[Paeoniflorin improves myocardial injury via inhibition of Src/VE-cadherin pathway in septic rats].

Objective: To study the protective effect and mechanism of paeoniflorin (pae) on myocardial injury in septic rats. Methods: Sprague-Dawley (SD) rats were randomly divided into 4 groups with 10 rats in each group. Rats were intraperitoneally injected with 1.4 ml normal saline and 1.4 ml 5% dimethyl sulfoxide (DMSO)solution independently in control group and DMSO group. Rats were intraperitoneally injected with 1.4 ml normal saline and 1.4 ml pae independently, then with 0.1 ml lipopolysaccharide (LPS) 1 hour later in sepsis group and pae group. Enzyme linked immunosorbent assay (ELISA) was used to detect serum cardiac troponin I (cTnI) levels and myocardial tissue tumor necrosis factor alpha (TNFα), interleukin(IL)-6, IL-1ß, chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-X-C motif) ligand 2 (CXCL2), vascular cell adhesion molecule 1 (VCAM-1) levels. Evans blue (EB) method was used to detect the EB content of myocardial tissue. HE staining method was used to observe the pathological changes, real-time quantitative polymerase chain reaction (RT-qPCR) to detect mRNA expression levels of the above molecules, and Western-blot to detect vascular endothelium-cadherin (VE-cadherin), phosphorylated p38 mitogen-activated protein kinase (P-p38MAPK), phosphorylated Src protein (P-Src), Ras-Related C3 Botulinum Toxin Substrate 1 (Rac1) levels. Results: Compared with control group, cTnI level and the EB content in sepsis group increased significantly, and the myocardial inflammatory cell infiltration was obvious. The cTnI level and EB content in pae group were significantly reduced, and myocardial inflammatory cell infiltration was reduced [cTnI: (227.7±15.9)pg/ml vs. (312.9±17.9)pg/ml;EB: (13.2±2.3)µg/g vs. (23.8±2.9)µg/g; P<0.05]. Compared with control group, the levels of TNFα, IL-6, IL-1ß, CXCL1, CXCL2, and VCAM-1 in sepsis group were increased. Compared with sepsis group, the above-mentioned molecular levels of pae group were significantly decreased [TNFα: (63.39±9.55)pg/ml vs. (126.54±19.17)pg/ml ;IL-6: (64.03±8.82)pg/ml vs. (85.60±9.52)pg/ml;IL-1ß: (69.52±9.23)pg/ml vs. (130.45±15.10)pg/ml;CXCL1: (2 600.19±379.54)pg/ml vs. (4 903.89±533.42)pg/ml;CXCL2: (93.71±10.83)pg/ml vs. (127.24±13.92)pg/ml;VCAM-1: (112.22±13.49)pg/ml vs. (149.32±15.65)pg/ml, both P<0.05]. RT-qPCR results showed that the mRNA expressions of TNFα, IL-6, IL-1ß, CXCL1, CXCL2 and VCAM-1 in the sepsis group were increased compared with the control group; Compared with sepsis group, the IL-6 mRNA (1.271±0.139 vs. 1.920±0.191, P<0.05), IL-1ßmRNA (1.180±0.130 vs. 1.817±0.191, P<0.05), VCAM-1 mRNA (1.088±0.144 vs. 1.460±0.166, P<0.05) expression decreased significantly in the pae group. Compared with control group, the levels of P-p38MAPK and P-Src in sepsis group increased, and the level of VE-cadherin decreased. Compared with sepsis group, the levels of p38MAPK and P-p38MAPK in pae group were significantly decreased, and the level of VE-cadherin was increased (p38MAPK/ß-actin: 1.125±0.078 vs. 1.520±0.164; P-p38MAPK protein: 1.639±0.133 vs. 2.112±0.222; both P<0.05). Conclusion: Paeoniflorin could improve the permeability of cardiac microvascular endothelium in sepsis rats and inhibit the secretion and expression of inflammation-related proteins and genes, which might be related to the inhibition of Src/VE-cadherin pathway by paeoniflorin.

A study of damage control theory in the treatment of multiple trauma mainly represented by emergency abdominal trauma.

OBJECTIVE: This study aimed to explore the measures of damage control theory (DCT) in the treatment of multiple trauma mainly represented by emergency abdominal trauma. PATIENTS AND METHODS: A total of 76 patients with severe multiple trauma in the Yiwu Central Hospital were selected. Among them, 37 patients with severe multiple trauma were treated with DCT (DCT group), and 39 patients were treated with traditional methods (control group). The prothrombin time (PT), the inflammation index, the duration of mechanical ventilation, the length of stay in the Intensive Care Unit (ICU), and the incidence of sepsis were compared between the two groups. RESULTS: A total of 60 cases (78.95%) were cured and discharged, and 4 cases (10.81%) died in the DCT group, while 12 cases (30.77%) died in the control group. There were 6 cases (16.22%) of sepsis in the DCT group and 15 cases (38.46%) of sepsis in the control group. This indicates that the mortality and the incidence of sepsis in the DCT group were lower than those in the control group (p<0.05 in all comparisons). The PT activated partial thromboplastin time (APTT), the length of stay in the ICU, and mechanical ventilation in the DCT group were notably shorter than those in the control group. The levels of serum tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), C-reactive protein (CRP), and IL-10 went up remarkably in both groups (p<0.05), but the levels of serum TNF-α, IL-6, and CRP in the DCT group were lower than those in the control group, while the IL-10 level in the former was significantly higher than that in the latter (p<0.05). CONCLUSIONS: It is feasible to apply DCT to rescue patients with multiple trauma, which can effectively reduce the mortality and complications, and shorten the length of stay in the ICU.

[The effect of para-aortic lymph node metastasis on the resectability of pancreatic cancer].

Pancreatic cancer has poor prognosis and lymph node metastasis is a poor prognostic factor in patients with resectable pancreatic cancer. The metastatic prevalence of para-aortic lymph node (PALN) ranges from 9.1% to 26.5% and it is listed as the distant metastatic group in pancreatic cancer. Nevertheless, it is controversial whether PALN metastasis is the contraindication of surgery in resectable pancreatic cancer for the shortage of level Ⅰ evidence.This study concluded that PALN metastasis indicated poor prognosis in patients with pancreatic cancer, but some patients with PALN metastases could benefit from surgery and their survival could be much improved after the combination of surgery and adjuvant therapy. Therefore, it is not wise to refuse surgery for all pancreatic cancer patients with PALN metastasis and the clinicians can cautiously choose the patients to do surgery. Besides, there are mainly retrospective studies rather than prospective and multicenter studies to explore the prognosis of pancreatic cancer patients with PALN metastasis. Thus, more prospective and multicenter studies are needed to decide whether PALN metastasis is an independent prognostic factor in patients with resectable pancreatic cancer.

Propensity score-matched analysis of robotic versus open surgical enucleation for small pancreatic neuroendocrine tumours.

BACKGROUND: Enucleation of pancreatic neuroendocrine tumours (pNETs) via robotic surgery has rarely been described. This study sought to assess the safety and efficiency of robotic surgery for the enucleation of small pNETs. METHODS: A comparison was conducted of enucleation of pNETs smaller than 2 cm by robotic or open surgery between January 2000 and May 2015. Propensity score matching was used to balance sex, age, BMI, tumour location and tumour diameter. Pathological results, safety-related outcomes (postoperative pancreatic fistula (POPF) rate, estimated blood loss, and short-term mortality and morbidity) and efficiency-related outcomes (duration of surgery and postoperative length of hospital stay) were compared between the groups. RESULTS: A cohort of 120 patients with pNET were enrolled in the study (1 : 1 matched for open or robotic surgery, 60 per group). Ninety-three patients (77·5 per cent) had a grade 1 tumour and 114 (95·0 per cent) had an insulinoma. Robotic surgery had a conversion rate of 5 per cent (3 of 60), and was not associated with an increased POPF rate (10 per cent versus 17 per cent after open surgery; P = 0·283) or grade III-V surgical complications according to the Dindo-Clavien classification (3 versus 10 per cent respectively; P = 0·272). Estimated blood loss was reduced with the robotic approach (32·5 versus 80·0 ml in the open group; P = 0·008), as was duration of surgery (117 versus 150 min; P < 0·001). Length of hospital stay after surgery was similar in the two groups (12·0 versus 13·5 days respectively; P = 0·071). CONCLUSION: Robotic surgery for enucleation of pNETs smaller than 2 cm did not increase POPF or major complication rates, and reduced the duration of surgery and estimated blood loss, compared with open surgery. REGISTRATION NUMBER: NCT02125929 ( https://www.clinicaltrials.gov/).

Flow regulation of 72-kD collagenase IV (MMP-2) after experimental arterial injury.

BACKGROUND: MMP-2 plays a key role in basement membrane degradation and in the migration of proliferating smooth muscle cells after vascular injury. Because low flow and shear stress have been related to the localization and progression of intimal hyperplasia, we hypothesized that flow conditions modulate in vivo MMP-2 transcription and activity in a model of injury-induced intimal thickening. METHODS AND RESULTS: The right common carotid artery (CCA) was balloon-injured in 21 New Zealand White male rabbits. Flow was thereafter preserved (normal flow, n=7), reduced by partial outflow occlusion (low flow, n=7), or increased by ligation of the left CCA (high flow, n=7). In 15 other animals (controls without injury), flow was reduced (n=5), increased (n=5), or preserved (n=5). Mean blood flow and pressure in the right CCA were measured before and after flow modulation (day 0) and before the rabbits were killed (day 7). Northern analysis, gelatin-gel zymography, and fluorometric assays were performed on day 7 to determine MMP-2 mRNA levels and activity in relation to flow and intimal thickening. Mean flow was reduced from 21+/-1 to 7+/-1 mL/min (P<0.05) by outflow occlusion and increased to 31+/-2 mL/min (P<0.05) by ligation of the contralateral CCA. Blood pressure was not different between the flow groups. Hemodynamic parameters were similar for days 0 and 7 after flow modulation. In the injured right CCA, there was a 186% increase in MMP-2 mRNA with normal flow (P<0.05), a 366% increase with low flow (P<0.005), and only a 38% increase with high flow (P>0.05) compared with the uninjured CCA with normal flow. In the uninjured CCA, MMP-2 mRNA levels were increased by only 39% and 26% in the low- and high-flow groups, respectively, compared with normal-flow controls. The zymographic signal and quantitative fluorescent activity of gelatinase were markedly increased in both injured and uninjured CCAs subjected to low flow. Intimal thickening was observed after 1 week only in CCA segments with low flow and injury. CONCLUSIONS: Hemodynamic forces such as low flow upregulate injury-induced MMP-2 mRNA and appear to be more important in regulating MMP-2 activity than injury alone. This may facilitate migration of the smooth muscle cells and subsequent development of intimal thickening.

[Comparison of lipoperoxidative damage in plasma and platelet with the ratio of thromboxane A2 and prostaglandin I2 in blood stasis syndrome with coronary heart disease].

In order to study the biochemical and pathophysiological mechanism of the Blood Stasis Syndrome (BSS) or Non-BSS of coronary heart disease (CHD) patients, the activities of SOD, Selenium-glutathione peroxidase, the content of LPO in plasma and platelets and the contents of TXB2 and 6-keto-PGF1 alpha in plasma were determined in 109 BSS and Non-BSS of CHD patients compared with 98 healthy controls. It was discovered that the contents of TXB2, LPO, PL-LPO, and the ratio of TXB2/6-keto-PGF1 alpha were significantly increased in BSS-CHD patients compared with controls and Non-BSS-CHD patients. It was also discovered that the SOD activities and the contents of 6-keto-PGF1 alpha decreased significantly in Non-BSS-CHD patients. The results suggested that the injury of platelets by oxygen free radicals might be one of the primary injury factors in BSS-CHD patients. Our conclusion is that PGI2, SOD belong to the category of Heart-Qi, while TXA2, LPO to the Blood category. Therefore TXB2, 6-keto-PGF1 alpha, SOD, LPO should serve as some of the objective indexes for BSS patients of CHD.