Objective:To explore the dosimetric differences of different dose accumulation method for brachytherapy combined with external beam radiation therapy (EBRT) of cervical cancer and establish clinical prediction models for radiation-induced late rectal injury (RLRI) after radiotherapy.Methods:A retrospective analysis was conducted for the clinical data of patients who received radical concurrent chemoradiotherapy (CCRT) for cervical cancer in the Department of Oncology of the Affiliated Hospital of North Sichuan Medical College from January 1, 2020 to November 30, 2021. EBRT combined with brachytherapy was employed for the patients, and dose assessment was performed in two means: the direct accumulation using equivalent dose in 2-Gy fractions (EQD2) and deformable image registration (DIR)-based dose accumulation of 3D planning images. The toxicity criteria of the Radiation Therapy Oncology Group were adopted as the RLRI grading criteria. The prediction models of RLRI using both dose assessment method were constructed. The areas under the receiver operating characteristic (ROC) curves were calculated to assess the predictive accuracy of the different dose assessment method.Results:In the case of brachytherapy, the D95% and D90% EQD2 doses to high-risk clinical target volumes (HR-CTVs) were 2.18 and 2.92 Gy higher respectively and the D2 cm 3, D1 cm 3, and D0.1 cm 3 EQD2 doses to the rectal were 1.74, 2.28, and 2.26 Gy higher, respectively compared to DIR-based dose accumulation ( t = 3.82, 5.21, 4.58, 5.17, 2.05, P < 0.05). For EBRT combined with brachytherapy, the D2 cm 3, D1 cm 3, and D0.1 cm 3 EQD2 doses to the rectal were 6.22, 7.61, 9.56 Gy higher than DIR-based doses, respectively, and the dosimetric differences were statistically significant ( t = 9.40, 10.59, 7.87, P < 0.001). The joint prediction model yielded an area under the ROC curve of 0.788. The sensitivity and specificity of the optimal cut-off value were 0.850 and 0.660, respectively. Furthermore, the Hosmer-Lemeshow goodness-of-fit tests indicated high goodness-of-fit ( P > 0.05). The prediction model for DIR-based dose accumulation of traditional predictors yielded areas under the ROC curves for D2 cm 3 and D1 cm 3 to the rectal of 0.784 and 0.763, respectively. The sensitivities of the optimal cut-off values were 0.850 and 0.750, respectively, and the specificities were 0.679 and 0.717, respectively. Conclusions:There are dosimetric differences between the direct dose accumulation using EQD2 and DIR-based dose accumulation of 3D planning images for brachytherapy combined with EBRT. Both the joint prediction model and the DIR-based dose accumulation of D2 cm 3 and D1 cm 3 to the rectal are effective in predicting RLRI. Given the complex calculation of the joint prediction model, it is recommended that RLRI should be predicted through DIR-based dose accumulation of D2 cm 3 and D1 cm 3 to the rectal clinically.

Background::Sentinel lymph node (SLN) biopsy is gradually accepted as the standard of care in breast cancer patients with down-staged axillary disease after neoadjuvant chemotherapy (NAC). However, it is still difficult to precisely define pre-NAC clinical node-positive (cN1) and post-NAC clinical node-negative (ycN0). This prospective single-center trial was designed to evaluate the feasibility and accuracy of standard targeted axillary dissection (TAD) after NAC in highly selective pre-NAC cN1 patients (not considering ultrasound-based axillary ycN staging).Methods::This prospective trial included patients with initial pre-NAC cT1–3N1M0 invasive breast cancer but with a rigorous definition of cN1 from the Affiliated Cancer Hospital of Zhengzhou University. When NAC was effective (including complete and partial responses) and preoperative axillary palpation was negative, preoperative ultrasound-based axillary staging was not considered, and all patients underwent TAD followed by axillary lymph node (LN) dissection. The detection rate (DR) and false-negative rate (FNR) of TAD were calculated.Results::A total of 82 patients were included, and 77 of them were eligible for data analysis. The DR for TAD was 94.8% (73/77). There were 26 patients with one abnormal LN at the time of diagnosis based on ultrasound, 45 patients with two, and 2 patients with three. One patient had one TAD LN, four patients had two TAD LNs, and 68 patients had three or more TAD LNs. Preoperative axillary palpation yielded negative results for all 73 patients who successfully underwent TAD. Preoperative ultrasound-based ycN0 and ycN+ conditions were detected for 52 and 21 cases, respectively. The FNR was 7.4% (2/27) for standard TAD (≥3 SLNs), which was lower than that of all successful TAD (≥1 SLN; 10.0%, 3/30).Conclusions::In rigorously defined pre-NAC cN1 breast cancer patients, standard TAD is feasible for those with negative axillary palpation after NAC, and FNR is also less than 10%.Registration::chictr.org.cn, ChiCTR2100049093

Objective:To evaluate the effect of rotational errors (antero-posterior) on dosimetric parameters of positive lymph nodes in the long target volumetric modulated arc therapy (VMAT) plan for advanced cervical cancer and investigate its coping strategies.Methods:Clinical data of patients with cervical cancer complicated with para-aortic or inguinal lymph node metastasis admitted to Affiliated Hospital of North Sichuan Medical College were randomly selected and retrospectively analyzed. The target areas of the lymph nodes at different distances from the center of the plan were outlined according to the requirements. After designing the VMAT plan on the CT images of each case, the rotational errors (antero-posterior) were introduced by changing the parameters of the treatment couch, and the dose distribution was reconstructed by dose calculation with other parameters unchanged. Then, the external boundary of the original lymph node target was added according to d=2πr(α/360) ( r is the distance from the center of the lymph node to the plan center), re-planned, and the changes of dosimetric parameters in the target area of the original lymph node were analyzed after the corresponding rotational errors were introduced. Results:When the distance between the lymph node target area and the plan center was 6 cm with an error of 3°, the distance was 9 cm and 12 cm with an error of 2.5°, the distance was 15 cm with an error of 2°, and the distance was 18 cm with an error of 1.5°, the mean change of D 95% was more than 5%. When the rotational errors were ≤1°, the mean change of D 95% in lymph node target area was less than 5%, and when the lymph node was 18 cm away from the treatment plan center, the mean change was more than 3%, reaching 3.75%. When the rotational errors were 0.5° and the distance from the plan center was 18 cm (0.5°, 18 cm), the dose change of lymph node target was more than 5%, reaching 5.58%. At (1°, 15 cm), the V 100% change reached 8.96%, and at (1°, 18 cm), the V 100% change was 14.5%. The D 95% and V 100% parameters of the original lymph node target were changed by less than 1% after adding the external boundary of the original lymph node target and introducing corresponding rotational errors. Conclusions:In the long target area radiotherapy of cervical cancer, the variation of dosimetric parameters of lymph node target was increased with the increase of rotational errors and with the increase of distance from the plan center. It is recommended to increase the efferent boundary of lymph nodes in different positions to avoid underdose by d=2πr(α/360).

Objective : To investigate the protective effect and related mechanisms of dexmedetomidine (Dex) on iron overload toxicity in mouse hippocampal neurons (HT22) induced by ferric ammonium citrate (FAC) . Methods: Selected HT22 cells in good condition were randomly divided into 4 groups: control group ( Ctrl group), FAC treatment group (FAC group), Dex treatment group (Dex group), ferroptosis inhibitor Fer⁃1 treatment group (Fer1 group) . The iron overload model was established by FAC⁃induced cells . Subsequently, the proliferation and survival rate of HT22 cells was detected by CCK⁃8 method; Western blot was used to detect the ferroptosis marker proteins prostaglandin⁃endoperoxide synthase 2 ( PTGS2 ) and acyl⁃CoA synthetase long⁃chain family member 4 (ACSL4) . The protein expressions of mammalian target of rapamycin ( mTOR), transferrin receptor 1 ( TFR1) and ferroportin (Fpn); the gene expression levels of PTGS2 and ACSL4 in HT22 cells were detected by qPCR; Reactive oxygen species (ROS) levels in HT22 cells was detected by DHE fluorescent probe; MDA detection kit was used to detect lipid oxidation levels in HT22 cells; Mito⁃FerroOrange—ferrous ion probe was used to detect ferrous ion levels in HT22 cells; electron microscopy was used to detect intracellular ultrastructural changes . Results: Dex group and Fer⁃1 group significantly decreased cell death rate after 2 h of pretreatment, the protein and gene expression levels of ferroptosis markers PTGS2 and ACSL4 significantly decreased . The degree of cell ultrastructural damage was significantly improved . The levels of ROS, lipid oxidation and Fe2 + were significantly lower than those of the FAC group (P < 0. 05) . Conclusion Dex pretreatment can attenuate FAC⁃induced iron overload toxicity in⁃ jury in HT22 cells, which may be related to the inhibition of ferroptosis .

Objective :To explore influence of intra—arterial thrombolysis combined hyperbaric oxygen on serum levels of soluble intercellular adhesion molecule—1 (sICAM—1) and calcitonin gene related peptide (CGRP) in patients with severe ischemic stroke .Methods : A total of 96 patients with severe ischemic stroke in our hospital were randomly and equally divided into thrombolysis group and combined treatment group (received intra—arterial thrombolysis +hyperbaric oxygen therapy ).United States National Institutes of Health Stroke score (NIHSS) was used to assess neurological function recovery , and modified Rankin rating score (mRS) was used to assess recovery of clinical symptoms.After two—week treatment ,clinical therapeutic effect etc .were compared between two groups .Results :Compared with thrombolysis group after treatment ,there was significant rise in total effective rate (77.08% vs. 93. 75%, P＝0.021) ;significant reductions in scores of NIHSS [ (8.10 ± 3.45) scores vs .(5.36 ± 2.11) scores] and mRS [ (2.58 ± 0. 80) scores vs .(1.81 ± 0.76) scores] ;significant reduction in serum sICAM—1 level [ (237.31 ± 18. 04) ng／ml vs.(220.25 ± 16.40) ng／ml] ,and significant rise in serum CGRP level [ (27.02 ± 6.06) pg／ml vs. (35.24 ± 6.13) pg／ml] in combined treatment group , P＝0.001 all.There was no significant difference in revascu—larization within two weeks between two groups , P＝0.551. Conclusion : Intra—arterial thrombolysis combined hy—perbaric oxygen possesses significant therapeutic effect on patients with severe ischemic stroke .It can relieve clinical symptoms ,recover cognitive function ,improve revascularization rate in these patients .

Objective To evaluate the effect of bispectral index (BIS) and muscle relaxation monitoring on robot-assisted laparoscopic radical prostatectomy in elderly patients.Methods One hundred elderly patients (aged 65-80 years,ASA Ⅰ or Ⅱ) who underwent robot-assisted laparoscopic radical prostatectomy were randomly allocated into BIS and muscle relaxation monitoring group (group AA,n=50) and control group (group AC,n=50).In group AA,propofol was infused to achieve the BIS value of 45-55,and we monitored the muscle relaxation to conduct closed-loop infusion of cisatracurium.In group AC,we regulated the depth of anesthetic with the patients` vital signs according to anesthetists` experience.Mean arterial pressures (MAP),heart rates (HR),airway platform pressure (Pplat),and airway peak pressure (Ppeak) were recorded at following time points: before anesthesia induction (T0),after anesthesia induction (T1),10 min (T2),60 min (T3) after artificial pneumoperitoneum,and the end of operation (T4).We recorded dosage of propofol,cisatracurium,sufentanil,remifentanil,vasoactive agent,extubation time and PACU stay time.Results At T1,T2 and T4,the MAP and HR in group AC were significantly higher than those in group AA (P<0.05);at T3,MAP in group AC were apparently lower than those in group AA (P<0.05).Compared with T0,MAP and HR in group AC were significantly increased at T1,T2 and T4(P<0.05),MAP in group AC were obviously reduced at T3 (P<0.05),MAP and HR in group AC were also fluctuated obviously at different time points.MAP and HR in group AA at each point had no statistically significant difference.Compared with T1,Pplat and Ppeak in the two groups were significantly increased at T2-T4 (P<0.05).Pplat and Ppeak in grpup AC were higher than those in group AA at T2,T3 (P<0.05).Compared with group AC,the dosages of propofol and cisatracurium were less in group AA.The postoperative extubation time and PACU stay time were shorter in group AA.Conclusion BIS and muscle relaxation monitoring in robot-assisted laparoscopic radical prostatectomy can effectively stablize hemodynamics,reduce airway pressure fluctuation and the dosage of anesthetics.It also shortens the extubation time and the PACU stay time and improves the anesthesia recovery quality.

Objective To evaluate the effects of intrathecal low-dose naloxone,morphine and fentanyl on the expression of motillin (MTL) in the hippocampus of rats with incisional pain.Methods Seventy-two healthy male Sprague-Dawley rats,weighing 180-220 g,aged 6-8 weeks,in which intrathecal catheters were successfully implanted,were randomly divided into 6 groups (n =12 each) using a random number table:normal saline group (NS group),incisional pain group (P group),morphine + fentanyl + incisional pain group (MFP group),and naloxone (0.2,1.0 and 5.0 ng/kg) + morphine + fentanyl groups (MFPN1,MFPN2 and MFPN3 groups).Incisional pain was induced by an incision made into the plantar surface of the right hindpaw.At 20 min before induction of incisional pain,the mixture of morphine 5 μg/kg and fentanyl 0.25 mg/kg was injected intrathecally in group MFP,and the mixture of naloxone 0.2,1.0 and 5.0 ng/kg,morphine and fentanyl were injected intrathecally in MFPN1,MFPN2 and MF-PN3 groups,respectively.Six rats in each group were selected,and the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before intrathecal catheterization (T0,baseline),at 24 h before induction of incisional pain (T1),and at 1,3 and 6 h after operation (T2-4).The left 6 rats in each group were selected and sacrificed at 6 h after operation,and the hippocampi,body of the stomach and duodenum were removed for detection of MTL content by enzyme-linked immunosorbent assay.Results Compared with group NS,the MWT was significantly decreased,and the TWL was shortened at T2-4 in P and MFPN3 groups,the MWT was significantly decreased,and the TWL was shortened at T4 in group MFPN1,and the TWL was prolonged at T2 in group MFPN2,the MTL contents in hippocampus and body of the stomach were significantly decreased in P,MFP,MFPN1 and MF-PN3 groups,the MTL contents in duodenum were increased in P and MFPN3 groups,and the MTL contents in duodenum were decreased in MFP and MFPN1 groups (P＜0.05),and no significant change was found in the parameters mentioned above in group MFPN2 (P＞0.05).Conclusion Intrathecal naloxone 1.0 ng/kg combined with morphine and fentanyl can inhibit up-regulation of the expression of MTL in the hippocampus of rats with incisional pain,and then is involved in the maintenance of stable gastrointestinal motility.

Objective To evaluate the effect of sufentanil postconditioning on acetylated histon H3 (Ac-H3) expression during myocardial ischemia-reperfusion (I/R) in rats.Methods Thirty-six adult male Sprague-Dawley rats,weighing 250-300 g,were randomly divided into 3 groups (n =12 each) using a random number table:sham operation group (S group),I/R group,and sufentanil postconditioning group (SP group).Myocardial I/R was induced by 30 min occlusion of the left anterior descending branch of the coronary artery followed by 120 min reperfusion in anesthetized rats.Sufentanil 1 μg/kg was injected through the femoral vein at 5 min before reperfusion in group SP,while the equal volume of normal saline was given in S and I/R groups.The rats were sacrificed at 120 min of reperfusion,and the myocardial specimens were obtained from the anterior wall of the left ventricle for determination of myocardial infarct size and cell apoptosis (by TUNEL),and myocardial specimens were obtained from the apex for detection of Ac-H3 expression (using Western blot).Apoptotic index was calculated.Results Compared with S group,the myocardial infarct size and apoptotic index were significantly increased,and Ac-H3 expression was down-regulated in I/R and SP groups (P＜0.05).Compared with I/R group,the myocardial infarct size and apoptotic index were significantly decreased,and Ac-H3 expression was up-regulated in SP group (P＜ 0.05).Conclusion Sufentanil postconditioning attenuates myocardial I/R injury through up-regulating AcH3 expression and restoring histone acetylation in rats.

Objective To investigate the effect of suberoylanilide hydroxamic acid (SAHA) on sufentanil postconditioning-induced cardioprotection in rats with type 2 diabetes mellitus (T2DM).Methods Male SPF Sprague-Dawley rats,weighing 250-300 g,aged 5-6 weeks,were used in the study.T2DM was induced by high-fat diet (4 weeks) and intraperitoneal 1％ streptozotocin 35 mg/kg,and confirmed by fasting blood glucose level≥ 16.7 mmol/L.Forty rats with T2DM were divided into 5 groups (n=8 each) using a random number table:sham operation group (grou T2DM-S);ischemia-reperfusion group (group T2DM-I/R);sufentanil postconditioning group (group T2DM-SP);SAHA group (group T2DM-SA);SAHA plus sufentanil postconditioning group (group T2DM-SASP).In T2DM-SA and T2DM-SASP groups,SAHA 25 mg/kg was injected intraperitoneally once a day for 5 consecutive days before operation.Their hearts were excised and retrogradely perfused in a Langendorff apparatus.The hearts were subjected to 30 min of global ischemia followed by 120 min of reperfusion to establish the model of ischemia/reperfusion injury.At 30 min of equilibration and 30,60 and 120 min of reperfusion,the left ventricular systolic pressure (LVSP),heart rate (HR),and the maximum rate of increase and decrease of ventricular pressure (±dp/dtmax) were recorded.At 120 min of reperfusion,the left ventricular mass (LVM) and infarct size (IS) were measured,and IS/LVM ratio was calculated.The expression of glycogen synthesis kinase 3β (GSK-3β) and phosphorylated GSK-3β (p-GSK-3β) in the myocardium was detected by Western blot.Results Compared with group T2DM-S,the LVSP,HR and ±dp/dtmax were significantly decreased,the IS and IS/LVM ratio were significantly increased,and the expression of myocardial p-GSK-3β was significantly down-regulated in group T2DM-I/R (P＜0.05).Compared with group T2DM-I/R,the ±dp/dtmax was significantly increased,the IS and IS/LVM ratio were significantly decreased,and the expression of myocardial p-GSK-3β was significantly up-regulated in group T2DM-SASP (P＜0.05),and no significant change was found in the parameters mentioned above in T2DM-SA and T2DM-SP groups (P＞0.05).Compared with group T2DM-SP,the ±dp/dt was significantly increased,the 1S and IS/LVM ratio were significantly decreased,and the expression of myocardial p-GSK-3β was significantly upregulated in group T2DM-SASP (P＜0.05).Conclusion SAHA can improve cardioprotection induced by sufentanil postconditioning to some extent in the rats with T2DM.

Objective To investigate the effects of a variety of different methods of analgesia on postoperative pain and cognitive function in elderly esophageal cancer patients.Methods Sixty elderly pa-tients scheduled for the left into the thoracic esophageal cancer surgery were randomly divided into two groups (n =30).Group A:Before the closure of thoracic cavity to block intercostal nerve with 0.375% rop-ivacaine,followed by intravenous pumps for analgesia,formulation of sufentanil 3 μg/kg+flurbiprofen 100 mg,pump speed 2 ml/h,self-controlled analgesia 0.5 ml/pressing,locking time 15 min.Group B:Before the closure of thoracic cavity given sufentanil 10 μg+flurbiprofen 50 mg as loading dose followed by epidural analgesia pump,recipe with group A.Two groups were observed mini mental state examination (MMSE) score 1 d before surgery and 3,5,7 d after surgery,each time point visual analogue pain score (resting and exercise VAS)score postoperative within 48 h,BCS comfort score and effective pressing times of postopera-tive analgesia pump.Results Compared with group B,the rest and exercise VAS scores of group A at post-operative recovery,4,8,12,24,48 h were significantly lower (P <0.05);the BCS scores of group A at postoperative 4,8,12,24,48 h were significantly higher (P <0.05);the pressing times of group A at postoperative 4,8,12,24,48 h were significantly reduced (P <0.05);the MMSE scores of group A at postoperative 3,5,7 d were significantly higher (P <0.05);the incidence of POCD of group A on postop-erative 3,5,7 d were significantly lower.Conclusion Thoracic surgery perioperative multimodal analgesia (intercostal nerve block and intravenous analgesia)can relieve postoperative pain,reduce the incidence of POCD,improve the postoperative patient comfort and help postoperative patients with rapid recovery.