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Kebing Lv,1,* Xiaoye Cheng,1– 3,* Yulan Zhou,1– 3 Min Yu,1– 3 Shixuan Wang,1– 3 Huimin Shen,1 Fei Li1– 3 1Center of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Jiangxi Clinical Research Center for Hematologic Disease, Nanchang, People’s Republic of China; 3Institute of Lymphoma and Myeloma, Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei Li, Email ndyfy01238@ncu.edu.cnBackground: Hemophagocytic lymphohistiocytosis (HLH) patients who need intensive care usually have multiple organ failure and poor prognosis. However, the clinical characteristics, therapeutic efficacy and outcome in these critically ill HLH patients have remained unclear.Methods: We performed a retrospective study of 50 critically ill HLH patients from September 2013 to October 2022. Patients’ information was collected, and the overall survival rate was estimated.Results: Fifty HLH patients need intensive care, and the median sequential organ failure assessment (SOFA) score was 8. 66.00% patients had septic shock, 60.00% had disseminated intravascular coagulation (DIC) and 56.00% had acute respiratory distress syndrome (ARDS). 64.00% patients needed vasoactive drugs, 60.00% needed invasive or non-invasive positive pressure mechanical ventilation, and 12.00% needed continuous renal replacement therapy (CRRT). Among 18 patients received the etoposide-based regimens, the median time for 17 patients to remove ECG monitoring was 13 days (4– 30 days); the median time to remove respiratory support in 10 patients was 8.5 days (4– 21 days); the median time for 5 patient to convert from dominant DIC to non-dominant DIC was 4 days (1– 14 days) and the median time for 6 patients to stop using vasoactive drugs was 10 days (2– 14 days). After 4 weeks of treatment, 7 patients were evaluated as NR, 6 achieved PR, and 5 could not be e

Peiying Fu,* Ling Zhang,* Ting Zhou, Shixuan Wang, Ronghua Liu Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ronghua Liu, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Anv., Wuhan, Hubei, 430030, People’s Republic of China, Tel/Fax +86-27-83663078, Email Liuzhu38@126.comObjective: Cesarean scar pregnancy (CSP) is an uncommon form of ectopic pregnancy that carries the risk of severe bleeding. To date, there has not been a universally accepted classification and treatment strategy. We performed this study to establish a risk scoring system and new CSP classification system for CSP and evaluate its efficacy.Methods: A total of five groups were generated based on different methods of treatment, and the factors that increase the risk of intraoperative bleeding were examined in our center from 2013 to 2018. The construction of a risk scoring system in this study was based on the use of the chi-square test and multivariate logistic regression analysis. To determine the appropriate cutoff scores, receiver operating characteristic (ROC) curves and the area under the curve (AUC) were generated.Results: We identified the main high-risk factors for excessive intraoperative hemorrhage during CSP surgery through univariate and multivariate analyses. Within this investigation, the risk factors included gestational sac location and gestational sac diameter. Through analysis, an optimal cutoff score of 3 was determined, and the area under the ROC curve was calculated to be 0.8113 (95% CI=0.7696– 0.8531). A score ranging from 0– 3 was classified as low risk, while a score ranging from 5– 7 was classified as high risk. Additionally, a new classification system for CSP has been esta

Peiying Fu, Ting Zhou, Pengfei Cui, Wenwen Wang, Shixuan Wang, Ronghua Liu Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Ronghua Liu, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Anv, Wuhan, Hubei, 430030, People’s Republic of China, Tel/Fax +86 27 83663078, Email Liuzhu38@126.comObjective: Cesarean scar pregnancy (CSP) can have catastrophic consequences, but a standardized diagnosis and treatment for CSP are lacking. At least 10 different treatments are currently available, further confusing treatment selection. The aim of this study was to compare the outcomes of using laparotomy or laparoscopy to treat CSP.Methods: We reviewed data from 935 patients with suspected CSP from 1 January 2013 to 31 December 2018. A total of 278 patients were included in the study, of whom 121 were treated with laparoscopy and 157 were treated with laparotomy. We compared and analyzed the characteristics of laparoscopic and open surgeries for treating CSP cases and the advantages and disadvantages of different vascular pretreatments.Results: Intraoperative bleeding, the transfusion rate, total days of hospitalization and postoperative hospital length of stay were lower with laparoscopy than laparotomy (P < 0.05). There was no difference in the factors (beta human chorionic gonadotropin [β-HCG] decrease, reoperation rate and tissue residues) closely related to the success of the surgery in the two groups. Furthermore, we used different blood vessel pretreatments among patients. The rates of tissue residue, reoperation and intraoperative blood transfusion were lower in patients with temporary vascular occlusion than in patients with permanent vascular occlusion.Conclusion: This study revealed that laparoscopic surgery is superior to laparotomic surgery fo

Multimodal therapy is attracting increasing attention to improve tumor treatment efficacy, but generally requires various complicated ingredients combined within one theranostic system to achieve multiple functions. Herein, a multifunctional theranostic nanoplatform based on a single aggregation-induced-emission luminogen (AIEgen), DDTB, is designed to integrate near-infrared (NIR) fluorescence, photothermal, photodynamic, and immunological effects. Intravenously injected AIEgen-based nanoparticles can efficiently accumulate in tumors with NIR fluorescence to provide preoperative diagnosis. Most of the tumors are excised under intraoperative fluorescence navigation, whereafter, some microscopic residual tumors are completely ablated by photodynamic and photothermal therapies for maximally killing the tumor cells and tissues. Up to 90% of the survival rate can be achieved by this synergistic image-guided surgery and photodynamic and photothermal therapies. Importantly, the nanoparticles-mediated photothermal/photodynamic therapy plus programmed death-ligand 1 antibody significantly induce tumor elimination by enhancing the effect of immunotherapy. This theranostic strategy on the basis of a single AIEgen significantly improves the survival of cancer mice with maximized therapeutic outcomes, and holds great promise for clinical cancer treatment. © 2021 Wiley-VCH GmbH

Biao Chen,1 Xiaoqi Dong,2 Xiyuan Dong,1 Quan Wang,2 Meng Wu,1 Jun Wu,2 Xiaoding Lou,2 Fan Xia,2 Wenwen Wang,1 Jun Dai,1 Shixuan Wang1 1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Engineering Research Center of Nano-Geomaterials of the Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, People’s Republic of ChinaCorrespondence: Wenwen Wang; Jun Dai 1095 Jiefang Avenue, Wuhan, Hubei, People’s Republic of ChinaTel +86-0276868907; +86-0276868907Email petrawang@163.com; dj_hust1987@sina.comObject: High targeting and efficient cytotoxicity toward tumor cells endow NPs excellent anti-tumor activity. Herein, a peptide polymer possessing dual-targeting ability and double therapeutic activity was developed and named TGMF, which can form NPs through self-assembly. It is composed of four functional modules: 1) Active targeting peptide TMTP1 (T) deliver NPs to tumors specifically; 2) Therapeutic peptide GO-203 (G), which can significantly inhibit tumor growth by disrupting the redox balance in cells; 3) A passively targeted enzyme-responsive peptide PLGLGA (M), which can be cleaved specifically by metalloproteinase-2 (MMP-2) highly expressed in the tumor microenvironment (TME); and 4) Hexadecyl (F), which has strong hydrophobicity, can promote the self-assembly of TGMF NPs.Methods: Five modular peptide probes, namely, TGF, TMF, TGM, GMF, and TGMF were synthesized and self-assembled into NPs in solution. The characterization, enzyme reactivity, and cytotoxicity of NPs were evaluated in vitro, and the pharmacokinetics, bio-distribution, anti-tumor activity of NPs were investigated in vivo. In addition, transcriptome sequencing identified the intracellular signaling pathway-related genes involved in the anti-tumor effect of TGMF.Results: Upon enzyme cleavage, two

Zhilan Chen,1,2,* Kecheng Huang,1,* Zhiyong Lu,1,3 Song Deng,1,4 Jiaqiang Xiong,1 Jia Huang,1 Xiong Li,5 Fangxu Tang,1 Zhihao Wang,6 Haiying Sun,1 Lin Wang,1 Shasha Zhou,1 Xiaoli Wang,1 Yao Jia,1 Ting Hu,1 Juan Gui,7 Dongyi Wan,1 Ding Ma,1 Shuang Li,1 Shixuan Wang11Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Techonology, Wuhan, 2Department of Obstetrics and Gynecology, Wuhan General Hospital of Guangzhou Military Command, Wuhan, 3Hubei Key Laboratory of Embryonic Stem Cell Research, Tai-He Hospital, Hubei University of Medicine, Shiyan, Hubei, 4Department of Obstetrics and Gynecology, University Hospital of Hubei University for Nationalities, Enshi, Hubei, 5Department of Obstetrics and Gynecology, Wuhan Central Hospital, Wuhan, 6Department of Pathology and Pathophysiology, Key Laboratory of Ministry of Education of China for Neurological Disorders, Huazhong University of Science and Techonology, Wuhan, 7Department of Obstetrics and Gynecology, Renmin Hospital, Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workAbstract: The purpose of this study was to identify risk factors in patients with surgically treated node-positive IB1-IIB cervical cancer and to establish a risk model for disease-free survival (DFS) and overall survival (OS). A total of 170 patients who underwent radical hysterectomy and bilateral pelvic lymphadenectomy as primary treatment for node-positive International Federation of Gynaecology and Obstetrics (FIGO) stage IB1-IIB cervical cancer from January 2002 to December 2008 were retrospectively analyzed. Five published risk models were evaluated in this population. The variables, including common iliac lymph node metastasis and parametrial invasion, were independent predictors of outcome in a multivariate analysis using a Cox regression model. Three distinct prognostic groups (low, intermediate, and high risk) we

Human papillomavirus (HPV) integration is a key genetic event in cervical carcinogenesis1. By conducting whole-genome sequencing and high-throughput viral integration detection, we identified 3,667 HPV integration breakpoints in 26 cervical intraepithelial neoplasias, 104 cervical carcinomas and five cell lines. Beyond recalculating frequencies for the previously reported frequent integration sites POU5F1B (9.7%), FHIT (8.7%), KLF12 (7.8%), KLF5 (6.8%), LRP1B (5.8%) and LEPREL1 (4.9%), we discovered new hot spots HMGA2 (7.8%), DLG2 (4.9%) and SEMA3D (4.9%). Protein expression from FHIT and LRP1B was downregulated when HPV integrated in their introns. Protein expression from MYC and HMGA2 was elevated when HPV integrated into flanking regions. Moreover, microhomologous sequence between the human and HPV genomes was significantly enriched near integration breakpoints, indicating that fusion between viral and human DNA may have occurred by microhomology-mediated DNA repair pathways2. Our data provide insights into HPV integration-driven cervical carcinogenesis.

Lei Zhang,1,2,* Xuan Xu,1,* Ruhao Yang,1,* Jingwen Chen,1 Shixuan Wang,5 Junqin Yang,3 Xudong Xiang,1 Zhibiao He,1 Yu Zhao,4 Zheng Dong,2,5 Dongshan Zhang11Department of Emergency Medicine, 2Department of Nephrology, 3Department of Minimally Invasive Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Nephrology, Harbin First Hospital, Harbin, Heilongjiang, People’s Republic of China; 5Department of Cellular Biology and Anatomy, Medical College of Georgia at Georgia Regents University and Charlie Norwood VA Medical Center, Augusta, GA, USA *Co-first authors in this studyAbstract: Recent studies have demonstrated that paclitaxel might inhibit renal fibrosis. However, the underlying molecular mechanism remains unclear. In this study, we hypothesized that low-dose paclitaxel may block the STAT3 (signal transducer and activator of transcription 3) signaling to attenuate fibrosis in a mouse model with unilateral ureteral obstruction. Both NRK-49F cells and mice with unilateral ureteral obstruction were treated with paclitaxel. The results showed that paclitaxel treatment resulted in a dose- and time-dependent decrease in tyrosine-phosphorylated STAT3, and inhibited the expression of fibronectin, alpha-smooth muscle actin (α-SMA), and collagen I in cultured NRK-49F cells. S3I-201, an STAT3 inhibitor, also suppressed the expression of fibronectin, α-SMA, and collagen I in cultured NRK-49F cells. Mechanistically, paclitaxel treatment blocked the STAT3 activity by disrupting the association of STAT3 with tubulin and inhibiting STAT3 nucleus translocation. Furthermore, paclitaxel also ameliorated renal fibrosis by down-regulating the expression of fibronectin, α-SMA, and collagen I, and suppressed the infiltration of macrophages and production of TNF-α, IL-1β, TGF-β, and ICAM-1 (intercellular adhesion molecule 1) by inhibition of ST

Dongshan Zhang,1,2 Ruhao Yang,1 Shixuan Wang,2 Zheng Dong1,2 1Departments of Emergency Medicine and Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University and Charlie Norwood VA Medical Center, Augusta, GA, USA Abstract: Paclitaxel (Taxol), one of the most important anticancer drugs, has been used for therapy of different types of cancers. Mechanistically, paclitaxel arrests cell cycle and induces cell death by stabilizing microtubules and interfering with microtubule disassembly in cell division. Recently, it has been found that low-dose paclitaxel seems promising in treating non-cancer diseases, such as skin disorders, renal and hepatic fibrosis, inflammation, axon regeneration, limb salvage, and coronary artery restenosis. Future studies need to understand the mechanisms underlying these effects in order to design therapies with specificity. Keywords: taxol inflammation, fibrosis, coronary artery restenosis, limb salvage, kidney

Recent years have witnessed companies abandon traditional open-loop supply chain structures in favour of closed-loop variants, in a bid to mitigate environmental impacts and exploit economic opportunities. Central to the closed-loop paradigm is remanufacturing: the restoration of used products to useful life. While this operational model has huge potential to extend product life-cycles, the collection and recovery processes diminish the effectiveness of existing control mechanisms for open-loop systems. We systematically review the literature in the field of closed-loop supply chain dynamics, which explores the time-varying interactions of material and information flows in the different elements of remanufacturing supply chains. We supplement this with further reviews of what we call the three ‘pillars’ of such systems, i.e. forecasting, collection, and inventory and production control. This provides us with an interdisciplinary lens to investigate how a ‘boomerang’ effect (i.e. sale, consumption, and return processes) impacts on the behaviour of the closed-loop system and to understand how it can be controlled. To facilitate this, we contrast closed-loop supply chain dynamics research to the well-developed research in each pillar; explore how different disciplines have accommodated the supply, process, demand, and control uncertainties; and provide insights for future research on the dynamics of remanufacturing systems.

Recent years have witnessed companies abandon traditional open-loop supply chain structures in favour of closed-loop variants, in a bid to mitigate environmental impacts and exploit economic opportunities. Central to the closed-loop paradigm is remanufacturing: the restoration of used products to useful life. While this operational model has huge potential to extend product life-cycles, the collection and recovery processes diminish the effectiveness of existing control mechanisms for open-loop systems. We systematically review the literature in the field of closed-loop supply chain dynamics, which explores the time-varying interactions of material and information flows in the different elements of remanufacturing supply chains. We supplement this with further reviews of what we call the three ‘pillars’ of such systems, i.e. forecasting, collection, and inventory and production control. This provides us with an interdisciplinary lens to investigate how a ‘boomerang’ effect (i.e. sale, consumption, and return processes) impacts on the behaviour of the closed-loop system and to understand how it can be controlled. To facilitate this, we contrast closed-loop supply chain dynamics research to the well-developed research in each pillar; explore how different disciplines have accommodated the supply, process, demand, and control uncertainties; and provide insights for future research on the dynamics of remanufacturing systems.

Over the last few decades, reliability analysis has gained more and more attention as it can be beneficial in lowering the maintenance cost. Time between failures (TBF) is an essential topic in reliability analysis. If the TBF can be accurately predicted, preventive maintenance can be scheduled in advance in order to avoid critical failures. The purpose of this paper is to research the TBF using deep learning techniques. Deep learning, as a tool capable of capturing the highly complex and non-linearly patterns, can be a useful tool for TBF prediction. The general principle of how to design deep learning model was introduced. By using a sizeable amount of automobile TBF dataset, we conduct an experiential study on TBF prediction by deep learning and several data mining approaches. The empirical results show the merits of deep learning in performance but comes with cost of high computational load.