Oncological and genetic factors impacting PDX model construction with NSG mice in pancreatic cancer.

A patient-derived xenograft (PDX) approach, which relies on direct transplantation of tumor specimens into an immunocompromised animal, is a commonly used method for investigating tumor therapy predictions in vivo. This study evaluated influencing factors, including clinical, oncological, and genetic variables, for a pancreatic PDX model in mice. Tumor specimens were obtained from 121 patients with pancreatic ductal adenocarcinoma who underwent surgical resection at the Changhai Pancreatic Surgery Medical Center (Shanghai, China) between April 2016 and February 2017. Pancreatic cancer (PC) samples <3 mm3 were subcutaneously implanted into the NOD/Shi-scid/IL-2Rγnull (NSG) mice. Once the xenograft reached 300-500 mm3 or reached 180 d after cell inoculation, the tumor was excised. Part of the tumor was subsequently transplanted to next-generation mice, and another part was analyzed by using immunohistochemistry. Among the 121 patients with PC, tumor xenograft was successfully generated in 86 patients (71.1%). Primary tumor >3.5 cm in size was independently associated with xenograft formation rate. In addition, several enriched mutated genes within the VEGF pathway and higher microvessel density were found in the positive group (with xenograft) compared with the negative group (without xenograft). We concluded that tumor size and mutated VEGF pathway in PC are important factors affecting PDX model construction with NSG mice.-Guo, S., Gao, S., Liu, R., Shen, J., Shi, X., Bai, S., Wang, H., Zheng, K., Shao, Z., Liang, C., Peng, S., Jin, G. Oncological and genetic factors impacting PDX model construction with NSG mice in pancreatic cancer.

The effects of fertility and synchronization variation on seed production in two Chinese fir clonal seed orchards.

Variations in fertility and synchronization information is fundamental to seed orchard management. Our objective was to determine clonal variation and stability in strobili production, phenology, synchronization, and seed production in two generation clonal seed orchards (CSO) of Chinese fir. The number of female and male strobili and the phenology of 42 clones in both the 2.0- and 2.5-generation clonal seed orchards were investigated and recorded to calculate the variation and stability of fertility and synchronization. In both seed orchards, an obvious variation in gamete contribution was found among clones, indicating deviation from random mating. Female receptivity was in the pollen shedding stage, which is favorable to pollination. However, low synchronization (mean POij = 0.283) between clones indicated low overlap between female receptivity and pollen shedding. A higher POij value within clones than within outcrossing combinations indicated a high risk of selfing in two seed orchards, particularly for early- and late-flowering clones. The number of female strobili and POij (as female) significantly influence seed production. Overall, fertility and synchronization variation had notable consequences for seed production. Scientific genetic management is indispensable for promoting fertility uniformity and synchronization to obtain maximal genetic gain.

Nomogram predicts CR-POPF in open central pancreatectomy patients with benign or low-grade malignant pancreatic neoplasms.

Introduction: Central pancreatectomy (CP) is a standard surgical procedure for benign and low-grade malignant pancreatic neoplasms in the body and neck of the pancreas. Higher incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) after CP than after pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) has been reported, but no nomogram for prediction of CR-POPF after open CP has been previously established. Methods: Patients undergoing open CP for benign or low-grade malignant pancreatic neoplasms in the department of Hepatobiliary and Pancreatic (HBP) surgery of Shanghai Changhai Hospital affiliated to Naval Medical University between January 01, 2009 and December 31,2020 were enrolled. Pre-, intra- and post-operative parameters were analyzed retrospectively. Results: A total of 194 patients, including 60 men and 134 women, were enrolled with median age of 52 years (21~85 years). 84 patients (43.3%) were overweight (BMI>23.0 Kg/m2) and 14 (7.2%) were obese (BMI>28.0 Kg/m2). Pathological diagnoses ranged from serous cystic neoplasm (32.5%), solid pseudopapillary neoplasm (22.2%), pancreatic neuroendocrine tumor (20.1%), intraductal papillary mucinous neoplasm (18.0%) to mucinous cystic neoplasm (5.2%). All patients had soft pancreatic texture. Main pancreatic duct diameters were ≤0.3cm for 158 patients (81.4%) and were ≥0.5cm in only 12 patients (6.2%). A stapler (57.7%) or hand-sewn closure (42.3%) were used to close the pancreatic remnant. The pancreatic anastomosis techniques used were duct to mucosa pancreaticojejunostomy (PJ)-interrupted suture (47.4%), duct to mucosa PJ-continuous suture (43.3%), duct to mucosa "HO" half-purse binding PJ (5.2%) and invaginating pancreaticogastrostomy (4.1%). Post-surgical incidences of CR-POPF of 45.9%, surgical site infection of 28.9%, postpancreatectomy hemorrhage of 7.7% and delayed gastric emptying of 2.1% were found. Obesity and pancreatic anastomosis technique were independent risk factors of CR-POPF, with a concordance index of 0.675 and an Area Under the Curve of 0.678. Discussion: This novel nomogram constructed according to obesity and pancreatic anastomosis technique showed moderate predictive performance of CR-POPF after open CP.

MiR-499a-5p promotes 5-FU resistance and the cell proliferation and migration through activating PI3K/Akt signaling by targeting PTEN in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) can be considered a representative cancer type of the human body. As demonstrated by some studies, microRNA (miR)-499 is dysregulated in various cancer types including PC, for which chemotherapy involving 5-fluorouracil (5-FU) has long been considered the first-line therapy. However, there are complex and comprehensive mechanisms related to 5-FU, which have not been fully elucidated. This study thus aimed to examine the molecular mechanisms of 5-FU resistance through miR-499a-5p in PC. METHODS: The expression of miR-499a-5p in PC was measured using quantitative polymerase chain reaction (PCR). MiR-499a-5p was examined in-vivo for its effects on the malignant phenotypes of PC cells. RESULTS: The results of the present study demonstrated miR-499a-5p to be upregulated in PC and 5-FU resistant PC tissues. According to in vitro assays in PC cells (PANC1/FR), miR-499a-5p was found to affect adenosine triphosphate (ATP) binding cassette subfamily B member 1 (P-gp), ATP binding cassette subfamily C member 1 (MRP1), and ATP binding cassette subfamily G member 2 (BCRP), thereby facilitating 5-FU resistance in PC cells. Functions assays indicated that suppressed miR-499a-5p expression inhibited the proliferation and migration of cells but facilitated apoptosis in the PC cell line; by contrast, miR-499a-5p overexpression triggered the inverse phenotypic changes of cells. Concerning the mechanisms involved, miR-499a-5p increased PI3K/Akt signaling by targeting phosphatase and tensin homolog (PTEN). CONCLUSIONS: Taken together, these findings demonstrate that miR-499a-5p can be potentially applied to PC therapy.

Identification and functional analysis of heterogeneous FOXP3+ Treg cell subpopulations in human pancreatic ductal adenocarcinoma.

CD4+ CD25+ regulatory T (Treg) cells express the transcription factor FOXP3 and play an essential role in preventing autoimmunity. Abundant Treg cell accumulation in tumors and tumor draining lymph nodes (TDLNs) has been reported to correlate with both poor and favorable prognosis in various cancers, which suggests that Tregs may have multiple effects on antitumor immunity. However, the heterogeneity of tumor- and TDLN-infiltrating Treg cells remains unclear. Here we provide heterogeneity analysis of tumor infiltrating human CD4+ Treg cells and their matched adjacent tissues and TDLNs. We defined three different subpopulations of tumor- and TDLN-infiltrating Treg cells by Helios and CCR8 expression in pancreatic ductal adenocarcinoma (PDAC) and confirmed their functional heterogeneity. Helios+ CCR8+ Treg cells with potent suppressor function and limited IL-2 and IFN-γ secretion were identified in tumors and TDLNs. On the contrary, Helios- CCR8- Treg cells have impaired suppressive activity, and elevated expression of pro-inflammatory cytokines. More advanced grades of PDAC have predominantly Helios+ CCR8+ Treg cells and few Helios- CCR8- Treg cells both in tumors and TDLNs that suggests poor prognosis. These data could help further define the role of Treg cells and their functional role in tumors and TDLNs.

[Treatment of cervical opening wound (report of 43 cases)].

OBJECTIVE: To summarize our experiences on surgical saving of the cervical opening wound. METHOD: Retrospectively analyze 43 cases with cervical opening wound in department of otolaryngology, suizhou central hospital from 1992-2010. RESULT: Forty-one among 43 cases healed with no complications, 1 case died of obstruction of air way and hemorrhagic shock, and 1 case occurred secondary laryngostenosis and resulted in fine prognosis af ter treating with laryngotracheoplasty in higher hospital. CONCLUSION: It is very important to give the appropriate treatment on the injuries of large cervical vessels, nerves, laryngeal cartilages, throat mucosa and complications. It is important to repair the wounds primarily. Correct diagnosis and treatment at first time, and well nursing are crucial for good prognosis.

[Observation on nasal septum surgery combined with multi-sinus surgery].

OBJECTIVE: To observe and summarize the clinical effect of nasal septum surgery combined with multi-sinus surgery and to discuss the safety and feasibility. METHOD: Fifty-six patients with nasal sinuses and nasal cavity diseases received nasal septal reconstruction, Caldwell-Lue procedure, polypectomy, ethmoidectomy and partial middle or inferior turbinate resection simultaneously under local anesthesia, and the complications after surgery were observed. RESULT: Operation in fifty-six patients were completed successfully. Thirty cases were cured, the cure rate of 56 case was 53.57Y, 23 cases were effective recovered (41.07%), 3 cases didn't recover (5.36%). The clinical cure rate was 94.64%. No severe complications occurred. CONCLUSION: The nasal septal surgery combined with multi-sinus surgery simultaneously under local anesthesia is effective and safety procedure. It can decrease the recurrence rate of nasal polyp and sinusitis and don't increase the rate of complication occurring.