Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expression. Notably, T2D patients showed increased cerebrospinal fluid lactate levels, which were strongly associated with their cognitive dysfunction. Intrahippocampal injection of lactate accelerated cognitive dysfunction and impaired adult hippocampal neurogenesis (AHN) in db/db mice. Conversely, reducing hippocampal lactate levels through the intrahippocampal injection of oxamate delayed the onset of memory deficits. Furthermore, asiatic acid was discovered to protect db/db mice from cognitive impairment by decreasing brain endothelial HIF-1α expression and subsequently reducing hippocampal lactate-induced AHN damage. Overall, this study elucidates the inhibiting role played by endothelial HIF-1α-driven lactate in AHN and highlights a potential tactic of targeting HIF-1α in brain ECs for treating cognitive impairment.

To evaluate the feasibility and safety of suprapubic three-arm robot-assisted laparoscopic radical prostatectomy (STA-RLRP). Fifteen patients with prostatic cancer underwent STA-RLRP. All the 15 procedures were completed successfully, without the need for ancillary trocars or additional instruments. No patient required conversion to standard laparoscopy or open surgery. STA-RLRP is feasible and safe with good short-term tumor control, satisfactory recovery of urinary control function and good cosmetic outcome, which is worthy of clinical application.

Objective To analyze and compare the outcomes of esophageal carcinoma treated with simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) and late course boost intensity-modulated radiation therapy (LCB-IMRT).Methods We retrospectively analyzed 128 patients with esophageal squamous cell carcinoma who were treated with SIB-IMRT or LCB-IMRT at the fifth department of radiation oncology in our hospital,from January 2009 to August 2015.Propensity score matching analysis was used to balance the variables differences in the two groups.Survival,failure patterns and toxicities were observed and compared between the two groups.Results one hundred and eleven patients were finally included after propensity scores matching.The 1-,3-and 5-year local control rates and survival rates were 83.6％ vs.81.7％,70.8％ vs.46.3％ and 66.0％ vs.38.2％ in the whole group,respectively.The 1-,3-and 5-year local control rates of SIB-IMRT and LCB-IMRT group were 81.6％ vs.88.0％,72.3％ vs.67.6％ and68.5％ vs.60.8％,respectively (P＞0.05).The 1-,3-and 5-year survival rates of SIB-IMRT and LCB-IMRT group were 81.3％ vs.82.4％,51.7％ vs.36.7％ and 45.8％ vs.26.7％,respectively (P ＞ 0.05).There was no statistical difference between the two group in ≥ grade 3 toxicities (P ＞ 0.05).There were 40 (36.0％) patients result in treatment failure in all.The treatment failure rates in SIB-IMRT and LCB-IMRT group were 33.8％ (26/77) vs.41.2％ (14/34),respectively (P ＞ 0.05).The local failure accounted for 65.0％ (26/40) of all treatment-related failures.Conclusions The toxicities of esophageal squamous cell carcinoma treated with SIB-IMRT and LCB-IMRT have no significant differences and were well tolerated.There were no significant differences in local control rates and survival rates between the two groups.However,SIB-IMRT had better trend than LCB-IMRT.Given SIB-IMRT's convenient manipulation,it could be a better choice in the treatment of advanced esophageal carcinoma.

Objective To evaluate the clinical efficacy and analyze relevant prognostic factors of simultaneous integrated boost intensity-modulated radiation therapy ( SIB-IMRT ) for esophageal squamous cell carcinoma. Methods A total of 101 patients diagnosed with esophageal squamous cell carcinoma received SIB-IMRT from 2009 to 2015. The prescribed dose of PTV was 5040 cGy/28 times ( 180 cGy/time) and the dose for planning gross tumor volume (PGTV) was 6020 cGy/28 times (215 cGy/time) or 6160 cGy/28 times ( 220 cGy/time) simultaneously. The total treatment time was 5. 5 weeks ( once a day, 5 times a week).The adverse events, mode of treatment failure,l-,3-and 5-year local control (LC) and overall survival ( OS) rates were observed. Results The quantity of patients who completed the 1-,3-and 5-year follow-up was 101, 84 and 45, respectively. The 1-,3-and 5-year LC rates were 81. 6％,70. 4％ and 68. 4％, respectively. The 1-, 3-and 5-year OS rates were 72. 3％, 49. 4％ and 45. 2％, respectively. The median survival time was 36 months. Univariate and multivariate analyses showed that clinical staging ( stageⅠ/Ⅱ/Ⅲ) and tumor response ( complete remission/ partial remission/no remission ) were the prognostic factors of OS (P=0. 016,0. 000,0. 005,0. 000).There were no significant differences in the LC and OS between the two groups of 215 cGy and 220 cGy (P=0. 283,0. 951).The incidence rates of grade 1,2,3 acute pneumonitis were 10. 9％(11/101),2. 0％(2/101) and 2. 0％(2/101), respectively. The incidence rates of grade 1, 2, 3 acute esophagitis were 63. 4％( 64/101 ) , 10. 9％( 11/101 ) and 4. 0％( 4/101 ) , respectively. No acute esophageal perforation or hemorrhage occurred. Five patients experienced late pneumonitis ( two died) . One case developed late lemostenosis, two cases developed esophageal perforation and hemorrhage, and two patients experienced esophageal hemorrhage. The patients treated with a fractionated dose of 220 cGy had a higher incidence rate of acute pneumonitis and upper gastrointestinal adverse reactions than those receiving 215 cGy ( P= 0. 062, 0. 024 ) . The local failure and recurrence accounted for 62. 5％ of all treatment-related failures. Conclusions SIB-IMRT yields high long-term clinical efficacy and tolerable adverse events in the treatment of esophageal squamous cell carcinoma. Compared with the dose of 215 cGy, the fractionated dose of 220 cGy fails to improve LC and OS rates, whereas enhances the risk of adverse events. The clinical staging and short-term clinical efficacy are the prognostic factors of survival rate.

Objective Because of statistical noise in Monte Carlo dose calculations,the effective point doses may not be accurately calculated.A user-defined sphere volume was adopted to substitute the effective point to take sphere sampling around the effective point,which minimize the random errors and improve the accuracy of statistical dose.Methods Direct dose measurements were performed at 0°and 90° using a 0.125 cm3 Semiflex ionization chamber (IC) 31010 isocentrically placed in the center of a homogeneous Cylindric sliced RW3 phantom (PTW,Germany).In the scanned CT phantom series,the sensitive volume length of the IC (6.5 mm) was delineated and the isocenter was defined as the simulated effective point.All beams were simulated in the treatment planning system (TPS) in accordance to the measured model.The grid spacing was calculated by 2 mm voxels and the relative standard deviation should be ≤ 0.5％.The statistical and measured doses were statistically compared among three IC models with different electron densities (ED;esophageal lumen ED =0.210 g/cm3 for model A,air ED =0.001 g/cm3 for model B and the default CT scanned ED for model C) at different sampling sphere radius (2.5,2.0,1.5 and 1.0 mm) to evaluate the effect of Monte Carlo.calculation uncertainty upon the dose accuracy.Results In the Monaco TPS,the statistical value was in the highest accordance with the measured value with an absolute average deviation of 0.49％ when the IC was set as esophageal lumen ED =0.210 g/cm3 and the sampling sphere radius was 1.5 mm.When the IC was set as air ED=0.001 g/cm3 and default CT scanned ED,and,the recommended statistical sampling sphere radius was 2.5 mm,the absolute average deviations were 0.61％ and 0.70％.Conclusion In the Monaco TPS,the calculation model with an ED of 0.210 g/cm3 and a sampling radius of 1.5 mm is recommended for the ionization chamber 31010 to substitute the effective point dose measurement to decrease the random stochastic errors of Monte Carlo.

Objective To analyze the clinical prevalence,distributed characteristic of different ages,clinical characteristics and pathogenic factors of chronic abdominal pain in children.Methods A database in which outpa-tient and inpatient of abdominal pain during 2 -14 years old were collected from January 2011 to December 2015 was established by utilizing HIS system.A statistical analysis was made in age,sex,onset time,time of duration,mesenteric lymph node status and surgical situation.Results A total of 13 256 times abdominalgia were enrolled from January 2011 to December 2015.7 390 patients were diagnosed as unexplained abdominal pain,including 1 005 patients (13.59%)were diagnosed as chronic abdominal pain.A male -to -female ratio was 1.06:1.The average age was 6 years(ranged 2 -14 years).The average age of the boys was (6.02 ±2.87)years,which of the girls was (5.93 ± 2.79)years,there was no statistically significant difference between them(t =0.47,P =0.63).The peak age of chro-nic abdominal pain in children was mainly from 3 to 7 years old.The incidence decreased with age increased.The average time of duration was (16.70 ±11.69)months,that of the boys was (17.39 ±12.12)months,and that of the girls was (15.96 ±11.19)months,there was statistically significant difference between them(t =1.93,P =0.05). Mesenteric lymphadenectasis was detected in 731 patients(72.74%).The age constituent ratio decreased with age increased.The peak age of the prevalence coincided with peak age of the mesenteric lymphadenectasis.21 patients underwent surgical procedures,organic lesions accounted for 2.08%.Conclusion The peak age of the prevalence of chronic abdominal pain in children is mainly from 3 to 7 years old.Potential organic causes are rarely linked to chronic abdominal pain in children.Most of them are functional abdominal pain.The appendix and mesenteric lymphadenecta-sis might play an important role in children with chronic abdominal pain.The therapeutic aim of CAP in children is to make the children back to their normal life by exclude the organic causes and relieve their pain.The natural history of chronic abdominal pain suggests that symptoms remit spontaneously with increasing age.

Objective To figure out the optimal parameters of a volumetric modulated arc therapy ( VMAT) plan for cervical and upper esophageal cancer by quality evaluation of VMAT plans with different parameters, and to provide a reference for the design of clinical VMAT treatment plan. Methods Ten patients with cervical esophageal cancer and ten patients with upper esophageal cancer were enrolled as subjects. The Nucletron Oncentra 4. 3 treatment planning system was used to generate plans for Elekta Synergy VMAT accelerator. Six VMAT plans were made with variation in the gantry angle ( 2°, 3°, and 4°), the maximum delivery time (80 s, 110 s, and 150 s), and the collimator angle (0° and 45°). The doses to the planning target volume and organs at risk were analyzed by paired t test. Results For cervical and upper esophageal cancer, the quality of VMAT plans with a collimator angle of 45° was better than those with a collimator angle of 0°(P=0. 003?0. 007). For cervical esophageal cancer, there was no significant difference in quality between VMAT plans with a maximum delivery time of 110 s or 150 s and those with a maximum delivery time of 80 s ( P>0. 05 );for upper esophageal cancer, there was also no significant difference in quality between VMAT plans with three different maximum delivery times ( P>0. 05 ) . For cervical esophageal cancer, the VMAT plans with a gantry angle of 3° had a better quality than those with a gantry angle of 2° or 4°(P=0. 010?0. 048). For upper esophageal cancer, the VMAT plans with a gantry angle of 3° had a better quality than those with a gantry angle of 4° ( P=0. 010?0. 048) . Compared with those with a gantry angle of 2° , the VMAT plans with a gantry angle of 3° had a slightly better dose distribution in the target volume ( P=0. 046 ) , but a slightly higher dose to lung tissue ( V25 and V30 , P=0. 007 and 0. 026) . Conclusions The optimal initial parameters of a VMAT plan for cervical and upper esophageal cancer are a collimator angle of 45°, a maximum delivery time of 80 s, and a gantry angle of 3°.

Objective To construct the uniform electron density couch model (model A ED =0.25) and two components non uniform electron density couch model (model B FD =0.5and foam core=0.1) in the Monaco treatment planning system for the iBEAM(R) evo Extension 415,and to compare which model can better quantify the treatment couch influence on radiation dose.Methods Phantom was positioned in the center of the couch,the attenuation of the couch was evaluated with 6 MV for a field size of 10 cm× 10 cm.Dose measurements of couch attenuation were performed at gantry angles from 180.0° to 122.8°,using a 0.125cc semiflex ionization chamber (PTW),isocentrically placed in the center of a homogeneous cylindrical phantom.Each experimental setup was first measured on the linear accelerator and then reproduced in the TPS.By adjusting the relative-to water electron density (ED) values of the couch,the measured attenuation was replicated.The model accuracies of the model A and model B were evaluated by comparing the measured and calculated results at the minimum computational grid (2 mm) and maximum computing grid (5 mm),respectively.Results The maximum measured and calculated percentage deviation for the central phantom position was 4.01％.The couch model was included in the TPS with a uniform ED of 0.25 or a 2 component model with a fiber ED=0.5 and foam core ED=0.1.For model A and B under 2 and 5 mm voxel grid size,the mean absorbed dose with couch was reduced to 0.61％,0.84％,0.71％ and 0.92％from 2.8％ without couch.Conclusions Model A has a good agreement between measured and calculated dose distributions for all different voxel grid sizes and gantry angles.It can accurately describes the dose perturbations due to the presence of the couch and should therefore be used during treatment planning.

Objective To investigate the therapeutic effects,adverse effects,and patterns of failure of elective irradiation of lymphatic drainage area (extended-field) and involved-field irradiation in three-dimensional radiotherapy (3DRT) in patients with esophageal cancer via a Meta-analysis.Methods The databases Wanfang Data,CNKI,VIP,CBM,PubMed,Embase,and Cochrane Library were searched to collect the controlled clinical trials on extended-field irradiation and involved-field irradiation in 3DRT in patients with esophageal cancer.Stata 11.0 was used for data analysis.The odds ratio (OR) with 95％ confidence interval was used to describe the differences between two groups.Results According to the inclusion and exclusion criteria,a total of 12 controlled clinical trials involving 1 095 patients with esophageal cancer were included in this meta-analysis.The results of the meta-analysis showed that compared with the involved-field irradiation group,the extended-field irradiation group had a significantly reduced rate of out-field failure in patients with esophageal cancer who received 3DRT (OR=3.727,P=0.007),but showed significantly higher rates of grade ≥ 3 acute radiation pneumonitis and radiation esophagitis (acute radiation pneumonitis:OR =0.348,P =0.001;radiation esophagitis:OR =0.385,P =0.000).The two groups had similar 1-,2-,and 3-year local control rate and overall survival rate (local control rate:OR=0.966/0.946/0.732,P=0.837/0.781/0.098;overall survival rate:OR=0.952/1.149/0.768,P=0.756/0.422/0.120),as well as a similar distant metastasis rate (OR=0.986,P=0.937).Conclusions Compared with involved-field irradiation,extended-field irradiation can reduce the rate of out-field failure in patients with esophageal cancer who receive 3DRT.However,it does not have significant advantages in local control rate and overall survival rate and has an increased incidence rate of adverse effects.

Objective Comparing the dosimetric characteristics of volumetric modulated arc therapy (VMAT) and constant dose rate intensity modulated arc therapy (IMAT) in esophagus cancer to evaluate the performance of the two different arc therapy delivery techniques.Methods 22 cases of esophageal cancer patients were selected for the planning comparison study.All plans were done for IMAT and VMAT treatment plans on Oncentra 4.1 treatment planning system,prescription dose of 2 Gy in total 30 fractions.Planning objectives for PTV were at least 95％ reached the prescription dose and V110 no more than 10％.The maximum dose of spinalcord below 45 Gy and double lung dose V20 ≤ 28％,V30 ≤ 18％ were constrained.Plans were evaluated based on the ability to meet the dose volume histogram.The dose homogeneity index (HI),radiation conformity index (CI),radiation delivery time,monitor units and γ pass rate were also compared.SPSS 19.0 software paired ttest analysis was carried out on the two sets of data.Results The results showed that the IMAT plans in terms of the PTV's CI (t =3.35,P=0.003),D2(t =-2.27,P=0.034) lung's V30(t =-2.46,P=0.023) were better than that of VMAT group.But the VMAT plans spinal's V40 (t =2.37,P =0.027),lung's V5 (t =2.43,P =0.024) were superior to that of IMAT plans.There were no significant differences between IMAT and VMAT plans in the average dose of PTV,CTV,GTV,heart,spinal cord,double lung and the γpass rate.Conclusion IMAT presents a slight improvement in the OAR sparing in high dose with shorter treatment time when compared to VMAT.While in terms of delivered MU and tissue of low dose irradiated area is higher than that of in VMAT.These two treatment methods all can meet the clinical demand,which should be selected according to the actual situation of the patient.