[A multicenter study on childhood Hodgkin lymphoma treated with HL-2013 regimen in China].

Objective: To evaluate the efficacy of the Hodgkin lymphoma (HL)-2013 regimen in the treatment of children with HL, and to investigate the prognostic factors of childhood HL. Methods: Clinical data of 145 children (aged ≤18 years) with newly diagnosed HL, treated with HL-2013 regimen in 8 tertiary referral centers for childhood cancer from August 2011 to April 2021 were analyzed retrospectively. All the diagnosis were confirmed by histopathological morphology and immunohistochemical examination. The clinical characteristics and treatment outcomes were summarized, and the patients were divided into different groups according to clinical characteristics. Kaplan-Meier method was used for survival analysis, and the comparison of survival rates between groups was performed with Log-rank test. Results: Of the 145 cases, there were 115 males and 30 females, the age at diagnosis was 7.9 (5.8, 10.6) years. Cervical lymph node enlargement (114 cases, 78.6%) was the common symptom of the disease, and 57 patients (39.3%) were accompanied by large masses. The most common pathological classification was mixed cell type (93 cases, 64.1%). According to the Ann Arbor staging system, there were 9 cases of stage Ⅰ, 62 cases of stage Ⅱ, 45 cases of stage Ⅲ, 29 cases of stage Ⅳ. According to the risk stratification: there were 14 cases of low-risk group, 76 cases of medium-risk group and 55 cases of high-risk group. Of all patients, 68 cases (46.9%) achieved an early complete remission (CR) after 2 courses of chemotherapy, and the CR rate was 93.8% (136/145) after first-line treatment. Disease recurrence or progression occurred in 22 cases (15.2%). Of all patients, 125 cases survived, 6 cases died and 14 cases were lost to follow-up. Among the survived cases, 123 cases were continuously at CR state,and the follow-up time was 55 (40, 76) months. The 5-year overall survival (OS) and event free survival (EFS) rates were (95.3±1.9)% and (84.2±3.0)% for the entire group, respectively. 5-year OS and EFS rates for patients with stage Ⅲ-Ⅳ were both lower than those for patients with stage Ⅰ-Ⅱ (χ2=6.28 and 7.58, both P<0.05), the 5-year OS and EFS rates for patients in high-risk group were both lower than those for patients in low-risk and medium-risk group (χ2=10.93, 7.79, both P<0.05). The 5-year OS rates for the patient with early CR and without early CR were 100.0% and (90.9±3.6)% (χ2=5.77, P=0.016). EFS rates for the patient with early CR (68 cases) and without early CR (77 cases) were (93.8±3.0)% and (75.8±5.0)% (χ2=8.78, P=0.003). Conclusions: HL-2013 regimen is significantly effective in the treatment of pediatric HL. However, the patients in high-risk group and those without early CR are prone to disease recurrence or progression. Stage Ⅲ-Ⅳ and without early CR were associated with worse prognosis.

[Clinical phenotype and genotype of Gaucher disease in 14 children].

Objective: To analyze the clinical and genetical characteristics of children with Gaucher disease and to explore the relationship between genotype and phenotype. Methods: In this retrospective study, the clinical data of 14 children with Gaucher disease diagnosed in Children's Hospital of Nanjing Medical University from August 2016 to October 2021 were analyzed. Their general conditions, clinical manifestations, laboratory tests and gene variations were collected, followed by the analysis of the clinical phenotypes and genotypes. Results: Among 14 children diagnosed with Gaucher disease, 9 were males and 5 were females, with the age of diagnosis ranging from 0.7 to 15.8 years. There were 10 patients with type 1 Gaucher disease, 2 patients with type 2, and 2 patients with type 3. The most common clinical manifestations were splenomegaly, thrombocytopenia (14 cases), hepatomegaly (8 cases) and anemia (8 cases). There were 6 patients with growth retardation, and 5 patients lag in height compared with their peers. Bone abnormalities were revealed by magnetic resonance imaging in 7 type 1 Gaucher disease patients, but only 1 patient experienced bone pain. Patients with type 2 and type 3 Gaucher disease also presented with convulsions, nystagmus and hearing loss. Gaucher cells were found in bone marrow smears in 12 patients. The glucocerebrosidase gene variations identified in 13 patients were heterozygous and in 1 type 1 patient was homozygous of L483P. L483P variation accounted for 33%(10/30) of the variation alleles, followed by V414L, D448H and R159W. The variation alleles were L483P and L422R, F252I and L483P in 2 children with severe neurological manifestations of Gaucher disease. A novel variation c.22A>G was detected. Conclusions: Splenomegaly and thrombocytopenia are the main clinical presentations of Gaucher disease in children and bone lesions revealed by radiologic imaging appear prior to the occurrence of bone diseases, type 2 and type 3 Gaucher disease also present growth retardation and neurological manifestation. The most frequent variant allele is L483P, which are detected in all 3 subtypes of Gaucher disease. The L422R, F252I gene variants correlated with the neuronopathic phenotype.

[Application of ultra-short echo time-T2* component analysis technology in monitoring morphological and biochemical changes of achilles tendon in amateur marathon athletes].

Objective: To explore the value of ultra-short echo time (UTE)-T2* component analysis techniques in dynamic monitoring the morphological and biochemical changes in amateur marathon athletes' achilles tendon before and after the marathon. Methods: Twenty-nine amateur marathon runners were recruited between October 2020 and March 2021 in Zhuhai City, Guangdong Province, including 25 males and 4 females, aged from 24 to 50 (40±6) years old. All volunteers underwent bilateral achilles tendon MRI examination 1 week before the marathon, 48 hours after the race, and 1 month after the race. The shape and signal of the achilles tendon were evaluated by routine T1-weighted, proton density weighted with fat saturation sequence and different echo time (TE) UTE sequence, and the changes of achilles tendon after running was quantitatively analyzed by UTE-T2* sequence. The values of single-component analysis (T2*M), short T2* components (T2*S), and long T2* components (T2*L) and Fraction values were obtained using UTE-T2* sequence. The value of the whole achilles tendon was measured on the sagittal images of achilles tendon, and the Achilles tendon was equally divided into three subregions [muscle-tendon junction (MTJ), middle (MID), and insertion (INS)]. The region of interest was delineated by two radiologists independently. The intra-group correlation coefficient (ICC) was used to evaluate the consistency of the data measured by two radiologists. Nonparametric Friedman M test was used to compare the differences of T2*M, T2*S, T2*L and Fraction values in different time points and different subregions. Wilcoxon rank-sum test was used to compare the difference between 48 h post-race and pre-race T2*S values (ΔT2*S) of different distance, different running posture, different pace and different amount of training, in which ΔT2*S equals the T2*S value of 48 h post-race minus the T2*S value of pre-race. Results: On the sequence of short TE (TE≤0.6 ms), achilles tendinopathy can manifest as scattered punctate hypointensity in areas of high signal intensity. The two radiologists showed a good consistency in measuring the T2*M, T2*S, T2*L and Fraction values of the achilles tendon, and the ICC values ​​were 0.96, 0.94, 0.83 and 0.94, respectively. The T2*s values was significantly higher in the whole Achilles tendon, MTJ and MID segment at 48 h post-exercise compared to pre-exercise, and decreased after 1 month of exercise, [0.49 (0.45, 0.59) vs 0.54 (0.49, 0.59) vs 0.53 (0.49, 0.57), 0.48 (0.44, 0.54) vs 0.53 (0.47, 0.58) vs 0.50 (0.46, 0.57), 0.48 (0.43, 0.58) vs 0.54 (0.47, 0.59) vs 0.52 (0.46, 0.57); respectively, all P<0.05]. The changes in T2*M, T2*L and Fraction values are not statistically significant (all P>0.05). In different running gestures, the ΔT2*S of achilles tendon who using the postures of front-middle feet is higher than that using the postures of back feet (0.03(-0.05, 0.07) vs -0.03(-0.17, 0.11), P=0.001). Conclusion: The Bi-component analysis of UTE-T2* technology is superior to single component analysis in monitoring the dynamic changes of achilles tendon before and after exercise, and T2*S is a more sensitive sequence to evaluate the subtle changes in the chemical composition of achilles tendon.

[Multicenter clinical study on the diagnosis and treatment of childhood renal tumor].

Objective: To summarize the effect of Chinese Children's Cancer Group (CCCG) Wilms tumor (WT)-2015 protocol. Methods: This was a prospective study. CCCG-WT-2015 protocol was revised on the basis of the CCCG-WT-2009 protocol. Clinical data of 288 children diagnosed with newly diagnosed kidney neoplasms in fourteen pediatric centers between September 2015 to December 2018 were summarized. The age of onset, distribution of pathological subtypes, staging, curative effect and prognostic factors of these children were analyzed. Kaplan-Meier method was used for survival curve and Log-Rank method was used for univariate analysis. Results: Among 288 cases with kidney neoplasms, there were 261 cases of WT, including 254 cases (97.3%) with favorable histology (FH) WT and 7 cases (2.7%) with unfavorable histology WT (UFHWT). The 3 year events free survival (EFS) rate for FHWT and UFHWT were (88.9±2.1)% and (80.0±17.9)%, which were better than that in WT-2009 (81.2% and 71.7%). In the 96 cases of stage Ⅲ/Ⅳ FHWT with indications for radiotherapy, 76 cases received radiation, another 20 cases received M protocol chemotherapy (cyclophosphamide, etoposide, gentamycin, vincristine and adriamycin) instead of radiation. The 3 year EFS rate for these two groups were (84.7±4.3)% and (84.7±8.1)%(χ2=0.015, P=0.902). There were 22 renal clear cell sarcoma and 5 malignant rhabdoid tumor, 3 year EFS rate of them was (94.4±5.4)% and (20.0±17.9)%. Univariate analysis was performed for age, gender, pathological type, stage, whether rupture occurred during operation, whether complete remission (CR) occurred at the end of treatment and radiotherapy. Pathological types (χ2=44.329,P<0.01) and failure to achieve CR at the end of the treatment (χ2=49.459,P<0.01) were independent factor for predicting survival. Conclusion: Compared with CCCG-WT-2009, treatment of renal tumors in CCCG-WT-2015 study yielded good survival outcome, which can be further applied.

[Clinical analysis of complications after laparoscopic radical gastrectomy for patients over 70 years old with low abdominal pressure].

Objective: To explore the safety and reliable of low pressure laparoscopy in old patients, and the advantage over conventional pressure laparoscopy. Methods: Sixty-six patients(≥70 year) with gastric cancer from 2014.4 to 2017.4 were enrolled, and they were divided into three groups randomly. The value of Ejection Fraction (EF), central venous pressure (CVP), B-type natriuretic peptide (BNP), O(2) pressure, CO(2) pressure, complications of three groups were compared and analysis. Results: There was no differences between low-pressure laparoscopic group, conventional laparoscopic group and laparotomy group in age, gender, EF, oxygen pressure, CVP (P>0.05). But the postoperative BNP, intraoperative carbon dioxide pressure of low-pressure laparoscopic group were significantly better than those of the other two groups. Compared with the conventional laparoscopic group and the laparotomy group, the low-pressure laparoscopic group has fewer postoperative complications (P=0.027, <0.05), especially in postoperative pulmonary infection (P=0.044, <0.05). Conclusion: The low pressure laparoscopy has decreased the stimulation of surgery to old patients, and reduced the postoperative complications. All this results demonstrate that the low pressure laparoscopy to old patients is safety and reliable.

[Metabolomics study of tris(2-chloroethyl) phosphate induced hepaotoxicity and nephrotoxicity in Sprague-Dawley rats].

Objective: To discuss the potential toxic target organ and the toxic effects and mechanisms of tris (2-chloroethyl) phosphate (TCEP) on SD rats. Methods: 40 female SD rats weaning from milk for 21 days, weighted (50±2.3)g were selected as subjects and marked by the weight. They were randomly divided into 4 groups, namely control group, 50 (L), 100 (M) and 250 (H) mg·kg(-1)·d(-1) dose of TCEP group. Each group has 10 rats, and administrated the corresponding dose of drug or vehicle by mouth, quaque die for 60 days. All rats were sacrificed after the last administration. The livers and kidneys were dyed by HE for pathological observation; and the blood samples were collected to analyze the biochemical index. H(1)-Nuclear Magnetic Resonance ((1)H-NMR)-based metabolomics methods coupling with histopathogy examination were used to investigate the toxic effects of TCEP. Results: Inflammatory cell infiltration and hepatic necrosis were observed in the liver of TCEP-treated rats. Inflammatory cells invaded and calcification/ossification foci were also found in renal of TCEP-treated rats and tumor hyperplasia were existed in renal tubule in H group. The level of HDL-C in the L, M and H group were separately (1.7±0.09) , (1.5±0.07) and (1.3±0.1) µmol/L, which were all significantly lower than that of control group ( (1.9±0.2) µmol/L) (P<0.05) . The activity of cholinesterase (CHE) in the L, M and H group were separately (918±14.8) , (828±28.6) and (674±36.5) U/L, which were all significantly lower than that of control group ((1056±28.8) µmol/L) (P<0.05). Moreover, The level of creatinine (CRE) in the L, M and H group were separately (29.8±4.6) , (28.9±5.3) and (25.8±6.2) µmol/L, which were all significantly lower than that of control group ((30.2±3.9) µmol/L) (P<0.05). In the H group, the enzyme activities of alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), alkaline phosphatase (ALP) and the contents of total bilirubin (TBIL), glucose (GLU) and uric acid (UA) were all significantly higher than the results in control group. The results of (1)H-NMR metabolomics showed that the contents of lactate, glycine, high-density lipoprotein, low-density lipoprotein and phosphatidylcholine in blood of rats would decrease by TCEP exposure, while N-acetylglycoprotein, acetate, alanine, glucose, lipids, lipoproteins and fatty acids would increase. Conclusion: TCEP caused disorders in endogenous energy metabolism, leading to the pathological changes of inflammatory cells infiltration and necrosis in liver and kidney, caused enzyme activity changes of ALT, ALP and the content changes of other liver and kidney injury-related markers.

[Application of lymph node labeling with carbon nanoparticles by preoperative endoscopic subserosal injection in laparoscopic radical gastrectomy].

Objective: To evaluate the application value of carbon lymph node tracing technique by preoperative endoscopic subserosal injection in laparoscopic radical gastrectomy. Methods: From June 2013 to February 2015, seventy eight patients with gastric cancer were enrolled and randomly divided into trial group and control group. Subserosal injection of carbon nanoparticles around the tumor was performed by preoperative endoscopic subserosal injection one day before the operation in trial group, while the patients routinely underwent laparoscopic gastrectomy in control group. Results of harvested lymph nodes, postoperative complications were compared between the two groups. Carbon nanoparticle-related side effect was also evaluated. Results: The average number of harvested lymph node in trial group was significantly higher than that in control group (35.5±8.5 vs 29.5±6.5, P<0.05). The rate of overall black-dyed harvested lymph node was 74.7% (1 035/1 386) in trial group, the black-dyed lymph node rate in D1 lymph node was 80.1%, which was significantly higher than that in D2 lymph node (69.8%, χ2=19.38, P<0.01). When comparing the lymph node with and without black-dyed in trial group, the rate of metastasis lymph node was significantly higher in lymph node with black-dyed (17.3% vs 4.0%, χ2=38.67, P<0.01). There was no significant difference in postoperative complications rate between two group (trial group 10.2%; control group 12.8%, χ2=0.00, P>0.05), and no carbon nanoparticle-related side effect was observed. Conclusion: Given a higher harvested lymph node number and a similar rate of complications, preoperative endoscopic subserosal injection of carbon nanoparticles was safe and feasible.

The small GTPase RhoA regulates the expression and function of the sodium channel Nav1.5 in breast cancer cells.

Voltage-gated Na+ channels (VGSCs) are highly expressed in several types of carcinomas including breast, prostate and lung cancers as well as in mesothelioma and cervical cancers. Although the VGSCs activity is considered crucial for the potentiation of cancer cell migration and invasion, the mechanisms responsible for their functional expression and regulation in cancer cells remain unclear. In the present study, the role of the small GTPase RhoA in the regulation of expression and function of the Nav1.5 channel in the breast cancer cell lines MDA-MB 231 and MCF-7 was investigated. RhoA silencing significantly reduced both Nav1.5 channel expression and sodium current indicating that RhoA exerts a stimulatory effect on the synthesis of an active form of Nav1.5 channel in cancer cells. The inhibition of Nav1.5 expression dramatically reduced both cell invasion and proliferation. In addition, a decrease of RhoA protein levels induced by Nav1.5 silencing was observed. Altogether, these findings revealed: i) the key role of the small GTPase RhoA in upregulation of Nav1.5 channel expression and tumor aggressiveness, and ii) the existence of a positive feedback of Nav1.5 channels on RhoA protein levels.

Genome-wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near PAX4.

AIMS/HYPOTHESIS: Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians. METHODS: We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations. RESULTS: We identified CDKN2A/B and four novel type 2 diabetes association signals with p < 1 × 10(-5) from the meta-analysis. Thirteen variants within these four loci were followed up in two independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11,067 cases and 7,929 controls (p meta = 2.6 × 10(-8); OR [95% CI] 1.18 [1.11, 1.25]). In silico replication revealed consistent associations across multiethnic groups, including five East Asian populations (p meta = 2.3 × 10(-10)) and a population of European descent (p = 8.6 × 10(-3)). The rs10229583 risk variant was associated with elevated fasting plasma glucose, impaired beta cell function in controls, and an earlier age at diagnosis for the cases. The novel variant lies within an islet-selective cluster of open regulatory elements. There was significant heterogeneity of effect between Han Chinese and individuals of European descent, Malaysians and Indians. CONCLUSIONS/INTERPRETATION: Our study identifies rs10229583 near PAX4 as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes.

ERCC1, defective mismatch repair status as predictive biomarkers of survival for stage III colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy.

BACKGROUND: Excision repair cross-complementation group 1 (ERCC1) expression status has been identified as a candidate marker for predicting efficacy of oxaliplatin (OX) treatment for metastatic colorectal cancer (CRC) in several trials. Also, an association between expression of mismatch repair (MMR) genes and favourable postoperative survival in stage II CRC receiving 5-FU chemotherapy has been identified. It is unknown if the expression of ERCC1 protein and MMR status are associated with survival of stage III colon cancer receiving OX-based chemotherapy. METHODS: Immunohistochemistry (IHC) analysis of the expression of MMR and ERCC1 was performed on tumour tissue of 255 patients with stage III colon cancer. In all, 95 patients received fluoropyrimidine-based chemotherapy and 160 patients received OX-based chemotherapy. A predictive model for 5-year disease-free survival (DFS) and overall survival (OS) was constructed using Kaplan-Meier analysis, logistic and Cox regression. RESULTS: Patients who were treated with OX-based therapy with positive ERCC1 tumours had lower 5-year DFS (54%) and OS (60%) than those with negative ERCC1 tumours (72% and 78%, respectively; DFS HR: 1.98, 95% confidence interval (CI): 1.19-3.31, P=0.009; OS HR: 2.44, 95% CI: 1.37-4.34, P=0.02). Excision repair cross-complementation group 1 status did not impact DFS or OS in fluorouracil group (DFS HR: 1.16, 95% CI: 0.63-2.14, P=0.62; OS HR: 1.16, 95% CI: 0.63-2.14, P=0.63), whereas MMR status had no impact on DFS or OS in either group. CONCLUSION: Excision repair cross-complementation group 1 status is highly predictive of which patients will benefit from the addition of OX to 5-FU for stage III colon cancer. Mismatch repair status had no predictive value in this setting.

Prognostic factors in surgically managed gastrointestinal stromal tumours.

OBJECTIVE: To determine prognostic factors associated with survival in patients with surgically managed gastrointestinal stromal tumours (GISTs). METHODS: This retrospective study included 374 patients with pathologically confirmed GISTs. Medical records were reviewed and prognostic factors associated with adverse outcomes were determined. RESULTS: A total of 337 patients underwent complete resection with curative intent; 37 underwent incomplete resection. Overall mean survival time was 127.3 months; 5-year survival rate was 70.4%. Multivariate analyses determined that tumour size, risk status (of recurrence or metastasis) and surgical procedure were significant predictive factors for survival. There was a significant difference in the 5-year survival rate between patients who received adjuvant imatinib compared with those who did not (75.1% versus 13.8%). CONCLUSIONS: Patients with GISTs managed by surgical resection combined with targeted chemotherapy had a good prognosis. Clinical factors predictive of survival included tumour size, risk status and surgical procedure.

Randomised clinical trial: high-dose vs. standard-dose proton pump inhibitors for the prevention of recurrent haemorrhage after combined endoscopic haemostasis of bleeding peptic ulcers.

BACKGROUND: The optimal dosage of intravenous proton pump inhibitors (PPIs) for the prevention of peptic ulcer rebleeding remains unclear. AIM: To compare the rebleeding rate of high-dose and standard-dose PPI use after endoscopic haemostasis. METHODS: A total of 201 patients with bleeding ulcers undergoing endoscopic treatment with epinephrine injection and heater probe thermocoagulation were randomised to receive a high-dose regimen (80 mg bolus, followed by pantoprazole 8 mg/h infusion, n = 100) or a standard-dose regimen (pantoprazole 40 mg bolus daily, n = 101). After 72 h, all patients were given 40 mg pantoprazole daily orally for 27 days. RESULTS: There were no statistical differences in mean units of blood transfused, length of hospitalisation ≦5 days, surgical or radiological interventions and mortality within 30 days between two groups. Bleeding recurred within 30 days in six patients [6.2%, 95% confidence interval (CI) 1.3-11.1%] in the high-dose group, as compared to five patients (5.2%, 95% CI 0.6-9.7%) in the standard-dose group (P = 0.77). The stepwise Cox regression analysis showed end-stage renal disease, haematemesis, chronic obstructive pulmonary disease (hazard ratio: 37.15, 10.07, 9.12, 95% CI: 6.76-204.14, 2.07-49.01, 1.66-50.00 respectively) were independent risk factors for rebleeding and Helicobacter pylori infection was associated with lower risk of rebleeding (hazard ratio: 0.20, 95% CI: 0.04-0.94). CONCLUSIONS: Following combined endoscopic haemostasis of bleeding ulcers, co-morbidities, haematemesis and H. pylori Status, but not PPI dosage, are associated with rebleeding (http://www.Clinical Trials.gov.ID: NCT00709046).

Circulating antibodies to carcinoembryonic antigen related to improved recurrence-free survival of patients with colorectal carcinoma.

This prospective study evaluated the prognostic value of antibodies to carcinoembryonic antigen (anti-CEA), detected by indirect immunosorbent assay, in the serum of colorectal carcinoma patients. Serum carcinoembryonic antigen (CEA) concentrations, measured by electrochemiluminescence immunoassay, were elevated in 26 (37.7%) of 69 patients with colorectal cancer and could not be detected among the 28 patients with benign intestinal conditions or 37 healthy individuals who comprised the control groups. Anti-CEA immuno globulin (Ig)G or IgM was detected by immunonephelometry in 44 (63.8%) patients with colorectal cancer, three (10.7%) with benign intestinal conditions and four (10.8%) healthy blood donors. Differences in antibody detection frequencies between the cancer patient group and the control groups were statistically significant. Titres of anti-CEA correlated significantly with CEA levels and Dukes' cancer stage. Antibody titre was an independent, significant, favourable predictor for 5-year recurrence-free survival. It is concluded that measurement of serum anti-CEA combined with CEA might be useful as a tumour marker and to assess prognosis. These results need to be confirmed in large, well-controlled, randomized clinical trials.

Dietary L-arginine supplementation beneficially regulates body fat deposition of meat-type ducks.

1. Unlike mammals, uricotelic species, such as the duck, cannot synthesise endogenous arginine (Arg). This study was conducted to test the hypothesis that dietary L-Arg supplementation might regulate body fat deposition in ducks without affecting their fast growth rate. 2. A total of 160 21-d-old male and female White Pekin ducks were assigned randomly to two treatments: a non-supplemented control and supplementation at 10 g/kg L-Arg of a maize and soybean meal-based diet. 3. The 3-week feeding trial showed that the addition of L-Arg had no significant effect on feed intake, but significantly increased body weight gain by 5·2 %, breast muscle weight relative to live body weight by 9·9%, carcase crude protein content by 9·2%, ether extract content in breast muscle by 11·9%. Arg supplementation significantly decreased skin with fat and abdominal fat pad contents by 7·6% and 4·9% respectively and the ether extract content of carcase by 7·2%. 4. The results of this study indicate that a diet with 10 g/kg supplemental L-Arg could reduce the fat deposition of carcase and abdominal adipose cell size (diameter and volume), enhance intramuscular fat in breast muscles, as well as increase muscle and protein gain. The decreased fat depot in the carcase may be attributed to a reduction of hepatic lipogenic enzyme activity.

Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer.

PURPOSE: Colorectal cancer is one of the most common cancers worldwide. We tested the hypothesis that differences in the expression of certain molecular markers of colon cancer may account for different clinical outcomes. METHODS: Tissue microarray technology was used to assay the expression of 17 biological markers [beta-catenin, CD44v7, c-myc, cyclin D1, estrogen receptor beta, mitogen-activated protein kinase/extracellular signal-regulated kinase, maspin, matrix metalloproteinase-7 (MMP7), p53, Pin1, peroxisome proliferators-activated receptor-gamma, survivin, T cell transcription factor 4 (TCF4), transforming growth factor beta receptor II (TGFbetaR II), TGFbeta, TROP2, and Wnt] by immunohistochemistry in 620 colon cancer patients. The Cox proportional hazards regression model was applied to analyze the lifetime data, including time to death, time to recurrence, and time to liver metastasis. RESULTS: All the markers were present at significantly higher expression levels in tumor specimens than in normal colonic specimens. Kaplan-Meier analysis showed that high expression of TROP2, MMP7, and survivin were related to decreased survival; TCF4 and TROP2 were related to disease recurrence; and CD44v7, cyclin D1, MMP7, p53, survivin, and TCF4 were related to liver metastasis. However, the results of the multivariate analysis only showed that expression of MMP7, survivin, and TROP2 were significant predictors of lower patient survival, while TROP2 and MMP7 were significantly related to disease recurrence and liver metastasis, respectively. CONCLUSIONS: We conclude that elevated survivin, MMP7, and TROP2 expression levels are related to decreased survival. In addition, elevated MMP7 and TROP2 expression levels are predictors of disease recurrence and liver metastasis, respectively.

Determination of fenoverine, a modulator of smooth muscle motility, in capsules and in human plasma: application to dosage form stability and a pilot study in humans.

Fenoverine is a novel, potent, musculotropic, spasmolytic agent that affects primarily the gastrointestinal tract, bile duct, and female genital organs. A simple, specific, and accurate HPLC method was developed for the determination of fenoverine in capsules and plasma. This method has been successfully applied to stability studies of fenoverine capsules and to a pilot study in a normal, healthy volunteer following oral administration of fenoverine. For the determination of fenoverine in capsules, a Nucleosil 5-micron CN column, with acetonitrile:0.1 M ammonium acetate (60:40) as mobile phase and detection at 254 nm, was employed. The mean correlation coefficient of the calibration curve (n = 6) for the assay was 0.9999 over a concentration range of 24.6 to 147.6 micrograms/mL of fenoverine standard solutions. Fenoverine did not decompose significantly at 4, 45, 55, and 65 degrees C for 3 months. The mean correlation coefficients of within-day and between-day calibration curves were 0.9995 and 0.9999, respectively, over a range of 10 to 1000 ng/mL of fenoverine in plasma. The limit of detection was 10 ng in plasma.