Study of miR-506 in M2 macrophage polarization and immune intervention in pancreatic cancer mice / 中华肝胆外科杂志

Objective:To analyze the effect of microRNA-506 (miR-506) on M2 macrophages polarization and immune intervention in pancreatic cancer mice.Methods:Macrophages from peripheral blood of healthy volunteers were cultured in vitro, polarized into M1 or M2 type macrophages, and transfected with miR-506 or control sequence (miR-ctrl), respectively. Polarized macrophages from M1+ miR-ctrl group, M1+ miR-506 group, M2+ miR-ctrl group and M2+ miR-506 group were collected. The relative expression of marker genes of M1 and M2 type macrophages of four groups were analyzed by qRT-PCR. The characteristic functions of M1 and M2 type macrophages of four groups were also detected, such as phagocytosis and nitric oxide (NO) synthesis (characteristic function of M1 type macrophages), arginase 1 activity and the secretion of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), interleukin-10 (IL-10) (characteristic function of M2 type macrophages). Sixty healthy male C57BL/6 mice without specific pathogen, weighing 20-25 g, were randomly divided into miR-ctrl programmed death-1 (PD-1) group, miR-506 PD-1 group, miR-ctrl iso group, and miR-506 iso group. They were injected with miR-506, miR-ctrl, PD-1 antibodies, and isotype control antibodies, with 15 in each group. The tumor volume, tumor weight, Ki-67 and interferon γ expression were analyzed three weeks later. Results:Compared with M2+ miR-ctrl group, the relative expression of M1 type macrophage marker genes increased, and the relative expression of M2 type macrophage marker genes decreased in M2+ miR-506 group, with significant difference (all P<0.05). Compared with M2+ miR-ctrl group, the phagocytic function and NO synthesis of macrophages in M2+ miR-506 group increased, the activity of arginase 1 and the secretion of VEGF, TGF-β and IL-10 decreased, with significant difference (all P<0.05). There was no significant differences in tumor weight, volume, Ki-67, and interferon γ expression between miR-ctrl iso and miR-ctrl PD-1 group (all P>0.05). The tumor weight, tumor volume and Ki-67 in miR-506 PD-1 group were lower than those in miR-ctrl PD-1 group [(0.32±0.13) g vs (0.85±0.24) g; (0.72±0.23) cm 3 vs (2.03±0.21) cm 3; (25.9±10.3)% vs (55.6±12.5)%], while interferon-γ expression was significantly higher than that in miR-ctrl PD-1 group [(122.4±15.3) ng/g vs (82.4±22.2) ng/g] (all P<0.05). Conclusion:miR-506 inhibits the polarization of M2 macrophages and increases the anti PD-1 immunotherapy sensitivity in pancreatic cancer.

The effect of miR-506 on the tumor associated macrophages and tumor microenvironment of pancreatic ductal adenocarcinoma / 中华肝胆外科杂志

Objective:To explore the effect of miR-506 on the tumor associated macrophage (TAM) and tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC).Methods:Panc02 cells were used to establish in situ tumorigenesis mouse model. Tumor bearing C57BL/6 mice were divided into miR-ctrl C57 group and miR-506 C57 group, with 15 mice in each group. miR-ctrl or miR-506 coated with DOPC liposomes (miR-ctrl/DOPC or miR-506/DOPC) were injected intraperitoneally. The tumor weight and volume were measured, the changes of tumor infiltrating immune cells were detected by flow cytometry and the survival time of mice was monitored. To eliminate the influence of immune system, tumor bearing nude mice were divided into miR-ctrl nude group and mir-506 nude group, with 5 mice in each group. miR-ctrl/DOPC or miR-506/DOPC were injected intraperitoneally. To eliminate the influence of macrophages, tumor bearing C57BL/6 mice were randomly divided into control group and macrophage clearance group and injected intraperitoneally with PBS or clodronate liposome (Clo), with 10 mice in each group. Then each group was randomly divided into two groups (miR-ctrl PBS group and miR-506 PBS group, miR-ctrl Clo group and miR-506 Clo group), miR-ctrl PBS group and miR-ctrl Clo group were injected with miR-ctrl/DOPC via intraperitoneal injection, miR-506 PBS group and miR-506 Clo group were injected with miR-506/DOPC. Results:In C57BL/6 mice model, the tumor volume (1.04±0.23)×10 3 mm 3 and tumor weight (0.51±0.10)g of miR-506 C57 group was lower than those in miR-ctrl C57 group (1.92±0.34)×10 3 mm 3 and (0.99±0.19) g, the overall survival of miR-506 C57 group was longer than that of miR-ctrl C57 group. The ratio of M2/M1 in miR-506 C57 group (1.19±0.46) was lower than that in miR-ctrl C57 group (2.85±0.40). In BALB/C nude mice model, the tumor volume and tumor weight showed no significant difference between miR-506 nude group and miR-ctrl nude group. Compared with the miR-ctrl PBS group, the proportion of regulatory T cells decreased [(4.70±1.86)% vs. (12.00±2.24)%], the proportion of cytotoxic T cells increased [(10.54±1.89)% vs. (4.54±1.25)%], the proportion of apoptotic cytotoxic T cells decreased [(14.00±4.00)% vs. (26.80±4.27)%] and the concentration of IFN-γ increased in miR-506 PBS group [(89.60±14.69) vs. (28.00±13.69) ng/g]. However, after clearance of macrophages by Clo, there was no significant difference in the above indexes between mir-506 Clo group and miR-ctrl Clo group. Conclusion:MiR-506 inhibits the progression of PDAC and reverses its immunosuppressive TME in a macrophage dependent manner.

Clinical characteristics of 27 patients with type 1 autoimmune pancreatitis / 中华肝胆外科杂志

Objective To analyze the clinical characteristics of type 1 autoimmune pancreatitis (AIP) in patients.Methods The clinical data of 27 patients with type 1 AIP treated at Fujian Provincial Hospital from January 2012 to October 2018 were retrospectively analyzed.Results There are 25 males (92.6％) and 2 females (7.4％) (ratio 12.5∶1).The age of disease onset was (59.5 ± 14.3) years.The most common presenting symptoms were jaundice and abdominal pain (both 59.3％).The most common complication was IgG4-related sclerosing cholangitis (63.0％).Magnetic Resonance Cholangiopancreatograhpy (MRCP) conducted on 26 patients showed the diffuse type 1 AIP was most common (53.8％),only 2 patients (7.7％) presented with a main pancreatic duct stricture.The pancreatic segment of bile duct narrowing was very common (84.6％),and most patients presented as tapered narrowings (65.4％).Standard glucocorticoid therapy was given to these 27 patients who responded well with clinical and laboratory remissions.Two patients were given maintenance glucocorticoid therapy for a high level of serum IgG4.Conclusions Type 1 AIP can present as a local manifestation of IgG4-related disease.The most common complication is IgG4-related sclerosing cholangitis.Glucocorticoid therapy was effective but some patients required maintenance therapy.

Preoperative serum alkaline phosphatase: a predictive factor for early hypocalcaemia following parathyroidectomy of primary hyperparathyroidism / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Postoperative hypocalcemia is one of the most common complications following parathyroidectomy for primary hyperparathyroidism (PHPT). The aim of this study was to analyze the predictive value of biochemical parameters as indicators for episodes of hypocalcemia in patients undergoing parathyroidectomy for PHPT.</p><p><b>METHODS</b>The patients with PHPT who underwent parathyroidectomy between February 2004 and February 2014 were studied retrospectively at a single medical center. The patients were divided into biochemical, clinical, and no postoperative hypocalcemia groups, based on different clinical manifestations. Potential risk factors for postoperative hypocalcemia were identified and investigated by univariate and multivariate Logistic regression analysis.</p><p><b>RESULTS</b>Of the 139 cases, 25 patients (18.0%) were diagnosed with postoperative hypocalcemia according to the traditional criterion. Univariate analysis revealed only alkaline phosphatase (ALP) and the small area under the curve (AUC) of receiver operating characteristics (ROC) curve for ALP demonstrates low accuracy in predicting the occurrence of postoperative hypocalcemia. Based on new criteria, 22 patients were added to the postoperative hypocalcemia group and similar biochemical parameters were compared. The serum ALP was a significant independent risk factor for postoperative hypocalcemia (P = 0.000) and its AUC of ROC curve was 0.783. The optimal cutoff point was 269 U/L and the sensitivity and specificity for prediction were 89.2% and 64.3%, respectively.</p><p><b>CONCLUSIONS</b>The risk of postoperative hypocalcemia after parathyroidectomy should be emphasized for patients with typical symptoms of hypocalcemia despite their serum calcium level is in normal or a little higher range. Serum ALP is a predictive factor for the occurrence of postoperative hypocalcemia.</p>

The palliative treatment of malignant gastroduodenal obstruction / 国际外科学杂志

Malignant obstruction of the stomach or duodenum is a preterminal event in patients with ad-vanced malignancies of the upper gastrointestinal.It severely limits the quality of life in affected patients.Most patients are in bad conditions and have an short expecting live time,so they not only can not bear but also do not need such an invasive operation.Because of this,a minimally invasive but effective palliative treatment is quite necessary.This paper makes a summary and contrastive analysis of several ways of pallia-five treatment which are widely used for malignant gastroduodenal obstruction in recent years.