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Wenhui Guo,1,* Xiang Lian,2,* Hong Li,2 Lushun Jiang,1 Yingsha Chen,3 Ping Shen,1 Wei Yu1 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Infectious Diseases, The Affiliated Xiangshan Hospital of Wenzhou Medical University; Xiangshan First People’s Hospital Medical and Health Group; Ningbo Fourth Hospital, Ningbo, People’s Republic of China; 3Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ping Shen; Wei Yu, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Tel/Fax +86 571 87236421, Email shenping123451@126.com; wyu@zju.edu.cnObjective: To evaluate the characteristics of immunocytes and cytokines associated with bloodstream infections (BSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP).Methods: Patients with BSIs K. pneumoniae (BSIs-Kpn) were enrolled in our hospital between 2015 and 2022. Whole blood and serum samples were collected on the first day after diagnosis. Immunocytes and cytokines profiles were assessed using multicolor flow cytometry and multiplex immunoassays, respectively. The test cytokines included interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A.Results: A total of 313 patients had BSIs-Kpn, including 145 with CRKP, 43 with extended-spectrum β-lactamases (ESBL) producing Kpn (ESBL-Kpn) and 125 with non-CRKP or non-ESBL-Kpn (susceptible Kpn, S-Kpn). Absolute number of leukomonocyte (CD45+) in CRKP, ESBL-Kpn and S-Kpn were 280.0 (138.0– 523.0) cells/μL, 354.5 (150.3– 737.3) cells/μL, and 637.0 (245.0– 996.5) cells/μL, respectively. Compared with S-Kpn group, the absolute numbers of leukomonocyte (including T lymphocytes, B lymphocytes and natural killer cells) in patients with CRKP were significantly lower than that in patients with S-Kpn (P

Feng Zhang, Rongfeng Cheng, Xiuqiao Yang, Xiaohui Lian, Ping Wen Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, People’s Republic of ChinaCorrespondence: Ping Wen, Department of Science and Education, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, People’s Republic of China, Email kjkwenping@smu.edu.cnPurpose: To assess the pain relief effects and safety of transitional therapy (TT) in the treatment of posterior teeth of pregnant women with symptomatic irreversible pulpitis and symptomatic apical periodontitis.Methods: A prospective cohort clinical study was conducted in the Department of Stomatology at Shenzhen Maternity & Child Healthcare Hospital, China, from January 2017 to December 2019. We enrolled 62 pregnant women with acute dental pain caused by posterior teeth with symptomatic irreversible pulpitis or symptomatic apical periodontitis. Among the 62 participants, 34 received TT, and 28 chose nontreatment during pregnancy. We evaluated the pain relief with the verbal numerical rating scale (VNRS) scores of pain perception in the clinical study, as well as the anti-bacterial medicament filling conditions of canals of in vitro models. Moreover, we investigated the safety outcomes, such as gestational age, neonatal head circumstance, birth weight, and body length.Results: The VNRS scores of the participants treated with TT were significantly lower than those of the nontreatment group 2 days after treatment (P< 0.001). TT treated pregnant women experienced significantly more pain decreases in VNRS scores than their counterparts(P< 0.05). The optimal anti-bacterial medicament filling conditions of canals of in vitro models by TT method were comparable with those of canals instrumented with traditional RCT method. Moreover, no significant differences of safety outcomes were observed between pregnant women of these two groups.Conclusion: The transitional therapy is efficient in alleviating acute dental pain of posterior teeth of pregnant women with symptomatic irreversible pulpitis and symptomatic apical periodontitis, and maintaining painless chains throughout pregnancy with no adverse effects on neonatal birth outcomes.Keywords: symptomatic irreversible pulpitis, symptomatic apical periodontitis, transitional therapy, root canal infection, pregnancy, neonatal outcome

Yingna Chen,1 Jieya Lu,2 Zhihao Xie,1 Jialing Tang,1 Xuejiao Lian,1 Xiuwen Li1 1School of Pharmacy, School of Medicine, Changzhou University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Nephrology, Yixing Hospital of Traditional Chinese Medicine, Yixing, Jiangsu, People’s Republic of ChinaCorrespondence: Yingna Chen, School of Pharmacy, School of Medicine, Changzhou University, No. 21, Lake Gehu Road, Wujin District, Changzhou, Jiangsu, People’s Republic of China, Tel +86-13813661630, Email chenyingna@cczu.edu.cn Jieya Lu, Department of Nephrology, Yixing Hospital of Traditional Chinese Medicine, 128 Yangquan East Road, Yicheng Street, Yixing, Jiangsu, People’s Republic of China, Tel +86-15906153777, Email ljy7011645@sina.comBackground: Tumor microenvironment has attracted more and more attention in oncology. Alisol B23 acetate (AB23A) inhibits the proliferation of tumor cells including non-small cell lung cancer (NSCLC) cells. However, whether AB23A plays a role in the tumor microenvironment of NSCLC still remains obscure.Methods: After THP-1 cells were polarized to M0 type by PMA, M0 macrophages were differentiated into M1 by LPS and IFNγ, and were differentiated into M2 by IL-4 and IL-13. The differentiation of THP-1 cells was detected by flow cytometry. After AB23A was given to macrophage RT-qPCR and ELISA detected the expressions of IL-6, IL-1β, IL-10 and TGF-β. Western blot and RT-qPCR detected the expressions of CD11b and CD18 at both mRNA and protein levels. Lung cancer cell A549 cells were induced by above related macrophage culture medium. Cell proliferation was detected by CCK-8. Tunel, wound healing and Transwell detected the apoptotic, migration and invasion capabilities. Next, M0 and M1-type macrophages were cultured in the cell culture medium of conventional A549 cells, to which AB23A was added. Subsequently, cell differentiation and inflammatory response were measured. Finally, the expression of CD18 in A549 cells was knocked down to construct NSCLC tumor-bearing mice and AB23A was applied for intragastric administration. Immunohistochemistry detected the polarization of macrophages in tumor tissues. Western blot detected the expressions of CD11b, CD18, invasion-, migration- and apoptosis-related proteins.Results: AB23A promoted the polarization of macrophages towards M1, thus promoting the apoptosis and inhibiting the invasion and migration of A549 cells. The tumor cell culture medium induced M0 macrophages to M2, while AB23A reversed this effect. AB23A targeted CD11b/CD18 and improved the polarization of macrophages, thereby affecting tumor invasion, migration and apoptosis.Conclusion: AB23A affected the polarization of tumor-associated macrophages through the targeted regulation of CD11b/CD18, thus inhibiting the development of lung cancer.Keywords: Alisol B23 acetate, lung cancer, CD11b/CD18, tumor microenvironment

Xue Lian,1,2 Dakui Cao,2 Xun Hu,3 Weiqiang Mo,2 Xiujuan Yao,4 Juanfen Mo,5 Haiqin Wang1,2 1Department of Respiratory Medicine, Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China; 2Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People’s Republic of China; 3Department of Thoracic Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People’s Republic of China; 4Department of Pathology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People’s Republic of China; 5The Key Laboratory, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People’s Republic of ChinaCorrespondence: Haiqin Wang, Department of Respiratory Medicine, The Second Hospital of Jiaxing, 1518 Huanchen North Road, Jiaxing, Zhejiang, 314000, People’s Republic of China, Email w_haiqin@163.comBackground: Lung adenocarcinoma (LUAD) is a life-threatening disease worldwide with a high mortality rate. The early diagnosis of LUAD is crucial for improving subsequent treatment and prognosis. However, biomarkers for early detection remain a clinical challenge in LUAD. Here, we aimed to develop circular RNAs (circRNAs) in circulating plasma from LUAD patients as valuable diagnostic biomarkers in LUAD.Methods: CircRNA expression was determined by circRNA microarray in three pairs of LUAD tumour tissues and patient-matched normal lung tissues. Hsa_circ_101555 and hsa_circ_008068 were selected as potential biomarkers in LUAD tissues and plasma by RT–PCR, respectively. The diagnostic value was analysed by the area under the curve (AUC) and the receiver operating characteristic (ROC) test.Results: Our results showed that 6261 circRNAs were upregulated and 7238 circRNAs were downregulated in LUAD tumour tissues compared with patient-matched normal lung tissues. Hsa_circ_101555 and hsa_circ_008068 were filtered as biomarkers for early-stage LUAD. Q-PCR results showed that hsa_circ_101555 and hsa_circ_008068 were significantly upregulated in both LUAD cancer tissues and circulating plasma. Hsa_circ_101555 and hsa_circ_008068 were positively associated with tumour differentiation, tumour size and CEA (P< 0.05). The ROC analysis showed that hsa_circ_101555 and hsa_circ_008068 had a better diagnostic potential compared to the traditional biomarkers (CEA, SCC, CYFRA21-1) in the detection of early-stage LUAD.Conclusion: The circular RNAs hsa_circ_101555 and hsa_circ_008068 could serve as novel diagnostic biomarkers for early-stage LUAD.Keywords: circRNAs, lung adenocarcinoma, diagnostic biomarker, circ101555

Sijie Tang,1,2 Xueqi Lian,1 Huiying Cheng,1 Jiaqian Guo,1 Daguang Ni,1 Can Huang,1 Xiang Gu,2 Hong Meng,3 Jiajia Jiang,1 Xiaohua Li1,4,5 1The Aoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, 215600, People’s Republic of China; 2Department of Urology, the Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, 215600, People’s Republic of China; 3Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Detroit, MI, 48201, USA; 4The Laboratory of Clinical Genomics, Hefei KingMed Diagnostics Ltd, Hefei, 230088, People’s Republic of China; 5National Center for Gene Testing Technology Application & Demonstration (Anhui), Hefei, 230088, People’s Republic of ChinaCorrespondence: Xiaohua Li; Jiajia JiangThe Aoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu University, 279 Jingang Blvd., Zhangjiagang, Suzhou, 215600, People’s Republic of ChinaEmail joshua28li@163.com; 2111913004@stmail.ujs.edu.cnPurpose: To study bacterial lipopolysaccharide (LPS)-induced cancer stem-like transformation and to investigate the inhibitory effect of Trichostatin A (TSA) on the malignant transformation through targeting p-Stat3 signaling.Methods: 2D, 3D, and serum-free suspension culture system were used to study LPS-induced malignant transformation in series malignant grade of prostate cancer (PCa) epithelial cells. Flow cytometry assay and RT-PCR were utilized to evaluate the CD44+CD133+ stem cell population, the expression of inflammatory cytokines and series tumor stemness biomarkers. Meanwhile, Western blot was used to analyze the alteration of cell signaling associated-molecules by treatment with TSA, an original antifungal antibiotic and a panel inhibitor of histone deacetylase.Results: Our study found that LPS promoted the migration, invasion and stem-like tumoroshpere forming in multiple PCa cell lines including DU145, PC3, 22RV1, LNCaP. LPS also enriched CD44+CD133+ stem cell population and increased the expression of series tumor stemness biomarkers (e.g., CD44, CD133, SOX-2, α-intergrin, Nestin, etc.). TSA was found to prevent tumor cell migration, invasion and tumorosphere forming in DU145 and PC3 cells with increasing tumor suppressive Maspin and reducing both phosphorylation of Stat3 (p-Stat3) and pro-oncogene c-Myc expression in LPS-treated DU145 cells. Furthermore, blocking Stat3 signaling pathway by treatment with TSA and/or small molecule compound Stattic of an p-Stat3 inhibitor effectively abrogated LPS-induced tumorosphere forming with decrease of IL-6, IL-8 and stemness biomarkers CD44, SOX-2 expression.Conclusion: Our data demonstrated that the inflammatory agent of bacterial LPS augmented malignant transformation and promoted the cancerous stemness in PCa epithelial cells. TSA could prevent, at least in part, the LPS-induced malignant transformation by targeting p-Stat3/c-Myc signaling pathway and reducing inflammatory IL-6, IL-8. In addition, the assay of LPS-induced tumorosphere forming could serve as a simple and an easy handling method for targeting cancer stem cells drug screening in vitro in clinical practice.Keywords: tumorosphere forming, prostate cancer, bacterial lipopolysaccharide, epithelial malignant transformation, cancer stemness

Guanglan Li,1,2 Xingji Lian,1 Wenke Hao,1 Wenxue Hu1 1Department of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, 510080, People’s Republic of China; 2Shantou University Medical College, Shantou, 515041, People’s Republic of ChinaCorrespondence: Wenxue Hu; Wenke HaoDepartment of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, 106th, Zhongshan Road II, Guangzhou, 510080, People’s Republic of ChinaTel +86 20-83827812-70811Email wuleihu@126.com; hwk1964@sina.comIntroduction: Older people in community are susceptible to acute kidney injury (AKI) and hemodialysis is the most important supportive measure used in the management of severe AKI. This study aims to investigate the clinical characteristics, outcomes and risk factors for mortality in older patients with dialysis-receiving-community-acquired AKI (CA-AKI).Methods: A total of 1953 CA-AKI patients aged 65 years old and above were recruited from 2013 to 2016. Among which, 200 patients received hemodialysis. Clinical characteristics, outcomes, suspected nephrotoxic drug use after CA-AKI and risk factors for mortality in older CA-AKI patients with dialysis were analyzed.Results: The percentage of CA-AKI patients receiving hemodialysis was 10.2%. Compared with non-dialysis patients, dialysis-receiving patients had more comorbidity, and worse renal function. The types of suspected nephrotoxic drugs used in dialysis patients were more than those in non-dialysis patients. Moreover, dialysis-receiving patients had worse outcomes, including complete recovery of renal function (42.0% vs 71.6%), intensive care unit (ICU) (69.0% vs 15.3%) transfer and in-hospital mortality (50.5% vs 5.6%) (P< 0.01). Age, moderate/severe liver disease, beta lactam antibiotics, glycopeptide antibiotics, antifungal agents, drugs for anti-heart failure, category of suspected nephrotoxic drugs, hyperkalemia, increased leucocyte count, ICU transfer, multiple organ dysfunction (MODS), cardiogenic shock and cardio-pulmonary resuscitation (CPR) were risk factors for mortality by univariate logistic regression analysis. After adjusting for confounding factors, the independent risk factors were glycopeptide antibiotics, drugs for anti-heart failure, ICU transfer, MODS and CPR.Conclusion: The percentage of older CA-AKI patients receiving dialysis was high, and these patients had more comorbidity and worse prognosis. Glycopeptide antibiotics, drugs for anti-heart failure, ICU transfer, MODS and CPR were independent risk factors for mortality.Keywords: community-acquired acute kidney injury, older people, dialysis, outcome, risk factors for mortality

Meng Jin,1,2,&ast; Xia Liu,1,&ast; Jiabin Ma,1,&ast; Xiansong Sun,1 Hongnan Zhen,1 Jing Shen,1 Zhikai Liu,1 Xin Lian,1 Zheng Miao,1 Ke Hu,1 Xiaorong Hou,1 Fuquan Zhang1 1Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaorong Hou; Fuquan ZhangDepartment of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel +86-10-6915-5482Fax +86-10-6915-5483Email hxr_pumch@163.com; zhangfuquan3@126.comPurpose: In the management of breast-conserving radiotherapy, computed tomography (CT) simulation is now commonly used to identify tumor bed while has difficulties defining precisely. We aimed to evaluate the impact of magnetic resonance (MR) and CT simulation on defining the postoperative tumor bed for breast-conserving radiotherapy in patients without the aid of surgical clips.Methods: From August 2018 to March 2019, twenty patients with T1-2N0M0 breast cancer at our institution were enrolled. All the patients underwent breast-conserving surgery without implantation of surgical clips and were prepared to receive radiotherapy. CT and MR images were acquired on the same day for each patient. Three radiation oncologists independently assigned cavity visualization score (CVS) and delineated the tumor bed based on first the CT then the MR images. Interobserver variability was assessed by volumes, generalized conformity index (CIgen) and the distance between the centers of mass (dCOM). Differences in mean values for parameters were tested by paired t-test or one-way analysis of variance, as appropriate.Results: First, the mean volumes of tumor bed derived from MR were 22%, 27% and 21% smaller than those based on CT images for each observer. In addition, the mean CIgen was significantly superior, and dCOM was smaller for MR than for CT images (CIgen: 0.59 vs 0.52, P= 0.008; dCOM: 1.30 cm vs 1.39 cm, P= 0.095). Moreover, the mean CVS was 3.23± 1.34 and 2.43± 0.92 for MR and CT images, respectively (P= 0.035). Last, a positive association was observed between the CVS and CIgen for both modalities (P< 0.01).Conclusion: Compared to CT, MR can improve the visualization of changes in the postoperative tumor bed. In addition, MR can yield a more precise definition of the tumor bed and improve the consistency of tumor bed contouring in patients without surgical clips.Keywords: breast cancer, radiotherapy, magnetic resonance simulation, target volume delineation

Chronic wounds and their treatment present a significant burden to patients and healthcare systems alike, with their management further complicated by bacterial infection. Historically, antibiotics have been deployed to prevent and treat infections, but the emergence of bacterial antimicrobial resistance and the frequent development of biofilms within the wound area necessitates the identification of novel treatment strategies for use within infected chronic wounds. Here, several non-antibiotic compounds, polyhexamethylene biguanide (PHMB), curcumin, retinol, polysorbate 40, ethanol, and D-α-tocopheryl polyethylene glycol succinate 1000 (TPGS) were screened for their antibacterial and antibiofilm capabilities. The minimum inhibitory concentration (MIC) and crystal violet (CV) biofilm clearance against two bacteria frequently associated with infected chronic wounds, Staphylococcus aureus and Pseudomonas aeruginosa, were determined. PHMB was observed to have highly effective antibacterial activity against both bacteria, but its ability to disperse biofilms at MIC levels was variable. Meanwhile, TPGS had limited inhibitory activity but demonstrated potent antibiofilm properties. The subsequent combination of these two compounds in a formulation resulted in a synergistic enhancement of their capability to kill both S. aureus and P. aeruginosa and disperse their biofilms. Collectively, this work highlights the utility of combinatory approaches to the treatment of infected chronic wounds where bacterial colonization and biofilm formation remains significant issues.

Wenxue Hu,* Xingji Lian,* Jieshan Lin, Yuanhan Chen, Yanhua Wu, Wei Liu, Feng Yu, Wenke Hao Department of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenke HaoDepartment of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, 106th, Zhongshan Road II, Guangzhou 510080, People’s Republic of ChinaTel + ± 8620-83827812-70811Email hwk1964@sina.comPurpose: Acute kidney injury (AKI) is a major health problem with poor prognosis. However, little is known about elderly community-acquired-AKI (CA-AKI). This study aimed to investigate the incidence, clinical characteristics, outcomes and use of suspected nephrotoxic medications after CA-AKI in the elderly.Materials and Methods: A total of 36,445 patients aged over 60 years were recruited from 2013 to 2016. Through an electronic database, we collected the demographic and medical history data, and admission lab results from all patients.Results: A total of 2371 patients with CA-AKI were identified. The incidence of CA-AKI was 26.03% in the elderly. The proportion of CA-AKI patients with chronic comorbidities and Charlson comorbidity index score were higher than that of non-AKI patients. After CA-AKI, the proportions of exposure to non-steroidal anti-inflammatory drugs (NSAIDs), iodine contrast agent, angiotensin converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) were significantly decreased (p < 0.001). However, the proportion of other possible nephrotoxic drugs (including aminoglycosides, glycopeptide antibiotics, antifungal agents, beta lactam antibiotics, diuretic, ferralia, adrenergic receptor agonists and drugs for cardiac insufficiency therapy) still increased after CA-AKI (p < 0.001). Compared with non-AKI patients, CA-AKI patients had higher percentage of cardiogenic shock, multiple organ failure, transferring to intensive care unit, cardio-pulmonary resuscitation, hemodialysis, and mortality (p < 0.001). Moreover, CA-AKI patients had worse prognosis when more kinds of suspected nephrotoxic drugs were used (p < 0.001).Conclusion: The incidence of CA-AKI in the elderly was high, with more complex chronic complications and poor clinical outcomes. The use of most suspected nephrotoxic drugs still increased and was associated with worse prognosis after CA-AKI.Keywords: acute kidney injury, community-acquired acute kidney injury, elderly, prognosis, nephrotoxic drug

Shuai Sun, Xin Lian, Xiaoliang Liu, Jiabin Ma, Xiaorong Hou, Fuquan Zhang, Ke Hu Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People’s Republic of ChinaCorrespondence: Fuquan ZhangDepartment of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing 100730, People’s Republic of ChinaTel +86-10-6915-5485Fax +86-10-65124875Email zhangfq@pumch.cnKe HuDepartment of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing 100730, People’s Republic of ChinaTel +86-10-69155482Fax +86-10-65124875Email huke8000@163.comObjective: To evaluate the prognostic factors and optimal management of cervical cancer patients with brain metastasis (BM).Materials and Methods: We retrospectively reviewed the medical records of 7098 consecutive patients with cervical cancer from January 2000 to December 2019. Data for a total of 24 BM patients with cervical cancer were analyzed retrospectively in the present study.Results: The incidence of BM from cervical cancer in our institution was 0.38%. The mean survival time was 7.2 months (median 6.2 months, 0.1– 21.2 months). In the univariate analysis, the histopathology of neuroendocrine cancer, 2018 FIGO stage, Karnofsky performance status (KPS) at BM diagnosis, and treatment strategy were identified to be significant prognostic indicators for the survival of patients with BM from cervical cancer. In the multivariate analysis, KPS, chemotherapy, and radiotherapy were independent prognostic factors for survival. Recursive partition analysis (RPA) appeared to be a better prognostic tool than the other prognosis scoring classification systems.Conclusion: When patients with BM from cervical cancer have good performance status and undergo comprehensive treatment, such as radiotherapy and chemotherapy, their survival time could be significantly prolonged. Patients with surgical indications may get better survival by postoperative radiotherapy and chemotherapy. Patients with BMs ≥ 3 may get better survival by whole-brain radiotherapy. But further studies are needed regarding the selection of surgical indications and radiotherapy modes. The prognosis scoring classification system for BM from cervical cancer needs to be improved.Keywords: cervical cancer, brain metastasis, prognostic factors

Jiabin Ma, Weiping Wang, Jing Shen, Xiaorong Hou, Xin Lian, Junfang Yan, Shuai Sun, Zheng Miao, Qingyu Meng, Ke Hu,* Fuquan Zhang* Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ke Hu; Fuquan Zhang Tel/Fax +86-10-69155482; +86-10-69155485Email huk@pumch.cn; zhangfuquan3@126.comObjective: To determine the toxicity and efficacy of radiotherapy for cervical cancer in patients with systemic lupus erythematosus (SLE).Methods: Medical records of patients with SLE who received radiation for cervical cancer from January 2011 to January 2019 were reviewed. For definitive radiotherapy, a dose of 50.4 Gy in 28 fractions was delivered by intensity-modulated radiation therapy (IMRT) combined with high-dose-rate brachytherapy of 28 to 30 Gy in 5 fractions. A dose of 45 to 50.4 Gy in 25– 28 fractions was delivered for postoperative radiation. All patients were in remission with or without a low dosage of prednisone or immunosuppressive medication. Survival data were analyzed with the Kaplan–Meier method. The incidence of severe toxicities among patients was compared with the chi-square test or Fisher’s exact test.Results: Twelve patients with SLE were included in this study. Definitive radiotherapy was delivered in 7 patients with FIGO (2009) stage II–III disease. Five patients with FIGO I disease received postoperative radiation. The median follow-up time was 22.1 months. The 3-year overall survival (OS) and 3-year progression-free survival (PFS) were 77.8% and 83.3%, respectively. One patient of definitive radiotherapy and one patient of postoperative radiation died due to distant metastasis of cervical cancer. Grade 3 or higher acute and chronic reactions occurred in 58.3% and 8.3% patients, respectively. Acute grade 3 or higher toxicity correlated with the presence of chemotherapy (p = 0.045).Conclusion: Modern radiotherapy for cervical cancer was well tolerated in SLE patients with remission and provided a favorable outcome.Keywords: systemic lupus erythematosus, SLE, cervical cancer, intensity-modulated radiation therapy, IMRT, radiotherapy, toxicity

Shuao Xiao,1,* Fan Feng,1,* Ni Liu,2,* Zhen Liu,1 Yinghao Guo,3 Xiao Lian,1 Hongwei Zhang1 1Division of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, Shaanxi, People’s Republic of China; 2Department of Anesthesiology, Weinan Central Hospital, Weinan 714000, Shaanxi, People’s Republic of China; 3Health Company, 92667 Army of PLA, Qingdao 266100, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongwei Zhang; Fan FengDivision of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 127 West Changle Road, Xi’an 710032, Shaanxi, People’s Republic of ChinaTel/Fax +86-029-84771531Email Zhanghwfmmu@126.com; surgeonfengfan@163.comObjective: The preoperative value of albumin level and albumin/globulin ratio (AGR) has been discovered to be a possibility for predicting gastric cancer. However, their predictive accuracy remains unknown. This study’s objective is to evaluate the predictive value of albumin, globulin and AGR in gastric cancer.Methods: A total of 3266 gastric cancer patients in our institution who underwent radical gastrectomy during the period from September 2008 to April 2015 were retrospectively analyzed. Levels of preoperative serum albumin and globulin were recorded. The optimal cut off points of albumin, globulin and AGR were calculated using X-tile software. The association of albumin and AGR with clinicopathological features and eventual prognosis was analyzed. The survival predictive accuracy and prognostic discriminatory ability among different variables were analyzed.Results: This study consisted of 2531 males (77.5%) and 735 females (22.5%). Ages ranged from 20 to 90, with a median age of 58.0 years. The optimal cut off values of albumin, globulin and AGR were set at 42.0, 28.2 and 1.80, respectively. Patients in the high albumin group and high AGR group were both associated with younger age, smaller tumor size, as well as earlier T and N stages. Univariate and multivariate analysis demonstrated that albumin level and AGR value were both significant prognostic factors, while globulin level was not. Furthermore, albumin level displayed a prognostic discriminatory ability and a predictive accuracy superior to that of AGR. The multivariate model based on albumin also revealed a superior predictive accuracy than that based on AGR.Conclusion: Preoperative albumin level is superior to AGR value in the prediction of prognosis of gastric cancer.Keywords: albumin-globulin ratio, albumin, gastric cancer, prognosis

Zhengxing Gao,1 Chunqing Song,2 Guangxin Li,1 Haishan Lin,1 Xiangyao Lian,1 Ninggang Zhang,1 Bangwei Cao11Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, People’s Republic of China; 2Department of Oncology, Beijing Daxing District Hopeople’s Hospital, Capital Medical University, Beijing 102600, People’s Republic of ChinaAims: Pyrotinib is a newly developed irreversible pan-ErbB receptor tyrosine kinase inhibitor for treatment of human epidermal growth factor receptor 2 (HER2)-positive cancers, and clinic trials of pyrotinib in treatment of HER2-positive gastric cancer (GC) are underway. Exosomes are tiny vesicles secreted by cancer cells and take essential roles in the progression of carcinoma. Whether pyrotinib application has any effect on the cancer cell-released exosomes has not been studied. The aim of our work was to address if pyrotinib treatment impacts the effect of HER2-positive GC cell-derived exosomes on endothelial cell (EC) progression.Methods: Isolation of exosomes released by HER2-positive NCI-N87 and MKN45 lines after pyrotinib treatment was performed. Then, human umbilical vein endothelial cells (HUVECs) were incubated with different concentrations of exosomes to address their proliferation by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS). Effect of pyrotinib-treated exosomes at concentration of 10 μg/mL was compared to that without pyrotinib treatment over 96-hr time course. Transwell assay and wound-healing assay were carried out by incubating with exosomes released by NCI-N87 and MKN45 cells with/without pyrotinib treatment over 24-hr time course. The aforementioned experiments were done under same conditions in order to evaluate the combined effect of apatinib and pyrotinib on HUVEC motility and invasive capacity.Results: We showed that HUVEC proliferation, motility and invasive capacity were further enhanced upon incubation with exosomes released by pyrotinib-treated GC cell lines, compared to those without pyrotinib treatment. Significantly, this effect was counteracted by the vascular endothelial growth factor receptor (VEGFR)-2 inhibitor apatinib which inhibits EC progression.Conclusion: Our study suggests that pyrotinib application on HER2-positive GC produces stronger exosomes that promote the proliferation and motility of vascular ECs, and combination of pyrotinib with apatinib provides potentially better therapy.Keywords: pyrotinib, HER2, gastric cancer, GC, exosome, human umbilical vein endothelial cells, HUVEC, apatinib

Huijing Ye,* Xiufen Lian,* Rongxin Chen, Yanling Zhu, Hongbin Chen, Jingxia Huang, Ling Xie, Wenfang Ma, Huasheng Yang, Wenjun Guo State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China *These authors contributed equally to this work Purpose: This study aimed to investigate postoperative analgesia achieved with intraoperative administration of intravenous flurbiprofen axetil and nalbuphine in patients undergoing orbital decompression. Methods: Sixty-three patients undergoing orbital decompression under general anesthesia at the Zhongshan Ophthalmic Center at Sun Yat-sen University (Guangzhou, China) were randomly allocated into one of the following three groups (1:1:1): intraoperative flurbiprofen axetil 100 mg (Group 1); intraoperative nalbuphine 0.1 mg/kg (Group 2); or intraoperative flurbiprofen axetil 100 mg combined with nalbuphine 0.1 mg/kg (Group 3). The primary end point was mean postoperative pain intensity during the first 24 hours. The secondary efficacy end points were the intensity of pain and discomfort at 0, 2, 6, 10, and 24 hours after surgery and side effects at 24 hours after surgery. Results: The demographic characteristics were similar among the three groups. Mean and peak postoperative pain scores during the first 24 hours in Group 3 were lower than those in Group 1 (P=0.007 and P=0.003, respectively) and Group 2 (P=0.001 and P=0.000, respectively). Additionally, the pain scores in Group 3 were significantly lower than those in Group 1 during the first 6 hours after surgery (P=0.003, 0.002, and 0.022 at 0, 2, and 6 hours, respectively) and those in Group 2 during the first 10 hours after surgery (P=0.008, 0.000, 0.001, and 0.019 at 0, 2, 6, and 10 hours, respectively). Discomfort scores were not significantly different among the three groups during the observation period, except at 2 hours after surgery, at which time the scores in Group 3 were significantly lower than those in Group 2 (P=0.033). Postoperative adverse effects and analgesic requirements were similar among the three groups. Conclusion: Intraoperative administration of a combination of intravenous flurbiprofen axetil and nalbuphine is superior to single-dose flurbiprofen axetil or nalbuphine in patients undergoing orbital decompression. Keywords: postoperative pain, flurbiprofen axetil, nalbuphine, orbital decompression

The rapid rise in the health burden associated with chronic wounds is of great concern to policymakers, academia, and industry. This could be attributed to the devastating implications of this condition, and specifically, chronic wounds which have been linked to invasive microbial infections affecting patients’ quality of life. Unfortunately, antibiotics are not always helpful due to their poor penetration of bacterial biofilms and the emergence of antimicrobial resistance. Hence, there is an urgent need to explore antibiotics-free compounds/formulations with proven or potential antimicrobial, anti-inflammatory, antioxidant, and wound healing efficacy. The mechanism of antibiotics-free compounds is thought to include the disruption of the bacteria cell structure, preventing cell division, membrane porins, motility, and the formation of a biofilm. Furthermore, some of these compounds foster tissue regeneration by modulating growth factor expression. In this review article, the focus is placed on a number of non-antibiotic compounds possessing some of the aforementioned pharmacological and physiological activities. Specific interest is given to Aloevera, curcumin, cinnamaldehyde, polyhexanide, retinoids, ascorbate, tocochromanols, and chitosan. These compounds (when alone or in formulation with other biologically active molecules) could be a dependable alternative in the management or prevention of chronic wounds.

Guanghui Xu,1,* Fan Feng,1,* Shushang Liu,1,* Fei Wang,1,2 Gaozan Zheng,1 Qiao Wang,1,3 Lei Cai,1 Man Guo,1 Xiao Lian,1 Hongwei Zhang1 1Division of Digestive Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi’an, Shaanxi, 2Department of General Surgery, No 534 Hospital of PLA, Luoyang, 3Department of Surgery, No 91 Center Hospital of PLA, Jiaozuo, Henan, China *These authors contributed equally to this work Background: Little is known about the clinicopathological features and prognosis in elderly gastric cancer (GC) patients aged 65–79 years. The aim of this study was to evaluate clinicopathological features and prognosis in elderly GC patients. Patients and methods: From May 2008 to December 2014, a total of 5,282 GC patients were enrolled in our present study. Patients were divided into elderly and middle-aged groups. The clinicopathological features and clinical outcomes were analyzed. Results: The proportion of dysphagia was significantly higher in elderly patients than that in middle-aged patients (P=0.002), whereas the proportion of abdominal pain and heartburn was significantly lower in elderly patients than that in middle-aged patients (P0.05). Age, tumor size, histological type, tumor depth, lymph node metastasis, carcinoembryonic antigen, alpha fetoprotein, CA19-9, and CA125 were independent risk factors for the prognosis of GC patients in univariate and multivariate analyses. Overall survival in elderly patients was significantly reduced compared with middle-aged patients (P=0.001), especially in patients with tumor size >5 cm (P=0.002), poorly differentiated tumor (P

Huijing Ye,1* Rongxin Chen,1* Xiufen Lian,1* Jingxia Huang,2 Yuxiang Mao,1 Rong Lu,1 Siming Ai,1 Wenfang Ma,1 Jingyi Lin,2 Huasheng Yang,1 Wenjun Guo2 1Department of Orbital Diseases and Ocular Oncology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China; 2Department of Anesthesia, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China *These authors contributed equally to this work Purpose: To evaluate patient pain and discomfort following oculoplastic surgery performed under general anesthesia and to assess key factors associated with postoperative pain and discomfort. Methods: A prospective observational cohort study was conducted among 212 consecutive patients who underwent oculoplastic surgery performed under general anesthesia. The patients were assessed according to quantified levels of pain and discomfort postoperatively. Analgesic requests were recorded, and responses were statistically analyzed. Results: Pain and discomfort after oculoplastic surgery under general anesthesia were reported by 32.1% and 28.3% of the patients, respectively; 2.8% of the patients requested analgesic medication within 18 hours after surgery. The patients who underwent orbital decompression, secondary orbital implantation, and orbital fracture repair were more likely to develop significant postoperative pain and discomfort (P

Lei Cai,1 Yan Li,2 Xue-wen Yang,1 Xiao Lian,1 Man Guo,1 Shu-ao Xiao,1 Wen-bin Wang,1 Hong-wei Zhang1 1Division of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 2Department of Anesthesiology, Northwest Women’s and Children’s Hospital, Xi’an, China Background: The mucinous component is a special histologic factor in gastric adenocarcinoma. The aim of this study was to assess the prognostic significance of mucinous component in gastric adenocarcinoma according to proportion.Patients and methods: Candidate patients with gastric adenocarcinoma were given radical D2 gastrectomies from September 2008 to May 2015 in our division. Clinicopathologic data and prognosis were monitored and analyzed among gastric adenocarcinoma patients with various proportions of mucinous component.Results: A total of 690 gastric adenocarcinomas with various proportions of mucinous component from 6,025 gastric adenocarcinoma patients were included. Higher numbers of patients with mucinous component came from: young patients, females, those with drinking history, at lower locations, Borrmann type III and IV, T4 stage, and positive for dissected lymph nodes. Tumors and pathological molecular markers showed more positivity in CEA, CA19-9, S100, and CD34. As the various proportions increased, more mucinous component seemed to be accompanied by more Borrmann type III and IV, T4 stage, and more positive expression of CEA and CA19-9. However, no significant difference in 5-year overall survival rate was observed among various proportions or existence of mucinous component. Also, proportion or existence of mucinous component was not an independent prognostic factor in multivariate analysis.Conclusion: Mucinous component was not a prognostic factor for gastric adenocarcinoma after radical D2 gastrectomy, no matter what proportion the component comprised. However, gastric adenocarcinoma with mucinous component showed specific clinicopathological characteristics, such as more advanced tumor stage, different age and sex, and more positive rate of molecular markers, which might provide a new strategy for optimal individual diagnosis and therapies. Keywords: mucinous component, mucinous gastric carcinoma, gastric adenocarcinoma with mucinous component, pure gastric adenocarcinoma, radical D2 gastrectomy, prognosis

Water use efficiency (WUE) is a key indicator to assess ecosystem adaptation to water stress. Rain use efficiency (RUE) is usually used as a proxy for WUE due to lack of transpiration data. Furthermore, RUE based on aboveground primary productivity (RUEANPP) is used to evaluate whole plant water use because root production data is often missing as well. However, it is controversial as to whether RUE is a reliable parameter to elucidate transpiration efficiency (TE), and whether RUEANPP is a suitable proxy for RUE of the whole plant basis. The experiment was conducted at three differently managed sites in the Inner Mongolia steppe: a site fenced since 1979 (UG79), a winter grazing site (WG) and a heavily grazed site (HG). Site HG had consistent lowest RUEANPP and RUE based on total net primary productivity (RUENPP). RUEANPP is a relatively good proxy at sites UG79 and WG, but less reliable for site HG. Similarly, RUEANPP is good predictor of transpiration efficiency based on aboveground net primary productivity (TEANPP) at sites UG79 and WG but not for site HG. However, if total net primary productivity is considered, RUENPP is good predictor of transpiration efficiency based on total net primary productivity (TENPP) for all sites. Although our measurements indicate decreased plant transpiration and consequentially decreasing RUE under heavy grazing, productivity was relatively compensated for with a higher TE. This offset between RUE and TE was even enhanced under water limited conditions and more evident when belowground net primary productivity (BNNP) was included. These findings suggest that BNPP should be considered when studies fucus on WUE of more intensively used grasslands. The consideration of the whole plant perspective and "real" WUE would partially revise our picture of system performance and therefore might affect the discussion on the C-sequestration and resilience potential of ecosystems.

Global environmental change is rapidly altering the dynamics of terrestrial vegetation, with consequences for the functioning of the Earth system and provision of ecosystem services. Yet how global vegetation is responding to the changing environment is not well established. Here we use three long-term satellite leaf area index (LAI) records and ten global ecosystem models to investigate four key drivers of LAI trends during 1982-2009. We show a persistent and widespread increase of growing season integrated LAI (greening) over 25% to 50% of the global vegetated area, whereas less than 4% of the globe shows decreasing LAI (browning). Factorial simulations with multiple global ecosystem models suggest that CO2 fertilization effects explain 70% of the observed greening trend, followed by nitrogen deposition (9%), climate change (8%) and land cover change (LCC) (4%). CO2 fertilization effects explain most of the greening trends in the tropics, whereas climate change resulted in greening of the high latitudes and the Tibetan Plateau. LCC contributed most to the regional greening observed in southeast China and the eastern United States. The regional effects of unexplained factors suggest that the next generation of ecosystem models will need to explore the impacts of forest demography, differences in regional management intensities for cropland and pastures, and other emerging productivity constraints such as phosphorus availability.

【Objective】To improve the linear fit between the reflected spectral center wavelength and external environmental variables in Fiber Bragg Grating (FBG) sensing system, this paper proposes to use particle swarm optimization of Gaussian process regression model to the field of FBG stress sensing.【Methods】For the reflectance spectral characteristics of the FBG, the paper studies the impact of the linear fit in the spectral fitting of FBG sensing system. The particle swarm algorithm is used to search for the optimal hyperparameters in the Gaussian process regression model in order to enhance the predictive performance of the reflectance spectral wavelength of the center. A FBG stress sensing experimental platform was built, and the FBG was laid on the strength beam. Different weights were applied to one end of the equal strength beam to produce axial strain on the FBG, and the reflectance spectral data were collected by the spectrometer and analyzed by linear fitting with the studied model. The results obtained by the unoptimized Gaussian process regression model, the maximum value method, the Gaussian fitting method, and the center of mass method were used as the control group.【Results】The results show that under the conditions of erbium-doped fiber amplifier output power of 10 dBm, transmission fiber distance of 50 m, and the number of sampling points of the spectrometer of 501, the linear fit between the reflected spectral center wavelength and the mass of the weights is better than that of the control group. The linear fit of the studied model can reach up to 0.951 9, which is improved compared with that of the control group. Under the conditions of 501, 251, 167 and 126 spectral sampling points, the studied model can improve the linear fit of the system to 0.990 0, which is a maximum improvement of 0.258 7 compared with the maximum value method.【Conclusion】The analysis results show that the Gaussian process regression model optimized by the particle swarm is able to effectively improve the linear fit of the FBG stress sensing system.