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Yanli Guo,1,&ast; Dinggui Huang,2,&ast; Jingxia Sun,3,&ast; Zhenwei Zhai,3,&ast; Hewei Xiao,4,&ast; Weiguang Hao,5 Qiu Wang,3 Jianhao Huang,3 Miaomiao Jin,1 Wensheng Lu3,&ast; 1Department of Endocrinology, Heji Affiliated Hospital of Changzhi Medical College, Changzhi, Shanxi, 046011, People’s Republic of China; 2Project Fund Supervision Center, Health Commission of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 4Scientific Research Cooperation Department, Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 5Department of Endocrinology, Tongde Hospital, Yuncheng, Shanxi, 044000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng Lu, Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, No. 6, Taoyuan Road, Nanning, Guangxi, 530021, People’s Republic of China, Email Lwswxqz@163.comAim: This study aimed to assess the efficacy of antithyroid drugs (ATDs) and radioactive iodine-131 (RAI) therapies in reducing the risk of major adverse cardiovascular events (MACEs) and all-cause mortality in patients with hyperthyroidism complicated with type 2 diabetes mellitus (T2DM).Methods: Between January 2013 and December 2021, 540 subjects were included in the analysis. All participants were followed up for 9 years, with a median of 54 months (2451 person-years). The subjects were categorized into two groups: the ATDs group (n = 414) and the RAI group (n = 126). According to the free triiodothyronine (FT3) tertiles, the patients receiving RAI were further grouped as follows: low-level (≤ 4.70 pmol/L, n = 42), moderate-level (4.70– 12.98 pmol/L, n = 42), and high-level (≥ 12.98 pmol/L, n = 42). The efficacy of ATDs and RAI therapies in reducing the risk of MACEs and all-cause mortality was assessed.Results: Of the 540 participants, 163 experienced MACEs (30.19%), 25 (15.34%) of whom died. Multivariate Cox regression analyses revealed that RAI was associated with a 38.5% lower risk of MACEs (P = 0.016) and a 77.1% lower risk of all-cause mortality (P = 0.046). Stratified analyses indicated that RAI had a protective effect on MACEs in patients aged ≥ 60 years (P = 0.001, P for interaction = 0.031) and patients with a duration of diabetes mellitus ≥ 6 years (P = 0.013, P for interaction = 0.002). Kaplan‒Meier analysis revealed a lower cumulative incidence of MACEs and all-cause mortality in the RAI group (log-rank, all P < 0.05). Moreover, the ROC curve suggested an optimal FT3 cut-off value of 5.4 pmol/mL for MACE (P < 0.001).Conclusion: Our findings suggested that RAI therapy effectively reduced the risk of MACEs and all-cause mortality in elderly patients with hyperthyroidism combined with T2DM.Keywords: hyperthyroidism, type 2 diabetes mellitus, radioactive iodine-131, major adverse cardiovascular events, all-cause mortality

Wensi Hao,1,2 Yaqin Gu,1,2 Shuyuan Hu,1,2 Xunming Ji,1,2 Yuping Wang,2 Jiangang Duan1,2 1Department of Emergency, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Jiangang Duan, Department of Emergency, Xuanwu Hospital, Capital Medical University, No. 45, Changchun St, Xicheng District, Beijing, 100053, People’s Republic of China, Email duanjiangang@xwhosp.orgBackground: Inflammation was associated with the severity of severe cerebral venous thrombosis (CVT) on admission and poor prognosis at discharge. Hereditary protein C/S deficiency (hereditary PCD/PSD) not only promotes thrombosis but also activates the inflammatory response, further inducing venous thrombosis. However, conventional treatments such as standard anticoagulant/endovascular therapy (EVT) do not seem to improve prognosis. Anti-inflammatory therapy may be a new way to treat the disease.Methods: We enrolled five patients with acute/subacute severe CVT with hereditary PCD/PSD from January 2020 to July 2022. In addition to standard anticoagulant therapy, all of them were given short-term methylprednisolone pulse therapy. Neurological deficit, increased intracranial pressure, venous recanalization, serum and cerebrospinal fluid (CSF) inflammatory markers and adverse events were retrospectively described before and after treatment and at 6 months after discharge.Results: Inflammatory indexes of all patients were significantly elevated on admission. After methylprednisolone pulse therapy, serum inflammatory indexes including neutrophil-to-lymphocyte ratio (P=0.043); platelet-to-lymphocyte ratio (P=0.043); systemic immune inflammatory index (P=0.043); interleukin-6 (P=0.043) and hypersensitive C-reactive protein (P=0.022) reduced dramatically compared with baseline. CSF inflammatory indexes had a decreasing trend compared with baseline (P> 0.05). In terms of venous recanalization, one patient achieved complete recanalization, four patients obtained partial recanalization. Compared with baseline on admission, the NIH Stroke Scale (NIHSS), modified Rankin Scale (mRS) and intracranial pressure were all considerably lower at discharge (P=0.029, P=0.041 and P=0.017). At 6-month follow-up, NIHSS and mRS further declined. During hospitalization and 6-month follow-up, none of the five patients experienced severe steroid-related adverse effects such as recurrence of venous thrombosis, spontaneous fracture or osteonecrosis, and gastroduodenal ulcer.Conclusion: Acute/subacute severe CVT with hereditary PCD/PSD has high levels of inflammation. In addition to conventional anticoagulant therapy, early anti-inflammatory therapy using steroids may be necessary. Nevertheless, substantial randomized controlled trials with larger sample sizes are required for further investigation.Keywords: severe cerebral venous thrombosis, hereditary protein C deficiency, hereditary protein S deficiency, thrombosis, inflammation, methylprednisolone pulse therapy

Yang Gao,1,&ast; Yuguang Guo,2,&ast; Wenjun Hao,1 Jin Meng,1 Zhilin Miao,1 Aijie Hou,1 Bo Luan1 1Department of Cardiology, the People’s Hospital of Liaoning Province, Shenyang, People’s Republic of China; 2Department of Clinical Laboratory, the People’s Hospital of Liaoning Province, Shenyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Luan, Department of Cardiology, the People’s Hospital of Liaoning Province, No. 33, Wenyi Road, Shenhe District, Shenyang, Liaoning Province, 110016, People’s Republic of China, Email Boluan369@hotmail.comBackground: Coronary angiography (CAG) is an invasive examination with high risks and costs and various complications may occur. It is necessary to find a diagnostic method, non-invasiveness, inexpensive with low risk. This study aims to analyze the correlation between the levels of serum homocysteine (Hcy), cystatin C (Cys C) and uric acid (UA) and Gensini score in patients with coronary heart disease (CHD) and assess their diagnostic value for CHD.Methods: A retrospective analysis was conducted on 1412 patients underwent CAG from October 2019 to December 2021, and we conducted this study from January to July 2022. A total of 765 patients with CHD confirmed by CAG were selected as the research group, while 647 patients revealed as non-obstructive stenosis by CAG as the control group. The serum Hcy, Cys C and UA levels were detected and the correlation between Gensini score and variables was analyzed. The receiver-operating characteristic (ROC) curve was performed to assess the diagnostic value of the Hcy, Cys C and UA for CHD.Results: The serum Hcy, Cys C and UA levels in the research group were higher as compared with the control group (p< 0.05). Spearman correlation and multivariate linear regression analysis showed that there was a significantly positive correlation between Gensini score and serum Hcy, Cys C and UA levels (p< 0.05). The ROC curve analysis presented the combined Hcy and Cys C with UA having the highest specificity of diagnostic value for CHD (area under the curve (AUC)=0.768, 95% CI 0.706– 0.823, specificity = 72.34%, sensitivity = 67.88%, Youden Index = 0.4022).Conclusion: The serum Hcy, Cys C and UA levels in patients with CHD were significantly increased, positive correlation with Gensini score. The combined Hcy and Cys C with UA could be used to assess the severity of coronary artery stenosis and provide predictive and early intervention treatment values for CHD and a new way of diagnosing CHD, which is cheap, safe, effective and deserving of clinical application.Keywords: serum homocysteine, cystatin C, uric acid, gensini score, correlation analysis, diagnostic value

Yang Gao,1,&ast; Ling Yue,2,&ast; Zhilin Miao,1 Fengrong Wang,3 Shuai Wang,3 Bo Luan,1 Wenjun Hao1 1Department of Cardiology, The People’s Hospital of Liaoning Province, Shenyang, Liaoning Province, People’s Republic of China; 2Department of Ultrasound, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of China; 3Department of Cardiology, The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjun Hao, Department of Cardiology, The People’s Hospital of Liaoning Province, NO. 33, Wenyi Road, Shenhe District, Shenyang, Liaoning Province, 110016, People’s Republic of China, Email wjunheart@sina.comPurpose: To observe the effect of cardiac rehabilitation (CR) in patients with partial revascularization performed on multiple coronary artery lesions and explore its possible mechanism.Patients and Methods: A total of 400 patients with multiple coronary artery lesions were enrolled and randomly divided into a complete revascularization group and a CR group, with 200 cases in each group. Target lesion revascularization was performed radically in the complete revascularization group, while it was partially completed in the CR group, and postoperative CR was performed. All the patients were put under conventional treatment. Left ventricular end diastolic dimension (LVEDD), left ventricular ejection fraction (LVEF), 6-minute walking distance (6-MWD), quality-of-life scores, safety and levels of serum nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD), and vascular endothelial growth factor (VEGF) were evaluated and compared between two groups before and after training.Results: There was no significant difference in LVEDD, LVEF, 6-MWD, quality-of-life scores, levels of serum NO, NOS, SOD, and VEGF between two groups before training (p> 0.05). 1 year later, compared with the complete revascularization group, the occurrence of major adverse events in the CR group declined (p> 0.05); the measurements of LVEDD decreased and LVEF increased (p> 0.05), 6-MWD increased significantly (p< 0.05), quality-of-life scores were higher (p< 0.05), the levels of serum NO, NOS, and SOD increased noticeably, and the levels of serum VEGF decreased significantly in the CR group (p< 0.05). There were significant differences within the same group, before and after training (p< 0.05).Conclusion: Cardiac rehabilitation training, not increase in the incidence of adverse events, is effective and safe after partial revascularization in patients with multiple coronary artery lesions, which has notable clinical advantages in promoting patients’ exercise endurance and quality-of-life by improving the nitric oxide synthase system and antioxidant system and reducing the level of VEGF.Keywords: multiple coronary artery lesions, cardiac rehabilitation, coronary revascularization, 6-MWD, quality-of-life, NO/NOS

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

Feng Yu,1,&ast; Guanglan Li,1,2,&ast; 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 China&ast;These authors contributed equally to this workCorrespondence: Wenxue HuDepartment 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 wuleihu@126.comIntroduction: The clinicopathologic characteristics of Hepatitis B virus-associated glomerulonephritis (HBV-GN) patients with different serum HBsAg are not well known. This study aims to investigate the characteristics and treatments between HBV-GN patients with positive and negative serum HBsAg.Methods: A retrospective review of patients with renal biopsies in Guangdong Provincial People’s Hospital from 2005 to 2018 was performed. Clinicopathological data, treatments and remission of proteinuria were collected and compared between HBsAg+ and HBsAg- group.Results: A total of 101 HBV-GN were recruited. Serum HBsAg+ and HBsAg- patients accounted for 62.4% and 37.6%, respectively. HBsAg+ group had poor kidney and liver functions. Pathological data showed the percentage of membranous nephropathy in HBsAg- group is significantly higher than that of HBsAg+ group (60.3% HBsAg+ vs 89.5% HBsAg-, P< 0.05). Chronic renal tubular/interstitial injury was more prevalent in HBsAg+ group (16.9% HBsAg+ vs 2.6% HBsAg-, P< 0.05). The deposition sites of immune complexes were significant different between the two groups. In addition, more HBsAg+ patients were given anti-HBV and less were given corticosteroid or immunosuppressants for treatment than that of HBsAg- patients. Percentages of clinical remission were increasing in both HBsAg+ and HBsAg- patients from 1, 3, 6 months to 1 year (18.75%, 45.2%, 67.8%, 82.4% vs 24.4%, 41.2%, 62.8%, 59.3%). The differences of remission betwen two groups were not significant (P> 0.05).Conclusion: The clinicopathological characteristics and treatments of HBV-GN with serum HBsAg+ and HBsAg- were distinct, which indicated that the pathogenesis might be different and specific treatments were needed for HBV-GN patients with different serum HBsAg.Keywords: hepatitis B, hepatitis B virus related glomerulonephritis, serum HBsAg

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

Xue Lv,1 Kun Fang,2 Wenqing Hao,1 Yuxin Han,1 Nailong Yang,1 Qing Yu1 1Department of Endocrinology and Metabolism, Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 2Division of Health Management Center, Qingdao Municipal Hospital, Qingdao, Shandong, People’s Republic of ChinaCorrespondence: Nailong YangDepartment of Endocrinology and Metabolism, Affiliated Hospital of Qingdao University, Qingdao University of Medicine, No. 1677, Wutai Mountain Road, Huangdao District, Qingdao, Shandong 266555, People’s Republic of ChinaTel +86 18661806185Email nailongy@163.comQing YuDepartment of Endocrinology and Metabolism, Affiliated Hospital of Qingdao University, Qingdao University of Medicine, No. 1677, Wutai Mountain Road, Huangdao District, Qingdao, Shandong 266555, People’s Republic of ChinaEmail yuqing121985@126.comPurpose: To identify the population susceptible to reactive hypoglycemia and explain the possible reasons for their susceptibility.Methods: Ninety-four patients were divided into normal weight, overweight and obese groups before a 75-gram prolonged oral glucose tolerance test (POGTT). The incidence of reactive hypoglycemia (blood glucose ≤ 3.1 mmol/L or 55 mg/dL at points of 0– 4 hours) was compared among three groups, and blood glucose and insulin levels were monitored simultaneously from 0 - 4 hours to assess the level of insulin resistance and insulin sensitivity. Furthermore, the degree of insulin resistance among three groups and within each subgroup (whether hypoglycemia events occurred) was compared.Results: Among the three groups, the incidence of hypoglycemia was significantly different at 3 (P=0.033) and 4 hours (P=0.020). At 4 hours, the incidence of reactive hypoglycemia in the obese group was approximately 3 times that in the normal weight group. The insulin level in obese group at 4 hours was nearly 4 times higher than that in normal group, and the same result also exists in the same subgroup of different groups. In addition, the hypoglycemia subgroup of obese group had higher insulin level than non-hypoglycemia (P=0.000). The homeostasis model assessment of insulin resistance index increased with increasing BMI among the three groups (P=0.000), while the Matsuda index decreased (P=0.000). The comparison of the homeostasis model assessment of insulin resistance index between subgroups in each group showed that the P values were 0.021, 0.038 and 0.085, successively, and the P values for the Matsuda index were 0.019, 0.013 and 0.119, respectively.Conclusion: Obese people has higher rate of reactive hypoglycemia than other groups in POGTT, in which insulin resistance may play an important role. But patients who are evaluated for reactive hypoglycemia need to be observed for at least 3 or 4 hours.Keywords: reactive hypoglycemia, prolonged oral glucose tolerance test, insulin resistance, low-carb ketogenic diet

Yinxing Shen,1,2,* Junqi Zhang,2,* Weiju Hao,1 Tong Wang,1 Jing Liu,2 Youhua Xie,2 Shouhong Xu,1 Honglai Liu1 1State Key Laboratory for Advanced Materials, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 2Department of Medical Microbiology and Parasitology, Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Efficient delivery of nucleic acids into target cells is crucial for nucleic acid-based therapies. Various nucleic acid delivery systems have been developed, each with its own advantages and limitations. We previously developed a nanoparticle-based delivery system for small chemical drugs using pH-responsive PEG8-PDPA100-PEG8 polymer micelles as carriers. In this study, we extend the application of these pH-responsive micelle-like nanoparticles (MNPs) to deliver oligonucleotides. We demonstrate that the MNPs efficiently encapsulate and deliver oligonucleotides of different lengths (20–100 nt) into cells. The cargo oligonucleotides are rapidly released at pH 5.0. We prepared MNPs carrying a Texas red-fluorescently labeled anti-human epidermal growth factor receptor 2 (HER2) aptamer (HApt). Compared to free HApt, the HApt-MNPs resulted in significantly better cellular uptake, reduced cell viability, and increased apoptosis in SKBR3 breast cancer cells, which overexpress HER2. Moreover, HApt-MNPs were significantly less cytotoxic to MCF7 breast cancer cells, which express low levels of HER2. After cellular uptake, HApt-MNPs mainly accumulated in lysosomes; inhibition of lysosomal activity using bafilomycin A1 and LysoTracker Red staining confirmed that lysosomal activity and low pH were required for HApt-MNP accumulation and release. Furthermore, HER2 protein expression declined significantly following treatment with HApt-MNPs in SKBR3 cells, indicating that HApt-induced translocation of HER2 to lysosomes exerted a potent cytotoxic effect by altering signaling downstream of HER2. In conclusion, this pH-responsive and lysosome-targeting nanoparticle system can efficiently deliver oligonucleotides to specific target cells and has significant potential for nucleic acid-based cancer therapies. Keywords: pH-responsive micelle-like nanoparticles, nucleic acid delivery, HER2-targeted therapy

The paramyosin (Pmy) protein has been presented as a potential vaccine candidate against Schistosoma spp. However, it remains elusive whether it works in controlling cystic echinococcosis (CE), which is caused by the larval stages of Echinococcus granulosus (E. granulosus). This study investigated the characteristics of E. granulosus Pmy (EgPmy) using in silico analysis and evaluated its potential as an epitope vaccine. The secondary structure was predicted by SOPMA software and linear B-cell epitopes were screened by the Kolaskar and Tongaonkar’s method on IEBD while conformational B-cell epitopes were predicted by the Ellipro. Additionally, the epitopes of cytotoxic T lymphocyte (CTL) were analyzed by the NetCTL-1.2 server. The results showed that α-helices, extended strands, random coils and β-turns accounted for 84.82 %, 6.60 %, 5.56 % and 3.01 % in EgPmy’s secondary structure, respectively. A total of 29 linear B-cell epitopes and 6 conformational epitopes were identified together with 25 CTL epitopes. The CTL epitope 709KLEEAEAFA717 showed a high potential to elicit CTL response. These results suggested that EgPmy has a strong immunogenicity, which could serve as a reference for the development of EgPmy-based epitope vaccine against CE.

Jia Jiang,1,2 Fang Wan,1 Jianjun Yang,1 Wei Hao,3 Yaxian Wang,3 Jinrong Yao,3 Zhengzhong Shao,3 Peng Zhang,1 Jun Chen,1 Liang Zhou,4 Shiyi Chen11Fudan University Sports Medicine Center and Department of Sports Medicine and Arthroscopy Surgery, Huashan Hospital, 2State Key Laboratory of Molecular Engineering of Polymers, 3Laboratory of Advanced Materials, National Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, People’s Republic of China; 4Department of Forest Products, Anhui Agricultural University, Hefei Anhui Province, People’s Republic of ChinaBackground: Application of artificial ligament in anterior cruciate ligament reconstruction is one of the research focuses of sports medicine but the biological tendon–bone healing still remains a problem. The preliminary study of hydroxyapatite (HAP) coating on the polyethylene terephthalate (PET) surface could effectively induce the osteoblast differentiation, but the tendon–bone healing was still not stable. As a green synthesis process, the biomimetic mineralization can simulate the natural bone growth in vitro and in vivo.Methods: HAP crystals were grown under the guide of silk fibroin (SF) PET surface by biomimetic route. Several techniques including scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy were utilized for proving the introduction of both SF and HAP. The viability and osseointegration of bone marrow stromal cells on the surface of three kinds of ligament, including PET group (non-coating group), PET+SF group (SF-coating group), and PET+SF+HAP group (combined HAP- and SF-coating group), were analyzed by CCK-8 assays and alkaline phosphatase (ALP) detection. Seventy-two mature male New Zealand rabbits were randomly divided into three groups. Among them, 36 rabbits were sacrificed for mechanical testing, and histological examination for the others. Results: The SF and SF+HAP were successfully coated on the surface of PET fiber. The CCK-8 assay showed that the cell proliferation on PET+SF+HAP group was better than the other two groups from 24 to 120 hours. After 14 days of culture, the cells in the PET+SF+HAP group delivered higher levels of ALP than the other two groups. After 3 days of culture, the expression level of integrin β1 in the PET+SF+HAP group and PET+SF group were higher than in the PET group. The mean load to failure and the stiffness value of the PET+SF+HAP group were both higher than the other two groups. Hematoxylin and eosin staining showed that new bone tissue formation was only found in the PET+SF+HAP group 8 weeks postoperatively. Masson staining showed that in the PET+SF+HAP group 8 weeks postoperatively, the PET fibers were almost completely encircled by collagen. Histomorphometric analysis showed that the width of the graft–bone interface in the PET+SF+HAP group was narrower than that in the other two groups 4 and 8 weeks postoperatively. The mRNA level of BMP-7 in the PET+SF+HAP groups was significantly higher than those in the other two groups 4 and 8 weeks postoperatively.Conclusion: The study showed that the combined SF and HAP coating by biomimetic route on the surface of PET artificial ligament could induce graft osseointegration in the bone tunnel, providing theoretical and experimental foundation for manufacturing novel artificial ligaments meeting the clinical needs.Keywords: biomineralization, tendon–bone healing, ligament reconstruction

CaCu3Ti4O12 ceramics with different polymorphs of TiO2 as starting materials were prepared by the conventional solid-state reaction technique. Their crystalline structure, microstructure and dielectric properties were systematically investigated. It has been found that all of the ceramic specimens prepared in the present study have a good polycrystalline structure, and no secondary phase is been found by XRD. However, large differences in dielectric properties and microstructure are observed in them: 1) the characteristic frequency of dielectric relaxation around 1 MHz in the CCTO ceramics prepared with rutile TiO2 is much lower than that in those ceramics prepared with anatase TiO2; 2) no matter dielectric properties or microstructure, the CCTO ceramics prepared with rutile TiO2 are more sensitive to the sintering temperature than those ceramics prepared with anatase TiO2.

Existing staining-based methodology for the detection of metal ions is not well suited for real-time or in situ use. This is a significant problem, given that these ions can have a considerable impact on both human health and the environment. Thus, there is growing interest and need for simple, rapid and in-situ monitoring techniques for the purpose of detecting various target analytes (e.g. heavy metals), which is of a significant importance in many fields ranging from environmental monitoring to the study of intracellular processes. Among various sensors developed, optical fiber-optic sensors (FOS), based on fluorescence, are one class of sensors that address this goal [1]. Optical fibers are ideal for environmental sensing applications because of their ability to transmit optical signals to and from the sensing region without the use of free-space optics. In this work, we present, for the first time, a simple FOS incorporating novel fluorescence turn-on mechanism [2] that could detect Cu (II) as low as 10−4 M. Traditionally, fluorescence quenching or “turn-off” was used to detect Cu (II) [3]. In recent years, fluorescence “turn-on” emerges as a preferable tool. The developed fiber-optic sensor has two fiber leads and one probe head. One fiber lead includes 6 fibers for He-Ne laser excitation light delivery (e-fibers). Another fiber lead has one receiving fiber (r-fiber) connected to an Ocean Optics QE65000 scientific grade spectrometer, which is interrogated by a computer via USB connection. The SpectroSuite software is used to observe and to record all spectra. The probe head combines all fibers together to form a coaxial structure with the r-fiber placed in the center. The key component in the proposed fluorescent sensing system is a probe prepared by binding a receptor containing a zwitterionic chromophore (M1), through noncovalent interactions, to the fluorescent polymer (P1) resulting in quenching its emission. The sensing mechanism involves the release of P1 (a fluorescent indicator) from its non-fluorescent indicator/receptor (P1/M1) pair upon exposure to Cu (II). The zwitterionic chromophore (M1) was found to show high selectivity and sensitivity to Cu (II), making it an ideal receptor for the recognition of Cu (II) [4]. The optimum operating conditions and performance characteristics for the new sensor will be discussed.

This paper was attempted to investigate the microstructure degradation and low cycle fatigue (LCF) performance of a serviced K465 Ni‐based superalloy turbine blade. LCF tests were carried out with small‐scale plate specimens sampled from the blades. Relationship between residual LCF life and microstructure state was estimated. The results indicate that the coarsening of γ/γ′ phases was the most significant microstructure degradation mode for the serviced blades. Both the γ matrix width and the γ′ precipitate diameter increased with the increase of service duration, while the γ′ precipitate volume fraction slightly decreased. The most severe microstructure degradation occurred at the leading edge along the chord direction, particularly at 50–70 % airfoil spans. The residual LCF life exhibited an accelerated decrease characteristic as increases of microstructure degradation degree. The coarsened microstructure diminished shear resistance of the superalloy, which resulted in additional accumulated inelastic deformation and a corresponding reduction in LCF life. Highlights: Service induced microstructure evolution and LCF life decay of a blade were investigated.Coarsening was identified as the main degradation form of γ/γ' phases in serviced blade.Accelerated decrease of residual LCF life was identified as increases of coarsening.Reduced plastic deformation resistance owing to coarsening is crucial to decay LCF life. [ABSTRACT FROM AUTHOR]

The Tropical Forest and Fire Emissions Experiment (TROFFEE) used laboratory measurements followed by airborne and ground based field campaigns during the 2004 Amazon dry season to quantify the emissions from pristine tropical forest and several plantations as well as the emissions, fuel consumption, and fire ecology of tropical deforestation fires. The airborne campaign used an Embraer 110B aircraft outfitted with whole air sampling in canisters, mass-calibrated nephelometry, ozone by UV absorbance, Fourier transform infrared spectroscopy (FTIR), and proton-transfer mass spectrometry (PTR-MS) to measure PM10, O-3, CO2, CO, NO, NO2, HONO, HCN, NH3, OCS, DMS, CH4, and up to 48 non-methane organic compounds (NMOC). The Brazilian smoke/haze layers extended to 2 - 3 km altitude, which is much lower than the 5 - 6 km observed at the same latitude, time of year, and local time in Africa in 2000. Emission factors (EF) were computed for the 19 tropical deforestation fires sampled and they largely compare well to previous work. However, the TROFFEE EF are mostly based on a much larger number of samples than previously available and they also include results for significant emissions not previously reported such as: nitrous acid, acrylonitrile, pyrrole, methylvinylketone, methacrolein, crotonaldehyde, methylethylketone, methylpropanal, '' acetol plus methylacetate,'' furaldehydes, dimethylsulfide, and C-1-C-4 alkyl nitrates. Thus, we recommend these EF for all tropical deforestation fires. The NMOC emissions were similar to 80% reactive, oxygenated volatile organic compounds (OVOC). Our EF for PM10 (17.8 +/- 4 g/kg) is similar to 25% higher than previously reported for tropical forest fires and may reflect a trend towards, and sampling of, larger fires than in earlier studies. A large fraction of the total burning for 2004 likely occurred during a two-week period of very low humidity. The combined output of these fires created a massive '' mega-plume '' > 500 km across that we sampled on 8 September. The mega-plume contained high PM10 and 10 - 50 ppbv of many reactive species such as O-3, NH3, NO2, CH3OH, and organic acids. This is an intense and globally important chemical processing environment that is still poorly understood. The mega-plume or '' white ocean '' of smoke covered a large area in Brazil, Bolivia, and Paraguay for about one month. The smoke was transported > 2000 km to the southeast while remaining concentrated enough to cause a 3 - 4-fold increase in aerosol loading in the S (a) over tildeo Paulo area for several days.

DNA methylation is a major epigenetic factor that has been postulated to regulate cell lineage differentiation. We report here that conditional gene deletion of the maintenance DNA methyltransferase I (Dnmt1) in neural progenitor cells (NPCs) results in DNA hypomethylation and precocious astroglial differentiation. The developmentally regulated demethylation of astrocyte marker genes as well as genes encoding the crucial components of the gliogenic JAK-STAT pathway is accelerated in Dnmt1(-/-) NPCs. Through a chromatin remodeling process, demethylation of genes in the JAK-STAT pathway leads to an enhanced activation of STATs, which in turn triggers astrocyte differentiation. Our study suggests that during the neurogenic period, DNA methylation inhibits not only astroglial marker genes but also genes that are essential for JAK-STAT signaling. Thus, demethylation of these two groups of genes and subsequent elevation of STAT activity are key mechanisms that control the timing and magnitude of astroglial differentiation.

To improve the application of wheat flour and the quality of noodles, in this study, 0.25%, 0.50%, 0.75%, 1.00% (w/w) grape seed proanthocyanins (GSP) were added to wheat flour. Rheology, moisture distribution and texture quality of the dough, as well as the cooking, digestive and sensory properties of the noodles were determined. The microstructure of the noodles added GSP was observed by scanning electron microscopy (SEM) to analyze the effect of GSP on the structure of wheat gluten proteins. As the results shown, with the addition of GSP rising (0~0.75%, w/w), the modulus of elasticity (G'), viscosity (G") (G'>G"), hardness, springiness and adhesiveness of the dough increased, The maximum tensile resistance and stretching distance increased by 7.22 g and 11.16 mm, respectively. It demonstrated that the rheology and texture quality were improved. The lateral relaxation time T2 shifted to the lower and the free water content declined, which exhibited the water-holding capability was enhanced. The cooking resistance of the noodles was improved, and the hydrolysis rate and glycemic index (GI) were obviously decreased which reduced from 68.45 with no additional GSP to 61.73 (1.00% addition). At the addition of GSP of 0.75%, the highest disulfide bond content and the lowest free thiol group content occurred, moreover, the score of sensory quality was the highest. The noodles exhibited the soft, chewy, and smooth mouthfeel. In conclusion, GSP could enhance the edible quality of the product by improving the structure of the gluten protein network and lowering the glycemic index (GI) value of noodles, which illustrated GSP could be used as a potential natural flour improver.

Introduction: Previous lipidomics studies have identified various lipid predictors for cardiovascular risk, however, with limited predictive increment, sometimes using too many predictor variables at the expense of practical efficiency. Objectives: To search for lipid predictors of future coronary heart disease (CHD) with stronger predictive power and efficiency to guide primary intervention. Methods: We conducted a prospective nested case-control study involving 1,621 incident CHD cases and 1:1 matched controls. Lipid profiling of 161 lipid species for baseline fasting plasma was performed by liquid chromatography-mass spectrometry. Results: In search of CHD predictors, seven lipids were selected by elastic-net regression during over 90% of 1000 cross-validation repetitions, and the derived composite lipid score showed an adjusted odds ratio of 3.75 (95% confidence interval: 3.15, 4.46) per standard deviation increase. Addition of the lipid score into traditional risk model increased c-statistic to 0.736 by an increment of 0.077 (0.063, 0.092). From the seven lipids, we found mediation of CHD risk from baseline diabetes through sphingomyelin (SM) 41:1b with a considerable mediation proportion of 36.97% (P

Currently, little is known about the characteristics of oxide films on Ti alloys exposed to the secondary circuit water environment of small modular reactors (SMRs). In this study, multiple microstructural characterization techniques were employed to meticulously characterize the oxide film characteristics of the TA16 alloy after 6000 h and 8000 h of exposure to a simulated SMR secondary circuit water environment. The results indicate that the oxide films on the 6000 h specimen are composed of a microcrystalline anatase TiO2 interior layer and a coarse-grained anatase TiO2 exterior layer, while the oxide film on the 8000 h specimen typically consists of a microcrystalline anatase TiO2 inner layer, an NiFe2O4 middle layer, and a coarse-grained anatase TiO2 outer layer. As the corrosion time is extended to 8000 h, the presence of NiFe2O4 oxide particles can be attributed to oxide deposition by the 316L stainless steel autoclave used in the corrosion experiments, which results in the migration of Ni and Fe ions onto the surface of the Ti alloy.

High entropy alloys (HEAs) were prepared using a vacuum arc melting method. The effect of Mo partially substituting Ni on the crystal structure and corrosion behaviors was studied. The results show that the HEAs exhibited a multiphase complex crystal structure which was composed of a BCC matrix and several intermetallic phases. The HEAs showed good corrosion resistance despite multiphase heterogeneity. But cyclic polarization showed that the HEAs were susceptible to pitting corrosion. Selective corrosion of Cr-depleted phases after polarization tests was attributed to the galvanic corrosion between Cr-depleted and Cr-rich phases. The spontaneous passive films on the HEAs surface were characterized by p-type semiconductor. Existence of Mo element of the HEAs accelerated passivation reaction kinetics, improved the stability of passive film, accordingly, acquired better general and pitting corrosion resistance.