[Efficacy of endoscopic treatment oncolorectal laterally spreading tumor and risk factors of delayed bleeding after operation].

Objective: To evaluate the endoscopic treatment efficacy of colorectal laterally spreading tumor (LST) and analyze the risk factors for delayed post-polypectomy bleeding (DPPB). Methods: Between January 2015 and December 2020, patients underwent colorectal endoscopic submucosal dissection (ESD) or hybrid ESD were recruited from the Second Affiliated Hospital of Zhejiang University. Complete resection rate, perforation rate, bleeding rate, operation time and lesion adhesion were compared between the ESD and hybrid ESD groups. Patients were divided into bleeding and non-bleeding groups based on the presence of DPPB. Multivariate logistic regression analysis was used to analyze the risk factors of DPPB. Results: A total of 665 patients with colorectal LST were enrolled, including 376 males and 289 females, with an average age of (57.4±0.4) years. There were 471 cases underwent ESD and 194 cases underwent hybridized ESD. There were no significant differences in gender, age, history of smoking and drinking, and prevalence of hypertension between the two groups (all P>0.05). Likewise, the rate of lesion adhesion (4.2% vs 7.7%, P=0.067), lesion complete resection (96.8% vs 93.8%, P=0.418), perforation (0.6% vs 1.0%, P=0.594), delayed bleeding (2.8% vs 2.1%, P=0.605) were not statistically significant between the two groups. Seventeen patients (2.6%) developed DPPB after endoscopic treatment. Multivariate logistic regression analysis showed that the lesion was in the rectum (OR=3.594, 95%CI: 1.237-10.443, P=0.019) and the diameter of the lesion>2 cm (OR=3.776, 95%CI: 1.411-10.106, P=0.008) were risk factors for DPPB. Conclusions: Both ESD and hybrid ESD are successful treatments for colorectal LST. Colorectal LST lesion site and lesion size>2 cm are risk factors of DPPB.

[The role and significance of digital reconstruction technique in liver segments based on portal vein structure].

Objective: To study the segment of liver according to the large amount of three-dimensional(3D) reconstructive images of normal human livers and the vascular system, and to recognize the basic functional liver unit based on the anatomic features of the intrahepatic portal veins. Methods: The enhanced CT primitive DICOM files of 1 260 normal human livers from different age groups who treated from October 2013 to February 2017 provided by 16 hospitals were analyzed using the computer-aided surgery system.The 3D liver and liver vascular system were reconstructed, and the digital liver 3D model was established.The vascular morphology, anatomical features, and anatomical distributions of intrahepatic portal veins were statistically analyzed. Results: The digital liver model obtained from the 3D reconstruction of CAS displayed clear intrahepatic portal vein vessels of level four.Perform a digital liver segments study based on the analysis of level four vascular distribution areas.As the less anatomical variation of left hepatic portal vein, the liver was classified into four types of liver segmentation mainly based on right hepatic portal vein.Type A was similar to Couinaud or Cho's segmentation, containing 8 segments(537 cases, 42.62%). Type B contained 9 segments as there are three ramifications of right-anterior portal vein(464 cases, 36.82%). The main difference for Type C was the variation of right-posterior portal vein which was sector shape(102 cases, 8.10%). Type D contained the cases with special portal vein variations, which needs three-dimensional simulation to design individualized liver resection plan(157 cases, 12.46%). These results showed that there was no significant difference in liver segmental typing between genders(χ(2)=2.179, P=0.536) and did not reveal any significant difference in liver segmental typing among the different age groups(χ(2)=0.357, P=0.949). Conclusions: The 3D digital liver model can demonstrate the true 3D anatomical structures, and its spatial vascular variations.The observation of anatomic features, distribution areas of intrahepatic portal veins and individualized liver segmentation achieved via digital medical 3D visualization technology is of great value for understand the complexity of liver anatomy and to guide the precise hepatectomy.

[Effects of intermediate conductance calcium-activated potassium channel blocker TARAM-34 on ß-glycerophosphate induced vascular smooth muscle cells calcification].

OBJECTIVE: To observe the role of TRAM-34 (1-((2-chlorophenyl)diphenylmethyl)-1H-pyrazole), the blocker of intermediate conductance calcium-activated potassium channel (KCa3.1), on ß-glycerophosphate induced vascular calcification in vitro. METHODS: Vascular smooth muscle cells(VSMCs) were obtained from rat thoracic aorta, and VSMCs after the fourth passage and aortic rings were divided into control group (cultured in DMEM with 10% fetal bovine serum), high phosphorus group (cultured in DMEM with 10% fetal bovine serum and 10% ß-glycerophosphate) and TRAM-34 group(20 nmol/L TRAM-34 was added into high phosphorus DMEM). Calcium deposition of VSMCs and aortic rings were measured by o-cresolphthalein complexone method.Calcium influx of VSMCs was measured by immunofluorescence probe Fluo-3 AM.The expression of runt-related transcription factor 2(Runx2)was detected by RT-PCR and Western blot for cells and immunohistochemistry for aortic rings.ALP activity was measured by alkaline phosphatase activity detection kit. RESULTS: (1) Compared with control group, calcification was significantly increased in high phosphorus group ((121.67±6.17) mg/g vs. (84.38±8.17) mg/g, P<0.05) and this effect could be attenuated by TRAM-34 ((93.31±11.36) mg/g, P<0.05 vs. high phosphorus group) after 12 days culture. Similar results were found in aortic rings cultured for 12 days-high phosphorus group: (7.17±0.57) mg/g vs. CONTROL: (1.18±0.13) mg/g (P<0.05) and TRAM-34: (4.71±0.42) mg/g, P<0.05 vs. high phosphorus group.(2) Compared with control group, the calcium influx was higher in high phosphorus group (349.22±40.47 vs. 151.67±16.94, P<0.05) and reduced in TRAM-34 group (194.67±22.21, P<0.05 vs. high phosphorus group) in VSMCs simulated for 4 days. (3) Both mRNA and protein expressions of Runx2 in high phosphorus groups were higher than in control group (0.630±0.033 vs.0.340±0.058 and 0.865±0.031 vs.0.414±0.011, both P<0.05) and lower in TRAM-34 group (0.399±0.023 and 0.575±0.014, both P<0.05 vs. high phosphorus group) in VSMCs simulated for 4 days.Besides, compared with high phosphorus group, the expression of Runx2 was decreased in control group(0.113±0.010 vs.0.067±0.008, P<0.05) and TRAM-34 group (0.069±0.006, P<0.05) after aortic rings were cultured for 4 days. (4) Compared with control group, the activity of ALP was significantly increased in high phosphorus group (96.56±9.84 vs.46.92±4.60, P<0.05) and decreased in TRAM-34 group(70.20±8.41, P<0.05 vs. high phosphorus group) in VSMCs simulated for 12 days. CONCLUSION: KCa3.1 blocker TRAM-34 can inhibit ß-glycerophosphate induced VSMCs and aortic ring calcification through inhibiting calcium influx, downregulating Runx2 expression and attenuating osteogenic differentiation.

N-acetylcysteine attenuates subcutaneous administration of bleomycin-induced skin fibrosis and oxidative stress in a mouse model of scleroderma.

BACKGROUND: Several lines of evidence suggest that the generation of reactive oxygen species (ROS) is of major importance in the pathogenesis of scleroderma, and thus antioxidant therapy may be useful for patients with an impaired oxidative defence mechanism. AIM: To examine the effect of N-acetylcysteine (NAC) on skin fibrosis and oxidative stress in a bleomycin (BLM)-induced mouse model of scleroderma. METHODS: We used this mouse model to evaluate the effect of NAC on skin fibrosis and oxidative stress. Skin fibrosis was evaluated by histopathological examination and hydroxyproline content. To measure lipid peroxidation, we used a thiobarbituric acid-reactive species, malondialdehyde (MDA). Oxidative protein damage (carbonyl content) and the activities of catalase (CAT) and superoxide dismutase (SOD) were determined to evaluate oxidative stress in the skin tissue. RESULTS: Treatment with NAC attenuated the skin fibrosis induced by BLM, significantly reducing the MDA and protein carbonyl content in these mice. SOD activity in BLM-only mice and BLM plus NAC-treated mice was increased compared with control mice. However, there was no significant difference in skin SOD activity of mice treated with both BLM and NAC compared with those treated with BLM only. In addition, CAT activity was not altered in the BLM plus NAC mice. CONCLUSIONS: NAC treatment attenuates skin fibrosis in a BLM-induced mouse model of scleroderma, and this is associated with diminished oxidative stress. The results suggest that NAC may be a potential therapeutic agent for patients with scleroderma.

Regulation of NK92-MI cell cytotoxicity by substance P.

The neuropeptide substance P (SP) can regulate a number of immunological functions in vitro and in vivo and may regulate natural killer (NK) cell activity. Here, we investigated whether SP has a role in regulating NK92-MI cell function in vitro, and how it influences NK cell activity. We found that SP dose dependently increased the cytotoxicity of NK92-MI cells and had a maximal effect at a concentration of 10(-12) and 10(-10) m. Furthermore, the expression of cytotoxic-associated molecules (perforin, granzyme) and activating receptor NKp46 [a member of natural cytotoxicity receptors (NCRs)] was observed to be upregulated by SP at optimal concentration, at which SP enhanced the cytotoxicity of NK92-MI cells. Neurokinin-1 receptor (NK-1R), a functional receptor of SP, was found on NK92-MI cells, and the observed effects of SP on NK92-MI cells could be more partially blocked by an NK-1R antagonist. Our data suggest that SP induces NK92-MI cell cytotoxicity by directly increasing the expression of cytotoxic granules and upregulates NK92-MI cell receptor-mediated functions indirectly. Thus, SP may regulate NK cell function mainly through NK-1R.