Objective To investigate the effect of Tip60 on the cellular radiosensitivity,and to explore the related mechanism.Methods siRNA and anacardic acid (AA,an inhibitor of Tip60 acetyltransferase) were used to inhibit Tip60 expression and its acetyltransferase activity,respectively.Radiosensitivity was analyzed by colony-forming ability assay.γ-H2AX foci were detected to analyze the DNA double-strand break (DSB).Immunoprecipitation was used to determine the interaction of proteins.Results siRNA-mediated silencing of Tip60 led to enhanced sensitivity of U2OS cells at 1,2 Gy after γ-ray irradiation,but had no significant effect at 4 Gy post-irradiation ( t =3.364,3.979,P ＜ 0.05 ).γ-H2AX foci detection indicated that Tip60 silencing resulted in a decreased capability of DNA doublestrand break repair at 1,4 and 8 h after irradiation( t =3.875,3.183 and 3.175,respectively,P ＜ 0.05 ).The interaction of Tip60 and DNA-PKcs was prompted by ionizing radiation.Anacardic acid largely abrogated the phosphorylation of DNA-PKcs at T2609 site induced by irradiation.Conclusions Tip60plays a role in the cellular response to ionizing radiation-induced DNA damage through,at least in part,interacting with DNA-PKcs and regulating its phosphorylation.

Objective To investigate the dose-response pattern on the inducible expression of PIG3 mRNA in normal human lymphoblastoid AHHI cells by 60Co γ-rays,and its possibility for developing novel radiation biodosimeter.Methods Laser confocal fluorescent microscopy was used to detect the γ-H2AX foci,a biomarker of DNA double-strand break.After irradiation with 0,1,2,4,6,8 and 10 Gy of 60Coγ- rays,AHH-1 cells were harvested at 4,10 and 24 h post-irradiation,and subjected to total RNA extraction and detection of PIG3 mRNA expression by quantitative real-time PCR.Results PIG3 protein foci were formed in the nuclei at 30 min after irradiation,and a part of these PIG3 foci were colocalized with γH2AX foci.After irradiation,PIG3 mRNA level was enhanced with the increased time of postirradiation,and remained an increased level at least till 24 h.The radiation-inducible expression of PIG3 mRNA was demonstrated in a dose-dependent manner.The dose-dependent range at 4 h post-irradiation was 0 - 6 Gy,and at 10 h and 24 h was 0 - 10 Gy.Conclusions PIG3 involves in the cellular response to DNA double-strand break.The dose-dependent inducible response of PIG3 mRNA expression might provide a valuable candidate for developing a novel radiation biodosimeter.

Objective To study features of the MRI and clinic in a family with pure hereditary spastic paraplegia (PHSPG) type 6.Methods Target loci (SPG3, 4, 6, 8 10 and 12) linkage analysis was performed in a SPG pedigree having 6 affected individuals using microsatellite markers and NIPA1 gene was screened for mutation by PCR-amplification and sequencing. MRI of brain and cervical and thoracic spinal cord were examined in these 6 patients and 6 normal controls matched for age and sex by two independent radiologists blinded to the clinical diagnosis. Cross-sectional areas and anteroposterior and transverse diameters of the spinal cord at the levels of C2～3, C7, T1～4, T9 were measured and data was statistically analyzed using the student's t test. Results A missense mutation of 316g→c in NIPA1 was identified in the affected subjects, presumably resulting in substitution of glutamic acid for arginine in residue 106. Evaluation of the brain MRI images revealed non-specific brain abnormalities. All patients presented thinning of cervical and upper thoracic spine with atrophy in both gray and white matter and enlarged subarachnoid cavity. In severe atrophic segments, a distinct boundary between grey and white matter was observed and the lesions in grey matter presented literal high intensity spots or patches with clear boundary on transaxial T2-weighted images (T2WI) and high signal intensity longitudinal strip on the sagittal T2WI. Cross-sectional areas and anteroposterior and transverse diameters of the spinal cord at C2～3, C7, T1～4 were significantly smaller in patients than in controls, while at the T9 level only transverse diameter showed significant difference (7.22±0.08 vs 8.17±0.41, t=2.870, P=0.046). Conclusions These findings indicate that the disease process in patients with SPG6 might be confined to the cervical and thoracic spinal cord, with atrophy in both white and grey matter having a distinct boundary.

Objective To evaluate the radioprotective effect of vanillin derivative VND3207 on DNA damage induced by different LET ionizing radiation.Methods The plasmid DNA in liquid was irradiated by 60Co γ-rays, proton or 7Li heavy ion with or without VND3207.The conformation changes of plasmid DNA were assessed by agarose gel electrophoresis and the quantification was done using gel imaging system.Results The DNA damage induced by proton and 7Li heavy ion was much more serious as compared with that by 60Co γ-rays, and the vanillin derivative VND3207 could efficiently decrease the DNA damage induced by all three types of irradiation sources, which was expressed as a significantly reduced ratio of open circular form (OC) of plasmid DNA.The radioprotective effect of VND3207 increased with the increasing of drug concentration.The protective efficiencies of 200 μmol/L VND3207 were 85.3% (t =3.70,P =0.033), 73.3% (t = 10.58, P =0.017)and 80.4% (t =8.57,P =0.008)on DNA damage induction by 50 Gy of γ-rays, proton and 7Li heavy ion, respectively.It seemed that the radioprotection of VND3207 was more effective on DNA damage induced by high LET heavy ion than that by proton.Conclusions VND3207 has a protective effect against the genotoxicity of different LET ionizing radiation, especially for γ-rays and 7 Li heavy ion.

Objective To explore the accuracy of the multiplication coefficient method and the moment synthesis method for determining the spatial position of the center of gravity(CoG)of the human body based on machine vision.Methods The mechanical measurement platform was built,and the three-dimensional(3D)human body CoG measurement method under static and dynamic conditions were designed to calculate the space coordinates of the CoG.Through experiments,the calculation accuracy of the multiplication coefficient and moment synthesis method were studied and analyzed.Results In the static experiments,the calculation results of the torque synthesis method were more accurate than those of the multiplication coefficient method for each dimension.The errors in the 3D CoG of the human body in the X,Y,and Z directions calculated using the torque synthesis method were 3.9%,4.1%,and 8.5%,respectively.In the dynamic experiment,the average and relative errors of the torque synthesis method in the X or Y direction were lower than those of the multiplication-coefficient method.When the action decomposition method was used to analyze the height direction of the CoG along the Z axis,the final rendering effect of the torque synthesis method improved.Conclusions The accuracy of the 3D CoG calculated by the moment synthesis method was relatively high,and was closer to the measurement data of the mechanical measurement platform.The 3D CoG calculated using the moment synthesis method can replace the mechanical measurement platform and can be used in subsequent studies.

Objective To explore the implementation effect of PDCA(plan-do-check-action)style training of severe ultrasound and hemodynamics in standardized training(residential training)for residents majoring in internal medicine on improving their clinical decision-making ability.Methods A retrospective research method was conducted,60 residents in Xinyang Central Hospital from July 2017 to July 2023 were selected as the research objects,and patients were randomly divided into experimental group and control group,with 30 residents in each group.After the routine entrance education,the experimental group applied the PDCA mode training of severe ultrasound and hemodynamics.The control group was trained with the training objectives and requirements of the department of critical care medicine in the contents and standards of standardized training for internal medicine residents for 2 months.At the end of the training period,the residents of the two groups were assessed and investigated by questionnaire,and the differences of theoretical knowledge assessment,clinical practice skills assessment,case assessment scores and satisfaction between the two groups were compared.Results The results of theoretical knowledge examination,diagnosis and differential diagnosis,and clinical decision-making in the experimental group were significantly higher than those in the control group(theoretical knowledge examination score:90.5±2.7 vs.85.7±3.8,diagnosis and differential diagnosis score:92.0±2.4 vs.87.9±3.7,clinical decision-making score:90.3±3.1 vs.85.5±3.9,all P<0.05),satisfaction with teaching methods,stimulating learning interest,firmly mastering knowledge,enhancing problem-solving ability,improving learning enthusiasm,improving clinical thinking ability and enhancing team consciousness was also significantly higher than that of the control group[teaching methods:80.0%(24/30)vs.46.7%(14/30),stimulate learning interest:83.3%(25/30)vs.56.7%(17/30),firmly mastering knowledge:80.0%(24/30)vs.40.0%(12/30),enhance problem-solving ability:70.0%(21/30)vs.43.3%(13/30),improving learning enthusiasm:83.3%(25/30)vs.50.0%(15/30),improving clinical thinking ability:60.0%(18/30)vs.40.0%(12/30),enhancing team consciousness:73.3%(22/30)vs.46.7%(14/30),all P<0.05].Conclusion The application of PDCA-style training of severe ultrasound and hemodynamics can help internal medicine residents master the basic theory and skills of severe diseases faster and better in the rotation of critical medicine departments,which is more conducive to improving the clinical decision-making ability of internal medicine residents.

Objective:To reduce the immunogenicity of vaccinia virus vector by replacing the D8L region, which is a neutralizing antibody epitope in vaccinia virus, with an exogenous gene.Methods:A gene fragment encoding influenza virus hemagglutinin (HA) was inserted into the D8L region to replace it using homologous recombination technique. Then, a recombinant vaccinia virus influenza vaccine was constricted. A recombinant vaccinia virus vaccine with the TK region expressing HA was used as a control. The expression of HA was validated by Western blot. BALB/c mice were immunized with the vaccines and the serum antibody titers two weeks after each immunization were evaluated by ELISA and hemagglutination inhibition assay. The protective efficacy of the recombinant vaccinia virus was assessed through a challenge experiment.Results:Western blot confirmed the successful expression of HAD8L protein in the constructed recombinant vaccines. ELISA and hemagglutination inhibition assay showed that after the primary immunization, the anti-HA antibody titer induced by the recombinant vaccinia virus with D8L region mutation was slightly higher than that induced by the vaccine with TK region mutation, and the difference was statistically significant with the increase of immunization times ( P<0.05). The recombinant vaccinia virus with D8L region mutation showed significantly lower immunogenicity than the recombinant virus with TK region mutation after the primary immunization, but there was no significant difference between them with the increase of immunization times ( P>0.05). After H1N1pdm challenge, no virus was detected in the mice immunized with the recombinant vaccinia virus with D8L region mutation and the mice showed mild lung inflammation and less tissue damage. Conclusions:This study indicated that inserting exogenous genes into the D8L region of the neutralizing antibody epitope in the vaccinia virus vector could help to reduce the immunogenicity of the vector itself and enhance the immunogenicity of the exogenous genes. This provided a reference for the use of the vaccinia virus vector as a delivery tool in the field of vaccines or gene therapy.

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.

Objective It conducted a rapid health technology assessment to evaluate the comparative safety,efficacy and economy of tumor treating fields(TTFields)combined with temozolomide treatment versus temozolomide(TMZ)alone for patients with glioblastoma(GBM).Methods It provided an extensive electronic search of databases,including PubMed,Embase,Cochrane Library,CNKI,and WanFang Data,to collect clinical evidence and health economic evaluations related to the,safety,efficacy,and economy of TTFields for Glioblastoma patients.The search covered literature from inception to July,2023,and assessed the risk of bias in the included studies.Descriptive analyses and data summaries were performed.Results A total of 19 references were included,comprising 5 randomized controlled trials,3 retrospective studies,8 systematic reviews or meta-analyses,and 3 cost-effectiveness analysis(CEA)studies.The quality of the literature evidence was heterogeneous.Recent meta-analyses mostly support the conclusion that TTFields combined with TMZ treatment provides a survival benefit compared to standard TMZ alone.However,the cost-effectiveness analysis literature from 2 countries showed different results,likely due to differences in socioeconomic levels,health systems,and heterogeneity in sources,model selection,and parameter selection.The majority of evidence supports the benefits of TTFields combined with TMZ for the treatment of GBM patients,but the results of CEAs tend to favor the view that this therapy is not cost-effective.Conclusion Current evidence indicates that TTFields combined with TMZ treatment have better safety and efficacy.However,there is still no consensus on whether it is cost-effective.

Objective It conducted a rapid health technology assessment to evaluate the comparative safety,efficacy and economy of tumor treating fields(TTFields)combined with temozolomide treatment versus temozolomide(TMZ)alone for patients with glioblastoma(GBM).Methods It provided an extensive electronic search of databases,including PubMed,Embase,Cochrane Library,CNKI,and WanFang Data,to collect clinical evidence and health economic evaluations related to the,safety,efficacy,and economy of TTFields for Glioblastoma patients.The search covered literature from inception to July,2023,and assessed the risk of bias in the included studies.Descriptive analyses and data summaries were performed.Results A total of 19 references were included,comprising 5 randomized controlled trials,3 retrospective studies,8 systematic reviews or meta-analyses,and 3 cost-effectiveness analysis(CEA)studies.The quality of the literature evidence was heterogeneous.Recent meta-analyses mostly support the conclusion that TTFields combined with TMZ treatment provides a survival benefit compared to standard TMZ alone.However,the cost-effectiveness analysis literature from 2 countries showed different results,likely due to differences in socioeconomic levels,health systems,and heterogeneity in sources,model selection,and parameter selection.The majority of evidence supports the benefits of TTFields combined with TMZ for the treatment of GBM patients,but the results of CEAs tend to favor the view that this therapy is not cost-effective.Conclusion Current evidence indicates that TTFields combined with TMZ treatment have better safety and efficacy.However,there is still no consensus on whether it is cost-effective.