Overexpression of miR-431-5p impairs mitochondrial function and induces apoptosis in gastric cancer cells via the Bax/Bcl-2/caspase3 pathway / 南方医科大学学报

OBJECTIVE@#To investigate the expression of microRNA miR-431-5p in gastric cancer (GC) tissues and its effects on apoptosis and mitochondrial function in GC cells.@*METHODS@#The expression level of miR-431-5p in 50 clinical samples of GC tissues and paired adjacent tissues was detected using real-time fluorescence quantitative PCR, and its correlation with the clinicopathological features of the patients was analyzed. A cultured human GC cell line (MKN-45 cells) were transfected with a miR-431-5p mimic or a negative control sequence, and the cell proliferation, apoptosis, mitochondrial number, mitochondrial potential, mitochondrial permeability transition pore (mPTP), reactive oxygen species (ROS) production and adenosine triphosphate (ATP) content were detected using CCK-8 assay, flow cytometry, fluorescent probe label, or ATP detection kit. The changes in the expression levels of the apoptotic proteins in the cells were detected with Western blotting.@*RESULTS@#The expression level of miR-431-5p was significantly lower in GC tissues than in the adjacent tissues (P < 0.001) and was significantly correlated with tumor differentiation (P=0.0227), T stage (P=0.0184), N stage (P=0.0005), TNM stage (P=0.0414) and vascular invasion (P=0.0107). In MKN-45 cells, overexpression of miR-431-5p obviously inhibited cell proliferation and induced cell apoptosis, causing also mitochondrial function impairment as shown by reduced mitochondrial number, lowered mitochondrial potential, increased mPTP opening, increased ROS production and reduced ATP content. Overexpression of miR-431-5p significantly downregulated the expression of Bcl-2 and increased the expressions of pro-apoptotic proteins p53, Bcl-2 and cleaved caspase-3 protein.@*CONCLUSION@#The expression of miR-431-5p is down-regulated in GC, which results in mitochondrial function impairment and promotes cell apoptosis by activating the Bax/Bcl-2/caspase3 signaling pathway, suggesting the potential role of miR-431-5p in targeted therapy for GC.

Chinese expert consensus on the management of immune-related adverse events of hepato-cellular carcinoma treated with immune checkpoint inhibitors (2021 edition) / 中华消化外科杂志

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.

Evidence-based medicine proof and development trends of first-line treatment for advanced hepatocellular carcinoma / 中华消化外科杂志

Tyrosine kinase inhibitors (TKIs) are used as the primary first-line treatment for advanced hepatocellular carcinoma, and the combination of immune checkpoint inhibitors (ICIs) and angiogenesis inhibitors have also been recommended as first-line treatment recently. For hepatocellular carcinoma patients with portal vein tumor thrombus, hepatic artery infusion chemotherapy (HAIC) is supported by progressively more evidence in improvement in the overall survival benefit. Based on relevant literatures and combined with clinical practices, the authors investigate the clinical application and development trends of TKIs, ICIs and HAIC in the first-line treatment for advanced hepatocellular carcinoma.

Analysis of the related factors of complications after laparoscopic D2 radical operation in the treatment of advanced gastric cancer / 中国基层医药

Objective To analyze the related factors of postoperative complications after laparoscopic assisted D2 radical resection for advanced gastric cancer.Methods From August 2015 to July 2017,80 patients with advanced gastric cancer admitted to the First Hospital of Jiaxing were selected.All the patients were treated with laparoscopic-assisted D2 radical resection,and the risk factors related to postoperative complications were analyzed by logistic regression analysis model.Results There were 33 cases (41.25％) with postoperative system complications,19 cases (23.75％) with complications of level Ⅱ and above;15 cases (18.75％) with postoperative local complications,among them 12 cases (15.00％) appeared level Ⅱ and above local complications.The number of concomitant diseases and age were related risk factors for systemic complications in patients with advanced gastric cancer after laparoscopic D2 radical resection (OR =1.982,95 ％ CI:2.183-34.405,OR =6.587,95 ％ CI:1.738-23.495,all P ＜ 0.05).The preoperative neoadjuvant chemotherapy,reconstruction method and age were the risk factors for local complications in patients with advanced gastric cancer after laparoscopic D2 radical resection (OR =8.273,95 ％ CI:4.982-35.394,OR =12.304,95 ％ CI:2.384-88.921,OR =6.365,95 ％ CI:2.183-21.384,all P ＜ 0.05).Conclusion Treatment of advanced gastric cancer patients with laparoscopic D2 radical mastectomy,attention should be paid to control the patients'age,preoperative neoadjuvant chemotherapy,reconstruction mode,associated disease and other related risk factors.In order to ensure the safety of patients and to avoid postoperative complications.

Analysis of the related factors of complications after laparoscopic D2 radical operation in the treatment of advanced gastric cancer / 中国基层医药

Objective@#To analyze the related factors of postoperative complications after laparoscopic assisted D2 radical resection for advanced gastric cancer.@*Methods@#From August 2015 to July 2017, 80 patients with advanced gastric cancer admitted to the First Hospital of Jiaxing were selected.All the patients were treated with laparoscopic-assisted D2 radical resection, and the risk factors related to postoperative complications were analyzed by logistic regression analysis model.@*Results@#There were 33 cases (41.25%) with postoperative system complications, 19 cases (23.75%) with complications of level Ⅱ and above; 15 cases (18.75%) with postoperative local complications, among them 12 cases (15.00%) appeared level Ⅱ and above local complications.The number of concomitant diseases and age were related risk factors for systemic complications in patients with advanced gastric cancer after laparoscopic D2 radical resection (OR=1.982, 95%CI: 2.183-34.405, OR=6.587, 95%CI: 1.738-23.495, all P<0.05). The preoperative neoadjuvant chemotherapy, reconstruction method and age were the risk factors for local complications in patients with advanced gastric cancer after laparoscopic D2 radical resection (OR=8.273, 95%CI: 4.982-35.394, OR=12.304, 95%CI: 2.384-88.921, OR=6.365, 95%CI: 2.183-21.384, all P<0.05).@*Conclusion@#Treatment of advanced gastric cancer patients with laparoscopic D2 radical mastectomy, attention should be paid to control the patients' age, preoperative neoadjuvant chemotherapy, reconstruction mode, associated disease and other related risk factors.In order to ensure the safety of patients and to avoid postoperative complications.

Vascular injury and anatomy during laparoscopy - assisted distal gastrectomy with D2 lymphadenectomy for gastric cancer / 中华胃肠外科杂志

Objective@#To evaluate the incidence of intraoperative vascular injury (IVI) and associated anatomical features during laparoscopy - assisted distal gastrectomy (LADG) with D2 lymphadenectomy for gastric cancer.@*Methods@#A descriptive cohort study was performed. Clinical data and operational videos of 278 consecutive gastric cancer patients who underwent LADG with D2 lymphadenectomy for gastric cancer at Department of General Surgery of Nanfang Hospital between January 2010 and December 2017 were retrospectively analyzed. IVI and vascular anatomy during lymphadenectomy were observed and recorded in the following four scenes: scene I: No. 4sb and No.4d of lower left (tail of pancreas) area; scene II: No.6 of lower right (subpyloric) area; scene III: No.5 and No.12a of upper right (suprapyloric) area; scene IV: No. 7, No. 8a, No. 9, No. 11p of central area posterior to the gastric body. IVI was defined as the injury of main perigastric vessel requiring additional procedure for hemostasis such as electrocauterization, gauze compression, clipping or suture.@*Results@#Among 278 patients, 125 (45.0%) had IVI. Two cases of IVI required conversion to open operation and the injuried vascular was left gastric artery (LGA) and right gastric artery (RGA), respectively. Higher incidence of IVI was found in scene II (92/278, 33.1%) and scene IV(39/278, 14.0%). More common IVI was observed in right gastroepiploic vein (RGeV, 57/278, 20.5%) and left gastric vein (LGV, 33/278, 11.9%). The right gastroepiploic vessels were observed in all 278 patients, including 3 (1.1%) cases with 2 RGeVs, and 2 cases with 2 right gastroepiploic arteries (RGeA). RGA was observed clearly in 265 (95.3%) patients, whose ramification pattern was as follows: from proper hepatic artery (PHA, 223/265, 84.2%), from gastroduodenal artery (GDA, 16/265, 6.0%), from left hepatic artery (LHA, 12/265,4.5%), from the crossing of PHA and GDA (8/265, 3.0%), and 6 (2.3%) patients with 2 RGAs simultaneously from PHA and GDA, respectively. The most common injury of RGA (4/12) occurred in LHA. Excluding 2 cases of conversion to open surgery due to intraoperative hemorrhage, among 276 patients, LGV was observed in 270 patients (97.1%), whose drainage pattern was as follows: into the portal vein (PV, 148/270, 54.8%), into the spleen vein (SV, 56/270, 20.7%), into the junction of these two veins (52/270, 19.3%), into left portal vein (LPV, 8/270, 3.0%), meanwhile 6 patients had 2 LGVs simultaneously, including LGVs of 5 cases into PV and SV, and of 1 case into PV-SV junction and SV. The most common IVI was found in those patients with two LGVs (4/6).@*Conclusions@#IVI during LADG with D2 lymphadenectomy is common. The highest risk of IVI is found in scene II and scene IV. Attentions should be paid to anatomic variation of vessels, especially the RGeV, LGV and RGA.

Expression and its clinical significance of programmed death ligant 1 on CD3+ T cells in colorectal cancer / 中华消化杂志

Objective To study on the expression and clinical significance of programmed death ligant 1 (PD-1) in the development of colorectal cancer.Methods Flow cytometry (FCM) was used to detect and analyse the positive expression rate of PD-1 on CD3+ T cells in peripheral blood samples of 88 colorectal cancer patients and 74 healthy volunteers,and in sixpairs of tissue specimens (colorectal cancer tumor and adjacent normal tissues).Colon cancer tumor-bearing mice models were constructed by subcutaneous implantation of murine colon cancer cell line CT26,and the changes of positive expression rate of PD-1 on CD3+ T cells in spleens and transplanted tumor tissues were also detected by FCM in different time points during five,eight,11,14,17,20 days after the model was constructed.Finally,the experimental results were analyzed by t test or variance analysis.Results The positive expression rate of PD-1 on CD3+ T cells in peripheral blood of colorectal cancer patients was significantly higher than that in healthy volunteers ((29.25 ± 9.37) ％ vs (19.35 ± 7.37) ％,t =7.375,P＜ 0.01),and the positive expression rates were significantly increased in colorectal cancer patients with lower degree of differentiation,lymph node metastasis and higher Duke's stage.The positive expression rate of PD-1 on CD3+T cells was significantly higher in colorectal cancer tissues compared to adjacent normal tissues ((52.38±12.28)％ vs (24.72±4.78)％,t=5.143,P＜0.01).In the colon cancer tumor-bearing mice models,along with the growth of transplanted tumors,PD-1 positive expression rates on the CD3+T cells of tumor-bearing mice spleens and transplanted tumors showed a gradually rising tendency.From the eighth day to the 20th day after subcutaneous transplanted colon cancer cells,the average positive expression rate of PD-1 on the CD3+T cells of tumor-bearing mice spleens rose from (52.83±6.17)％ to (77.30± 6.84) ％,and the average positive expression rate of transplanted tumors rose from (60.43 ± 2.77)％ to (90.47±4.31) ％.Conclusion There is a correlation between the expression of PD-1 on mature T cell surface and the development of colorectal cancer,and the high specific expression of PD-1 may promote the invasion and metastasis of colorectal cancer.

Serum Levels and Clinical Significance of IL-18 and IL-1βin Patients with Gastric Cancer / 胃肠病学

Background:Chronic inflammation is closely associated with occurrence and development of gastric cancer,and inflammatory cytokines,interleukin-18(IL-18)and IL-1β are involved via a variety of mechanisms. Aims:To determine the serum levels of IL-18 and IL-1β in patients with different gastric mucosal lesions and to explore the role of these two cytokines in gastric cancer and their clinical significance. Methods:Serum levels of IL-18 and IL-1β were detected by ELISA in patients with different gastric mucosal lesions,including 324 gastric cancer,40 chronic non-atrophic gastritis (CNAG),13 chronic atrophic gastritis with or without intestinal metaplasia(CAG/ IM)and 20 mild to moderate dysplasia. Helicobacter pylori(Hp)IgG antibody was detected in patients with gastric cancer. Correlations of serum levels of IL-18 and IL-1β with clinicopathological parameters and Hp infection were analyzed in patients with gastric cancer. RoC curve was used to assess the performance of serum IL-18 and IL-1β for diagnosis of gastric cancer. Results:Serum levels of IL-18 and IL-1β increased gradually from CNAG,CAG/ IM,dysplasia to gastric cancer;except for IL-1β between CNAG and CAG/ IM groups,significant differences were found between any two groups(P < 0. 05). In gastric cancer group,they were positively correlated with tumor size,lymph node and distant metastases,depth of invasion,TNM stage and Hp infection(P < 0. 05). Area under the RoC curve(AUC)of combined detection of serum IL-18 and IL-1β for diagnosis of gastric cancer was superior to that of IL-18 or IL-1β detection alone(0. 867 vs. 0. 837 and 0. 795). Conclusions:Serum levels of IL-18 and IL-1β increase dynamically with the tumorigenesis of gastric cancer,and are closely related to growth, invasiveness and metastasis of gastric cancer. Combined detection of serum IL-18 and IL-1β might be used as a biomarker for diagnosis and tumor progression and prognosis assessment of gastric cancer.

Expression of Peripheral Blood PD-1 and its Clinical Significance in Patients with Colorectal Cancer / 胃肠病学

Background:The abnormal expression of costimulatory molecules is closely related to immune escape of tumor cells. Programmed death-1(PD-1)is an important negative costimulatory molecule,and can induce and maintain the immune tolerance of tumor cells by binding with related ligands,thus promotes the development and progress of tumor. Aims:To investigate the expression of peripheral blood PD-1 and its clinical significance in patients with colorectal cancer. Methods:Eighty-eight patients with colorectal cancer from March 2015 to September 2015 at the First Affiliated Hospital of Soochow University were enrolled,and 16 healthy volunteers were served as controls. Level of soluble PD-1(sPD-1)was determined by ELISA. The expression of PD-l on CD3 + T cells in peripheral blood was measured by flow cytometry. Results:Level of sPD-1 and expression of PD-l on CD3 + T cells in peripheral blood in colorectal cancer patients were significantly higher than those in controls(P ﹤ 0. 05). Level of sPD-1 in colorectal cancer patients was closely related to tumor differentiation,lymph node metastasis and Dukes’stage( P ﹤ 0. 05),but not related to gender,age and tumor location(P ﹥ 0. 05). Conclusions:Peripheral blood PD-1 is highly expressed in patients with colorectal cancer,and is positively correlated with tumor stage and metastasis. The detection of PD-1 is helpful to estimate the progress of colorectal cancer,and it may become a new tumor marker or a target for anti-tumor targeted therapy.

The technique and development of total skin electron irradiation-Taiwan experiences / 中华放射肿瘤学杂志

Objective The aim of this study is to present two novel technique?Lying on position and rotational board TSEI in which uniform dose to the whole body as well as the soles and vertex of scalp can be achieved in one electron beam treatment fraction. Methods Patients are treated with two groups in prone and supine position by leaning on inner rotational board in prone and supine position, each group can further be separated into two subgroup with tilting and rotation positions for treatment. By incorporating all these setting on the aswirl board with the optimal gantry angle, the patient will final accumulate compensated dosages on whole body surface. Results The dose uniformity for the rotational board?TSET or Lying on position could be control within ±10%. Conclusions The two TSEItechnique?Lying on and Rotational board TSEI techniques presented in this study is able to deliver a uniform dose to the patient’s skin surface as well as to the vertex and the soles all in one time, eliminating the troubles of having to further boost fields for these two regions when using the Stanford Six Field Technique.

Research progression on preoperative mechanical bowel preparation for elective colorectal surgery / 中华胃肠外科杂志

Preoperative mechanical bowel preparation (MBP) has been established as a standard procedure for elective colorectal surgery in most surgical centers since 1950s. However, the routine use of MBP for elective colorectal surgery is still in debate, as the researches on the evaluation of MBP have been carried out in recent 20 years. By searching and analyzing the existing evidence, we conclude that MBP should be routinely abandoned for elective open colorectal surgery, but should be routinely used for elective laparoscopic rectal surgery, and it still awaits large-scale RCTs for further evaluation of MBP for elective laparoscopic colonic surgery.

Anatomy of the perigastric vessels in laparoscopy-assisted distal gastrectomy with D2 lymphadenectomy for gastric cancer / 中华胃肠外科杂志

The laparoscopic approach is rapidly becoming the preferred method of treatment for patients with early gastric cancer due to advantages of minimally invasive surgery. As laparoscopic experience has accumulated, laparoscopy-assisted distal gastrectomy (LADG) with D2 lymphadenectomy has become a valuable alternative for the treatment of patients with advanced gastric cancer. However, laparoscopic gastric surgery is demanding from a technical point of view, especially when a D2 lymphadenectomy is performed. Surgeons seeking to undertake LADG are concerned about unpredictable intraoperative bleeding that may occur during LADG. Comprehensive knowledge of the perigastric vascular anatomy is essential for LADG with D2 lymphadenectomy.

Curative effect of interference current and direct current pharmaceutical iontophoresis in patients with retrograde gonarthritis / 中国基层医药

Objective To observe and analyse the efficacy of retrograde gonarthritis with interference current and drug-iontophoresis direct current. Methods 185 patients with retrograde gonarthritis were randomly divided into treatment group 92 cases and control group 93 cases. The patients in treatment group underwent interference current and drug-iontophoresis direct current and patients in control group performed modulated medium frequency drug-ionto-phoresis direct current for two treatment courses. Results The comprehensive score of various kind of symptom such as pain、swelling、flexion、walking ability, up-down stair ability in treatment group significantly improved than that of control group (P < 0.01). Conclusion The interference current and drug-iontophoresis direct current is one of effec-tive and safe measurement in treating arthritis with main manifestation of pain and soft tissue disease.

Curative effect of cervical traction combined with low-cycle or intermediate frequency electrical current in cervical vertebrae / 中国基层医药

Objective To observe the curative effect of cervical traction combined with low-cycle or intermediate frequency electrical current in cervical vertebrae.Methods 171 patients with cervical vertebrae were randomly divided into the therapy group and control group,86 cases in therapy group were performed the curative measure of cervical traction and low-cycle,85 cases in control group underwent the curative measure of cervical traction and intermediate frequency electrical current.Both of the two groups carried out continuous therapy for 10 days.Results There was significant difference before and after treatment within each group in CASCS score(P ＜ 0.01)and there was also significant difference after treatment between the two groups(P ＜ 0.05),the effective rate of therapy groupwas significant higher than that of control group(P ＜ 0.05).Conclusion The methods of cervical traction and low cycle or intermediate frequency electrical current has better curative effect in cervical vertebrae and cervical traction and low-cycle do much benefit in cervical vertebrae treatment.

金钠多结合早期康复治疗对缺血性脑卒中患者功能结局的影响 / 中国康复理论与实践

@#目的观察金钠多结合早期康复治疗急性缺血性脑卒中的临床疗效。方法将80例缺血性脑卒中患者随机分为金钠多加早期康复组和低分子右旋糖酐加早期康复组(对照组)。观察两组患者治疗前后血脂及血液流变学、神经功能缺损、肢体运动功能及日常生活活动能力评分的变化。结果金钠多加早期康复组治疗后血脂、红细胞压积、纤维蛋白原均降低,神经功能缺损评分减少值、肢体运动功能及日常生活能力增加值均高于对照组(P<0.05～0.01)。结论金钠多结合早期康复能减轻急性缺血性脑卒中患者的神经功能缺损,提高患者独立生活能力,改善功能结局,提高康复效率。

Effect of neuromuscular facilitation combined with faradism on limbs motor function in hemiplegic patients with stroke / 中国康复理论与实践

@#ObjectiveTo explore the effect of neuromuscular facilitation combined with faradism on limbs motor function in hemiplegic patient with early stroke.Methods108 patients were randomly divided into the therapy group(who accepted neuromuscular facilitation combined with faradism) and control group (who accepted neuromuscular facilitation only). The limbs motor function was evaluated with Fugl-Meyer Assessment (FMA) before and after 10 weeks by the same doctor. ResultsThere were not significant difference of scores of FMA between the two groups before rehabilitation(P>0.05), but there were significant difference 10 weeks after rehabilitation(P<0.01). ADL in therapy group was significantly higher than that in control group(P<0.01).ConclusionFaradism can significantly improve the effect of neuromuscular facilitation on limbs motor function and ADL.

The advances of angiogenesis assay models / 中国药理学通报

Anti-angiogenesis has been one of the important strategies in treating tumor metastasis,diabetic retinopathy,rheumatic arthritis etc.Angiogenesis models have played an active role in studying the mechanism of angiogenesis and developing drugs of pro-or anti-angiogenesis.A common problem faced by angiogenesis researchers has been the difficulty of choosing suitable models.This paper reviews principal models in use for some details and their advantages and shortages.