Objective To study the relationship between the oncosis of pancreatic acinar cells and activa-tion of macrophage in rat model of acute pancreatitis (AP). Methods The pancreatic acinar cells were isolated by two-step enzyme digestion, and then they were divided into control group, AP group and test group. Pancreatic acinar cells were cultured with caerulein in AP group, with caerulein and endothelin in test group, and with culture medium in control group. The oncesis rate of the pancreatic acinar cells was detected after acridine orange and ethidium bromide fluorescent staining. The supernatant was collected to detect the release of amylase and lactate dehydrogenase (LDH). The macrophages were cultured with 1 ml of supematant for 6 hours, and then the protein level of tumor necrosis factor-α (TNF-α) was measured by ELISA. Results Few oncotic pancreatic acinar cells were observed in the control group, and the levels of amylase and LDH secreted by pancreatic acinar cells and TNF-α secreted by macrophage were (1175±165)kU/L, (846±118)U/L and (36±5)μg/L, respectively. Oncotic pancreatic acinar cells were observed in AP group, and the levels of amylase, LDH and TNF-α were (7130±680) kU/L, (4262±626) U/L and (155±18) μg/L, respectively, which were significantly higher than those in control group (t = 5.184, 4.277, 3.665, P < 0.05). The levels of amylase, LDH and TNF-α were even higher in test group, and they were (9240±1177) kU/L, (6937±893)U/L and (268±35)μg/L, respectively, which were significantly higher than those in AP group (t = 2.251, 2.825, 2.843, P < 0.05). Conclusions The release of amylase was changed as the oncosis of pancreatic acinar cells occurred. The secretion of TNF-α was along with the degree of oncosis of pancreatic acinar cells. The results of the study indicate that a relationship exists among the inflammatory response of macrophage, the release of contents of pancreatic acinar cells and the oncosis of the pancreatic acinar cells.

Objective To observe the apoptosis or oncosis of pancreatic acinar cells of different severity of acute pancreatitis (AP) and the release level of enzymes in vitro, and to investigate the relationship between them. Methods Two-step enzymatic digestion method was used to separate pancreatic acinar cells into 4 groups. 0. 1 μg/ml of the caerulein was added in the AP group. Caerulein and LPS (bacterial lipopolysaccharide, 10 mg/L) were added in LPS group. Caerulein and OCT (octreotide, 100 ng/ml) were added in OCT group. Medium was added in the control group. AO (acridine orange) and EB (ethidium bromide) double staining method was used to detect the incidence of apoptosis or oncosis of acinar cell. The release of intracellular enzyme was detected by measuring the concentrations of amylase and LDH in cell culture media by colorimetry method. Results The apoptosis index was 2.2 + 0.4, 6.4 ± 0.6, 4.6 + 0.4, 11.2 +1.2 in the control group, AP group, LPS group, OCT group; while the oncosis index was 3.0 +0.4, 17.2 ±1.6, 23.0 ± 2.2, 12.8 ± 1.4 in the control group, AP group, LPS group, OCT group; the release of LDH was (2180 ±240), (8060 ±930), (9460 +920), (6860 ±740) U/dl, the level of amylase was (1750 ± 190),(3820 ±460), (4420 ±480), (2260 ±260)U/L. All the values in the experiment groups were significantly higher than that in control group ( P ＜ 0.05 ). The oncosis index, LDH, amylase in LPS group was significantly higher than that in AP group ( P ＜ 0.05 ), but the apoptosis index in LPS group was significantly lower than that in AP group ( P ＜ 0.05 ). The apoptosis index in OCT group was significantly higher than that in AP group ( P ＜ 0. 05 ), but the oncosis index, LDH, amylase was significantly lower than that in AP group ( P ＜ 0. 05 ).Conclusions Induction of apoptosis and reduction of oncosis in AP pancreatic acinar cells can reduce the release of enzyme in acinar cells.

This paper is to report the determination of the skeletal muscle cellular membrane potential (SMCMP) in vivo with the technique of "Semi-floating"glass microelectrode. The changes of SMCMP and the distribution of extra- and intracellular electrolytes and water in different phases of irreversible hemo-rrhagic shock in rabbits were studied systematically.It was found that SMCMP decreased significantly and immediately as soon as hypotension occurred, which means that the functions of the cellular membrane begin to deteriorate in the early stage of shock; SMCMP continued to decrease when the shock was progressing, which reflects that besides the failure of the cellular membrane function, there is also the degradation of the functions of the cell proper; the leakage of the intracellular potassium across the cellular membrane and the retention of the intracellular sodium and water occurred three hours after the onset of the shock, which indicates that the inability of cells to regulate their volume.

PURPOSE: Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. Exosomes or extracellular vesicles are nanosized vesicles of endosomal origin released from inflammatory and epithelial cells that have been implicated in allergic diseases. In this study, we characterized the microRNA (miRNA) content of exosomes in AR. METHODS: Extracellular vesicles were isolated from nasal mucus from healthy control subjects (n=10) and patients with severe AR (n=10). Vesicle RNA was analyzed by using a TaqMan microRNA assays Human Panel-Early Access kit (Applied Biosystems, Foster City, CA, USA) containing probes for 366 human miRNAs, and selected findings were validated with quantitative RT-PCR. Target prediction and pathway analysis for the differentially expressed miRNAs were performed using DIANA-mirPath. RESULTS: Twenty-one vesicle miRNAs were up-regulated and 14 miRNAs were under-regulated significantly (P<0.05) in nasal mucus from AR patients when compared to healthy controls. Bioinformatic analysis by DIANA-mirPath demonstrated that 32 KEGG biological processes were significantly enriched (P<0.05, FDR corrected) among differentially expressed vesicle miRNA signatures. Among them, the B-cell receptor signaling pathway (P=3.709E-09), the natural killer cell-mediated cytotoxicity (P=8.466E-05), the T-cell receptor signaling pathway (P=0.00075), the RIG-I-like receptor signaling pathway (P=0.00127), the Wnt signaling pathway (P=0.00130), endocytosis (P=0.00440), and salivary secretion (P=0.04660) were the most prominent pathways enriched in quantiles with differential vesicle miRNA patterns. Furthermore, miR-30-5p, miR-199b-3p, miR-874, miR-28-3p, miR-203, and miR-875-5p, involved in B-cell receptor and salivary secretion signaling pathways, were selected for validation using independent samples from 44 AR patients and 20 healthy controls. MiR-30-5p and miR-199b-3p were significantly increased in extracellular vesicles from nasal mucus when compared to healthy controls, while miR-874 and miR-28-3p were significantly down-regulated. In addition, miRNA-203 was significantly increased in AR patients, while miRNA-875-5p was found to be significantly decreased in AR patients. CONCLUSIONS: This study demonstrated that vesicle miRNA may be a regulator for the development of AR.
B-Lymphocytes ; Biological Processes ; Endocytosis ; Epithelial Cells ; Exosomes ; Humans ; MicroRNAs* ; Mucus* ; Receptors, Antigen, T-Cell ; Rhinitis* ; RNA ; Wnt Signaling Pathway

Objective To summarize the preliminary clinical outcomes of combination therapy with molecular targeted agents/immunological agents and to explore the potential value of multidisciplinary therapy in the treatment of postoperative refractory recurrent hepatobiliary tumor.Methods 52 cases of postoperative refractory recurrent hepatobiliary tumor during June 2016 to January 2019 from outpatient and inpatient departments at the First Medical Center of PLA General Hospital were prospectively collected,including 37 males and 15 females,with a mean age of (56.2 ± 8.5) years.Referring to the results of next-generation sequencing (NGS) and other-omics,we designed individualized therapy options for each patient.Follow-ups were done regularly and tumor responses were assessed by modified response evaluation criteria in solid tumors (mRECIST).Results Of 52 patients,median follow-up was 10 months (range 3-31 months).14 (26.9％) patients achieved a complete response (CR).8 (15.3％) patients achieved a partial response (PR).14 (26.9％) patients had stable disease (SD).16 (30.8％,including 4 deaths) had progressive disease (PD).Objective response rate and disease control rate were 42.3％ (22/52) and 69.2％ (36/52),respectively.The median progression-free survival (PFS) was 7 months.6-and 12-month overall survival rates were 100％ (48/48),87.5％ (21/24),respectively.Conclusions Precision medicine has good guidance on the treatment of refractory recurrence of hepatobiliary tumors.The combination therapy of multi-target tyrosine kinase inhibitors and immune checkpoint inhibitors may achieve better disease control and deserve further promotion in clinical application.

Objective:To evaluate the efficacy of preoperative neoadjuvant chemoradiotherapy for low and locally advanced rectal cancer.Methods:Clinical data of 46 patients with low rectal tumors located within 6 cm from the edge of anal admitted to our hospital between February 2014 and December 2018 were retrospectively analyzed. SIB-IMRT technique was adopted for preoperative radiotherapy. Rectal tumors and positive lymph nodes were irradiated with a dose of 58.75 Gy in 25 fractions (2.35 Gy/fraction), and pelvic lymphatic drainage area was given with 50 Gy in 25 fractions (2.0 Gy/fraction). Oral administration of capecitabine was delivered for concurrent chemotherapy. Radical surgery for rectal cancer was performed at 6 to 12 weeks after the end of chemoradiotherapy. The overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), local recurrence-free survival (LRFS) and metastasis-free survival (MFS) were calculated by using Kaplan- Meier method. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox’s regression model. Results:After a median follow-up of 47 months, local recurrence occurred in 3 patients and distant metastasis in 6 patients. The ypCR rate was 26%(12/46), the sphincter-preservation rate was 74%(34/46), the R 0 resection rate was 100%(44/44), the overall tumor response TN down staging rate was 87%(40/46), and the postoperative complication rate was 13%(6/46). The 3-year OS, DFS, and PFS were 93%, 91% and 87%, respectively. In univariate analysis, ypN staging was an important factor affecting OS, DFS, PFS, LRFS and MFS (all P<0.05). In multivariate analysis, ypN staging was significantly correlated with DFS, PFS, LRFS and MFS (all P<0.05). Conclusions:Preoperative SIB-IMRT 58.75 Gy in 25 fractions combined with capecitabine chemotherapy is a safe and efficacious treatment for patients with low and locally advanced rectal cancer, which improves the ypCR rate and quality of life, and yields tolerable adverse reactions. Nevertheless, the long-term survival benefits remain to be validated.