Treatment patterns and survival outcomes in patients with non-metastatic early-onset pancreatic cancer.

BACKGROUND: The incidence of patients with early-onset pancreatic cancer (EOPC; age ≤ 50 years at diagnosis) is on the rise, placing a heavy burden on individuals, families, and society. The role of combination therapy including surgery, radiotherapy, and chemotherapy in non-metastatic EOPC is not well-defined. AIM: To investigate the treatment patterns and survival outcomes in patients with non-metastatic EOPC. METHODS: A total of 277 patients with non-metastatic EOPC who were treated at our institution between 2017 and 2021 were investigated retrospectively. Overall survival (OS), disease-free survival, and progression-free survival were estimated using the Kaplan-Meier method. Univariate and multivariate analyses with the Cox proportional hazards model were used to identify prognostic factors. RESULTS: With a median follow-up time of 34.6 months, the 1-year, 2-year, and 3-year OS rates for the entire cohort were 84.3%, 51.5%, and 27.6%, respectively. The median OS of patients with localized disease who received surgery alone and adjuvant therapy (AT) were 21.2 months and 28.8 months, respectively (P = 0.007). The median OS of patients with locally advanced disease who received radiotherapy-based combination therapy (RCT), surgery after neoadjuvant therapy (NAT), and chemotherapy were 28.5 months, 25.6 months, and 14.0 months, respectively (P = 0.002). The median OS after regional recurrence were 16.0 months, 13.4 months, and 8.9 months in the RCT, chemotherapy, and supportive therapy groups, respectively (P = 0.035). Multivariate analysis demonstrated that carbohydrate antigen 19-9 level, pathological grade, T-stage, N-stage, and resection were independent prognostic factors for non-metastatic EOPC. CONCLUSION: AT improves postoperative survival in localized patients. Surgery after NAT and RCT are the preferred therapeutic options for patients with locally advanced EOPC.

Nomograms for predicting overall survival and cancer-specific survival in elderly patients with epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) is one of the most fatal gynecological malignancies among elderly patients. We aim to construct two nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) in elderly EOC patients. METHODS: Elderly patients with EOC between 2000 and 2019 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Enrolled patients were randomly divided into the training and validation set at a ratio of 2:1. The OS and CSS were recognized as endpoint times. The independent prognostic factors from the multivariate analysis were used to establish nomograms for predicting the 3-, 5- and 10-year OS and CSS of elderly EOC patients. The improvement of predictive ability and clinical benefits were evaluated by consistency index (C-index), receiver operating characteristic (ROC), calibration curve, decision curve (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Finally, the treatment efficacy of surgery and chemotherapy in low-, medium-, and high-risk groups were displayed by Kaplan-Meier curves. RESULTS: Five thousand five hundred eighty-eight elderly EOC patients were obtained and randomly assigned to the training set (n = 3724) and validation set (n = 1864). The independent prognostic factors were utilized to construct nomograms for OS and CSS. Dynamic nomograms were also developed. The C-index of the OS nomogram and CSS nomogram were 0.713 and 0.729 in the training cohort. In the validation cohort, the C-index of the OS nomogram and CSS nomogram were 0.751 and 0.702. The calibration curve demonstrated good concordance between the predicted survival rates and actual observations. Moreover, the NRI, IDI, and DCA curves determined the outperformance of the nomogram compared with the AJCC stage system. Besides, local tumor resection had a higher benefit on the prognosis in all patients. Chemotherapy had a better prognosis in the high-risk groups, but not for the medium- risk and low-risk groups. CONCLUSIONS: We developed and validated nomograms for predicting OS and CSS in elderly EOC patients to help gynecologists to develop an appropriate individualized therapeutic schedule.

Risk factors, prognostic predictors, and nomograms for pancreatic cancer patients with initially diagnosed synchronous liver metastasis.

BACKGROUND: Liver metastasis (LM) remains a major cause of cancer-related death in patients with pancreatic cancer (PC) and is associated with a poor prognosis. Therefore, identifying the risk and prognostic factors in PC patients with LM (PCLM) is essential as it may aid in providing timely medical interventions to improve the prognosis of these patients. However, there are limited data on risk and prognostic factors in PCLM patients. AIM: To investigate the risk and prognostic factors of PCLM and develop corresponding diagnostic and prognostic nomograms. METHODS: Patients with primary PC diagnosed between 2010 and 2015 were reviewed from the Surveillance, Epidemiology, and Results Database. Risk factors were identified using multivariate logistic regression analysis to develop the diagnostic mode. The least absolute shrinkage and selection operator Cox regression model was used to determine the prognostic factors needed to develop the prognostic model. The performance of the two nomogram models was evaluated using receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA), and risk subgroup classification. The Kaplan-Meier method with a log-rank test was used for survival analysis. RESULTS: We enrolled 33459 patients with PC in this study. Of them, 11458 (34.2%) patients had LM at initial diagnosis. Age at diagnosis, primary site, lymph node metastasis, pathological type, tumor size, and pathological grade were identified as independent risk factors for LM in patients with PC. Age > 70 years, adenocarcinoma, poor or anaplastic differentiation, lung metastases, no surgery, and no chemotherapy were the independently associated risk factors for poor prognosis in patients with PCLM. The C- index of diagnostic and prognostic nomograms were 0.731 and 0.753, respectively. The two nomograms could accurately predict the occurrence and prognosis of patients with PCLM based on the observed analysis results of ROC curves, calibration plots, and DCA curves. The prognostic nomogram could stratify patients into prognostic groups and perform well in internal validation. CONCLUSION: Our study identified the risk and prognostic factors in patients with PCLM and developed corresponding diagnostic and prognostic nomograms to help clinicians in subsequent clinical evaluation and intervention. External validation is required to confirm these results.

Survival benefits and disparities in radiation therapy for elderly patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Older patients represent a unique subgroup of the cancer patient population, for which the role of cancer therapy requires special consideration. However, the outcomes of radiation therapy (RT) in elderly patients with pancreatic ductal adenocarcinoma (PDAC) are not well-defined in the literature. AIM: To explore the use and effectiveness of RT in the treatment of elderly patients with PDAC in clinical practice. METHODS: Data from patients with PDAC aged ≥ 65 years between 2004 and 2018 were collected from the Surveillance, Epidemiology, and End Results database. Multivariate logistic regression analysis was performed to determine factors associated with RT administration. Overall survival (OS) and cancer-specific survival (CSS) were evaluated using the Kaplan-Meier method with the log-rank test. Univariate and multivariate analyses with the Cox proportional hazards model were used to identify prognostic factors for OS. Propensity score matching (PSM) was applied to balance the baseline characteristics between the RT and non-RT groups. Subgroup analyses were performed based on clinical characteristics. RESULTS: A total of 12245 patients met the inclusion criteria, of whom 2551 (20.8%) were treated with RT and 9694 (79.2%) were not. The odds of receiving RT increased with younger age, diagnosis in an earlier period, primary site in the head, localized disease, greater tumor size, and receiving chemotherapy (all P < 0.05). Before PSM, the RT group had better outcomes than did the non-RT group [median OS, 14.0 vs 6.0 mo; hazard ratio (HR) for OS: 0.862, 95% confidence interval (CI): 0.819-0.908, P < 0.001; and HR for CSS: 0.867, 95%CI: 0.823-0.914, P < 0.001]. After PSM, the survival benefit associated with RT remained comparable (median OS: 14.0 vs 11.0 mo; HR for OS: 0.818, 95%CI: 0.768-0.872, P < 0.001; and HR for CSS: 0.816, 95%CI: 0.765-0.871, P < 0.001). Subgroup analysis revealed that the survival benefits (OS and CSS) of RT were more significant in patients aged 65 to 80 years, in regional and distant stages, with no surgery, and receiving chemotherapy. CONCLUSION: RT improved the outcome of elderly patients with PDAC, particularly those aged 65 to 80 years, in regional and distant stages, with no surgery, and who received chemotherapy. Further prospective studies are warranted to validate our results.

Mechanism of endometrial MUC2 in reproductive performance in mice through PI3K/AKT signaling pathway after lipopolysaccharide treatment.

The objective of this study was to investigate the effects of exposure to endotoxin on the reproductive performance of humans and animals in pregnancy and delivery period. Mucin is considered to play a critical role in protecting the tissue epithelium. At pregnancy period, the MUC2 expression of uterus in the High LPS group was significantly higher than that in the Control group. The glycosaminoglycans of gland cells were secreted into the uterine cavity to protect the uterus. Then, the MUC2 layer became thinner, and LPS entered the lamina propria of the uterus. The mRNA expression of tight junction proteins showed a marked drop, and morphological damage of the uterus occurred. Subsequently, the glycosaminoglycans of gland cells in the High LPS and Low LPS groups increased with the increasing LPS dose, and the damage to the endometrial epithelium was repaired in female mice at Day 5 postdelivery. A low dose of LPS activated the PI3K/AKT signaling pathways to increase the glycosaminoglycans particles, while a high dose of LPS inhibited the PI3K/AKT signaling pathway to decrease the glycosaminoglycans particles. Taken together, our results suggest that gland cells secreted glycosaminoglycans particles into the uterine cavity by exocytosis to increase the thickness of the mucus layer to protect the uterus and that this process was regulated by PI3K/AKT signaling pathways.

Effects of lipopolysaccharide on T lymphocyte cell subsets and cytokine secretion in mesenteric lymph nodes of mice: Histological and molecular study.

Lipololysaccharides (LPS) can disrupt the gut barrier. How dose LPS affects the immune performance of mesenteric lymph nodes? The results showed the hematological parameters significantly changed after LPS treatment. The length of intestinal villus was shortened and the depth of crypts was deepened, especially on the ileum. After LPS treatment 6 h, 12 h, the number of CD3+ T cells and CD4/CD8 in the mesenteric lymph nodes of ileum were reduced significantly; the levels of IFN-γ, TNF-ɑ and IL-2 were significantly decreased, and the levels of IL-6 and IL-10 were significantly increased in the ileum. The content of sIgA in the ileum was significantly decreased after LPS treatment 3 h, 6 h and was increased after LPS treatment 12 h. LPS through mesenteric lymph nodes, which induces the immune function reduced and the ileum injured obviously after treatment 6 h. Furthermore, the performance of intestinal immune performance was the lowest after LPS treatment 6 h.

The effects of swainsonine on the activity and expression of α-mannosidase in BRL-3A cells.

Swainsonine (SW) is the principal toxic ingredient of locoweeds, which can cause intensive vacuolar degeneration because of α-mannosidase inhibition after animal ingestion. While SW can lead to obvious liver damage in vivo, the mechanism of hepatotoxic damage caused by SW is not clear. Therefore, BRL-3A cells were treated for 24, 48, and 72 h with SW at various concentrations (0, 700, 900, 1100 µg/mL). The α-mannosidase (AMAN) activity was determined in BRL-3A cells using an enzyme substrate technique. The expression of mRNA and proteins of GM II (MAN2A1) and LAM (MAN2B1) in BRL-3A cells was detected by qPCR and Western-blot. The results showed that SW could significantly reduce the activity of AMAN in a time-dose effect relationship. Compared with the control group, the activity of AMAN significantly decreased only in the group treated with 1100 µg/mL SW for 24 h (P < 0.01), but the activity decreased significantly (P < 0.05 or P < 0.01) in all experimental groups treated for 48 or 72 h. SW also significantly reduced the expression of MAN2A1 and MAN2B1 mRNA and proteins in a time-dose effect relationship (P < 0.05 or P < 0.01), while the inhibition of SW was stronger for MAN2B1 than for MAN2A1. These results suggest that SW can significantly reduce the activity and expression of α-mannosidase thus causing SW-induced hepatotoxic damage.

Gender-specific differences in associations of overweight and obesity with asthma and asthma-related symptoms in 30 056 children: result from 25 districts of Northeastern China.

OBJECTIVE: The relationship between obesity and allergic respiratory diseases in childhood is still controversial. Furthermore, significant debate on the issue of whether or not gender modifies this association also exists due to inconsistent findings. The objective of this study is to evaluate the association between obesity and respiratory health in children, and to investigate the modifications of gender on this association. METHODS: 30 056 children (aged 2-14 years) were randomly selected from 25 districts within 7 cities in Northeastern China in 2009. A standard questionnaire from the American Thoracic Society was used to characterize the children's histories of respiratory symptoms and illnesses. Child weight and height were measured, and obesity was calculated with an age and sex-specific body mass index. RESULTS: The overall prevalence rates of obesity and overweightness were 14.08% and 12.32%, respectively. Compared to the children with normal body weights, asthma and asthma-related symptoms were more prevalent in overweight and obese children. Analysis stratified by gender showed that obesity was associated with more respiratory symptoms and diseases in females than in males. A significant association between obesity and diagnosed asthma [adjusted odds ratio (aOR) = 1.28; 95% confidence interval (CI): 1.02-1.60], as well as current wheezing (aOR = 1.46; 95%CI: 1.20-1.79) was found in females but not in males. CONCLUSIONS: There is an association between asthma symptoms and obesity in these Chinese children, and obesity had a significantly larger effect on females than males.

Dietary pseudopurpurin effects on bone mineral density and bone geometry architecture in rats.

The objective of our study was to evaluate whether feeding pseudopurpurin affects bone mineral density and bone geometry architecture in rats. Pseudopurpurin was extracted, analyzed and purified using an HLPC-ESI-MS. Rats were given 0% and 0.5% pseudopurpurin powder in their diet. Femurs of rats were examined at 0.5, 1 and 2 months after pseudopurpurin feeding. Compared with rats in the group 0%, the bone mineral density, and the calcium, magnesium, zinc and manganese concentrations in the rats femur in the group 0.5% increased significantly at 1 month and 2 months after pseudopurpurin feeding. Analytical results of micro-computed tomography showed that the group 0.5% displayed an increase in the trabecular volume fraction, trabecular thickness and trabecular number of the distal femur at 1 and 2 months after pseudopurpurin feeding, and the mean thickness, inner perimeter, outer perimeter, and area of the femur diaphysis were significantly increased at 2 months after pseudopurpurin feeding compared with the group 0%. In parallel, the trabecular separation and structure model index of the distal femur were decreased, compared with the group 0% at 1 and 2 months after pseudopurpurin feeding. In the 0.5% and 0% groups, there was no damage to kidney and liver by histopathology analysis. The long-term feeding of pseudopurpurin is safe for rats. The feeding of 0.5% pseudopurpurin which has specific chemical affinities for calcium for bone improvement and level of bone mineral density, enhances the geometry architecture compared with the 0% group.

Molecular characterization and tissue-specific expression of the acetyl-CoA carboxylase α gene from Grass carp, Ctenopharyngodon idella.

Acetyl-CoA carboxylase α (ACC1), the major regulatory enzyme of fatty acid biosynthesis, catalyzes the conversion of acetyl-CoA to malonyl-CoA. The full-length cDNA coding ACC1 isoform was cloned from liver of grass carp. The cDNA obtained was 7515bp with a 7173bp open reading frame encoding 2389 amino acids. The ACC1 protein has a calculated molecular weight of 269.2kDa and isoelectric point of 6.23. Tissue distribution of ACC1 mRNA in brain, mesenteric adipose, spleen, white muscle and liver of grass carp was analyzed by real-time PCR method using ß-actin as an internal control for cDNA normalization. The results showed that the expressions of ACC1 mRNA were detected in all examined tissues. Relative expression profile of ACC1 mRNA in liver normalized with ß-actin level was 15, 92, 135 and 165-fold compared with the level in brain, white muscle, mesenteric adipose and spleen, respectively. In addition, we present evidence for the presence of two isoforms of ACC1 (265.7kDa and 267.2kDa) in grass carp liver that differ from the 269.2kDa ACC1 by the absence of 34 and 15 amino acids. In conclusion, the liver is one of the main ACC1 producing tissues in grass carp and ACC1 gene was highly homologous to that of mammals.