AGEs in DRG Participates in Gastric Hypersensitivity by Regulating Expression of Kv4.2 in Diabetes Mellitus Rat Model / 胃肠病学

Background: Diabetic gastroparesis (DGP) is one of the most common complications of diabetes mellitus (DM), and its main symptoms include upper abdominal pain, nausea, vomiting, abdominal distension, etc. Gastric hypersensitivity is the main pathogenesis of DGP. Advanced glycation end products (AGEs) is the initiating factor of chronic complications of DM, and its relationship with gastric hypersensitivity has not yet been clear. Kv4.2 channel plays an important role in regulating visceral sensation. Subunit inactivation of Kv4.2 can reduce potassium current, enhance pain sensation, and increase gastric sensitivity. Aims: To investigate the mechanism of AGEs participating in gastric hypersensitivity by regulating the expression or activity of Kv4.2 channel in DM rat model. Methods: Fifty⁃four rats were randomly divided into control group, DM group and DM+AG group. Streptozocin (STZ) was intraperitoneally injected to induce DM rat model. Blood glucose, body weight, gastric sensitivity and gastric emptying rate were monitored. Western blotting and ELISA were used to detect CML content in stomach tissue and serum, respectively. The expression of RAGE and its co⁃expression with Kv4.2 in dorsal root ganglia (DRG) neurons were detected by immunofluorescence. Western blotting was used to detect RAGE expression and phosphorylation levels of ERK1/2 and Kv4.2 in DRG neurons. Results: Compared with control group, gastric sensitivity was significantly increased in DM group (P<0.01), gastric emptying rate was significantly decreased (P<0.05), AGEs marker CML content in serum and gastric tissue were significantly increased (P<0.05), co ⁃ expression rate of RAGE and Kv4.2 in DRG neurons was significantly increased (P<0.01), and phosphorylation levels of ERK1/2 and Kv4.2 were up⁃regulated (P<0.05). After intervention with AG, above⁃mentioned indices were significantly ameliorated (P<0.05). Conclusions: AGEs is an upstream factor leading to gastric hypersensitivity in DM rat model. AGEs increases the excitability of DRG neurons by inhibiting Kv4.2 channel, leading to gastric hypersensitivity. RAGE and ERK1/2 signal may be involved in the above process.

Study on deep brain magnetic stimulation method based on magnetic replicator / 生物医学工程学杂志

Existing neuroregulatory techniques can achieve precise stimulation of the whole brain or cortex, but high-focus deep brain stimulation has been a technical bottleneck in this field. In this paper, based on the theory of negative permeability emerged in recent years, a simulation model of magnetic replicator is established to study the distribution of the induced electric field in the deep brain and explore the possibility of deep focusing, which is compared with the traditional magnetic stimulation method. Simulation results show that a single magnetic replicator realized remote magnetic source. Under the condition of the same position and compared with the traditional method of stimulating, the former generated smaller induced electric field which sharply reduced with distance. By superposition of the magnetic field replicator, the induced electric field intensity could be increased and the focus could be improved, reducing the number of peripheral wires while guaranteeing good focus. The magnetic replicator model established in this paper provides a new idea for precise deep brain stimulation, which can be combined with neuroregulatory techniques in the future to lay a foundation for clinical application.

Preliminary imaging study on the distribution of female Volumetric Breast Density / 中华放射医学与防护杂志

Objective:To describe the distribution of volumetric breast density(VBD) in different ages of Chinese women based on X-ray mammograms.Methods:Based on mammographic images of 1 140 patients from January 2010 to December 2016 in a hospital in Beijing, the VBD of women was assessed by Volpara 1.5.1 and graded according to breast imaging reporting and data system published by American College of Radiology. The patients were divided into two groups according to the median age, and the two independent samples t-test was used to compare them. The patients were also divided into four groups according to age ( <40 years, 40-49 years, 50-59 years, ≥ 60 years), and the breast thickness, breast volume, glandular volume, and VBD were compared using a One-way ANOVA analysis. Results:The median age was 50 years. The compressed breast thickness and breast volume in patients over 50 years were significantly higher than those in patients below 50 years ( t= -8.99, -7.92, P<0.001), while glandular volume and VBD were significantly lower than those below 50 years ( t= 8.11, 18.49, P<0.001). The compressed breast thickness, breast volume, glandular volume, and VBD were statistically significant different among four groups ( F=27.10, 22.34, 25.70, 122.03, P<0.001). Patients over 60 years had the lowest VBD ( t=-12.56, -15.27, -4.57, P<0.001). VBD was negatively correlated with ages ( r=0.47, P<0.001). Conclusions:The compressed breast thickness and breast volume increased with ages, while the glandular volume and VBD decreased with ages.

Clinical Characteristics of Gastroesophageal Reflux Disease Patients With Laryngopharyngeal Symptoms / 胃肠病学

Background: The laryngopharyngeal symptoms of gastroesophageal reflux disease (GERD) include hoarseness, foreign body sensation, chronic cough, dysphagia, etc. Its pathogenic mechanisms and reflux characteristics may be different from those of GERD patients simply with typical esophageal symptoms. Aims: To explore the clinical characteristics of GERD patients complicated with laryngopharyngeal symptoms. Methods: Fifty-nine patients having a gastroesophageal reflux disease questionnaire (GerdQ) score ≥8 and abnormal reflux identified by 24 h esophageal impedance-pH monitoring were selected from the outpatients at the First Affiliated Hospital of Nanjing Medical University from January 2019 to December 2021. Twenty-nine cases simply with typical esophageal symptoms were allocated into typical symptom group, and 30 cases complicated with laryngopharyngeal symptoms were allocated into laryngopharyngeal reflux (LPR) group. The general information, results of gastroscopy, 24 h esophageal impedance - pH monitoring and esophageal manometry, as well as the efficacy of proton pump inhibitor (PPI) were collected and compared between the two groups. Results: The proportion of esophagitis in GERD patients in typical symptom group was significantly increased than that in LPR group (P<0.05), while the values of mean nocturnal baseline impedance at 7-3 cm above lower esophageal sphincter (LES) were significantly lower (all P<0.05). Compared with typical symptom group, increased frequency of weak acid reflux, prolonged mean acid clearance time, higher LES relaxation rate, lower velocity of peristaltic waves at 11-7 cm above LES, and poor efficacy of PPI treatment were observed in LPR group (all P<0.05). The severity of heartburn was positively correlated with the percentage of total acid exposure time and DeMeester score (all P<0.05); while the severity of foreign body sensation was positively correlated with the frequency of weak acid reflux and mean time of acid clearance (all P<0.05). Conclusions: The esophageal mucosal injury was mild in GERD patients complicated with laryngopharyngeal symptoms. Laryngopharyngeal symptoms are more likely to be associated with the decreased acid clearance capacity due to esophageal body dysmotility. Strengthened acid suppression therapy should be recommended.

Research Progress on Relationship Between Potassium Channels and Visceral Hypersensitivity / 胃肠病学

Visceral hypersensitivity is one of the pathogenesis of functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome and functional dyspepsia. In recent years, more and more studies have suggested that the occurrence of gastrointestinal hypersensitivity is related to the changes of neuronal plasticity in the intestinal nervous system or afferent pathway, and potassium channels play a crucial role in controlling neuronal excitability. Lots of studies have shown that decreased expressions or activities of voltage-gated potassium channels, calcium-activated potassium channels, and two-pore domain potassium channels in nociceptors can increase the excitability of neurons, increase visceral pain, and participate in the occurrence of FGIDs. This article reviewed the research progress on relationship between potassium channels and visceral hypersensitivity.

Irradiated dose to unprotected lymph node stations in the VMAT and IMRT treatment of patients with upper thoracic esophageal cancer / 中华放射医学与防护杂志

Objective To compare the irradiated dose to unprotected lymph node stations (LNS) between volume-modulated arc therapy (VMAT) and 5-field intensity-modulated radiotherapy (5F-IMRT) in the treatment of patients with upper thoracic esophageal cancer.Methods A total of 20 patients were selected for re-planning.LNS were not included in the GTV and CTV,instead,LNS were contoured as normal tissues.However,LNS were not constrained in the VMAT and 5F-IMRT inverse optimization for protection.Dosimetric parameters of conformal index (CI),homogeneity index (HI) of targets,V95,V110 of planning target volume (PTV),D V5,V20,V30 of lung,D V25 of heart,Dmax of spinal cord,MU,as well as the equivalent uniform dose (EUD) and V40 of LNS were compared between the two plans.Results 5F-IMRT was superior in PTV_ V95％ (t=-9.4,P＜0.05),but worse in terms of CI (t=-5.3,P＜0.05) compared with VMAT.5F-IMRT reduced the V5 of lung by 10.9％ (t=-7.8,P＜0.05) and the Dmax of spinal cord by 9％ (t=-10.2,P＜0.05),but increased the MU (t=-6.2,P＜0.05) compared with VMAT.The average EUD and V40 of LNS in upper thoracic were significantly increased by 4.7％ and 2.4％ in 5F-IMRT compared with VMAT,respectively.The irradiated doses to LNS were significantly associated with the volume of PTV (R =0.716-0.933,P＜0.05) expect for 106tbL.Conclusions The irradiated doses to unprotected LNS were less for IMRT plans and were highly associated with PTV volume in patients with upper thoracic esophageal cancer.

Irradiated dose to unprotected lymph node stations in the VMAT and IMRT treatment of patients with upper thoracic esophageal cancer / 中华放射医学与防护杂志

Objective@#To compare the irradiated dose to unprotected lymph node stations (LNS) between volume-modulated arc therapy (VMAT) and 5-field intensity-modulated radiotherapy (5F-IMRT) in the treatment of patients with upper thoracic esophageal cancer.@*Methods@#A total of 20 patients were selected for re-planning. LNS were not included in the GTV and CTV, instead, LNS were contoured as normal tissues. However, LNS were not constrained in the VMAT and 5F-IMRT inverse optimization for protection. Dosimetric parameters of conformal index (CI), homogeneity index (HI) of targets, V95, V110 of planning target volume (PTV), Dmean, V5, V20, V30 of lung, Dmean, V25 of heart, Dmax of spinal cord, MU, as well as the equivalent uniform dose (EUD) and V40 of LNS were compared between the two plans.@*Results@#5F-IMRT was superior in PTV_V95% (t=-9.4, P<0.05), but worse in terms of CI (t=-5.3, P<0.05) compared with VMAT. 5F-IMRT reduced the V5 of lung by 10.9% (t=-7.8, P<0.05) and the Dmax of spinal cord by 9% (t=-10.2, P<0.05), but increased the MU (t=-6.2, P<0.05) compared with VMAT. The average EUD and V40 of LNS in upper thoracic were significantly increased by 4.7% and 2.4% in 5F-IMRT compared with VMAT, respectively. The irradiated doses to LNS were significantly associated with the volume of PTV (R=0.716-0.933, P<0.05) expect for 106tbL.@*Conclusions@#The irradiated doses to unprotected LNS were less for IMRT plans and were highly associated with PTV volume in patients with upper thoracic esophageal cancer.

Factors associated with set-up errors in intensity-modulated radiotherapy after breast conserving surgery / 中华放射医学与防护杂志

Objective To evaluate the difference of set-up errors between thermoplastic mask and breast bracket in patients receiving intensity-modulated radiotherapy after breast conserving surgery,and the impact of clinical factors associated with set-up errors.Methods A total of 34 patients treated with intensity-modulated radiotherapy after breast conserving surgery from January 2016 to June 2018 were reviewed.Eighteen patients were fixed with thermoplastic mask,and sixteen were with breast bracket.Weekly CBCT scan records were used to analyze set-up errors,and group systematic and random errors were computed.The influence of clinical factors on set-up errors was also analyzed.Results The immobilization technique with thermoplastic mask showed great superior in comparison with breast bracket;however,only in the Ty(translation) and Ry(rotation),the differences had significance.Based on group systematic and random errors,PTV margins in Tx,Ty and Tzwere 2.65,4.36 and 2.87 mm in thermoplastic mask group,as well as 5.71,6.07 and 4.20 mm in breast bracket group,respectively.Multi-factor regression analysis showed that BMI was independent factors affecting set-up errors.Conclusions Compared with breast bracket,the immobilization technique with thermoplastic mask has the potential of reducing set-up errors and PTV margins in patients receiving intensity-modulated radiotherapy after breast conserving surgery,especially in patients with high BMI.

Target setup margin and dose evaluation for cervical cancer cases based on the off-line adaptive radiotherapy / 中华放射医学与防护杂志

Objective To study the target setup margin and dose evaluation for cervical cancer patients with volume-modulated arc therapy in the off-line adaptive radiation therapy (off-line ART),Methods A total of fifty patients with cervical cancer were randomly divided into test group and control group.Cone beam CT scanning was performed twice a week,the setup errors in directions of LR,AP and CC were recorded in the whole treatment process.The target setup formula was used to calculate the new CTV-PTV setup margin.At the same time,the setup error was returned to planning isocenter (ISO).For the control group,the dose was recalculated on the basis of the original PTV after considering ISO shift.For the test group,the dose was also recalculated after the new extended boundary of the target.The dosimetric parameters of CTV and organs at risk (OAR) were evaluated between two groups after dose recalculation.Results According to the target setup formula,extended boundaries of CTV in the direction of LR,AP,CC were 0.45,0.46 and 0.82 cm,respectively.The test group increased in CTV with D100％ and D95％ (t =-8.16,-6.73,P ＜0.05) and decreased in femoral head with V40,V30 and D (t=3.14,-9.52,-7.48,P＜0.05) than the control group.The test group decreased in the pelvis with V34 and D than control group (t =10.14,-9.38,P ＜0.05).Conclusions The CTV-PTV setup margin and the dose of OAR were effectively reduced,and the coverage of target area was extended when the off-line ART technology was conducted in the volume-modulated arc therapy for cervical cancer.

Research on the geometric difference between different ITV generation methods in non-small cell lung cancer treated with stereotactic radiotherapy / 中华放射肿瘤学杂志

Objective To study the geometric difference between six different ITV generation methods from 4DCT for patients with non?small cell lung cancer ( NSCLC) treated with stereotactic ablative radiotherapy technique ( SABR) . Methods Between Dec. 2013 and Mar. 2014,16 patients were enrolled in this retrospective study. All patients underwent imaging with 4DCT scans. The MI and DI index were evaluated between six ITV generation methods:combining GTV from all 10 respiratory phases ( ITV10 );combining GTV from four respiratory phases, including two extreme phases ( 0% and 50%) plus two intermediate phases ( 20% and 70%) ( ITVYeo ) which was proposed by Seung?Gu Yeo of Soonchunhyang University;combining GTV from two extreme phases ( ITVEI+EE ) . And combining GTV from five odd phases (10%,30%,50%,70%,90%)(ITVodd).Accordingly the ITVEVEN which was combined from the remaining five even phases (20%,40%,60%,80%,0%),and ITVAVG,ITVMIP were contoured from two reconstructed 4DCT sequences,finally,a method which was not sensitive to the tumor volume and motion characteristic was selected for clinical use. Data were compared using a variance analysis followed by Student?Newman?Keulsa test both in same group or between groups. At the same time, the volume and the three dimensional movements of the tumor, the relativity of MI and DI were analyzed by Multi?parameter regression analysis. Results The mean (range) tumor motion (RLR,RAP,RCC,and R3D) are 3. 5 mm (1. 4?8. 4 mm),4. 5 mm (1. 1?8. 6 mm),9. 5 mm (0?10 mm),12. 3 mm (2. 5?55. 3 mm) respectively. The IGTVx volume are Underestimated by 25. 7%,35. 6%,17. 9%,12. 8%,3. 6%,4. 8%( P=0. 000) respectively. The MI index comparisons between six ITV generation methods and ITV10 showed statistical significance:0. 69,0. 62,0. 80, 0. 86,0. 93,0. 91 ( P=0. 006 ) . The DI index showed no statistical significance:0. 98, 0. 98, 0. 97, 0. 97, 0. 99,0. 98(P=0. 130).The tumor size and motion amplitude were certified not the independent factors for the MI index of ITVodd and ITVEVEN . Conclusions IGTVODD/EVEN based on odd or even 4DCT phases is not sensitive to the tumor size or motion characteristic and is proved to have a good marching with ITV10 meanwhile maintaining a reasonable contouring efficiency,it can be recommend to the institutions which was not equipped with the deformable registration systems.

Analysis of dosimetric results of postoperative intensity modulated radiation therapy using single-energy or mixed-energy photons in invasive thymoma patients / 中华放射医学与防护杂志

Objective To compare the dosimetric results of postoperative intensity modulated radiation therapy (IMRT) using single-energy or mixed-energy photons in invasive thymoma patients.Methods Simulation CT images were acquired and clinical target volume (CTV),planning target volume (PTV) and organs at risk (OARs) were defined.Three sets of fixed-field IMRT planning were generated using 6 MV,10 MV and mixed 6/10 MV photons for each case.Monitor Units (MUs) for each plan were recorded after optimization,and parameters of PTV such as conformity index (CI),homogeneity index (HI) and dose to OARs were evaluated on dose-volume histograms.Results Near-Maximal dose (D2％) received by PTV was better in mixed-energy IMRT as compared with 6 MV(t =3.107,P ＜0.05).HI was better in mixed-energy than in 6 MV(t =2.924,P ＜0.05).There were statistically significant differences in CI among three IMRT plans.MU was higher in 6 MV than in both 10 MV and mixed-energy IMRT.The percentages of lung volumes receiving 5 Gy (V5),10 Gy(V10),20 Gy (V20),30 Gy (V30) and the mean lung dose (D) were also significantly different in most plans.V30 and V40 of the heart were comparable between 6 MV and mixed energy plans but better than in 10 MV plan.Conclusions If the reasonable choice of beam angles and number,and capability of energy selection according to beam directions,with combined advantages of low and high energy photons,mixed IMRT plans can improve the quality of IMRT plans in general and has clinical potential for postoperative radiotherapy of invasive thymomas.

Dosimetric comparison of two arcs VMAT plan and IMRT plan for breast cancer post-mastectomy / 中华放射医学与防护杂志

Objective To analyze the biophysical dosimetric characteristics and clinical application ability of VMAT technology for breast cancer post-mastectomy.Methods 28 patients with breast cancer (10 at left side and the other at right side) were planned in different ways respectively.One was two 90 degree arc VMAT plan and the other were 5 beam IMRT plan.The dosimetric parameters of two different plans including tumor control probability (TCP),conformity index(CI),homogeneity index (HI),V95and V110 in target,normal tissue complication probability (NTCP),V5,V20,V30 for ipsilateral lung,NCTP,D V25 for heart,D for the contralateral breast in OARs,MU and times were compared.Results The average tumor control probability (TCP) in VMAT and IMRT group was(96 ±2)％ and (90 ±2)％ (t =-6.28,P ＜ 0.01),respectively.The PTV dose average homogeneity index (HI) of VMAT plans was better than that of IMRT plan (0.15 ±0.04 vs 0.22 ±0.02,t =13.29,P ＜0.01).For cancer position in left side,the mean dose of heart was decreased by 433.24 cGy in the VMAT plan.The NTCP of the hearts in VMAT plans had statistically significant difference compared with IMRT plans [(1.00±0.12)％ vs (1.70±0.13)％,t =2.14,P ＜0.05].For plans of right breast cancer,the average mean dose of hearts in two control group was (3.27 ± 0.26) Gy and (6.00 ± 0.47) Gy (t =9.21,P＜0.01).The total monitor unit (MU) was 530.7 in the VMAT arm and 693.9 in the IMRT arm (t =9.58,P ＜0.01).The treatment time was shorter in VMAT arm (t =8.40,P ＜0.05).Conclusions VMAT plans have better clinical value and more superior biophysical dosimetric characteristics for breast cancer post-mastectomy.