Application of 3D-CT simulation image in the description of gastric artery variation to guide laparoscopic total gastrectomy / 中华胃肠外科杂志

Objective: Anatomic variations in the perigastric vessels during laparoscopic radical gastrectomy often affect the operator's judgment and prolong the operation time, and even cause accidental injury and surgical complications, and hence the safety and quality of the operation cannot be ensured. In this study, multiple slice CT was reconstructed by 3-dimensional CT simulation software (3D-CT), and 3D-CT images were used to describe the variation of celiac trunk and splenic artery before surgery. The guiding role of the different variation of vessels was analyzed for laparoscopic total gastrectomy+D2 lymph node dissection (LTG+D2LD). Methods: A retrospective cohort study was conducted. Case inclusion criteria: (1) Gastric cancer was at an advanced stage. All the patients were preoperatively examined by digestive endoscopy and 64-row enhanced CT scan, and were histopathologically diagnosed with gastric adenocarcinoma. (2) 3D-CT simulation images were reconstructed to guide the operation. (3) LTG+D2LD surgery was performed by the same surgical team. (4) Clinical data were complete, and all the patients had signed the informed consent. From 2014 to 2018, 98 patients with gastric cancer at the Gastrointestinal Surgery Department of Henan Provincial People's Hospital were enrolled. According to the Adachi classification, celiac trunk variation was divided into common type (Adachi type I) and rare type (Adachi type II-VI). According to the Natsume classification, splenic artery was classified into "flat type" and "curved type". Based on 3D-CT simulation images, variation of celiac trunk and splenic artery was described, and the differences in operation time, intraoperative blood loss and the number of postoperative retrieved lymph nodes were compared between groups with different types of arterial variation. Results: For celiac trunk, common type was found in 84 cases (86%) and rare type was found in 14 cases, including 6 cases (6%) of type II, 2 cases (2%) of type III, 2 cases (2%) of type IV, 3 cases (3%) of type V, 1 case (1%) of type VI. No other types were found. There were no statistically significant differences in clinical characteristics and number of retrieved lymph nodes between patients of the common type group and rare type group (all P>0.05). Compared with common type patients, those of rare type had longer operative time [(321.1±29.0) minutes vs. (295.1±46.5) minutes, t=2.081, P=0.040] and more intraoperative blood loss (median: 66.0 ml vs. 32.0 ml, Z=-4.974, P=0.001). For splenic artery, 41 patients (42%) were flat type and 57 patients (58%) were curved type. There were no statistically significant differences between the two groups in terms of clinical characteristics, intraoperative blood loss, operative time and number of retrieved lymph nodes (all P>0.05). Conclusions: The method of describing the variation in the perigastric vessels by 3D-CT simulation has certain clinical value in laparoscopic radical gastrectomy. The duration of LTG+D2LD is prolonged and the intraoperative blood loss is increased with the variation of celiac trunk, while the variation of splenic artery has no effect on LTG+D2LD.

Association Between the Circumferential Pulmonary Veins Scar and Atrial Fibrillation Recurrence in Patients Undergoing Catheter Ablation of Atrial Fibrillation / 中国循环杂志

Objectives: This study aims to analyze the relationship between late gadolinium enhancement cardiac magnetic resonance imaging (LGE-cMRI) detected scar formation of circumferential pulmonary vein and recurrence rate after catheter ablation in patients with atrial fibrillation, and to compare the efficacy of the single-step cryoballoon ablation with the point-by-point radiofrequency current ablation. Methods: A total of 56 patients with nonvalvular atrial fibrillation who underwent catheter ablation from July 2014 to December 2016 in Fujian Provincial Hospital were enrolled in this study. Among them, 27 patients underwent radiofrequency ablation (RFA), and 29 cases underwent cryoballoon ablation (CBA). Scar formation of circumferential pulmonary vein was detected by LGE-cMRI in all patients at 3 months after ablation. All patients were monitored by telephone or outpatient follow-up (patients complaint, ECG or 24-hour Holter, etc.) at 6 months post ablation. Recurrent atrial tachyarrhythmias were defined as ≥ 30 seconds AF, atrial flutter, or atrial tachycardia. Results: AF recurrence was defined in 13 (23.21%) patients. The ratio of scar formation in circumferential pulmonary vein was significantly lower in recurrence patients than that in the non-recurrent patients ([63.23±5.86]% vs [79.95±7.47]%, P<0.001). The ratio of scar formation in each pulmonary vein of 56 patients was as follows: (76.80±11.60)% in the left superior pulmonary vein, (78.90±10.64)% in the left inferior pulmonary vein, (83.35±9.44)% in the right superior pulmonary vein (P<0.05 vs the left superior pulmonary vein), which was significantly lower in the right inferior pulmonary vein (66.13±13.44)% than above veins (all P<0.05). The ratio of scar formation of all four pulmonary vein was significantly lower in recurrence patients than in the non-recurrent patients, especially in left superior pulmonary vein ([61.19±4.89]% vs [81.52±8.43]%) and the right lower pulmonary vein ([52.47±7.62] % vs [70.26±12.03]%), both P<0.001.Univariate analysis showed that the recurrence rate , the total ratio of scar formation in circumferential pulmonary vein and the ratio of scar formation in recurrence patients were similar between the CBA group and the RFA group. Conclusions: Lower circumferential pulmonary vein scar is associated with higher recurrence rate post catheter ablation in atrial fibrillation patients. The scar formation ratio is low in the right inferior pulmonary vein and the left superior pulmonary vein. The circumferential pulmonary veins scar after cryoablation and radiofrequency catheter ablation is equivalent, indicating the pulmonary vein isolation efficacy of the two procedual methods is comparable.

Rapamycin ameliorates neuropathic pain by activating autophagy and inhibiting interleukin-1β in the rat spinal cord / 华中科技大学学报（医学）（英德文版）

Autophagy acts as an important homoeostatic mechanism by degradation of cytosolic constituents and plays roles in many physiological processes. Recent studies demonstrated that autophagy can also regulate the production and secretion of the proinflammatory cytokine interleukin-1β (IL-1β), which plays a critical role in the development and maintenance of neuropathic pain. In the present study, the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were significantly decreased after spinal nerve ligation (SNL), and the changes were accompanied by inhibited autophagy in the spinal microglia and increased mRNA and protein levels of IL-1β in the ipsilateral spinal cord. We then investigated the antinociceptive effect of rapamycin, a widely used autopahgy inducer, on SNL-induced neuropathic pain in rats and found that treatment with intrathecal rapamycin significantly attenuated the mechanical allodynia and thermal hyperalgesia. Moreover, rapamycin significantly enhanced autophagy in the spinal microglia, whereas it reduced the mRNA and protein levels of IL-1β in the ipsilateral spinal cord. Our results showed that rapamycin could ameliorate neuropathic pain by activating autophagy and inhibiting IL-1β in the spinal cord.

Rapamycin ameliorates neuropathic pain by activating autophagy and inhibiting interleukin-1β in the rat spinal cord / 华中科技大学学报（医学）（英德文版）

Autophagy acts as an important homoeostatic mechanism by degradation of cytosolic constituents and plays roles in many physiological processes. Recent studies demonstrated that autophagy can also regulate the production and secretion of the proinflammatory cytokine interleukin-1β (IL-1β), which plays a critical role in the development and maintenance of neuropathic pain. In the present study, the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were significantly decreased after spinal nerve ligation (SNL), and the changes were accompanied by inhibited autophagy in the spinal microglia and increased mRNA and protein levels of IL-1β in the ipsilateral spinal cord. We then investigated the antinociceptive effect of rapamycin, a widely used autopahgy inducer, on SNL-induced neuropathic pain in rats and found that treatment with intrathecal rapamycin significantly attenuated the mechanical allodynia and thermal hyperalgesia. Moreover, rapamycin significantly enhanced autophagy in the spinal microglia, whereas it reduced the mRNA and protein levels of IL-1β in the ipsilateral spinal cord. Our results showed that rapamycin could ameliorate neuropathic pain by activating autophagy and inhibiting IL-1β in the spinal cord.

Effect of neurotrophin p75 receptor activation on transmural dispersion repolarization in rabbits with myocardial infarction / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To elucidate the effect of neurotrophin p75 receptor (p75NTR)on transmural dispersion repolarization (TDR) of the layers of left ventricular myocytes in rabbits with myocardial infarction (MI).</p><p><b>METHODS</b>Forty Japanese rabbits were divided into four groups (n = 10): (1) Sham group, (2) Heald myocardial infarction (HMI) group, (3) p75 NTR activation group, (4) p75 NTR inhibition group. Cardiomyocytes were isolated with enzyme digestion and the currents were recorded by whole-cell patch-clamp technique.</p><p><b>RESULTS</b>Compared with those in the sham group, the duration of 90% action potential repolarization (APD90) and transmural dispersion repolarization of three layers of left ventricular myocytes were obviously raised (P < 0.05). But significant reduction was observed in p75NTR(-) group. Current densities of Ito and I(Ks, tail) in the p75NTR(+) group and HMI group were significantly reduced (P < 0.05), especially in mid myocytes. And no obvious changes were observed in p75NTR(-) group.</p><p><b>CONCLUSION</b>Activation of p75NTR(+) increases transmural dispersion repolarization, which may lead to the incidence of arrhythmia.</p>

Effect of hepatocyte growth factor and transforming growth factor-β(1) on atrial fibroblasts fibrosis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of hepatocyte growth factor (HGF) and transforming growth factor-β(1) (TGFβ(1)) on the expression of α-smooth muscle actin (α-SMA) and collagen I in human atrial fibroblast in vitro, and to explore the possible molecular mechanism of atrial fibrosis in patients with atrial fibrillation (AF).</p><p><b>METHODS</b>Human atrial fibroblast, isolated from aseptic right atrial appendage tissues of 10 sinus rhythm (SR) and 10 chronic atrial fibrillation (CAF) patients, were cultured with HGF and TGFβ(1). mRNA expressions of collagen I and α-SMA were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), the protein expression of α-SMA was determined by immunofluorescence and Western blot.</p><p><b>RESULTS</b>(1) Compared with SR group, left atrium was significantly dilated in CAF group (t = 2.692, P < 0.05), the mRNA expression of collagen I and α-SMA of atrial fibroblasts were significantly upregulated (all P < 0.01), mRNA expression of collagen I was positively correlated with left atrial dimension (LAD) (r = 0.836, P = 0.014), AF duration (r = 0.739, P = 0.045) and α-SMA mRNA level (r = 0.886, P = 0.012). (2) Compared with SR group, the expression of α-SMA protein in CAF atrial fibroblasts were significantly increased (P < 0.01). (3) TGFβ(1) further stimulated while HGF significantly attenuated the expression of collagen I and α-SMA in CAF atrial fibroblasts (all P < 0.01).</p><p><b>CONCLUSIONS</b>Increasing expression of collagen I and α-SMA in human atrial fibroblasts might promote atria remodeling leading to the development and sustaining of AF. HGF is involved in the negative regulation on the expression of α-SMA and collagen I.</p>

Effect of carvedilol on T-type calcium current in myocytes of non-infarcted area of the rabbit healed myocardial infarction / 药学学报

This article reports the investigation of the effect of carvedilol (Car) on T-type calcium current (I(Ca,T)) of noninfarcted ventricular myocytes in rabbit models of healed myocardial infarction (HMI). Rabbits with left anterior descending artery ligation were prepared and allowed to recover for 8 weeks, as HMI group. Animals undergoing an identical surgical procedure without coronary ligation were served as the sham-operated group (sham group). Whole cell voltage-clamp techniques were used to measure and compare currents in cells from the different groups. Noting that I(Ca,T) density in HMI cells increased markedly to -2.36 +/- 0.12 pA/pF (at -30 mV) compared with cells of sham, where little I(Ca,T) (-0.35 +/- 0.02 pA/pF) was observed. Meanwhile, further analysis revealed a significant hyperpolarizing shift of steady-state activation curve of I(Ca,T) in HMI cells, where the time constants of deactivation were prolonged and the time of recovery from inactivation was shortened. Finally, the amplitude of I(Ca,T) was increased. Carvedilol (1 micromol x L(-1)) was found to decrease the amplitude of I(Ca,T) to -1.38 +/- 0.07 pA/pF through inhibiting process of I(Ca,T) activation. Furthermore, carvedilol delayed recovery from inactivation of I(Ca,T) and shortened the time constants of deactivation in HMI cells. This study suggested that the application of carvedilol in HMI cells contributes to the dynamic changes in I(Ca,T) and may account for reduction of incidence of arrhythmia after myocardial infarction.

Relationship between atrial fibroblast proliferation/fibrosis and atrial fibrillation in patients with rheumatic heart disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between gene expressions of basic fibroblast growth factor (bFGF), smooth muscle alpha-actin (alpha-SMA) and proliferating cell nuclear antigen (PCNA) and atrial fibrosis in patients with atrial fibrillation (AF).</p><p><b>METHODS</b>The right atrial tissue samples were taken from 75 patients with rheumatic heart disease underwent heart valve replacement surgery (34 patients with sinus rhythm, 11 patients with paroxysmal AF and 30 patients with persistent AF) and stained with picrosirius red for quantitative analysis of collagen accumulation. The mRNA and protein levels of bFGF, alpha-SMA and PCNA were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical technique, respectively.</p><p><b>RESULTS</b>The percent volume fraction of collagen (CVF) was the highest in persistent AF group and the lowest in the sinus rhythm group (all P < 0.01). CVF significantly correlated with AF duration (r = 0.390, P = 0.010) and left atria (LA) dimension (r = 0.320, P = 0.005). The mRNA and protein levels of bFGF, alpha-SMA and PCNA were significantly higher in the persistent AF group than those in the paroxysmal AF group (all P < 0.05) and significantly higher in both AF groups than those in the sinus rhythm group (P < 0.05-0.01). The mRNA and protein levels of bFGF were positively correlated with CVF (r = 0.330, P = 0.004 and r = 0.292, P = 0.013, respectively), AF duration (r = 0.330, P = 0.005 and r = 0.299, P = 0.010, respectively) and left atrial dimension (r = 0.342, P = 0.003 and r = 0.285, P = 0.015, respectively).</p><p><b>CONCLUSION</b>The increased gene expressions of bFGF, alpha-SMA and PCNA in atrium during AF may contribute to atrial fibrosis by promoting fibroblast proliferation in AF patients.</p>

Changes in gelatinases expression and activity in human atria during atrial fibrillation / 中华心血管病杂志

<p><b>OBJECTIVE</b>To determine whether expression and activity of atrial gelatinases are altered in patients with atrial fibrillation (AF).</p><p><b>METHODS</b>The right atrial tissue samples were taken from 75 patients with rheumatic heart disease who underwent heart valve replacement surgery. 34 patients were in sinus rhythm, 11 patients had paroxysmal AF and 30 patients had persistent AF. The mRNA and protein level of MMP-2, MMP-9, TIMP-1, TIMP-2 were measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western-blotting analysis respectively. The activity of MMP-2 and MMP-9 was measured by zymographic analysis.</p><p><b>RESULTS</b>(1) The mRNA level of MMP-2 increased significantly in the persistent AF group followed by the paroxysmal AF group compared with the sinus rhythm group (P < 0.01, respectively). MMP-9 mRNA expression remained compatible within groups (P > 0.05). MMP-2 and MMP-9 protein expression was prominent in the persistent AF group compared with the sinus rhythm and paroxysmal AF groups (P < 0.01), the significant difference was also observed between the paroxysmal AF and sinus groups (P < 0.05). (2) TIMP-1 and TIMP-2 expression at mRNA and protein level were all down-regulated in the persistent AF group compared with the sinus rhythm group (P < 0.05), however, the trends of reduction did not reach statistical significance in the paroxysmal AF group (P > 0.05) except that of the mRNA level of TIMP-2 (P < 0.05). (3) The activity of MMP-2 and MMP-9 significantly increased in both paroxysmal AF and persistent AF groups compared with the sinus rhythm group (P < 0.05). The significant difference in MMP-9 was also observed between the persistent AF and paroxysmal AF groups (P < 0.01). (4) MMP-2 and MMP-9 expression at mRNA and protein level were positively correlated with left atrial dimension and AF duration (P < 0.05) and were negatively correlated with the mRNA and protein level of TIMP-2 and TIMP-1 respectively (P < 0.01).</p><p><b>CONCLUSIONS</b>The upregulation of MMP-2,9 gene expression and activity, along with the selective downregulation of TIMP-1,2 may have contributed to the atrial structural remodeling during AF through influencing collagen metabolism.</p>

Clinical on molecular basis of atrial fibrosis in patients with atrial fibrillation investigation / 中华心血管病杂志

<p><b>OBJECTIVE</b>To determine the molecular mechanisms involved in atrial fibrosis which occurs in patients with atrial fibrillation (AF) and to investigate their effects on the initiation and maintenance of AF.</p><p><b>METHODS</b>The right atrial tissue samples were taken from 73 patients with rheumatic heart disease who underwent heart valve replacement surgery. 34 patients had no history of AF (sinus rhythm group), 9 patients had paroxysmal AF and 30 patients had persistent AF. The mRNA content of collagen type I, collagen type III, MMP-2, TIMP-1, TIMP-2, TIMP-3 and TIMP-4 was measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and normalized to beta-actin or GAPDH.</p><p><b>RESULTS</b>Compared to sinus rhythm group, the mRNA of collagen type I and MMP-2 increased significantly in the persistent AF group (all, P < 0.01), followed by the paroxysmal AF group (all, P < 0.05). The mRNA of collagen type III was slightly higher in both AF groups than in the sinus rhythm group, but the differences were not statistically significant (P > 0.05). The mRNA of TIMP-1, TIMP-2 and TIMP-3 was down-regulated in the persistent AF group (all, P < 0.01, respectively), however, the trends of reduction did not reach statistical significance in the paroxysmal AF group (P > 0.05). The mRNA of TIMP-4 remained compatible in each group. The mRNA of collagen type I was significantly correlated with left atrial dimension (r = 0.336, P = 0.004) and AF duration (r = 0.339, P = 0.003). The mRNA of MMP-2 was significantly correlated with the mRNA of TIMP-2 (r = -0.326, P = 0.006), the mRNA of collagen type I (r = 0.322, P = 0.006), left atrial dimension (r = 0.300, P = 0.011) and AF duration (r = 0.300, P = 0.010).</p><p><b>CONCLUSION</b>The increased level of collagen type I associated with selective downregulation of TIMP-2 and upregulation of MMP-2 gene expression in atrium could be one of the molecular mechanisms of atrial fibrosis during atrial fibrillation, which correlates with the initiation and maintenance of AF.</p>