[Pre- and post-diagnosis body mass index in association with colorectal cancer death in a prospective cohort study].

Objective: To evaluate the association between pre-and post-diagnosis body mass index (BMI) and risk of colorectal cancer (CRC) death. Methods: The cohort consisted of 3, 057 CRC patients from Shanghai who were diagnosed from Jan. 1, 2009 to Dec. 31, 2011 and aged from 20 to 74 years. The pre- and post-diagnosis BMI and clinical and lifestyle factors were collected at baseline. Death information was collected using record linkage with the Shanghai Cancer Registry and telephone confirmation during follow-up by the end of 2019. The Cox proportional regression model was used to estimate HR with 95% CI. Results: Analysis by multivariable Cox model showed no association between pre-diagnosis BMI and death risk in both male and female patients. Male patients with a post-diagnosis underweight BMI had an elevated risk of death compared to those in normal weight (HR=1.69, 95% CI: 1.21-2.37), especially in early stage cases. Overweight patients (HR=0.74, 95% CI: 0.61-0.89) and patients with obesity class Ⅰ (HR=0.63, 95% CI: 0.45-0.89)had better survival with decreased risks of death, especially in advanced stage cases. The decreased death risk in patients with obesity class Ⅱ was not significant (HR=0.57, 95% CI: 0.24-1.39). The P(trend) value for decreased risk of death with increased BMI in female patients was statistically significant (P<0.001), and the overweight and obesity class Ⅰ categories had better survival in advanced stage(HR(overweight)=0.62, 95% CI: 0.42-0.93; HR(obesity class Ⅰ)=0.39, 95% CI: 0.16-0.98). Both male and female patients with post-diagnosis BMI loss >2.0 kg/m(2) had an increased death risk when compared with those with stable BMI (change≤1.0 kg/m(2)) between pre- and post-diagnosis. BMI gain after diagnosis did not change death risk. Conclusions: Post-diagnosis BMI in the overweight or obesity class Ⅰ groups might be conducive to prolonging male CRC patients' survival, while underweight might result in poor prognosis. Keeping weight and avoiding excessive weight loss should be suggested for all CRC patients after diagnosis.

MicroRNA-802 promotes the progression of osteosarcoma through targeting p27 and activating PI3K/AKT pathway

PurposeIncreasing evidences suggest dysfunctions of microRNAs (miRNAs) are playing important part in tumors. Therefore, the role of miR-802 in osteosarcoma (OS) was exploited. The object was to evaluate the effect of miR-802 and verify its influence on p27 Kip1 (p27) in OS.MethodsRT-qPCR experiment was used to detect miR-802 and p27 expression in OS tissues and cells. We explored the function of miR-802 through Transwell assays. The phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase pathway and epithelial–mesenchymal transition (EMT) was detected by Western blot assays. Luciferase assay was used to testify the target of miR-802.ResultsMiR-802 expression was elevated in OS, which was related to poor clinical outcome in OS patients. MiR-802 overexpression promoted OS migration, invasion and EMT. Further, p27 is a direct target of miR-802. P27 elevation counteracted the promotion effect of OS on EMT, migration and invasion induced by miR-802. In addition, miR-802 overexpression inactivated PI3K/AKT pathway via targeting p27 in OS.ConclusionMiR-802 promoted the progress of EMT, migration and invasion in OS via targeting p27. This newly identified miR-802/p27/PI3K/AKT axis may represent potential targets for OS.

MicroRNA-802 promotes the progression of osteosarcoma through targeting p27 and activating PI3K/AKT pathway.

PURPOSE: Increasing evidences suggest dysfunctions of microRNAs (miRNAs) are playing important part in tumors. Therefore, the role of miR-802 in osteosarcoma (OS) was exploited. The object was to evaluate the effect of miR-802 and verify its influence on p27 Kip1 (p27) in OS. METHODS: RT-qPCR experiment was used to detect miR-802 and p27 expression in OS tissues and cells. We explored the function of miR-802 through Transwell assays. The phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase pathway and epithelial-mesenchymal transition (EMT) was detected by Western blot assays. Luciferase assay was used to testify the target of miR-802. RESULTS: MiR-802 expression was elevated in OS, which was related to poor clinical outcome in OS patients. MiR-802 overexpression promoted OS migration, invasion and EMT. Further, p27 is a direct target of miR-802. P27 elevation counteracted the promotion effect of OS on EMT, migration and invasion induced by miR-802. In addition, miR-802 overexpression inactivated PI3K/AKT pathway via targeting p27 in OS. CONCLUSION: MiR-802 promoted the progress of EMT, migration and invasion in OS via targeting p27. This newly identified miR-802/p27/PI3K/AKT axis may represent potential targets for OS.

[Effect of peritoneum reconstruction on postoperative complications after laparoscopic low anterior resection for rectal cancer].

Objective: To determine the effect of peritoneum reconstruction on postoperative complications after laparoscopic low anterior resection (LAR) for rectal cancer. Methods: Retrospective cohort study and propensity score matching were conducted. Case inclusion criteria: (1) pathologically confirmed rectal adenocarcinoma; (2) 18 to 80 years; (3) patients with middle to low rectal cancer undergoing laparoscopic LAR; (4) patients staging cT1-4aN0-2M0 or ycT1-4aN0-2M0 after neoadjuvant therapy; (5) the distance of 4-10 cm from tumor low margin to anal verge. Exclusion criteria: (1) abdominal surgery history (except appendicitis, cholecystitis, ectopic pregnancy); (2) anastomosis above the peritoneal reflection; (3) tumor distant metastasis or clinical staging of T4b during surgery; (4) conversion to open surgery; (5) severe incapacitating disease (American Society of Anesthesiologists classification IV or V, ASA). A total of 666 patients with middle to low rectal cancer undergoing laparoscopic LAR in The First Affiliated Hospital of Army Medical University from January 2017 to June 2020 were enrolled. There were 473 males and 193 females with the median age of 59 (18-80) years. Laparoscopic LAR with peritoneum reconstruction was performed in 188 cases (PR group), and laparoscopic LAR without peritoneum reconstruction was performed in 478 cases (NPR group). After 1:1 propensity score matching according to 1:1 based on age, gender, body mass index, TNM staging, ASA classification, intraoperative blood loss, distance from tumor low margin to anal edge, 153 cases were included in each group. Postoperative complications were classified according to Clavien-Dindo classification. Anastomotic leakage was defined and graded according to the International Study Group of Rectal Cancer (ISGRC) criteria. Results: After propensity score matching, there were no significant differences in baseline demographic characteristics between the 2 groups (all P>0.05), indicating that these two groups were comparable. (1) Operative conditions: All the patients in both groups completed operation successfully. Compared with the NPR group, the PR group had longer operation time [(181.3±60.3) minutes vs. (168.9±51.5) minutes, t=2.185, P=0.029], shorter postoperative median hospital stay [8 (7, 10) days vs. 9 (7, 11) days, Z=-2.282, P=0.022], and the differences were statistically significant (P<0.05). (2) Postoperative complications: The overall morbidity of postoperative complication in PR group and NPR group was 20.3% (31/153) and 24.2% (37/153) respectively, and the incidence of anastomotic leakage was 9.8% (15/153) and 11.1%(17/153) respectively, whose differences were not statistically significant (both P>0.05). Compared with NPR group, PR group had lower morbidity of grade III to IV complications [3.9% (6/153) vs. 11.1% (17/153), χ(2)=5.688, P=0.017] and lower secondary operation rate [1.3% (2/153) vs. 5.9% (9/153), χ(2)=4.621, P=0.032], the differences were statistically significant (both P<0.05). Though PR group had lower incidence of grade C anastomoic leakage [1.3% (2/153) vs. 3.9% (6/153), χ(2)=2.054, P=0.152], but the differences were not statistically significant. (3) Postoperative inflammation: The difference of the procalcitonin level of both PR and NPR groups at postoperative 1-d, 3-d, and 5-d was statistically significant (F=5.222, P=0.010) in time-dependent manner, while the difference was not significant in the interaction effect (P>0.05). No statistically significant differences in the C-reactive protein level between two groups at postoperative 1-d, 3-d, and 5-d were found (all P>0.05). Conclusion: Peritoneum reconstruction in laparoscopic LAR can decrease the morbidity of postoperative complication of grade III to IV and the reoperation rate, and plays an important role in controlling the inflammatory reaction, which has great clinical value.

Down-regulation of miR-320 exerts protective effects on myocardial I-R injury via facilitating Nrf2 expression.

OBJECTIVE: Nuclear factor NF-E2 related factor 2 (Nrf2) plays crucial roles in the regulation of oxidative stress (OS) or myocardial ischemia-reperfusion (I-R) injury. During the process of I-R injury, the miR-320 is down-regulated. Bioinformatics analysis showed complementary binding sites between miR-320 and 3'-UTR of Nrf2 mRNA. Therefore, this study aimed to investigate the role of miR-320 in mediating Nrf2 expression and myocardial I-R injury. MATERIALS AND METHODS: Rat I-R model was established. Fluorescent quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot were used to measure the expression of miR-320, Nrf2, HO-1 in myocardial tissues. Contents of malondialdehyde (MDA), superoxide dismutase (SOD) and caspase-3 activity, serum assay of creatine kinase (CK) and lactate dehydrogenase (LDH) activity were evaluated. I-R rat models were transfected with antagomir-320 followed by measuring those proteins. Cultured H9C2 cells were transfected with antagomir-320 to measure miR-320, Nrf2 and heme oxygenase 1 (HO-1) expression, cell apoptosis and reactive oxygen species (ROS) content. RESULTS: Compared to the sham group, I-R rats had significantly lower miR-320 or HO-1 expression in the myocardium, plus higher levels of Nrf2, MDA, CK and LDH, and decreased SOD activity (p<0.05). Antagomir-320 transfection suppressed miR-320 expression, elevated Nrf2 and HO-1 expression, decreased levels of MDA, CK or LDH, and increased SOD activity. In H9C2 cells, antagomir-320 transfection also elevated Nrf2 and HO-1 expression and suppressed myocardial cell apoptosis or ROS production under I-R treatment. CONCLUSIONS: Down-regulation of miR-320 exerts protective effects on myocardial I-R injury. The inhibition of mir-320 expression can enhance OS potency of the myocardium, alleviate I-R injury or reduce cell apoptosis by facilitating Nrf2 expression.

[A nested case-control study of cruciferous vegetables intake, urinary isothiocyanates level and lung cancer risk among men in urban Shanghai].

Objective: To investigate the association between consumption of cruciferous vegetables (CV), level of urinary isothiocyanates (ITC) and the risk of lung cancer among man in urban Shanghai. Methods: A nested case-control study was conducted within the Shanghai Men's Health Study. Using incidence density sampling with a 2∶1 control to case selection ratio, 885 controls were selected to match 443 lung cancer cases diagnosed prior December 31, 2010. A food-frequency questionnaire was administered to estimate CV consumption. The high performance liquid chromatography method was applied to measure urinary ITC level. The CV intake and urinary ITC level were divided into quartiles according to distribution of control group. The lowest quartile was as a reference group. Conditional logistic regression model was used to analyze the relationship between CV intake, urinary ITC level and the risk of lung cancer. Results: The cruciferous vegetables intake median (P(25), P(75)) in cases and controls were 80.05 (46.89, 129.04) and 97.68 (55.25, 151.72) g/d (Z=-3.93, P<0.001). The urinary ITC level were 1.256 (0.474, 3.836) and 1.244 (0.484, 3.004) µmol/g Cr (Z=-0.39, P=0.697). After adjusting for potential confounding factors such as age, education level, smoking and alcohol consumption, for urinary ITC level, the OR(95%CI) for the highest quartile(≥3.004 µmol/g Cr) was 1.25 (0.87-1.80) compared with the lowest quartile(<0.484 µmol/g). For CV intake, the OR(95%CI) for the highest quartile(≥151.71 g/d) was 0.66 (0.43-1.02) compared with the lowest quartile(<55.25 g/d). Conclusion: No association was found between the CV intake, urinary ITC level and lung cancer risk in men.

[The joint effects of major lifestyle factors on stomach cancer risk among Chinese men: a prospective cohort study].

Objective: To investigate the combined impact of lifestyle factors on stomach cancer risk. Methods: We analyzed the data from the Shanghai Men's Health Study (SMHS) (2002-2013). The SMHS was conducted in eight neighborhood communities of urban Shanghai. From 2002 through June 2006, 61 480 residents aged 40 to 74 years old with no history of cancer were recruited. Failure time was the date of stomach cancer incidence, death or date of the last follow-up (December 31, 2013). The first two in-person follow-up surveys were conducted in 2004-2008, and 2008-2011, respectively. Using data on lifestyle, the healthy lifestyle index (HLI) was developed. The following lifestyle factors were included: smoking, alcohol consumption, diet habit, overweighted and physical activity. Cox proportional hazard models were used to evaluate the association of stomach cancer risk with lifestyle factors and HLI. Results: Over 9.28 years' follow-up, 477 incident cases of stomach cancer were identified from 59 503 study participants. Participants with zero, one, two, three, four, and five favorable lifestyle behaviors accounted for 3.44% (n=2 045), 18.14% (n=10 793), 33.68% (n=20 041), 29.43% (n=17 511), 12.82% (n=7 627), and 2.50% (n=1 486), respectively. Among all the five lifestyle factors, smoking and alcohol use were significantly related to stomach cancer risk. The relative risk of stomach cancer was 0.71 (95%CI: 0.57-0.87) for those who never smoked or quitted smoking for no less than 10 years and 0.70 (95%CI: 0.55-0.90) for those who consumed alcohol no more than 14 drinks per week. For each increment of healthy lifestyle index, the relative risk of stomach cancer was 0.86 (95%CI: 0.79-0.95). Compared to men with none or one healthy lifestyle factor, the relative risk for those with four or five was 0.62 (95%CI: 0.46-0.83). When we rebuilt HLI using more categories of each lifestyle factors, the HLI ranged from 0 to 11. For each point increase, the relative risk of stomach cancer was 0.93 (95%CI: 0.89-0.97). Compared those with 0 to 3 points, the relative risk of those with 8 to 11 points was 0.64 (95%CI: 0.47-0.87). Conclusion: In the SMHS, only a small proportion of men adhered to all the five healthy lifestyle factors. Compared to those with none or one healthy lifestyle behaviors, those with five may prevent about 1/3 stomach cancer incidence and the HLI was inversely associated with stomach cancer risk.

Effect of age on the immune system and pathology of mice with chronic graft-versus-host disease lupus nephritis.

We investigated the effect of age on the expression of immune molecules [ANA, C4, double stranded DNA (dsDNA), CD16/32, CD19, CD3, and CD64], urine protein, and pathology in mice with chronic graft-versus-host disease (cGVHD) lupus nephritis (LN), and their relationship with reactivity index score. Mouse models of cGVHD LN were established, and mice were randomly divided into four aged-based groups of nine mice each. Serum levels of ANA, C4, and dsDNA were determined, the urine protein levels were assessed, and expression levels of CD16/32, CD19, CD3, and CD64 were measured. Expression levels of CD16/32+CD19(T1), CD16/CD32+CD3(T2), and CD64+CD3 or CD19(T3) were defined in the thymus, in bone marrow they were defined as CD16/32+CD19(B1), CD16/32+CD3(B2), CD64+CD3 or CD19(B3), and in spleen they were defined as CD16/32+CD19(P1), CD16/32+CD3(P2), CD64+CD3 or CD19(P3), respectively. There were significant differences in the levels of dsDNA and urine protein among the four groups (P < 0.05), which were negatively correlated with age. B1, B2, S1, and S2 were significantly different among the four groups (P < 0.05), with a positive correlation with age for B1 and B2. There was no correlation of expression of ANA, C4, dsDNA, T1-T3, B1-B3, S2-S3 with reactivity index score; S1 was the exception (r = -0.440, P = 0.011). Age influenced levels of dsDNA and urine protein in the mouse cGVHD model of LN. S1 was associated with reactivity index score and might also affect pathological changes.

Association between the TRAIL single nucleotide polymorphism rs1131580 and type 2 diabetes mellitus in a Han Chinese population.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is expressed in different tissues and cells, including the pancreas and lymphocytes, and it can selectively induce apoptosis in tumor cells but not in most normal cells. TRAIL plays critical roles in type 1 diabetes mellitus, and is involved in type 2 diabetes mellitus (T2DM). We recently discovered the association of nonalcoholic fatty liver disease, a risk factor for T2DM, with a single nucleotide polymorphism (SNP) in the TRAIL (TNFSF10) gene at site 1595C/T (rs1131580), indicating the possible association of T2DM with this TRAIL polymorphism. The aim of this study was to investigate the relationship of the TRAIL SNP at site 1595C/T (rs1131580) with T2DM susceptibility and the biometabolic parameters of T2DM in a Han Chinese population. The polymerase chain reaction-restriction fragment length polymorphism method was used to genotype SNP rs1131580 in 292 patients with T2DM and 266 healthy controls. We found that the frequency of the CC genotype and that of the C allele of rs1131580 were significantly higher in T2DM patients than in the control group. Additionally, the triglyceride and serum creatinine levels of T2DM patients with the CC genotype were significantly higher than those of patients with the TT genotype. Thus, the CC genotype of the TRAIL SNP at 1595C/T (rs1131580) confers increased susceptible to T2DM in a Han Chinese population from Shandong Province. These data suggest that the CC genotype at this SNP is related to diabetic severity and it might be a candidate for the prognostic assessment of T2DM.

One hundred and one new microsatellite loci derived from ESTs (EST-SSRs) in bread wheat.

Four hundred and seventy-eight microsatellite markers derived from expressed sequence tags (EST-SSRs) were screened among three mapping populations (W-7984xOpata 85, WOpop; LumaixHanxuan, LHpop; WenmaixShanhongmai, WSpop). The number of polymorphic EST-SSR primer pairs found in WOpop, LHpop and WSpop was 92, 58 and 29 respectively. A total of 101 EST-SSR loci amplified from 88 primer sets were distributed over the 20 chromosomes of the reference maps (no markers were located on chromosome 4B). These 101 mapped EST-SSR markers add to the existing 450 microsatellite loci previously mapped in bread wheat. Seventy-four of the 101 loci showed significant similarities to known genes, including 24 genes involved in metabolism, 4 in cellular structures, 9 in stress resistance, 12 in transcription, 2 in development, 2 transporters and 21 storage proteins. Besides gliadin and glutenin, most of the 53 genes with putative functions were mapped for the first time by EST-SSR markers in bread wheat. Sequence alignment of the mapped wheat EST-SSR loci allowed tentative assignment of functionality to the other members of grasses family. Colinearity combined with homology information offers an attractive approach to comparative genomics.

Genetic diversity of rhizobia isolated from Caragana intermedia in Maowusu sandland, north of China.

AIMS: Thirty-three rhizobial strains isolated from nodules of Caragana intermedia in Maowusu sandland were examined for their genetic diversity and putative phylogenetic position. METHODS AND RESULTS: Isolates from Caragana intermedia were classified into 12 genotypes by 16S rDNA polymerase chain reaction-restriction fragment length polymorphism (RFLP), which showed no distinct relationships with those of the reference strains. The genotypes of rhizobia were not related to geographical location. Thr 16S rDNA sequence of representative strain GH2001 from dominant genotype 2 shared high homologuey with some Rhizobium species: Rh. giardinii (96.4%), Rh. huautlense (95.3%), Rh. galegae (95.7%), Rh. yanglingense (95.2%), Rh. mongolense (95.6%), Rh. radiobacter (99%) and Rh. rubi (98.3%). CONCLUSIONS: A high degree of genetic diversity existed among rhizobia nodulating Caragana intermedia in Maowusu sandland. Most of the new isolates might belong to Rhizobium. SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest that the rich diversity of rhizobia might have contributed to the adaptation of the arid region. These strains could be valuable at the economic and ecosystem level.