Reconstruction of damaged corneal epithelium using Venus-labeled limbal epithelial stem cells and tracking of surviving donor cells.

Limbal epithelial stem cells are responsible for the self-renewal and replenishment of the corneal epithelium. Although it is possible to repair the ocular surface using limbal stem cell transplantation, the mechanisms behind this therapy are unclear. To investigate the distribution of surviving donor cells in a reconstructed corneal epithelium, we screened a Venus-labeled limbal stem cell strain in goats. Cells were cultivated on denuded human amniotic membrane for 21 days to produce Venus-labeled corneal epithelial sheets. The Venus-labeled corneal epithelial sheets were transplanted to goat models of limbal stem cell deficiency. At 3 months post-surgery, the damaged corneal epithelia were obviously improved in the transplanted group compared with the non-transplanted control, with the donor cells still residing in the reconstructed ocular surface epithelium. Using Venus as a marker, our results indicated that the location and survival of donor cells varied, depending on the corneal epithelial region. Additionally, immunofluorescent staining of the reconstructed corneal epithelium demonstrated that many P63(+) cells were unevenly distributed among basal and suprabasal epithelial layers. Our study provides a new model, and reveals some of the mechanisms involved in corneal epithelial cell regeneration research.

Prognostic Implications of an Autophagy-related Gene Signature in Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose and resistant to therapy and has a poor prognosis. Autophagy plays a vital role in PDAC development and progression. This study aimed to establish an autophagy-related gene (ARG) signature to predict the prognosis of patients with PDAC. MATERIALS AND METHODS: The expression profiles of PDAC and healthy pancreatic tissues were obtained from The Cancer Genome of Atlas (TCGA) and GTEx (Genotype-Tissue Expression) databases, respectively. Univariate and multivariate Cox regression analyses were performed on differentially expressed ARGs to identify the optimal prognosis-related genes. RESULTS: A total of 73 ARGs demonstrated significant differences in expression levels between PDAC and healthy pancreatic tissues. Several pathways that play crucial roles in biological processes were identified via enrichment analyses. Furthermore, an ARG signature was established based on overall survival-related ARGs (CASP4, BAK1, PIK3R4, CASP8, BIRC5, RPTOR, and CAPN1) using least absolute shrinkage and selection operator (LASSO) regression. Cox regression analysis confirmed that the 7-gene signature was an independent prognostic factor for patients with PDAC (P<0.001). In addition, the GSE21501 and GSE28735 datasets were used to validate the predictive value of the prognostic model for PDAC. We also constructed a clinical nomogram with a concordance index of 0.712 to predict the overall survival of patients by integrating clinical characteristics and the ARG signature. Calibration curves substantiated fine concordance between nomogram prediction and actual observation. CONCLUSION: We constructed a new ARG-related prognostic model, which can be a prognostic biomarker and offers insights into identifying potential therapeutic targets for PDAC.

Dmrt1 regulates the immune response by repressing the TLR4 signaling pathway in goat male germline stem cells.

Double sex and mab-3-related transcription factor 1 (Dmrt1), which is expressed in goat male germline stem cells (mGSCs) and Sertoli cells, is one of the most conserved transcription factors involved in sex determination. In this study, we highlighted the role of Dmrt1 in balancing the innate immune response in goat mGSCs. Dmrt1 recruited promyelocytic leukemia zinc finger (Plzf), also known as zinc finger and BTB domain-containing protein 16 (Zbtb16), to repress the Toll-like receptor 4 (TLR4)-dependent inflammatory signaling pathway and nuclear factor (NF)-κB. Knockdown of Dmrt1 in seminiferous tubules resulted in widespread degeneration of germ and somatic cells, while the expression of proinflammatory factors were significantly enhanced. We also demonstrated that Dmrt1 stimulated proliferation of mGSCs, but repressed apoptosis caused by the immune response. Thus, Dmrt1 is sufficient to reduce inflammation in the testes, thereby establishing the stability of spermatogenesis and the testicular microenvironment.

Celiac Plexus Block After Stereotactic Body Radiotherapy Improves Pain Relief in Locally Advanced Pancreatic Cancer.

PURPOSE: This study evaluated the analgesic effect of stereotactic body radiotherapy (SBRT) in combination with celiac plexus block (CPB), relative to SBRT alone, in locally advanced pancreatic cancer (LAPC) patients. PATIENTS AND METHODS: We reviewed medical records of all patients with LAPC, who received SBRT between 1 January 2017 to 31 August 2019 at our center. The average numeric rating scale (NRS) of ≥3 was used in all patients at admission. We recorded average and worst NRS in a 24-hour period, and daily narcotic doses before SBRT, followed by weekly for 1 month and monthly for 3 months. RESULTS: A total of 23 patients in the SBRT group and 12 under SBRT+CPB who met the inclusion criteria were enrolled. All patients in the SBRT+CPB group received CPB within 10 days after SBRT. Pain intensity and narcotic consumption were comparable in both groups at initial assessment. However, a significant decrease (P < 0.05) in average NRS was recorded in the SBRT+CPB group relative to SBRT at 2, 3 and 4 weeks after SBRT. A comparison of daily narcotic consumption with baseline values showed a significant decrease in the SBRT+CPB group at 3 and 4 weeks after SBRT (P < 0.05), while no significant differences were observed in the SBRT group. CONCLUSION: CPB after SBRT appears to be an effective therapeutic option in patients with LAPC and warrants further evaluation with increased number of patients in prospective clinical trials.

Contribution of Opiate Analgesics to the Development of Infections in Advanced Cancer Patients.

OBJECTIVES: Literature is limited on the relationship between opiate analgesics and the development of infections in cancer patients. This study aimed to determine whether opiate analgesics contribute to the advancement of infections and how infection rates differ among the various opiates used for cancer management. MATERIALS AND METHODS: From January 2013 to October 2014, we analyzed retrospectively 642 consecutive advanced cancer patients who received single types of opiates, including morphine, oxycodone, or fentanyl, or a combination of these drugs, continuously for >14 days. Binominal logistic regression analysis was used to analyze the factors that may promote the development of infections. RESULTS: A total of 303 patients were included in the final analysis. Of these patients, 85, 41, and 68 patients received only morphine, oxycodone, and fentanyl, respectively. Altogether, 87 (28.7%) patients developed infections; 20 (23.5%), 10 (24.4%), and 14 (20.6%) patients developed infections in the groups that received only morphine, oxycodone, and fentanyl, respectively (P>0.05). Logistic regression analysis found that the daily oral morphine equivalent (OME) is the an independent factor that influences the development of infection in the single-opiate group (odds ratio=1.002, P<0.01). The risk for developing infection increased by 2% per 10 mg increase in the daily OME. CONCLUSIONS: Our clinical results did not display any difference among the single-opiate groups in the development of infections. However, the increase in daily OME may serve as a risk factor for the development of infections in advanced cancer patients using one opiate type for pain management.

Nonpain Symptom Prevalence and Intensity of Inpatients With Moderate to Severe Cancer Pain in China.

OBJECTIVES: To identify prevalence and severity of nonpain symptoms and to clarify possible influences on each nonpain symptom. METHODS: The study used a descriptive survey design. Chinese version of the Edmonton Symptom Assessment System was used. Patients' demographic and pain characteristics were collected. RESULTS: The most common symptoms reported were loss of appetite (94.3%) followed by insomnia (93.3%), and tiredness (91.6%). Prevalence rates of nonpain symptom were all above 70% except "thinking clearly." Prevalence and severity of nonpain symptoms varied by gender, age, primary cancer, and pain characteristics, especially intensity, number of breakthrough pain episodes per day, and number of pain sites. CONCLUSIONS: Most inpatients with cancer pain experienced concurrent nonpain symptoms. Comprehensive symptom assessment and intervention managing multiple symptoms are essential for these inpatients.

Prognostic value of epidermal growth factor receptor mutations in resected lung adenocarcinomas.

The purpose of this study was to evaluate the association between epidermal growth factor receptor (EGFR) mutations and prognosis in patients with completely resected lung adenocarcinoma. A total of 131 patients were included in this study. EGFR mutation status in exons 18-21 of the tyrosine kinase-binding domain was detected using nested PCR amplification of individual exon. The χ (2) test was used to analyze the associations between EGFR mutations and the different variables. The log-rank test and Cox regression model were used to evaluate the factors influencing disease-free survival (DFS) and overall survival (OS). EGFR mutations in 18-21 exons were detected in 58 of the 131 patients (44.3 %). Smoking status (P = 0.029), N stage (P = 0.021), and pathologic stage (P = 0.048) were significantly associated with EGFR mutations. The median DFS in mutant EGFR and wild-type EGFR groups was 36.6 and 25.7 months, respectively (P = 0.533). No significant correlation was observed between EGFR mutations and OS (P = 0.564). However, patients with exon 19 mutation tended to have longer DFS than those with exon 21 mutation (46.2 vs. 21.9 months, P = 0.056), and the 1-, 2-, and 3-year OS rates were significantly higher in patients with exon 19 mutation compared to patients with exon 21 mutation (100, 96.7, 93.3 vs. 91.3, 82.6, 60.9 %, respectively, P = 0.01). Our data demonstrated that EGFR mutations do not have significant prognostic value in primary resected lung adenocarcinomas, but patients with exon 19 mutation tended to have better prognostic value compared to patients with exon 21 mutation.