Research Progress of Glucose Metabolism Reprogramming in Basic Research and Clinical Diagnosis and Treatment of Tumor / 肿瘤防治研究

Tumors provide materials and energy for themselves through glucose metabolic reprogramming to meet the needs of their rapid growth. Studies have shown that a variety of metabolic enzymes and signal molecules involved in glucose metabolism play an important role in tumorigenesis and development, and are considered to be important targets for the diagnosis and treatment of malignant tumors. The detection technology based on tumor glucose metabolism has been widely used in basic research and clinical diagnosis and treatment of tumor. This paper summarizes the characteristics, driving factors and key regulatory targets of tumor glucose metabolism, and the detection techniques and functions of tumor glucose metabolism from the aspects of basic medical research and clinical diagnosis and treatment.

Effectiveness of continuing care in patients with endonasal endoscopic conjunctivorhinostomy / 中国实用护理杂志

Objective:To analyze the effect of continuing care in patients treated with endonasal endoscopic conjunctivorhinostomy, so as to guide its clinical application.Methods:A total of 192 patients were selected with endonasal endoscopic conjunctivorhinostomy who were admitted to the Aier Eye Hospital of Wuhan University from June 2013 to June 2019 as the research objects. Randomized digital table method was used to divide them into control group and observation group, 96 cases in each group. The control group was given routine instructions before discharge, while the patients in observation group were given continuing care intervention on the basis of control group, including establishment of a continuing care group, establishment of health files of discharged patients, regular follow-up through telephone, establishment of WeChat groups for patients or their families, opening WeChat official account, organization of doctor-patient discussion meeting, and setting up reexamination services. The reexamination adherence rate, medication adherence rate, care satisfaction and treatment efficacy were compared between the two groups 6 months after implementation.Results:The reexamination adherence rate of the observation group on 1, 3, and 6 months after discharge were 85.42%(82/96), 96.88%(93/96), 72.92%(70/96), and the control group were 62.50%(60/96), 73.96%(71/96), and 43.75%(42/96), respectively, the difference between the two groups was statistically significant ( χ2 value was 13.088,20.237, 16.800, P<0.05); the medication adherence rate of the observation group was 89.58%(86/96), and the control group was 62.50%(60/96), the difference between the two groups was statistically significant ( χ2 value was 19.326, P<0.05); the observation group's care satisfaction was 94.79%(91/96), the control group was 78.13%(75/96), the difference between the two groups was statistically significant ( χ2 value was 11.388, P<0.05); the total treatment efficacy in the observation group was 96.88%(93/96), and the control group was 87.50%(84/96), the difference between the two groups was statistically significant ( χ2 value was 5.858, P<0.05). Conclusion:The application of continuing care for patients treated with endonasal endoscopic conjunctivorhinostomy can improve patients′ reexamination and medication adherence, improve care satisfaction, promote patients′ good recovery and achieve better surgical effects, which is worthy to recommend its clinical application.

Application value of three-dimensional reconstruction technique in laparoscopic hepatectomy / 中华消化外科杂志

Objective To evaluate the application value of three-dimensional (3D) reconstruction technique in laparoscopic hepatectomy.Methods The retrospective cohort study was conducted.The clinicopathological data of 189 patients with liver cancer who were admitted to the Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine from January 2014 to December 2018 were collected.There were 142 males and 47 females,aged from 27 to 86 years,with an average age of 60 years.According to the difficulty score of surgery,50 of 189 patients underwent laparoscopic complex hepatectomy,including 23 with preoperative 3D reconstruction in the complex reconstruction group and 27 with no preoperative 3D reconstruction in the complex control group;other 139 patients underwent laparoscopic non-complex hepatectomy,including 25 with preoperative 3D reconstruction in the non-complex reconstruction group and 114 with no preoperative 3D reconstruction in the non-complex control group.Observation indicators:(1) vascular assessment of patients who received 3D reconstruction;(2) surgical and postoperative situations;(3) typical case analysis.Measurement data with normal distribution were presented as Mean±SD,and comparison between groups was done using the t test.Measurement data with skewed distribution were presented as M (range),and comparison between groups was done using the Mann-Whitney U test.Count data were represented as absolute number or percentage,and comparison between groups was analyzed using the chi-square test or Fisher exact probability.Results (1) Vascular assessment of patients who received 3D reconstruction:48 of 189 patients were performed preoperative 3D reconstruction.Vascular assessment of 48 patients showed 41 of hepatic arterial Michels Ⅰ type,4 of Michels Ⅱ type,1,1,and 1 of Michels Ⅲ,Ⅳ,Ⅷ type,respectively.There were 35 belonging to hepatic venous Ⅰ type and 12 belonging to hepatic venous Ⅱ type and 1 with unclear distribution of hepatic vein.There were 5 and 3 belonging to portal venous Ⅰ type and Ⅱ type,38 with normal distribution of portal vein,and 2 with unclear distribution of portal vein,respectively.(2) Surgical and postoperative situations:50 of 189 patients underwent laparoscopic complex hepatectomy,and 139 underwent laparoscopic non-complex hepatectomy.The operation time and volume of intraoperative blood loss were (234±64)minutes and 200 mL (range,100-408 mL) in the complex reconstruction group,and (289±80)minutes and 500 mL (range,400-800 mL) in the complex control group,respectively,showing statistically significant differences between the two groups (t=-2.474,Z=-2.981,P＜ 0.05).Cases with postoperative complications and duration of postoperative hospital stay of complex reconstruction group were 8 and 6 days (range,4-12 days),respectively,versus 13 and 8 days (range,6-13 days) of complex control group.There was no significant difference (x2=0.911,Z =-1.634,P＞0.05).The operation time,volume of intraoperative blood loss,cases of postoperative complications and duration of postoperative hospital stay were 160.0 minutes (range,117.5-221.0 minutes),100 mL (range,75-200 mL),8,5 days (range,4-8 days) in the non-complex reconstruction group,157.5 min (range,100.0-222.5 minutes),100 mL (range,50-200 mL),43,6 days (range,4-7 days) in the non-complex control group,showing no significant difference between the two groups (Z=-0.525,-0.797,x2 =0.289,Z=-0.011,P＞0.05).(3) Typical case analysis:one 48-year-old male patient with primary liver cancer developed a personalized hepatectomy plan through simulation function of vascular drainage area in 3D reconstruction.One 49-year-old female patient achieved indirect intraoperative navigation through emulation function of 3D reconstruction.Conclusions The 3D reconstruction of liver in preoperative assessment is beneficial to choice of surgical options and personalized surgical plan in the precise hepatectomy.Especially in the laparoscopic complex hepatectomy,preoperative 3D reconstruction can shorten operation time,and reduce volume of intraoperative blood loss.

Laparoscopic liver tumor resection under indocyanine green fluorescent navigation: A single center experience of 60 patients to study the optimal preoperative injection timing of indocyanine green / 中华肝胆外科杂志

Objective To study the optimal timing of preoperative injection of indocyanine green in laparoscopic liver tumor resection under indocyanine green fluorescent navigation to obtain the most satisfactory fluorescence imaging effects.Methods 60 patients with liver tumors who underwent laparoscopic hepatectomy from April 2017 to October 2018 were retrospectively studied on the intraoperative fluorescence imaging effects.A simple grading of the fluorescence imaging effects was developed.The ICG R15 and preoperative injection times of ICG were correlated with the intraoperative fluorescence imaging effects.Results Of 60 patients with liver tumors,59 patients underwent laparoscopic liver resection and one patient was converted to open surgery.The overall satisfaction rate of intraoperative fluorescence imaging was 73.4％ (44/60).In the patients with an ICG R15 rate ≤ 7％,it was easier to obtain good fluorescence imagings when the preoperative administration time was longer than 48 hours.Even when the preoperative administration time was longer than 5 days,satisfactory fluorescence imaging effect could still be obtained in these patients.In the patients with an ICG R15 rate ＞ 7％,intraoperative fluorescence imagings were unsatisfactory when the administration time was less than 6 days.Relative better imagings were obtained in these patients when the preoperative administration time was more than 6 days.Conclusions When the pre-operative ICG injection dose was not changed,the preoperative administration time should be adjusted according to the value of the ICG R15 to obtain better intraoperative fluorescence imaging effects of the liver tumors.The optimal timing needs to be further studied by a large case study.

Advances in the research and application of cell penetrating peptides / 生物工程学报

Cell-penetrating peptides (CPPs) are short peptides that can penetrate the cell membrane or tissue barrier. CPPs can deliver a variety of biomacromolecules, such as proteins, RNA and DNA, into cells to produce intracellular functional effects. Endocytosis and direct penetration have been suggested as the two major uptake mechanisms for CPPs-mediated cargo delivery. Compared with other non-natural chemical molecules-based delivery reagents, the CPPs have better biocompatibility, lower cytotoxicity, are easily degraded after cargo delivery, and can be fused and recombined expressed with bioactive proteins. Because of these advantages, the CPPs have become an important potential tool for delivery of developing drugs which targets intracellular factors. As a novel delivery tool, the CPPs also show promising application prospects in biomedical researches. This review summarized recent advances regarding the classification characteristics, the cellular uptake mechanisms and therapeutic application potentials of CPPs.

Clinical efficacy and experiences of laparoscopic hepatectomy for segment Ⅶ and Ⅷ liver tumors / 中华消化外科杂志

Objective To investigate the clinical efficacy and experiences of laparoscopic hepatectomy (LH) for segment Ⅶ and Ⅷ liver tumors.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 94 patients who underwent LH for segment lⅦ or Ⅷ liver tumors in the Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine from June 2010 to August 2016 were collected.The operating space for operation was built under laparoscopy.According to liver cirrhosis grading,tumor size,adjacent relationship with major blood vessels and residual liver volume,non-anatomical and anatomical hepatectomies were selected by patients.During the operation,tumors were precisely pinpointed and plane of liver resection was determined,and then proper instruments of liver partition and techniques of hepatic inflow occlusion were selected.Observation indicators:(1) surgical and postoperative recovery situations;(2) postoperative pathological examination;(3) follow-up and survival situation.Follow-up using outpatient examination and telephone interview was performed to detect the patients' survival up to July 2017.Measurement data with normal distribution were represented as (x)±s.Measurement data with skewed distribution were described as M (interquartile range).Survival rate was caculated by the Kaplan-Meier method.Results (1) Surgical and postoperative recovery situations:all 94 patients received successful operations,without perioperative death,including 73undergoing non-anatomical hepatectomy and 21 undergoing anatomical hepatectomy.Fourteen patients had conversion to open surgery and 27 received hepatic inflow occlusion.The median operation time,median volume of intraoperative blood loss and cases with intraoperative blood transfusion were respectively 187.5 minutes (75.0minutes),200 mL (200 mL) and 15.Eighteen patients had postoperative complications,including 6 with pleural effusion,6 with abdominal effusion,1 with wound infection,1 with abdominal infection,1 with venous thrombosis,1 with bleeding,1 with coagulation disorders and 1 with hepatic insufficiency.Clavien-Dindo classification of complications:11,1,5 and 1 patients were detected in grade Ⅰ,lⅡ,Ⅲ and Ⅳ,respectively.All complications were improved by symptomatic treatment.The median duration of hospital stay was 7 days (6 days).(2) Postoperative pathological examination:results of tumor pathological examination showed that 45,5,9 and 35 patients were respectively confirmed as hepatocellular carcinoma,cholangiocarcinoma,metastatic hepatic carcinoma and benign liver tumor.(3) Follow-up and survival situation:59 patients with malignant tumors were followed up for 6.0-52.0 months,with a median time of 42.6 months.Postoperative 1-and 3-year overall survival rates of 59 patients with malignant tumors were 98.3％ and 84.7％,respectively.Conclusions LH for segment Ⅶ and Ⅷ liver tumors which is conducted in experienced medical center is safe and feasible,with definite effects.Building operating space for operation under laparoscopy,determining precise positioning of the tumor and plane of liver resection,and selecting proper instruments of liver partition and techniques of hepatic inflow occlusion are the key points of successful operation.

Antitumor effects and mechanisms of DC-CIK biotherapy combined with sorafenib against lung ade-nocarcinoma cells / 中华微生物学和免疫学杂志

Objective To investigate the antitumor effects and the possible mechanisms of dendrit-ic cells co-cultured with cytokine-induced killer cells(DC-CIK)in combination with sorafenib on two lung adenocarcinoma cell lines,A549 cells(harboring KRAS gene mutation)and PC-9 cells(harboring EGFR gene mutation). Methods DC and CIK cells were routinely generated in vitro by stimulating PBMCs isola-ted from lung cancer patients with different cytokines and then co-cultured after a week of culturing. Flow cy-tometry analysis(FCM)was used to analyze the phenotype of DC-CIK cells after 7 days of co-culturing. The 50% inhibitory concentration(IC50 )of sorafenib against tumor cells was detected by MTT assay. The tumor cells were treated with DC-CIK cells alone or in combination with sorafenib. The proliferation of tumor cells was tested by CCK-8 kit and dynamically monitored by real-time cellular analysis(RTCA). Annexin-V/ PI staining was used to examine the apoptosis rates in each group. Real-time fluorescent quantitative PCR and FCM were respectively performed to detect the expression of natural killer group 2 member D ligands (NKG2DLs)at mRNA and protein levels after the treatment with sorafenib for 24 h. Results There was no significant difference between the IC50 of sorafenib against A549 and PC-9 cells after a 24-hour exposure(P﹥0. 05). Compared with the DC-CIK biotherapy,treating the tumor cells with DC-CIK cells in combination with sorafenib significantly inhibited the cell proliferation and increased the total apoptosis rates of tumor cells(P﹤0. 05). Moreover,the inhibition rates to tumor cell proliferation were enhanced along with the in-crease of effect-to-target ratio(E/ T). Compared with the single-factor treatment groups,the normalized cell index(NCI)in the combined treatment group was significantly decreased. Blocking NKG2D could abate the inhibitory effect of DC-CIK cells on tumor cell proliferation(P﹤0. 05). The expression of NKG2DLs(inclu-ding ULBP1,UBLP2 and ULBP3)on tumor cells at mRNA and protein levels were increased to different ex-tent after treating with 5 μmol/ L of sorafenib for 24 h. Conclusion There was no significant different be-tween the inhibitory effects of sorafenib on the proliferation of lung adenocarcinoma cancer cells harboring KRAS or EGFR gene mutation. The antitumor effects of DC-CIK cells combined with sorafenib on lung ade-nocarcinoma cells might be induced by regulating the NKG2D-NKG2DLs pathway and enhancing apoptosis. Moreover,the antitumor effects of the combined treatment were better than those of single-factor treatments.