bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydrogen Sulfide Ameliorates High Glucose-induced Inflammation Through SIRT1-mTOR/NF-κB Signaling Pathway in HT-22 cells
Authors: Li Xinrui , Yu Yinghua , Yu Peiquan , Xu Ting , Liu Jiao , Cheng Yuan , Yang Xia , Cui Xiaoying , Yin Cui , Liu Yi 
Published: July 2020

Abstract
Background: Hyperglycemia-induced neuroinflammation promotes the progression of diabetic encephalopathy (DE). Hydrogen sulfide (H2S) exerts anti-inflammatory and neuroprotective activities against neurodegenerative diseases. However, its role in hyperglycemia-induced neuronal inflammation has not been investigated. Herein, we examined the effects and its related signaling pathway of H2S on inflammatory response in high glucose-treated HT-22 cells.Methods: A hippocampal neuronal cell line, HT-22, was used as an in vitro model to explore the function of H2S on inflammatory response triggered by high glucose. A dicyanoisophorone-based near-infrared fluorescent probe (NIR-NP) was synthesized to detect H2S levels in HT-22 cells. Western blotting, immunofluorescence and real time-qPCR were carried out to study the mechanism of action for H2S.Results: We found that high glucose (85 mM) decreased the level of endogenous H2S and the expression of cystathionine-β-synthase (CBS) which is the main enzyme for H2S production in the brain. Sodium hydrosulfide (NaHS, a H2S donor) or S-adenosylmethionine (SAMe, an allosteric activator of CBS) administration restored high glucose-induced downregulation of CBS and H2S levels. Importantly, high glucose upregulated the level of pro-inflammatory factors (IL-1β, IL-6, TNF-α) in HT-22 cells. Treatment with NaHS or SAMe alleviated this enhanced transcription of these pro-inflammatory factors, suggesting that H2S might ameliorate high glucose-induced inflammation in HT-22 cells. We also found that high glucose reduced SIRT1 protein levels. SIRT1 reduction elevated the level of p-mTOR, p-NF-κB and pro-inflammatory factors, which were restored by resveratrol (a SIRT1 agonist). These results suggested that SIRT1 might be an upstream mediator of mTOR/NF-κB signaling pathway. Furthermore, NaHS or SAMe treatment reversed the expression of SIRT1, mTOR and NF-κB under high glucose conditions.Conclusions: Our study revealed that high glucose decreased CBS to reduce the production of H2S, which in turn decreased the expression of SIRT1. The reduction of SIRT1 activated mTOR/NF-κB signaling to promote inflammation. Given that promoting H2S production using NaHS or SAMe can reverse high glucose-induced inflammatory response, our study might shed light on the prophylactic treatment of DE.
Extraction And Quality Evaluation of Exosomes From Joint Effusion
Authors: Ruan Anmin , Yin Yueshan , Chen Pu , Zhou Jun , Zhang Xiaozhe , Ma Yufeng , Wang Qingfu 
Published: July 2020

Abstract
Objective: The aim of this study was to compare the quality and efficiency of exosomes extracted from knee joint effusion by different methods, laying a foundation for further research on exosomes from knee joint effusion. Methods: Separate and extract joint exosomes by 8% polyethylene glycol (PEG) precipitation method, ultracentrifugation method (UC) and ultrafiltration with exclusion chromatography (SECF). Transmission electron microscopy (TEM) and nanoparticle tracing technology (NTA) were used to detect particle morphology and particle size, and Western Blot (WB) was used to detect granule protein surface marker proteins (CD9, CD63, Flotillin-1 and calnexin).Results: All three methods successfully separated vesicle-like round particles from joint effusion. TEM results show that the particles obtained by the three extraction methods are round or oval vesicles, the plasma membrane is intact, the size is different, and the diameter is distributed between 30 and 150 nm. Compared with SECF group, PEG group had more background particle impurities. and the broken vesicle fragments can be seen in the UC group; NTA results show that the main peaks of the three groups of particles are between 100-120nm, and the particle concentration is greater than 1×1010/ml; WB results show that the expressions of CD9, CD63 and Flotillin-1 protein in the suspension extracted by the three methods were all higher, the expression of calnexin protein was higher in the PEG group than the UC group and SECF group.Conclusion: The three extraction methods can successfully extract the exosomes of joint effusion. The quality of exosomes obtained by the SECF method is relatively high, while the PEG precipitation method contains a small amount of impurity particles. UC method does not guarantee the integrity of exosomes. In summary, when further studying the role of exosomes in the pathogenesis of knee osteoarthritis, we recommend the SECF method to extract and isolate joint exudates.
Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage. An autopsy study with clinical correlation and review of the literature.
Authors: Valdivia-Mazeyra Mariel F. , Salas Clara , Nieves-Alonso Jesús M. , Martín-Fragueiro Luz , Bárcena Carmen , Muñoz-Hernández Patricia , Villar-Zarra Karen , Martín-López Javier , Ramasco-Rueda Fernando , Fraga Javier , Jiménez-Heffernan José A. 
Published: July 2020

Abstract
Megakaryocytes are normally present in the lung where they play a role in platelet homeostasis. The latter are well known to participate in the pathogenesis of lung damage, particularly in acute lung injury. Although megakaryocytes are usually not mentioned as a characteristic histopathologic finding associated to acute pulmonary injury, a few studies point out that their number is increased in the lungs of patients with diffuse alveolar damage. In this autopsy study we have observed a relevant number of pulmonary megakaryocytes in COVID-19 patients dying with acute respiratory distress syndrome. We have studied pulmonary tissue samples of 18 patients most of which died after prolonged disease and use of mechanical ventilation. Most samples showed fibroproliferative or fibrotic diffuse alveolar damage and an increased number of megakaryocytes. In six, thrombi of the pulmonary microcirculation were seen. We compare our findings with previous published autopsy reports, mainly focusing on the description of megakaryocytes. Our patients showed abnormal coagulation parameters with high levels of fibrinogen, D-dimers and variable thrombocytopenia. Since the lung is considered an active site of megakariopoiesis, a prothrombotic status leading to platelet activation, aggregation and consumption may trigger a compensatory pulmonary response. An increased number of pulmonary megakaryocytes suggests and supports a relation with the thrombotic events so often seen in COVID-19. Regardless of its etiology, future studies of patients dying with acute pulmonary injury should include pulmonary megakaryocytes as a histologic variable of interest.
Mental Health Impacts for International Students During the COVID-19 Pandemic in China
Authors: Wang Xiaoping , Hujjaree Khamlesh , Wang Fanglan 
Published: July 2020

Abstract
The outbreak of Coronavirus disease 2019 (COVID-19), has led to the quarantine of many residents in their homes worldwide. Some of these people might develop mental health problems, and many solutions have been put in place to address the mental health issues of patients and health professionals affected by the disease. However, not much attention has been given to international students studying in China. The present study aims to conduct an online survey to investigate the mental health status of international students from Changsha city, China.Materials and Methods: A WeChat-based survey program comprised of questions on demographic information gender, grade year, duration and status of quarantine, duration of sleep, worries about graduation, being able to go to school and presence or absence of a sense of security; as well as questions from the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) scale and State-Trait Anxiety Inventory(STAI).Results: The prevalence of depression was 59.4% and the prevalence of anxiety was 37.8%. The STAI-Y1 STATE scores had a mean value (mean) of 41.42, standard deviation (S.D) of 10.89 and STAI-Y2 TRAIT scores had a mean value (mean) of 41.85, standard deviation (S.D) of 11.13. The risk factors of anxiety or depression were Sleep duration, worrying about graduation in varying degrees, School time, and feeling secure in varying degrees. Higher the Patient Health Questionnaire-9 score and higher Generalized Anxiety Disorder-7 score and higher STAI-Y1 STATE scores were associated with higher STAI-Y2 TRAIT scores.Conclusion: The present study implies that the university needs to consider planning for acute and long-term psychological help services for international students.
Complete Response Associated With Combination Treatment Regorafenib and Sintilimab in a Sorafenib-refractory Hepatocellular Carcinoma Patient
Authors: Zhang Erlei , Zhang Zunyi , Zhang Lei , Xiang Shuai , Chen Xiaoping , Huang Zhiyong 
Published: July 2020

Abstract
Background

Most of patients diagnosed with Hepatocellular carcinoma (HCC) have advanced diseases and many are not eligible for curative therapies. There is a growing evidence suggesting that combination treatment of PD-1/PD-L1 inhibitors and tyrosine kinase inhibitors (TKIs) becomes a prospective trend for advanced HCC. For those HCC patients with sorafenib resistance, the efficacy of regorafenib combined with PD-1/PD-L1 inhibitors remains unclear.
Case presentation:

Herein, we represent a case of HCC with lung metastasis in the setting of HBV-induced liver cirrhosis responding dramatically to the combination treatment of sorafenib-regorafenib sequential and PD-1 inhibitor after initial liver resection. A 56-year-old man diagnosed with AFP-negative HCC underwent liver resection in September 2015, and was found to have solitary liver recurrence and lung metastases in March 2017. He received microwave coagulation therapy and trans-arterial chemoembolization (TACE) for liver tumor and treatment was started with sorafenib 400 mg twice daily for controlling lung metastases. In December 2018, abdominal computerized tomography (CT) scan showed two new lesions in liver. In March 2019, disease progression of lung metastases was measured and he received 160 mg regorafenib once daily. After a short period of partial response, he started treatment with regorafenib 160 mg in combination with sintilimab (200 mg, 3 weeks as a cycle) in December 2019 due to disease progression. Surprisingly, after 5 cycles of sintilimab injection, it showed complete response in target lesions. There is no clinical evidence of disease progression and the side effects were mild and well tolerated. The current overall survival is 57 months.
Conclusion

Data from this clinical case report suggests that combination therapy of regorafenib and PD-1 inhibitor is a promising therapeutic option for the treatment of advanced HCC. This is the first article reporting the complete response to regorafenib combination therapy with PD-1inhibitor for sorafenib-regractory HCC.
Prevalence and Genotypic Characterization of Hbv In Hiv- Infected Patients From Kwazulu-Natal, South Africa
Authors: Modise Lorato Mosetsanagape 
Published: July 2020

Abstract
Introduction: The co-infection of HIV with HBV is very common due to shared mode of transmission. HBV/HIV co-infection impact on low HBeAg expression, high HBV replication, causes progressive liver disease, cirrhosis, liver cancer and high mortality. Co-infection may lead to cross-resistance of HBV and HIV drugs due to drug-related immune therapeutic pressure or hepatotoxicity. These challenges necessitate continuous surveillance for HBV among HIV infected individuals to aid patient treatment management. Hence we conducted this study to characterise HBV among HIV infected patients in Durban, KwaZulu-Natal of South Africa. Methods: Serum was screened for HBsAg using ELISA, followed by DNA extraction from all samples. Genotyping of HBV was done through PCR amplification, Sanger sequencing and phylogenetic analysis. Results: Of the 50 samples in this study 100% (n = 50/50) were HBsAg positive. HBV/HIV co-infection was 82% (n = 41/50) based on PCR amplification of the HBV partial surface gene and 63% (n = 26/41) of the amplicons were successfully sequenced. Phylogenetic and sequence analyses identified patients nucleotide sequence as genotype A. Mutations prevalence in the HBsAg region was 43% (n = 18/26); including mutations associated with diagnostic failure (K122R and T143S) and 7 vaccines escape mutations (P127T, G145R, S207N, Y200T, E164D, Y206H and L209V). Mutations were determined within the polymerase region of HBV and the amino acid substitutions were identified at 54% (14/26) in different positions within the reverse transcriptase (RT) region The prevalence of mutations associated with drug resistance was 43% (n = 6/14) within the RT region. Drug resistance mutations was 67% (n = 4/6) for both lamivudine (LMV) and telbivudine (LdT) resistance, 17% (n = 1/6) for entecavir (ETV) and 33% (n = 2/6) for adefovir (ADV) resistance. Mutations causing resistance to lamivudine and telbivudine were M204V, L180M, V163I, and S202K; with S202K also causing resistance to entecavir and adefovir resistance mutation were I253Y and M250I. Multiple drug resistance mutations within a single sample contained L180M, M204V, S202K and M250I mutations. Conclusion: This study shows the predominance of HBV genotype A in HIV-infected patients and the HBV mutations present in HBV/HIV co-infected individuals. HBV mutations associated with drug resistance suggest the need for continuous HBV screening and use of tenofovir ART regimen among HBV/HIV co-infected individuals.
Engaging Patients and Family Members to Design and Implement Patient-Centered Kidney Disease Research
Authors: Browne Teri , Swoboda Amy , Ephraim Patti L. , Lang-Lindsey Katina , Green Jamie A. , Hill-Briggs Felicia , Jackson George L. , Ruff Suzanne , Schmidt Lana , Woods Peter , Danielson Patty , Bolden Shakur , Bankes Brian , Hauer Chelsie , Strigo Tara , Boulware L. Ebony 
Published: July 2020

Abstract
Background: This article describes a method for successful engagement of patients and family members in a 5-year comparative effectiveness research trial to improve transitions of care for patients from chronic kidney disease to end-stage kidney disease.Methods: This project utilized the Patient-Centered Outcomes Research Institute's conceptual model for engagement with patients and family members. We conducted a qualitative analysis of grant planning meetings to determine our patient and family member Co-Investigators' priorities for research and to include these engagement efforts in the research design. Patient and family member Co-Investigators partnered in writing this paper.Results: Patients and family members were successfully engaged in remote and in-person meetings to contribute actively to research planning and implementation stages. Three patient-centered themes emerged from our data related to engagement that informed our research plan: kidney disease treatment decision-making, care transitions from chronic to end-stage kidney disease, and patient-centered outcomes. Conclusions: The model we have employed represents a new paradigm for kidney disease research in the United States, with patients and family members engaged as full research partners. As a result, the study tests an intervention that directly responds to their needs, and it prioritizes the collection of outcomes data most relevant to patient and family member Co-Investigators.Trial registration: Clinical Trials.gov, NCT02722382. Registered 30 March 2016, https://clinicaltrials.gov/ct2/show/NCT02722382?term=NCT02722382&draw=2&rank=1
Mechanical Loading Prevents Obesity-Associated Bone Loss by Maintaining the Balance between Adipocytes and Osteoblasts
Authors: Li Xinle , Li Jie , Liu Daquan , Wang Keyu , Yokota Hiroki , Zhang Ping 
Published: July 2020

Abstract
Background: Globally increasing obesity is closely linked to bone homeostasis. Maintaining the balance between differentiate of adipocytes and osteoblasts from bone marrow mesenchymal stem cells (BMSCs) is important for bone homeostasis. While mechanical loading has been shown to improve bone remodeling by promoting osteoblast differentiation, little is known about its effects on obesity-associated bone loss. Methods: Using obese mice induced by high-fat diet and ovariectomy (OVX), the effects of mechanical loading in a form of knee loading (1 N, 5 Hz, 6 min/day) was applied with for 4 weeks. The mice were sorted into five groups: standard diet control (SC), high-fat diet control (HF), HF and loading (HFL), HF and ovariectomy (HO), and HO and loading (HOL). Femurs were harvested for histomorphometry analysis. Bone marrow-derived cells were isolated to examine the banlance between differentiation of adipocytes and osteoblasts. Immunohistochemical analyses and Western blotting analyses were performed to evaluate markers for adipocytes, osteoblasts, and Wnt signaling.Results: High-fat diet presented higher body weight, body fat, and body mass index (BMI), as well as bone loss than standard diet, and the detrimental changes in OVX mice were even higher. The daily application of knee loading significantly decreased BMI, the numbers and perimeter of adipocytes, and the differentiation of adipocytes. The expression of C/EBPα and PPARγ were suppressed by knee loading. The loaded group also presented a significant increase in bone mineral density and contents, and the circumference of trabecular bone. Regarding osteoblasts, knee loading enhanced the number of osteoblasts on bone surface, differentiation of osteoblasts, and the level of Runx2 and ALP. Furthermore, Wnt signaling involved in the effect of knee loading on attenuating obesity-induced bone loss. Conclusions: This study supported evidence that knee loading offers a new therapeutic option to prevent obesity-related bone loss by altering the balance between adipocytes and osteoblasts in the bone marrow, and the effect is associated with Wnt signaling.
Impaired Skeletal Muscle Regeneration Induced by Macrophage Depletion could not be Improved by IGF-1 Injection
Authors: Zeng Zhigang , Liu Xiaoguang , Zhao Linlin , Zheng Lifang , Zhou Yongzhan , Chen Peijie , Xiao Weihua 
Published: July 2020

Abstract
Background: Our previous study found that the depletion of macrophages led to the downregulation of insulin-like growth factor 1 (IGF-1) and impaired muscle regeneration after contusion. It was speculated that IGF-1 injection might improve the muscle repair impairment induced by macrophage depletion. Therefore, we explored whether injected IGF-1 plays an important role in improving impaired muscle repair. Methods: Animal models of muscle contusion and macrophage depletion with and without IGF-1 injection were established with gastrocnemius muscles in mice. Comprehensive histomorphological and genetic analyses were performed on the contused muscles after macrophage depletion and IGF-1 injection. Results: IGF-1 injection could promote the partial recovery of macrophage subpopulations (CD206) and the expression of vascular endothelial growth factor (VEGF) and angiopoietin -1 (Angpt-1) after macrophage depletion. However, after IGF-1 injection, the levels of regenerative myofibers and fibrosis, as well as the levels of proinflammatory macrophages (CD68) and the expression of muscle differentiation factor (MyoD), myogenin, VEGF and Angpt-1 still did not return to the levels found after simple muscle contusion in the late stage of repair. Conclusions: These results suggest that IGF-1 injection did not improve the impaired regeneration and repair of contused muscles induced by macrophage depletion.
Effect of Warm-Needling Acupuncture in Overweight and Obese Adults: Protocol for a Systematic Review and Meta-Analysis
Authors: YAO Junpeng , Chen Liping , Zheng Hui , Zhang Lin , Li Ying 
Published: July 2020

Abstract
Background: Overweight and obesity are chronic metabolic diseases characterized by abnormal or excessive fat accumulation that presents a risk to health. Warm-needling acupuncture (WNA), which combines the characteristics of acupuncture and moxibustion, has been commonly used to manage obesity with reasonable weight control in recent years. Therefore, our objective is to systematically appraise the efficacy and safety of WNA for overweight and obesity.Methods: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via PubMed), Excerpt Medica Database (EMBASE), ALT HealthWatch, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), the Chinese Biomedical Literature Database (CBM), Wanfang Data, and grey literature (trial registries, conference proceedings and academic degree dissertations) will be searched for the identification of articles. All randomized controlled trials (RCTs) involving WNA independently or as an adjunct to other active therapies, compared with the same therapies alone, will be included. The principal outcome will be the difference in BMI from baseline to the end of studies. Secondary outcomes include the change of weight, waist circumference, percentage of body fat, serum lipid before and after treatment. The severity and incidence of adverse events will be measured as the safety assessment. Study selection, data extraction, and assessment of risk of bias will be performed independently by two reviewers. A third reviewer will resolve and determine disagreements. The Review Manager software (V.5.3.5) and Stata software (V.14.0) will be used for data synthesis. Furthermore, the quality of the evidence for the results will be described according to the Grading of Recommendations Assessment, Development and Evaluation system (GRADE) with GRADEprofiler software (V.3.6.1).Discussion: This is the first systematic review to evaluate the effect of WNA in the management of obesity. This program will provide a high-quality synthesis of the current evidence to identify whether WNA is an effective therapeutic approach for overweight and obesity.Systematic review registration: PROSPERO CRD42019146380.
Characterization and Outcomes of ARDS secondary to pneumonia in patients with and without SARS-CoV-2: A single center experience
Authors: Mahida Rahul Y. , Chotalia Minesh , Alderman Joseph , Patel Chhaya , Hayden Amber , Desai Ruchi , Beesley Emily , Crowley Louise E. , Bangash Mansoor N. , Parekh Dhruv , Patel Jaimin M. , Thickett David R. 
Published: July 2020

Abstract
ARDS is the major cause of mortality in patients with SARS-CoV-2 pneumonia. We report a single-centre study comparing the characteristics of ARDS patients with and without SARS-CoV-2. A greater proportion of SARS-CoV-2 patients were from an Asian ethnic group (p=0.002). SARS-CoV-2 patients had lower circulating leukocytes, neutrophils and monocytes (p<0.0001), but higher CRP (p=0.016) on ICU admission. SARS-CoV-2 patients required a longer duration of mechanical ventilation (p=0.01), but had lower vasopressor requirements (p=0.016). While the clinical syndromes of SARS-CoV-2 and CAP-ARDS are similar, the dysregulated inflammation observed in SARS-CoV-2 may contribute to the increased duration of respiratory failure.