurocutaneous flaps for one-staged reconstruction of defects caused by high energy at lower legs, ankles and feet / 中华整形外科杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of dominant perforator neurocutaneous flaps for one-staged reconstruction of defects caused by high energy at lower legs, ankles and feet.</p><p><b>METHODS</b>From July 2003 to Feb. 2011, 39 cases, with defects caused by high energy at lower legs, ankles and feet, were retrospectively studied. The defects were covered primarily by one or two perforator neurocutaneous flaps (free or pedicled) which were based on a dominant perforator arising from the posterior tibial or peroneal artery (including the lateral supramalleolar perforating artery which is also from the peroneal vessel) respectively through sural, saphenous and superficial peroneal neurocutaneous vascular axis.</p><p><b>RESULTS</b>39 cases with 44 defects were treated by 32 sural neurocutaneous flaps based on the peroneal perforator (5 free and 27 pedicled), 6 saphenous neurocutaneous flaps on the posterior tibial perforator (1 free and 5 pedicled) and 6 superficial peroneal ones on the lateral supramalleolar perforating artery. The largest flap size was 22 cm x 10 cm. All flaps were survived successfully without necrosis. The average in-hospital time was 23 days ( ranged from 12-36 days).</p><p><b>CONCLUSIONS</b>The three kinds of dominant perforator neurocutaneous flaps have reliable blood supply with a relatively large size. They can be chosen and designed individually for all kinds of defects over the lower leg, ankle and foot. There are many advantages in a primary procedure, such as easier dissection, better vessel status in or around recipient areas, less secondary necrosis and lower risk of chronic infection. Moreover, the reduction of granulation and scar tissues benefit functional rehabilitation.</p>

Correlation analysis between abundance of K-ras mutation in plasma free DNA and its correlation with clinical outcome and prognosis in patients with metastatic colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect K-ras gene mutations in plasma free DNA by peptide nucleic acid clamp PCR assay (PNA-PCR) and nested primer PCR, and to analyze the correlation between K-ras mutations and prognosis in patients with metastatic colorectal cancer (mCRC).</p><p><b>METHODS</b>Peripheral blood was collected and free DNA was extracted from plasma in 106 patients with mCRC. Nested primer PCR and PNA-PCR were used to detect K-ras gene mutation in the plasma free DNA. The patients were divided into three groups by K-ras status: wild-type group (wild-type determined by both methods), low mutation group (mutation by PNA-PCR method, wild-type by nested primer PCR method) and high mutation group (mutation by two methods). The correlation between K-ras mutations and prognosis was analyzed.</p><p><b>RESULTS</b>The mutation rate of K-ras in tumor tissues of the 106 patients was 40.6%. The Mutation rate of K-ras in plasma free DNA detected by PNA-PCR was 31.1%, significantly higher than that of 15.1% detected by nested primer PCR (P = 0.006). The consistent rate of the K-ras status in plasma free DNA detected by PNA-PCR and that in tumor tissue detected by traditional method was up to 83.0%. The median overall survival (OS) of patients of the wild type, low mutation and high mutation groups was 23.5 months, 17.3 months and 13.9 months, respectively (P = 0.002). The median progression-free survival (PFS) of the K-ras wild-type, low mutation and high mutation groups with first-line chemotherapy was 6.8 months, 6.1 months and 3.2 months, respectively (P = 0.002), and the median OS of them were 23.0 months, 15.5 months and 13.9 months, respectively (P = 0.036). The overall response rate (ORR) was improved in the K-ras wide-type patients who received cetuximab combined with chemotherapy as first-line therapy (75.0% vs. 23.4%, P = 0.058). Cetuximab combined with in second-line therapy chemotherapy led to a significant improvement in disease control rate (DCR) ( 100% vs. 35.7%, P < 0.001) as compared with those of chemotherapy alone. COX regression model showed that K-ras status detected by PNA-PCR, ECOG PS, number of surgery and initially metastatic site were independent factors for prognosis.</p><p><b>CONCLUSIONS</b>PNA-PCR for the detection of K-ras mutation in plasma free DNA can be used to substitute the traditional method for detection of K-ras mutation in tumor tissues. The abundance of K-ras mutation in plasma free DNA is an independent prognostic factor for patients with metastatic colorectal cancer.</p>

Analysis of therapeutic effect and prognosis in patients with metastatic colorectal cancer and different K-ras status / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the correlation of clinical effect and prognosis between patients with metastatic colorectal cancer (mCRC) and different K-ras status.</p><p><b>METHODS</b>The clinical characteristics, chemotherapeutic regimens and survival of 153 mCRC patients with different K-ras status were analyzed retrospectively.</p><p><b>RESULTS</b>The median overall survival (OS) in patients without K-ras mutation were 31.7 months, significantly longer than 21.3 months in the patients with K-ras mutation (P = 0.037). The median progression-free survival (PFS) and OS in patients who received chemotherapy followed by anti-EGFR antibody treatment were 11.5 and 39.3 months, respectively, significantly longer as compared with the PFS and OS in those received chemotherapy in combination with anti-EGFR antibody concomitantly (5.7, P = 0.02, and 28.7 months, P = 0.034, respectively).</p><p><b>CONCLUSIONS</b>K-ras status is a prognostic biomarker for mCRC patients treated with anti-EGFR antibody. The combination settings of anti-EGFR in combination with chemotherapy may improve survival of mCRC patients with wild-type K-ras status.</p>

Trastuzumab in combination with chemotherapy versus chemotherapy alone for first-line treatment of HER2-positive advanced gastric or gastroesophageal junction cancer: a Phase III, multi-center, randomized controlled trial, Chinese subreport / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer.</p><p><b>METHODS</b>Fifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival.</p><p><b>RESULTS</b>Eighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively.</p><p><b>CONCLUSIONS</b>Addition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.</p>

Clinical characteristics of the adaptive phenomenon of antituberculosis drug-induced liver injury / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics of the adaptation phenomenon occurring in antituberculosis drug-induced liver injury.</p><p><b>METHODS</b>Our department's clinical records were searched using the standardized diagnostic criteria and monitoring programs parameters of drug-induced liver injury to identify cases with the adaptation phenomenon. The 32 identified cases were classified according to whether or not the drug was discontinued after development of the drug-induced liver injury: withdrawal group (n = 11) and continuing group (n = 21). The types of patients with adaptation phenomenon were assessed to determine the relationship between liver injury and development time, and between the severity grade of liver injury (determined by biomarker expression) and symptoms.</p><p><b>RESULTS</b>All of the 32 cases of drug-induced liver injury with the adaptation phenomenon were classified as the hepatocellular injury type. The average overall incubation period was 16.59+/-13.05 days (range: 6-60 days), while that of the continuing group was 17.05 +/-13.71 days (6-60 days) and that of the withdrawal group was 16.46+/-12.09 days (6-43 days). The average overall time for peak transaminase levels to decrease to the normal range was 11.34 +/-5.97 days (6-30 days), while that of the continuing group was 11.20+/-5.92 days (6-30 days) and that of the withdrawal group was 11.91/-6.20 days (7-30 days). Thirty of the overall patients showed grade 1 degree of liver injury and only two showed grade 2.</p><p><b>CONCLUSION</b>The clinical characteristics of the adaptation phenomenon include a transient increase in biochemical indicators of the antituberculosis drug-induced liver injury. It is important to understand the clinical variations in the adaptation phenomenon to formulate feasible and appropriate programs for monitoring and prevention.</p>

Clinical analysis of the current treatment status of gastric cancer in 636 patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the current clinical treatment status of gastric cancer in China.</p><p><b>METHODS</b>A retrospective analysis of clinicopathological characteristics of 636 patients with gastric cancer was conducted. Tumor response was evaluated using RECIST version 1.1 criteria.</p><p><b>RESULTS</b>Six hundred and thirty-six patients were included in this retrospective cohort: 479 men and 157 women. The median age was 57 years (14 to 86). The tumor site was: proximal (41.4%), distal (46.4%) or unknown (12.2%). The histology was: adenocarcinoma (85.8%), signet ring cell carcinoma (6.9%), or other and unknown (7.2%). The differentiation of the adenocarcinomas was: well differentiated (31.0%), moderately differentiated (13.4%), poorly differentiated (37.0%), or unknown (18.7%). The pTNM stage was: 0 (0.3%), I (3.6%), II (10.1%), III (36.8%), IV (45.6%), or unknown (3.6%). In 284 patients who underwent radical resection, the ratio of examined ten and/or more lymph nodes was higher in hospitals at or above provincial level than in hospitals at regional level (57.9% vs. 39.6%, P = 0.009). The disease-free survival was longer (21.7 m vs. 14.6 m, P = 0.005), and the overall survival was longer too (52.9 m vs. 33.8 m, P = 0.040). In 205 patients who received adjuvant chemotherapy, the ratio of administered six and/or more cycles chemotherapy was 42.1% vs. 35.2% (P = 0.318), and the disease-free survival was 22.7 m vs. 16.3 m (P = 0.005) between hospitals at or above provincial level and hospitals at regional level. In 387 patients with metastatic or unresectable gastric cancer who received palliative chemotherapy, the overall survival was 11.1 m (95%CI 9.9 - 12.3 m). Among them, 198 patients received second and/or more line chemotherapy, and the overall survival was longer (12.5 m vs. 7.7 m, P < 0.001). Except a longer progression-free survival (10.2 m, P < 0.05) and a longer overall survival (16.9 m, P < 0.05) were corresponded with the regimen containing trastuzumab, no other significant difference was observed among regimens in first line chemotherapy.</p><p><b>CONCLUSION</b>Chinese doctors working in different level hospitals have a different understanding of the treatment standard of gastric cancer, which resulted in different outcomes.</p>

Significance of plasmic homocysteine, folate and Vitamin B(12) in ulcerative colitis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical significance of plasmic homocysteine (Hcy), folate (FA) and Vitamin B(12) (VitB(12)) in patients with ulcerative colitis (UC).</p><p><b>METHODS</b>Plasmic Hcy in 112 cases of UC patients and 110 controls were detected by HPLC-FD method. Plasmic FA, VitB(12) in 76 cases of UC patients and 12 controls were detected by enzyme-linked immunosorbent assay (ELISA) method.</p><p><b>RESULTS</b>The level of plasmic Hcy in UC patients was(11.27±7.26) μmol/L, significantly higher than that in controls[(8.19±4.81) μmol/L, P<0.05], and was not significantly correlated with disease index, extent and duration of UC(P>0.05). The level of FA and VitB(12) in UC patients were (7.64±1.95) nmol/L and (108.64±32.22) pmol/L respectively, lower than those in controls[(9.14±1.23) nmol/L and (112.64±33.33) pmol/L, P<0.05]. The level of plasmic Hcy was negatively correlated with the level of FA and VitB(12) in UC patients(P<0.05). The level of plasmic FA decreased to some extent with UC disease duration.</p><p><b>CONCLUSION</b>Plasmic Hcy is elevated in UC patients, which may be related to the decrease of FA and VitB(12).</p>

Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial / 癌症

The efficacy and safety of bevacizumab with modified irinotecan, leucovorin bolus, and 5-fluorouracil intravenous infusion (mIFL) in the first-line treatment of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized clinical trials in Chinese patients. We conducted a phrase III trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan (125 mg/m(2)), leucovorin (20 mg/m(2)) bolus, and 5-fluorouracil intravenous infusion (500 mg/m(2)) weekly for four weeks every six weeks] plus bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co-primary objectives were progression-free survival (PFS) and 6-month PFS rate. In total, 214 patients were enrolled. Our results showed that addition of bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-month PFS rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7 months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group). No wound-healing complications or congestive heart failure occurred. Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC. Clinical benefit and safety profiles were consistent with those observed in pivotal phase III trials with mainly Caucasian patients.

HER-2 expression in advanced gastric cancer and its correlation with clinical features, outcome and prognosis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the HER-2 status in Chinese advanced gastric cancer patients and explore its correlation with clinical features, treatment response and prognosis.</p><p><b>METHODS</b>A total of 107 patients with advanced gastric cancer treated in our hospital from December 2005 to November 2008 were included in this retrospective analysis. HER-2 status was determined by immunohistochemisty (IHC) and/or fluorescence in situ hybridization (FISH). The correlations of HER-2 status with tumor location, pathology, treatment response and prognosis were analyzed and the efficacy of different chemottherapy regimens was compared.</p><p><b>RESULTS</b>The overall positive rate of HER-2 expression was 14.7% (15/102). The HER-2 status was detected by both methods in 102 patients, and the concordance of the two methods was 66.5%. The tumor site distribution was gastroesophageal junction (GEJ) 28.0%, proximal stomach 19.4%, gastric corpus 16.1%, antrum 26.9% and whole stomach 9.7%, respectively. There was no significant difference of HER-2 status among different tumor sites (P = 0.726), and no significant correlation between HER-2 expression and differentiation (P = 0.110). Among the evaluable 51 patients treated by first-line chemotherapy, the total objective effective rate was 23.5%. The median time-to-progression was 7.47 months, and median overall survival time was 11.07 months. The effective rate was 43.8% in patients who received XP regimen chemotherapy (cisplatin + capecitabine), significantly higher than the 14.3% in patients treated with other regimens (P = 0.033). Their overall survival was 14.17 months and 9.53 months, respectively (P = 0.059). The TTP was 6.63 months in HER-2 positive patients and 7.47 months in HER-2 negative patients, with a non-significant difference (P = 0.510). However, there was a improving tendency in the efficacy and OS, showing a effective rate of 45.5% and 17.5% (P = 0.102) and OS of 14.17 months and 10.63 months, respectively (P = 0.205).</p><p><b>CONCLUSIONS</b>HER-2-positivity rate in Chinese patients with advanced gastric cancer is similar to those reported in the literature. Along with the increasing use of targeted therapy and targeted agents, the efficacy and survival of gastric cancer patients is improving. HER-2-positive patients may benefit from it.</p>

Correlation of epidermal growth factor receptor mutations and HER2/3 protein expression with clinical outcome in advanced non-small cell lung cancer patients treated with gefitinib / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>The effect of gefitinib on advanced non-small cell lung cancer (NSCLC) was various. How to choose the sensitive patients and improve the effect was difficulty in clinic. This study was to assess the correlation of epidermal growth factor receptor (EGFR) mutations and HER2/3 protein expression with the effect of gefitinib on Chinese patients with advanced NSCLC.</p><p><b>METHODS</b>From May 2002 to February 2005, a total of 106 Chinese NSCLC patients who had failed at least one chemotherapy regimen were treated with gefitinib 250 mg once a day. The mutations in the exons 18-24 of EGFR gene were detected in the tumor tissues from 106 patients before the treatment of gefitinib, and HER2/3 expression in 84 tumor samples were detected by immunohistochemistry.</p><p><b>RESULTS</b>Mutation was identified in 32 (30.2%) tumor tissues. Overall remission rate was significantly higher in the HER2 high expression patients than in the HER2 low expression patients (36.8% vs 17.4%, P=0.044). HER2 and HER3 expression levels were not associated with time to progression (TTP) and overall survival (OS). The patients with HER2/3 single high expression had relatively longer TTP and OS than those with HER2/3 single low expression (6.1 vs 9.1 months, P=0.725; 6.1 vs 9.0 months, P=0.862), while those with concomitant HER2/3 high expression had significant longer TTP and OS. EGFR-mutated patients with HER2 expression or high HER2 and HER3 expressions were more sensitive to gefitinib.</p><p><b>CONCLUSION</b>EGFR mutations combined with HER2/3 expressions is a significant predictor for gefitinib efficacy on Chinese patients with advanced NSCLC.</p>

Evaluation of bevacizumab combined with irinotecan-based regimen as the first-line treatment for patients with metastatic colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the efficacy and safety of bevacizumab plus irinotecan-based regimen for the first line treatment in metastatic colorectal cancer (mCRC) patients, and to investigate the correlation between serum tumor markers including CEA and CA19-9 and response as well as prognosis.</p><p><b>METHODS</b>From May 2007 to July 2008, 67 previously untreated mCRC patients received treatment of IFL (n = 25), IFL plus Bevacizumab (n = 20) or FOLFIRI (n = 22). The treatment continued until disease progression or unacceptable toxicity. The data were retrospectively analyzed.</p><p><b>RESULTS</b>All patients were evaluable for response, survival and toxicity analysis. The objective response rate of IFL, IFL plus Bevacizumab or FOLFIRI regimen groups was 16.0% (4/25), 35.0% (7/20) and 18.2% (4/22), respectively (χ(2) = 6.026, P = 0.049). The median progression-free survival (PFS) of IFL plus bevacizumab group was 7.5 months, significantly improved as compared with 3.7 months in the IFL group and 4 months in FOLFIRI group (χ(2) = 11.97, P = 0.003). Of all 67 cases, the one-year survival rate was 47.0%, two-year survival rate was 27.0%, and the median overall survival (OS) was 13.0 months, with no significant difference among the three treatment groups (χ(2) = 3.42, P = 0.18). The serum CEA and CA19-9 levels were decreased after treatment, but with no significant difference among the three groups (P > 0.05). The common toxicity profiles of IFL and FOLFIRI regimens were diarrhea and neutropenia, while the toxicity related to bevacizumab was consistent with that documented in previous literature, such as hypertension, hemorrhage, cardiac toxicity and delayed wound healing.</p><p><b>CONCLUSION</b>The addition of bevacizumab to irinotecan-based regimen significantly improves the response rate and PFS in first-line treatment for patients with mCRC and its toxicity is well tolerated.</p>

Effect of balsalazide on intestinal mucosal permeability of dextran sulfate sodium-induced colitis in mice / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of balsalazide on intestinal mucosal permeability of experimental colitis induced by dextran sulfate sodium(DSS) in a mouse model and its possible mechanism.</p><p><b>METHODS</b>Forty-five C57BL/6J mice were randomly divided into five groups. Normal group was only fed with distilled water, DSS group and Balsalazide groups at doses of 42,141,423 mg/kg were fed with 5% DSS. Balsalazide was given by intragastric administration. DAI was evaluated daily. At the end of the experiment, colon tissue was collected for assessment of histological changes, MDA content, MPO, SOD and GSH-PX activity. Small intestinal mucosa was collected for assessment of transmission electron microscope(TEM), and detection of permeability by Evans blue.</p><p><b>RESULTS</b>Compared with normal group, DSS group mice all manifested severe weight loss associated with hematochezia and diarrhea with significant increase of DAI and HI score(P<0.01). MDA content and MPO activity was increased with the reverse result of SOD and GSH-PX(P<0.01) in DSS group. Intestinal mucosa showed a focal reduction in thinning of microvillous carpet and even a total disarrangement of epithelial surface, with decurtated and broaden junctional complex and enlarged intercellular space under TEM observations in DSS group. The amount of Evans blue permeated into intestinal wall was obvious in DSS group. Compared with DSS group, balsalazide improved gross findings, decreased MPO activity and MDA content, but increased the activity of SOD and GSH-PX(P<0.05). The amount of Evans blue permeated into intestinal wall was less(P<0.05). Ileal microvillous carpet was ameliorated in dose-dependent manner by balsalazide.</p><p><b>CONCLUSIONS</b>Intestinal mucosal permeability is increased in DSS group. Balsalazide can significantly ameliorate intestinal mucosal permeability in colitis model.</p>

Combination with SN-38 on human colon cancer LoVo cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the anti-proliferation effect of bevacizumab and SN-38 (active metabolite of irinotecan), and investigate the possible mechanisms of these two agents.</p><p><b>METHODS</b>Human colon cancer LoVo cells were cultured under hypoxic conditions. Inhibition of cell proliferation was evaluated by MTT assay. The drug modulation on HIF-1alpha, VEGF, ERK and AKT were assessed by the following assays. The mRNA expression of HIF-1alpha and VEGF were measured by RT-PCR. The protein expression of HIF-1alpha, ERK and AKT were evaluated by Western blot analysis, and VEGF by ELISA assay.</p><p><b>RESULTS</b>Among different combination schedules, Bevacizumab given after SN-38 show most synergistic anti-proliferation effect. Under hypoxic conditions, the expression of HIF-1alpha and VEGF increased as time accumulated, Bevacizumab combined with SN-38 almost completely inhibited the expression of HIF-1alpha and VEGF. Moreover, the MAP kinase pathway was involved in the drug modulation of HIF-1alpha and VEGF.</p><p><b>CONCLUSION</b>These findings suggest the anti-proliferation effect of bevacizumab and SN-38 was schedule-dependent, and the synergistic effect of Bevacizumab and SN-38 was related to drug modulation of the HIF-1alpha and MAP kinase pathway.</p>

Irinotecan plus fuorouracil/leucovorin (FOLFIRI) as a second line chemotherapy for refractory or metastatic colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Irinotecan (CPT-11), a specific inhibitor of topoisomerase I, has been proven to be effective in the treatment of refractory or metastatic colorectal cancer. Furthermore, several first line phase III trials of the combination therapy (FOLFIRI) using CPT-11 and fuorouracil/leucovorin (5-Fu/LV) were reported to have significant improvement in treatment result. Therefore, we designed a multicenter clinical study to observe the overall survival (OS), time to death (TTD), time to progression (TTP), efficacy and safety of FOLFIRI regimen for patients with refractory or metastatic colorectal cancer after first line chemotherapy failure.</p><p><b>METHODS</b>Patients with metastatic or refractory colorectal cancer after first line oxaliplatin-based chemotherapy failure were enrolled into this prospective, one arm and open-labeled multicenter study. Irinotecan 180 mg/m2 was administered biweekly on D1, LV 200 mg/m2 by intravenous infusion in 2 hours before bolus intravenous injection of 5-Fu 400 mg/m2, then followed immediately by intravenous infusion of 5-Fu 2.4 g/m2 in 46 hours. OS, TTD, TTP, response rate (RR) and adverse events were assessed according to RSCIST criteria and NCIC-CTG CTCAE (3.0).</p><p><b>RESULTS</b>Sixty-six patients were valuable for safety assessment and and 61 for efficacy. There was no CR patient in this series. Ten patients had PR, 35 SD (57.4% ) and 16 PD (26.2%) with a response rate of 16.4% (10/61). The median TTP was 5.0 months (1-12 months), median TTD 9.9 months (5-27 months)and median OS 18.2 months (7-33 months). The adverse events including nausea,vomiting, anorexia,diarrhea, leucopenia and cholinergic syndrome were frequent, but usually in I - II degree. The rate of III/IV degree diarrhea and leucopenia was 7.6% and 22.7%, respectively.</p><p><b>CONCLUSION</b>The regimen of irinotecan plus fuorouracil/leucovorin (FOLFIRI) is effective and well-tolerated as a second-line chemotherapy and may prolong the overall survival for the patient with refractory or metastatic colorectal cancer.</p>

Therapeutic effects of aspiration with a directional soft tube and conservative treatment on mild hemorrhage in the basal ganglion / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the therapeutic effects of aspiration via a directional soft tube and conservative treatment in patients with mild hemorrhage in the basal ganglion.</p><p><b>METHODS</b>Seventy-five patients with mild cerebral hemorrhage (10~30 ml) were randomly divided into two groups for aspiration treatment with minimally invasive directional soft tube placement (minimally invasive group, n=36) and conservative treatment (medication group, n=39). The patients in the two groups had comparable mean GCS scores of 11-15 on admission. The clinical outcomes of the patients were compared between the two groups.</p><p><b>RESULTS</b>In the minimally invasive group, complete removal or absorption of the hematoma occurred within an average of 3.8 days, significantly shortened in comparison with the 24 days in the medication group. The short-term (1 month) follow-up of the patients showed good neurological recovery in 58% of the patients in the minimally invasive group, significantly greater than the rate of 29% in the medication group; 6 months after the treatment, good neurological recovery was achieved in 50% of the patients in the minimally invasive group, but only 16% in the medication. No death occurred in the minimally invasive group, and 2 patients died in the medication group. The cost of hospitalization averaged 5136.3 Yuan in the minimally invasive group and 11843.6 Yuan in the medication group.</p><p><b>CONCLUSION</b>Compared with conservative treatment, the minimally invasive treatment with soft tube placement can significantly shorten the hospital stay, promote neurological function recovery, lower the mortality rate, and reduce the cost of hospitalization.</p>

Polymorphisms of UGT1A gene and irinotecan toxicity in Chinese colorectal cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the polymorphism of UGT1A gene in Chinese, and to investigate the correlation between UGT1A polymorphism and irinotecan toxicity in colorectal cancer patients.</p><p><b>METHODS</b>70 patients with advanced colorectal cancer were treated with irinotecan and 5-fluorouracil. Polymorphism analysis was performed in all those patients and 100 healthy subjects. Genomic DNA was extracted from peripheral blood and genotyped using polymerase chain reaction and direct sequencing.</p><p><b>RESULTS</b>14 patients exhibiting grade 3 - 4 neutropenia (20.0%), 16 patients experienced grade 2 - 4 diarrhea (22.9%), including only 4 patients with grade 3 - 4 diarrhea (5.7%). Compared with TA6/7 and TA7/7, UGT1 A1 * 28 wild genotype TA6/6 was significantly associated with reduced toxicity (42.1% vs. 15.7%, P = 0.027). There was no significant difference in the distribution of UGT1A genotypes between colorectal cancer patients and healthy subjects.</p><p><b>CONCLUSION</b>Chinese patients exhibit less irinotecan-related diarrhea due to higher frequence of UGT1A A1 * 28 wild genotype TA6/6.</p>

Influence of cervical sympathetic nerve block on blood flow volume and barrier function of intestinal mucosa after combined radiation and burn injury in rat / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the influence of cervical sympathetic nerve block (SB) on blood flow volume and barrier function of intestinal mucosa after combined radiation and burn injury in rat.</p><p><b>METHODS</b>SD rats were divided into three groups: control (n = 18), combined injury group (n = 100, rats with Co gamma ray body irradiation with a dose of 5 Gy plus 15% TBSA full-thickness burn injury), and combined injury with SB treatment (n = 100, with the same dose of gamma-ray irradiation and burn injury, treated with SB). Twenty rats were sacrificed on 0, 1, 5, 7 days after combined injuries for various observations. SB was conducted with injection of ropivhydrochloride into the neck bilaterally for the SB group, and same amount of normal saline was injected instead in the combined injury group. Blood flow volume, changes in villus height and crypt depth in jejunum, Na(+)-K+ ATPase activity, permeability of small intestine were measured at different time-points.</p><p><b>RESULTS</b>The blood flow volume in small intestinal mucosal on 1 post-injury days (PID) [(0.29 +/- 0.07) ml x min(-1) x g(-1)] were obviously decreased than that in normal controls [(1.26 +/- 0.23) ml x min(-1) x g(-1), P < 0.01 ], with serious destruction of pit cells, decrease in intestinal mucosal Na(+)-K+ ATPase activity, and increase in intestinal mucosal permeability. Compared with combined injury group, the blood flow volume was [(0.82 +/- 0.11) ml x min(-1) x g(-1) 1 day after combined injury, P < 0.01], and the Na(+)-K+ ATPase activity was obviously increased, and the permeability of small intestine was ameliorated.</p><p><b>CONCLUSION</b>SB can increase blood flow volume of rat small intestine after combined radiation and burn injury, promote the repair of intestinal epithelium and improve the barrier function of the intestinal wall.</p>