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Xingzhi Li,1,2,&ast; Zhihong Tang,1,&ast; Qingqing Pang,1,&ast; Xiaobo Wang,1 Tao Bai,1 Jie Chen,1 Meng Wei,1 Tao Wei,1 Lequn Li,1 Feixiang Wu1,3 1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Department of Hepatobiliary Surgery, Nanchong Central Hospital, The Second Clinical College of North Sichuan Medical College, Nanchong, People’s Republic of China; 3Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feixiang Wu; Lequn Li, Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of China, Email wufeixiang@gxmu.edu.cn; lilequngx@163.comBackground: The prognosis of initially unresectable hepatocellular carcinoma (iuHCC) has been improved by TACE with TKIs and PD-1 inhibitors (TTP). However, the role of timing of tumor progression and and early salvage surgery during TTP therapy remains unclear.Patients and Methods: The data of 151 patients who received TTP for iuHCC consecutively between November 2019 and December 2022 were retrospectively analyzed. The X-Tile software was used to determine the optimal threshold of progression timing to differentiate the post-progression survival (PPS) for patients with tumor progression, ultimately yielding 9 months as the optimal cut-off time. Early tumor progression was defined as patients with tumor recurrence (surgical patients) or progressive disease by mRECIST (nonsurgical patients) within 9 months of initial treatment. Accordingly, early salvage surgery was defined as salvage surgery performed within 9 months of the initial treatment.Results: Out of all the patients, 55 (36.4%) patients showed early tumor progression, 33 (34.4%) showed late tumor progression, and 63 (41.7%) showed non-progression. Patients who experienced early tumor progression had a median PPS of 5.2 months, while those with late tumor progression had a median PPS of 16.8 months (P < 0.001). Multivariable analysis revealed a robust independent correlation between early tumor progression and PPS (HR = 3.279, 95% CI: 1.591– 6.756; P = 0.001). Patients who received early salvage surgery showed a considerably lower early tumor progression rate when compared with patients who did not receive early surgery (12.5% vs 42.9%, P = 0.002). The multivariable analysis revealed that early salvage surgery was an independent factor influencing early tumor progression (OR = 0.246; 95% CI: 0.078– 0.773; P = 0.016).Conclusion: Early tumor progression is associated with worse PPS in patients with iuHCC receiving TTP therapy. Early salvage surgery can further improve patient outcomes by lowering the incidence of early progression.Keywords: Hepatocellular carcinoma, salvage surgery, early tumor progression, post-progression survival, real-world

Lingli Jiang,1,&ast; Lei Peng,1,&ast; Miaoling Rong,2 Xiaozhi Liu,3 Qinxia Pang,1 Huaping Li,1 Ying Wang,1 Zhou Liu1 1Department of Obstetrics and Gynecology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 2Department of Obstetrics and Gynecology, First Maternity and Infant Hospital Affiliated to Tongji University, Shanghai, People’s Republic of China; 3Department of Ultrasound, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhou Liu, Department of Obstetrics and Gynecology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, No. 1500, Zhouyuan Road, Pudong New Area, Shanghai, 201318, People’s Republic of China, Tel +86 18930837705, Email zp_liuz@sumhs.edu.cnBackground: The majority of women who experience spontaneous preterm delivery (SPTD) have low-risk, asymptomatic pregnancies with a cervical length (CL) ≥ 25mm and no clear risk factors. Despite the fact that cervical elastography is a potential tool for predicting SPTD, there is currently no feasible solution to make a reliable prediction for preventing SPTD.Objective: The aim of this study was to construct a nomogram including multimodal transvaginal ultrasound parameters during the second trimester to predict SPTD in low-risk women.Methods: This multi-center study enrolled 1260 women with singleton pregnancies between 20 and 24 weeks’ gestation. CL and cervical elastography data were obtained when they were undergoing the second-trimester anomaly scan. Univariate and multivariate Logistic regression were utilized to screen predictors independently related to SPTD from the maternal characteristics and multimodal ultrasound data. Then construct a nomogram to determine the likelihood of SPTD in pregnant women.Results: A total of 66 pregnancies in the training cohort (7.8%, 66/842) and 37 pregnancies (8.9%, 37/418) in the validation cohort ended in SPTD. Age, uterine curettage, CL, and strain in the anterior lip of internal os were the independent predictors of SPTD (P < 0.001, < 0.001, = 0.007, and < 0.001, respectively). These predictors constituted a nomogram to predict the probability of SPTD for a pregnant woman in her second trimester. It showed good discrimination (C-index = 0.898 and 0.839), calibration (P = 0.258 and 0.115), and yielded net benefits both in the training and validation cohorts.Conclusion: The nomogram including data of multimodal transvaginal ultrasound at 20 to 24 weeks’ gestation is expected to identify women with SPTD in the low-risk, asymptomatic population.Keywords: cervical length measurement, elasticity imaging techniques, nomograms, pregnancy trimester, second, premature birth

Heming Lu,1,&ast; Yuying Wu,2,&ast; Xu Liu,1 Huixian Huang,1 Hailan Jiang,1 Chaohua Zhu,1 Yuping Man,3 Pei Liu,4 Xianglong Li,1 Zhaohong Chen,1 Xianfeng Long,1 Qiang Pang,1 Shan Deng,1 Junzhao Gu1 1Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, People’s Republic of China; 2Department of Gynecology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, People’s Republic of China; 3Department of Radiology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, People’s Republic of China; 4Department of Oncology, Youjiang Medical University for Nationalities, Baise, 533000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Heming LuDepartment of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, No. 6 Taoyuan Road, Nanning, 530021, People’s Republic of ChinaTel +86-771-218-6806Email luhming3632@163.comPurpose: To evaluate the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting early treatment response.Materials and Methods: Patients with locally advanced cervical cancer (LACC) treated with concurrent chemoradiotherapy (CCRT) were enrolled. Pelvic DCE-MRI scans were performed before RT (pre-RT), in the middle of RT (mid-RT), and at the end of RT (post-RT), separately. Parameters (ie, Ktrans, Kep, and Ve) were measured. Pre-, mid-, and post-RT Ktrans were denoted as Ktrans-preTx, Ktrans-midTx, and Ktrans-postTx, respectively. And the same denoting rule also went for Kep and Ve. Difference for the same parameter such as Ktrans measured between two consecutive time points was calculated as second Ktrans value minus first Ktrans value. The differences in Ktrans between pre-RT and post-RT, between pre-RT and mid-RT, and between mid-RT and post-RT were denoted as ΔKtrans-post-preTx, ΔKtrans-mid-preTx, and ΔKtrans-post-midTx, respectively, and the same denoting rule was also applied to Kep and Ve.Results: A total of 57 patients were enrolled. After the treatment, 31 patients had complete response (CR group). The remaining 26 patients had partial response (NCR group). Significant differences were found in Ktrans-postTx, Kep-postTx, Ve-midTx, ΔKtrans-post-preTx, ΔKtrans-post-midTx, ΔKep-post-preTx, ΔKep-mid-preTx and ΔKep-post-midTx between the two groups. Receiver operating characteristic (ROC) analysis for their performances in predicting treatment response showed an area under curve (AUC) of 0.656– 0.849, sensitivity of 61.3– 93.5%, specificity of 46.1– 73.1%, and maximal Youden Index of 36.5– 66.6. Among those parameters, Kep-postTx was the best, and its AUC, sensitivity, specificity, maximal Youden Index, and cutoff value were 0.849, 87.1%, 73.1%, 60.2, and 0.341, respectively. These combined parameters showed an AUC of 0.952, with sensitivity of 87.1%, specificity of 96.1%, and maximal Youden Index of 83.2.Conclusion: DCE-MRI parameters can predict early treatment outcome. Among those parameters, Kep-postTx is the best predictor. The combination of multi-parameters can increase the predictive potency.Keywords: cervical cancer, locally advanced disease, dynamic contrast-enhanced magnetic resonance imaging, concurrent chemoradiotherapy, prognosis prediction

Shuangchi Liu,1 Zhiduan Xu,1 Zhuling Fang,2 Dengyong Zhang,1 Zhongqiang Qin,1 Longfei Fan,1 Jiakang Duan,1 Hongxiang Yin,1 Yigang Zhang,1 Qing Pang,1,3 Yi Tan1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, Anhui, People’s Republic of China; 2Department of Medical Laboratory, Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China; 3Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, People’s Republic of ChinaCorrespondence: Yi Tan; Qing PangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of ChinaEmail doctortanyi2007@126.com; portxiu2@126.comBackground: Advanced liver fibrosis can lead to cirrhosis, portal hypertension and liver failure. Besides, advanced liver fibrosis and cirrhosis are the major risk factors for hepatocellular carcinoma (HCC). Almost all patients with HCC also have liver cirrhosis. This study aims to predict the survival rate of hepatitis B-related hepatocellular carcinoma (HCC) by age, international standardized ratio, albumin and γ-glutamyl transpeptidase (AIAG), an indicator measuring the degree of cirrhosis.Methods: A total of 501 hepatitis B-related HCC patients experiencing radical surgery were analyzed, retrospectively. General data about demographics and labs were collected at the date of diagnosis to calculate AIAG [age, international standardized ratio (INR), albumin and gamma-glutamyl transferase (GGT)]. The Kaplan–Meier curves and Cox analysis were used to evaluate overall survival (OS) and recurrence-free survival (RFS). The C-index was calculated in R software (version 4.0.3) to evaluate the accuracy of the prognostic model.Results: During a median follow-up period of 30 months, 31.1% (156/501) of the patients died, and 34.3% (172/501) experienced the recurrence of HCC. Compared with patients with lower AIAG score, patients with higher AIAG score had higher Child-Pugh grade and were at higher Barcelona Clinic Liver Cancer (BCLC) stage (both P< 0.05). Multivariate analysis suggested that GGT, alpha fetoprotein (AFP), tumor size, BCLC stage and AIAG grade were independent predictors of OS and RFS. Furthermore, the combined use of tumor size, AFP and AIAG stage could predict survival significantly better (C-index=0.710, 95% CI: 0.669– 0.751) than BCLC stage.Conclusion: AIAG is significantly associated with survival of HCC patients, and provides additional prognostic information for patients with HCC. Our findings suggest that the combination of AIAG, tumor size and AFP stage has a better predictive value for the prognosis of patients with hepatitis B-related hepatocellular carcinoma. However, it is necessary for more external evidences to determine clinical utility.Keywords: AIAG, hepatocellular carcinoma, survival, prognosis

Dan Chen,1,* Zhi-qi Gao,1,* Ying-ying Wang,1 Bin-bin Wan,1 Gang Liu,1 Jun-liang Chen,1 Ya-xian Wu,1 Qin Zhou,2 Shan-yu Jiang,2 Ren-qiang Yu,2 Qing-feng Pang1 1Department of Physiopathology, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu Province, People’s Republic of China; 2Department of Neonatology, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, 214002, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ren-qiang Yu 48 Huaishu Lane, Liangxi District, Wuxi, Jiangsu Province, People’s Republic of ChinaTel +86510-82709790Fax +86-510-82725094Email yurenqiang553@163.comQing-feng Pang 1800 Lihu Avenue, Binhu District, Wuxi, Jiangsu Province, People’s Republic of ChinaTel +8651052430172Fax +86-510-85329042Email qfpang@jiangnan.edu.cnBackground: Alveolar arrest and the impaired angiogenesis caused by chronic inflammation and oxidative stress are two main factors in bronchopulmonary dysplasia (BPD). Short-chain fatty acids (SCFAs), especially propionate, possess anti-oxidant and anti-inflammatory effects. The present study was designed to examine the roles of sodium propionate (SP) on lipopolysaccharide (LPS)-challenged BPD and its potential mechanisms.Methods: WT, Nrf2-/- mice and pulmonary microvascular endothelial cells (HPMECs) were used in this study. LPS was performed to mimic BPD model both in vivo and vitro. Lung histopathology, inflammation and oxidative stress-related mRNA expressions in lungs involved in BPD pathogenesis were investigated. In addition, cell viability and angiogenesis were also tested.Results: The increased nuclear factor erythroid 2-related factor (Nrf2) and decreased Kelch-like ECH-associated protein-1 (Keap-1) expressions were observed after SP treatment in the LPS-induced neonatal mouse model of BPD. In LPS-induced wild-type but not Nrf2-/- neonatal mice, SP reduced pulmonary inflammation and oxidative stress and exhibited obvious pathological alterations of the alveoli. Moreover, in LPS-evoked HPMECs, SP accelerated Nrf2 nuclear translocation presented and exhibited cytoprotective and pro-angiogenesis effects. In addition, SP diminished the LPS-induced inflammatory response by blocking the activation of nuclear factor-kappa B pathway. Moreover, pretreatment with ML385, an Nrf2 specific inhibitor, offsets the beneficial effects of SP on inflammation, oxidative stress and angiogenesis in LPS-evoked HPMECs.Conclusion: SP protects against LPS-induced lung alveolar simplification and abnormal angiogenesis in neonatal mice and HPMECs in an Nrf2-dependent manner.Keywords: sodium propionate, lipopolysaccharide, Nrf2, angiogenesis, bronchopulmonary dysplasia

Jing Zeng,1,2 Ziqi Liu,3 Shan Jiang,3 Qingsong Pang,1 Ping Wang1 1Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 2Department of Gynecologic Oncology, Tianjin Central Hospital of Gynecology and Obstetrics, Affiliated Hospital of Nankai University, Tianjin, People’s Republic of China; 3School of Mechanical Engineering, Tianjin University, Tianjin, People’s Republic of ChinaCorrespondence: Ping WangTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of ChinaEmail wangping2019@foxmail.comPurpose: Our previous research demonstrated that under ideal conditions, rigid registration between MRI images and US images had high accuracy for real-time image guidance. The work presented in this paper focused on the application of the previously established procedures to a new context, including preoperative CT images.Materials and Methods: We used a template to calibrate the US probe and completed the registration between preoperative CT images and US images. Marker experiments on the accuracy of real-time needle trajectories in CT images were performed using micro electromagnetic sensors. Pelvic phantom experiments were carried out to test the registration accuracy between CT and US images, in addition to registration accuracy between US images and real-time needle trajectories (real-time space model).Results: The US probe calibration error in CT images was 0.879 ± 0.149 mm. The difference of registration between US images and CT images was 0.935 ± 0.166 mm in the axial plane (n = 30) and 0.916 ± 0.143 mm in the sagittal plane (n =12). The difference of registration between US images and the needle’s real-time trajectories was 0.951 ± 0.202 mm.Conclusion: Under ideal conditions, rigid registration between CT images and US images had high accuracy for real-time image guidance.Keywords: registered ultrasound image, gynecologic brachytherapy, rigid registration, image-guidance

Defeng Qing,1,* Yuying Wu,2,* Xu Liu,1,* Hailan Jiang,1,* Chaohua Zhu,1,* Pei Liu,3 Junming Dang,4 Xianglong Li,1 Zhaohong Chen,1 Xianfeng Long,1 Qiang Pang,1 Luxing Peng,1 Shan Deng,1 Junzhao Gu,1 Renfeng Zhao,2 Changyi Chen,2 Heming Lu1 1Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, People’s Republic of China; 2Department of Gynecology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, People’s Republic of China; 3Department of Radiation Oncology, Youjiang Medical University for Nationalities, Baise 533000, People’s Republic of China; 4Department of Oncology, Guangxi University of Chinese Medicine, Nanning 530001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Heming LuDepartment of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning City 530021, People’s Republic of ChinaTel +86-771-218-6504Email luhming3632@163.comPurpose: We aimed to evaluate the long-term survival outcomes of concurrent chemoradiotherapy (CCRT) combined with nimotuzumab followed by surgery in patients with locally advanced cervical cancer (LACC).Patients and Methods: Patients received whole pelvic intensity-modulated radiation therapy (IMRT) and concomitantly with weekly cisplatin (40 mg/m2) or nedaplatin (30 mg/m2) and weekly nimotuzumab (200 mg). After assessment of the treatment response, patients then underwent radical surgery.Results: Between June 2013 and July 2016, 33 patients with FIGO IB2–IIIB cervical cancer were recruited. Clinical complete response and partial response were observed in 8 (24.3%) and 23 patients (69.7%), respectively. Twenty-seven patients (81.8%) were successfully treated with radical hysterectomy and pelvic lymphadenectomy: 9 (33.3%) showed pathological complete response; 10 (37.1%) showed partial response and 8 (29.6%) presented with persistent macroscopic/microscopic residual carcinoma. For the intention-to-treat population, the median follow-up time was 53.7 months. Locoregional recurrence and distant metastases were observed in three and seven patients, respectively. The 5-year overall survival, progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival were 81.5%, 72.7%, 90.9%, and 78.3%, respectively. Both acute and late toxicities were manageable and mainly limited to grade 1 or 2.Conclusion: Concurrent chemoradiotherapy combined with nimotuzumab followed by surgery for patients with LACC is safe and results in excellent long-term treatment outcomes. Further randomized controlled studies are warranted to confirm the findings.Keywords: locally advanced cervical cancer, neoadjuvant chemotherapy, intensity-modulated radiotherapy, anti-EGFR monoclonal antibody, radical surgery

Qing Pang,1,2,* Shuangchi Liu,1,* Luyao Wang,3,* Huadong Pan,3 Chunfang Wang,3 Lei Zhou,1 Yimin Lu,1 Huichun Liu1 1Department of Hepatobiliary Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui Province 233000, People’s Republic of China; 2Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province 710061, People’s Republic of China; 3Clinical Medical College of Bengbu Medical College, Bengbu, Anhui Province 233000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huichun Liu; Yimin LuDepartment of Hepatobiliary Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, People’s Republic of ChinaEmail liuhcdoctor@126.com; yimludoctor@126.comBackground: Platelet–albumin–bilirubin (PALBI) has been demonstrated to be superior to conventional Child–Pugh (C-P) grade in evaluating liver function and prognosis of HCC patients. However, both thrombocytosis and thrombocytopenia are unfavorable for HCC survival. The aim of this study was to preliminarily investigate the prognostic value of PALBI in HCC patients with thrombocytopenia and excluding thrombocytopenia.Methods: In this retrospective cohort study, we reviewed 465 cases of HCC patients who underwent radical surgery. PALBI grade was calculated based on preoperative serological examinations. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS), which were assessed by Kaplan–Meier method and Cox regression. The prognostic performances of PALBI and other models were estimated by using the concordance index (C-index).Results: During a median follow-up time of 28 months, 31.6% (147/465) of patients died and 33.5% (156/465) experienced recurrence. Multivariate analyses revealed that both thrombocytosis and thrombocytopenia were independently associated with poor OS and RFS compared with normal platelet count (PLT) in HCC patients. Stratified analysis further revealed that PALBI was a significant predictor for HCC survival in patients excluding thrombocytopenia but not in patients with thrombocytopenia. In particular, in HCC patients excluding thrombocytopenia, the combination of tumor size with PALBI (C-index = 0.730, 95% CI: 0.674– 0.786) may be superior to the classical Barcelona Clinic Liver Cancer (BCLC) and Cancer of Liver Italian Program (CLIP) staging systems in predicting survival.Conclusion: In conclusion, PALBI grade, in particular the combination with tumor size, is an effective model for discriminating survival in HCC patients excluding thrombocytopenia but not in thrombocytopenic HCC patients.Keywords: hepatocellular carcinoma, survival, platelet–albumin–bilirubin, platelet count

Jing Zeng,1,2 Pengpeng Qu,1 Qingsong Pang,2 Ping Wang2 1Department of Gynecologic Oncology, Tianjin Central Hospital of Gynecology and Obstetrics, Affiliated Hospital of Nankai University, Tianjin 300100, People’s Republic of China; 2Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, People’s Republic of ChinaCorrespondence: Pengpeng Qu Email qu.pengpeng@hotmail.comIntroduction: This study aims to measure the air-kerma rate of 192-Ir-HDR-afterloading source with an ionization chamber in air and a solid cylindrical phantom separately and to compare the dose calibration by the American Association of Physicists in Medicine (AAPM) Task Group TG-43U1 formalism with the Abacus treatment planning system (TPS).Materials and Methods: The air-kerma rate of 192Ir source was measured by an ionization chamber in air and a solid cylindrical phantom separately. For the interesting point position P (8cm, 90°), the values of the dose were calculated with the TG-43U1 formula and compared with data from the Abacus TPS with single and multiple dwell positions, respectively.Results: The air-kerma rate percentage deviations between the detector measurements in air and the source certificate were − 1.28%, − 0.91%, − 0.71%, and 0.33% at the distances of 25cm, 50cm, 75cm, and 100cm, respectively. For the measurement in solid cylindrical phantom, the percent deviation from the air-kerma rate certificate was 1.85%. The percentage deviations of the dose calibration between Abacus TPS and TG-43U1 formalism at P (8cm, 90°) were − 2.30%, 1.76%, and 2.10% with different distances (between the dwell positions) of 0cm, 0.5cm, and 1cm, respectively.Conclusion: The in-air technique was a new attempt for clinic routine measurement. Further studies are still necessary. As a treatment planning system, the Abacus TPS should apply the AAPM TG-43U1 formulism for the development required in the future.Keywords: brachytherapy, 192Ir source, calibration, ionization chamber

Jiaqi Zhang, Wencheng Zhang, Baozhong Zhang, Dong Qian, Xiaoxia Li, Hualei Zhang, Qi Wang, Lujun Zhao, Qingsong Pang, Ping Wang Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, People’s Republic of ChinaCorrespondence: Ping WangTianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin 300060, People’s Republic of ChinaTel +86 222 334 1405Fax +86 222 334 1405Email wangping@tjmuch.comPurpose: To evaluate and analyze the efficacy and prognostic factors of intensity-modulated radiotherapy in 250 patients with cervical and upper esophageal carcinoma.Patients and methods: From September 2009 to September 2016, we retrospectively analyzed 250 patients with cervical and upper esophageal carcinoma treated with intensity-modulated radiotherapy (IMRT). In our study, all patients received IMRT, 54 patients with cervical esophageal carcinoma and 196 patients with upper esophageal carcinoma. Treatment response, survival status and failure modes of treatment were observed, and prognostic factors were analyzed.Results: The median survival time was 22.60 months and 3-year survival rate was 42%. The median progress-free survival time was 14.52 months and 3-year progress-free survival rate was 29.3%. The median survival time and the median progress-free survival time for cervical esophageal carcinoma were 20.40 and 15.15 months, respectively. The median survival time and the median progress-free survival time for upper esophageal carcinoma were 25.80 and 14.52 months, respectively (P>0.05). The significant clinical factors associated with survival were patient age, radiotherapy dose and T stages (P

Yanjun Wang,1,* Bo Pang,2,* Rui Zhang,1 Yibing Fu,3 Qi Pang1 1Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, People’s Republic of China; 2Department of Neurosurgery, Shandong University, Jinan 250021, People’s Republic of China; 3Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qi PangDepartment of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan 250021, Shandong Province, People’s Republic of ChinaTel +86 136 1531 6688Email pangqi@sdu.edu.cnYibing FuDepartment of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan 250021, Shandong Province, People’s Republic of ChinaTel +86 151 6888 9696Email fuyi_bing@163.comPurpose: Ubenimex, an aminopeptidase N (APN) inhibitor, is widely known for its use as an adjunct therapy for cancer therapy. However, in recent studies, it has also conferred antitumour effects in many cancers, but its anticancer mechanism is largely unknown. This study aims to investigate the specific anticancer activities and mechanisms of ubenimex in GH3 and MMQ cells.Materials and methods: In this study, we investigated the anticancer effects of ubenimex in GH3 and MMQ cells. Cell viability and cell death were assessed by the Cell Counting Kit-8 kit (CCK-8) and a LIVE/DEAD cell imaging kit. Apoptosis and intracellular reactive oxygen species (ROS) generation were assessed by flow cytometry and fluorescence microscopy. Autophagosome formation was detected by transmission electron microscopy, and autophagic flux was measured with mRFP-GFP-LC3 adenoviral transfection. The protein expression level was detected by Western blotting.Results: The results revealed that treatment with ubenimex induced apoptotic and autophagic cell death in GH3 and MMQ cells, which resulted in decreased viability, an increased proportion of apoptotic cells, and autophagosome formation. Further experiments showed that ubenimex induced ROS generation and activated the ROS/ERK pathway. The ROS scavenger NAC could attenuate ubenimex-induced apoptosis and autophagy.Conclusion: Our studies revealed that ubenimex exerted anticancer effects by inducing apoptotic and autophagic cell death in GH3 and MMQ cells, rendering it a possible effective adjunctive therapy for pituitary treatment.Keywords: pituitary, ubenimex, autophagy, apoptosis, ROS

Fei Lu,1,2 Zhiyong Pang,2,3 Jingjing Zhao,2 Kai Jin,4 Haichun Li,2 Qiang Pang,2 Long Zhang,2 Zhiqing Pang2 1Department of Pharmacy, Xianju People’s Hospital, Xianju, Zhejiang, 2Department of Pharmaceutics, Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, 3Chongyang Center for Disease Control and Prevention, Xianning, Hubei, 4School of Life Science, Fudan University, Shanghai, People’s Republic of China Abstract: The blood–brain barrier is a formidable obstacle for glioma chemotherapy due to its compact structure and drug efflux ability. In this study, a dual-targeting drug delivery system involving Angiopep-2-conjugated biodegradable polymersomes loaded with doxorubicin (Ang-PS-DOX) was developed to exploit transport by the low-density lipoprotein receptor-related protein 1 (LRP1), which is overexpressed in both blood–brain barrier and glioma cells. The polymersomes (PS) were prepared using a thin-film hydration method. The PS were loaded with doxorubicin using the pH gradient method (Ang-PS-DOX). The resulting PS were uniformly spherical, with diameters of ~135 nm and with ~159.9 Angiopep-2 molecules on the surface of each PS. The drug-loading capacity and the encapsulation efficiency for doxorubicin were 7.94%±0.17% and 95.0%±1.6%, respectively. Permeability tests demonstrated that the proton diffusion coefficient across the PS membrane was far slower than that across the liposome membrane, and the common logarithm value was linearly dependent on the dioxane content in the external phase. Compared with PS-DOX, Ang-PS-DOX demonstrated significantly higher cellular uptake and stronger cytotoxicity in C6 cells. In vivo pharmacokinetics and brain distribution experiments revealed that Ang-PS-DOX achieved a more extensive distribution and more abundant accumulation in glioma cells than PS-DOX. Moreover, the survival time of glioma-bearing rats treated with Ang-PS-DOX was significantly prolonged compared with those treated with PS-DOX or a solution of free doxorubicin. These results suggested that Ang-PS-DOX can target glioma cells and enhance chemotherapeutic efficacy. Keywords: Angiopep-2, dual targeting, biodegradable polymersomes, doxorubicin, glioma treatment

Hongqing Zhuang,1–4 Zhiyong Yuan,1–4 Jun Wang,1–4 Lujun Zhao,1–4 Qingsong Pang,1–4 Ping Wang1–41Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, 2National Clinical Research Center of Cancer, 3Tianjin Key Laboratory of Cancer Prevention and Therapy, 4Tianjin Lung Cancer Center, Tianjin, People’s Republic of ChinaAbstract: The aim of this paper is to explore the efficacy of whole brain radiotherapy (WBRT) versus WBRT concurrent with erlotinib in patients with multiple brain metastases of lung adenocarcinoma. WBRT was administered at 30Gy/10f in both arms. In the combination arm, 150 mg erlotinib was given each day, starting the first day of radiotherapy and continuing for 1 month following the end of radiotherapy. Thereafter, pemetrexed or docetaxel monotherapy or the best supportive therapy was given to both arms. The intracranial objective response rate and the local progression-free survival (LPFS) were primary endpoints. Toxicity, progression-free survival (PFS) and overall survival (OS) were secondary endpoints. Thirty-one patients in the WBRT group and 23 patients in the combination group were enrolled from November 2009 to December 2011. In the WBRT and the combination arms, respectively, the objective response rate was 54.84% and 95.65% (P = 0.001), the median local progression-free survival was 6.8 months and 10.6 months (P = 0.003), the median PFS was 5.2 months and 6.8 months (P = 0.009), and median OS was 8.9 months and 10.7 months (P = 0.020). In the combination group, there were no differences of LPFS, PFS, and OS between the epidermal growth factor receptor (EGFR) mutation patients and EGFR wild-type patients. No Grade 4 or higher side effects were observed in either group. A multivariate analysis indicated that erlotinib was the most important prognostic factor for a prolonged survival. Data showed that erlotinib in combination with WBRT had a tolerable toxicity profile and prolonged the LPFS, PFS, and OS of lung adenocarcinoma patients with multiple brain metastases compared with WBRT monotherapy.Keywords: WBRT, tyrosine kinase inhibitor, radiosensitizer, erlotinib

Xiao-Man Huang,&ast; Yan-Xiang Guo,&ast; Qiu-Ling Pang, Xiao-Yi Yan, Hui Yan, Jing-Yi Li, Gan-Ling Tang, Hui-Xian Jiang, Hong-Liang Zhang The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong-Liang Zhang, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email 277749097@qq.comPurpose: 2-Dodecyl-6-methoxy-2,5-diene-1,4-cyclohexanedione (DMDD), isolated from Averrhoa carambola L. root, has demonstrated the potential to reduce blood sugar levels. However, DMDD has poor solubility and bioavailability. This study aimed to formulate DMDD-loaded nanoparticles (DMDD-NPs) using chitosan crosslinked with sodium tripolyphosphate through the ionic crosslinking method and to investigate their effect on diabetic kidney disease (DKD) treatment by inhibiting the development of the epithelial-mesenchymal transition (EMT).Methods: DMDD-NPs were prepared by ionic crosslinking with sodium tripolyphosphate, optimizing six factors that affect nanoparticle characteristics, including particle size and zeta potential. Encapsulation efficiency (EE) and drug loading rate (DL) were optimized using a Box-Behnken design. The structure and characteristics of DMDD-NPs, including size, EE, DL, and release rates, were analyzed. Cytotoxicity was assessed using the Cell Counting Kit-8 (CCK-8) assay, while the migration capacity of HK-2 cells was evaluated through scratch-wound assays. The expression of EMT-related markers (E-cadherin, Vimentin, and TGF-β 1) was assessed by qRT-PCR.Results: The optimized formulation for DMDD-NPs was CS:TPP:DMDD = 10:3:3 (w), at pH 3.5, with 1.0 mg/mL of CS and stirring at 500 rpm for 30 min. In these conditions, the nanoparticles had a particle size of 320.37 ± 2.93 nm, an EE of 85.09 ± 1.43%, and a DL of 15.88 ± 0.51%. The DMDD-NPs exhibited a spherical shape, no leakage and minimal adhesion. The optimal freeze-drying protectant was a combination of 0.025% mannitol and 0.025% lactose. The drug release followed the Higuchi model. DMDD-NPs improved HK-2 cell proliferation at lower concentrations (< 24 μg/mL) and showed greater cell migration inhibition than DMDD. DMDD-NPs promoted E-cadherin expression and inhibited vimentin and TGF-β 1 expression, suggesting their potential role in preventing EMT for DKD treatment.Keywords: DMDD, drug delivery system, nanoparticles, epithelial-mesenchymal transformation, diabetic kidney disease

A cross-sectional study was conducted to investigate the health-related quality of life (HRQoL) of 2-5 years esophageal cancer survivors cured by definitive radiotherapy(dRT). The study was based on a cross-sectional survey of survivors of esophageal cancer undergoing dRT at 25 institutions across the country between July 2017 and July 2020. Patients who survived without disease progression were subject to our study. The investigation included European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and OES18, Malnutrition Universal Screening Tool (MUST), Distress Thermometer (DT) scales, and late toxicity grade ≥ 3 associated with dRT. A total of 11,573 patients with esophageal cancer received dRT from 25 institutions during July 2017 and July 2020, and 1,140 survivors were eligible with this investigation and the median time to completed dRT was 43.6 months. The results indicated that the global health status score of 1140 survivors was 80.4 ± 19.2, the functional scores were more than 85, and the appetite loss and dysphagia scored higher on the symptom scale. There were 7.5% of patients were low weight and 9.4% were at high risk for malnutrition. The proportion of high psychological distress were 4.1%, and 10.1% of the patients occurred late toxicity grade ≥ 3 related to radiotherapy, mainly esophageal toxicity and pulmonary toxicity. Multivariate analysis showed that MUST score ≥ 1 and DT score ≥ 4 were significantly associated with quality of life score < 80. Although the global HRQoL of esophageal cancer survivors are satisfactory within 2-5 years after dRT, appetite loss and dysphagia may persist in some survivors for a long time. Nutritional status and psychological distress, rather than late toxicity, were the important factors affecting HRQoL in the long time. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of individualized comprehensive early pulmonary rehabilitation in elderly patients requiring mechanical ventilation for severe community-acquired pneumonia (SCAP). Methods Totally 100 elderly patients requiring mechanical ventilation for SCAP were randomly divided into the control group and study group, with 50 cases in each group. Patients of the control group received routine comprehensive nursing during treatment, and those in the study group were given individualized comprehensive early pulmonary rehabilitation based on the routine care. The respiratory physiological indexes ( oxygenation index, lactic acid, rapid-shallow-breathing index), inflammation-related indicators, duration of ventilatory support, first-time success rate of ventilator extubation, length of ICU stay, incidence of complications of mechanical ventilation(pulmonary atelectasis and limb thrombus) were compared between two groups. Results The oxygenation index in the study group was higher than that in the control group(P＜0. 05). Patients in the study group had lower rapid-shallow-breathing index, lactic acid level, white blood cell count, procalcitonin level and C-reactive protein level compared with those in the control group(P＜0. 05). The first-time success rate of ventilator extubation in the study group was lower than that in the control group(P＜0. 05). Patients in the study group had a shorter duration of ventilatory support, shorter length of ICU stay and lower incidences of pulmonary atelectasis and limb thrombus compared with those in the control group(P＜0. 05). Conclusion The individualized comprehensive early pulmonary rehabilitation is effective to improve the pulmonary function of oxygenation, reduce the risk of complications of mechanical ventilation and improve the recovery of elderly patients requiring mechanical ventilation for SCAP. (目的 探索个性化早期综合肺康复护理在老年重症社区获得性肺炎(SCAP)行机械通气治疗患者中的应用效果。方法 选取医院收治100例老年重症社区获得性肺炎行机械通气患者为研究对象, 随机分为对照组50例和试验组50例。对照组实施常规综合护理干预, 试验组在对照组基础上实施个性化早期综合肺康复护理。比较两组干预后的呼吸生理指标(肺氧合功能、乳酸、浅快呼吸指数)、炎症相关指标、机械通气时间、首次脱机成功率、ICU治疗时间、机械通气并发症(肺不张发生率、肢体血栓发生率)。结果 干预后, 试验组氧合指数值高于对照组(P＜0. 05), 浅快呼吸指数、血清乳酸值、白细胞计数、降钙素原、C反应蛋白水平低于对照组(P＜0. 05)。试验组的首次脱机成功率高于对照组(P＜0. 05), 机械通气时间、ICU治疗时间、肺不张发生率、肢体血栓发生率及并发症总发生率低于对照组(P＜0. 05)。结论 个性化早期肺综合康复护理能够有效改善老年SCAP机械通气患者的肺氧合功能, 减轻炎症反应, 降低并发症发生率, 促进患者康复。)