Objective:To design and evaluate a novel arcuate multi-channel rectal endoluminal applicator to enhance dose coverage of tumors in the upper and middle rectum and reduce pressure on the rectal wall.Methods:Pelvic MRI images of 200 Chinese cases without rectal lesions in the Peking University Third Hospital from July 2022 to August 2022 were retrospectively analyzed. Based on the image data, a rectal model with general characteristics of the population and two novel hard and soft rectal endoluminal applicators were designed and fabricated. The following properties of the conventional applicators and two new applicators were compared: deformation to the model rectal wall, maximum pressure, stable pressure, D 90%, D 100%, V 100%, V 150% and V 200% of the GTV, and D 2 cm3, D 1 cm3, and D 0.1 cm3 of the organs at risk (OAR). ANOVA or Kruskal-Wallis H-test was used to compare the differences among three applicators, and Dunnett's multiple comparison test was used for pairwise comparisons. Results:The novel hard and soft rectal endoluminal applicators caused less deformation of the model rectal wall. The maximum pressure on the rectal wall was (0.606 ± 0.182) kPa and (0.481 ± 0.229) kPa for the hard arcuate applicator and soft arcuate applicator, respectively, and the stable pressure was (0.207 ± 0.137) kPa and (0.055 ± 0.097) kPa, respectively, which were significantly smaller than those of the conventional applicator ( P <0.001, <0.001; P =0.024, <0.001), and the degree of reduction was at or near 50%. Under the premise of ensuring target dose, the D 2 cm3, D 1 cm3, and D 0.1 cm3 of OAR in the treatment plan designed with the novel applicator were significantly reduced compared to the cylindrical applicator (all P<0.001). Conclusion:The novel arcuate multi-channel rectal endoluminal applicator can significantly reduce rectal wall pressure and deformation, while also reducing the dose to OAR without compromising target dose coverage, offering certain therapeutic advantages.

Objective:To evaluate the role of histogram analysis based on amide proton transfer weighted (APTw) and apparent diffusion coefficient (ADC) imaging in predicting alpha-thalassemia/mental retardation syndrome X-linked ( ATRX) mutation in isocitrate dehydrogenase ( IDH)-mutant WHO grading 2/3 gliomas. Methods:Seventy-eight patients with IDH-mutant WHO grading 2/3 gliomas, admitted to and confirmed by surgical pathology in Department of Functional Neurosurgery, Neurosurgery Center, Zhujiang Hospital, Southern Medical University from June 2017 to October 2023, including 52 with ATRX wild and 26 with ATRX mutant-type, were selected. Preoperative 3D-APTw and ADC imaging data were collected; after post-processing, the lesions were segmented using lesion outlining method based on inclusion of peri-tumor edema and lesion outlining method based on tumor entity, respectively; after that, the histogram features (the 10 th percentile, 90 th percentile, maximum, mean, median, minimum, skewness, kurtosis, entropy, range, uniformity, and variance) were extracted from 3D-APTw and ADC imaging, respectively. Univariate Logistic regression was used to compare the differences in histogram features between patients in the ATRX mutant group and ATRX wild-type group, and multivariate Logistic regression was used to screen the independent predictors for ATRX mutation (a Logistic regression prediction model was constructed). Predictive values of independent predictors and Logistic regression prediction models in ATRX mutation were evaluated by receiver operating characteristic (ROC) curve. Results:(1) With lesion outlining method based on inclusion of peri-tumor edema, univariate analysis indicated significant difference between ATRX mutant group and ATRX wild-type group in 9 histogram features: relative 3D-APTw minimum, 3D-APTw skewness, relative ADC 90 th percentile, relative ADC mean, relative ADC median, ADC kurtosis, ADC skewness, ADC uniformity, and ADC entropy ( P<0.05). With lesion outlining method based on tumor entity, univariate analysis indicated significant difference between ATRX mutant group and ATRX wild-type group in 9 histogram features: relative 3D-APTw 90 th percentile, 3D-APTw skewness, relative ADC 90 th percentile, relative ADC mean, relative ADC median, ADC kurtosis, ADC skewness, ADC uniformity and ADC entropy ( P<0.05). (2) With lesion outlining method based on inclusion of peri-tumor edema, multivariate Logistic regression showed that 3D-APTw skewness and ADC kurtosis were the independent predictor for ATRX mutation in IDH mutant WHO grading 2/3 glioma patients ( OR=0.168, 95% CI: 0.034-0.800, P=0.025; OR=0.508, 95% CI: 0.319-0.807, P=0.004). The constructed Logistic regression prediction model was P(Y=1|X)=1/1+e -(1.827-1.785×3D-APTw skewness-0.678×ADC kurtosis). With lesion outlining method based on tumor entity, multivariate Logistic regression showed that 3D-APTw skewness and ADC kurtosis were independent predictors for ATRX mutation in IDH mutant WHO grading 2/3 glioma patients ( OR=0.164, 95% CI: 0.034-0.791, P=0.024; OR=0.496, 95% CI: 0.312-0.788, P=0.003); the constructed Logistic regression prediction model was P(Y=1|X)=1/1+e -(1.585-1.810×3D-APTw skewness-0.702×ADC kurtosis). (3) ROC curve analysis showed that, with lesion outlining method based on inclusion of peri-tumor edema, area under ROC curve (AUC) of 3D-APTw skewness and ADC kurtosis was 0.725 (95% CI: 0.608-0.842, P=0.001) and 0.794 (95% CI: 0.685-0.904), respectively ( P<0.001); AUC of Logistic regression prediction model was 0.836 (95% CI: 0.729-0.942, P<0.001), and its sensitivity and specificity were 73.10% and 90.40% when the best threshold was 0.505. ROC curve showed that, with lesion outlining method based on tumor entity, AUC of 3D-APTw skewness and ADC kurtosis was 0.705 (95% CI: 0.587-0.823, P=0.003) and 0.808 (95% CI: 0.704-0.913), respectively ( P<0.001); AUC of Logistic regression prediction model was 0.844 (95% CI: 0.739-0.949, P<0.001), and its sensitivity and specificity were 84.60% and 80.80% when the best threshold was 0.399. Conclusion:Histogram analysis based on 3D-APTw and ADC imaging can predict ATRX mutation in IDH mutant WHO grading 2/3 gliomas to a certain extent.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

Objective:To evaluate the efficacy and safety of lumen-apposing metal stent (LAMS) for the treatment of pancreatic walled-off necrosis (WON).Methods:A retrospective cohort study was performed on data of 43 consecutive patients with pancreatic WON who underwent endoscopic ultrasound-guided drainage by LAMS or plastic stents (PS) in Hangzhou First People's Hospital from December 2010 to June 2020. According to the type of stent used, the patients were divided into the LAMS group ( n=16) and the PS group ( n=27). The technical success rate, the clinical success rate, the operation time, the session of endoscopic necrosectomy, the stent insertion time and adverse events were compared between the two groups. Results:All 43 patients were successfully stented, indicating a technical success rate of 100% in both groups. For the LAMS group, the clinical success rate, the operation time, the session of endoscopic necrosectomy, the stent insertion time and overall incidence of adverse events were 75.0% (12/16), 26.0 (19.1, 39.8) min, 0.5 (0, 2.0) times, (41.3±28.4) days, and 43.7% (7/16), respectively, whereas these indices of the PS group were 37.0% (10/27) ( χ2=5.795, P=0.016), 31.0 (26.0, 48.0) min ( Z=1.221, P=0.222), 0 (0, 0) times ( Z=2.245, P=0.025), (176.1±99.1) days ( t=5.187, P<0.001) and 14.8% (4/27) ( χ2=8.893, P=0.064), respectively. Conclusion:LAMS placement is safe and effective for the treatment of pancreatic WON with a higher clinical success rate compared with PS. However, it requires more endoscopic intervention.

Objective:To investigate and analyze the hospital staff and patients, awareness about anesthesiologists′ work.Methods:A questionnaire survey was conducted among the hospital staff in the non-anesthesiology departments and non-operating room and the patients undergoing elective surgery at the same time in tertiary hospitals.Logistic regression was used to analyze the factors affecting the level of awareness of the respondents.Results:Sixty point three percent of the respondents had a low level of awareness about the anesthesiologists′ work.Compared with the patients, the physicians ( OR=2.866, 95%CI: 1.405-5.848) had higher level of awareness.There was no significant difference in the levels of awareness among the nurses ( OR=1.633, 95%CI: 0.815-3.273), medical technicians ( OR=1.359, 95%CI: 0.630-2.935), administrative staff ( OR=1.470, 95%CI: 0.651-3.317) and the patients.The respondents, aged 36-50 yr ( OR=1.848, 95%CI: 1.224-2.792), with master′s degree ( OR=2.068, 95%CI: 1.090-3.925) and bachelor′ s degree ( OR=3.624, 95%CI: 1.701-7.723), had higher level of awareness, and the respondents without history of anesthesia and surgery ( OR=0.574, 95%CI: 0.380-0.867) and without medicine-related education background ( OR=0.354, 95%CI: 0.145-0.865) had lower level of awareness. Conclusion:There is insufficient awareness about anesthesiologists′ work among hospital staff and patients.Hospital staff are generally better than patients in terms of the level of awareness, but there are differences among different job categories.There is no significant difference in the level of awareness among nurses, medical technicians, administrative staff and patients.The respondents who are middle-aged, with higher education level, with history of anesthesia and surgery and with medicine-related education background, have higher level of awareness.

Objective:To investigate the accuracy and feasibility of 3D-printing individualized template-guided and CT-guided 192Ir interstitial brachytherapy in the central recurrent gynecologic tumors by comparing pre-plan and intraoperative physical dosimetric parameters. Methods:This study involved 38 patients with central recurrent gynecologic tumors who underwent 3D printing individual template (3D-PIT)-assisted and CT-guided 192Ir interstitial brachytherapy in the Department of Radiation Oncology of the Peking University Third Hospital from Jan 2018 to Dec 2019.The prescription doses for the target tumor areas were 10-36 Gy to be delivered at 5-6 Gy/fraction for 2-6 fractions.The pre-plan and intraoperative dosimetric parameters were compared, including the minimum prescription doses delivered to 90% and 100% of target volume( D90, D100)and the mean percentage of volume receiving 100% of the prescription doses ( V100). Meanwhile, the doses delivered to 2 cm 3 ( D2 cm 3) of organs at risk (bladders, rectums, and colons) were analyzed.The quality parameters of the brachytherapy were studied, including conformity index (CI), homogeneity index (HI), and external index (EI) of the target volume.Perioperative complications were also observed. Results:A total of 194 treatments were included.During the treatment, 5-13 (median 6) needles were inserted, with a prescription dose of 5-6 Gy per fraction.There were no statistical differences between pre-plan and intraoperative D90, D100, V100, CI, HI, and EI as well as the D2 cm 3 of bladders and colons at risk ( P>0.05). In contrast, for the D2 cm 3 of rectums, the intraoperative dose was slightly higher than the pre-plan dose, showing a statistical difference ( t=-0.335, P=0.027). Conclusions:The 3D-PIT-assisted and CT-guided 192Ir interstitial brachytherapy at a high dose rate is accurate and feasible in the treatment of recurrent gynecologic tumors, meeting the pre-plan dose requirement.

Objective:To detect the expression of fibroblast-specific protein 1 (FSP1/S100A4) , ɑ-smooth-muscle actin (ɑ-SMA) and fibroblast-activated protein (FAP-ɑ) in tumor-associated fibroblasts (TAFs) in papillary thyroid carcinoma (PTC) , and to investigate its relationship with the origination and development of PTC.Methods:The expression of FSP1/S100A4, ɑ-SMA and FAP-ɑ in normal thyroid and PTC was determined by SP method of immunohistochemistry, and the relationship between these indicators and important clinicopathological parameters were analyzed.Results:The positive expression of FSP1/S100A4, ɑ-SMA and FAP-ɑ was observed in PTC, but not detected in the follicular epithelium or stromal cells of normal thyroid. In addition, the expression of FAP-ɑ was significantly related to tumor size, lymph node metastasis and TNM classification ( χ2=6.833, P<0.05; χ2=10.296, P<0.05; χ2=4.910, P<0.05) . The expression of ɑ-SMA was positively related to the invasion of capsule and lymph node metastasis ( χ2=6.008, P<0.05; χ2=11.766, P<0.05) . The expression of FSP1/S100A4 was negatively related to the clinicopathological parameters above ( P>0.05) in PTC. Conclusion:TAFs in PTC may indicate the infiltration and metastasis, which provideds new thinking for the treatment strategies of papillary thyroid carcinoma.

OBJECTIVE: To investigate the efficacy of image-guided radioactive 125I seed (IGRIS) implantation for pelvic recurrent cervical cancer (PRCC) after external beam radiotherapy (EBRT), and analyze the influence of clinical and dosimetric factors on efficacy. METHODS: From July 2005 to October 2015, 36 patients with PRCC received IGRIS. We evaluated local progression-free survival (LPFS) and overall survival (OS). RESULTS: The median follow up was 11.5 months. The 1- and 2-year LPFS rate was 34.9% and 20%, respectively. The multivariate analysis indicated recurrence site (central or pelvic wall) (hazard ratio [HR]=0.294; 95% confidence interval [CI]=0.121–0.718), lesion volume (HR=2.898; 95% CI=1.139–7.372), D 90 (HR=0.332; 95% CI=0.130–0.850) were the independent factors affecting LPFS. The 1- and 2-year OS rate was 52.0% and 19.6%, respectively. The multivariate analysis suggested pathological type (HR=9.713; 95% CI=2.136–44.176) and recurrence site (HR=0.358; 95% CI=0.136–0.940) were the independent factors affecting OS. The dosimetric parameters of 33 patients mainly included D 90 (128.5±47.4 Gy), D 100 (50.4±23.7 Gy) and V 100 (86.7%±12.9%). When D 90 ≥105 Gy or D 100 ≥55 Gy or V 100 ≥91%, LPFS was extended significantly, but no significant difference for OS. The 79.2% of 24 patients with local pain were suffering from pain downgraded after radioactive 125I seed implantation. CONCLUSION: IGRIS implantation could be a safe and effective salvage treatment for PRCC after EBRT, which could markedly release the pain. Recurrence site, tumor volume and dose were the main factors affected efficacy. Compared with central recurrence, it was more suitable for patients with pelvic wall recurrent cervical cancer after EBRT.
Brachytherapy ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Radiometry ; Radiotherapy* ; Radiotherapy, Image-Guided ; Recurrence ; Salvage Therapy* ; Tumor Burden ; Uterine Cervical Neoplasms*

Objective To explore changes in coagulation function,assessed by thromboelastography (TEG) combined with D-dimer (D-D),in patients undergoing percutaneous vertebroplasty(PVP)or percutaneous kyphoplasty(PKP).Methods A total of 52 elderly patients with osteoporosis-associated vertebral compression fractures admitted into our hospital from May 2016 to November were enrolled in this study,including 13 men aged 64-91 years,with a mean age of(74.3 ± 10.5) years,and 39 women aged 60-89 years,with a mean age of(71.4 ± 7.3) years.Patients received vertebroplasty under local anesthesia,with 29 patients undergoing PVP and 23 cases taking PKP.Thromboelastography(TEG)and D-dimer(D-D)levels were measured at 1 h before,0.5 h,1 h and 3 h after bone cement injections,in order to analyze changes in patients' coagulation function.Results Compared with the coagulation parameters in patients 1 h before bone cement injections,the values of R,K,Angle,Ma,CI,EPL,LY30 and D-D had no significant difference in patients 0.5 h after bone cement injections (P ＞ 0.05);the values of R,Angle,CI,EPL and LY30 were significantly different(P ＜0.05),but the values of K,Ma and D-D had no significant difference(P ＞0.05)in patients 1 h after bone cement injections;the values of R,K,Angle,Ma,CI,LY30 and D-D had no significant difference(P＞0.05),but the value of EPL was significantly different in patients 3 h after bone cement injections(P ＜0.05).Conclusions The blood is in a transient hypercoagulable state during the time of 0.5 h to 3 h after PVP or PKP,which reaches the peak at the time of 1 h after operation,thereby increasing the risk of thrombosis.Therefore,some interventions such as anticoagulants could be carried out during the preoperative and postoperative period.Changes in coagulation function should be closely monitored after operation.Patients should start postoperative exercise early.

Objective To investigate the mediating effects of self-evaluation of depressive symptoms between psychosocial function and negative automatic thinking in patients with depression in remission.Methods The Hamilton depression scale (HAMD-17),generic quality of life inventory(GQOLI),Beck depression inventory(BDI) and automatic thoughts questionnaire (ATQ) were applied to 122 subjects who were patients with depression in remission.Results (1) There was significantly negative correlation between self-evaluation of depressive symptoms and physical function and psychological function and social function(r=-0.559,r=-0.435,r=-0.388,all P＜0.01),and negative correlation between negative automatic thinking and physical function,psychological function and social function(r=-0.563,r=-0.449,r=-0.468,all P＜0.01).(2)The score of physical function,psychological function and social function in the group with low self-evaluation of depressive symptoms was higher than those in the group with high self-evaluation of depressive symptoms (low group:70.27±11.33,69.54±11.53,69.09±10.41;high group:53.33±9.32,57.24±13.80,57.69± 12.77),and the differences were statistically significant (t=7.40,4.82,4.48,P＜0.01).(3) Negative automatic thinking had a significant negative effect on physical function (B =-0.17,P＜0.01),which was affected by self-evaluation of depressive symptoms.The relationship between negative automatic thinking and psychological function was affected by self-evaluation of depressive symptoms.Conclusion Self-evaluation of depressive symptom plays a mediating role between negative automatic thinking and physical function,which also was a mediator in the relationship between negative automatic thinking and mental function.