bluuebunny/crossref_metadata_2025 huggingface dataset:
Hematological and immunological abnormalities among children receiving highly active antiretroviral therapy at Hawassa University College of Medicine and Health Sciences, Southern Ethiopia
Authors: Fenta Demissie Assegu , Wube Temesgen Bizuayehu , Nuru Metsihet Mohammed
Published: May 2020

Background: The human immunodeficiency virus (HIV) epidemic remains a serious challenge and continues to take its roll, on vulnerable populations such as children. Hematological and immunological abnormalities are common complications in children infected with human immunodeficiency virus. They are associated with an increased risk of disease progression and death. Hence; specific diagnosis and determination of these parameters are required for monitoring of treatment to avert disease progression. Therefore, this study was aimed to determine hematological and immunological parameters among HAART-experienced children at Hawassa University comprehensive specialized Hospital. METHODS A hospital-based cross-sectional study was conducted among 273 HIV-infected children from July to December 2019. Data were collected using a structured questionnaire that included variables related to sociodemographic characteristics and clinical conditions of the study individuals. Blood samples for hematological and immunological parameters were collected and analyzed using SPSS version 20. P-Value < 0.05 considered statistically significant.RESULTSA total of 273 HAART-experienced children were enrolled. Of whom 139 (50.9%) and 134 (49.1%) were females and males respectively. The baseline means hemoglobin level of the study participants was 12mg/dl and 40.7% of children were anemic. A baseline CD4+ T-cell median percentage was 18.4% and increased to 29.2% and the mean hemoglobin level at baseline was 12 mg/dl and increased to 13.1mg/dl after treatment. The prevalence of anemia, thrombocytopenia, Leucopenia, Pancytopenia, and neutropenia was 11.4, 4%, 14.3%, 2.9%, and 18.3%, respectively. All forms of hematological abnormalities were highly prevalent in children with a CD4-cell percentage <15%. It was statistically significant with leucopenia (P=0.02), Leucocytosis (P=0.02), and lymphopenia (P=0.001). Similarly, they were highly prevalent with children who had a viral load greater than 150 viral copies /mm3. It was statistically significant with anemia (P=0.002), Lymphopenia (P=<0.001), and pancytopenia (P=0.001).Prevalence of anemia (25%) and Leucocytosis (18.8%) were high among children of age group <5 years.CONCLUSION:Hematologic and immunological abnormalities were common problems among children taking highly active antiretroviral therapy. Therefore, clinicians need to routinely investigate for hematological and immunological changes with appropriate therapeutic interventions for hematological and immunological abnormalities after treatment. Furthermore, large scale and longitudinal studies are recommended to strengthen and explore the problem in-depth
The IFN-γ-IDO1-Kynureine Pathway-Induced Autophagy in Cervical Cancer Cell Promotes Phagocytosis of Macrophage
Authors: Yang Shao-Liang , Tan Hai-Xia , Niu Tian-Tian , Liu Yu-Kai , Gu Chun-Jie , Li Da-Jin , Li Ming-Qing , Wang haiyan
Published: May 2020

Bachground: Cervical cancer is a common malignant disease in female patients accompanied by active autophagy in tumor cells. However, much remains unknown about the regulatory factors of autophagy and its effect on immune response.Methods: Autophagy in HeLa and SiHa cells treated with IFN-γ, tryptophan depletion, kynurenine, and epacadostat was detected by western blot and autophagy detection kit. After co-cultured with pre-treated HeLa and SiHa cells, U937 was detected by flow cytometry to analyze the CD80, CD86, CD163, CD206 expression and the phagocytosis. Results: IFN-γ could significantly increase the autophagy level of HeLa and SiHa cells by promoting the indoleamine-2,3-dioxygenase-1 (IDO1) expression. HeLa and SiHa cells treated with recombinant human IFN-γ could significantly increase the phagocytosis and CD80, CD86 expression of U937, and this effect was associated with the autophagy in tumor cells. IFN-γ treatment and IDO1 overexpression promote tryptophan depletion and kynurenine accumulation in cervical cancer cells, and the latter was proved to be more potent in inducing autophagy of cervical cancer cells and promoting phagocytosis of macrophage. In vivo, IDO1 overexpression could significantly restrict the tumor growth in C57 mice, and the phagocytosis of macrophage was enhanced.Conclusions: IFN-γ promotes the autophagy of cervical cancer cell possibly through IDO1 expression and kynurenine metabolism, and further promotes macrophage phagocytosis in cervical cancer.
Using Regions of Homozygosity to Evaluate the Use of Dogs as Preclinical Models in Human Drug Development
Authors: Smieszek Sandra Paulina , Polymeropoulos Mihael
Published: May 2020

BACKGROUND Animals are used as preclinical models for human diseases in drug development. Dogs, especially, are used in preclinical research to support the clinical safety evaluations during drug development. Comparisons of patterns of regions of homozygosity (ROH) and phenotypes between dog and human are not well known. We conducted a genome-wide homozygosity analysis (GWHA) in the human and the dog genomes.RESULTS We calculated ROH patterns across distinct human cohorts including the Amish, the 1000 genomes, Wellderly, Vanda 1 k genomes, and Alzheimer’s cohort. The Amish provided a large cohort of extended kinships allowing for in depth family oriented analyses. The remaining human cohorts served as statistical references. We then calculated ROH across different dog breeds with emphasis on the beagle - the preferred breed used in drug development. Out of five studied human cohorts we reported the highest mean ROH in the Amish population. We calculated the extent of the genome covered by ROH (FROH) (human 3.2 Gb, dog 2.5 Gb). Overall FROH differed significantly between the Amish and the 1000 genomes, and between the human and the beagle genomes. The mean FROH per 1 Mb was ~ 16 kb for Amish, ~ 0.6 kb for Vanda 1 k, and ~ 128 kb for beagles. This result demonstrated the highest degree of inbreeding in beagles, far above that of the Amish, one of the most inbred human populations. ROH can contribute to inbreeding depression if they contain deleterious variants that are fully or partially recessive.CONCLUSIONS The differences in ROH characteristics between human and dog genomes question the applicability of dog models in preclinical research, especially when the goal is to gauge the subtle effects on the organism’s physiology produced by candidate therapeutic agents. Importantly, there are huge differences in a subset of ADME genes, specifically cytochrome P450 family (CYPs), constituting major enzymes involved in drug metabolism. We should use caution when generalizing from dog to human, even if human and beagle are relatively close species phylogenetically
A Simple Ecological Model Captures the Transmission Pattern of COVID-19 Outbreak in China
Authors: Zhang Feng , Zhang Jinmei , Cao Menglan , Hui Cang
Published: May 2020

Background The rapid spread of the 2019 novel coronavirus disease (COVID-19), initially reported in the city of Wuhan in China, and quickly transmitted to the entire nation and beyond, has become an international public health emergency. Estimating the final number of infection cases and the turning point (time with the fastest spreading rate) is crucial to assessing and improving the national and international control measures currently being applied.Methods We develop a simple model based on infectious growth with a time-varying infection rate, and estimate the final number of infections and the turning point using data updated daily from 3 February 2020, when China escalated its initial public health measures, to 10 February.Results Our model provides an extremely good fit to the existing data and therefore a reasonable estimate of the time-varying infection rate that has largely captured the transmission pattern of this epidemic outbreak. Our estimation suggests that (i) the final number of infections in China could reach 78,000 with an upper 95% confidence limit of 88,880; (ii) the turning point of the fastest spread was on the 4th or the 5th of February; and (iii) the projected period for the end of the outbreak (i.e., when 95% of the final predicted number of infection is reached) will be the 24th of February, with an upper 95% confidence limit on the 19th of March.Conclusions Our results suggest that the current control measures in China are excellent, and more than sufficient to contain the spread of this highly infectious novel coronavirus, and that the application of such measures could be considered internationally for the global control of this outbreak.
Coptidis Rhizome inhibits cell growth in HONE-1 cell line by inducing cell cycle arrest and apoptosis
Authors: Leu Kim Fey , Subramaniam Menaga , Wang Xinghua , Yang Zao , Yap Lee Fah , Lo Kwok Wai , Lim Yang Mooi
Published: May 2020

Background Nasopharyngeal carcinoma (NPC) is among the most common head and neck malignancies seen among adults in Malaysia. Therefore, discovery of novel anti-cancer herbal drugs is of importance. In this study, the cytotoxic effect was conducted on a traditional Chinese herbal prescription (Xiao Xian Xiong Decoction (XXXD) that is made up of 3 Chinese herbal medicines, namely Huanglian (Coptidis Rhizome), Banxia (Pinellia Rhizome), Gualuo (Fructus Trichosanthis).Methods The cytotoxic effect of the individual herb and in combination of two and three herbs was studied on 8 nasopharyngeal cancer cell lines. Global gene expression analysis was carried on extracted RNA using nCounter XT Gene Expression Assay.Results TWO-1, TWO-4, HONE-1, SUNE-1, CNE-2, HK-1, CNE-1 and C666-1 treated with Huanglian, the IC50 values obtained were 24.48, 11.77, 4.48, 10.72 6.32, 11.10, 6.77 and 27.30 µg/ml, respectively. For combination of Huanglian and Banxia, the IC50 values obtained were 74.09 µg/ml (TWO-1), 25.80 µg/ml (TWO-4), 38.10 µg/ml (HONE-1), 29.46 µg/ml (SUNE-1), 19.0 µg/ml (CNE-2) and 20.12 µg/ml (HK-1) but did not exert 50% cell killing in CNE-1 and C666-1 cell lines. The IC50 value attained for the combination of Huanglian and Gualuo was 40.70 µg/ml in HONE-1 cell line. The IC50 values obtained for XXXD (triple combination of Huanglian, Banxia and Gualuo)-treated in HONE-1 and CNE-2 cell lines were 88.55 and 92.42 µg/ml, respectively. Out of all these 7 groups of herbal samples, Huanglian showed the highest cytotoxicity against 8 NPC cell lines with the lowest IC50 value of 4.48 µg/ml recorded in HONE-1. Global gene expression showed Huanglian significantly downregulated genes associated with cell cycle arrest and apoptosis, and thus inhibit HONE-1 cell growth.Conclusions This study suggest that Huanglian could be a potent anticancer herb targeting HONE-1 cancer cell line.
A qualitative evaluation of Southwark Council’s public health approach for mitigating the mental health impact of the 2017 London Bridge and Borough Market terror attack
Authors: Jumbe Sandra , Milner Adrienne , Clinch Megan , Kennedy Jonathan , Pinder Richard J , Sharpe Carolyn A , Fenton Kevin
Published: May 2020

Background
Over recent years there have been several major terror attacks in cities across Europe. These attacks result in deaths, physical injuries, and pose long-term threats to mental health and wellbeing of large populations. Despite this, the mental health and wellbeing impacts of such attacks have been comparatively less examined in academic literature than the acute health response to physical injuries. This paper reflects on Southwark Council’s pioneering public health response to the June 2017 terror attack at London Bridge and Borough Market. It aims to understand the mental health and wellbeing impact of the incident, and evaluate Council led efforts to minimise mental health and wellbeing sequelae following the attack.
Methods
A rapid qualitative evaluation informed by the logic underpinning Southwark Council’s response was conducted. Nineteen in-depth semi-structured interviews with consenting Southwark Council employees, residents and workers from the London Borough of Southwark affected by the 2017 terror attack were conducted. Seven interviews were with actors involved in developing and delivering the response to ascertain the logic that underpinned it. Twelve interviews were with residents, business owners and council employees to examine the mental health and wellbeing impacts of the attack and the effectiveness of the response. A thematic analysis of transcribed interviews was undertaken.
Results
When establishing a health and wellbeing response, public health expertise and capacity provides an opportunity to dynamically identify and respond to emerging mental health and wellbeing needs. A comprehensive systematic approach to health needs assessment which draws on knowledge and relationships of key Council workers and community stakeholders is imperative. This improves communication and working relationships between statutory organisations and community stakeholders, and ensures all groups in the community are reached and supported in a manner appropriate for them. It is also critical that mental health needs of Council staff involved in delivering such a response are met. Failure to do this risks extending the negative impacts of such events.
Conclusions
This article highlights the potential of taking a public health approach in the aftermath of terror attacks. This approach has already influenced the response to the Christchurch mosque shooting in 2019.
The Effect of Temperature and Humidity May Reduce the Growth Rate of the Coronavirus Disease 2019 Epidemic
Authors: Qin Lei , Sun Qiang , Shao Jiani , Chen Yang , Zhang Xiaomei , Li Jian , Chen Mingchih , Shia Ben-Chang , Wu Szu-Yuan
Published: May 2020

Background: The effects of temperature and humidity on the epidemic growth of coronavirus disease 2019 (COVID-19)remains unclear.Methods: Daily scatter plots between the epidemic growth rate (GR) and average temperature (AT) or average relative humidity (ARH) were presented with curve fitting through the “loess” method. The heterogeneity across days and provinces were calculated to assess the necessity of using a longitudinal model. Fixed effect models with polynomial terms were developed to quantify the relationship between variations in the GR and AT or ARH.Results: An increased AT dramatically reduced the GR when the AT was lower than −5°C, the GR was moderately reduced when the AT ranged from −5°C to 15°C, and the GR increased when the AT exceeded 15°C. An increasedARH increased theGR when the ARH was lower than 72% and reduced theGR when the ARH exceeded 72%.Conclusions: High temperatures and low humidity may reduce the GR of the COVID-19 epidemic. The temperature and humidity curves were not linearly associated with the COVID-19 GR.
The Weibull Distribution on Reliability Evaluation of Mechanical Property for Impaction Bone Grafting
Authors: Yishake Mumingjiang , Tang Lan , Ye Chenyi , He Rongxin
Published: May 2020

Background: The mechanical properties of bone grafts used to reconstruct defects during revision surgery, and their long-term reliability, are important in terms of treatment outcomes. However, few relevant studies have appeared. Herein, we use a new method, the Weibull distribution, to evaluate reliability.Methods: We created impacted bone grafts of two distinct sizes (7–10 mm and small slurry) using an impacting apparatus. The elastic moduli were evaluated in vitro and the Weibull moduli (m values) were calculated.Results: The elastic moduli fitted the Weibull distribution well. Large bone grafts (7–10 mm) exhibited high elastic moduli but low Weibull moduli, suggestive of poor reliability.Conclusions: The Weibull distribution was useful to evaluate the reliability of bone graft mechanical properties. A high Weibull modulus indicated high reliability and thus low variability. Both the values and reliability of mechanical properties must be considered when contemplating bone grafting.
Effect of facet-joint degeneration on the in vivo motion of the lower lumbar spine
Authors: Yin Jun , Liu Zhang , Li Chao , Luo Shiwei , Lai Qi , Wang Shaobai , Zhang Bin , Wan Zongmiao
Published: May 2020

Objective
This research studied the in vivo motion characteristics of the L3-S1 lumbar spine with facet-joint degeneration during functional activities.
Methods
Thirteen male and 21 female patients with facet-joint degeneration at the L3-S1 spinal region were included in the study. The L3-S1 lumbar segments of all the patients were divide into 3 groups according to the degree of facet joints degeneration (mild, moderate or severe). The ranges of motion (ROM) of the vertebrae was analyzed using a combination of computed tomography and dual fluoroscopic imaging techniques. During functional postures, the ROMs were compared between the 3 groups at each spinal level (L3-L4, L4-L5, and L5-S1).
Results
At L3-L4 level, the primary rotations between the mild and moderate groups during left-right twisting activity were significantly different. At L4-L5 level, the primary rotation of the moderate group was significantly higher than the other groups during flexion-extension. During left-right bending activities a significant difference was observed only between the moderate and severe groups. At L5-S1 level, the rotation of the moderate group was significantly higher than the mild group during left-right bending activity.
Conclusions
Degeneration of the facet joint alters the ROMs of the lumbar spine. As the degree of facet-joint degeneration increased, the ROMs of the lumbar vertebra that had initially increased, declined. However, when there was severe facet-joint degeneration, the ROMs of lumbar spine declined to levels comparative to the moderate group. The relationship between the stability of the lumbar vertebra and the degree of facet-joint degeneration requires further study.
Combined posterior percutaneous pedicle screw fixation with delayed anterior monosegmental column reconstruction for unstable thoracolumbar burst fractures
Authors: Lou Chao , Yu Weiyang , Chen Zhenzhong , Jin Kangtao , Gao Jiawei , Pan Bin , Liu Feijun , He Dengwei
Published: May 2020

Objective: This study aimed to assess the feasibility as well as the clinical and radiological outcomes of posterior percutaneous pedicle screw fixation (PPSF) combined with anterior monosegmental column reconstruction in unstable thoracolumbar burst fractures. Methods: From January 2011 to August 2017, thirty-five patients with unstable thoracolumbar burst fractures were enrolled in this study. The patients underwent posterior PPSF combined surgery with delayed anterior monosegmental reconstruction utilizing titanium mesh cages. Clinical outcomes, radiological parameters, and treatment-related complications were assessed. Results: The mean age of the patients was 44.8 years. The mean operative time and blood loss were 205 min and 560 ml, respectively. The mean follow-up period was 25.2 months. The Visual analog scale (VAS) pain score was significantly improved postoperatively, and the improvement was maintained until the final follow-up. The mean sagittal kyphosis was corrected from 16.3 preoperatively to 1.5 postoperatively, which increased slightly to 2.6 at the final follow-up. In 24 patients with neurologic dysfunction, 21 (87.5 %) patients had improvement after surgery. None obvious subsidence of the titanium mesh cage and none dislodgement, loosening or breakage of the instrumentation was observed in any patient during the follow-up period. Solid bony fusion was achieved in all patients. Conclusions: Combined posterior PPSF with delayed anterior monosegmental column reconstruction for unstable thoracolumbar burst fractures can produce good clinical and radiological outcomes.
A new surgical treatment for post-tubercular thoracic kyphosis, a retrospective study.
Authors: Hu Wenhao , Liu Huawei , Hu Fangqi , Wang Qi , Li Teng , Wang Yan , Zhang Xuesong
Published: May 2020

Background: In the late stage of Spinal tuberculosis, the bony destruction and vertebral collapse often leads to significant kyphosis, presenting clinically as a painful gibbus deformity, with increased instability, vertebral body translations. Deformity more commonly occurs and rapidly progresses in the thoracic spine. The surgical treatment of deformity in the thoracic region poses a challenge to the spine surgeon because its high neurological risk. Vertebral column decancellation，a new spinal osteotomy technique, is thought to be suitable for most patients with severe rigid kyphosis. In the current study, we report VCD technique as another surgical strategy for correction of post-tubercular thoracic kyphosis and evaluate the clinical and radiographic patient results.Methods: Between January 2016 and January 2018, 16 patients with post-tubercular thoracic kyphosis underwent the Vertebral column decancellation. Preoperative and postoperative Konstam’s angle were measured. Oswestry Disability Index(ODI) ,Visual analog scale(VAS) and American Spinal Injury Association(ASIA) were documented. The mean follow-up was 31.4 months Results: The average operation time was 226 minutes (range, 200–260 minutes) with a mean intraoperative blood loss of 466 mL (range, 400–580 mL).The Konstam’s angles decreased from 88.8°(range, 76°–103°)preoperatively to 19.0°(range, 9°–32°)at the final follow-up (P<0.01). The mean VAS score was reduced from preoperative 7.0(range, 6–8) to 1.7 (range, 1–3, P<0.01) and the ODI improved from 67.6% (range, 59%–77%) to 20.7% (range, 15%–33%, P<0.01). At final follow-up, there was radiographic evidence of solid fusion at the osteotomy site and fixed segments in all patients. Neurological function improved from ASIA scale D to E in 6 patients, C to D in 3 patients.Conclusion: Our results suggest that VCD is a safe and effective treatment option for post-tubercular thoracic kyphosis. This technique achieves higher correction and fusion rates with adequate decompression of neurological elements.
Evaluation of the Risk Factors for Postoperative Neurocognitive Disorder in Elderly Patients Following Coronary Artery Bypass Grafting.
Authors: Huang Xiao , Zhang Juxia , Luo Ting , Wei Changwei , Wu Anshi
Published: May 2020

Background The incidence and risk factors of postoperative neurocognitive disorder (PND) following coronary artery bypass grafting (CABG) is still controversial. Exploring an effective and reliable predictor of PND is essential to the prevention of PND. This prospective observational study aimed to find the incidence rate as well as possible risk factors of PND in CABG.Methods Patients who underwent CABG were included. A battery of neuropsychological tests was performed preoperatively and 7 days after surgery. We used the Z score to analyze and comprehensively evaluate PND. The clinical characteristics of the patients were recorded. The levels of TNF-α, IL-1 (interleukin-1), IL-6 (interleukin-6), S100β, MDA (malondialdehyde) and T-AOC (total antioxidant capacity) were measured at different time points.Results A total of 82 patients were enrolled in the study. The incidence of PND was 25.6% 7 days after surgery. Patients were divided into the control group (N = 61) and the PND group (N = 21). The average age of patients in the PND group was 68.1 years, which was 64 years in the control group (P < 0.05). The average years of education in the PND group were significantly shorter than those in the control group (P < 0.05). The serum levels of IL-6, MDA, Il-1, and S100β in the PND group were significantly lower than those in the control group 1 day after surgery, and the T-AOC level was higher than that in the control group (P < 0.05) 1 day after surgery. The concentration of S100β in the PND group significantly higher than that in the control group 3 days after surgery (P < 0.05). Age, years of education, IL6, TAOC, MDA, IL1, and S100B were included in the multiple regression to search for risk factors of PND. The results showed that higher age (95%CI = 0.776–0.984, P = 0.026), lower years of education (95%CI = 1.006–1.736, P = 0.045) and higher MDA level (95%CI = 0.304–0.964, P = 0.037) were risk factors for PND.Conclusions Older age, lower educational level and higher MDA might be risk factors for PND 7 days after surgery. More researches in the future on this field needs to be conducted to prevent PND effectively and timely.Trail registration: The trail has been registered to the Chinese Clinical Trail Registry (ID: ChiCTR1800015606) on April 11, 2018.
Therapeutic value of curcumin on the initiation and development of inflammation in Takayasu’s arteritis mediated by HSP65-induced CCL2 overexpression
Authors: Wu Sifan , Wang Yujiao , Kong Xiufang , Fan Xiaoyong , Huang Qingrong , Sun Ying , Chen Rongyi , Yu Wensu , Ma Lili , Jiang Lindi
Published: May 2020

Background

Takayasu’s arteritis (TAK) is a chronic inflammatory disease characterized by macrophage infiltration. During the active stage, aorta adventitial fibroblasts (AAFs) proliferate excessively and produce numerous pro-inflammatory factors in the adventitia, the primary target of TAK therapy. Although the monocyte chemokine, CCL2, may contribute to macrophage infiltration in TAK arteries, whether there is an associated relationship with HSP65 remains unknown. Moreover, there are no reports of the activation of AAFs to produce inflammatory factors involvement in TAK pathogenesis. TAK treatment is associated with several challenges and contradictions. Curcumin is a traditional Chinese medicine with anti-inflammatory effects; however, its effectiveness for TAK and the underlying mechanism remains unclear.
Methods

We first verified high HSP65 expression in the aortic adventitia of TAK patients by IHC. mRNA-seq was used to profile differentially expressed genes (DEGs) between AAFs stimulated by HSP65 with or without pretreatment with curcumin, and untreated AAFs. The key chemokine, CCL2, screened by mRNA-seq was detected in the adventitia of the TAK aorta, and its correlation with HSP65 expression was analyzed by double-labelled immunofluorescence. We subsequently explored how HSP65 affected the production of inflammatory factors by AAFs at a cellular level and the related signaling pathway. We explored whether curcumin could hinder this process and verified the effect of curcumin on the level of serum CCL2 in patients with TAK.
Results

HSP65 was highly expressed in the adventitia of TAK arteries. The DEG analysis showed a key role of CCL2. The expression of CCL2 in the adventitia of TAK arteries was significantly higher than that of healthy subjects, and was correlated with HSP65. HSP65 facilitated the production of CCL2, IL-6, and IL-1β by AAFs via activation of the TLR4-JAK2/AKT/STAT3 pathway, among which the change in CCL2 was the greatest. Curcumin treatment reversed HSP65-induced CCL2 upregulation in vitro, which was more obvious than that of MTX and tofacitinib. Finally, curcumin significantly downregulated the level of serum CCL2 in TAK patients.
Conclusion

HSP65 initiates and promotes TAK inflammation by upregulating CCL2 in AAFs through the JAK2/AKT/STAT3 pathway, whereas curcumin could reverse this process and slow the initiation and development of TAK.
Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement and SLE disease activity
Authors: Zhang Mingjiao , Jie Hongyu , Wu Yong , Han Xinai , Li Xing , He Yi , Shi Xingliang , Luo Yuwei , Sun Ying , Yang Jinlong , Yang Jing , Quan Shulv , Lao Xiaobin , Tan Liping , Sun Erwei
Published: May 2020

Background
Necroptosis is a form of regulated necrosis that is involved in various autoimmune diseases. Mixed lineage kinase domain-like pseudokinase (MLKL) has been identified as a key executor of necroptosis, however, the significance of MLKL in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) has not been investigated. In this study, we aimed to determine the mRNA level of MLKL in PBMCs and examine its relationship with clinical features and serological parameters in SLE.
Methods
Real-time transcription-polymerase chain reaction analysis (RT-PCR) was used to determine expression of MLKL mRNA in PBMCs from 59 patients with SLE, 25 patients with rheumatoid arthritis (RA) and 30 age- and sex-matched healthy controls(HC). Spearman's correlation test was performed to assess the correlation of MLKL mRNA with clinical variables. The receiver operating characteristic curve (ROC) was created to evaluate the diagnostic value.
Results
Our results showed MLKL mRNA in PBMCs was upregulated in SLE patients compared to that in RA and HC individuals. SLE patients positive for anti-nuclear antibodies had significantly higher MLKL mRNA than antibody-negative patients. In SLE patients, MLKL mRNA was found to be upregulated in patients with lupus nephritis (LN) as compared with patients without LN, and also higher in active patients than in stable patients. MLKL mRNA level was significantly and positively correlated with c-reaction protein (CRP) (r = 0.3577, p = 0.0237), erythrocyte sedimentation rate (ESR) (r = 0.4091, p = 0.0043), serum immunoglobulin G (IgG) concentration (r = 0.3546, p = 0.0289) and the numbers of positive antinuclear antibodies (ANAs) (r = 0.3945, p = 0.0432). ROC analysis showed that MLKL mRNA in PBMCs had an area under the curve of 0.9277 (95% CI 0.8779–0.9775, p < 0.001) to discriminate SLE from controls.
Conclusions
These results suggest that increased MLKL mRNA level in the PBMCs of SLE patients is correlated with renal involvement and disease activity, identifying a subgroup of patients with SLE or LN who may benefit from early diagnosis and therapies targeting MLKL.
A novel prognostic model predicts overall survival in patients with nasopharyngeal carcinoma based on clinical features and blood biomarkers
Authors: Lai Changchun , Zhang Chunning , Lv Hualiang , Huang Hanqing , Ke Xia , Zhou Chuchan , Chen Hao , Chen Shulin , Zhou Lei
Published: May 2020

Background
To develop and validate a novel prognostic model to estimate overall survival (OS) in nasopharyngeal carcinoma (NPC) patients based on clinical features and blood biomarkers. And assess its incremental value to TNM staging system, clinical treatment, and Epstein-Barr virus DNA (EBV DNA) for individual OS estimation.
Methods
We retrospectively analyzed 519 consecutive NPC. A prognostic model was generated by using the Lasso-Cox regression model in training cohort (n = 346). Then comparison of predictive accuracy between the novel prognostic model, TNM staging, clinical treatment, and EBV DNA using concordance index (C-index), time-dependent ROC (tdROC), and decision curve analysis (DCA). Subsequently, a nomogram for OS incorporating the prognostic model, TNM staging and clinical treatment was built. Finally, we stratified patients into high- risk and low-risk groups according to the model risk score, and the survival time of these two groups was analyzed using Kaplan–Meier survival plots. All the results were validated in the independent validation cohort (n = 173).
Results
Using the Lasso-Cox regression, a prognostic model was established consisting of 13 variables with respect to patient prognosis. The C-index, tdROC and DCA all showed the prognostic model had good predictive accuracy and discriminatory power than TNM staging, clinical treatment and EBV DNA in training cohort. Nomogram consisting of the prognostic model, TNM staging, clinical treatment and EBV DNA shown some superior net benefit. According to the model risk score, we split the patients into two subgroups: low- risk (risk score ≤ -1.423) and high-risk (risk score > -1.423). There had significant differences in OS between the two subgroups of patients. In the validation cohort, similar results were obtained.
Conclusion
The proposed novel prognostic model based on clinical features and serological markers represents a promising signature for estimating OS in NPC patients.
Connection for TESPA1 Polymorphisms to ankylosing spondylitis incidence in the Chinese Population
Authors: Liu Hua-Wei , Wei Dai-Xu , He Da-Wei , Deng Jiu-Zheng , Zhu Jian-Jin , Xu Kai , Hu Dong , Li Jing , Hu Wen-Hao , Wang Yan- , Xiao Song-Hua , Fu Li-Gong
Published: May 2020

Background

The aim of this study was to investigate whether thymocyte-expressed, positive selection-associated 1 (TESPA1) gene polymorphisms were associated with increased risk of developing ankylosing spondylitis(AS) in a Chinese Han population.
Methods

A total of 99 AS patients were recruited as case group and 96 healthy individuals were collected as control group. TESPA1 polymorphisms were genotyped by polymerase chain reaction (PCR) and sequencing methods. The genotype distribution of TESPA1 gene rs4758993 and rs4758994 polymorphism was detected by Hardy-Weinberg equilibrium (HWE). The genotype and allele distributions of each polymorphism were also compared between groups. Moreover, odds ratios (OR) with 95% confidence intervals (95%CI) were calculated using the χ2 test to evaluate the association between AS susceptibility and TESPA1 polymorphisms.
Results

rs4758993 and rs4758994 polymorphisms were conformed to be in HWE in genotypes distribution of the control group (P > 0.05 for both). A remarkable decrease trend of rs4758993 AG genotype and A allele were detected in AS patients than in healthy controls (P = 0.01 and 0.02, respectively), indicating that they obviously decreased the risk of AS in a Chinese Han population (OR = 0.303, 95%CI = 0.144–0.637; OR = 0.002, 95%CI = 0.173–0.703). However, No significant differences were detected for TESPA1 gene rs4758994 polymorphism in both genotype and allele distributions between case and control groups (P > 0.05).
Conclusions

Our findings suggest that TESPA1 gene rs4758993 polymorphism was significantly associated with AS susceptibility in the Chinese Han population and the mutant A allele severed as a protect factor for the development of AS.
Effect of carbon nanotubes on the microstructure and properties of CPED ceramic coating
Authors: Wang Ping , Chen Xiaomin , Zhang Chunqing , Jiao Di , Jiao Shangyi , Yao Min
Published: May 2020

Cathode plasma electrolytic deposition ceramic coating modified by carbon nanotubes was prepared on Al-Si alloy. The microstructure and the heat insulation performance, fracture toughness and bending strength of the coating were investigated by SEM, XRD, the heat insulation test device and tensile testing machine. Carbon nanotubes(CNTs) are staggered in the ceramic layer and partially filled with plasma discharge micropores. To some extent, CNTs can promote the cathode plasma discharge and improve the film formation rate. The content of α-Al2O3 and t-ZrO2 phases increased with the increase of CNTs concentration. A certain amount of carbon nanotubes can effectively improve the insulation temperature of ceramic layer. With the increase of the content of carbon nanotubes, the fracture toughness and bending strength gradually increase.
Nationwide survey of patients’ and doctors’ perceptions of what is needed in doctor - patient communication in a Southeast Asian context
Authors: Tran Trung Quang , Dalen Jan van , Scherpbier Albert , Do Dung van , Wright E. Pamela
Published: May 2020

Background Asian countries are trying to apply the partnership model in doctor-patient communication that has been effectively applied in Western countries. The study aimed to investigate whether communication model used in the Western world are appropriate in Southeast Asia and to identify key items in doctor-patient communication that should be included in a doctor-patient communication model for training in Vietnam (a Southeast Asian country).Methods In six provinces, collaborating medical schools collected data from 480 patients interviewed using a structured guideline after a consultation session and from 473 doctors using a cross-sectional survey on how they conduct consultation sessions with patients. Data collection tools covered a list of communication skills based on Western models, adapted to fit with local legislation.Results Both patients and doctors considered most elements in the list necessary for good doctor-patient communication. Both also felt that while actual communication was generally good, there was also room for improvements. Furthermore, the doctors had higher expectations than the patients. Four items in the Western model for doctor-patient communication, all promoting the partnership relation between them, appeared to have lower priority for both patients and doctors in Vietnam.Conclusion The communication model used in the Western world could be applied in Vietnam with minor adaptations. Increasing patients’ understanding of their partner role needs to be considered. The implications for medical training in universities are to focus first on the key skills perceived as needed to be strengthened by both doctors and patients. In the longer term, all of these items should be included in the training to prepare for the future.
Comprehensive analysis of alternative splicing and transcriptome related to the prognosis of cervical squamous cell cancer
Authors: Li Chen , Yan Fang , Chen Gang , Li Qiang , Xian Hua , Xie Jingdun
Published: May 2020

Background: Cervical squamous cell cancer (CESC) is a common malignancy tumor with high incidence and mortality in women globally. Increasing studies have indicated that there was an indivisible association between alternative mRNA splicing (AS) and multiple types of cancer. However, comprehensive analysis of alternative mRNA splicing events is scarce in CESC. Methods: In this study, alternative mRNA splicing events data and clinical information of 216 CESC patients were downloaded from TCGA SpliceSeq database and TCGA website. We used identified survival-associated splicing events (SASEs) to construct prognostic signatures. Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curve were performed to evaluate the clinical value of prognostic signatures. A nomogram was carried out to quantitatively predict individuals’ survival probability. Regulatory network between splicing factors (SFs) and SASE was analyzed to explore the upstream regulators of a certain SASE. Additionally, we explored potential downstream pathways of a certain SASE. Results: A total of 41776 alternative splicing events in 9961 genes were collected. After sorting out SASEs, multivariable regression analysis was used to acquire 70 SASEs that could be independent prognostic factors for overall survival in CESC. Kaplan-Meier survival analyses showed that the difference was statistically significant (P＜0.01). The area under ROC curve (AUC) for all AS pattern was 0.932. A nomogram was constructed with a concordance index of 0.82 to predict individuals’ survival probability. EIF3A positively regulated SEC23A-27346-AP with highest correlation coefficient (P＜0.001, R=0.69). Besides, the most significant SASEs and KEGG pathways were SEC23A-27346-AP and adherens junction pathway (P=0.02, R=0.65). Conclusions: Prognostic signatures of survival-associated splicing events were independent prognostic factors for overall survival among CESC patients. A nomogram could quantitatively predict individuals’ survival probability. Moreover, we proposed that splicing factor EIF3A positively regulated SEC23A-27346-AP, and adherens junction pathway may be the downstream pathway of SEC23A-27346-AP. The aforementioned signaling pathway could play a crucial role in the development of CESC.
Clinical symptoms and treatment of common respiratory tract infections in relation to microbiological profiles in rural health facilities in China: implications for antibiotic stewardship
Authors: Shen Xingrong , Shen Jilu , Pan Yaping , Cheng Jing , Chai Jing , Bowker Karen , MacGowan Alasdair , Oliver Isabel , Lambert Helen , Wang Debin
Published: May 2020

Background

This study aims to identify the extent to which current clinical practice in the treatment of common respiratory tract infections (RTIs) is consistent with presenting symptoms and microbiological characteristics at health care settings in rural Anhui Province and implications for future antibiotic stewardship.
Methods

The study was implemented in one village clinic and one township health center in each of four rural residential areas in Anhui Province, China. Observations, structured and semi-structured interviews in village clinics and township health centers were conducted to investigate antibiotic use. Sputum and throat swabs were collected for bacterial culture and susceptibility testing.
Results

A total of 1068 (51.0% males and 49.0% females) completed the study. Antibiotics were prescribed for 87.8% of RTI patients. Of all the specimens tested, 329 (30.8%) specimens were isolated with bacteria. The most frequently detected bacteria were K. pneumonia (24.15% in all specimens), H. influenza (16.19%), H. parainfluenzae (14.77%), S.aureus (5.11%), M. catarrhalis (3.41%) and S. pneumoniae (2.27%). The bacteria detection was associated with age (OR = 1.91), season (OR = 0.41 to 0.60), days since infection onset (OR = 1.54 to 1.81), and runny or blocked nose (OR = 1.39 to 1.61), cough with green or white sputum (OR = 1.47 to 1.59). Antibiotic use was only linked with limited non-specific clinical manifestations e.g., days since infection onset (OR = 0.53) and sore throat (OR = 1.64).
Conclusions

The study reveals that antibiotics prescription is still very common in rural China which is driven mainly by patient reassurance and other non-pathological factors rather than treatment of bacterial infections. The study establishes the feasibility of conducting microbiological testing outside Tier 2 and 3 hospitals in rural China.
Bone mineral density in adults with osteoarthritis or rheumatoid arthritis: a cross-sectional study of a nationwide population.
Authors: Zhu Zhongxin , Hu Gangfeng , Jin Hongting , Tong Peijian
Published: May 2020

Background

It is reported that osteoporosis commonly occurs in rheumatoid arthritis (RA), whereas there is a controversial relationship with osteoarthritis (OA). In this study, we aimed to investigate the relations between OA, RA and bone mineral density (BMD) in adults aged 20–59 years.
Methods

We merged and analyzed the database from the National Health and Nutrition Examination Survey (NHANES) 2011–2018. Arthritis status and types of arthritis were obtained from questionnaires. Lumbar BMD was measured by dual-energy X-ray absorptiometry. The associations between OA, RA and lumbar BMD were evaluated using logistic regression models. Subgroup analyses stratified by gender and race were performed. The association between disease duration of arthritis and lumbar BMD was also investigated.
Results

A total of 11094 adults aged 20–59 years were analyzed in this study. Compared with the non-arthritis group, participants with OA had a higher lumbar BMD (β = 0.023; 95% CI: 0.011–0.035), while no significant association was observed in rheumatoid arthritis (β = 0.014; 95% CI: -0.003–0.031). In the subgroup analyses stratified by gender, males with OA had a higher lumbar BMD compared with those without (β = 0.014; 95% CI: -0.003–0.031). However, this association changed in females (β = 0.007; 95% CI: -0.008–0.021). On the other hand, no significant association was observed in RA in both males and females (males: β = 0.023; 95% CI: -0.003–0.048, females: β = 0.008; 95% CI: -0.015–0.031). Moreover, the disease duration of arthritis was not associated with lumbar BMD in both OA (β=-0.0001; 95% CI: -0.0017–0.0015) and RA (β = 0.0006; 95% CI: -0.0012–0.0025).
Conclusions

The correlation between OA and lumbar BMD differed by sex. Patients with OA were more likely to have higher lumbar BMD in males, but not in females. On the other hand, no significant association was found in RA both in males and females.
Layer‐specific strain and dyssynchrony index alteration in new-onset systemic lupus erythematosus patients without cardiac symptom
Authors: Luo Tingting , Wang Zhenhua , Chen Zhen , Yu Ermei , Fang Chenglong
Published: May 2020

Background

Layer-specific speckle-tracking echocardiography (STE) is a noninvasive approach assessing subclinical left ventricular (LV) dysfunction. We aimed to investigate: (I) layer‐specific strain and dyssynchrony index alteration; (II) disease parameters associated with layer-specific STE change; (III) effects of hydroxychloroquine (HCQ) therapy on layer-specific STE parameters in drug-naïve patients with new-onset systemic lupus erythematosus (SLE) without cardiac symptoms.
Methods

35 drug-naïve patients with new-onset SLE and 25 age-and-sex-matched healthy controls were enrolled. All individuals received both conventional echocardiographic and two-dimensional STE assessment. Layer-specific global longitudinal strain (GLS), global circumferential strain (GCS) and peak systolic dispersion (PSD) were acquired in layer-specific STE. The effect of HCQ monotherapy on GLS parameters and PSD was assessed in 7 SLE patients with stable disease.
Results

All patients had normal left ventricular ejection fraction (LVEF). Conventional echocardiographic parameters were comparable between patients and controls. Decreased layer-specific GLS and elevated PSD were observed in SLE patients. In contrast, there’s no difference of layer-specific GCS at the basal level, papillary muscle level and apical level between patients and controls. More severely impaired GLS was observed in patients with higher disease activity, high-risk aPL profile or renal involvement. PSD increased in patients with higher disease activity or high-risk aPL profile. Correlational analysis showed that GLS at three layers and PSD correlated with high-sensitivity CRP (hsCRP) levels. PSD correlated with epicardial GLS, when treating hsCRP level, renal involvement, profile of aPL and disease activity as control variables. Multivariate regression showed hsCRP level and epicardial GLS are the predictors of layer-specific GLS impairment and elevated PSD, respectively. No change of GLS at three layers or PSD was observed in the first 6 months of HCQ treatment, compared with baseline. During the second 6 months of HCQ treatment, increase of endocardial GLS and whole layer GLS, and decrease of PSD were detected. There was no change of epicardial GLS during follow-up.
Conclusion

Drug-naïve patients with new-onset SLE, even having normal LVEF, are likely to have subclinical GLS impairment and LV dyssynchrony. SLE-related risk factors are associated with these dysfunctions. Continuous use of HCQ may provide beneficial effects to the silent cardiac impairment.