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Jing Ning,1 Fang Wang,1 Shui-Qing Liu,2 Ru-Zhi Zhang,3 Dan-Min Liu,1 Yan Li1 1Department of Dermatology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Ultrasound in Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 3Department of Dermatology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 240000, People’s Republic of ChinaCorrespondence: Ru-Zhi Zhang, Email zhangruzhi628@163.comBackground: Hematoporphyrin monomethyl ether (HMME) is a promising photosensitizer for photodynamic therapy (PDT) and has found wide application in the treatment of port-wine stains (PWS).Objective: This study aims to observe and analyze the clinical efficacy and safety of HMME-PDT in the treatment of PWS patients. It also aims to evaluate the usefulness of color Doppler flow imaging (CDFI), an ultrasound technique for detecting blood flow in skin lesions, in assessing clinical efficacy.Methods: Thirty-three patients with PWS underwent HMME-PDT at our dermatology outpatient clinic between January 2019 and March 2020. Data on patient demographics, lesion location, lesion type (pink, purple, nodular thickening), treatment frequency, and pre- and post-treatment images were collected and retrospectively analyzed. CDFI was performed on three patients.Results: All patients received intravenous HMME and underwent irradiation with 532 nm green LED light. Of these, 5 patients received 1 session of HMME-PDT, 14 received 2 sessions, 9 received 3 sessions and the remaining 5 patients received more than 3 sessions. Of the 33 patients, 9 were cured (27.27%), 10 showed improvement (30.30%), 11 experienced a reduction in symptoms (33.33%), and 3 showed no significant improvement (9.09%). Most patients reported local pain and oedema, and no systemic adverse effects were observed. Clinical efficacy correlated with lesion type and total number of treatment sessions. CDFI appears to be an excellent technique for assessing clinical efficacy.Conclusion: HMME-PDT is a safe and effective method for the treatment of PWS. CDFI examination appears to be a promising assessment tool. However, further validation with larger sample sizes is warranted.Keywords: port-wine stains, hematoporphyrin monomethyl ether, photodynamic therapy, color Doppler flow imaging

Jie Hao,1– 3,* Yu Liu,1,* Fengli Guo,1,4 Guiming Fu,1,5 Junya Ning,2,3 Xianhui Ruan,1 Xiangqian Zheng,1 Ming Gao1– 3 1Department of Thyroid and Neck Tumor, 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, People’s Republic of China; 2Department of Breast and Thyroid Surgery, Tianjin Union Medical Center of Nankai University, Tianjin, People’s Republic of China; 3Tianjin Key Laboratory of General Surgery in Construction, Tianjin Union Medical Center Nankai University, Tianjin, People’s Republic of China; 4Department of Thyroid and Breast Surgery, Binzhou Medical University Hospital, Binzhou, People’s Republic of China; 5Thyroid-Otolaryngology Department, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangqian Zheng; Ming Gao, Email xzheng05@tmu.edu.cn; headandneck2008@126.comBackground: We planned to explore the underlying mechanism and clinical significance of lnc-SNHG5 and RPS3 in hepatocellular carcinoma in this current study.Methods: The expression of Lnc-SNHG5 and RPS3 in HCC tissues and several cell lines were affirmed, respectively, using UALCAN, TIMER, TCGA and RT-qPCR assay. Cell proliferation ability was detected by colony formation assay and CCK8 assay. Cell apoptosis was monitored by flow cytometry assay. Next, the RPS3 expression levels and the related proteins in NFκB pathway were examined using Western blot analysis. The role of lnc-SNHG5 and RPS3 in vivo was identified by subcutaneous tumor bearing experiment.Results: Lnc-SNHG5 was significantly increased in hepatocellular carcinoma tissues and in hepatocellular carcinoma cells. Further investigation showed that up-regulated lnc-SNHG5 promoted cell viability and cell proliferation ability of SMMC-7721 cells by regulating the cell apoptosis, while down-regulation of lnc-SNHG5 revealed opposite results in QGY-7703 cells. In terms of mechanism, we found that lnc-SNHG5 interacted with RPS3. Lnc-SNHG5 regulated the NFκB pathway through RPS3 in vitro and in vivo.Conclusion: This study suggested that lnc-SNHG5 expression was signally up-regulated in hepatocellular carcinoma, and lnc-SNHG5 promoted the malignant phenotypes in vitro and in vivo via directly regulating RPS3-NFκB pathway. Lnc-SNHG5 might be a target for molecular targeted therapy, a potential and novel diagnostic marker for HCC patients.Keywords: long non-coding RNA, SNHG5, RPS3, HCC, NFκB pathway

Peizhuang Zhao,* Jiajia Ning,* Jun Huang,* Binqian Wei, Zhen Wang, Xue Huang Department of Geriatrics and Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xue Huang, Department of Geriatrics and Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530000, People’s Republic of China, Email hb960305@163.comPurpose: Microrchidia 2 (MORC2) is a universally expressed molecule that has recently been identified as a chromatin modulator and elevated in many malignancies. However, its prognostic value and immunological role of MORC2 in colon adenocarcinoma (COAD) have never been illustrated.Methods: The clinical parameters and MORC2 expression datasets of COAD patients were obtained from The Cancer Genome Atlas (TCGA). Cancer and adjacent tissue specimens from surgically resected COAD patients were collected, and quantitative real-time PCR was used to detect MORC2 expression. Differentially expressed genes related to MORC2 were discovered and used for functional enrichment analysis. The diagnostic and prognostic values of MORC2 in COAD were conducted using receiver operating characteristics (ROC), Kaplan–Meier survival curve analysis, PrognoScan, Gene Expression Profiling Interactive Analysis (GEPIA) public databases and nomograms. Eventually, the association of MORC2 with tumor microenvironment was analyzed by using TIMER and GSVA package of R (v3.6.3).Results: MORC2 expression was upregulated in COAD tissues, and the RT-qPCR results further verified the reliability of our differential analysis at the transcriptional level. Additionally, higher expression of MORC2 was correlated to a poor prognosis for COAD patients. MORC2 was an independent prognostic factor for COAD and could be a diagnostic factor for early COAD. Furthermore, MORC2 expression was positively correlated with immune cells such as NK cells, TFH cells and so on.Conclusion: The findings demonstrated that overexpression of MORC2 was correlated with worse prognosis and immune infiltrates of COAD. MORC2 can serve as a reliable diagnostic and prognostic biomarker and a target of immunotherapy for COAD patients.Keywords: MORC2, colon adenocarcinoma, diagnosis, prognosis, immune cell infiltration, biomarker

Jinrong Ning,1,* Guodong Zheng,1,* Yi Cai,1,* Yunguang Hu,2,* Yiqi Liu,1 Enping Lai,1 Baizhong Chen,3 Yujie Liu,1 Ziqi Liang,1 Jijun Fu,1 Minyan Wei1 1Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China; 2Medical Department, Guangdong Yifang Pharmaceutical Co., Ltd, Foshan, Guangdong, 528200, People’s Republic of China; 3Guangdong Xinbaotang Biological Technology Co., Ltd, Jiangmen, Guangdong, 529000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Minyan Wei; Jijun Fu, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China, Tel +86-20-37103268, Email weiminyan@163.com; fujj@gzhmu.edu.cnPurpose: APAP-induced liver injury (AILI) is a common cause of acute liver failure (ALF). Nobiletin (NOB) is a potential hepatoprotective agent for the treatment of APAP-induced liver injury. However, the poor solubility and low bioavailability of NOB hinders its application. In this study, a novel self-assembly nano-drug delivery system of nobiletin (solid dispersion of NOB, termed as NOB/SD) was developed based on solid dispersion technology to improve the bioavailability and hepatoprotective ability of NOB for APAP-induced liver injury therapy.Methods: The optimized NOB/SD system was constructed using the amphiphilic copolymers of Soluplus and PVP/VA 64 via hot melt extrusion technology (HME). NOB/SD was characterized by solubility, physical interaction, drug release behavior, and stability. The bioavailability and hepatoprotective effects of NOB/SD were evaluated in vitro and in vivo.Results: NOB/SD maintained NOB in matrix carriers in a stable amorphous state, and self-assembled NOB-loaded nanomicelles in water. Nanostructures based on solid dispersion technology exhibited enhanced solubility, improved release behavior, and promoted cellular uptake and anti-apoptosis in vitro. NOB/SD displayed significantly improved bioavailability in healthy Sprague Dawley (SD) rats in vivo. Furthermore, NOB/SD alleviated the APAP-induced liver injury by improving anti-oxidative stress with reactive oxygen species (ROS) scavenging and nuclear factor erythroid 2-related factor 2 (Nrf2) activation.Conclusion: These results suggested that NOB/SD could be considered as a promising hepatoprotective nano-drug delivery system for attenuating APAP-induced acute liver injury with superior bioavailability and efficient hepatoprotection, which might provide an effective strategy for APAP-induced acute liver injury prevention and treatment.Graphical Abstract: Keywords: nobiletin, self-assembly micelles, solid dispersion technology, hot melt extrusion, acetaminophen-induced liver injury

Dan Yang, Jing Ning, Xiaomin Liao, Haixing Jiang, Shanyu Qin Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Shanyu Qin, Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, No. 6. Shuangyong Road, Nanning, Guangxi, 53000, People’s Republic of China, Tel +86 139 7711 0511, Email qinshanyu@gxmu.edu.cnPurpose: Endoscopic ultrasound-guided fine-needle injection (EUS-FNI) offers a promising minimally invasive approach for locally targeted management of advanced pancreatic cancer. However, the efficacy is limited due to the rapid plasma clearance of chemotherapeutic agents. Injectable hydrogels can form drug release depots, which provide a feasible solution for optimizing targeted chemotherapy through EUS-FNI.Methods: A drug delivery system was developed, consisting of gemcitabine (GEM) and thermo-sensitive hydrogel (PLGA-PEG-PLGA, PPP). The injectability, gel formation ability, biocompatibility and sustained drug delivery properties of PPP hydrogel were verified in vitro and in vivo. The effects of GEM/PPP hydrogel on cell proliferation, invasion, metastasis, and apoptosis were explored through co-culturing with PANC-1 cells. The therapeutic effects of GEM/PPP hydrogel on xenograft mice were compared with those of GEM, ethanol and polidocanol using the precisely targeted EUS-FNI technology. Tumor sections were examined by H&E, Ki-67, and TUNEL staining.Results: GEM/PPP hydrogel exhibited excellent injectability, biocompatibility, and the capability of sustained drug delivery for up to 7 days by forming a gel triggered by body temperature. It demonstrated the best therapeutic effects, significantly reducing proliferation, invasion and migration of PANC-1 cells while promoting apoptosis. After precise injection using EUS-FNI technology, GEM/PPP hydrogel resulted in a reduction of tumor weight by up to 75.96% and extending the survival period by 14.4 days with negligible adverse effects. Pathological examination revealed no systemic toxicity and significant apoptosis and minimal proliferation as well.Conclusion: The combination of GEM/PPP hydrogel and EUS-FNI technology provides an optimal approach of precise chemotherapy for pancreatic cancer, builds a bridge for clinical translation of basic research, and brings great hope for innovation of minimally invasive treatment modalities. The first-hand EUS image data obtained in this study also serves as a crucial reference for future clinical trials.Keywords: drug delivery systems, thermo-sensitive hydrogel, endoscopic ultrasound-guided fine needle injection, pancreatic cancer, translational medical research

Jun Huang,* Peizhuang Zhao,* Jialing Shi, Jiajia Ning, Zhen Wang, Yihua Luo, Jingqian Qin, Xue Huang Department of Geriatrics and Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xue Huang, Department of Geriatrics and Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530000, People’s Republic of China, Email hb960305@163.comPurpose: Prolyl 4-hydroxylase subunit alpha 3 (P4HA3) has been proven to participate in the occurrence and development of multiple cancers. However, the functional role of P4HA3 in the tumor immune microenvironment (TIME) of colon adenocarcinoma (COAD) and the prognosis of COAD patients has not been clarified. This study aimed to elucidate the immunological role and prognostic value of P4HA3 in COAD.Methods: P4HA3 expression in COAD tissues was analyzed via experiments and a bioinformatics algorithm. Based on the COAD patients in The Cancer Genome Atlas database, we comprehensively evaluated whether the expression levels of P4HA3 affected clinical prognosis, TIME, and immunotherapy of COAD using the R platforms and several public databases, including GEPIA, TIMER, TISIDB, and TCIA.Results: The results of the pan-cancer analysis indicated that P4HA3 expression was significantly different in most tumor tissues compared with normal tissues. P4HA3 was overexpressed in COAD tissues, and overexpression of P4HA3 was associated with a worse overall survival and a shorted progression-free interval in COAD patients. The expression of P4HA3 was positively correlated with pathological stage, T stage, N stage, perineural infiltration, and lymphatic infiltration. There were significant correlations of P4HA3 expression levels with immune cell infiltration and their makers, as well as immunomodulators, chemokines, and microsatellite status. Moreover, overexpression of P4HA3 was associated with a lower response rate to immunotherapy in the IMvigor210 cohort.Conclusion: Overexpression of P4HA3 is closely related to the poor prognosis of COAD patients, and P4HA3 is a potential target for immunotherapy in COAD patients.Keywords: P4HA3, colon adenocarcinoma, prognosis, immunotherapy, tumor immune microenvironment

Mengzhu Hou,1,* Nan Chen,2,* Lili Dong,3,* Yulian Fang,1 Rui Pan,2 Wei Wang,1 Lu Wang,1 Jing Ning,3 Hanquan Dong3 1Tianjin Pediatric Research Institute, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin, People’s Republic of China; 2Department of Clinical Lab, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin, People’s Republic of China; 3Department of Respiratory, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Ning; Hanquan Dong, Department of Respiratory, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), No. 238 Longyan Road, Beichen District, Tianjin, 300134, People’s Republic of China, Tel +86 13752230008 ; +86 13820476506, Email jingning2022@126.com; mifits@sina.comPurpose: The data on pediatrics with Multidrug-Resistant (MDR) Klebsiella pneumoniae infections are scarce. This study aims to investigate the molecular epidemiology of MDR Klebsiella pneumoniae, detect the mechanism of drug resistance, and determine the clinical risk factors for carbapenem-resistant Klebsiella pneumonia (CRKP) bloodstream infections (BSIs) in a children’s hospital.Methods: A total of 62 strains were collected from Tianjin Children’s Hospital. Carba NP and polymerase chain reactions (PCR) were performed to detect MDR mechanisms. Multilocus sequence typing (MLST) was used for analyzing strain homology. Clinical data were collected and logistic regression was used for BSI risk factors.Results: ST11 was the principal ST among the CRKP isolates clinically, accounting for 56.45% (35/62); there were also 57.14% (20/35) ST11 CRKP strains co-carrying blaNDM-5 and blaKPC-2, which were resistant to most of the tested antibiotics, being susceptible only to cotrimoxazole and tigecycline. The clinical data showed that 72.73% (40/55) of children with CRKP infection had serious underlying diseases; 20.00% (11/55) patients developed BSIs with the potential to cause multiple organ failure, shock and death. The logistic regression showed that the risk of BSIs caused by CRKP strain infections in children with hematological malignancies after chemotherapy was 7 times that of other children (95%Cl: 1.298– 45.415, P=0.025).Conclusion: ST11 was the prevalent clone in our hospital. The emergence of ST11 CRKP co-carrying blaNDM-5 and blaKPC-2 should be a cause for alarm as they were resistant to most of the tested antibiotics. CRKP strain infections are mainly occurring in young immunocompromised patients and the chemotherapy for hematological malignancies is an independent risk factor for BSIs.Keywords: carbapenem-resistantKlebsiella pneumonia, blaKPC-2, blaNDM-5, ST11, children, bloodstream infection

Ling Feng,1,2,* Tong Chen,3,* Xuan Wang,1 Chongxiang Xiong,1,4 Jianhui Chen,1 Shiquan Wu,3 Jing Ning,3 Hequn Zou1,3 1Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Nephrology, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 3Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 4Department of Nephrology, The First Dongguan Affiliated Hospital of Guangdong Medical University, Dongguan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hequn Zou, Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, 183, Zhongshan West Avenue, Tianhe District, Guangzhou, 510630, People’s Republic of China, Email Hequnzou@hotmail.comPurpose: Metabolic disorders are closely related to the occurrence and development of chronic kidney disease (CKD). We explored the prospective association between the Metabolic Score for Visceral Fat (METS-VF) and CKD in a 5-year follow-up study.Patients and Methods: In this cohort study, 631 adults not suffering from CKD from Wanzhai Town, in China in 2012 were included at baseline and followed up in 2017 and 2018. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between METS-VF and CKD risk. Area under the receiver operating characteristic curve (AUC) analyses were used to evaluate the ability of METS-VF, waist-to-height ratio (WhtR), visceral adiposity index (VAI), homeostatic model assessment of insulin resistance (HOMA-IR), body mass index (BMI) to predict CKD risk.Results: We identified 103 CKD cases during follow-up. After adjustment for confounding factors, comparing the lowest quartile of METS-VF, the OR (95% CI) of CKD risk in the highest quartile was 3.04 (1.39– 6.64). The per Standard deviation (SD) increase in METS-VF was positively correlated with CKD risk. The AUC of METS-VF for predicting CKD risk was, in general, higher than that for WhtR, VAI, HOMA-IR, and BMI.Conclusion: METS-VF may be an indicator for predicting CKD risk.Keywords: CKD, METS-VF, visceral obesity

Benhui Zhao,1,&ast; Xingtong Chen,1,&ast; Qian Chen,1,2 Gaoming Li,3 Zhe Chen,4 Ziheng Yang,1 Li Gu,1 Xudong Xiao,5 Zhen Wang,6 Jiaolin Ning,1 Bin Yi,1 Kaizhi Lu,1 Hongyan Zhang,7 Jianteng Gu1 1Department of Anesthesiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 2Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK; 3Department of Health Statistics, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 4Quality Management and Control Department, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 5Department of Anesthesiology, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 6Department of Anesthesiology; 7Hospital Office, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianteng Gu; Hongyan Zhang Email jiantenggu@hotmail.com; etengyan@163.comBackground: Blood pressure fluctuation is very common during non-cardiac surgery in elderly. This retrospective study was to analyse whether intraoperative hypotension in elderly and other risk factors relate to the postoperative mortality.Methods: A total of 118 cases (Observational group), who underwent noncardiac surgery in three medical centers between September 2014 and March 2017, and died in the hospital after the noncardiac surgery. With 1:2 ratio of propensity matching, 236 survival cases (Control group) were selected for comparison analyses with the death cases. Intraoperative blood pressure and perioperative parameters from both groups were collected from electronic anaesthesia charts. Data were analysed with univariate logistic regression analysis where variables with p values less than 0.05 were analysed with multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was constructed.Results: There are five risk factors related to postoperative death in elderly patients: ASA grade, COPD, emergency surgery, general anesthesia, 60 < MAP ≤ 65mmHg (OR > 1), and one factor may reduce the risk of postoperative mortality, which is PACU therapy (OR < 1). Compared with the Control group, the Observational group had a higher proportion of cerebral hernia, kidney injury and trauma (p < 0.001). The intraoperative blood transfusion volume and intraoperative blood loss volume were higher in the Observational group than the Control group (p < 0.001). The proportion of using vasoactive drugs was higher in the Observational group (p < 0.001), and there was more urine output during the operation in the Observational group (p = 0.005).Conclusion: The intraoperative MAP of geriatric patients lower than 65mmHg is highly related to the postoperative mortality. Elderly patients with emergency surgery, high ASA grade and a history of COPD have an increased risk of postoperative mortality. General anesthesia is a risk factor for postoperative death in elderly patients, and the PACU therapy is a protective factor to avoid postoperative death.Trial Registration: This study has been retrospectively registered in the Chinese Clinical Trials Registry (ChiCTR2000038912, 10/10/2020).Keywords: intraoperative hypotension, geriatric patients, COPD, postoperative mortality, non-cardiac surgery

Abstract Background To evaluate the dosimetric and biological benefits of the fixed-jaw (FJ) intensity-modulated radiation therapy (IMRT) technique for patients with T-shaped esophageal cancer. Methods FJ IMRT plans were generated for thirty-five patients and compared with jaw tracking (JT) IMRT, static jaw (SJ) IMRT and JT volumetric modulated arc therapy (VMAT). Dosimetric parameters, tumor control probability (TCP) and normal tissue complication probability (NTCP), monitor units (MUs), delivery time and gamma passing rate, as a measure of dosimetric verification, were compared. The correlation between the length of PTV-C below the upper boundary of lung tissue (PTV-Cinferior) and dosimetric parameters and NTCP of the lung tissue were analyzed. Results The homogeneity and conformity of the target in the four plans were basically equivalent. When compared to the JT IMRT and SJ IMRT plans, FJ IMRT plan led to a statistically significant improvement in the NTCP and low-middle dosimetric parameters of the lung, and the improvement had a moderately positive correlation with the length of PTV-Cinferior, with a correlation coefficient ranging from 0.523 to 0.797; the FJ IMRT plan exhibited better lung sparing in low-dose volumes than the JT VMAT plan. The FJ IMRT plan had similar MUs (888 ± 99) and delivery times (516.1 ± 54.7 s) as the JT IMRT plan (937 ± 194, 522 ± 5.6 s) but higher than SJ IMRT (713 ± 137, 488.8 ± 45.2 s) and JT VMAT plan (517 ± 59, 263.7 ± 43.3 s). Conclusions The FJ IMRT technique is superior in reducing the low-dose volumes of lung tissues for patients with T-shaped esophageal cancer.

(1) Background: An increasing amount of research has supported the role of radiomics for predicting pathological complete response (pCR) to neoadjuvant chemoradiation treatment (nCRT) in order to provide better management of locally advanced rectal cancer (LARC) patients. However, the lack of validation from prospective trials has hindered the clinical adoption of such studies. The purpose of this study is to validate a radiomics model for pCR assessment in a prospective trial to provide informative insight into radiomics validation. (2) Methods: This study involved a retrospective cohort of 147 consecutive patients for the development/validation of a radiomics model, and a prospective cohort of 77 patients from two institutions to test its generalization. The model was constructed using T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI to understand the associations with pCR. The consistency of physicians’ evaluations and agreement on pathological complete response prediction were also evaluated, with and without the aid of the radiomics model. (3) Results: The radiomics model outperformed both physicians’ visual assessments in the prospective test cohort, with an area under the curve (AUC) of 0.84 (95% confidence interval of 0.70–0.94). With the aid of the radiomics model, a junior physician could achieve comparable performance as a senior oncologist. (4) Conclusion: We have built and validated a radiomics model with pretreatment MRI for pCR prediction of LARC patients undergoing nCRT.

Luna Liu,1,2 Shuang Liu,1,2 Qianmei Song,1,2 Dandan Luo,1,2 Yu Su,1,2 Xiangyu Qi,1,2 Qian Wang,3 Jing Ning,1,2 Youyuan Lv,1,2 Qingbo Guan1,2,4 1Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, People’s Republic of China; 2Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong 250021, People’s Republic of China; 3Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, People’s Republic of China; 4Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, People’s Republic of ChinaCorrespondence: Qingbo Guan Tel +86-531-68776375Fax +86-531-87068707Email doctorguanqingbo@163.comObjective: Obesity and metabolic syndrome have been reported to exert an impact on the male reproductive system with decreasing levels of serum total testosterone (TT); however, the effect of different metabolic obesity phenotypes on testosterone has been poorly studied. We aimed to evaluate the association of metabolic obesity phenotypes and total testosterone levels in a Chinese male population.Methods: We performed a retrospective study based on an epidemiological investigation, a total of 4,081 male individuals aged from 40– 75 years old were recruited. The population was classified as metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO) according to normal weight (BMI< 25.0) and overweight/obesity (BMI≥ 25.0) with or without metabolic syndrome.Results: We collected 563 hypotestosteronemia among 4,081 male individuals. The odds ratios (ORs) (95% CIs) of hypotestosteronemia in obesity and metabolic syndrome were 3.072 (2.414– 3.911) and 3.294 (2.631– 4.125), respectively, after adjusting for age, luteinizing hormone, smoking status, and alcohol consumption. Compared to the MHNW group, male subjects in MHO, MUNW, and MUO groups had decreased serum TT levels. Additionally, the MUO group had a lowest concentration of serum TT and a highest proportion of hypotestosteronemia. There was no significant difference of TT levels between the MHO and MUNW groups.Conclusion: Obesity and metabolic syndrome are independent risk factors of hypotestosteronemia in Chinese male populations. Our study also suggested that individuals with MHO, MUNW, and MUO have a higher risk of developing hypotestosteronemia.Keywords: metabolic obesity phenotypes, testosterone, metabolically healthy overweight/obese, metabolically unhealthy normal weight, hypotestosteronemia

Ling Feng,* Haishan Chen,* Jianhui Chen, Chongxiang Xiong, Xiaofei Shao, Xin Wang, Jing Ning, Zhicong Xiang, Xuan Wang, Tong Chen, Hua Xiao, Hongjuan Tang, Xiaolin Li, Guobao Hong, Hequn Zou Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, People’s Republic of China*These authors contributed equally to this work.Correspondence: Hequn Zou; Xiaofei ShaoDepartment of Nephrology, The Third Affiliated Hospital, Southern Medical University, 183, Zhongshan West Avenue, Tianhe District, Guangzhou 510630, People’s Republic of ChinaEmail Hequnzou@hotmail.com; 413151187@qq.comObjective: To explore whether the red blood cell count multiplied by hematocrit index (RBCHct) in blood routine parameters can indicate the risk of impaired fasting blood glucose (IFG), and whether it is related to insulin resistance and inflammation.Methods: In this cross-sectional study, previous history of diabetes was excluded, and people with normal and impaired IFG were included. We use Spearman analysis to evaluate the correlation between RBCHct index and fasting plasma glucose, insulin resistance homeostasis model assessment (HOMA-IR), and hypersensitive C-reactive protein (hs-CRP). Binary logistic regression analysis was used to evaluate the RBCHct index for assessing the potential risk of IFG, and the receiver operating characteristic (ROC) curve was used to evaluate the RBCHct index for diagnosing insulin resistance and chronic low-grade inflammatory efficacy among those with IFG.Results: Correlation analysis showed that the RBCHct index and fasting plasma glucose (r=0.088, P=0.003); HOMA-IR (r=0.199, P< 0.001); and hs-CRP (r=0.097, P=0.001) were positively correlated. After adjusting for confounding factors, the risk of IFG in the third and fourth quartiles of the RBCHct index increased to 1.889 and 3.048 times. The area under the ROC curve of the RBCHct index for diagnosis of insulin resistance state (HOMA-IR) was 0.695 (p< 0.001), and the area under the ROC curve of the RBCHct index for the diagnosis of chronic low-inflammatory state (hs-CRP) was 0.641 (P=0.010).Conclusion: The RBCHct index may be a potential indicator for assessing the risk of prediabetes and is closely related to whether the body is in a state of insulin resistance and inflammation under IFG.Keywords: diabetes mellitus, erythrocyte, RBCHct index, insulin resistance, inflammation

Zhixiao Yao,1,* Juehong Li,1,* Xu Wang,1 Shiqiao Peng,2 Jiexin Ning,3 Yun Qian,1 Cunyi Fan1 1Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, People’s Republic of China; 2Department of Endocrinology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, People’s Republic of China; 3Department of Plastics, Binzhou People’s Hospital, Binzhou 256610, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun Qian; Cunyi FanDepartment of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, People’s Republic of ChinaTel +86 21-64369181Email lollipopcloudland@foxmail.com; cyfan@sjtu.edu.cnPurpose: As a common complication of tendon injury, tendon adhesion is an unresolved problem in clinical work. The aim of this study was to investigate whether human umbilical cord mesenchymal stem cell-derived exosomes (HUMSC-Exos), one of the most promising new-generation cell-free therapeutic agents, can improve tendon adhesion and explore potential-related mechanisms.Methods: The rat Achilles tendon injury adhesion model was constructed in vivo, and the localization of HUMSC-Exos was used to evaluate the tendon adhesion. Rat fibroblast cell lines were treated with transforming growth factor β 1 (TGF-β 1) and/or HUMSC-Exos in vitro, and cell proliferation, apoptosis and gene expression were measured. MicroRNA (miRNA) sequencing and quantitative PCR (qPCR) analysis confirmed differential miRNAs. A specific miRNA antagonist (antagomir-21a-5p) was used to transform HUMSC-Exos and obtain modified exosomes to verify its efficacy and related mechanism of action.Results: In this study, we found HUMSC-Exos reduced rat fibroblast proliferation and inhibited the expression of fibrosis genes: collagen III (COL III) and α-smooth muscle actin (α-SMA) in vitro. In the rat tendon adhesion model, topical application of HUMSC-Exos contributed to relief of tendon adhesion. Specifically, the fibrosis and inflammation-related genes were simultaneously inhibited by HUMSC-Exos. Further, miRNA sequencing of HUMSCs and HUMSC-Exos showed that miR-21a-3p was expressed at low abundance in HUMSC-Exos. The antagonist targeting miR-21a-3p was recruited for treatment of HUMSCs, and harvested HUMSC-Exos, which expressed low levels of miR-21a-3p, and expanded the inhibition of tendon adhesion in subsequent in vitro experiments.Conclusion: Our results indicate that HUMSC-Exos may manipulate p65 activity by delivering low-abundance miR-21a-3p, ultimately inhibiting tendon adhesion. The findings may be promising for dealing with tendon adhesion.Keywords: HUMSC, exosome, tendon adhesion, TGF-β 1, p65, miR-21a-3p, NF-κB

Jing Ning, Zhicong Xiang, Chongxiang Xiong, Qin Zhou, Xin Wang, Hequn Zou Department of Nephropathy, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, People’s Republic of ChinaCorrespondence: Hequn ZouDepartment of Nephropathy, The Third Affiliated Hospital of Southern Medical University, 183 Zhongshan West Avenue, Tianhe District, Guangzhou 510630, People’s Republic of ChinaTel +86 20 6278 4391Email hequnzou@hotmail.comPurpose: Diabetic kidney disease (DKD), which is related to inflammation and immune response, is the primary vascular complication of diabetes mellitus and also the leading etiology of end-stage renal disease. Urinary extracellular vesicles (UEVs) are an attractive source for biomarker detection as they involve molecular constituents derived from their parental sections of the nephron. In this study, we aimed to search for a potential biomarker in UEVs for the early diagnosis and prediction of DKD, especially before the emergence of microalbuminuria.Patients and Methods: UEVs were isolated from the urine of healthy subjects, pre-diabetic, and diabetic patients with varying degrees of kidney damage by ultracentrifugation, and the extracted UEVs were used to measure alpha1-antitrypsin (α 1-AT) by Western blot. To explore the function of α 1-AT in the inflammatory process leading to DKD, we silenced the expression of α 1-AT in renal tubular epithelial cells using cell transfection techniques to assess the differential expression of the inflammatory factors such as MCP-1 and TNF-α using qRT-PCR.Results: There was no expression of α 1-AT in the UEVs of either healthy or pre-diabetic subjects. Its expression was significantly increased in the UEVs of diabetic patients with normoalbuminuria (prior to microalbuminuria), which was more sensitive and more stable than other renal indexes to predict DKD. Additionally, the expression of α 1-AT in UEVs was gradually upregulated with the aggravation of DKD and the decline of renal function. In vitro, the mRNA expression of MCP-1 and TNF-α was significantly decreased when the generation of α 1-AT in tubular epithelial cells was inhibited under high glucose stimulation.Conclusion: Our results suggest that α 1-AT derived from UEVs, especially in diabetic patients with normoalbuminuria, might serve as a potential noninvasive biomarker for diagnosis of DKD early in the development of the disease and may predict the future decline of renal function.Keywords: diabetic kidney disease, urinary extracellular vesicles, biomarker, alpha1-antitrypsin, inflammation, tubular epithelial cell

Xin Wang,* Haishan Chen,* Xiaofei Shao, Chongxiang Xiong, Guobao Hong, Jianhui Chen, Xiaolin Li, Xu You, Peichun Gao, Yunying Chen, Ziliang Zou, Jing Ning, Hua Xiao, Hequn Zou, Lixin Wei Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hequn ZouDepartment of Nephrology, The Third Affiliated Hospital, Southern Medical University, 183, Zhongshan West Avenue, Tianhe District, Guangzhou 510630, People’s Republic of ChinaEmail Hequnzou@hotmail.comLixin WeiDepartment of Nephrology, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian 350001, People’s Republic of ChinaEmail lixinwei66@126.comObjective: To investigate which plasma lipid parameters are useful for detecting chronic kidney disease (CKD) in a Chinese population without known CKD or renal impairment.Methods: This was a prospective study. In southern Chinese cities from 2012 to 2013, a total of 1037 subjects aged ≥ 18 years old received a survey. Logistic regression and multiple linear regression analyses were performed. The lipid parameters studied included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (nHDL-C), TG/HDL-C ratio, TC/HDL-C ratio and nHDL-C/HDL-C ratio.Results: After adjusting for confounding factors, the fourth percentile of logTG/HDL-C was observed to be an independent risk factor for CKD (OR = 2.453, P < 0.001), and the highest quantile of the logTG/HDL-C ratio was associated with a higher prevalence of CKD (P < 0.05). This risk was reduced when the model was adjusted with Insulin resistance (IR) (OR = 2.034, P < 0.05). In the group of women, glucose metabolism disorders, high uric acid, and obesity, this risk was increased. Multiple regression models showed that log TG and nonHDL-C/HDL-C were negatively correlated with eGFR (P < 0.05), while log TG and TC were positively correlated with logACR (P < 0.05). The area under the curve (ROC) of lgTG/HDL was 0.623 (p < 0.001).Conclusion: The serum logTG/HDL-C ratio is the only suitable predictor of CKD, and IR may be the mechanism. This risk needs to be controlled in a specific population. Log TG and nonHDL-C/HDL-C were negatively correlated with eGFR, while log TG and TC were positively correlated with logACR.Keywords: lipid, chronic kidney disease, CKD, urinary albumin to creatinine ratio, ACR, estimated glomerular filtration rate, eGFR

Hua Xiao,* Chongxiang Xiong,* Xiaofei Shao,* Peichun Gao, Haishan Chen, Jing Ning, Yunying Chen, Ziliang Zou, Guobao Hong, Xiaolin Li, Xu You, Jieli Sheng, Fan Wu, Xin Wang, Hequn Zou Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, People’s Republic of China *These authors contributed equally to this workCorrespondence: Hequn ZouDepartment of Nephrology, The Third Affiliated Hospital, Southern Medical University, 183, Zhongshan West Avenue, Tianhe District, Guangzhou 510630, People’s Republic of ChinaTel +86 20 6278 4391Email hequnzou@hotmail.comPurpose: To investigate the correlation between visceral obesity and pathogenesis of chronic kidney disease (CKD) among non-diabetic individuals, and to evaluate the potential of visceral adiposity index (VAI) as a predictor of CKD.Patients and Methods: From December 2017 to March 2018, 1877 non-diabetic participants (male n=699, female n=1208) in southern China were recruited for a cross-sectional survey. Males and females were divided into four groups according to gender-specific quartiles of VAI scores. A logistic regression model was established to analyze the correlation between visceral adiposity index and CKD.Results: Visceral adiposity index was positively correlated with CKD and was negatively associated with estimated glomerular filtration rate (eGFR). Using group one as the control, odds ratios (ORs) were calculated to determine the risk of developing CKD as VAI increased (male: group four 2.73 [P< 0.005]; female: Group three 1.76 [P< 0.05], Group four 2.88 [P< 0.005]). When related factors such as history of hypertension, smoking, alcohol use, and physical inactivity were normalized in the logistic model before calculation, ORs became 2.73 (male: P< 0.05), and 2.18 (female: P< 0.05), respectively. The results differed after normalizing further for systolic blood pressure (SBP), diastolic blood pressure (DBP), hypersensitive c-reactive protein (hsCRP), interleukin-6 (IL-6), homocysteine (Hcy), superoxide dismutase (SOD), and retinol-binding protein (RBP). There were no significant differences in ORs among the female groups.Conclusion: Visceral adiposity index was significantly associated with CKD in non-diabetic individuals. It may be a good predictor of the pathogenesis of CKD and was dependent on hsCRP, IL-6, Hcy, SOD, RBP, and blood pressure levels in females and males with VAI scores of 1.41 and higher. Visceral adiposity index may be used to predict CKD in males with VAI less than 0.983.Keywords: visceral adiposity index, chronic kidney disease, non-diabetic population

Guo-bao Hong,1,2 Pei-chun Gao,1,3 Yun-yin Chen,1 Yue Xia,1 Xiao-su Ke,1 Xiao-fei Shao,1 Chong-xiang Xiong,1 Hai-shan Chen,1 Hua Xiao,1 Jing Ning,1 He-qun Zou1 1Department of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, People’s Republic of China; 2Department of Nephrology, The Affiliated Nanhai Hospital of Southern Medical University, Foshan 528200, People’s Republic of China; 3School of Public Health, Southern Medical University, Guangzhou, Guangdong 510630, People’s Republic of ChinaCorrespondence: He-qun ZouDepartment of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, People’s Republic of ChinaTel +86-20-6278-4391Email hequnzou@hotmail.comPurpose: Metabolic syndrome (MetS), characterized by a constellation of insulin resistance, central obesity, hypertension, and hyperlipidemia, is a global health threat. High-sensitivity C-reactive protein (hs-CRP) has been shown to be associated with type 2 diabetes and cardiovascular disease; however, its association with incident MetS is less known. Therefore, the aim of this study was to examine the prospective association between hs-CRP and MetS among a Chinese population in a 5-year follow-up study.Patients and Methods: The levels of hs-CRP were measured using serum samples collected at baseline recruitment in 2012 from 886 participants without MetS. Follow-up interviews were conducted in 2018, and MetS was diagnosed by 2017 criteria from the Chinese Diabetes Society. Multivariate logistic regression models were used to assess the overall and sex-specific associations between hs-CRP and incident MetS. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were computed with adjustment for demographic, socioeconomic, clinical, and lifestyle factors.Results: After a mean follow-up duration of 5.40 ± 0.56 years, 116 (13.3%) participants developed MetS. In the total study population, increased hs-CRP levels were associated with a higher risk of MetS (OR comparing extreme quartiles of hs-CRP: 4.06 [95% CI: 1.91– 8.65]) in the fully-adjusted model. When stratified by sex, the positive association was only observed in women (OR: 4.82 [1.89– 12.3]) but not in men (OR: 3.15 [0.82– 12.1]; P-interaction = 0.039).Conclusion: In this study of a Chinese population, a positive association between hs-CRP and incident MetS was found only in women and not in men. Sex-specific prediction and intervention of MetS using hs-CRP as a target should be further evaluated.Keywords: inflammation, high-sensitivity C-reactive protein, metabolic syndrome, cohort study, follow up

ObjectivesThe beam output of a double scattering proton system varies for each combination of beam option, range, and modulation and therefore is difficult to be accurately modeled by the treatment planning system (TPS). This study aims to design an empirical method using the analytical and machine learning (ML) models to estimate proton output in a double scattering proton system.Materials and MethodsThree analytical models using polynomial, linear, and logarithm–polynomial equations were generated on a training dataset consisting of 1,544 clinical measurements to estimate proton output for each option. Meanwhile, three ML models using Gaussian process regression (GPR) with exponential kernel, squared exponential kernel, and rational quadratic kernel were also created for all options combined. The accuracy of each model was validated against 241 additional clinical measurements as the testing dataset. Two most robust models were selected, and the minimum number of samples needed for either model to achieve sufficient accuracy ( ± 3%) was determined by evaluating the mean average percentage error (MAPE) with increasing sample number. The differences between the estimated outputs using the two models were also compared for 1,000 proton beams with a randomly generated range, and modulation for each option.ResultsThe polynomial model and the ML GPR model with exponential kernel yielded the most accurate estimations with less than 3% deviation from the measured outputs. At least 20 samples of each option were needed to build the polynomial model with less than 1% MAPE, whereas at least a total of 400 samples were needed for all beam options to build the ML GPR model with exponential kernel to achieve comparable accuracy. The two independent models agreed with less than 2% deviation using the testing dataset.ConclusionThe polynomial model and the ML GPR model with exponential kernel were built for proton output estimation with less than 3% deviations from the measurements. They can be used as an independent output prediction tool for a double scattering proton beam and a secondary output check tool for a cross check between themselves.

Abstract Purpose To develop a novel approach to accurately verify patient set up in proton radiotherapy, especially for the verification of the nozzle – body surface air gap and source-to-skin distance (SSD), the consistency and accuracy of which is extremely important in proton treatment. Methods Patient body surfaces can be captured and monitored with the optical surface imaging system during radiation treatment for improved intrafraction accuracy. An in-house software package was developed to reconstruct the patient body surface in the treatment position from the optical surface imaging reference capture and to calculate the corresponding nozzle – body surface air gap and SSD. To validate this method, a mannequin was scanned on a CT simulator and proton plans were generated for a Mevion S250 Proton machine with 20 gantry/couch angle combinations, as well as two different snout sizes, in the Varian Eclipse Treatment Planning Systems (TPS). The surface generated in the TPS from the CT scan was imported into the optical imaging system as an RT Structure for the purpose of validating and establishing a benchmark for ground truth comparison. The optical imaging surface reference capture was acquired at the treatment setup position after orthogonal kV imaging to confirm the positioning. The air gaps and SSDs calculated with the developed method from the surface captured at the treatment setup position (VRT surface) and the CT based surface imported from the TPS were compared to those calculated in TPS. The same approach was also applied to 14 clinical treatment fields for 10 patients to further validate the methodology. Results The air gaps and SSDs calculated from our program agreed well with the corresponding values derived from the TPS. For the phantom results, using the CT surface, the absolute differences in the air gap were 0.45 mm ± 0.33 mm for the small snout, and 0.51 mm ± 0.49 mm for the large snout, and the absolute differences in SSD were 0.68 mm ± 0.42 mm regardless of snout size. Using the VRT surface, the absolute differences in air gap were 1.17 mm ± 1.17 mm and 2.1 mm ± 3.09 mm for the small and large snouts, respectively, and the absolute differences in SSD were 0.81 mm ± 0.45 mm. Similarly, for patient data, using the CT surface, the absolute differences in air gap were 0.42 mm ± 0.49 mm, and the absolute differences in SSD were 1.92 mm ± 1.4 mm. Using the VRT surface, the absolute differences in the air gap were 2.35 mm ± 2.3 mm, and the absolute differences in SSD were 2.7 mm ± 2.17 mm. Conclusion These results showed the feasibility and robustness of using an optical surface imaging approach to conveniently determine the air gap and SSD in proton treatment, providing an accurate and efficient way to confirm the target depth at treatment.

Lung cancer treatment is constantly evolving due to technological advances in the delivery of radiation therapy. Adaptive radiation therapy (ART) allows for modification of a treatment plan with the goal of improving the dose distribution to the patient due to anatomic or physiologic deviations from the initial simulation. The implementation of ART for lung cancer is widely varied with limited consensus on who to adapt, when to adapt, how to adapt, and what the actual benefits of adaptation are. ART for lung cancer presents significant challenges due to the nature of the moving target, tumor shrinkage, and complex dose accumulation because of plan adaptation. This article presents an overview of the current state of the field in ART for lung cancer, specifically, probing topics of: patient selection for the greatest benefit from adaptation, models which predict who and when to adapt plans, best timing for plan adaptation, optimized workflows for implementing ART including alternatives to re-simulation, the best radiation techniques for ART including magnetic resonance guided treatment, algorithms and quality assurance, and challenges and techniques for dose reconstruction. To date, the clinical workflow burden of ART is one of the major reasons limiting its widespread acceptance. However, the growing body of evidence demonstrates overwhelming support for reduced toxicity while improving tumor dose coverage by adapting plans mid-treatment, but this is offset by the limited knowledge about tumor control. Progress made in predictive modeling of on-treatment tumor shrinkage and toxicity, optimizing the timing of adaptation of the plan during the course of treatment, creating optimal workflows to minimize staffing burden, and utilizing deformable image registration represent ways the field is moving toward a more uniform implementation of ART.

Haishan Chen,* Chongxiang Xiong, Xiaofei Shao,* Jing Ning, Peichun Gao, Hua Xiao, Yunying Chen, Ziliang Zou, Guobao Hong, Xiaolin Li, Mengjiao Shao, Jieli Sheng, Xingyan Yang, Xu You, Hequn Zou Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hequn ZouDepartment of Nephrology, The Third Affiliated Hospital, Southern Medical University, 183 Zhongshan West Avenue, Tianhe District, Guangzhou 510630, People’s Republic of ChinaEmail Hequnzou@hotmail.comPurpose: Metabolic syndrome (MetS), which is a global public health problem, is a state of chronic low-grade inflammation. This study looked at the changes in hematological parameters and the predictive value of the lymphocyte to high-density lipoprotein cholesterol (HDL-C) ratio (LHR) as a new index in subjects with and without MetS in coastal cities in southern China.Patients and methods: In this cross-sectional study, there were 852 participants (n = 598 with MetS and n = 254 without MetS). MetS was defined in accordance with the National Cholesterol Education Program, Adult Treatment Panel III (NCEP-ATP III) criteria.Results: MetS was positively correlated with white blood cell count, total lymphocyte count, neutrophil count, red blood cell count, hematocrit, hemoglobin, and high-sensitivity C-reactive protein levels (p

Abstract Background To investigate the setup uncertainties and to establish an optimal imaging schedule for the prone-positioned whole breast radiotherapy. Methods Twenty prone-positioned breast patients treated with tangential fields from 2015 to 2017 were retrospectively enrolled in this study. The prescription dose for the whole breast treatment was 266 cGy × 16 for all of the patients and the treatments were delivered with the SSD setup technique. At every fraction of treatment, patient was firstly set up based on the body localization tattoos. MV portal imaging was then taken to confirm the setup; if discrepancy (> 3 mm) was found between the portal images and corresponding plan images, the patient positioning was adjusted accordingly with couch movement. Based on the information acquired from the daily tattoo and portal imaging setup, three sets of data, named as weekly imaging guidance (WIG), no daily imaging guidance (NIG), and initial 3 days then weekly imaging guidance (3 + WIG) were sampled, constructed, and analyzed in reference to the benchmark of the daily imaging guidance (DIG). We compared the setup uncertainties, target coverage (D95, Dmax), V5 of the ipsilateral lung, the mean dose of heart, the mean and max dose of the left-anterior-descending coronary artery (LAD) among the 4 imaging guidance (IG) schedules. Results Relative to the daily imaging guidance (IG) benchmark, the NIG schedule led to the largest residual setup uncertainties; the uncertainties were similar for the WIG and 3 + WIG schedules. Little variations were observed for D95 of the target among NIG, DIG and WIG. The target Dmax also exhibited little changes among all the IG schedules. While V5 of the ipsilateral lung changed very little among all 4 schedules, the percent change of the mean heart dose was more pronounced; but its absolute values were still within the tolerance. However, for the left-sided breast patients, the LAD dose could be significantly impacted by the imaging schedules and could potentially exceed its tolerance criteria in some patients if NIG, WIG and 3 + WIG schedules were used. Conclusions For left-side whole breast treatment in the prone position using the SSD treatment technique, the daily imaging guidance can ensure dosimetric coverage of the target as well as preventing critical organs, especially LAD, from receiving unacceptable levels of dose. For right-sided whole breast treatment in the prone position, the weekly imaging setup guidance appears to be the optimal choice.

Background: The world faced crises of prevention and control and shortage of medical resources during the COVID-19 (Corona Virus Disease 2019) outbreak. The establishment of temporary integrated isolation wards in hospitals, which is universal and representative in China, is one of the most-effective strategies in solving these problems according to China's experiences.Aim: To conduct a preliminary study on the establishment of a temporary integrated isolation ward during the outbreak of COVID-19 and to evaluate related impact.Methods: SWOT analysis was used to analyze the advantages, disadvantages, opportunities, and risks in the establishment of the temporary integrated isolation ward, and corresponding corrective measures were made according to the analysis results.Findings: The ward has formulated more than 10 related work procedures and prevention and control measures. A total of 93 patients with 18 critically ill patients were admitted for treatment and isolation. They were all evaluated based on established procedures and protocols. Twenty-four supplementary nucleic acid tests were ordered and conducted. One new patient with COVID-19 was confirmed and was successfully transferred to the designated COVID-19 infectious control hospital. There were no missed diagnosis or misdiagnosis, no cross-infection of patients, no cluster outbreak, and no infection of medical workers during the entire process.Conclusion: SWOT analysis is helpful in guiding the establishment of a temporary integrated isolation ward and the formulation of prevention and control measures in Hebei General Hospital during the COVID-19 outbreak. It provides the guidance and reference of significance for the establishment of similar types of wards in the future.

Purpose: This study aimed to evaluate whether the coronavirus disease of 2019 (COVID-19) pandemic resulted in treatment delays in patients scheduled for or undergoing brachytherapy. Methods and Materials: A retrospective cohort study was conducted across 4 affiliated sites after local institutional review board approval. The eligibility criteria were defined as all patients with cancer whose treatment plan included brachytherapy during the COVID-19 pandemic from February 24, 2020 to June 30, 2020. Treatment delays, cancellations, alterations of fractionation regimens, and treatment paradigm changes were evaluated. Results: A total of 47 patients were eligible for the analysis. Median patient age at the time of treatment was 62 years (interquartile range, 56-70 years). Endometrial, cervical, and prostate cancers were the most common sites included in this analysis. Three patients (6.4%) with cervical cancer were diagnosed with COVID-19 during the course of their treatment. Interruptions of external beam radiation therapy (EBRT), cancellations of EBRT, cancellations of brachytherapy, and treatment delays due to COVID occurred in 5 (10.6%), 3 (6.4%), 8 (17%), and 9 (19%) patients, respectively. The mean and median number of days delayed for patients who experienced treatment interruptions were 16.3 days (standard deviation: 13.9 days) and 14 days (interquartile range, 5.75-23.75 days), respectively. For patients with cervical cancer, the mean and median overall treatment times defined as the time from the start of EBRT to the end of brachytherapy were 56 and 49 days, respectively. Conclusions: Despite the challenges the health care system faced during the pandemic, most patients with cancer were safely treated with minor treatment delays and interruptions. Long-term follow up is needed to assess the impact of COVID-19 and treatment interruptions on oncologic outcomes.

Background and purpose: Although patients with esophageal squamous cell carcinoma (ESCC) can achieve a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) followed by surgery, one-third of these patients with a pCR may still experience recurrence. The aim of this study is to develop and validate a predictive model to estimate recurrence-free survival (RFS) in those patients who achieved pCR.Materials and methods: Two hundred six patients with ESCC were enrolled and divided into a training cohort (n = 146) and a validation cohort (n = 60). Radiomic features were extracted from contrast-enhanced computed tomography (CT) images of each patient. Feature reduction was then implemented in two steps, including a multiple segmentation test and least absolute shrinkage and selection operator (LASSO) Cox proportional hazards regression method. A radiomics signature was subsequently constructed and evaluated. For better prediction performance, a clinical nomogram based on clinical risk factors and a nomogram incorporating the radiomics signature and clinical risk factors was built. Finally, the prediction models were further validated by calibration and the clinical usefulness was examined in the validation cohort to determine the optimal prediction model.Results: The radiomics signature was constructed using eight radiomic features and displayed a significant correlation with RFS. The nomogram incorporating the radiomics signature with clinical risk factors achieved optimal performance compared with the radiomics signature (P < 0.001) and clinical nomogram (P < 0.001) in both the training cohort [C-index (95% confidence interval [CI]), 0.746 (0.680–0.812) vs. 0.685 (0.620–0.750) vs. 0.614 (0.538–0.690), respectively] and validation cohort [C-index (95% CI), 0.724 (0.696–0.752) vs. 0.671 (0.624–0.718) vs. 0.629 (0.597–0.661), respectively]. The calibration curve and decision curve analysis revealed that the radiomics nomogram outperformed the other two models.Conclusions: A radiomics nomogram model incorporating radiomics features and clinical factors has been developed and has the improved ability to predict the postoperative recurrence risk in patients with ESCC who achieved pCR after nCRT followed by surgery.

Yunjia Song,1,2 Aobo Ma,1 Jia Ning,1 Xue Zhong,1 Qian Zhang,1 Xu Zhang,1 Guang Hong,3,4 Ying Li,1 Keiichi Sasaki,2 Changyi Li1 1School of Dentistry, Stomatological Hospital, Tianjin Medical University, Tianjin, China; 2Division of Advanced Prosthetic Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan; 3Liaison Center for Innovative Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan; 4Faculty of Dental Medicine, Airlangga University, Surabaya, Indonesia Purpose: Icariin (ICA) is one of the main active constituents of Herba Epimedii for improving osteogenesis. It is necessary to create a simple and efficient method to load ICA onto the surface of titanium (Ti) implant. The purpose of this study was to establish a local ICA delivery system via a layer-by-layer (LbL) self-assembly system on phase-transited lysozyme (PTL)-primed Ti surface.Materials and methods: A PTL nanofilm was first firmly coated on the pristine Ti. Then, the ICA-loaded hyaluronic acid/chitosan (HA/CS) multilayer was applied via the LbL system to form the HA/CS-ICA surface. This established HA/CS-ICA surface was characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and contact angle measurement. The ICA release pattern of the HA/CS-ICA surface was also examined. MC3T3-E1 osteoblast culture test and a rat model were used to evaluate the effects of the HA/CS-ICA surface in vitro and in vivo.Results: SEM, XPS and contact angle measurement demonstrated successful fabrication of the HA/CS-ICA surface. The HA/CS-ICA surfaces with different ICA concentrations revealed a controlled release profile of ICA during a 2-week monitoring span. Osteoblasts grown on the coated substrates displayed higher adhesion, viability, proliferation and ALP activity than those on the polished Ti surface. Furthermore, in vivo histological evaluation revealed much obvious bone formation in the ICA-coated group by histological staining and double fluorescent labeling at 2 weeks after implantation.Conclusion: The present study demonstrated that ICA-immobilized HA/CS multilayer on the PTL-primed Ti surface had a sustained release pattern of ICA which could promote the osteogenesis of osteoblasts in vitro and improve early osseointegration in vivo. This study provides a novel method for creating a sustained ICA delivery system to improve osteoblast response and osseointegration. Keywords: icariin, controlled release, phase-transited lysozyme, layer-by-layer self-assembly, surface modification of titanium, osteogenesis

Zixin Huang,1,* Shuibin Lin,2,* Chongde Long,1 Xin Zhou,1 Yuting Fan,1 Xielan Kuang,1,3 Jia He,1 Jie Ning,1 Han Zhang,1 Qingjiong Zhang,1 Huangxuan Shen1,3 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China; 2Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 3Biobank of Eye, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China *These authors contributed equally to this work Background: Doxorubicin is a widely used chemotherapy drug for the treatment of a variety of cancers, however it also has serious side effects such as anaphylaxis and heart damage. Therefore, it’s very important to understand the downstream molecular pathways that are essential for Doxorubicin function in cancer treatment.Methods: HeLa S3 cells were treated with different concentrations of Doxorubicin for 24 hours. Then, the mRNA levels of Notch pathway components in the Doxorubicin treated cells were determined by Real-Time qRT-PCR. Lentiviral transfection was used to up-regulate and down-regulate HES1 expression. Cell proliferation and apoptosis were measured with MTT assay and flow cytometry. Finally, immunofluorescence was used to detect protein subcellular location.Result: Doxorubicin treatment strongly increases the expression of multiple Notch pathway components in cancer cells. The Notch target HES1 is activated by Doxorubicin and is required for the Doxorubicin driven apoptosis. In addition, over-expression of HES1 can further enhances Doxorubicin’s role in promoting apoptosis. Mechanistically, HES1 activates PARP1 and regulates the subcellular location of AIF to mediate the apoptosis response under Doxorubicin treatment.Conclusion: Our results provided novel insights into the downstream molecular pathways underlying Doxorubicin treatment and suggested that manipulation of Notch signaling pathway could have synergistic effect with Doxorubicin for cancer treatment. Keywords: Doxorubicin, Notch, HES1, PARP1, apoptosis, cancer treatment

Quality of care has been a long-standing issue in US nursing homes. The culture change movement attempts to transition nursing homes from health care institutions to person-centered homes. While the adoption of culture change has been spreading across nursing homes, barriers to adoption persist. Nursing homes that disproportionately serve minority residents may have additional challenges implementing culture change compared with other facilities due to limited financial and staffing resources. The objective of this study was to examine how nursing home characteristics are associated with culture change adoption in Central Florida nursing homes. This cross-sectional study included 81 directors of nursing (DONs) who completed the Artifacts of Culture Change survey. In addition, nursing home organizational data were obtained from the Certification and Survey Provider Enhanced Reports (CASPER). A logistic regression was conducted to examine the relationship between high culture change adoption and nursing home characteristics. The overall adoption of culture change scores in Central Florida nursing homes was low. Nevertheless, there was variability across nursing homes in the adoption of culture change. High culture change adoption was associated with nursing homes having lower proportions of Medicaid residents.

Thousands of women diagnosed with breast cancer each year receive breast conserving surgery followed by adjuvant radiation therapy. For women with left-sided breast cancer, there is risk of potential cardiotoxicity from the radiation therapy. As data has become available to quantify the risk of cardiotoxicity from radiation, strategies have also developed to reduce the dose of radiation to the heart without compromising radiation dose to the breast. Several broad categories of techniques to reduce cardiac radiation doses include breath hold techniques, prone positioning, Intensity Modulated Radiation Therapy, and Accelerated Partial Breast Irradiation, as well as many small techniques to improve traditional 3 dimensional conformal radiation therapy. This review summarizes the published scientific literature on the various techniques to decrease cardiac irradiation in women treated to the left breast for breast cancer after breast conserving surgery.