Study on the Biological Function of Abemecilib in Inhibiting the Proliferation, Invasion and Migration of Small Cell Lung Cancer with High c-Myc Expression / 中国肺癌杂志

BACKGROUND@#Small cell lung cancer (SCLC) with high c-Myc expression is prone to relapse and metastasis, leading to extremely low survival rate. Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor Abemaciclib plays a key role in the treatment of tumors, but the effects and mechanisms on SCLC remain unclear. This study was to analyze the effect and molecular mechanism of Abemaciclib in inhibiting proliferation, migration and invasion of SCLC with high c-Myc expression, with a view to expanding a new direction for reducing the recurrence and metastasis.@*METHODS@#Proteins interacting with CDK4/6 were predicted using the STRING database. The expressions of CDK4/6 and c-Myc in 31 cases of SCLC cancer tissues and paired adjacent normal tissues were analyzed by immunohistochemistry. The effects of Abemaciclib on the proliferation, invasion and migration of SCLC were detected by CCK-8, colony formation assay, Transwell and migration assay. Western blot was used to detect the expressions of CDK4/6 and related transcription factors. Flow cytometry was used to analyze the effects of Abemaciclib on the cell cycle and checkpoint of SCLC.@*RESULTS@#The expression of CDK4/6 was associated with c-Myc by STRING protein interaction network. c-Myc can directly modalize achaete-scute complex homolog 1 (ASCL1), neuronal differentiation 1 (NEUROD1) and Yes-associated protein 1 (YAP1). Moreover, CDK4 and c-Myc regulate the expression of programmed cell death ligand 1 (PD-L1). Immunohistochemistry showed that the expressions of CDK4/6 and c-Myc in cancer tissues were higher than those in adjacent tissues(P<0.0001). CCK-8, colony formation assay, Transwell and migration assay verified that Abemaciclib could effectively inhibit the proliferation, invasion and migration of SBC-2 and H446OE(P<0.0001). Western blot analysis further showed that Abemaciclib not only inhibited CDK4 (P<0.05) and CDK6 (P<0.05), but also affected c-Myc (P<0.05), ASCL1 (P<0.05), NEUROD1 (P<0.05) and YAP1 (P<0.05), which are related to SCLC invasion and metastasis. Flow cytometry showed that Abemaciclib not only inhibited the cell cycle progression of SCLC cells (P<0.0001), but also significantly increased PD-L1 expression on SBC-2 (P<0.01) and H446OE (P<0.001).@*CONCLUSIONS@#Abemaciclib significantly inhibits the proliferation, invasion, migration and cell cycle progression of SCLC by inhibiting the expressions of CDK4/6, c-Myc, ASCL1, YAP1 and NEUROD1. Abemaciclib can also increase the expression of PD-L1 in SCLC.

Predictive value of postoperative C-reactive protein for serious complications after Da Vinci robotic surgical system radical gastrectomy of gastric cancer / 中华消化外科杂志

Objective:To investigate the predictive value of postoperative C-reactive protein for serious complications after Da Vinci robotic surgical system radical gastrectomy of gastric cancer.Methods:The retrospective case-control study was conducted. The clinicopathological data of 298 patients with advanced gastric cancer who underwent Da Vinci robotic surgical system radical gastrectomy in the 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army from January 2017 to June 2019 were collected. There were 253 males and 45 females, aged from 24 to 86 years, with a median age of 60 years. Of the 298 patients, 275 cases underwent no serious postoperative complications and 23 cases underwent serious postoperative complications. Observation indicators: (1) serious postoperative complications; (2) analysis of risk factors for serious postoperative complications after Da Vinci robotic surgical system radical gastrectomy of gastric cancer; (3) performance evaluation of the predictive indicators. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the rank sum test. Univariate analysis was conducted using the chi-square test. Multivariate analysis was conducted using Logistic regression model. The receiver operating characteristic curve was drawn and the area under curve (AUC) was used to compare and estimate the efficiency of diagnostic criteria. The value of Youden index was used to determine the optimal cut-off point. Results:(1) Serious postoperative complications: of the 298 patients, 23 cases underwent complications classified ≥grade Ⅲa of Clavien-Dindo classifica-tion, including 10 cases with grade Ⅲa complications, 7 cases with grade Ⅲb complications, 4 cases with grade Ⅳa complications, 1 case with grade Ⅳb complications and 1 case with grade Ⅴ complications. (2) Analysis of risk factors for serious postoperative complications after Da Vinci robotic surgical system radical gastrectomy of gastric cancer. Results of univariate analysis showed that operation time, indicators of C-reactive protein concentration and neutrophil count at post-operative day 1, and indicators of C-reactive protein concentration, white blood cells count, neutrophil count and platelet count at postoperative day 3 and pathological stage were related factors affecting serious complications for advanced gastric cancer after Da Vinci robotic surgical system radical gastrectomy ( χ2=7.671, 4.504, 5.045, 48.293, 9.575, 15.436, 13.731, 9.537, P<0.05). Results of multivariate analysis showed that the operation time ≥250 minutes, the concentration of C-reactive protein at postoperative day 3 ≥16.65 mg/dL, the neutrophil count at postoperative day 3 ≥8.167×10 9/L, the platelet count at postoperative day 3 ≥218×10 9/L and the pathological stage of tumor as stage Ⅱ and stage Ⅲ were independent risk factors affecting serious complications for advanced gastric cancer after Da Vinci robotic surgical system radical gastrectomy ( odds ratio=3.721, 16.084, 6.056, 6.893, 12.455, 95% confidence interval: 1.032-13.421, 4.657-55.547, 1.073-34.163, 1.798-26.423, 1.338-115.930, P<0.05). (3) Performance evaluation of the predictive indicators: the C-reactive protein concentration at postoperative day 3 was a high-performance predictor with the AUC as 0.851 (95% c onfidence interval: 0.780-0.921, P<0.05) and neutrophil count and platelet count at postoperative day 3 were low-performance predictors with the AUC as 0.659 and 0.666 (95% confidence interval: 0.570-0.748 and 0.581-0.750, P<0.05). Conclusion:The C-reactive protein concentration ≥16.65 mg/dL at postoperative day 3 is a high performance predictive indicator for serious complications after Da Vinci robotic surgical system radical gastrectomy of gastric cancer.

Newborn screening and genetic analysis of methylmalonic acidemia in Shaanxi province / 中华围产医学杂志

Objective:To analyze the incidence, biochemical and molecular characteristics, and gene mutation spectrum of neonatal methylmalonic acidemia (MMA) in Shaanxi province.Methods:This study involved 146 152 newborns undergoing neonatal screening for methylmalonic acidemia by tandem mass spectrometry in Northwest Women's and Children's Hospital from January 2014 and December 2019. Clinical manifestations and follow-up data of newborns diagnosed with MMA and their acylcarnitine profiles and gene mutations were analyzed. According to whether they had elevated homocysteine or not, these patients were divided into two groups, the complicated group and the isolated MMA group. The control neonates were those excluded from having methylmalonic acid by re-examination. Kruskal-Wallis and Mann-Whitney U test was conducted for statistical analysis. Results:(1) Twenty-one cases of MMA were confirmed with an incidence of 1/6 960, including 11 cases (52.4%) of isolated MMA (isolated MMA group) and 10 (47.6%) complicated by elevated homocysteine (complicated group). Eight patients in the isolated group had symptoms within one month after birth, mainly feeding difficulties, vomiting, drowsiness, poor response and infection, and five died. Patients in the complicated group were all diagnosed before developing typical clinical symptoms, and no developmental abnormalities were reported during follow-up. (2) Blood propionyl carnitine and its ratios to acetylcarnitine and free carnitine in the isolated MMA and complicated groups were higher than those in the control group [ M (min-max), 9.26 (3.70-37.78) μmol/L and 7.27 μmol/L (3.58-13.62 μmol/L) vs 4.51 μmol/L (1.48-8.69 μmol/L), H=23.239; 1.12 (0.32-2.43) and 0.74 (0.36-1.90) vs 0.25 (0.09-0.45), H=47.061; 0.94 (0.12-1.92) and 0.56 (0.18-1.03) vs 0.17 (0.06-0.38), H=36.868; all P<0.001]. The blood methionine level in the complicated group was significantly lower than that in the isolated MMA group [7.64 μmol/L (3.40-19.25 μmol/L) vs 24.22 μmol/L (10.73-56.55 μmol/L), U=3.000, P<0.001]. (3) All 21 patients carried complex heterozygous mutations or homozygous mutations in pathogenic genes, including 15 distinct MMUT mutations and 13 distinct MMACHC mutations. In the isolated MMA group, the most common mutation was c.323G>A (p.Arg108His) in the MMUT gene with a positive rate of 13.6%, and an unreported mutation, c.1676+11A>G, with unidentified clinical significance, was also found. The most common mutations in the complicated group were c.609G>A (p.Trp203Ter) and c.567dupT (p.Ile190fs) in the MMACHC gene, and the positive rates were both 20.0%. Moreover, two unreported variants, c.430-2A>C and c.648_650delAGA (p.216_217delSEinsS), were detected and suspected to be pathogenic. Conclusions:MMA is not uncommon in Shaanxi province. Children with isolated MMA tend to be more severe clinically. The identification of hotspot mutations, including c.609G>A (p.Trp203Ter) and c.567dupT (p.Ile190fs) in MMACHC gene and c.323G>A (p.Arg108His) in MMUT gene, provides a foundation for further genetic screening, counseling, and prenatal diagnosis, and is conducive to reduce the mortality and disability rate of neonatal MMA.

Surveillance of drug resistance of clinically isolated fungi strains from 46 hospitals in Shandong Province / 中华临床感染病杂志

Objective:To analyze the distribution of clinically isolated fungal strains and their resistance to common antifungal drugs in Shandong province.Methods:Through the Shandong Children’s Bacterial & Fungal Drug Resistance Surveillance and Research Collaborative Network, a total of 1 030 fungi were collected in 46 hospitals of Shandong province from January 1 to December 31, 2018. The source and type of strains were analyzed, and antifungal drug sensitivity tests were performed by using the micro-dilution method. Whonet 5.6 and SPSS 22.0 were applied to analyze the data.Results:The overall main strains were Candida albicans (38.74%, 399/1 030), Candida tropicalis (16.99%, 175/1 030) and Candida parapsilosis (16.41%, 169/1 030); the main fungi strains in child patients were C. albicans (52.50%, 63/120), C. parapsilosis (12.50%, 15/120) and C. tropicalis (9.17%, 11/120); the main fungi strains in adult patients were C. albicans (36.37%, 331/910), C. tropicalis (17.03%, 155/910) and C. parapsilosis (15.27%, 139/910). The isolation rate of main Candida strains from January to March and August to December was much higher than that of other months. The drug resistance rates of C. albicans to fluconazole and voriconazole were 7.14% and 7.43%, respectively, and the drug resistance rates to itraconazole were 50.44%. The resistance rates of C. tropicalis to fluconazole, voriconazole and itraconazole were 29.05%, 23.29% and 48.65%, respectively. The sensitivity rates of C. parapsilosi to fluconazole, voriconazole and itraconazole were 93.06%, 93.75% and 94.44%, respectively. Candida glabrata showed a dose-dependent sensitivity rate of 2.33% to fluconazole. Analysis of 244 blood fungi strains showed that non-candida albicans bacteremia accounted for 70.08%. In the pathogen spectrum covering 92.22%, fluconazole was sensitive to 64.65% of the pathogens, voriconazole was 68.88%, and amphotericin B was 88.75%. After quantification, the effective rates of fluconazole, voriconazole and amphotericin B in the clinical treatment of fungal bacteremia were 70.10%, 74.69% and 96.23%, respectively. Among them, the sensitivity rate of voriconazole to C. tropicalis was lower than that of fluconazole. Conclusions:Candida is the main clinical fungus isolates in hospitals of Shandong province. The resistance rate of C. tropicalis to azole antifungal drugs is on the rise, and the sensitivity of other Candida species to clinically used antifungal drugs is basically stable.

Strategies and tools for metabolic engineering in Bacillus subtilis / 生物工程学报

As a typical food safety industrial model strain, Bacillus subtilis has been widely used in the field of metabolic engineering due to its non-pathogenicity, strong ability of extracellular protein secretion and no obvious codon preference. In recent years, with the rapid development of molecular biology and genetic engineering technology, a variety of research strategies and tools have been used to construct B. subtilis chassis cells for efficient synthesis of biological products. This review introduces the research progress of B. subtilis from the aspects of promoter engineering, gene editing, genetic circuit, cofactor engineering and pathway enzyme assembly. Then, we also summarized the application of B. subtilis in the production of biological products. Finally, the future research directions of B. subtilis are prospected.

Comparative study on safety and feasibility between robot splenectomy and laparoscopic splenectomy / 中华普通外科杂志

Objective To explore the safety and feasibility of robot splenectomy.Methods 65 patients undergoing robotic or laparoscopic splenectomy at No.940 Hospital of Chinese people's Liberation Army Joint Service Support Force from Jan 2015 to Sep 2019 were analyzed retrospectively.Results The operation time and total hospitalization cost of robot spleen resection group and laparoscopic splenectomy group were [(167 ± 34) min vs.(123 ± 24) min,t =8.554,P =0.00] and (73 002 ± 21 009) yuan vs.(42 095 ± 9 999) yuan,(t =6.484,P =0.00),respectively.In laparoscopy group,3 cases were converted to laparotomy.In the subgroup of splenic hilum thickness ≥ 5 cm,the intraoperative bleeding volume of robot group and laparoscopic group was (145 ± 67) ml vs.(263 ± 180) ml,(t =-2.195,P =0.04).There were significant differences in VAS score (3 ±1) vs.(4 ±1),(t=2.175,P=0.04).Conclusion Robotic splenectomy is safe and feasible.For patients with splenomegaly,robot surgery has more minimally invasive advantages than laparoscopy,but it is expensive and time-consuming.

Application value of early postoperative enteral eco-immune nutrition in the nutritional support treatment for intra-abdominal infection: a prospective analysis / 中华消化外科杂志

Objective@#To explore the application value of early postoperative enteral eco-immune nutrition in the nutritional support treatment for intra-abdominal infection.@*Methods@#The prospective study was conducted. The clinicopathological data of 62 patients with intra-abdominal infection who were admitted to the 940 Hospital of the People′s Liberation Army Joint Service Support Force from February 2018 to December 2018 were collected. All patients were randomly divided into two groups by the envelope method with double-blind technique, including patients who began being given enteral eco-immune nutrition preparation at postoperative 24-48 hours in eco-immune group and patients who began being given simple enteral nutrition preparation at 24-48 hours in control group. Observation indicators: (1) analysis of immune function indices before treatment and after 7 days of treatment in the two groups; (2) postoperative conditions in the two groups; (3) follow-up. Follow-up using telephone interview was performed to detect complications and recurrence of infection up to May 2019. Measurement data with normal distribution were represented as Mean±SD, and intra-group comparison and comparison between groups were analyzed using the t test. Count data were represented as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test.@*Results@#Sixty-two patients were screened for eligibility, including 38 males and 24 females, aged (54±14)years, with the range of 22-81 years. There were 30 in the eco-immune group and 32 in the control group. (1) Analysis of immune function indices before treatment and after 7 days of treatment in the two groups: before treatment, the percentages of CD3+, CD4+, CD8+, ratio of CD4+ /CD8+, count of natural killer (NK) cells, levels of blood endotoxin and immunoglobulin A (IgA) for the eco-immune group were 61%±12%, 34%±5%, 28%±5%, 1.25±0.34, 17.26%±2.74%, (2.4±0.3)ng/L, and (1.7±0.5)g/L, versus 59%±11%, 33%±5%, 27%±4%, 1.27±0.36, 16.96%±2.99%, (2.5±0.5)ng/L, (1.8±0.5)g/L for the control group, respectively, there were no significant differences between the two groups (t=-0.563, -0.354, -0.987, 0.327, -0.462, 0.887, 0.991, P>0.05). After 7 days of treatment, the above indices for the eco-immune group were 62%±8%, 37%±6%, 27%±8%, 1.45±0.32, 22.63%±7.25%, (2.2±0.4)ng/L, and (2.3±0.4)g/L, versus 58%±8%, 32%±4%, 27%±6%, 1.26±0.22, 16.26%±2.10%, (2.7±0.6)ng/L, and (2.0±0.4)g/L for the control group, respectively, there were significant differences in the percentages of CD3+, CD4+, ratio of CD4+ /CD8+, count of NK cells, levels of blood endotoxin and IgA (t=-2.393, -4.336, -3.074, -5.338, 4.010, -3.155, P<0.05), but no significant difference in the percentage of CD8+ between the two groups (t=0.077, P>0.05). In the eco-immune group, the percentage of CD4+, ratio of CD4+ /CD8+, count of NK cells, levels of blood endotoxin and IgA showed significant differences after 7 days of treatment (t=-2.899, -2.739, -4.385, 2.157, -5.788, P<0.05), but the percentages of CD3+ and CD8+ showed no significant differences after 7 days of treatment (t=-0.490, 1.193, P>0.05). In the control group, the percentage of CD8+ and level of IgA showed significant differences after 7 days of treatment (t=3.659, -2.258, P<0.05), but the percentage of CD4+, ratio of CD4+ /CD8+, count of NK cells, and level of blood endotoxin showed no significant differences after 7 days of treatment (t=0.157, 0.759, 1.132, 1.212, -0.532, P>0.05). (2) Postoperative conditions in the two groups: the time to first flatus and duration of postoperative hospital stay of the eco-immune group were (2.4±0.5)days and (8±4)days, respectively, versus (2.9±0.7)days and (11±7)days of the control group; there were significant differences in the above indices between the two groups (t=-3.017, -2.764, P<0.05). In the eco-immune group, the incidence of complication was 6.7%(2/30), including 1 case of wound infection, 1 case of pulmonary infection. In the control group, the incidence of complication was 31.2%(10/32), including 6 cases of wound infection, 2 cases of pulmonary infection, 1 case of intra-abdominal infection, and 1 case of systemic inflammatory response syndrome. There was a significant difference in the incidence of complication between the two groups (χ2=4.122, P<0.05). The patients with infection were recovered after corresponding systematic conservative treatments. (3) Follow-up: of the 62 patients, 46 were followed up for 3-9 months, with a median follow-up time of 6 months, including 26 in the eco-immune group and 20 in the control group. During the follow-up, no complication or infection recurred in the two groups.@*Conclusion@#Compared with simple enteral nutrition, early postoperative enteral eco-immune nutrition in the nutritional support treatment is safe and effective for patients with intra-abdominal infection, which can enhance the immune function of patients, shorten the recovery time of patients, and reduce the incidence of infection complications.

Application value of early postoperative enteral eco-immune nutrition in the nutritional support treatment for intra-abdominal infection: a prospective analysis / 中华消化外科杂志

Objective To explore the application value of early postoperative enteral eco-immune nutrition in the nutritional support treatment for intra-abdominal infection.Methods The prospective study was conducted.The clinicopathological data of 62 patients with intra-abdominal infection who were admitted to the 940 Hospital of the People's Liberation Army Joint Service Support Force from February 2018 to December 2018 were collected.All patients were randomly divided into two groups by the envelope method with double-blind technique,including patients who began being given enteral eco-immune nutrition preparation at postoperative 24-48 hours in eco-immune group and patients who began being given simple enteral nutrition preparation at 24-48 hours in control group.Observation indicators:(1) analysis of immune function indices before treatment and after 7 days of treatment in the two groups;(2) postoperative conditions in the two groups;(3) follow-up.Follow-up using telephone interview was performed to detect complications and recurrence of infection up to May 2019.Measurement data with normal distribution were represented as Mean ± SD,and intra-group comparison and comparison between groups were analyzed using the t test.Count data were represented as absolute numbers or percentages,and comparison between groups was analyzed using the chi-square test.Results Sixty-two patients were screened for eligibility,including 38 males and 24 females,aged (54± 14)years,with the range of 22-81 years.There were 30 in the eco-immune group and 32 in the control group.(1) Analysis of immune function indices before treatment and after 7 days of treatment in the two groups:before treatment,the percentages of CD3+,CD4+,CD8+,ratio of CD4+/CD8+,count of natural killer (NK) cells,levels of blood endotoxin and immunoglobulin A (IgA) for the eco-immune group were 61％ ± 12％,34％ ± 5％,28％ ± 5％,1.25 ± 0.34,17.26％±2.74％,(2.4±0.3)ng/L,and (1.7±0.5)g/L,versus 59％±11％,33％±5％,27％±4％,1.27± 0.36,16.96％ ±2.99％,(2.5± 0.5) ng/L,(1.8± 0.5) g/L for the control group,respectively,there were no significant differences between the two groups (t =-0.563,-0.354,-0.987,0.327,-0.462,0.887,0.991,P＞ 0.05).After 7 days of treatment,the above indices for the eco-immune group were 62％±8％,37％±6％,27％± 8％,1.45±0.32,22.63％±7.25％,(2.2±0.4) ng/L,and (2.3±0.4) g/L,versus 58％±8％,32％±4％,27％ ±6％,1.26±0.22,16.26％±2.10％,(2.7±0.6)ng/L,and (2.0±0.4)g/L for the control group,respectively,there were significant differences in the percentages of CD3+,CD4+,ratio of CD4+/CD8+,count of NK cells,levels of blood endotoxin and IgA (t =-2.393,-4.336,-3.074,-5.338,4.010,-3.155,P＜0.05),but no significant difference in the percentage of CD8+ between the two groups (t =0.077,P＞0.05).In the coo-immune group,the percentage of CD4+,ratio of CD4+/CD8+,count of NK cells,levels of blood endotoxin and IgA showed significant differences after 7 days of treatment (t =-2.899,-2.739,-4.385,2.157,-5.788,P＜0.05),but the percentages of CD3+ and CD8+ showed no significant differences after 7 days of treatment (t =-0.490,1.193,P＞ 0.05).In the control group,the percentage of CD8+ and level of IgA showed significant differences after 7 days of treatment (t=3.659,-2.258,P＜0.05),but the percentage of CD4+,ratio of CD4+/CD8+,count of NK cells,and level of blood endotoxin showed no significant differences after 7 days of treatment (t =0.157,0.759,1.132,1.212,-0.532,P＞0.05).(2) Postoperative conditions in the two groups:the time to first flatus and duration of postoperative hospital stay of the eco-immune group were (2.4± 0.5) days and (8± 4) days,respectively,versus (2.9±0.7)days and (11±7)days of the control group;there were significant differences in the above indices between the two groups (t =-3.017,-2.764,P＜0.05).In the eco-immune group,the incidence of complication was 6.7％(2/30),including 1 case of wound infection,1 case of pulmonary infection.In the control group,the incidence of complication was 31.2％ (10/32),including 6 cases of wound infection,2 cases of pulmonary infection,1 case of intra-abdominal infection,and 1 case of systemic inflammatory response syndrome.There was a significant difference in the incidence of complication between the two groups (x2=4.122,P＜ 0.05).The patients with infection were recovered after corresponding systematic conservative treatments.(3) Follow-up:of the 62 patients,46 were followed up for 3-9 months,with a median follow-up time of 6 months,including 26 in the eco-immune group and 20 in the control group.During the follow-up,no complication or infection recurred in the two groups.Conclusion Compared with simple enteral nutrition,early postoperative enteral eco-immune nutrition in the nutritional support treatment is safe and effective for patients with intra-abdominal infection,which can enhance the immune function of patients,shorten the recovery time of patients,and reduce the incidence of infection complications.

Clinical efficacy of Da Vinci robot-assisted radical gastrectomy for gastric cancer / 中华消化外科杂志

Objective To explore the clinical efficacy of Da Vinci robot-assisted radical gastrectomy for gastric cancer.Methods The retrospective cohort study was conducted.The clinicopathological data of 472 patients who underwent radical gastrectomy for gastric cancer in the 940 Hospital of the People's Liberation Joint Service from June 2016 to June 2018 were collected.There were 372 males and 100 females,aged (57± 11) years,with a range from 17 to 85 years.Patients underwent gastrointestinal angiography,magnetic resonance imaging,computed tomography or gastrointestinal endoscopy before surgery,and were diagnosed with gastric cancer by biopsy.Of the 472 patients,241 underwent Da Vinci robot-assisted radical gastrectomy for gastric cancer were allocated into robotic group and 231 underwent laparoscopy-assisted radical gastrectomy were allocated into laparoscopic group.Observation indicators:(1) surgical situations;(2) postoperative situations;(3) follow-up and survival.Follow-up using outpatient examination and telephone interview was performed to detect the tumor recurrence and metastasis and survival of patients up to January 30,2019.Measurement data with normal distribution were expressed as Mean±SD,and comparison between groups was done using the t test.Measurement data with skewed distribution were described as M (range).Count data were described as absolute number or percentage,and the chi-square test was used for comparison between groups.Comparison of ordinal data was done using the rank-sum test.The accumulative survival rate,tumor-bearing survival rate and mortality of tumor recurrence were calculated by the Kaplan-Meier method,and Log-rank test was used for survival analysis.Results (1) Surgical situations:472 patients underwent successful operation,with R0 margin.Cases with total gastrectomy + D2 lymph node dissection + Roux-en-Y anastomosis,cases with distal subtotal gastrectomy + D2 lymph node dissection + Billroth Ⅱ anastomosis,operation time,upper margin distance,lower margin distance,tumor diameter,cases with shallow muscular invasion,deep muscular invasion,subserosal invasion and serosal invasion (depth of tumor invasion)were 107,134,(234±44)minutes,(4±3)cm,(6±4)cm,(5 ±3)cm,8,17,32,184 in the robotic group,and 94,137,(239±46)minutes,(4±3)cm,(6±4) cm,(5±3)cm,7,19,30,175 in the laparoscopic group,respectively;there was no significant difference in above indicators between the two groups (x2 =0.200,2.459,t =-1.212,-1.074,-0.420,-1.236,Z =0.171,P＞ 0.05).The volume of i ntraoperative blood loss,number of lymph nodes dissected in total gastrectomy,number of lymph nodes dissected in distal subtotal gastrectomy were (126±113)mL,45±14,and 36±18 in the robotic group,and (149±132) mL,39±14,30± 16 in the laparoscopic group,showing statistically significant differences between the two groups (t=-2.093,3.275,2.195,P＜0.05).(2) Postoperative situations:the time to recovery of gastrointestinal function,time of postoperative abdominal drainage tube removal,and hospitalization cost in the robotic group were (2.6 ± 0.6)days,(5.7± 1.2) days,and (100 157±44 888) yuan,respectively.The above indices of the laparoscopic group were (3.1±0.7)days,(7.0±3.0)days,and (82 220± 18 941)yuan,respectively.There were statistically significant differences between the two groups (t =-5.371,-3.212,5.603,P ＜ 0.05).The duration of postoperative hospital stay was (12±6)days in the robotic group and (12±6)days in the laparoscopic group,with no significant difference between the two groups (t =0.755,P＞ 0.05).Eighteen out of 472 patients had complications.There were 3 cases of anastomotic leakage in the robotic group,2 cases of gastroplegia,1 case of duodenal stump,and 1 case of pulmonary infection,with a incidence of postoperative complication as 2.90％ (7/241).There were 4 cases of anastomotic leakage in the laparoscopic group,1 case of gastroplegia,1 case of duodenal stump,and 3 cases of pulmonary infection,with a incidence of postoperative complication as 3.90％ (9/231).There was no statistically significant difference in the incidence of postoperative complication between the two groups (x2 =1.503,P ＞ 0.05).Patients with digestive tract fistula were re-explored and performed continuous flushing-negative pressure aspiration and nutritional support treatment,and then discharged after improvement.Patients with gastroplegia and lung infection were discharged after corresponding conservative treatment.(3) Follow-up and survival:404 out of 472 patients were followed up for 7-31 months,with a median follow-up time of 19 months,including 212 in the robotic group and 192 in the laparoscopic group.The 3-year survival rates were 96.70％ and 91.67％ in the robotic group and laparoscopic group,with no statistically significant difference between the two groups (x2=1.037,P＞0.05).During the follow-up,the tumor-beating survival rate and mortality of tumor recurrence of the robotic group were 0.47％ and 2.36％,respectively,versus 1.04％ and 6.77％ of the laparoscopic group,with statistically significant differences between the two groups (x2 =3.198,4.208,P＜0.05).Conclusion The Da Vinci robot-assisted radical gastrectomy for gastric cancer is safe and effective,which can reduce volume of intraoperative blood loss,shorten the postoperative recovery time,increase the number of lymph node dissection,however,it will increase the treatment expense.

Functional Connectivity-Based Modelling Simulates Subject-Specific Network Spreading Effects of Focal Brain Stimulation / 神经科学通报·英文版

Neurostimulation remarkably alleviates the symptoms in a variety of brain disorders by modulating the brain-wide network. However, how brain-wide effects on the direct and indirect pathways evoked by focal neurostimulation elicit therapeutic effects in an individual patient is unknown. Understanding this remains crucial for advancing neural circuit-based guidance to optimize candidate patient screening, pre-surgical target selection, and post-surgical parameter tuning. To address this issue, we propose a functional brain connectome-based modeling approach that simulates the spreading effects of stimulating different brain regions and quantifies the rectification of abnormal network topology in silico. We validated these analyses by pinpointing nuclei in the basal ganglia circuits as top-ranked targets for 43 local patients with Parkinson's disease and 90 patients from a public database. Individual connectome-based analysis demonstrated that the globus pallidus was the best choice for 21.1% and the subthalamic nucleus for 19.5% of patients. Down-regulation of functional connectivity (up to 12%) at these prioritized targets optimally maximized the therapeutic effects. Notably, the priority rank of the subthalamic nucleus significantly correlated with motor symptom severity (Unified Parkinson's Disease Rating Scale III) in the local cohort. These findings underscore the potential of neural network modeling for advancing personalized brain stimulation therapy, and warrant future experimental investigation to validate its clinical utility.

The effects of IL-8-activated tumor-associated macrophages on hepatocellular carcino-ma invasion and metastasis / 中国肿瘤临床

Objective:To study the effects of IL-8 on the polarization of monocytes and the effects of IL-8-induced tumor-associated macrophages(TAMs)on the invasion and metastasis of hepatocellular carcinoma(HCC).Methods:After exogenous IL-8 stimulation of THP-1 cells for 72h,the percentages of M1 and M2 TAMs were examined.RT-PCR and Western blot assays were used to study epitheli-al-mesenchymal transition(EMT),and wound-healing and transwell assays were preformed to study the invasion potential of HCC cells after co-culturing with TAMs and HCC cell lines in vitro.Lastly,100 cases of HCC tissue samples were used to validate the correlation among TAM numbers,IL-8,and EMT features of HCC cells via immunohistochemistry(IHC)staining methods.Results:Exogenous IL-8 induced significant M2 polarization of TAMs in THP-1 cells.TAMs further promoted EMT in HCC and enhanced the invasion potential of HCC in vitro.Finally,significant positive correlations among the numbers of TAMs,IL-8 expression,and N-cadherin expression were identified in primary HCC tissue samples(r=0.22,r=0.20,P<0.05).Conclusions:IL-8 locally attracted and activated TAMs,and promot-ed M2 polarization of TAMs,which further promoted the EMT and invasion potential of HCC cells both in vitro and in vivo.

Short-term effect analysis of Da Vinci robotic surgical system-assisted and laparoscopy-assisted operations for gastrointestinal stromal tumor / 中华消化外科杂志

Objective To compare the short-term clinical effects of Da Vinci robotic surgical systemassisted and laparoscopy-assisted operations for gastrointestinal stromal tumor (GIST).Methods The retrospective cohort study was conducted.The clinical data of 98 patients with GIST who were admitted to the Lanzhou General Hospital of Chinese People's Liberation Army from June 2016 to May 2018 were collected.Of 98 patients,45 undergoing Da Vinci robotic surgical system-assisted surgery for GIST and 53 undergoing laparoscopy-assisted surgery for GIST were respectively allocated into the robotic group and laparoscopic group.The associate senior and above doctors performed the surgery.The wedge resection was applied to patients with diameter of gastric stromal tumor ＜ 5 cm,and subtotal gastrectomy + digestive tract reconstruction (gastrojejunostomy and Brauns anastomosis) were applied to patients with diameter of gastric stromal tumor ＞ 5 cm or tumor located in the cardia and pylorus.Patients with intestinal stromal tumor underwent intestinal resection + end-to-side anastomosis.Observation indicators:(1) surgical and postoperative situations;(2) follow-up.Follow-up using outpatient examination and telephone interview was performed to detect tumor recurrence or metastasis up to July 2018.Measurement data with normal distribution were represented as x-±s,and comparison between groups was done using the independent-sample t test.Measurement data with skewed distribution were represented as M (range),and comparison between groups was done using nonparametric test.Comparisons of count data were analyzed using chi-square test.Results (1) Surgical and postoperative situations:98 patients underwent successful surgery.The operation time,volume of intraoperative blood loss,recovery time of gastrointestinal function,time of gastrointestinal decompression tube removal,time of abdominal drainage tube removal and duration of postoperative hospital stay were respectively (152± 49) minutes,100 mL (range,10-300 mL),(2.6 ± 0.6) days,(1.1 ± 0.3)days,(5.7±1.2)days,(8.3±1.3)days in the robotic group and (201±62)minutes,100 mL (range,5-600 mL),(3.1±0.7) days,(2.1 ± 1.5) days,(6.9 ± 3.4) days,(11.6 ± 7.0) days in the laparoscopic group,with statistically significant difference between groups (t =-3.983,Z =2.104,t =-3.776,-3.637,-2.018,-2.817,P＜0.05).(2) Follow-up:98 patients were followed up for 2-24 months,with a median time of 13 months.During the follow-up,there was no tumor recurrence or metastasis between groups.Conclusion Compared with laparoscopy-assisted surgery,Da Vinci robotic surgical system-assisted surgery for GIST is safe and feasible,with advantages of shorter operation time,faster postoperative recovery and shorter duration of hospital stay.

Prediabetes and ischemic stroke / 国际脑血管病杂志

Prediabetes is a glucose metabolism status between normal glucose metabolism and diabetes.It can not only increase the risks of occurrence and recurrence of stroke, but also affect stroke outcomes.Prediabetes causes ischemic stroke mainly through the insulin resistance and blood-brain barrier damage.Non-drug or drug intervention in patients with prediabetes can delay progression from prediabetes to diabetes and reduce the risks of occurrence and recurrence of stroke.

Analysis of surgery treatment and feasibility of gastric stump carcinoma in the elderly patients over 70 years of age / 中国现代普通外科进展

Objective:To investigate whether elderly patients over 70 years of age with gastric stump carcinoma should be treated with operation and which surgical approaches should be selected.Methods:A retrospective analysis was performed on 36 patients with gastric stump carcinoma without any significant surgical contraindications hospitalized in lanzhou general hospital of lanzhou military area from January 2001 to January 2013.All these patients were over 70 years of age,with an active score of 0-3.The patients were divided into surgical and non-surgical treatment groups,and the surgical treatment group was further subdivided into radical surgery group and palliative surgery group.The treatment modalities,complications and survival of each group were analyzed.Results:A one-year and a three-year survival rate of surgical treatment group was 45.5％ and 22.7％,respectively,whereas the one-year and three-year survival rate of non-surgical treatment group was only 18.2％ and 0％,the difference was statistically significant (P ＜ 0.05).In the surgical treatment group,the radical surgery subgroup had a better survival rate than palliative surgery subgroup,with a one-year and a three-year survival rate of 58.3％ and 33.3％ respectively for the former,and 30％ and 10％ for the latter.The incidence of complications of radical surgery group and palliative surgery group was of no significant difference (P ＞ 0.05).Conclusions:Elderly patients over 70 years of age with gastric stump carcinoma can still benefit from radical surgery;while palliative surgery does not improve the survival rate of the patients,radical surgery is appropriate for elderly patients with gastric stump carcinoma.

Effects of MT01 on expressions of TLR9,TRAF6 and IL6 in periodontal tissue during experimental tooth movement of rats / 吉林大学学报(医学版)

Objective:To investigate the changes of expression levels of TLR9 and IL-6 in the periodontal tissue during the experimental tooth movement of the rats, and the effecst of the MT01 on the expression of TLR9,TRAF6 and IL-6 in periodontal tissue,and to clarify its related mechanisms.Methods:Thirty Wistar rats were randomly divided into MT01 intervention group(n=6) and non-MT01 group(n=24).Force of 0.49 N was applied to move the upper first molars mesially. The rats in Non-MT01 intervention group were sacrificed on the days 3,7,14 and 21, and the rats in MT01 intervention group were all sacrificed on the day 7. RT-qPCR was used to detect the expression levels of TLR9,TRAF6 and IL-6 mRNA in maxillary first molar alveolar bone in each group.Results:The expression levels of IL-6 and TLR9 mRNA in loaded side were higher than those in control side(P<0.05), and reached the maximum levels on the day 7(P<0.01);with the interpose of MT01, the expression levels of TLR9 and TRAF6 mRNA were lower than control side(P<0.01).Conclusion: MT01 could down-regulate the expression levels of TLR9 and TRAF6 during orthodontic tooth movement and eventually resists the inflammation during the tooth movement.

Roles of spleen and interferon-γ in ischemic brain injury / 国际脑血管病杂志

Secondary immune response is an important endogenous mechanism of neurological injury after ischemic stroke.Spleen and interferon-γγplay an important role in it.Monitoring the spleen size and the level of interferon-γγhave an important reference significance for the severity of stroke and outcome assessment.

Surgical treatment of infra-cardiac total anomalous pulmonary venous connection in 13 neonates / 中国小儿急救医学

Objective To evaluate the effectiveness of urgent surgical correction for infra-cardiac total anomalous pulmonary venous connection(TAPVC)in neonates.Methods From October 2009 to Janu-ary 2015,13 patients with infra-cardiac TAPVC received surgical correction.The age of patients ranged from 6 to 28 days[(15.08 ±7.42)days],the body weight ranged from 2.5 to 4.8 kg [(3.34 ±0.67)kg].A median sternotomy was performed.Continuous cardiopulmonary bypass using bicaval cannulation with aortic cross-clamping and mild systemic hypothermia were used in all patients.Bi-atrial incision technique making anastomosis between the posterior left atrial wall and the vertical vein were employed in 3 cases.In the other 10 cases,the heart was elevated upward and to the right to expose the anomalous descending vertical vein to facilitate the anastomosis between the posterolateral left atrial wall and vertical vein.Results Emergent or subemergent operations were performed in all patients without surgical death.In the early stage after opera-tion,delayed sternal closure was employed in 1 1 patients,pulmonary hypertension crisis occurred in 3 pa-tients,small atrial septal defect was kept open for hemodynamic stabilization in 6 patients,temporary cardiac pacemaker for proper heart rate in 3 patients.All patients were uneventfully discharged except 2 patients died of severe low cardiac output syndrome.During the period of follow up,2 patients presented with recurrent pulmonary infection and signs of pulmonary venous obstruction including the increased flow speed at the site of anastomosis.One of 2 patients was lost of follow up and the other patient was uneventfully discharged after the second operation.The rest 9 patients received postoperative follow up for 1 month to 5 years,echocardio-graphy,X ray chest radiography,and electrocardiogram were performed during this period.As a result,all children had good cardiac function and with sinus rhythm on electrocardiogram and apparently reduced pul-monary congestion on radiography.No obstructive pulmonary venous return was observed on echocardio-graphy.Conclusion Corrective operation for infra-cardiac TAPVC in neonate on urgent basis may provide favorite outcomes.

The role of heat shock protein 70 in regulating neuroinflammation / 药学学报

Neurodegenerative disease is characterized by progressive loss of neurons in specific brain regions that results in neuronal dysfunction of the central nervous system. Although the pathological mechanism is not fully established, the activation of glial cells mediated neuroinflammation appears to be involved. Heat shock protein 70 (HSP70) is originally described as intracellular chaperone, which plays an important role in protein quality control in cells. However, recent study showed that up-regulation of HSP70 had anti-inflammatory effects in the brain. HSP70 protected neurons from damage and improved neurological function by decreasing inflammatory response as indicated by inactivation of glial cells and inhibition of pro-inflammatory cytokine release. So it is of great significance to find new compounds targeting at HSP70 as neuroprotective agents to delay the progress of neurodegenerative disease. This review will focus on the role of HSP70 in neuroinflammation and the recent advances in using HSP70 as a target for the treatment of neurodegenerative disease.

Isolation and identification of lung cancer stem-like cells based on a 3D cell culture system / 中国肿瘤临床

Objective:To highlight the developmental process of 3D cell culture technology system, which is more suitable for isolating and identifying lung cancer stem-like cells than 2D cell culture technology system, and to explore the application of 3D cell cultures in the evaluation of proliferation, apoptosis, invasion, and drug resistance of lung cancer. Methods:Cells (104/well) from the human lung adenocarcinoma cell lines A549 and RPMI 1640 were cultured in complete medium containing 10%fetal bovine serum. Cell suspension was cultured in a BME basal medium. A growth curve was drawn after 7 d of culture. The stem-like cell was identified through a mammosphere culture, drug resistance and invasion assay, and flow cytometry. Data of A549 cells cultured in 3D and 2D tra-ditional cell culture technologies were compared. Results: Cells from the 3D cell culture had higher tumor formation rates [(20.75 ± 0.85) d vs. (60.25 ± 1.49) d, P<0.01)] and tumor sphere formation (28.50%± 1.17%vs. 8.67%± 0.80%, P<0.01) than those from the 2D cell culture. Moreover, cells from 3D cell culture were more invasive and resistant to therapy (58.17%± 2.19%vs. 41.70%±5.81%in 48 h, P<0.01;33.27%±5.76%vs. 27.30%±4.25%in 72 h, P<0.01). Phenotype experimental results demonstrated that the CD44 and CD326 cells were double-positive, whereas the CD24 cell was negative. Conclusion:The proportion of stem-like cells in A549 cell line after 3D cell culture significantly increased compared with 2D cell culture. The 3D cell culture can promote the proliferation of lung cancer stem cells.

Low expression profiling of microRNA in non-small cell lung cancer tissues / 中国肿瘤临床

Objective:To describe the expression profiling of microRNAs of patients with non-small cell lung cancer. Methods:We reduced the scope of downregulated microRNAs in patients with non-small lung cancer by high throughput microarray based on quantitative real-time PCR (qRT-PCR). In this process, the downregulated microRNAs of non-small cell lung cancer tissues can be de-tected and compared with adjacent healthy lung tissues with relatively small samples. Different microRNA expression levels in non-small cell lung cancer and adjacent healthy lung tissues were verified in a large sample by RT-PCR. Results:A total of 20 types of microRNAs were significantly downregulated in non-small cell lung cancer tissues compared with adjacent healthy lung tissues. These microRNAs were listed as follows: hsa-miR-1; hsa-miR-22; hsa-miR-27a; hsa-miR-27b; hsa-miR-125a-5p; hsa-miR-125b;hsa-miR-142-5p;hsa-miR-143;hsa-miR-148a;hsa-miR-148b;hsa-miR-370;hsa-miR-373;hsa-miR-381;hsa-miR-489;hsa-miR-519a;hsa-miR-376c;hsa-miR-206;hsa-miR-380-5p;hsa-miR-223-5p;and hsa-miR-520c-3p. Among these microRNAs, 13 types were down-regulated in non-small cell lung cancer tissues as verified by RTPCR. These 13 types of microRNAs were listed as follows:hsa-miR-125a-5p; hsa-miR-143; hsa-miR-519a; hsa-miR-223-5p; hsa-miR-1; hsa-miR-520c-3p; hsa-miR-489; hsa-miR-27a;hsa-miR-373; hsa-miR-125b; hsa-miR-27b; hsa-miR-142-5p; and hsa-miR-206. Conclusion: In non-small lung cancer tissue, several kinds of microRNAs were significantly downregulated. Changes in microRNA expressions were significantly associated with tumori-genesis, progression, or other cancer cell functions in non-small cell lung cancer.