Signatures of selection reveal candidate genes involved in production traits in Chinese crossbred buffaloes.

Identification of selection signature is important for a better understanding of genetic mechanisms that affect phenotypic differentiation in livestock. However, the genome-wide selection responses have not been investigated for the production traits of Chinese crossbred buffaloes. In this study, an SNP data set of 133 buffaloes (Chinese crossbred buffalo, n = 45; Chinese local swamp buffalo, n = 88) was collected from the Dryad Digital Repository database (https://datadryad.org/stash/). Population genetics analysis showed that these buffaloes were divided into the following 2 groups: crossbred buffalo and swamp buffalo. The crossbred group had higher genetic diversity than the swamp group. Using 3 complementary statistical methods (integrated haplotype score, cross population extended haplotype homozygosity, and composite likelihood ratio), a total of 31 candidate selection regions were identified in the Chinese crossbred population. Here, within these candidate regions, 25 genes were under the putative selection. Among them, several candidate genes were reported to be associated with production traits. In addition, we identified 13 selection regions that overlapped with bovine QTLs that were mainly involved in milk production and composition traits. These results can provide useful insights regarding the selection response for production traits of Chinese crossbred buffalo, as identified candidate genes influence production performance.

[Prognosis factors for death within 90 days of discharge in patients with acute kidney injury requiring continuous renal replacement therapy after surgery for Stanford type A acute aortic dissection].

Objective: To investigate the prognosis factors for death within 90 days after discharge in patients with acute kidney injury(AKI) treated requiring continuous renal replacement therapy(CRRT) undergoing surgery for acute Standford type A aortic dissection. Methods: The clinic data of 126 patients undergoing CRRT for postoperative AKI after acute type A aortic dissection surgery in the Center for Cardiac Intensive Care, Beijing Anzhen Hospital from July 2016 to February 2019 were analyzed retrospectively. There were 83 males and 43 females, aging (52.9±11.2) years(range: 25 to 70 years). The patients' demographic characteristics, disease-related information, perioperative data, laboratory indexes during CRRT, complications, and survival information within 90 days after discharge were recorded. Independent prognosis factors for death within 90 days of discharge were determined by Kaplan-Meier survival analysis, univariate and multifactorial Cox regression analysis. Results: Totally 57 of 126 patients(45.2%) died over the first 90 days after discharge. Kaplan-Meier survival analysis and univariate Cox regression analysis showed that there were significant differences between the non-survival and survival group including ≥65 years old, high lactate values 12 hours after CRRT, pulmonary infection, liver dysfunction, presence of permanent neurological complications, and postoperative ejection fraction(EF)<45%. Multifactorial Cox regression analysis revealed that ≥65 years old(HR=2.14, 95%CI: 1.09 to 4.21, P=0.03), high lactate values 12 hours after CRRT(HR=1.13, 95%CI: 1.06 to 1.20, P=0.01) and postoperative EF<45%(HR=2.21, 95%CI: 1.09 to 4.51, P=0.03) were independent prognosis factors for patients' death within 90 days after hospital discharge. Conclusions: ≥65 years old, high lactate values 12 hours after CRRT and postoperative EF<45% are independent prognosis factors for death within 90 days after discharge in patients undergoing CRRT for AKI after acute type A aortic dissection surgery. Proper identification and management of prognosis factors could be beneficial to improve patients' outcomes.

[Construction of artificial neural network model for predicting the efficacy of first-line FOLFOX chemotherapy for metastatic colorectal cancer].

Objective: To explore and establish an artificial neural network (ANN) model for predicting the efficacy of first-line FOLFOX chemotherapy for metastatic colorectal cancer. Methods: A set of FOLFOX chemotherapy data from a group of patients with metastatic colorectal cancer (mCRC) (GSE104645) was downloaded from the GEO database as a training set. According to the FOLFOX protocol, the efficacy was divided into two groups: the chemo-sensitive group (including complete response and partial response) and the chemo-resistant group (including stable disease and progressive disease), including 31 cases in the sensitive group and 23 in the resistant group. Then, chip data (accessible number: GSE69657) from Fujian Medical University Union Hospital were chosen as a test set. A total of 30 patients were enrolled in the study, including 13 in the sensitive group and 17 in the resistant group. The batch effect correction was performed on the expression values of the two sets of matrices using the R 3.5.1 software Combat package. The gene expression difference of sensitive and resistant group in GSE104645 was analyzed by the GEO2R platform. P<0.05 and the absolute value of log(2)FC>0.33 (FC abbreviation of fold change) were used as the threshold value to screen the drug resistance and sensitive genes of the FOLFOX regimen. An ANN was constructed using the multi-layer perceptron (MLP) to perform the FOLFOX regimen on the GSE104645 dataset. The GSE69657 expression matrix and clinical efficacy parameters were then used for retrospective verification. Receiver operating characteristic(ROC) curves were used to evaluate the test results and predictive power. Results: A total of 2, 076 differentially expressed genes in GSE104645 were selected, of which 822 genes were up-regulated and 1, 254 genes were down-regulated in the chemo-resistance group. The down-regulated genes were sensitive genes. GO analysis of the biological processes in which the differentially expressed genes were involved, revealed that they were mainly involved in the regulation of substance metabolism. A total of 39 genes were included in the final model construction. This was a neural network model with two hidden layers. The accuracy of predicting training samples and test samples was 75.7% and 76.5%, respectively, and the area under the ROC curve was 0.875. The chip data set of our department (GSE69657) was set as the test set, and the area under the ROC curve was 0.778. Conclusions: In this study, an artificial neural network model is successfully constructed to predict the efficacy of first-line FOLFOX regimen for metastatic colorectal cancer based on the microarray, and an independent external verification is also conducted. The model has good stability and well prediction efficiency. Besides, the results of this study suggest that the gene functions related to oxaliplatin resistance are mainly enriched in the regulation process of substance metabolism.

Genome-wide analysis reveals genetic diversity, linkage disequilibrium, and selection for milk production traits in Chinese buffalo breeds.

The water buffalo is an important dual-purpose livestock that is widespread throughout central and southern China. However, there has been no characterization of the population genetics of Chinese buffalo. Using an Axiom buffalo genotyping array (Thermo Fisher Scientific, Wilmington, DE), we analyzed the genetic diversity, linkage disequilibrium pattern, and signature of selection in 176 Chinese buffaloes from 13 breeds. A total of 35,547 SNP passed quality control and were used for further analyses. Population genetic analysis revealed a clear separation between swamp and river types. Ten Chinese indigenous breeds were clustered into the swamp group, the Murrah and Nili-Ravi breeds were clustered into the river group, and the crossbred breed was closer to the river group. Genetic diversity analysis showed that the swamp group had a lower average expected heterozygosity. Linkage disequilibrium decay distance was much shorter in the swamp group compared with the river group, with an average square of correlation coefficient value of 0.2 of approximately 50 kb. Analysis of runs of homozygosity indicated extensive remote and recent inbreeding within swamp and river groups, respectively. Moreover, one genomic region under selection was detected between the river and swamp groups. Our findings contribute to our understanding of the characterization of population genetics in Chinese buffaloes, which in turn may be used in buffalo breeding programs.

Suberoylanilide hydroxamic acid, a novel histone deacetylase inhibitor, improves the development and acetylation level of miniature porcine handmade cloning embryos.

Histone deacetylase inhibitors (HDACis) can change the histone acetylation and significantly enhance the developmental competence of the pre-implantation SCNT embryo. To select a proper histone deacetylase inhibitor to improve the success rate and potentially developmental ability of handmade cloning (HMC) embryos of miniature porcine, we compared the effect of two histone deacetylase inhibitors (SAHA vs. VPA) on HMC embryo development, their histone acetylation level and the expression level of relevant genes. The blastocyst rate and number of blastocyst cells of HMC embryos treated with SAHA (SAHA-HMC) or VPA (VPA-HMC) were significantly higher than those of control (Control-HMC), respectively, but there were no significant difference between SAHA-HMC and VPA-HMC groups. In addition, the acetylation level (AcH4K8) of Control-HMC and VPA-HMC embryos at the blastocyst stage, respectively, was significantly lower than that of in vitro fertilized (IVF) and SAHA-HMC embryos. However, the acetylation H4K8 of the blastocysts had no significant difference between SAHA-HMC and the IVF groups. The SAHA-HMC blastocysts indicated comparative expression levels of Oct4 and HDAC1 (histone deacetyltransferase gene) with those of IVF blastocysts. In contrast, the expression levels of Oct4 were lower and those of HDAC1 were higher in the VPA-HMC and Control-HMC blastocysts, respectively, compared to those of the IVF blastocysts. Our results demonstrated that the HMC embryos treated by SAHA could promote the pre-implantation development and increase the levels of histone H4K8 acetylation and the expression of the OCT4 gene, yet decrease the expression of the HDAC1 gene to the comparable level of the IVF embryos. Our results proved that SAHA may be a better histone deacetylase inhibitor for porcine HMC compared to VPA, and furthermore, it may indicate that SAHA can effectively correct the abnormal histone acetylation during the HMC embryo development and subsequently improve the full-term developmental potential of the HMC embryos after embryo transplantation.

[Determination of iodine content in the left ventricular myocardium of healthy subjects using dual-source dual-energy CT myocardial first perfusion imaging: a preliminary study].

Objective: To analyze the normal value of the iodine content in the left ventricular myocardium of healthy subjects and to observe if there is a segmental differences on iodine distribution by using the second generation dual-source dual-energy computed tomography myocardial first perfusion imaging. Methods: In this retrospective study, 42 healthy subjects, who admitted to our department between January to June 2016, with normal second generation dual-source dual-energy computed tomography and coronary CT angioghphy (CTA), electrocardiogram (ECG) results, normal cardiac, hepatic, renal function, normal myocardial enzymes results were enrolled, data from 38 out of 42 subjects with satisfactory image quality were analyzed using Siemens Dual Energy-Heart PBV image processing software.In accordance with the standards of the American Heart Association myocardial 17 fractionation method, content of iodine was measured at different segmental left ventricular myocardium and aorta (left coronary artery from the opening level). The standardized containing iodine value (nIC) was calculated. Results: The iodine content of left ventricular myocardium in normal subjects was 3.1-7.8 mg/ml.The nIC of myocardium from 1st to 17th segments was 0.28±0.06, 0.31±0.07, 0.30±0.07, 0.30±0.04, 0.28±0.04, 0.29±0.05, 0.29±0.01, 0.30±0.07, 0.31±0.07, 0.27±0.06, 0.28±0.08, 0.28±0.07, 0.29±0.08, 0.31±0.07, 0.27±0.06, 0.29±0.06 and 0.21±0.07, respectively.The nIC of the 17th segment was the lowest and was significantly lower than in other segments (all P<0.05), the nIC was similar among the rest 16 segments (all P>0.05). Conclusion: The normal iodine content range in left ventricle myocardium is 3.1-7.8 mg/ml, and the lowest iodine content is detected in the apex and which is significantly lower than the other left ventricular segments.

Selecting stage ypT0-1N0 for locally advanced rectal cancer following preoperative chemoradiotherapy: implications for potential candidates of organ-sparing management.

AIM: Local excision or a wait-and-see policy may offer the possibility of organ preservation for locally advanced rectal cancer (LARC) after preoperative chemoradiotherapy (CRT). Identifying associated factors of good responders (GR) with stage ypT0-1N0 would probably influence the selection of potential candidates who were theoretically eligible for organ-sparing management. This study was to establish a scoring system to select stage ypT0-1N0 for LARC following preoperative CRT. METHOD: Between 2009 and 2014, 262 patients with middle and low LARC were treated with CRT and radical surgery. Clinicopathological data which were found to be significantly associated with GR were incorporated into a scoring system. RESULTS: Fifty-seven (21.8%) patients were GR with stage ypT0-1N0 in the operative specimen. Multivariate analyses indicated that a low level of pretreatment carcinoembryonic antigen (CEA) and post-treatment CEA <2.55 ng/ml (P = 0.008 and P = 0.009 respectively) and long-axis diameter of residual tumours (P = 0.006) were independently associated with stage ypT0-1N0. The three factors were incorporated into a scoring system. Using receiver operating characteristic curve analysis, we determined a cutoff value of -0.3 for scores, at which the system's sensitivity was 71.9% and specificity 73.1%. When applied to testing samples, the sensitivity was 74.1% and specificity 76.2%. CONCLUSION: We demonstrated that low levels of pretreatment and post-treatment CEA and the long-axis diameter of residual tumours were associated with stage ypT0-1N0 for LARC after CRT. Therefore, the three-factor scoring system may be used to select potential candidates for organ-sparing management.

[Effects of neoadjuvant chemoradiotherapy on the rates of sphincter preserving surgery in lower rectal cancer and analysis of their prognostic factors].

Objectives: To identify independent factors of sphincter preserving surgery, and to evaluated whether preoperative chemoradiotherapy (CRT) improves the sphincter preservation rate for lower rectal cancers. Methods: A total of 541 consecutive patients who underwent curative surgery for locally advanced rectal cancer (cT3-4Nx or cTxN+ ) within 6 cm of the anal verge with or without neoadjuvant CRT in Department of Colorectal Surgery, Union Hospital, Fujian Medical University between September 2000 and September 2013 were reviewed. Of these, 333 patients underwent surgery alone (Non-CRT group) and 208 patients also received preoperative chemoradiotherapy (CRT group). Clinical data were retrospectively reviewed to determine the factors influencing sphincter preservation, and to evaluate sphincter preservation rate according to tumor height over 1-cm intervals. The categorical variables were compared using χ2 test and Fisher exact test. Continuous variables were compared using t test. Logistic regression was used to identify factors influencing sphincter preservation. A receiver operating characteristic (ROC) curve was constructed, and Youden's index was calculated to evaluate the predictive abilities of factors. Results: Multivariate analysis indicated that the independent factors influencing sphincter preservation were tumor height (OR=5.867, 95% CI: 4.155 to 8.285, P=0.000), pathological T stage (OR=0.688, 95% CI: 0.462 to 1.025, P=0.066), CRT (OR=2.088, 95% CI: 0.971 to 4.492, P=0.060) and histopathological type (OR=0.288, 95% CI: 0.136 to 0.611, P=0.001). The results of ROC analysis showed that the cut-off points for factors affecting sphincter preservation were as follows: (1) tumor height prior to CRT higher than 4.5 cm, (2) not mucinous or signet ring adenocarcinoma, (3) pathological T stage higher than T3, (4) had received preoperative CRT. In an analysis according to tumor height, the sphincter preservation rate was higher in CRT group only when tumor was located in 3.0 to 3.9 cm and 4.0 to 4.9 cm from the annal verge (3.0 to 3.9 cm, 59.4% vs. 2.8%, χ2=26.138, P=0.000; 4.0 to 4.9 cm, 76.9% vs. 37.9%, χ2=10.563, P=0.001). Conclusions: There is a large increased rate of sphincter preservation when patients meet the following conditions: (1) tumor height prior to CRT higher than 4.5 cm, (2) not mucinous or signet ring adenocarcinoma, (3)pathological T stage higher than T3, (4) had received preoperative CRT. Only when tumors are between 3 and 5 cm from the anal verge, CRT could increase the rate of anal sphincter preservation.

[Prognostic factors of postoperative incisional surgical site infections for colorectal cancer].

Objective: To explore the prognostic factors of postoperative incisional surgical site infections (I-SSI) for colorectal cancer. Methods: Clinical data of 2 385 colorectal cancer patients undergoing resection by the same surgical team in Department of Colon and Rectum Surgery, Fujian Medical University Union Hospital from January 2000 to February 2014 was analyzed retrospectively. There were 1 421 male and 964 female patients, with a mean age of (59±13) years. Univariate analysis and multivariate Logistic regression analysis were performed for independent prognostic factors of I-SSI. Results: The I-SSI occurred in 77 patients (3.23%). The results of univariate analysis showed that there were statistical differences in body mass index (t=-3.356), operation time (t=-3.609), length of incision (t=-5.492), radical operation (χ2=8.963), laparoscopic surgery (χ2=25.884), combined evisceration (χ2=6.349) and intraoperative blood infusion (χ2=4.176) between two groups (all P<0.05) . The results of multivariate Logistic regression analysis showed that independent prognostic factors of I-SSI were identified to be body mass index (OR=1.087, 95%CI: 1.023 to 1.155, P=0.007), operation time (OR=1.007, 95%CI: 1.002 to 1.012, P=0.006), preoperative chemoradiotherapy (OR=2.434, 95%CI: 1.099 to 5.393, P=0.028) and combined evisceration (OR=2.596, 95%CI: 1.060 to 6.357, P=0.037). The independent protective prognostic factor of I-SSI was identified to be the laparoscopic surgery (OR=0.386, 95%CI: 0.170 to 0.877, P=0.023). Conclusions: Body mass index, operation time, preoperative chemoradiotherapy and combined evisceration are identified to be independent prognostic factors for I-SSI. High-risk patients should receive individualized perioperative intervention. Nevertheless, the laparoscopic surgery can decrease the incidence of I-SSI.

[Analysis on epidemiological characteristics of central obesity/pre-central obesity and influencing factors in Jilin Province].

Objective: To understand the epidemiological characteristics of central obesity and pre-central obesity and influencing factors in residents in Jilin Province, and provide reference for the prevention and control of central obesity and pre-central obesity. Methods: Based on the results of early screening and comprehensive intervention program in high-risk groups of cardiovascular disease in Jilin dyring 2017-2018, a total of 11 903 participants aged 35-75 years in 6 project areas in Jilin were included as the survey subjects for physical examination, laboratory test and questionnaire survey. The prevalence of central obesity and pre-central obesity in populations with different characteristic and health status were analyzed by χ2 test, trend χ2 test, F-test. Multivariate logistic regression model was used for influencing factor analysis. Results: The central obesity rate was 33.35% (3 970/11 903), the standardized rate was 31.73%, the pre-central obesity rate was 28.79% (3 427/11 903), the standardized rate was 28.86%. Multifactor analysis results showed that being rural resident (OR=1.99, 95%CI: 1.78-2.23), being woman (OR=1.76, 95%CI: 1.57-1.97), 65-75 years old (OR=1.21, 95%CI: 1.03-1.45), senior high school and technical secondary school education level (OR=1.38, 95%CI: 1.17-1.63), annual family income >100 000 yuan (OR=1.65, 95%CI: 1.20-2.26), overweight (OR=9.27, 95%CI: 8.26-10.41), obesity (OR=82.82, 95%CI: 62.63-109.52), normal high blood pressure (OR=1.49, 95%CI: 1.27-1.74), hypertension (OR=1.70, 95%CI: 1.42-2.04), diabetes (OR=2.30, 95%CI: 1.94-2.73), dyslipidemia (OR=1.33, 95%CI: 1.18-1.50) were positively related to the risk for central obesity and pre central obesity. Conclusions: The prevalence rates of central obesity and pre central obesity in residents in Jilin were at high levels, being rural resident, being woman, older age, senior high school and technical secondary school education level, high income, overweight and obesity, normal high blood pressure and hypertension, diabetes, dyslipidemia were risk factors for central obesity and pre-central obesity in Jilin.

Microscopic Coexistence of Superconductivity and Antiferromagnetism in Underdoped Ba(Fe(1-x)Ru(x))2As2.

We use (75)As nuclear magnetic resonance to investigate the local electronic properties of Ba(Fe(1-x)Ru(x))(2)As(2) (x = 0.23). We find two phase transitions: to antiferromagnetism at T(N) ≈ 60 K and to superconductivity at T(C) ≈ 15 K. Below T(N), our data show that the system is fully magnetic, with a commensurate antiferromagnetic structure and a moment of 0.4µ(B)/Fe. The spin-lattice relaxation rate 1/(75)T(1) is large in the magnetic state, indicating a high density of itinerant electrons induced by Ru doping. On cooling below T(C), 1/(75)T(1) on the magnetic sites falls sharply, providing unambiguous evidence for the microscopic coexistence of antiferromagnetism and superconductivity.

[Strengthening the Reporting of Pharmacogenetic Studies (STROPS) guideline].

Pharmacogenetic studies are designed to investigate the associations between genetic variation and treatment response for a particular drug in terms of both efficacy and adverse events and have high sample size requirements. To improve the quality of pharmacogenetic studies and facilitate the Meta-analyses to investigate statistically significant associations, Strengthening the Reporting of Pharmacogenetic Studies (STROPS) guideline was developed in 2020 based on the Strengthening the Reporting of Genetic Association Studies (STREGA) statement. The objective of this article is to present a brief introduction to the STROPS guideline and an interpretation of the key points in some items with examples for the better understanding and application.

[Rectum-preserving surgery after consolidation neoadjuvant therapy or totally neoadjuvant therapy for low rectal cancer: a preliminary report].

Objective: To investigate the feasibility and safety of sphincter-preserving surgery after neoadjuvant chemoradiotherapy (nCRT) with consolidation chemotherapy in the interval period or total neoadjuvant therapy (TNT) for low rectal cancer. Methods: A descriptive case series study was carried out. Clinical data of patients with locally advanced low rectal cancer (LALRC) who achieved complete clinical response (cCR) or nearly cCR (near-cCR) after nCRT at the Department of Colorectal Surgery of Fujian Medical University Union Hospital from May 2015 to February 2019 were retrospectively analyzed. Case inclusion criteria: (1) Low rectal adenocarcinoma within 6 cm from the anal verge. (2) After nCRT, tumor presented markedly regression as mucosal nodule or abnormalities, superficial ulcer, scar or a mucosal erythema (< 2 cm); no regional lymph node metastasis or distant metastasis was found in rectal ultrasonography, pelvic MRI and PET-CT; MRI showed obvious fibrosis in the original tumor site; and post-treatment CEA was normal. (3) The patient and the family members adhered to receive the transanal full-thickness local excision with informed consent. (4) When the residual lesions were difficult to detect after nCRT, patients received the watch and wait (W&W) strategy. Exclusion criteria: (1) Before nCRT, pathological results showed poorly differentiated or signet-ring cell carcinoma; lateral lymph node metastasis was suspected. (2) When the residual lesion size was more than 3 cm after nCRT, it was difficult to perform local excision. The consolidation nCRT group received 3-4 cycles of CAPOX regimen (oxaliplatin and capecitabine) or six cycles of mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) combined with the long-course radiotherapy (intensity-modulated radiation therapy with a total dose of 50.4Gy). Patients with concurrent chemotherapy more than or equal to five cycles of CAPOX or eight cycles of mFOLFOX6 were defined as total neoadjuvant therapy (TNT) group. Local resection was recommended for patients who were near-cCR according to modified MSKCC criteria 8-33 weeks after the end of radiotherapy. Patients with a near-cCR, who were judged as ycN0 according to PET-CT and MRI and were ypT0 after local excision, could enter the W&W strategy. Patients with pathologic stage more advanced than ypT1, and those with positive resection margin, or lymphovascular invasion were recommended for salvage radical surgery after local excision. The ypT1 patients with a negative resection margin and without lymphovascular invasion might receive the W&W management carefully if they refused radicalsurgery to sacrifice the sphincter for low rectal cancer. Results: Of 32 patients, 14 were males and 18 were females with the average age of 59 years old. Twenty-three patients underwent consolidation nCRT, and 9 received TNT. The first evaluation after treatments showed 19 cases with cCR and 13 with near-cCR. Twenty-nine patients received local excision while 3 patients with undetectable lesions received W&W policy. Four cases (12.5%) underwent salvage radical surgery with abdominoperineal resection. After local excision, 3 cases underwent salvage radical surgery immediately, and the final pathologic result was ypT3N0, ypT2N0, and ypT2N0 respectively, of whom 2 cases were in the group of consolidation CRT and 1 was in the TNT group. Of these 3 cases, 1 case with an initial cT3 stage showed a pathologic stage of ypT1 and a negative circumferential resection margin after consolidation nCRT and local excision, however, the final pathologic stage was ypT3 with fragmented tumor deposits in the mesorectum after the salvage radical surgery. Meanwhile 1 patient in the TNT group receiving W&W suffered from intraluminal regrowth after 7.4 months follow-up and underwent salvage abdominoperineal resection. One patient in the consolidation nCRT group died of stroke 42.5 months after local resection. Another patient in the TNT group had cerebral metastasis 10 months after the W&W policy, but no local recurrence was found in the pelvic cavity, then received resection of the metastatic tumors. The average follow-up for all the patients was 23 (5-51) months. The cumulative local regrowth rate was 5.0%. The overall survival rate was 85.7%, and the sphincter-preservation rate was increased from 25.0% (28/32) in the original plan to 87.5% (28/32) actually. The 3-year disease-free survival rate was 89.7%. The 3-year organ-preserving survival rate was 85.7%, and the 3-year stoma-free survival rate was 82.5%. At present, 31 patients still survived. Conclusions: After nCRT with consolidation chemotherapy or TNT for low rectal cancer, patients with cCR, ycN0 according to PET-CT and MRI, and ypT0 after local excision, can consider the W&W strategy. Strict patient selection with a near-cCR for local resection and sphincter-preserving strategy can reduce the local regrowth of cancer, and the short-term outcomes are satisfactory.

[Identification of gene biomarkers to predict responses to neoadjuvant chemoradiotherapy in patients with rectal cancer and pathways enrichment analysis].

Objective: To screen out the potential gene biomarkers to predict responses to neoadjuvant chemoradiotherapy (CRT) in patients with rectal cancer and to explore the main downstream pathways of resistance. Methods: The gene expression profiles (GSE35452) of locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy from 46 specimens (24 responders, TRG 0/1, and 22 non-responders, TRG 2/3) were downloaded from the GEO database. The differentially expressed genes were identified to screen out the potential biomarkers by use of the GCBI platform. GO and KEGG pathways enrichment analysis were performed to integrate enrichment results of differentially expressed genes. Signal-signal interaction network was constructed and analyzed to screen out potential main downstream pathways. Results: A total of 1079 differentially expressed genes were screened, including 657 up-regulated and 422 down-regulated ones. Among these genes, REG4 had the maximum fold change value of -6.029 491. In GO term, these differentially expressed genes were mainly enriched in molecule metabolic process, cell cycle, DNA-dependent transcription, signal transduction and apoptotic process. The KEGG pathways enrichment analysis showed that the differentially expressed genes were enriched in 65 KEGG pathways, including metabolic pathways, cell cycle and metabolism pathways. Signal-signal interaction network analysis showed that MAPK signaling pathway and cell cycle pathway might play a determinant role in the development of neoadjuvant chemoradiotherapy resistance. Further analysis showed that CDKN1B, CDKN2A, RBL1, TFDP1, CCND2, CCNE2, CDC6 and CDK6 in cell cycle might induce chemoradiotherapy resistance by blocking G1/S phase cell cycle arrest, decreasing the apoptosis of tumor cells and increasing S phase ratio of chemoradiotherapy resistance. Conclusion: G1/S phase cell cycle arrest blocking plays an important role in the development of chemoradiotherapy resistance in patients with rectal cancer. Moreover, the key genes, such as REG4, may be useful in predicting responses to neoadjuvant chemoradiotherapy.

Associations between polymorphisms of the gene and milk production traits in water buffaloes.

Signal transducer and activator of transcription 1 () is an important regulator of mammary gland differentiation and cell survival that has been regarded as a candidate gene affecting milk production traits in mammals. Therefore, this study was conducted to evaluate significant associations between SNP of the gene and milk production traits in buffaloes. Here, 18 SNP were identified in the buffalo gene, including 15 intronic mutations and 3 exon mutations. All the identified SNP were then genotyped using matrix-assisted laser desorption/ionization time of flight mass spectrometry methods from 192 buffaloes. All the SNP were in Hardy-Weinberg equilibrium, and 2 haplotype blocks were successfully constructed based on these SNP data, which formed 5 and 3 major haplotypes in the population (>5%), respectively. The results of association analysis showed that only SNP13 located in exon 10 was significantly associated with the milk production traits in the population ( < 0.05). Single nucleotide polymorphism 2, SNP5, SNP8, and SNP9 were associated with protein percentage, and SNP4 and SNP10 were associated with 305-d milk yield ( < 0.05). Our results provide evidence that polymorphisms of the buffalo gene are associated with milk production traits and can be used as a candidate gene for marker-assisted selection in buffalo breeding.

TGF alpha and v-fos cooperation in transgenic mouse epidermis induces aberrant keratinocyte differentiation and stable, autonomous papillomas.

To assess the synergistic effect of growth and transcription factor deregulation on carcinogenesis in vivo, mating experiments were performed between transgenic mice expressing human TGF alpha or v-fos exclusively in the epidermis by means of a human keratin K1-based targeting vector (HK1.fos, HK1.TGF alpha and HK1.fos/alpha). While HK1.TGF alpha mice exhibited mild epidermal hyperplasia resulting in a wrinkled appearance, this hyperplasia was significantly increased in HK1.fos/alpha mice which also exhibited a novel opalescent and peeling skin phenotype. HK1.fos/alpha keratinocyte differentiation was considerably deregulated with cornified cells appearing in the granular layer, granular cells in the spinous layer and a sixfold increase in BrdU labeling over normal. In addition, hyperplastic HK1.fos/alpha epidermis exhibited aberrant loricrin, filaggrin and novel K13 expression associated with v-fos expression. Unlike adult HK1.TGF alpha controls, hyperplasia persisted in HK1.fos/alpha adults which also rapidly developed autonomous squamous cell papillomas. These results demonstrate that v-fos and TGF alpha over-expression can cooperate to reprogram keratinocyte differentiation and elicit the early stages of neoplasia. Moreover, TGF alpha over-expression appeared to play an early, initiating role in HK1.fos/alpha papilloma etiology, and a promotion role in the accelerated appearance of v-fos wound-associated preneoplastic phenotypes. However, the stable persistence of HK1.fos/alpha papillomas for up to 12 months, suggests that additional events are required for malignant conversion.

Vascular alpha-2 adrenoceptor function is decreased in rats with congestive heart failure.

OBJECTIVE: Vascular alpha-2 adrenoceptor function of rats with congestive heart failure (CHF) was characterized in both in vivo and in vitro experiments. METHODS: CHF was induced in Sprague-Dawley rats by coronary artery ligation. Sham-operated rats served as normal controls. Postjunctional alpha-2 adrenergic responsiveness was assessed in vivo using the pithed rat model and in vitro in organ bath. Vascular alpha-2 adrenoceptor density was studied by receptor binding assay. RESULTS: Four to 6 weeks after this surgical procedure, plasma catecholamines were markedly increased in CHF rats. In vivo vascular responses to alpha-2 adrenoceptor agonists BHT933 and clonidine were significantly decreased in CHF rats (P < 0.001). Clonidine elicited dose-dependent responses in endothelium intact mesenteric arteries in both CHF and sham-operated rats. The dose-response curve in CHF was shifted to the right with a pD2 value of 5.5 +/- 0.2 compared with control rats 6.2 +/- 0.2 (P < 0.05). The response to clonidine was selectively blocked by an alpha-2 adrenergic antagonist rauwolscine in both groups. Endothelium denuded arteries showed an enhanced response to clonidine in both CHF and control rats. However, the response to clonidine is still decreased in CHF compared to sham-operated rats (P < 0.05). Alpha-2 adrenoreceptor density, as determined by [3H]yohimbine binding in membrane preparations from mesenteric arteries was decreased in CHF compared to sham-operated rats (Bmax 43 +/- 6 vs. 104 +/- 20 fmol/mg protein, P < 0.05). CONCLUSIONS: Vascular alpha-2 adrenoceptor function is decreased in rats with CHF.

Distribution of hydroxynonenal-modified proteins in the kainate-lesioned rat hippocampus: evidence that hydroxynonenal formation precedes neuronal cell death.

Decomposition of lipid peroxides gives rise to a wide range of aldehydes. 4-Hydroxyalkenals and in particular 4-hydroxynonenal (HNE) are often the most toxic products. Frequently, it is unclear at which stage in the tissue injury process HNE is formed, i.e., is it a late stage or an early stage in which HNE contributes to subsequent cell death? The present study was carried out using an antibody to HNE-modified proteins to elucidate the time course and distribution of HNE in the lesioned hippocampus after kainate injections. HNE was absent from normal neurons, but dense staining to HNE was observed in degenerating neurons after kainate injection. The increase in HNE staining occurred as early as 1 d postinjection, at a time when there was no histological evidence of cell death. HNE immunoreactivity was observed in the degenerating CA1 and CA3 fields at 3 d and 1 week postinjection, but was confined to a cluster of neurons at the edge of the degenerating CA fields, at 2 and 3 weeks postinjection. These observations suggest that HNE formation is an early event after this tissue injury, and may contribute to later cell death.

Differential effects of calcium-dependent and calcium-independent phospholipase A(2) inhibitors on kainate-induced neuronal injury in rat hippocampal slices.

Brain tissue contains multiple forms of intracellular phospholipase A(2) (PLA(2)) activity that differ from each other in many ways including their response to specific inhibitors. The systemic administration of kainic acid to rats produces a marked increase in cPLA(2) activity in neurons and astrocytes. This is associated with increased lipid peroxidation as evidenced by accumulation of 4-hydroxynonenal (4-HNE) modified proteins. The present study describes the effect of specific inhibitors of Ca(2+)-dependent or Ca(2+)-independent PLA(2) on kainite-induced excitotoxic injury in rat hippocampal slices. Specific inhibitors of Ca(2+)-dependent PLA(2) prevented the decrease of a neuronal marker, GluR1, and increase in cPLA(2) and 4-HNE immunoreactivities in slices treated with kainate. This shows that cPLA(2) plays an important role in kainite-induced neurotoxicity and that cPLA(2) inhibitors can be used to protect hippocampal slices from damage induced by kainate.

Cardiovascular effects of Buthus martensii (Karsch) scorpion venom.

Buthus martensii (Karsch) (BMK) scorpion envenomation is a common medical problem in China and BMK scorpion has been widely used in traditional Chinese medicine. However, the cardiovascular effects of this venom have not been systematically investigated. In the present study, i.v. BMK venom injection significantly increased the blood pressure in conscious rats in a concentration-dependent manner (ED50 = 59 +/- 12 micrograms/kg). The increase in blood pressure occurred within 1 min of injection of the venom and was sustained for more than 50 min. Heart rate was not changed by the venom in conscious rats. In vitro studies with BMK venom revealed the increase in the force of contraction, without modification of the contraction frequency (within 20 min) of isolated atrial strips. Contractions of isolated arterial strips from aorta, renal and vertebral arteries were also enhanced by BMK venom with a time lag of 8 min between the application of the venom and the initiation of the contraction. Furthermore, BMK venom-induced rises in blood pressure in vivo and increased contraction of isolated vessel strips were inhibited by prazosin and tolazoline, respectively, two alpha 1-adrenergic antagonists. BMK venom alone did not alter intracellular calcium concentrations, [Ca2+]i, in cultured vascular smooth muscle cells and endothelial cells. However, BMK venom significantly increased the metabolism of InsP3 in dispersed cardiac myocytes, indicating a direct effect on cardiac myocytes. These results demonstrate the significant cardiovascular effects of BMK venom, which may be mediated by an alteration in InsP3 in cardiac myocytes but not by [Ca2+]i in vascular smooth muscle cells.