Gastrodin is a phenolic glycoside that has been demonstrated to provide neuroprotection in preclinical models of central nervous system disease, but its effect in subarachnoid hemorrhage (SAH) remains unclear. In this study, we showed that intraperitoneal administration of gastrodin (100 mg/kg per day) significantly attenuated the SAH-induced neurological deficit, brain edema, and increased blood-brain barrier permeability in rats. Meanwhile, gastrodin treatment significantly reduced the SAH-induced elevation of glutamate concentration in the cerebrospinal fluid and the intracellular Ca overload. Moreover, gastrodin suppressed the SAH-induced microglial activation, astrocyte activation, and neuronal apoptosis. Mechanistically, gastrodin significantly reduced the oxidative stress and inflammatory response, up-regulated the expression of nuclear factor erythroid 2-related factor 2, heme oxygenase-1, phospho-Akt and B-cell lymphoma 2, and down-regulated the expression of BCL2-associated X protein and cleaved caspase-3. Our results suggested that the administration of gastrodin provides neuroprotection against early brain injury after experimental SAH.
Animals ; Apoptosis ; drug effects ; Astrocytes ; drug effects ; metabolism ; Benzyl Alcohols ; administration & dosage ; Blood-Brain Barrier ; drug effects ; metabolism ; Brain ; drug effects ; metabolism ; Brain Edema ; etiology ; prevention & control ; Calcium ; metabolism ; Glucosides ; administration & dosage ; Glutamic Acid ; metabolism ; Male ; Microglia ; drug effects ; metabolism ; Neurons ; drug effects ; Neuroprotective Agents ; administration & dosage ; Oxidative Stress ; drug effects ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; complications ; metabolism ; prevention & control

Objective To evaluate the effect of hydrogen on mitochondrial fusion during myocardial ischemia-reperfusion (I/R) in aged rats.Methods One hundred and fifty pathogen-free healthy male Sprague-Dawley rats,aged 18 months old,weighing 400-500 g,were divided into 5 groups (n=30 each) using a random number table:control group (group C),sham operation group (group S),group I/R,normal saline group (group NS) and hydrogen-rich saline group (group H).Group C received no treatment.The anterior descending branch was only exposed but not ligated in group S.Myocardial I/R was induced by occlusion of the anterior descending branch of the left coronary artery for 30 rmin followed by reperfusion in I/R,NS and H groups.Hydrogen-rich saline 1 ml/100 g was injected intraperitoneally at 5 min before reperfusion in group H,while normal saline 1 ml/100 g was injected intraperitoneally at 5 min before reperfusion in group NS.The rats were sacrificed at 12 and 24 h of reperfusion,and hearts were removed for examination of the pathological changes and for determination of apoptosis in cardiomyocytes (by TUNEL) and expression of Mfn1 and Mfn2 protein and mRNA in myocardial tissues (by Western blot or real-time polymerase chain reaction).The apoptosis index was calculated.Results Compared with C and S groups,the apoptosis index of cardiomyocytes was significantly increased and the expression of Mfn1 and Mfn2 protein and mRNA in myocardial tissues was down-regulated at 12 and 24 h of reperfusion in I/R,NS and H groups (P＜0.05).Compared with NS and I/R groups,the apoptosis index of cardiomyocytes was significantly decreased and the expression of Mfn1 and Mfn2 protein and mRNA in myocardial tissues was up-regulated at 12 and 24 h of reperfusion in group H (P＜0.05).The pathological changes of myocardial tissues were significantly attenuated in group H when compared with group I/R.Conclusion The mechanism by which hydrogen attenuates myocardial I/R injury is related to promoting mitochondrial fusion and inhibiting apoptosis in cardiomyocytes of aged rats.

Objective To explore the clinicopathologic factors impacting recurrence and survival in rectal cancer patients after radical resection.Methods Clinicopathologic data of 1 166 patients with rectal cancer in Changhai Hospital,were recruited between 2005 and 2010.Kaplan-Meier analysis and the logrank test were used to evaluate the effects of the pathology on patients' survival.Cox regression model was used to assess independent factors associated with clinical prognosis.Results The 1,3,5-year overall survival rates were 94.3％,81.2％ and 76.5％,median survival time was 53 months.328 patients had recurrence and metastases,with a median recurrence time of 18 months.The independent prognostic factors for overall survival time were CEA,CA19-9,tumor distance to dentate line,surgical modality,radical operation,tumor invasion,tumor differentiation,lymph node metastasis and postoperative treatment.Surgical treatment,radical operation or not,tumor invasion and lymph node metastasis were statistically significant associated with tumor recurrence and metastases.Conclusions The important factors inffuencing the prognosis of rectal cancer patients were CEA,CA19-9,tumor distance to dentate line,surgical modality,radial operation,tumor in vasion,tumor differentiation,lymph node metastasis,and post operative treatment.

OBJECTIVETo investigate the relationship between tumor regression grade (TRG) and lymph node regression grade (LRG) after neoadjuvant chemoradiotherapy (CRT) for rectal cancer and its clinical implication.

METHODSClinicopathological data of 176 rectal cancer patients undergoing radical excision after neoadjuvant CRT from January 2005 to December 2013 in our department were retrospectively analyzed.

INCLUSION CRITERIA(1) Radiology indicated locally advanced low rectal cancer and patients had strong desire to preserve the sphincter before neoadjuvant CRT; (2) there was no definite metastatic lesion before neoadjuvant CRT; (3) patients received whole course of neoadjuvant CRT (regular radiotherapy plus synchronous fluorouracil-like drugs chemotherapy); (4) patients underwent radical operation after neoadjuvant CRT. Patients with short-course CRT and emergency surgery were excluded. TRG and LRG of postoperative specimens (including tumor and lymph nodes) were carried out based on the percentage of the fibrosis and the cancer residue. No cancer residue was defined as TRG1 and LRG1; rare cancer cell residue as TRG2 and LRG2; fibrosis growth over residual cancer as TRG3 and LRG3; residual cancer growth over fibrosis as TRG4 and LRG4; absence of regressive changes as TRG5 and LRG5; and normal lymph nodes as LRG0. Spearman correlation test was used to assess the correlation between TRG and LRG.

RESULTSOf 176 patients, 111 were men and 65 were women. The mean age was (53.9±13.0) years. The number of patients with stage I(, II(, and III( before operation was 10, 49 and 62 while other 55 patients were unknown. Transabdominal low anterior resection (LAR) was performed in 118 cases and abdominal-perineal resection(APR) in 47 cases following the principle of total mesorectal excision (TME). Postoperative pathology of specimens revealed that the number of patients from TRG1 to TRG5 was 19 (10.8%), 25 (14.2%), 66 (37.5%), 47 (26.7%), 19 (10.8%), and from LRG0 to LRG5 was 35 (19.9%), 68 (38.6%), 10 (5.7%), 14 (8.0%), 15(8.5%), 34 (19.3%), respectively. TRG was correlated to LRG (P=0.005) while the Spearman correlation coefficient was only 0.24. The analysis of subgroup without LRG1 also showed that TRG was correlated to LRG(P=0.0005) and the Spearman correlation coefficient was 0.40.

CONCLUSIONSTRG can not represent LRG. Therefore, both TRG and LRG should be assessed when evaluating the response of rectal cancer to neoadjuvant CRT.

OBJECTIVETo compare the short-term outcomes between transrectal specimen extraction during laparoscopic sigmoid radical resection and conventional laparoscopy-assisted sigmoid radical resection.

METHODSSixteen patients(transrectal specimen extraction group,4 females and 12 males), who were planned to undergo laparoscopically assisted sigmoid radical resection with BMI<28 kg/mand were evaluated as T1-T3 tumor by iconography without distant metastasis, were selected to undergo transrectal specimen extraction during laparoscopic sigmoid radical resection from December 2015 to April 2016 in the Department of Anorectal Surgery of Changhai Hospital. The procedure of specimen extraction was as follows: Perineal anal expansion was performed. The rectum was cut in rectal distal ligature within the abdominal cavity. Telescope cover was placed through Trocar hole in right low abdomen and rectal stump was pulled out of the body through the anus to form an access tunnel. Planned resected bowel was placed in the tunnel and the specimen was dissociated and removed completely from anus. Each patient in transrectal specimen extraction group was individually matched with two patients who underwent laparoscopically assisted sigmoid radical resection by gender, age, BMI and date of surgery. The perioperative outcomes and pathological evaluation of surgical specimen of two groups were retrospectively collected and compared.

RESULTSThe differences of baseline data (gender, age, BMI, distance from tumor to anal verge measured by colonoscopy and clinical tumor category) between two groups were not significant (all P>0.05). Compared to laparoscopy-assisted group, transrectal specimen extraction group presented longer operation time [(140.6±8.3) minutes vs. (122.2±26.2) minutes, t=-3.629, P=0.001], and more blood loss[(43.8±9.2) ml vs. (35.3±10.2) ml, t=-2.795, P=0.008], but shorter time to first flatus [(43.1±8.3) hours vs. (52.0±11.4) hours, t=2.756, P=0.008] and lower pain score at operative day and the first postoperative day (3.8±0.8 vs. 4.8±1.1, t=3.558, P=0.001; 2.6±0.6 vs. 3.8±0.8, t=5.165, P=0.000). The case ratio of additional analgesia [6.3%(1/16) ns. 18.8%(6/32)], postoperative hospital stay [(6.8±3.4) days vs. (5.6±0.8) days] and postoperative morbidity of complication [12.5%(2/16) vs. 9.4%(3/32)] were not significantly different between the two groups (all P>0.05). Within postoperative 30-day follow-up, transrectal specimen extraction group had ileus in one patient and anastomotic leakage in one patient, and laparoscopy-assisted group had fat necrosis of assisted incision in two patients and gastric retention in one patient. There were also no significant differences in specimen length[(18.2±4.8) cm vs. (19.8±5.7) cm, P>0.05], tumor size [(4.0±1.2) cm vs. (4.4±1.5) cm, P>0.05] and number of harvested lymph node (14.6±2.6 vs. 16.0±3.0, P>0.05] between two groups. During follow-up of 7-10(mean 9) months of transrectal specimen extraction group and 2-16 (mean 7) months of laparoscopically assisted group, no tumor local relapse and distant metastasis were found in the both groups.

CONCLUSIONAs compared to laparoscopy-assisted sigmoid radical resection, transrectal specimen extraction laparoscopic sigmoid radical resection has better short-term efficacy, meanwhile they have comparable oncologic clearance.

OBJECTIVETo investigate the risk factors of metachronous bone metastasis after radical resection of colorectal cancer within 5 years.

METHODSClinical data of 1 749 patients with colorectal cancer, of whom 50(2.8%) patients developed metastasis to bone after operation, in the Department of Colorectal Surgery, Changhai Hospital of The Second Military Medical University from January 2001 to December 2010 were analyzed retrospectively. Univariate and multivariate analysis were performed to find the risk factors of metachronous bone metastasis from colorectal cancer using Chi square test and Logistic regression, respectively.

RESULTSOf 50 colorectal cancer cases with bone metastasis, 29 were male and 21 were female. The age was ≥ 60 years old in 28 cases. Tumors of 36 cases were located in the rectum and of 14 cases located in the colon. Pathology examination showed 43 cases were adenocarcinomas, 7 cases were mucinous adenocarcinoma. Forty-two cases had T3-4 stage lesions, 30 cases had lymph node metastasis, 14 cases had pulmonary metastasis, and 5 cases had liver metastasis. Univariate Chi square test indicated that factors associated with the metachronous bone metastasis of colorectal cancer within 5 years were tumor site (χ=4.932, P=0.026), preoperative carbohydrate antigen 199 (CA199) level (χ=4.266, P=0.039), lymph node metastasis (χ=13.054, P=0.000) and pulmonary metastasis(χ=35.524, P=0.000). The incidence of bone metastasis in patients with rectal cancer (3.6%, 36/991) was higher compared to those with colon cancer (1.8%, 14/758). The incidence of bone metastasis in patients with higher(> 37 kU/L) preoperative serum CA199 level (4.9%, 12/245) was higher compared to those with lower serum CA199 level (2.5%, 38/1504). The incidence of bone metastasis in patients with lymph node metastasis(4.8%,30/627) and pulmonary metastasis (11.6%, 14/121) was significantly higher compared to those without lymph node metastasis (1.8%, 20/1122) and pulmonary metastasis(2.2%, 36/1628), respectively. Logistic multivariate analysis showed that rectal cancer(OR:0.508, 95%CI:0.268 to 0.963, P=0.038), lymph node metastasis (OR:2.291, 95%CI:1.273 to 4.122, P=0.006) and metachronous pulmonary metastasis(OR:4.796, 95%CI:2.473 to 9.301, P=0.000) were the independent risk factors of metachronous bone metastasis of colorectal cancer within 5 years.

CONCLUSIONPatients with rectal cancer, lymph node metastasis and metachronous pulmonary metastasis are high risk groups of metachronous bone metastasis after radical resection of colorectal cancer within 5 years.

Adenocarcinoma ; surgery ; Aged ; Biomarkers, Tumor ; blood ; Bone Neoplasms ; epidemiology ; secondary ; Chi-Square Distribution ; Colonic Neoplasms ; surgery ; Colorectal Neoplasms ; surgery ; Colorectal Surgery ; statistics & numerical data ; Disease-Free Survival ; Female ; Humans ; Incidence ; Liver Neoplasms ; secondary ; Logistic Models ; Lung Neoplasms ; secondary ; Lymphatic Metastasis ; physiopathology ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Rectal Neoplasms ; surgery ; Retrospective Studies ; Risk Factors

OBJECTIVETo investigate the factors in the disease-free interval (DFI) of metachronous pulmonary metastasis from rectal cancer.

METHODSClinical data of 92 patients with metachronous pulmonary metastasis from rectal cancer in the Department of Colorectal Surgery at the Changhai Hospital of the Second Military Medical University from January 2001 to December 2013 were analyzed retrospectively. Univariate and multivariate analysis were performed to find the factors affecting disease-free interval of metachronous pulmonary metastasis from rectal cancer using Log-rank test and Cox proportional hazards model, respectively.

RESULTSThe median age of all the cases was 61 (range, 26-81) years. Of the 92 cases, 59 were males and 33 were females. Thirty-six cases were confirmed to have <5 cm distance from lower margin to dentate line. Forty-four cases were examined to have 5 μg/L carcinoembryonic antigen(CEA) level. Of these cases reviewed pathologically, 69 cases were adenocarcinoma, 23 were mucinous adenocarcinoma; 19 cases had stage T1-2 lesions, 73 had stage T3-4 lesions; 43 cases had stage N0 metastasis, 49 had stage N1-2 metastasis. Thirty cases received preoperative radiotherapy, 63 cases received postoperative chemotherapy. The median follow up time of all the cases was 62(range, 3-140) months. The DFI of all the cases was (25.9±21.0) months. Univariate Log-rank test indicated that the factors associated with the disease-free interval of metachronous pulmonary metastasis of rectal cancer were location of the tumor(χ(2)=4.496, P=0.034), preoperative CEA level (χ(2)=5.553, P=0.018), T stage (χ(2)=5.796, P=0.016), N stage (χ(2)=6.780, P=0.009), preoperative neoadjuvant radiotherapy (χ(2)=11.718, P=0.001) and postoperative adjuvant chemotherapy (χ(2)=9.214, P=0.002). A shorter distance from lower margin to dentate line(<5 cm), a lower preoperative CEA level(<5 μg/L), advanced T stage lesions(T3-4), advanced N stage metastasis(N1-2), no use of preoperative radiotherapy and use of postoperative chemotherapy were associated with shorter DFI of patients with metachronous pulmonary metastasis from rectal cancer. Multivariate analysis showed that N stage(OR=0.525, 95% CI: 0.309-0.891, P=0.017), location of the tumor (OR=1.770, 95% CI:1.115-2.812, P=0.016) and preoperative neoadjuvant radiotherapy (OR=1.976, 95% CI:1.228-3.401, P=0.006) were the independent risk factors associated with the disease-free interval of metachronous pulmonary metastasis from rectal cancer.

CONCLUSIONSAdvanced N stage, low location of the tumor and no use of preoperative neoadjuvant radiotherapy are risk factors of shorter disease-free interval of metachronous pulmonary metastasis from rectal cancer.

Adenocarcinoma ; diagnosis ; secondary ; Adult ; Aged ; Aged, 80 and over ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Lung Neoplasms ; diagnosis ; secondary ; Male ; Middle Aged ; Multivariate Analysis ; Neoadjuvant Therapy ; Postoperative Period ; Proportional Hazards Models ; Rectal Neoplasms ; pathology ; radiotherapy ; Retrospective Studies ; Risk Factors

OBJECTIVETo identify the risk factors associated with lymph node metastasis in rectal cancer after neoadjuvant chemoradiotherapy (CRT).

METHODSFrom January 2005 to December 2013, the clinical data of 178 patients with advanced rectal cancer undergoing radical excision after neoadjuvant CRT in our department were reviewed retrospectively. A total of 11 clinicopathologic factors relating to lymph node metastasis were studied using univariate and multivariate Logistic regression analyses.

RESULTSThere were 74(41.6%) cases with lymph node metastasis, while 104 cases without lymph node metastasis. Univariate analysis showed that age(P=0.000 2), post-CRT CEA level(P=0.011 2), ypT stage(P=0.000 0), pathologic type(P=0.004 0), and tumor regression grade(TRG)(P=0.033 8) were significantly associated with lymph node metastasis. Multivariate analysis showed that age(OR=2.385, 95% CI:1.372 ~ 4.147, P=0.002 1), post-CRT CEA level(OR=2.310, 95% CI:1.005 ~ 5.307, P=0.048 6) and ypT stage(OR=2.592, 95% CI:1.236 ~ 5.432, P=0.011 7) were independent risk factors. However, 15.8% of the patients who achieved TRG1 had lymph node metastasis and TRG failed to independently correlate with lymph node metastasis in rectal cancer after neoadjuvant CRT.

CONCLUSIONSThere was a higher ratio of lymph node metastasis in rectal cancer patients who were young, CEA≥5 μg/L or deep invasion after neoadjuvant CRT. Therefore, neoadjuvant CRT should be carefully considered in these patients.

Age Factors ; Carcinoembryonic Antigen ; blood ; Chemoradiotherapy ; Female ; Humans ; Lymphatic Metastasis ; diagnosis ; Male ; Neoadjuvant Therapy ; Neoplasm Grading ; Neoplasm Invasiveness ; Rectal Neoplasms ; complications ; epidemiology ; therapy ; Remission Induction ; Retrospective Studies ; Risk Factors ; Treatment Outcome

AIM:ToinvestigatetheeffectofP21-activatedkinase1(PAK1)andlymphoidenhancer-binding factor 1(LEF1) on the proliferation of esophagus cancer cells .METHODS:Real-time PCR was applied to detect the mR-NA expression of PAK1 and LEF1 in the esophagus cancer tissues .MTT assay were used to measure the proliferation of hu-man esophagus cancer cell line KYSE transfected with PAK 1 and LEF1.RESULTS: The mRNA expression of PAK1 in the esophagus cancer tissues was lower than that in control group (P<0.05).The mRNA expression of LEF1 and tran-scription factor 4 (TCF4) in the esophagus cancer tissues was higher than that in control group (P<0.05).The prolifera-tion of KYSE cells with over-expression of PAK1 and LEF1 was higher than that in control group .No significant change of apoptosis between the KYSE cells with over-expression of PAK1 and LEF1 and control group was observed .CONCLU-SION:The expression of PAK1 decreases and the expression of LEF 1 increases in esophagus cancer tissues .LEF1 domi-nantly regulates the proliferation of esophagus cancer cells .

OBJECTIVETo investigate the risk factors associated with lymph node metastasis of T1 and T2 rectal cancer.

METHODSClinicopathological data of 576 patients with stage T1 to T2 rectal cancer without serosal invasion confirmed by pathology undergoing curative resection in Changhai Hospital from January 1999 to December 2013 were analyzed retrospectively. The relationship of clinicopathological factors of overall patients and stage T1 patients with lymph node metastasis was analyzed by univariate or multivariate analysis.

RESULTSThe lymph node metastasis rate of stage T2 rectal cancer was significantly higher than that of stage T1[22.9% (108/463) vs. 9.7%(11/113), P=0.002], and the difference of stage T2a and T2b was not significant[22.0%(38/173) vs. 23.4% (68/290), P=0.733]. Multivariate analysis showed that poor differentiation(HR=1.54, 95% CI:1.12 to 2.13), abnormal carbohydrate antigen (CA) 199 level (HR=2.05, 95% CI:1.16 to 3.62), ulcerative mass (HR=1.58, 95% CI:1.05 to 2.39) and invasion of muscle (of inner ring muscle HR=3.55, 95% CI:1.79 to 7.02; of outer longitudinal muscle, HR=2.35, 95% CI:1.21 to 4.60) were independent risk factors of lymph node metastasis in patients with stage T1-T2 rectal cancer(all P<0.05). Meanwhile poor differentiation(HR=4.43, 95% CI:1.51 to 13.03), abnormal carcinoembryonic antigen(CEA) level (HR=4.66, 95% CI:1.18 to 20.11) and ulcerative mass (HR=6.23, 95% CI:1.51 to 25.66) were risk factors of lymph node metastasis in patients with stage T1 rectal cancer.

CONCLUSIONPoor differentiation, preoperative high CA199, ulcerated tumor, invasion of inner ring muscle or outer longitudinal muscle are risk factors of lymph node metastasis in patients with stage T1-T2 rectal cancer, while the invasion depth of muscularis propria is not risk factor. Besides, poor differentiation, abnormal CEA level, ulcerated tumor are risk factors of lymph node metastasis in stage T1 rectal cancer patients, which can be used as reference for local excision in patients with stage T1 rectal cancer.