ObjectiveTo develop a predictive model and application for spontaneous passage of common bile duct stones using automated machine learning algorithms given the complexity of treatment decision-making for patients with common bile duct stones， and to reduce unnecessary endoscopic retrograde cholangiopancreatography （ERCP） procedures. MethodsA retrospective analysis was performed for the data of 835 patients who were scheduled for ERCP after a confirmed diagnosis of common bile duct stones based on imaging techniques in Changshu First People’s Hospital （dataset 1） and Changshu Traditional Chinese Medicine Hospital （dataset 2）. The dataset 1 was used for the training and internal validation of the machine learning model and the development of an application， and the dataset 2 was used for external testing. A total of 22 potential predictive variables were included for the establishment and internal validation of the LASSO regression model and various automated machine learning models. The area under the receiver operating characteristic curve （AUC）， sensitivity， specificity， and accuracy were used to assess the performance of models and identify the best model. Feature importance plots， force plots， and SHAP plots were used to interpret the model. The Python Dash library and the best model were used to develop a web application， and external testing was conducted using the dataset 2. The Kolmogorov-Smirnov test was used to examine whether the data were normally distributed， and the Mann-Whitney U test was used for comparison between two groups， while the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsAmong the 835 patients included in the study， 152 （18.20%） experienced spontaneous stone passage. The LASSO model achieved an AUC of 0.875 in the training set （n=588） and 0.864 in the validation set （n=171）， and the top five predictive factors in terms of importance were solitary common bile duct stones， non-dilated common bile duct， diameter of common bile duct stones， a reduction in serum alkaline phosphatase （ALP）， and a reduction in gamma-glutamyl transpeptidase （GGT）. A total of 55 models were established using automated machine learning， among which the gradient boosting machine （GBM） model had the best performance， with an AUC of 0.891 （95% confidence interval： 0.859‍ ‍—‍ ‍0.927）， outperforming the extreme randomized tree mode， the deep learning model， the generalized linear model， and the distributed random forest model. The GBM model had an accuracy of 0.855， a sensitivity of 0.846， and a specificity of 0.857 in the test set （n=76）. The variable importance analysis showed that five factors had important influence on the prediction of spontaneous stone passage， i.e.， were solitary common bile duct stones， non-dilated common bile duct， a stone diameter of <8 mm， a reduction in serum ALP， and a reduction in GGT. The SHAP analysis of the GBM model showed a significant increase in the probability of spontaneous stone passage in patients with solitary common bile duct stones， non-dilated common bile duct， a stone diameter of <8 mm， and a reduction in serum ALP or GGT. ConclusionThe GBM model and application developed using automated machine learning algorithms exhibit excellent predictive performance and user-friendliness in predicting spontaneous stone passage in patients with common bile duct stones. This application can help avoid unnecessary ERCP procedures， thereby reducing surgical risks and healthcare costs.

[摘 要] 目的：探讨程序性死亡蛋白1（PD-1）抑制剂与恶性黑色素瘤患者癌性疲劳（CRF）之间的关系及其影响因素。方法：选取2019年4月至2024年4月期间在济南市人民医院接受治疗的100例恶性黑色素瘤患者作为研究对象，使用中文版Piper疲劳量表评估这些患者在接受首次PD-1抑制剂治疗前后3个月内的疲劳状况。结果：使用PD-1抑制剂前后的患者疲劳评分存在显著差异（P < 0.001）。单变量分析发现，性别、吸烟史、肿瘤位置以及使用的PD-1抑制剂类型对于疲劳程度没有明显影响（均P > 0.05），而与年龄、疾病分期、贫血状态、白细胞减少症、继发性甲状腺机能减退（甲减）、继发性肾上腺皮质醇功能减退（AI）、继发性促肾上腺皮质激素降低（P < 0.05或P < 0.01或P < 0.001）相关联。进一步的多变量回归分析揭示，继发性甲减、继发性AI、贫血、白细胞减低是导致此类患者出现严重CRF的关键独立风险因素（均P < 0.05）。结论: PD-1抑制剂的不良反应继发性甲减、继发性AI、贫血、白细胞减低是恶性黑色素瘤患者CRF的独立风险因素。

Objective To propose a deep learning neural network approach for transforming megavoltage computed tomography(MVCT)images of cervical cancer into pseudo kilovoltage computed tomography(kVCT)images with high signal-to-noise ratio and contrast-to-noise ratio,thus providing three-dimensional anatomical images and localization information required for adaptive radiotherapy of cervical cancer,and guiding the accelerator to achieve precise treatment.Methods The MVCT and kVCT images of 54 patients treated with cervical cancer radiotherapy were collected,with 44 cases randomly selected as the training set,and the remaining 10 cases as the test set.A cyclic generative adversarial network with gating mechanism and multi-channel data input was used to synthesize pseudo-kVCT images from MVCT images.The network training results were evaluated with imaging quality evaluation parameters,such as mean absolute error(MAE),peak signal-to-noise ratio(PSNR),and structural similarity index(SSIM).Results The MAE,PSNR,and SSIM of MVCT imagesvspseudo-kVCT(5:5)images were(24.9±0.7)HUvs(17.8±0.3)HU,(29.8±0.2)dBvs(30.7±0.2)dB,and 0.841±0.007 vs 0.898±0.003,respectively.Conclusion The generated pseudo-kVCT images have advantages in noise reduction and contrast enhancement,and can reduce the need for additional MV-kVCT electron density calibration in dose calculations.The dose calculation ability of pseudo-kVCT is comparable to that of MVCT,providing a possibility for the application of pseudo-kVCT images in image-guided adaptive radiotherapy.

【Objective】 To systematically evaluate the efficacy and safety of targeted drugs in the treatment of metastatic non-clear cell renal cell carcinoma (nccRCC) and to provide guidance for clinical treatment. 【Methods】 All observational studies and randomized controlled trials (RCTs) of nccRCC treated with targeted drugs were retrieved from the PubMed, Embase, the Cochrane Library and Web of Science. Three independent investigators screened the literature, extracted data and evaluated the quality of literature. The RCTs were evaluated using the Cochrane Handbook. One research with insufficient outcome data (follow-up bias) was assessed as high risk, and the other studies showed low or uncertain risk. The non-RCTs were evaluated with the JBI Quality Assessment Tool, and all studies displayed a low risk of bias. The data were analyzed with Stata 17.0 software. 【Results】 A total of 16 studies involving 989 patients were included. Meta-analysis showed that the objective response rate (ORR) was 12.6% (95%CI:8.1%-17.9%), the total disease control rate (DCR) was 65.3% (95%CI:58.3%-72.1%), the total median progression-free survival (PFS) was 5.80 (95%CI:4.69-6.91) months, and the median overall survival (OS) was 15.93 (95%CI:12.17-19.68) months. In subgroup analysis, the total ORR of patients with metastatic nccRCC treated with sunitinib and cabozantinib were 11.7% (95%CI:6.5%-18.0%) and 17.2% (95%CI:8.4%-28.2%), respectively. The total ORR of patients with papillary renal cell carcinoma was 9.1% (95%CI:2.4%-18.9%). 【Conclusion】 Targeted drugs have a significant effect on patients with metastatic nccRCC, but adverse reactions may occur. Targeted drugs have poor effects on metastatic papillary renal cell carcinoma, and cabozantinib may have greater survival benefits.

Objective:To investigate the risk factors for biochemical recurrence after radical prostatectomy.Methods:The clinical data of 558 radical prostatectomy patients admitted to the First Affiliated Hospital of Air Force Military Medical University from January 2010 to December 2020 were retrospectively analyzed. The average age was 67.9 (40-87) years old, and the average body mass index was 24.56 (15.12-35.94) kg/m 2. The average PSA was 41.07 ng/ml, including 48 cases<10 ng/ml, 98 cases 10-20 ng/ml, and 412 cases>20 ng/ml. There were 123, 214, 118, 89, and 14 cases with biopsy Gleason 6-10 score, respectively. The clinical stage : 90 cases in ≤T 2b, 273 cases in T 2c, and 195 cases in ≥T 3 . 558 cases underwent radical prostatectomy, including 528 robotic-assisted laparoscopic surgery, 25 laparoscopic surgery, and 5 open-surgery. The risk factors for postoperative biochemical recurrence were analyzed by Cox regression. Results:A total of 63 patients had postoperative pathological stage pT 2a, 32 patients had pT 2b, 241 patients had pT 2c, and 222 patients had ≥pT 3. A total of 210 cases developed biochemical recurrence after surgery, and the mean time to biochemical recurrence was 33.3 (3-127) months after the radical prostatectomy. The biochemical recurrence rates at 1, 3, and 5 years were 9.7% (54/558), 21.5% (120/558), and 31.7% (177/558), respectively. Among pT 2a and pT 2b patients, 7 (11.1%) and 4 (12.5%) cases developed biochemical recurrence, respectively. Among pT 2c stage patients, 145 (60.17%) cases had positive cut margins, treated with androgen-deprivation therapy (ADT) after surgery. 68 (28.21%) cases of pT 2c stage patients had biochemical recurrence at mean 36.1 (3-106)months after the radical prostatectomy. Among ≥pT 3 patients, 147 patients with positive margins, perineural invasion, seminal vesicle invasion and positive pelvic lymph nodes were treated with postoperative androgen deprivation therapy (ADT) + radiotherapy. 98 of 147 patients (66.67%) had biochemical recurrence, and the average time to biochemical recurrence was 30.6 (24-98) months.75 patients of ≥pT 3 without positive margins, perineural invasion, seminal vesicle invasion or positive pelvic lymph nodes, were treated with postoperative ADT. 33 of them (44%) had biochemical recurrence, and the average time to biochemical recurrence was 32.5 (21-106) months. 5-and 10-year survival rates of 210 patients with biochemical recurrence were 89.05% (187/210) and 78.09% (164/210) respectively, 5- and 10-year tumor-specific survival rates were 92.57% and 87.69%, respectively. 46 of 210 cases died, of which 31 (67.39%) died from prostate cancer, and 15 cases (32.61%) died from cardiovascular and cerebrovascular diseases. Multifactorial Cox regression analysis showed that patient's age ≥70 years, initial PSA > 20ng/ml, ≥pT 3 and Gleason score ≥7 were independent risk factors for biochemical recurrence. Conclusions:After radical prostatectomy, patients were treated according to their pathological stage and surgical margins. Patients with positive margins have a higher risk of biochemical recurrence. The independent risk factors for biochemical recurrence included age ≥70 years, initial PSA > 20ng/ml, ≥pT 3 and Gleason score ≥7.

Objective: To explore the independent predictors for recurrence-free survival (RFS) in patients with papillary renal cell carcinoma (PRCC), and establish a nomogram to predict individual 2-year RFS. Methods: The data of patients diagnosed in Xijing Hospital of the Air Force Medical University from June 2009 to May 2018 were retrospectively analyzed. A total of 71 patients with primary T_1-4N₀M₀ unilateral tumor were included in this study. The median age was 54 (range from 25 to 83) years. There were 51 males and 20 females. There were 27 cases of typeⅠ, 44 cases of type Ⅱ, 36 cases of left tumor and 35 cases of right tumor. Patients with clinical Ⅰ, Ⅱ, Ⅲ, Ⅳ stage were 47 cases, 12 cases, 9 cases and 3 cases, respectively. Tumor necrosis occurred in 15 cases (21.1%). The average preoperative alkaline phosphatase (ALP) was 89.0(43.0-217.0) U/L, the average preoperative hemoglobin (Hb) was (132.5±19.9) g/L, with 20 cases (28.2%) of Hb<120 g/L before surgery; the average of preoperative Hb was (132.5±19.9) g/L, among which 20 cases (28.2%) had Hb<120 g/L before surgery; the average of preoperative neutrophils/lymphocytes (NLR) was 2.40 (1.03-6.77); radical nephrectomy was performed in 43 patients and nephrectomy was performed in 28 patients. The 1-, 2-, and 3-year RFS were calculated using Kaplan-Meier method and the differences among different subgroups were assessed using Log-rank test. Univariate and multivariate Cox regression analysis were used to identify the independent predictors for RFS, and the nomogram was developed using R software according to the results of multivariate Cox regression analysis. Furthermore, the predictive ability of the nomogram was internally validated using the Bootstrap method by calculating the C-index and drawing the calibration plot. Results: After a median follow-up of 41 ( range from 25 to 83) months, 16 (22.5%) recurrence occurred, including 4 local recurrence and 12 distant recurrence, and 11 (68.8%) patients relapsed within 2 years after surgery. The 1, 2, and 3-year RFS were 88.6%, 80.4%, and 78.7%, respectively. Clinical stage Ⅱ (HR=3.655, 95%CI 1.036-12.890, P=0.044) and stage ≥Ⅲ(HR=3.654, 95%CI 1.008-13.248, P=0.049), preoperative ALP≥90U/L(HR=3.274, 95%CI 1.044-10.267, P=0.042), preoperative Hb<120 g/L (HR=4.771, 95%CI 1.553-14.660, P=0.006), and preoperative NLR≥2.40(HR=4.701, 95%CI 1.238-17.849, P=0.023) were identified as independent risk factors for RFS. On internal validation, the nomogram which integrates the four predictors of clinical stage, preoperative ALP, preoperative HB and preoperative NLR, has a good predictive performance (C-index =0.829, 95%CI 0.819-0.839). Conclusions In the present study based on single center data, clinical stage Ⅱ and ≥Ⅲ, preoperative ALP≥90 U/L, preoperative Hb<120 g/L and preoperative NLR ≥2.40 were independent predictors for postoperative RFS in patients with PRCC, and a new preoperative nomogram for predicting individual postoperative 2-year RFS was established, which would be helpful for urologists to develop more systematic treatment plans.

Objective To use helical tomotherapy ( HT ) for determining the difference between actual doses and planning doses to the target volume and organs at risk ( OARs ) in patients with nasopharyngeal carcinoma receiving radiotherapy, and to provide guidance for the clinical treatment. Methods Localization and delineation of the target volume and OARs were performed by computed tomography ( CT) in 21 patients with nasopharyngeal carcinoma receiving radical radiotherapy using HT. All patients underwent megavoltage CT ( MVCT) scan prior to treatment. The obtained MVCT images were used for dose reconstruction in the adaptive module of HT, in which the actual dose was obtained and the non?image?guided dose was simulated. Each single dose distribution and the corresponding CT image were sent to software MIM6. 0 for superimposition, and the overall dose was obtained. The initial plan, image?guided plan, and non?image?guided plan were named Plan?1, 2, and 3, respectively. The dose distribution in the target volume and OARs was compared between the three plans with t ? test or wilcoxon test . Results Compared with those in Plan?1, the D98 values for the planning gross tumor volume ( PGTV) and planning target volume ( PTV) in Plan?2 were significantly reduced by 1. 16% and 2. 3%, respectively ( P=0. 025;P=0. 043);the volumes of the left and right parotids in Plan?2 were significantly reduced by 46. 0% and 46. 5% on average, respectively ( P=0. 000);the distances between the midline and the center?of?mass for left and right parotids were significantly reduced by 6. 9% and 6. 5%, respectively ( P=0. 000);the V26 and Dmean for both parotid glands were significantly elevated by 32. 8% and 25. 2%, respectively ( P=0. 000) . Compared with those in Plan?1, the D98 values for PGTV, PTV?1, and PTV?2 in Plan?3 were significantly reduced by 2. 0%, 1. 9%, and 2. 4%, respectively ( P=0. 001;P=0. 007;P=0. 036);the V26 and Dmean for both parotid glands in Plan?3 were significantly elevated by 33. 6% and 25. 3%, respectively ( P=0. 000);Dmax to the spinal cord was significantly increased by 6. 9%( P=0. 005) . There was no significant difference in D2 to the spinal cord between Plan?2 and Plan?1( P=0. 392) . Conclusions The doses to both parotid glands increase during HT for nasopharyngeal carcinoma, which is closely associated with the shift of the parotid glands toward the midline. Image?guided radiotherapy does not enhance the dose to the target volume, but reduces the dose to the spinal cord.

Objective To assess the safety and efficacy of preoperative intensity-modulated radiotherapy(IMRT) with oral capecitabine in patients with locally advanced mid-low rectal cancer using a simultaneous integrated boost (SIB) of tomotherapy.Methods Total 16 patients with resectable locally advanced mid-low rectal cancer (patients with T3 to T4 and/or N ± rectal cancer) were enroll in current study.Patients were received IMRT to 2 dose levels simultaneously (55 and 47.5 Gy in 25 fractions) with concurrent capecitabine 825 mg/m2 twice daily,5 days/week.Total mesorectal excision was performed at 8 to 9 week after the completion of chemoradiation.The primary end point included side effect,the rate of sphinctersparing,postoperative complication and pathological complete response rate (pCR) were observed.Side effects were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.Results All patients were received chemoradiotion therapy without any break.Tomotherapy showed superiority with respect to target coverage,homogeneity and conformality.Two patients refused to perform radical surgery because of almost complete primary tumor regression and complete symptom relief after neoadjuvant therapy.Fourteen patients underwent surgical resection and 11 patients (78.6％) underwent sphincter-sparing lower anterior resection.Four patients(28.6％) had a pathological complete response.The incidence of grade 1-2 hematologic,gastro-intestinal toxicities were 62.5％ (10/16) and 18.8％ (3/16).The incidence of grade 3 skin toxicities were 68.8％(10/16).Grade Ⅳ side effect was not observed.Surgical complications (incisional infection on thirteen after surgery) were observed in 1 patient.Conclusion Preoperative simultaneous integrated boost of tomotherapy with concurrent oral capecitabine is safe and well tolerated in patients with a promising local control.However,a larger number of patients and a long follow-up are required to assess its potential superiority.

Objective To analyze the impact of parotid's position and volume changing on radiation dose for head and neck cancer treated with TomoTherapy.Methods Totally 12 patients with head and neck cancer were treated with TomoTherapy.Before the treatment,the dose distribution was recalculated with MVCT images,which would obtain the parameters of position,volume and actual radiation dose for parotids.Results The volume of parotids in Plan2 was significantly lower than in Plan1,and the percentage reduction was 29.06％ and 31.78％ for left and right parotid,respectively (Z =6.77,3.06,P ＜ 0.05).Distance between the COM (center of mass) of parotids and the midline of body was significantly smaller in Plan2 than in Plan1,and the percentage reduction was 6.72％ and 6.19％ (t =5.14,5.80,P ＜ 0.05) at left and right side,respectively.Average dose and V26 for both parotids were higher than those in Plan1,increasing by an average of 37.74％,25.08％ (Z =-6.03,-5.31,P ＜ 0.05) for left parotid and 30.45％,19.33％ (Z =-5.43,-3.26,P ＜0.05) for right parotid,respectively.Conclusions The actual radiation dose to parotids was significantly increased during the radiation therapy for patients with head and neck cancer.There was a linear correlation between the decrease of distance between the COM of parotids and the midline of body and the percentage increase of parotids' radiation dose.No correlation between the reduction of parotids' volume and dose to parotids.In order to reduce the parotids' radiation dose,modification of treatment plan at the appropriate time is essential.

Objective To study the expression and interactions of DNA methyltransferase 1 (DNMT1),enhancer of zeste homolog 2 (EZH2) and histone deacetylase 1 (HDAC1) in gastric cancer cell lines and tissue specimens.Methods The expression of DNMT1,EZH2 and HDAC1 was detected at mRNA and protein level in gastric cancer lines MKN28,SGC7901,BGC823,AGS,normal gastric epithelium cell line GES-1 and 10 pairs of fresh gastric cancer tissues and corresponding normal gastric tissues by real-time polymerase chain reaction and Western blot.Whether DNMT1,EZH2 and HDAC1 forming complex or not was detected by co-immunoprecipitation (Co-IP) in well-differentiated gastric cancer cell line MKN28,medium-differentiated gastric cancer cell line SGC7901,lowdifferentiated gastric cancer cell line BCG823,normal gastric epithelium cell line GES-1,mediumdifferentiated,medium to low-differentiated,low-differentiated gastric cancer tissues and corresponding normal gastric tissues.Results Compared with that of normal gastric epithelium cell and gastric tissue,the expression of DNMT1,EZH2 and HDAC1 in gastric cancer cell lines and gastric tissue was higher.The results of Co-IP indicated that DNMT1,EZH2 and HDAC1 formed complex in the high,medium,and poor differentiated gastric cancer cells and the medium,mediumlow,poor differentiated gastric cancer tissues,but not in normal gastric epithelium cell and tissue.Conclusion DNMT1,EZH2 and HDAC1 highly expressed in gastric cancer and there was interaction effects among them,which might be an important mechanism in the correlation between DNA methylation and histone modifications in gastric cancer.