bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of PCSK9 inhibitors on HDL cholesterol efflux and serum cholesterol loading capacity in familial hypercholesterolemia subjects: a multi-lipid-center real-world evaluation
Authors: Palumbo Marcella , Giammanco Antonina , Purrello Francesco , Pavanello Chiara , Mombelli Giuliana , Di Pino Antonino , Piro Salvatore , Cefalù Angelo Baldassare , Calabresi Laura , Averna Maurizio , Bernini Franco , Zimetti Francesca , Adorni Maria Pia , Scicali Roberto 
Published: July 2022

Proprotein convertase subtilisin/kexin type 9 (PCSK9), beyond regulating LDL cholesterol (LDL-c) plasma levels, exerts several pleiotropic effects by modulating lipid metabolism in extrahepatic cells such as macrophages. Macrophage cholesterol homeostasis depends on serum lipoprotein functions, including the HDL capacity to promote cell cholesterol efflux (CEC) and the serum capacity to promote cell cholesterol loading (CLC). The aim of this observational study was to investigate the effect of PCSK9 inhibitors (PCSK9-i) treatment on HDL-CEC and serum CLC in patients with familial hypercholesterolemia (FH). 31 genetically confirmed FH patients were recruited. Blood was collected and serum isolated at baseline and after 6 months of PCSK9-i treatment. HDL-CEC was evaluated through the main pathways with a radioisotopic cell-based assay. Serum CLC was assessed fluorimetrically in human THP-1 monocyte-derived macrophages. After treatment with PCSK9-i, total cholesterol and LDL-c significantly decreased (−41.6%, p &lt; 0.0001 and −56.7%, p &lt; 0.0001, respectively). Total HDL-CEC was not different between patients before and after treatment. Conversely, despite no changes in HDL-c levels between the groups, ABCG1 HDL-CEC significantly increased after treatment (+22.2%, p &lt; 0.0001) as well as HDL-CEC by aqueous diffusion (+7.8%, p = 0.0008). Only a trend towards reduction of ABCA1 HDL-CEC was observed after treatment. PCSK9-i significantly decreased serum CLC (−6.6%, p = 0.0272). This effect was only partly related to the reduction of LDL-c levels. In conclusion, PCSK9-i treatment significantly increased HDL-CEC through ABCG1 and aqueous diffusion pathways and reduced the serum CLC in FH patients. The favorable effect of PCSK9-i on functional lipid profile could contribute to the cardiovascular benefit of these drugs in FH patients.
Casein kinase 2 attenuates brain injury induced by intracerebral hemorrhage via regulation of NR2B phosphorylation
Authors: Sun Zhimin , Li Qiyao , Li Xiaopeng , Shi Yunpeng , Nan Chengrui , Jin Qianxu , Wang Xiaoyan , Zhuo Yayu , Zhao Zongmao 
Published: July 2022

ObjectiveIntracerebral hemorrhage (ICH) is a common cerebrovascular disease with high incidence, disability, and mortality. Casein kinase 2 (CK2) is a serine/threonine kinase with hundreds of identified substrates and plays an important role in many diseases. This study aimed to explore whether CK2 plays protective roles in ICH-induced neuronal apoptosis, inflammation, and oxidative stress through regulation NR2B phosphorylation.MethodsCK2 expression level of brain tissues taken from ICH patients was determined by immunoblotting. Neurons from embryonic rat and astrocytes from newborn rats were cultured and treated by Hemoglobin chloride (Hemin). The proliferation of astrocytes, the apoptosis and oxidative stress of neurons and the inflammatory factors of astrocytes were detected. CK2 expression was determined in ICH model rats. The effects of CK2 overexpression plasmid (pc-CK2) on neurobehavioral defects and brain water content in ICH rats were observed.ResultsCK2 expression in ICH patients was down-regulated. Overexpression of CK2 promoted the astrocyte proliferation, inhibited neuronal apoptosis, and reduced astrocyte-mediated inflammation. N-methyl-D-aspartate receptor 2B (NR2B) reversed the effects of pc-CK2 on neurons and astrocytes. CK2 phosphorylated NR2B at the S1480 site, down-regulated the expression of NR2B and interfered with the interaction between NR2B and postsynaptic density protein 95 (PSD95). In vivo experiments showed that the expression of CK2 decreased and the expression of NR2B increased in ICH rats. Furthermore, pc-CK2 attenuated neurobehavioral defects, brain water content and neuronal damage in ICH rats.ConclusionCK2 phosphorylated NR2B, down-regulated the expression of NR2B, interfered with the interaction between NR2B and PSD95, alleviated inflammatory reactions, inhibited neuronal apoptosis and oxidative stress after ICH. CK2 and NR2B may be new potential therapeutic targets for the treatment of ICH. However, the limitation of this study is that we only investigated the regulation of NR2B by CK2.
Non-invasive brain stimulation associated mirror therapy for upper-limb rehabilitation after stroke: Systematic review and meta-analysis of randomized clinical trials
Authors: Zhao Qingqing , Li Hong , Liu Yu , Mei Haonan , Guo Liying , Liu Xianying , Tao Xiaolin , Ma Jiang 
Published: July 2022

BackgroundNon-invasive brain stimulation (NIBS) techniques and mirror therapy (MT) are promising rehabilitation measures for stroke. While the combination of MT and NIBS has been employed for post-stroke upper limb motor functional rehabilitation, its effectiveness has not been examined.ObjectiveThis study aimed to evaluate the effectiveness of combined MT and NIBS in the recovery of upper limb motor function in stroke patients.MethodsThe search was carried out in PubMed, EMBASE, Cochrane Library, Web of Science, Science Direct, CNKI, WANFANG and VIP until December 2021. Randomized clinical trials (RCTs) comparing MT or NIBS alone with the combination of NIBS and MT in improving upper extremity motor recovery after stroke were selected. A meta-analysis was performed to calculate the mean differences (MD) or the standard mean differences (SMD) and 95% confidence intervals (CI) with random-effect models. Subgroup analyses were also conducted according to the types of control group, the types of NIBS, stimulation timing and phase poststroke.ResultsA total of 12 articles, including 17 studies with 628 patients, were reviewed in the meta-analysis. In comparison with MT or NIBS alone, the combined group significantly improved body structure and function (MD = 5.97; 95% CI: 5.01–6.93; P &lt; 0.05), activity levels (SMD = 0.82; 95% CI 0.61–1.02; P &lt; 0.05). For cortical excitability, the motor evoked potential cortical latency (SMD = −1.05; 95% CI:−1.57–−0.52; P &lt; 0.05) and the central motor conduction time (SMD=-1.31 95% CI:−2.02-−0.61; P &lt; 0.05) of the combined group were significantly shortened. A non-significant homogeneous summary effect size was found for MEP amplitude (SMD = 0.47; 95%CI = −0.29 to 1.23; P = 0.23). Subgroup analysis showed that there is an interaction between the stimulation sequence and the combined treatment effect.ConclusionIn this meta-analysis of randomized clinical trials, in comparison to the control groups, MT combined with NIBS promoted the recovery of upper extremity motor function after stroke, which was reflected in the analysis of body structure and function, activity levels, and cortical excitability.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022304455.
Neurological recovery and antioxidant effect of erythropoietin for spinal cord injury: A systematic review and meta-analysis
Authors: Zhang Ya-yun , Yao Min , Zhu Ke , Xue Rui-rui , Xu Jin-hai , Cui Xue-jun , Mo Wen 
Published: July 2022

BackgroundTo critically evaluate the neurological recovery effects and antioxidant effects of erythropoietin (EPO) in rat models of spinal cord injury (SCI).MethodsThe PubMed, EMBASE, MEDLINE, ScienceDirect, and Web of Science were searched for animal experiments applying EPO to treat SCI to January 2022. We included studies which examined neurological function by the Basso, Beattie, and Bresnahan (BBB) scale, as well as cavity area and spared area, and determining the molecular-biological analysis of antioxidative effects by malondialdehyde (MDA) levels in spinal cord tissues. Meta-analysis were performed with Review Manager 5.4 software.ResultsA total of 33 studies were included in this review. The results of the meta-analysis showed that SCI rats receiving EPO therapy showed a significant locomotor function recovery after 14 days compared with control, then the superiority of EPO therapy maintained to 28 days from BBB scale. Compared with the control group, the cavity area was reduced [4 studies, weighted mean difference (WMD) = −16.65, 95% CI (−30.74 to −2.55), P = 0.02] and spared area was increased [3 studies, WMD =11.53, 95% CI (1.34 to 21.72), P = 0.03] by EPO. Meanwhile, MDA levels [2 studies, WMD = −0.63 (−1.09 to −0.18), P = 0.007] were improved in the EPO treatment group compared with control, which indicated its antioxidant effect. The subgroup analysis recommended 5,000 UI/kg is the most effective dose [WMD = 4.05 (2.23, 5.88), P &lt; 0.0001], although its effect was not statistically different from that of 1,000 UI/kg. Meanwhile, the different rat strains (Sprague-Dawley vs. Wistar), and models of animals, as well as administration method (single or multiple administration) of EPO did not affect the neuroprotective effect of EPO for SCI.ConclusionsThis systematic review indicated that EPO can promote the recovery of the locomotor function of SCI rats. The mechanism exploration of EPO needs to be verified by experiments, and then carefully designed randomized controlled trials are needed to explore its neural recovery effects.
Disrupted Brain Structural Network Connection in de novo Parkinson's Disease With Rapid Eye Movement Sleep Behavior Disorder
Authors: Chen Amei , Li Yuting , Wang Zhaoxiu , Huang Junxiang , Ruan Xiuhang , Cheng Xiaofang , Huang Xiaofei , Liang Dan , Chen Dandan , Wei Xinhua 
Published: July 2022

ObjectiveTo explore alterations in white matter network topology in de novo Parkinson's disease (PD) patients with rapid eye movement sleep behavior disorder (RBD).Materials and MethodsThis study included 171 de novo PD patients and 73 healthy controls (HC) recruited from the Parkinson's Progression Markers Initiative (PPMI) database. The patients were divided into two groups, PD with probable RBD (PD-pRBD, n = 74) and PD without probable RBD (PD-npRBD, N = 97), according to the RBD screening questionnaire (RBDSQ). Individual structural network of brain was constructed based on deterministic fiber tracking and analyses were performed using graph theory. Differences in global and nodal topological properties were analyzed among the three groups. After that, post hoc analyses were performed to explore further differences. Finally, correlations between significant different properties and RBDSQ scores were analyzed in PD-pRBD group.ResultsAll three groups presented small-world organization. PD-pRBD patients exhibited diminished global efficiency and increased shortest path length compared with PD-npRBD patients and HCs. In nodal property analyses, compared with HCs, the brain regions of the PD-pRBD group with changed nodal efficiency (Ne) were widely distributed mainly in neocortical and paralimbic regions. While compared with PD-npRBD group, only increased Ne in right insula, left middle frontal gyrus, and decreased Ne in left temporal pole were discovered. In addition, significant correlations between Ne in related brain regions and RDBSQ scores were detected in PD-pRBD patients.ConclusionsPD-pRBD patients showed disrupted topological organization of white matter in the whole brain. The altered Ne of right insula, left temporal pole and left middle frontal gyrus may play a key role in the pathogenesis of PD-RBD.
Maternal Factors in Pregnancy and Ethnicity Influence Childhood Adiposity, Cardiac Structure, and Function
Authors: Khan Sophia , Whatmore Andrew , Perchard Reena , Khan Aysha , Vyas Avni , Dua Jaspal , Cruickshank J. Kennedy , Clayton Peter 
Published: July 2022

ImportanceThe links between maternal and offspring adiposity and metabolic status are well established. There is much less evidence for the impact of these relationships combined with ethnic background on cardiac structure and function in childhood.ObjectiveTo test the hypothesis that ethnicity, maternal adiposity and glycemic status, and child adiposity affect cardiac structure and function.DesignA prospective cohort study.SettingA single-center mother-child cohort study. The cohort is a subset of the international multi-center Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study.ParticipantsThis study included 101 healthy pre-pubertal British-born children [56 White Europeans (WEs) and 45 South Asians (SAs)] with a median age of 9.1 years, range 6.0–12.2 years, at the time of the investigation.Main Outcomes and MeasuresAnthropometric and echocardiographic measurements were made on the cohort. Maternal pregnancy and birth data were available. Relationships between maternal parameters (BMI and glucose status), child adiposity, and echo measures were assessed.ResultsDespite no ethnic difference in BMI SDS at a median age of 9.1 years, SA children exhibited higher levels of body fat than WE children (whole body, right arm, and truncal fat all p &lt; 0.001). SA children also exhibited greater changes in weight and height SDS but not BMI SDS from birth than WE children. As expected, maternal BMI correlated with child BMI (r = 0.28; p = 0.006), and body fat measures (e.g., whole body fat r = 0.25; p = 0.03). Maternal fasting glucose levels were associated with child body fat measures (r = 0.22–0.28; p = 0.02–0.05). Left ventricular (LV) indices were not different between SA and WE children, but E/A and E′/A′ (measures of diastolic function) were lower in SA when compared with WE children. LV indices correlated positively to BMI SDS and body fat markers only in SA children. Maternal fasting and 2-h glucose were negatively correlated with E′/A′ in SA children (r = −0.53, p = 0.015, and r = −0.49, p = 0.023, respectively) but not in WE children.Conclusion and RelevanceSA and WE children exhibit differences in adiposity and diastolic function at a median age of 9.1 years. Novel relationships between maternal glycemia, child adiposity, and cardiac structure and function, present only in SA children, were identified.
TGF-β1-Mediated Leukocyte Cell-Derived Chemotaxin 2 Is Associated With Liver Fibrosis in Biliary Atresia
Authors: Zhao Jinfeng , Xu Xiaodan , Gou Qingyun , Zheng Qipeng , Ge Liang , Chen Lingzhi , Zhang Cong , Ma Hui , Lin Shuxiang , Hu Xiaoli , Zhan Jianghua 
Published: July 2022

ObjectiveBiliary atresia (BA) presents as a severe infantile cholangiopathy disease, characterized by progressive liver fibrosis and the resulting poor prognosis. Leukocyte cell-derived chemotaxin 2 (LECT2) was proposed as the key gene associated with hepatic fibrosis in BA, but the molecular mechanism is unclear. This study aims to investigate the function of LECT2 in BA.MethodsA total of 53 patients were enrolled in this study; 36 patients with BA, and 17 control patients with cholestasis, including congenital biliary dilations, biliary hypoplasia, and inspissated bile syndrome. The role of LECT2 in BA was analyzed using histological and cytological tests. The correlation between LECT2 and infiltrating immune cells was further analyzed by bioinformatics. The analyses were conducted using correlational analyses and ROC curves.ResultsLECT2 was highly expressed in infants with BA and positively related with fibrosis (0.1644 ± 0.0608 vs. 0.0779 ± 0.0053, p &lt; 0.0001; rs = 0.85, p &lt; 0.0001). Serum levels of LECT2 showed high distinguishing features for patients with BA having an AUC of 0.95 (95% CI: 0.90–1.00). CD163 was highly expressed in the aggravation of fibrosis (0.158 ± 0.062 vs. 0.29 ± 0.078, p &lt; 0.0001), and the expression of LECT2 was positively correlated with the accumulation of CD163+ macrophages (r = 0.48, p = 0.003). The bioinformatic analysis also showed that LECT2 was positively correlated with macrophage M2 (r = 0.34, p = 0.03). TGF-β1 and CD163 colocalized to the portal area in the livers of patients with BA. Moreover, TGF-β1 upregulated the expression of LECT2.ConclusionLECT2 is highly expressed in both BA liver tissue and serum, and serum LECT2 is a potential diagnostic biomarker of BA. Meanwhile, TGF-β1 is secreted by macrophages to regulate LECT2 associated with BA liver fibrosis.
Hermansky-Pudlak syndrome type 2: A rare cause of severe periodontitis in adolescents—A case study
Authors: Chen Jun , Yang Yifan , Liu Binjie , Xie Xiaoli , Li Wenjie 
Published: July 2022

Background and aimsHermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism (OCA) and platelet storage pool deficiency. The HPS-2 subtype is distinguished by neutropenia, and little is known about its periodontal phenotype in adolescents. AP3B1 is the causative gene for HPS-2. A 13-year-old Chinese girl presented to our department suffering from gingival bleeding and tooth mobility. Her dental history was otherwise unremarkable. Suspecting some systemic diseases as the underlying cause, the patient was referred for medical consultation, a series of blood tests, and genetic tests. In this case study, periodontal status and mutation screening of one HPS-2 case are presented.MethodsBlood analysis including a complete blood count (CBC) and glycated hemoglobin levels were measured. Platelet transmission electron microscopy (PTEM) was performed to observe the dense granules in platelets. Whole-exome sequencing (WES) and Sanger sequencing were performed to confirm the pathogenic variants.ResultsA medical diagnosis of HPS-2 was assigned to the patient. Following the medical diagnosis, a periodontal diagnosis of “periodontitis as a manifestation of systemic disease” was assigned to the patient. We identified novel compound heterozygous variants in AP3B1 (NM_003664.4: exon7: c.763C&gt;T: p.Q255*) and (NM_003664.4: exon1: c.53_56dup: p.E19Dfs*21) in this Chinese pedigree with HPS-2.ConclusionThis case study indicates the importance of periodontitis as a possible indicator of underlying systemic disease. Systemic disease screening is needed when a young patient presents with unusual, severe periodontitis, as the oral condition may be the first of a systemic abnormality. Our work also expands the spectrum of AP3B1 mutations and further provides additional genetic testing information for other HPS-2 patients.
Efficacy and safety of ultrasound-guided bleomycin combined with dexamethasone in the treatment of pediatric lymphangiomas
Authors: Zhang Yu-Tong , Zhang Chao , Wang Yu , Chang Jian 
Published: July 2022

PurposeThis work aimed to report our experience with ultrasound-guided instillation for the treatment of lymphangiomas in children, so as to determine whether the combined use of bleomycin and dexamethasone achieved a higher response rate and a lower side effect rate.MethodsThe medical records from patients with lymphangiomas between January 1st, 2013 and September 31st, 2020, were reviewed. Patients who received bleomycin combined with dexamethasone sclerotherapy were classified as the dexamethasone group, while those receiving bleomycin without dexamethasone were classified as the control group.ResultsAltogether one hundred and twenty-seven patients were diagnosed with lymphangiomas. Among them, one hundred and five patients received bleomycin combined with dexamethasone injection, while the remaining twenty-two received bleomycin injection alone. The excellent rates were 89.52% [95% confidence interval (CI), 81.64–94.40%] in the dexamethasone group and 72.73% (95% CI, 52.51–92.94%) in the control group (p &lt; 0.05). Additionally, the recurrence rates were 3.81% (95% CI, 1.22–10.03%) in the dexamethasone group and 13.64% (95% CI, 3.6–36.0%) in the control group (p &gt; 0.05). After comparison between the two groups, the following risk factors were identified. These include &gt;10 sacs at the initial stage of diagnosis, larger size after all injections, and response to the first injection.ConclusionsAlthough there was no significant difference in the recurrence rate between the two groups, this retrospective study demonstrated that the excellent response rates were dramatically improved between the two groups, suggesting that bleomycin combined with DEX was an effective and highly safe treatment for all types of pediatric lymphangiomas. Moreover, this study also identified three novel features as the significant risk factors for recurrence.
Efficacy and Safety of Iclaprim for the Treatment of Skin Structures and Soft Tissue Infections: A Methodological Framework
Authors: Wang Lian , Fan Jin , Zheng Linli , Chen Lingmin 
Published: July 2022

Background: Skin and soft tissue infections (SSTIs) are among the most common infections worldwide. They manifest in a variety of forms, such as erysipelas, cellulitis, and necrotizing fasciitis. Antibiotics are the significant method for clinical treatment of SSTIs. This study reported a methodology framework to determine the efficacy and safety of iclaprim in treatment of SSTIs.Methods: We will search the PubMed, EMbase, CNKI, WanFang Data, VIP, and ClinicalTrials.gov from their inception to June 2022 for randomized controlled trials and cohort studies on iclaprim with SSTIs. Two authors will independently screen the eligible studies, assess the quality of the included papers, and extract the required information. Randomized controlled trials will be assessed using the Cochrane risk-of-bias tool. The Newcastle–Ottawa Scale will be used to evaluate observational studies. The quality of the evidence will be evaluated using the Grading of Recommendations Assessment Development and Evaluation system. RevMan 5.3 will be used for the data synthesis and quantitative analysis.Results and Discussions: This study will provide the clinicians with more high-quality evidence to choose iclaprim for patients with SSTIs.Ethics and Dissemination: This systematic review and meta-analysis will be based on published data, so ethical approval is not necessary. The results of this meta-analysis will be published in a peer-reviewed journal.
Proteomics and Metabolomics Unveil Codonopsis pilosula (Franch.) Nannf. Ameliorates Gastric Precancerous Lesions via Regulating Energy Metabolism
Authors: He Rupu , Ma Ruyun , Jin Zheng , Zhu Yanning , Yang Fude , Hu Fangdi , Dai Jianye 
Published: July 2022

Objective: This study aimed to systematically evaluate the efficacy of Codonopsis pilosula (Franch.) Nannf. (Codonopsis Radix, CR) and reveal the mechanism of its effects on suppressing Gastric Precancerous Lesions.Methods: First, we established the GPL rat model which was induced by N-methyl-N′-nitro-N-nitrosoguanidine, a disordered diet, and 40% ethanol. The CR’s anti-Gastric Precancerous Lesions effect was comprehensively evaluated by body weight, pathological section, and serum biochemical indexes. Then, quantitative proteomics and metabolomics were conducted to unveil the disturbed protein-network and pharmacodynamic mechanism. Furthermore, serum pharmacology was employed to confirm that CR’s anti-gastritis and anti-cancer phenotype in cell models.Results: In animal models, CR had been shown to control inflammation and ameliorate Gastric Precancerous Lesions. Considering the combination of proteomics and metabolomics, we found that CR could significantly reverse the biological pathways related to energy metabolism which were disturbed by the Gastric Precancerous Lesions model. Furthermore, the results of serum pharmacology indicated that the Codonopsis Radix containing serum could ameliorate gastritis injury and selectively inhibit the proliferation of gastric cancer cells rather than normal cells, which was closely related to ATP production in the above mentioned cells.Conclusion: In summary, CR exerted anti-Gastric Precancerous Lesions effects by ameliorating gastritis injury and selectively inhibiting the proliferation of gastric cancer cells rather than normal cells. Proteomics and metabolomics unveiled that its efficacy was closely related to its regulation of the energy-metabolism pathway. This research not only provided new ideas for exploring the mechanism of complex systems such as Chinese herbals but also benefited the treatment strategy of Gastric Precancerous Lesions via regulating energy metabolism.