Objective To investigate the effect of Bmal1 on proliferation in gastric cancer cells and the molecular mechanism, and to provide theoretical and experimental basis for further research targeting circadian therapy for gastric cancer. Methods Applying RNAi technique to silence Bmal1 gene in BGC823 was regarded as experimental group. The normal BGC823 was as control group. The inhibitory effect of the cell line was measured by MTT assay. The mRNA expression of p53, c-Jun and c-Fos was evaluated by real-time RT-PCR. Results Comparing with the data of control group,the inhibitive rates of cell growth in experimental group after 6 h,12 h,24 h were 5.78%(P=0.001),9.20%(P=0.00)and 83.08%(P=0.00)respectively. Down-regulation of Bmal1 decreased p53 (P<0.05), while increased c-Fos and c-Jun expression (P > 0.05). Conclusion RNAi targeting Bmal1 has effects on gastric cancer proliferation by down-regulating p53 mRNA.

Objective To study the value of combined parenteral and enteral nutrition support with chemotherapy for advanced gastrointestinal cancer in elder patients.Methods Totally 79 patients admitted from 2006 to 2011 were randomly divided into two groups using random number table:the treatment group (n=42) was provided with combined parenteral and enteral nutrition support and chemotherapy,the control group(n =37) was treated with chemotherapy only.Nutritional risks were screened at admission.After two cycles of chemotherapy,the nutritional status,Karnofsky performance score,toxic reaction,and nosocomial infection rate were compared betweeen these two groups.Results After 2 cycles of chemotherapy,the body mass index[(19.00±3.31) kg/m2 vs.(18.24±1.98) kg/m2,P=0.04],albumin [(33.90±1.50) g/Lvs.(29.90±2.38) g/L,P=0.02],prealbumin [(28.19±1.50) g/Lvs.(25.51 ±8.38) g/L,P=0.01],hemoglobin [(107.0 ± 6.90) g/L vs.(104.20 ± 9.70) g/L,P =0.02],and lymphocyte levels [(2.99 ±0.55) × 109/L vs.(2.63 ±0.20) × 109/L,P =0.03] were all significantly higher in the treatment group.The incidence of myelosuppression in the treatment group was 28.57％,significantly lower than that in the control group (83.78％,P =0.00) ; such difference was also detected in patients with nutritional risk in the 2groups (31.03％ vs.95.45％,P =0.00).The incidences of nosocomial infection in the treatment group were significantly lower than in the control group after both the first and the second cycle of chemotherapy (0 vs.10.81％,P=0.03; 2.38％ vs.27.03％,P=0.02).Conclusions Combined enteral and parenteral nutrition support with chemotherapy in elderly patients with advanced gastrointestinal caner could improve nutritional status,reduce toxic reaction,and prevent nosocomial infection.Therefore combined nutrition support is a safe and effective approach for elderly patients with advanced gastrointestinal cancer.

Objective To investigate the influence of high-fat diet in the intestinal flora,fecal weight and its water content in rats, and to clarify the effect and significance of high-fat diet in the occurrence of obesity forming. Methods Twenty Sprague-Dawley (SD)rats were randomly divided into normal diet (ND)group and high-fat diet (HF)group (n=10).The rats in ND group were fed with normal diet,and the rats in HF group were fed with diet rich in oil and fat.The fresh feces were collected separately on days 1,15,30,and 49 for analysis of weight, water content,and intestinal flora.Results On the 49th day,the wet weight and water content of feces of the rats in ND group were (6.61 ± 0.17)g and (37.07 ± 3.04)%,respectively,while those in HF group were (4.46±0.30)g and (18.04±2.23)% (P<0.05).Compared with ND group ,the fecal pellets in HF group were increased obviously from the 7th day (P<0.05).There were obvious changes in intestinal microbial populations of HF group. The counts of enterococci, bifidobacteria, Lactobacillus, Bacteroides bacteria were significantly decreased on the day 49, but the count of Escherichia coli was increased significantly (P < 0.05 ). Conclusion High-fat diet can result in decrease for weight,water content,and pellets of feces;it can change the structure of intestinal flora. As result, there is a possibility that all of changes above can promote obesity in the future.

Objective To explore the effects and mechanism of hydrogen sulfide on myocardial ischemia reperfusion in rats. Methods With sodium hydrogen sulfide (NaHS) as a donor of hydrogen sulfide ( H2S), we established myocardial ischemia-reperfusion injury model in rats. The SD rats were randomly divided into control group,myocardial ischemia reperfusion group (I/R group), H2S group,and H2S and glibenclamide (H2S + GLI)group. We monitored the hemodynamics index of rats, including heart rate, arterial pressure, left ventricular pressure. The rate of ventrical arrhythmia was also observed in each group. Results H2 S significantly reduced the ventricular arrhythmia (VA) occurrence (H2S group 66.5% vs I/R group 33.5% (P ＜0.05) and score in myocardial ischemia reperfusion rats (H2S group 2. 6 ±0. 7 vs I/R group 4. 5 ±0. 8(P＜0.05). The KATP channel blocker,glibenclamide,could weaken the antiarrhythmic effects of H2S ( H2S group 2. 6 ±0. 7 vs. H2S + GLI group 4. 0 ± 0. 6, P ＜ 0.05 ). Conclusions H2S has the protective effect against myocardial ischemia reperfusion damage. This function may be associated with the KATP signal transduction pathway in cells.

Objective To investigate clinical and genetic characteristics of Chinese patients with hereditary spastic paraplegia (HSP).Methods To perform retrospective analyses of clinical data from 179 HSP Han Chinese patients from Xiangya Hospital and National Laboratory of Medical Genetics of China.Results The 179 patients comprised of 114 familial cases (from 41 families with AD inheritance and 37 families with AR inheritance ) and 65 sporadic cases.Genetic anticipation was not found, and nonpenetrance was observed in some HSP families.Male to female ratio was 1.84 to 1.The mean age of onset was ( 18.1 ± 14.0) years, and the mcan duration of disease was ( 12.3 ± 11.5) years.AD-HSP patients had an older age of onset ( ( 19.7 ± 14.0) years) and a longer duration ( ( 17.9 ± 14.4) years) than ARHSP patients (t =2.196 and 4.404, P value were less than 0.05 and 0.01 respectively).Most AD patients manifested as "pure" form, while "complicated" form occurred more frequently in AR patients (F =19.322, P ＜ 0.01 ).Leg stiffness and clumsiness were often the early symptoms at the beginning of the disease, and the most common leg signs were hypertonia, hyperreflexia and pathological reflexes.Other signs included ankle clonus (46.9% ), weakness (42.5% ) and deformities (30.7% ).Ataxia, dysarthria,mental retardation, and foot deformity were more frequently seen in AR-HSP patients than AD-HSP patients,but the frequency of urinary symptoms was higher in AD-HSP patients.Among 65 patients with MRI examination of the head, 13 cases and 9 cases showed corpus callosal dysplasia and cerebellar atrophy,respectively.In addition, spinal cord atrophy was found in 7 of 45 patients undergone MRI examination of the spine.Conclusions Adolescent onset of HSP is common, and more males than females are affected.When compared with AR-HSP, AD-HSP patients have an older age of onset, a longer duration, and more marked urinary symptoms.Most AD-HSP cases are of "pure" form, while most AR-HSP cases manifest as "complicated" form with ataxia, dysarthria, and mental retardation.Dysplasia of corpus callosum is commonly seen in AR-HSP individuals than AD-HSP.HSP manifest gender-related clinical heterogeneity,illustrating the phenomenon of "female protection".

Objective To evaluate the efficacy of chemoradiotherapy alone and prognostic factors for locally advanced rectal cancer. Methods The clinical data of 47 patients with locally advanced rectal cancer who were admitted to our hospital and mostly treated with chemoradiotherapy alone from 2003 to 2010 were retrospectively analyzed. Three of the patients received radiotherapy alone. The Kaplan?Meier method was used to estimate overall survival (OS), progression?free survival (PFS), and distant metastasis?free survival ( DMFS ) rates, and the log?rank test was used for survival difference analysis and univariate prognostic analysis. The Cox regression model was used for multivariate prognostic analysis. Results In all patients, the 3?and 5?year OS rates were 53?2% and 33?2%, respectively, while the 3?and 5?year PFS rates were 37% and 31%, respectively. During the follow?up, 15 patients (32%) had local progression with PFS of 1?60 months (median PFS, 14 months);23 patients (49%) had distant metastasis with DMFS of 2?60 months ( median DMFS, 17 months) . Patients treated with high?dose radiotherapy had significantly lower 3?and 5?year local progression rates than patients treated with medium?dose radiotherapy ( 11% vs. 54%;11%vs. 57%;P=0?004). After chemoradiotherapy, 9 patients (19%) had clinical complete response (cCR), and the 3?and 5?year OS and PFS rates in those patients were all 8/9. The univariate analysis indicated that tumor distance from the anus and cCR were influencing factors for prognosis ( P= 0?026;P= 0?000 ) . However, the multivariate analysis showed that cCR was the only influencing factor for survival ( HR=12?24;95% CI, 1?64 ?91?29;P= 0?015 ) . Conclusions Chemoradiotherpay or radiotherapy alone is effective and safe in the treatment of patients with locally advanced rectal cancer who have to give up surgery or have unresectable tumors. High?dose radiotherapy may improve local control rate. Complete response to chemoradiotherapy predicts satisfactory treatment outcomes.

Objective To investigate the efficacy and toxicities of neoadjuvant chemoradiotherapy (neoCRT) in the management of unresectable locally advanced adherent colon cancer (LAACC).Methods A retrospective analysis was performed on the clinical records of 40 patients with initially diagnosed unresectable LAACC who received preoperative neoCRT in our center from October 2010 to December 2015.Results Thirty-nine patients completed the preoperative neoCRT.Thirty-four patients underwent radical resection after neoCRT, and the R0 resection rate, pathological complete response rate (pCR), tumor downstaging rate, nodal downstaging rate, and clinical downstaging rate were 91%, 24%(8/34patients), 76%(26/34patients),100%(32/32patients), and 94%(32/34patients), respectively.Among the 21 patients with bladder invasion, the full bladder was preserved in 7 patients (33%) and partial cystectomy was performed in 11 patients (52%).During the course of neoCRT, the grade 3-4 hematologic toxicity rate, grade 3 hand-foot syndrome rate, grade 3 radiodermatitis, and incomplete intestinal obstruction rate were 23%, 3%, 3%, and 5%, respectively.The 3-year sample size was 25 patients.For all the patients, the 3-year overall survival (OS) and progression-free survival (PFS) rates were 75% and 80%, respectively.Of the 34 patients who received surgical radical resection, the 3-year OS and disease-free survival (DFS) rates were 87% and 81%, respectively.In addition, local tumor recurrence was identified in 3 patients, and distant metastasis was identified in 6 patients.Conclusions NeoCRT is an effective treatment for unresectable LAACC that results in significant tumor downstaging and enhanced R0 resection rate without an increase in surgical complications.The patients treated with radical surgical resection after neoCRT show a satisfactory short-term outcome.Further studies will be required to determine the clinical value of neoCRT in treating LAACC.

Objective To evaluate the mid-to long-term survival benefits of preoperative sandwich-like neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC).Methods A total of 45 LARC patients who underwent neoadjuvant sandwich CRT in the form of XELOX regimen prior to,concurrently with,and following volumetric modulated arc radiotherapy (VMAT) in 2012 were enrolled in this study.VMAT was given at a gross tumor volume dose of 50 Gy in 25 fractions,and a clinical target volume dose of 45-46 Gy in 25 fractions.Total mesorectal excision was performed 6 to 8 weeks after completion of VMAT.The overall survival (OS) and disease-free survival (DFS) were determined by the Kaplan-Meier method,and survival comparison and univariate prognostic analysis were performed using the log-rank test.Results The median follow-up time was 46.7 months.There was no local recurrence detected among the patients.The 3-year distant metastasis (DM) rate was 18%,and the 3-year OS and DFS were 96% and 84%,respectively.Univariate analysis indicated that perineural invasion,N1-N2 pathology (pathological stage Ⅲ),and Ca-199>35 U/ml before treatment were risk factors for DM (P=0.000,0.000,and 0.013,respectively).Conclusions The significant short-term efficacy of preoperative sandwich-like neoadjuvant CRT can be extended to a positive mid-term survival in LARC patients.However,further phase Ⅲ clinical studies will be needed to confirm this finding.

Objective To investigate the function of sorafenib on the growth of hepatocellular carcinoma by establishing subcutaneous transplantation tumor model with nude mice.To explore the effect of sorafenib on circadian clock gene expression in hepatoma cells.Methods Mouse tumor model was established by implanting hepatocarcinoma cell (HepG2) subcutaneously in Balb/C nude mice.Sixteen experimental mice were randomly divided into two groups:sorafenib treatment group (n =8) and solvent control group (n =8).The nude mice were treated with sorafenib (100 mg/kg) and DMSO daily by intragastric administration,respectively.The volume of tumors was recorded every 3 days.The expressions level of circadian clock genes (Per1,Per2,Per3,CLOCK,Cry1,Cry2,BMAL1 and CKIε) were detected by real-time polymerase chain reaction (Real-time PCR).The correlations between the size of the xenografts and the expressions of the circadian clock genes were further analyzed.Results Compared with the control group,the tumor size in the sorafenib treatment group were significantly smaller comparing with the control group.Results of Real-time PCR showed that the expression level of Per1,Cry1 and BMAL1 mRNA was remarkably decreased in the treatment group (Per1,P =0.02;Cry1,P =0.002;BMAL1,P =0.035),the differences were statistically significant.Correlation analysis showed that the size of subcutaneous transplantation tumorsin nude mice was negatively correlated with the expressions of Per1,Per2,Cry1 and Cry2 mRNA in control group.While,the size of subcutaneous transplantation tumors was negatively correlated with the expressions of Per2,Per3 and BMAL1 levels in the sorafenib treatment group.Conclusions There is a negative correlation between the expression levels of some biological clock genes and the size of transplantation tumor in nude mice.Sorafenib treatment significantly inhibited the growth of hepatocellular carcinoma in nude mice and down-regulation the expressions of Per1,Cry1 and BMAL1 mRNA in hepatoma cells.

Objective:To explore the repeatability of ultrasound shear wave elastography (SWE) in evaluating the Young′s modulus (E) of the lumbar multifidus (LM) and the difference in E of the bilateral LM, and to analyze the E′s change ratio of LM and its impact factors at upright and 90° forward bend positions.Methods:A total of 60 healthy volunteers, selected from interns, standardized training residents and refresher doctors in department of diagnostic ultrasound of Sir Run Run Shaw Hospital of Zhejiang University School of Medicine from July to December in 2020, were examined twice by SWE to estimate the E value of LM at prone, upright and 90° flexion positions, respectively. Firstly, the intraclass correlation coefficient (ICC) was applied to test the reliability between the two repeated measurements.Secondly, the differences in E of the bilateral LM were discussed. The discrepancies in the E value of male and female volunteers at prone, upright and 90° flexion positions and the change ratio of the E value at upright and 90° forward bend positions were also discussed, respectively. Finally, Spearman correlation coefficient was utilized to evaluate the correlations of E and its change ratio with gender, age, BMI and activity level at upright and 90° forward bend positions, respectively.Results:The ICC value in LM measured by SWE was in the range of 0.691 to 0.951. No obvious change in bilateral E values of the same posture was observed for an individual(all P>0.05). The change ratios of E at upright and 90° flexion positions were approximate to 2 and 7, respectively. Moreover, at prone position, the E value exhibited negative correlation with age and activity level of self-assessment ( rs=-0.300, P=0.020; rs=-0.383, P=0.002). The E in female was higher compared with that in male. At active states the change ratio in E was positively correlated with age and activity level ( rs=0.278, P=0.031; rs=0.495, P<0.001), and the E′s change ratio in male was higher than that in female. Conclusions:SWE possesses excellent repeatability in evaluating the E value of LM with no significant difference in E of bilateral LM. The E′s change ratio in LM varies with different contraction strategies and changes with age, sex and self-reported activity level.