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Objective The present study aimed to investigate the recent trends in Helicobacter pylori infection associated with peptic ulcer disease in a large population in Shanghai. Methods We analyzed the medical records of all patients who had undergone upper gastrointestinal endoscopy (EGD) for uninvestigated dyspepsia at Ren Ji Hospital between 2013 and 2019 to determine the prevalence of H. pylori infection in patients with peptic ulcers. Results Peptic ulcers were found in 40,385 of the 383,413 patients who underwent EGD during the study period. Over the 7-year study period, the annual prevalence of H. pylori among patients receiving EGD declined from 32.2% to 26.5%. H. pylori was present in 60% of ulcers and the incidence was higher (66.9%) in duodenal compared with gastric ulcers (48.5%). The proportion of H. pylori-associated gastric ulcers declined from 52.2% to 49.3% and that of H. pylori-positive duodenal ulcers declined from 70.0% to 63.9%. Conclusion The prevalence of H. pylori-positive peptic ulcers, mainly duodenal ulcers, fell from 2013 to 2019. However, the proportion of non- H. pylori-associated peptic ulcer disease increased, especially in elderly people, possibly due to the use of nonsteroidal anti-inflammatory drugs. Further research is needed to confirm this hypothesis.

In this paper, we first propose a new block splitting (NBS) iteration method for solving the large sparse complex symmetric linear systems. The NBS iteration method avoids complex arithmetic compared with the combination method of real part and imaginary part (CRI) one established by Wang et al. (2017). The unconditional convergence and the quasi-optimal parameter of the NBS iteration method are given. Moreover, by further accelerating the NBS one with another parameter, we construct the parameterized BS (PBS) iteration method and establish its convergence theory. Also, the spectral properties of the PBS-preconditioned matrix are analyzed and the parameter selection strategy of the PBS iteration method is given. Numerical experiments are reported to illustrate the feasibility and effectiveness of the proposed methods.

Supersonic fine particles bombarding (SFPB) technology opens a new territory for engineering materials towards improved performances. Owing to its merits and emerging applications, 300M steel (tensile strength ≥1800 MPa) was treated with SFPB to create surface gradient nanostructures. The time dependent SFPB process was implemented on various 300M steel surface to investigate the microstructural evolution and mechanical property. 300M steel surface grains were sufficiently refined down to nanometer scale under high energy SFPB. In the subsurface layer, acicular martensite was found to be bent and broken, resulting in the high-density dislocation. At the early stage of SFPB, the impact affected area of 300M steel surface was deepened with increasing SFPB time, and the grains were constantly refined, which further lead to higher strength and improved hardness. However, after longer treatments of more than 90 s, bombardment energy accumulated at 300M steel surface resulted in grain growths and deteriorations of hardness. In particular, the newly formed microcracks substantially reduced the tensile strength. After SFPB treatment, the dimple size of the 300M steel surface fracture decreased significantly, and a large area of cleavage plane appeared, showing typical characteristics of ductile-brittle mixed fracture.

Blue lasers are very useful for applications in fundamental sciences and advanced technologies. Although the frequency doubling with a first-order quasi-phase-matched (QPM) crystal is an effective approach to obtain blue and UV lasers, the crystal should be poled with a short period, which is technically difficult to fabricate compared with a long period. Using a third-order QPM can be an alternative way to generate blue light, in which the poling period is 3 times larger than that in first-order QPM. In this work, we report on the generation of a 402.5 nm laser by using cavity-enhanced second-harmonic generation and a periodically poled KTP (PPKTP) crystal with a poling period of 10.02 µm. About 36.49 mW output power and 15.3% conversion efficiency are achieved in our experiment.

Genomic defect and Casein Kinase II-mediated hyper-phosphorylation of Ikaros tumor suppressor cause the loss of function of Ikaros, and Ikaros dysfunction is characteristics of high-risk B-cell acute lymphoblastic leukemia (HR B-ALL) with poor prognosis. The increased activation of the PI3K/AKT/mTOR pathway is also observed in HR B-ALL and identifies mTOR as an attractive therapeutic target in HR B-ALL. Here, we report that Ikaros represses MTOR transcription and Ikaros' ability to repress MTOR in leukemia is impaired by oncogenic CK2 kinase. Treatment with the CK2 inhibitor, CX-4945, enhances Ikaros activity as a repressor of MTOR, resulting in reduced expression of MTOR in HR B-ALL. Thus, we designed a novel therapeutic approach that implements dual targeting of mTOR: direct inhibition of the mTOR protein (with rapamycin), in combination with Ikaros-mediated transcriptional repression of the MTOR gene (using the CK2 inhibitor, CX-4945). Combination treatment with rapamycin and CX-4945 shows synergistic therapeutic effects in vitro and in patient-derived xenografts from HR B-ALL. These data suggest that such therapy has the potential to reduce the death rate in HR B-ALL. The dual targeting of oncogene transcription, combined with inhibition of the corresponding oncoprotein provides a paradigm for a novel precision medicine approach for treating hematological malignancies. Citation Format: Chunhua Song, Zheng Ge, Yali Ding, Bihua Tan, Elanora Dovat, Yiping Yang, Chandrika Gowda, Sinisa Dovat. Dual targeting of CK2 and MTOR as a novel therapeutic approach for high-risk B-cell acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1047.

Background/Aims: Acute rejection (AR) is a major complication post renal transplantation, with no widely-accepted non-invasive biomarker. This study aimed to explore the expression profiles of long non-coding RNAs (lncRNAs) in the peripheral blood (PB) of renal transplant recipients and their potential diagnostic values. Methods: The genome-wide lncRNA expression profiles were analyzed in 150 PB samples from pediatric and adult renal transplant (PRTx and ARTx) cohorts. The diagnostic performance of differentially expressed lncRNA was determined using receiver operator characteristic curve, with area under the curve (AUC) and 95% confidential interval (CI). Finally, a risk score was constructed with logistical regression model. Results: A total of 162 lncRNAs were found differentially expressed in PRTx cohort, while 163 in ARTx cohort. Among these identified lncRNAs, 23 deregulated accordingly in both cohorts, and could distinguish AR recipients from those without AR. Finally, a risk score with two most significant lncRNAs (AF264622 and AB209021) was generated and exhibited excellent diagnostic performance in both PRTx (AUC:0.829, 95% CI:0.735-0.922) and ARTx cohorts (AUC: 0.889, 95% CI: 0.817-0.960). Conclusion: A molecular signature of two lncRNAs in PB could serve as a novel non-invasive biomarker for the diagnosis of AR in both pediatric and adult renal transplant recipients.

The study aimed to evaluate the new modification of the Duckett technique in decreasing the incidence of urethral strictures for urethral plate transected hypospadias and also explored its clinical application. Thirty-three patients (aged 7 months to 12 years, mean age 2.8 years) who underwent repair of primary hypospadias using the new one-stage urethroplasty were enrolled. Clinical data, including cosmetic and its complications, and uroflowmetry data were documented. Uroflowmetry data of 19 patients who underwent Duckett urethroplasty were used as a comparison. The length of the urethral defect ranged from 2.5 to 5.0 cm. The postoperative follow-up was 14–30 months. Ten patients (30.3%) had fistulas; no patients had strictures or diverticula. All ten fistulas were small (

In this paper, several new estimates of the minimum H-eigenvalue for weakly irreducible nonsingular $$\mathcal {M}$$ -tensors, including the new Brauer-type estimates and the new S-type estimates, are derived. It is proved that the new estimates are tighter than some existing ones and numerical examples are given to verify this fact. The other main result of this paper is to provide a sharper Ky Fan-type theorem which is better than the original Ky Fan theorem for the nonsingular $$\mathcal {M}$$ -tensors.

// Qing-Wei Zhang 1, * , Xiao-Lu Lin 1, 5 * , Chi-Hao Zhang 2, * , Chen-Yue Tang 3, * , Xin-Tian Zhang 1, * , La-Mei Teng 1, 4, * , Zhi-Zheng Ge 1 and Xiao-Bo Li 1 1 Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai 200001, China 2 Department of General Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Baoshan 201999, Shanghai, China 3 Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200000, China 4 Division of Gastroenterology and Hepatology, Liqun Clinical Medicine College, The Second Military Medical University, Liqun Hospital, Shanghai 200001, China 5 Department of Digestive Endoscopy, Provincial Clinic Medical College, Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, China * These authors have contributed equally to this work Correspondence to: Zhi-Zheng Ge, email: zhizhengge@aliyun.com Xiao-Bo Li, email: lxb_1969@163.com Keywords: esophageal cancer, marital status, SEER, OS, CSS Received: February 22, 2017 Accepted: April 04, 2017 Published: July 22, 2017 ABSTRACT Background and aims: Multiple studies have shown that marital status is associated with the survival of various types of cancer patients. However, there has not been adequate evidence of the association between marital status and the survival of patients with esophageal cancer (EC). We aimed to investigate the effect of marital status on survival of EC patients. Methods: We identified 15,598 EC patients from the Surveillance, Epidemiology, and End Results (SEER) database. Meanwhile, propensity scores for marital status, which were calculated for each patient using a nonparsimonious multivariable logistic regression model, were used to match 6,319 unmarried patients with 9,279 married patients. We performed Kaplan–Meier analysis and multivariate Cox regression to analyze the association between marital status and the overall survival (OS) and EC cause-specific survival (CSS) of EC patients before matching and after matching. Results: We matched 2,986 unmarried patients with 2,986 married patients. Unmarried patients had poorer OS than married patients before matching (hazard ratio [HR]: 1.22; 95% confidence interval [CI]: 1.18–1.27; P < 0.0001) and after matching (HR: 1.20; 95% CI: 1.13–1.27; P < 0.0001) and poorer CSS than married patients before matching (HR: 1.21; 95% CI: 1.16–1.26; P < 0.0001) and after matching (HR: 1.17; 95% CI: 1.10–1.24; P < 0.0001). Further analysis showed that among different unmarried patients, widowed patients had the poorest OS (HR: 1.46; 95% CI: 1.38–1.55; P < 0.0001) and CSS (HR: 1.43; 95% CI: 1.34–1.52; P < 0.0001) compared with married patients. Conclusions: Unmarried EC patients had poorer survival rates than married EC patients. Meanwhile, widowed patients with EC had the highest risk of death compared with single, married, and divorced patients.

For the nonsymmetric saddle point problems with nonsymmetric positive definite (1,1) parts, the modified generalized shift-splitting (MGSS) preconditioner as well as the MGSS iteration method is derived in this paper, which generalize the modified shift-splitting (MSS) preconditioner and the MSS iteration method newly developed by Huang and Su (J. Comput. Appl. Math. 317:535–546, 2017), respectively. The convergent and semi-convergent analyses of the MGSS iteration method are presented, and we prove that this method is unconditionally convergent and semi-convergent. Meanwhile, some spectral properties of the preconditioned matrix are carefully analyzed. Numerical results demonstrate the robustness and effectiveness of the MGSS preconditioner and the MGSS iteration method and also illustrate that the MGSS iteration method outperforms the generalized shift-splitting (GSS) and the generalized modified shift-splitting (GMSS) iteration methods, and the MGSS preconditioner is superior to the shift-splitting (SS), GSS, modified SS (M-SS), GMSS and MSS preconditioners for the generalized minimal residual (GMRES) method for solving the nonsymmetric saddle point problems.

// Li Yang 1, * , Xiao-Lu Lin 1, * , Wei Liang 3, * , Seng-Wang Fu 4, * , Wen-Feng Lin 1, * , Xiao-Qing Tian 1 , Yun-Jie Gao 1 , Hao-Yan Chen 2 , Jun Dai 1 and Zhi-Zheng Ge 1 1 Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai 200001, China 2 Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai 200001, China 3 Department of Digestive Endoscopy, Provincial Clinic Medical College, Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, China 4 Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China * These authors have contributed equally to this work Correspondence to: Zhi-Zheng Ge, email: zhizhengge@aliyun.com Jun Dai, email: lx19980507@126.com Keywords: GPR116, prognosis, metastasis, colorectal carcinoma Received: March 22, 2017 Accepted: May 01, 2017 Published: May 25, 2017 ABSTRACT Previous studies have found that G-protein-coupled receptor 116 (GPR116) is a regulator of breast cancer metastasis. However, the role of GPR116 in colorectal carcinoma (CRC) carcinogenesis and progression is unknown. In this study, We found GPR116 expression was significantly up-regulated in CRC specimens compared with corresponding non-cancerous tissues. Increased GPR116 expression in CRC was correlated with histological differentiation and distant metastasis. In addition, high expression of GPR116 was significantly associated with poor overall survival of CRC patients, which was also confirmed by GSE14333, GSE17536 and GSE33113 datasets from the Gene Expression Omnibus (GEO). Furthermore, we demonstrated that the ability of proliferation and invasion of CRC cell lines HCT116 and LOVO was markedly reduced after transfected with siRNA-GPR116. Meanwhile, GPR116 may drive EMT in CRC cells through AKT/EKR signaling pathway, resulting in metastasis. Thus, GPR116 may be a novel reliable prognostic indicator and a risk factor in CRC progression.

Background and aims Magnifying endoscopy with narrow-band imaging (M-NBI) has been widely used in the differential diagnosis of deep submucosal colorectal cancers (dSMCs) from superficial submucosal cancers (sSMCs) and intramucosal neoplasms. We aimed to pool the diagnostic efficacy of M-NBI and compare it with that of magnifying chromoendoscopy (M-CE) in diagnosing colorectal dSMC. Methods PubMed, EMBASE, and the Cochrane Library were searched to identify eligible studies. Meeting abstracts were also searched. A bivariate mixed-effects binary regression model was used in the meta-analysis to calculate the pooled diagnostic efficacy of M-NBI and compare it with that of M-CE in the diagnosis of dSMC. Subgroup analyses and meta-regression were conducted to explore sources of heterogeneity. Results We included 17 studies: 14 full texts and 3 meeting abstracts. The pooled sensitivity, specificity, and area under the summary receiver operating characteristic curve (AUC) with 95 % confidence intervals (CIs) in diagnosing dSMC were 74 % (66 % – 81 %; I2 = 84.6 %), 98 % (94 % – 99 %; I2 = 94.4 %), and 0.91 (0.88 – 0.93), respectively, for M-NBI. The pooled sensitivity, specificity and AUC (95 %CI) were 84 % (76 % – 89 %; I2 = 76.9 %), 97 % (94 % – 99 %; I2 = 90.2 %), and 0.97 (0.95 – 0.98), respectively, for M-CE. M-NBI had lower sensitivity (P Conclusions M-NBI and M-CE had comparable specificities in diagnosing dSMC, but the sensitivity of M-NBI was slightly lower than that of M-CE.

// Chang-Cheng Zhou 1,* , Wen-Tao Yao 1,* , Yu-Zheng Ge 1 , Lu-Wei Xu 1 , Ran Wu 1 , Xiao-Fei Gao 2 , Kai-Wei Song 1 , Xiao-Min Jiang 2 , Min Wang 1 , Wen-Juan Huang 3 , Yun-Peng Zhu 1 , Liang-Peng Li 4 , Liu-Hua Zhou 1 , Zhong-Le Xu 1,5 , Sheng-Li Zhang 1 , Jia-Geng Zhu 1 , Wen-Cheng Li 1 and Rui-Peng Jia 1 1 Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China 2 Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China 3 Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China 4 Department of Cardiothoracic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China 5 Department of Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China * These authors have contributed equally to this work Correspondence to: Rui-Peng Jia, email: // Yu-Zheng Ge, email: // Keywords : remote ischemic conditioning, contrast-induced acute kidney injury, randomized controlled trial, meta-analysis, trial sequential analysis Received : December 21, 2016 Accepted : May 12, 2017 Published : May 23, 2017 Abstract Objective: We conducted this meta-analysis to examine the effect of remote ischemic conditioning (RIC) on contrast-induced acute kidney injury (CI-AKI) in patients undergoing intravascular contrast administrationon. Methods: Pubmed, Embase, and Cochrane Library were comprehensively searched to identify all eligible studies by 15th March, 2017. Risk ratio (RR) and weighted mean difference with the corresponding 95% confidence intervals (CI) were used to examine the treatment effect. The heterogeneity and statistical significance were assessed with Q-test and Z-test, respectively. Results: A total of 16 RCTs including 2175 patients were eventually analyzed. Compared with the control group, RIC could significantly decrease the incidence of CI-AKI (RR=0.58; 95% CI: 0.46, 0.74; P < 0.001), which was further confirmed by the trial sequential analysis. Subgroup analyses showed that remote ischemic preconditioning (RIPrC) and remote ischemic postconditioning (RIPoC) were both obviously effective, and perioperative hydration might enhance the efficiency of RIC. RIC also significantly reduced the major adverse cardiovascular events within six months. Conclusion: RIC, whether RIPrC or RIPoC, could effectively exert renoprotective role in intravascular contrast administration and reduce the incidence of relevant adverse events.

This study demonstrates that by incorporating a microbial electrochemical unit into an anaerobic osmotic membrane bioreactor (AnOMBR), the system addressed several challenges faced by traditional anaerobic membrane bioreactors and recovered biogas, nitrogen, and phosphorus while maintaining high effluent quality with low dissolved methane. The microbial recovery cell (MRC)-AnOMBR system showed excellent organic (>93%) and phosphorus removal (>99%) and maintained effluent COD below 20 mg/L. Furthermore, the reactor effectively recovered up to 65% PO 4 3− and 45% NH 4 + from the influent, which can be further improved if membranes with higher selectivity are used. Nutrients removal from bulk solution mitigated NH 4 + penetration to the draw solution and reduced scaling potential caused by PO 4 3− . The maximum methane yield was 0.19 L CH 4 /g COD, and low methane ( 4 /L) was detected in the effluent. Further improvement can be made by increasing charge efficiency for better nutrient and energy recovery.

For a nonsymmetric saddle point problem, the modified shift-splitting (MSS) preconditioner has been proposed by Zhou etźal. By replacing the parameter α in (2,2)-block in the MSS preconditioner by another parameter β, a generalized MSS (GMSS) preconditioner is established in this paper, which results in a fixed point iteration called the GMSS iteration method. We provide the convergent and semi-convergent analysis of the GMSS iteration method, which show that this method is convergence and semi-convergence if the related parameters satisfy suitable restrictions. Meanwhile, the distribution of eigenvalues and the forms of the eigenvectors of the preconditioned matrix are analyzed in detail. Finally, numerical examples show that the GMSS method is more feasibility and robustness than the MSS, Uzawa-HSS and PU-STS methods as a solver, and the GMSS preconditioner outperforms the GSOR, Uzawa-HSS, MSS and LMSS preconditioners for the GMRES method for solving both the nonsingular and the singular saddle point problems with nonsymmetric positive definite and symmetric dominant (1,1) parts.

Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent histologic subtype of kidney cancers in adults, which could be divided into two distinct subgroups according to the BRCA1 associated protein-1 (BAP1) mutation status. In the current study, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in ccRCC, with the aim to identify the differentially expressed miRNAs between BAP1 mutant and wild-type tumors, and generate a BAP1 mutation-specific miRNA signature for ccRCC patients with wild-type BAP1. Methods: The BAP1 mutation status and miRNA profiles in BAP1 mutant and wild-type tumors were analyzed. Subsequently, the association of the differentially expressed miRNAs with patient survival was examined, and a BAP1 mutation-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate and multivariate Cox regression analyses. Finally, the bioinformatics methods were adopted for the target prediction of selected miRNAs and functional annotation analyses. Results: A total of 350 treatment-naive primary ccRCC patients were selected from The Cancer Genome Atlas project, among which 35 (10.0%) subjects carried mutant BAP1 and had a shorter overall survival (OS) time. Furthermore, 33 miRNAs were found to be differentially expressed between BAP1 mutant and wild-type tumors, among which 11 (miR-149, miR-29b-2, miR-182, miR-183, miR-21, miR-365-2, miR-671, miR-365-1, miR-10b, miR-139, and miR-181a-2) were significantly associated with OS in ccRCC patients with wild-type BAP1. Finally, a BAP1 mutation-specific miRNA signature consisting of 11 miRNAs was generated and validated as an independent prognostic parameter. Conclusions: In summary, our study identified a total of 33 miRNAs differentially expressed between BAP1 mutant and wild-type tumors, and generated a BAP1 mutation-specific miRNA signature including eleven miRNAs, which could serve as a novel prognostic biomarker for ccRCC patients with wild-type BAP1.

Introduction: Severe aplastic anemia (SAA) is a hematologic disorder characterized by bone marrow hypoplasia and peripheral pancytopenia. Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine (CsA) is the standard first-line treatment for patients with SAA who are ineligible for hematopoietic stem cell transplantation (HSCT). For those refractory to or relapsed after IST, eltrombopag (an oral thrombopoietin receptor agonist) were recommended as the second-line therapy by US FDA and European Medicines Agency (EMA). However, in several countries including China, eltrombopag has not been approved for use in patients with SAA, so there is an urgent unmet medical need for additional efficient treatment options. Hetrombopag, another oral thrombopoietin receptor agonist, has similar mechanism in stimulating thrombopoietin receptor signaling pathway as eltrombopag and better pharmacological performance than eltrombopag in pre-clinical study (Xie et al, JCMM 2018). In a phase 1 trial, hetrombopag was safe and well-tolerated in healthy subjects with potent thrombopoietic activity and acceptable pharmacokinetic profiles (Zheng et al, BCPT 2017). Here, in this phase 2 trial (NCT03557099), we aimed to assess the activity and safety of hetrombopag in patients with SAA who have had an insufficient response to IST. Methods: This open-label, single-arm, phase 2 study enrolled patients with SAA who have had an insufficient response to IST and were ineligible for transplantation. Patients were given hetrombopag orally at an initial dose of 7.5 mg once daily after overnight fasting. If increase of platelet count was less than 20×109/L from baseline, the dose of hetrombopag was gradually up-titrated by 2.5 mg every 2 weeks to a maximum of 15 mg once daily, for a total of 52 weeks. The primary endpoint was proportion of patients achieving hematologic responses in at least one lineage at week 18. Results: Between June 20, 2018 and May 24, 2019, 55 eligible patients were enrolled and received hetrombopag treatment. The median age was 40 years (range 19-65) and 34 (61.8%) patients were male. As of data cutoff on June 12, 2020, 52 (94.5%) patients received the maximum dose of 15 mg once daily, and the final dose of the other three patients was 7.5 mg, 10 mg, and 12.5 mg, respectively. A total of 24 (43.6%, 95% CI 30.3-57.7) of the 55 patients met primary endpoint, achieving at least one lineage hematologic response at week 18 after the initiation of hetrombopag treatment (Figure 1). Of them, 11 (20.0%) patients had unilineage responses, 7 (12.7%) had bilineage responses, and 6 (10.9%) had trilineage responses. Twenty-four (43.6%, 95% CI 30.3-57.7) patients responded in at least one lineage at week 24 and 27 (49.1%, 95% CI 35.4-62.9) patients responded in at least one lineage at week 52 (Figure 1). Of the 32 patients with responses at week 18, 24, or 52, median time to initial hematologic response was 7.9 weeks (range 2.0-32.1). The responses were durable in majority of patients who remained on hetrombopag treatment, with only six patients relapsed, achieving a probability of recurrence-free survival at 12-month of 79.5% (95% CI 59.9-90.3). Adverse events of any attribution were reported in 54 (98.2%) of the 55 patients, with the most common ones being upper respiratory tract infection (22, 40.0%), increased aspartate aminotransferase (12, 21.8%), and pyrexia (12, 21.8%). Twenty-eight (50.9%) patients had treatment-related adverse events. Adverse events of grade 3 or higher occurred in 17 (30.9%) patients, with only one (1.8%) related to hetrombopag. Three (5.5%) patients underwent dose reduction or treatment interruption and three (5.5%) patients were discontinued from treatment because of adverse events, but none of which was considered as drug-related. Fifteen (27.3%) patients had serious adverse events. Three (5.5%) deaths were reported, and all of them were judged to be not treatment-related. Clonal cytogenetic evolution occurred in two (3.6%) patients during hetrombopag administration, with one patient had a loss of chromosome 7 and one had an increase of chromosome 8. Conclusions: Hetrombopag showed encouraging activity with multilineage hematologic responses in patients with SAA who have had an insufficient response to prior IST. Hetrombopag was well-tolerated and safe. This study provided evidences that hetrombopag might represent a novel treatment option for patients with SAA. Disclosures He: LongBio Pharma: Consultancy, Research Funding; F. Hoffmann-La Roche: Consultancy, Other: Medical writing support, furnished by Scott Battle, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Shen:Jiangsu Hengrui Medicine Co., Ltd: Current Employment. Tai:Jiangsu Hengrui Medicine Co., Ltd: Current Employment. Zhang:Jiangsu Hengrui Medicine Co., Ltd: Current Employment. Zhu:Jiangsu Hengrui Medicine Co., Ltd: Current Employment. Zou:Jiangsu Hengrui Medicine Co., Ltd: Current Employment.

// Zheng Ge 1, 2 , Xilian Zhou 3 , Yan Gu 3 , Qi Han 3 , Jianyong Li 3 , Baoan Chen 1, 2 , Qinyu Ge 4 , Elanora Dovat 5 , Jonathon L. Payne 5, 6 , Tianyu Sun 7 , Chunhua Song 2, 5 , Sinisa Dovat 2, 5 1 Department of Hematology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China 2 International Cooperative Leukemia Group and International Cooperative Laboratory of Hematology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China 3 Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China 4 State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China 5 Department of Pediatrics, Pennsylvania State University Medical College, Hershey, PA 17033, USA 6 Loma Linda University School of Medicine, Department of Basic Sciences, Loma Linda, CA 92350, USA 7 Department of Internal Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA Correspondence to: Zheng Ge, email: Janege879@hotmail.com Sinisa Dovat, email: sdovat@hmc.psu.edu Keywords: BCL6, BACH2, IKZF1, acute lymphoblastic leukemia Received: October 11, 2016 Accepted: November 24, 2016 Published: December 20, 2016 ABSTRACT B-Cell CLL/Lymphoma 6 ( BCL6 ) is a proto-oncogene that is highly expressed in acute lymphoblastic leukemia (ALL). BTB and CNC Homology 1 Basic Leucine Zipper Transcription Factor 2 (BACH2) is a suppressor of transcription. The BACH2 – BCL6 balance controls selection at the pre-B cell receptor checkpoint by regulating p53 expression. However, the underlying mechanism and the clinical relevance of the BCL6/BACH2 axis are unknown. Here, we found that Ikaros, a tumor suppressor encoded by IKZF1 , directly binds to both the BCL6 and BACH2 promoters where it suppresses BCL6 and promotes BACH2 expression in B-cell ALL (B-ALL) cells. Casein kinase 2 (CK2) inhibitors increase Ikaros function thereby inhibiting BCL6 and promoting BACH2 expression in an Ikaros-dependent manner. We also found that the expression of BCL6 is higher while BACH2 expression is lower in patients with B-ALL than normal bone marrow control. High BCL6 and low BACH2 expression is associated with high leukemic cell proliferation, unfavorable clinical and laboratory features, and inferior outcomes. Moreover, IKZF1 deletion is associated with high BCL6 and low BACH2 expression in B-ALL patients. CK2 inhibitors increase Ikaros binding to the promoter of BCL6 and BACH2 and suppress BCL6 while promoting BACH2 expression in the primary B-ALL cells. Our data indicates that Ikaros regulates expression of the BCL6/BACH2 axis in B-ALL. High BCL6 and low BACH2 expression are associated with Ikaros dysregulation and have a potential effect on the development of B-ALL.

BACKGROUND This study investigated the approach for detection of small-bowel (SB) Crohn's disease (CD) in the absence of complications at diagnosis using advanced modalities. MATERIAL AND METHODS Patients diagnosed with CD in Renji Hospital from 2005 to 2014 were divided into 2 groups by year of diagnosis: 2005 to 2009 and 2010 to 2014. The modalities used and the clinical characteristics of patients were retrospectively examined. RESULTS Advanced modalities did not detect higher rate of non-stricturing/non-penetrating disease in 2010 to 2014 than older modalities in 2005 to 2009. Further analysis showed that a stricturing complication was significantly more common in patients with SB CD than in those who had CD with SB and colonic involvement, and the duration from symptom onset to lesion detection was significantly longer in patients with SB CD than in those who had CD with SB and colonic involvement. Fewer patients with SB CD underwent SB capsule endoscopy compared to the other advanced modalities. Abdominal pain (74.4%) was the most common presentation, and 94.0% patients with SB CD presented gastrointestinal bleeding and anemia. CONCLUSIONS Early detection of SB CD without complications remains difficult even if advanced modalities are introduced. Our hypothesis is that the fecal occult blood test and routine blood test should be administered to patients with abdominal pain or gastrointestinal manifestations. Once the patients are found to have GI bleeding or anemia, they would be further examined according to the guideline and SBCE would be used in the early stage of SB CD.

Background Superficial colorectal cancer (SCRC) is defined as colorectal cancer (CRC) confined to the mucosa or submucosa. Endoscopic resection (ER) is widely used to resect differentiated SCRC from patients without lymph node metastasis (LNM). However, it is unclear whether ER is suitable for use with patients with differentiated early-onset SCRC because early-onset CRC is more aggressive. Therefore, we aimed to investigate the association between age of CRC onset and LNM. Materials and Methods We retrieved data for patients with surgically resected differentiated-type SCRCs from the Surveillance, Epidemiology, and End Results (SEER) database. Rate of LNM was compared among patients aged 18–39, 40–49, 50–59, 60–69, and ≥70 years. The association between age and LNM was further examined using multivariate logistic regression. Results We retrieved 34,506 records of differentiated SCRCs from the SEER database, including 667 patients aged 18–39 years, 2,385 aged 40–49, 8,075 aged 50–59 years, 9,577 aged 60–69 years, and 13,802 aged ≥70 years. Rates of LNM were 15.74%, 14.13%, 10.67%, 8.07%, and 6.76% for patients aged 18–39, 40–49, 50–59, 60–69, and ≥70 years, respectively. We found an inverse correlation between age at diagnosis and risk of LNM from the univariate analysis (p < .001). Compared with patients aged 18–39, the odds ratios with 95% confidence interval (CI) for patients aged 40–49, 50–59, 60–69, and ≥70 years were 0.90 (0.71–1.15, p = .376), 0.69 (0.56–0.87, p = .001), 0.54 (0.43–0.68, p < .001), and 0.47 (0.38–0.60, p < .001), respectively. Conclusion In differentiated SCRCs, younger age at diagnosis was associated with higher risk of LNM. Implications for Practice Endoscopic resection (ER) is widely used to resect differentiated superficial colorectal cancer (SCRC) without lymph node metastasis (LNM). However, no study has ever investigated risk of LNM of early-onset SCRC compared with average onset SCRC to explore whether ER is suitable for early-onset SCRC. To the authors' knowledge, this population-based study is the first study to find inverse correlation between age at diagnosis and risk of LNM in differentiated SCRCs. This finding indicates that ER may not be suitable for young patients with differentiated SCRC. Because the 30-day operative mortality after surgery is higher but the risk of LNM is lower in older patients compared with younger patients, ER for differentiated SCRCs may be advantageous over surgery for older patients.

Purpose: The early BCR-ABL1 reduction had the prognostic impact of the chronic-phase chronic myeloid leukemia (CML-CP) patients. This study was to find a more precise early prognosis index at 3 months in the patients with newly diagnosed CML-CP, especially for the patients with BCR-ABL1IS >10%. Methods: We retrospectively analyzed the data of 79 newly diagnosed CML-CP patients from October 2013 to April 2017. All patients took imatinib regularly and continuously and monitored BCR-ABL1 transcript level at baseline and 3, 6, 9, 12, 18 months after starting imatinib treatment. Results: Among the 44(55.7%) patients with BCR/ABL1IS ≤10% at 3 months after imatinib treatment, 12(27.3%) cases did not achieve major molecular response (MMR) at 12 months, and 7(14.9%) patients with the halving time BCR-ABL1 transcript ≤40 days failed to achieve MMR at 12 months. However, approximately twenty-six percent of the patients with BCR-ABL1IS >10% still obtained MMR. Moreover, the patients with BCR-ABL1IS ≤10% and halving time ≤40 days had a significantly better MMR than that of the patients with the BCR-ABL1IS ≤10% and halving time >40 days (88.6% versus 11.1%, P 10% and halving time >40 days rarely achieved MMR at 12 months. Conclusion: These data indicated that the halving time of BCR-ABL1 transcript was also an important prognostic factor as that of the BCR-ABL1IS. Combined observations of these two prognosis indexes are more accurate predictor for the long-term molecular response, especially for the CML-CP patients with BCR-ABL1IS >10%, and which is helpful for TKI switching as early as possible to improve patients' survival and reduce drug costs.

Background: Surgery is the only way to cure gastric adenocarcinoma (GAC), and chemotherapy is the basic adjuvant management for GAC. A prognostic model for predicting the individual disease-specific survival (DSS) rates of GAC patients who receive surgery and chemotherapy has not been established. Objective: We aimed to establish a survival nomogram for GAC patients who receive surgery and chemotherapy. Methods: We identified 5764 GAC patients who had received surgery and chemotherapy from the SEER (Surveillance, Epidemiology, and End Results) database. Approximately 80% (n=4034) of the included patients were randomly assigned to the training set, and the remaining patients (n=1729) were assigned to the external validation set. Nomogram was established by the training set and validated by the validation set. Results: Based on the results of a multivariate analysis, a nomogram was developed that encompassed age at diagnosis, number of regional lymph nodes examined, number of positive regional lymph nodes, sex, race, grade, derived AJCC stage, summary stage, and radiotherapy status. The C-index (Harrell’s concordance index) of the model was higher than that of the traditional seventh AJCC staging system (0.707 vs 0.661). Calibration plots of the nomogram showed that the probability of DSS optimally corresponded to the survival rate. Integrated discrimination improvement (IDI) and categorical net reclassification improvement (NRI) showed visible improvement. IDI for 3-, 5- and 10- year DSS were 0.058, 0.059 and 0.058, respectively (P>0.05), and NRI for 3-, 5- and 10- year DSS were 0.380 (95% CI=0.316–0.470), 0.407 (95% CI=0.350–0.505), and 0.413 (95% CI=0.336–0.519), respectively. Decision curve analysis supported that the constructed nomogram was superior to the AJCC staging system. Conclusion: The proposed nomogram provides more-reliable DSS predictions for GAC patients who receive surgery and chemotherapy in the general population. According to validation, the new nomogram will be beneficial in facilitating individualized survival predictions and useful when performing clinical decision-making for GAC patients who receive surgery and chemotherapy.

RAG1 plays important roles in lymphopoiesis and immune system, its dysfunction may result in the malignancies of hemopoietic system. The aim of this study was to investigate the characteristics of RAG1 expression in adult B-cell acute lymphoblastic leukemia (B-ALL), and to analyze the clinical significances.Quantitative PCR (q-PCR) was performed to evaluate the expression of RAG1 in 104 newly diagnosed, 22 relapsed adult B-ALL patients and 30 normal controls, the clinical significances of RAG1 expression were analyzed.Compared with normal controls, newly diagnosed and relapsed adult B-ALL patients showed higher RAG1 expression level (3.94 vs 1.23) (P＜0.01), (5.86 vs 1.23) (P＜0.01). The analysis of paired simples from 6 cases of newly diagnosed and relapsed B-ALL showed that the expression level of RAG1 at relapse was significantly higher than that at new diagnosis (13.65 vs 2.31) (P＜0.01). The RAG1 expression level in IK6 positive patients was higher than that in IK6 negative patients (5.30 vs 2.11) (P＜0.05). The ratio of patients with LDH＞1 000 U/L in RAG1 high expression group was higher than that in RAG1 low expression group (42.2% vs 20.5%) (P＜0.05).RAG1 up-regulation may play an important role in the development of adult B-ALL especially when relapsed, which may also take part in the formation of Ik6. Monitoring RAG1 expression may provide a new method to evaluate the prognosis of adult B-ALL patients.成人B细胞性急性淋巴细胞白血病RAG1表达特点及临床意义.探讨成人B细胞性急性淋巴细胞白血病（B-ALL）中RAG1基因的表达特点及其临床意义.应用实时定量PCR方法检测104例初发、22例复发成人B-ALL患者和30例正常对照者RAG1基因的表达，分析基因表达特点及其与临床和实验室参数之间的关系.初发、复发成人B-ALL患者RAG1基因表达水平均高于正常对照者（3.94 vs 1.23）（P＜0.001）；（5.86 vs 1.23）（P＜0.01）。6例初发与复发患者成对标本分析显示，RAG1表达水平在疾病复发时显著高于初发（13.65 vs 2.31）（P＜0.01）。IKZF1基因外显子3-6缺失的异构体Ikaros isoform 6（Ik6）阳性患者RAG1基因表达水平显著高于Ik6阴性患者（5.30 vs 2.11）（P＜0.05）。RAG1高表达组LDH水平大于1 000 U/L患者的比例显著高于低表达组（42.2% vs 20.5%）（P＜0.05）.RAG1基因表达上调在成人B-ALL发生发展中尤其在复发过程中可能起重要作用，其上调与IKZF1基因缺失相关。监测RAG1表达水平的变化可能为临床预测成人B-ALL患者疾病进展提供帮助.

Acetaminophen (APAP)-induced acute hepatotoxicity is the leading cause of drug-induced acute liver failure. The aim of this study was to evaluate the effects of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) on the protection of APAP-induced hepatotoxicity in mice. Mice were pretreated with a single dose of tempol (20 mg/kg per day) orally for 7 days. On the seventh day, mice were injected with a single dose of APAP (300 mg/kg) to induce acute hepatotoxicity. Our results showed that tempol treatment markedly improved liver functions with alleviations of histopathological damage induced by APAP. Tempol treatment upregulated levels of antioxidant proteins, including superoxide dismutase, catalase, and glutathione. Also, phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) and protein expression of nuclear factor erythroid 2-related factor (Nrf 2) and heme oxygense-1 (HO-1) were all increased by tempol, which indicated tempol protected against APAP-induced hepatotoxicity via the PI3K/Akt/Nrf2 pathway. Moreover, tempol treatment decreased pro-apoptotic protein expressions (cleaved caspase-3 and Bax) and increased anti-apoptotic Bcl-2 in liver, as well as reducing apoptotic cells of TUNEL staining, which suggested apoptotic effects of tempol treatment. Overall, we found that tempol normalizes liver function in APAP-induced acute hepatotoxicity mice via activating PI3K/Akt/Nrf2 pathway, thus enhancing antioxidant response and inhibiting hepatic apoptosis.

For the large sparse complex symmetric linear systems, we construct a preconditioned triangular splitting (PTS) iteration method based on utilizing the preconditioned technique and the triangular splitting of a matrix. Compared with the two-parameter two-step scale-splitting one established by Salkuyeh and Siahkolaei (Calcolo 55:8, 2018), PTS iteration method does not involve the complex arithmetic. The convergence theory of the PTS iteration method is established and the spectral properties of the PTS-preconditioned matrix are analyzed. In addition, by applying the minimum residual technique to the PTS iteration method, we develop the minimum residual PTS (MRPTS) iteration method to further improve the efficiency of the PTS one, then establish the corresponding convergence theory. Also, inexact version of the MRPTS iteration method and its convergence properties are presented. Numerical experiments are reported to verify the effectiveness of the proposed methods.

Recently, the incidence of colorectal cancer has increased each year. Natural orifice specimen extraction surgery (NOSES) removes the specimen from a natural cavity of the human body (anal or vaginal) and completes reconstruction of the digestive tract. There are only a few trocar scars in the abdomen after surgery. Transvaginal specimen extraction for right-sided colon cancer is one of the classic NOSES surgeries. As NOSES is accepted by increasing numbers of colorectal surgeons, NOSES technology is becoming increasingly widely used in China and abroad. Studies have confirmed the feasibility and safety of NOSES. Therefore, it is necessary to conduct further clinical studies to evaluate the short-term efficacy of the NOSES procedure.To investigate the short-term efficacy of transvaginal specimens for laparoscopic right colon cancer (NOSES).We conducted a retrospective analysis of 90 cases of laparoscopic right colon cancer radical surgery performed continuously in the anorectal surgery of our Hospital from June 2015 to December 2018. Thirty-two patients underwent complete laparoscopic anastomosis and transvaginal specimen removal (NOSES group), and 58 patients underwent conventional abdominal wall removal specimen surgery (LAP group). The general data of the patients were matched by the propensity score matching (PSM) method 1:1. Thirty-one pairs of cases were successfully matched, and the intraoperative and postoperative data were analysed.After PSM, the baseline data were balanced between the two groups. A total of 62 patients in the two groups were successfully operated without conversion. There were no significant differences in intraoperative blood loss, lymph node dissection, sputum tumour cell positive rate, bacterial culture positive rate, postoperative follow-up and postoperative pelvic floor function evaluation (P 0.05). Neither tumour cells nor bacteria were detected in the rinse solution at the start of the operation. Compared with the LAP group, the incidence of postoperative complications was lower in the NOSES group (6.4% vs. 29.0%, P = 0.006), and the gastrointestinal function recovery time was shorter (2.58 ± 0.92 vs. 3.42 ± 0.92, P = 0.001), postoperative hospital stay was shorter (6.68 ± 1.47 vs. 9.58 ± 2.22, P 0.001), postoperative pain score was lower (postoperative day 1: 2.35 ± 1.52 vs. 4.87 ± 1.50; postoperative day 3: 1.81 ± 1.11 vs. 4.00 ± 1.18; postoperative day 5: 1.45 ± 1.00 vs. 2.97 ± 1.17; P 0.001), additional analgesic drug use rate was lower (12.9% vs. 61.3%, P 0.001), and patients were more satisfied with the appearance of the abdominal wall after surgery (100% vs. 23.6%, P 0.001).This study used PSM to remove confounding factors and retrospectively analysed the short-term efficacy of transvaginal specimens for laparoscopic right colon cancer radical resection. The results showed that the laparoscopic right colon cancer radical resection was satisfactory, ensuring sterility. At the same time, there is a clear advantage in reducing postoperative pain, shortening postoperative hospital stays, reducing the incidence of postoperative complications, and improving the appearance of the abdominal wall.

Chronic myeloid leukemia (CML) and Non-Hodgkin Lymphoma (NHL) are two different origins of hematological malignancies, which rarely occur at the same time. Moreover, NHL secondary to CML is common in T cell lymphoma, while NHL of B cell origin is rare. Since 1999, only 22 cases with B cell lymphoma have been reported, of which 4 cases have diffuse large B-cell lymphoma (DLBCL). The lesions of DLBCL were in lymph node, liver, jejunum, and soft palate. To our knowledge, it has no report for the primary gastric DLBCL (PG-DLBCL) occurring in CML. Here we reported a 63-year-old man of chronic phase (CP) CML associated with PG-DLBCL. The patient was diagnosed with CML nearly eight years ago and was treated with imatinib and nilotinib successively. However, gastroscopy found malignant lesions in the patient’s stomach in March 2018, and the masses were diagnosed as PG-DLBCL. Subsequently, with the treatment of the RCOP + lenalidomide regimen chemotherapy for 3 cycles, the patient achieved nearly complete remission (CR).

Anaerobic ammonium oxidation (Anammox) is a cost-effective process for treating highly nitrogenous wastewater. However, the fate of organic nitrogen during Anammox treatment is still unclear, which limits its practical application. In this work, the changes in the quality of dissolved organic nitrogen (DON) in coal liquefaction wastewater (CLW) during Anammox were studied in relation to its chemical composition, which was determined by Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). The molecular-level characterization of extracellular polymeric substances (EPS) in the Anammox sludge is also reported for the first time in this paper. The relative contribution of N-containing compounds to the total dissolved organic matter (DOM) determined by summating the normalized intensities exceeded 30%, highlighting the complexity of the nitrogenous compounds in the influent. Additionally, Anammox appeared to be better suited to removing DON compounds with fewer carbonyl or carboxyl groups, more aromatic structures, and higher oxidative properties. Lignin-like substances were verified as the predominant component of N-containing compounds in Anammox EPS, followed by protein and substances with condensed aromatic structures. DON compounds with higher degrees of saturation, lower molecular weight, and higher lignin-like properties were more prone to absorption by Anammox EPS. A series of microbe-mediated pathways were demonstrated to be responsible for DON biodegradation, which revealed the organic and inorganic nitrogen removal mechanisms in the Anammox reactor. The obtained results provide great support to the ongoing efforts to optimize the Anammox process. Keywords: Fourier-transform ion cyclotron resonance, Wastewater, Dissolved organic nitrogen, Anammox, Extracellular polymeric substances

ObjectiveTransverse island pedicle flap (TIPF) plus transected urethral plate-preserving urethroplasty is increasingly used for treatment of severe hypospadias. We aimed to reduce the occurrence of urethral strictures in patients undergoing such procedures.MethodsSixty-five patients with severe hypospadias were enrolled. Thirty-two patients underwent onlay-tube-onlay urethroplasty (Group A), and 33 patients underwent modified Duplay urethroplasty (Group B). Postoperative complications were recorded, including fistulas, urethral strictures, and diverticula.ResultsThree patients (9.4%) in Group A and 10 patients (30.3%) in group B had urethrocutaneous fistulas. Three patients (9.4%) in Group A and 0 patients (0%) in Group B had urethral strictures. No patient in the two groups had symptoms of diverticulum or penile chordee. The results of uroflowmetry were better in Group B than Group A, when comparing uroflow patterns.ConclusionsTIPF plus transected urethral plate-preserving urethroplasty can lower the occurrence of stricture, which is a challenging complication. The occurrence of stricture was lower in patients who underwent modified Duplay urethroplasty, and neourethral function and quality were better in these patient. Thus, this modified procedure can be used for treatment of severe hypospadias.

BACKGROUND Urinary tract infection (UTI) is common in children. The purpose of this retrospective study was to determine the various risk factors that usually affect the prognosis of UTI in children diagnosed with the disease. METHODS In the present retrospective study, we enrolled all pediatric patients diagnosed with UTI and hospitalized between 1 January 2013 and 31 July 2016 at Nanjing Children's Hospital. We then collected all the relevant patient clinical demographics and characteristics. RESULTS The study involved 2,092 pediatric patients diagnosed with UTI. On logistic regression analysis, factors that could affect the prognosis of pediatric UTI were complications, hospitalization, intensive care unit (ICU) admission, type of UTI, urine culture results, blood lymphocytes, urine nitrites (NIT) and antibiotics (unstandardized coefficients, 0.06