bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network pharmacology identify intersection genes of quercetin and Alzheimer’s disease as potential therapeutic targets
Authors: Wei Caihui , Li Shu , Zhu Yu , Chen Wenzhi , Li Cheng , Xu Renshi 
Published: August 2022

BackgroundCurrently, there are no efficient therapies for Alzheimer’s disease (AD) among the elderly, although it is the most common etiology of dementia among the elderly. Quercetin, which has a variety of therapeutic properties, may pave the way for novel approaches to AD treatment. In the AD patients’ frontal cortex, current study aims to identify the potential mechanisms of quercetin’s pharmacological targets.Materials and methodsThe pharmacological targets of quercetin have been studied from DrugBank and SwissTarget. In order to distinguish AD-associated genes targeted by quercetin (Q-ADGs), we utilized an integrated intersection of gene expressions of the frontal cortex in combination with transcriptome analysis. To detect cortex-related Q-ADGs and immune-related Q-ADGs, a drug screening database and the immune infiltration analysis was utilized. The Q-ADGs were then linked with the AD severity scores (MMSE scores) to find severity-associated Q-ADGs. In addition, the miRNA-seq datasets were examined to identify severity-associated Q-ADG-miRNAs. Twelve genes, more frequently related to AD by previous studies among all the genes identified in the present study, were subjected to the verification of qRT-PCR in AD cell model.ResultsIn the frontal lobe of AD, 207 Q-ADGs were discovered and found that axonogenesis, glial differentiation, and other biological processes had been enriched. There were 155 immune-related Q-ADGs (e.g., COX2, NOS2, HMGB1) and 65 cortex-related Q-ADGs (e.g., FOXO1, CXCL16, NOTCH3). Sixteen Q-ADGs (e.g., STAT3, RORA, BCL6) and 28 miRNAs (e.g., miR-142-5p, miR-17-5p) were found to be related to MMSE scores. In the qRT-PCR results, six out of twelve genes were significantly regulated by quercetin. DYRK1A, FOXO1, NOS2, NGF, NQO1, and RORA genes were novel target of quercetin in AD. DYRK1A, NOS2, and NQO1 genes targeted by quercetin have benefits in the treatment of AD. However, FOXO1, NGF, and RORA genes targeted by quercetin might have a negative impact on AD.ConclusionThe role of quercetin in AD appears to be multifaceted, and it can affect patients’ frontal cortex in a variety of pathways, such as axonogenesis, immune infiltration, and glial cell differentiation. DYRK1A, NOS2, and NQO1 might be potential novel effective drug targets for quercetin in AD.
Association between physical exercise, executive function, and cerebellar cortex: A cross-sectional study among the elderly in Chinese communities
Authors: Li Wei , Li Yong , Chen Yaopian , Yue Ling , Xiao Shifu 
Published: August 2022

BackgroundPrevious studies have confirmed that physical exercise may be beneficial for brain health, but there is little data on this among older Chinese.ObjectiveThe purpose of this study was to explore the relationship between physical exercise and cognitive impairment, and to explore the possible mechanism by which physical exercise prevents cognitive decline.Materials and methods192 older adults with dementia, 610 older adults with mild cognitive impairment (MCI), and 2,218 healthy older adults were included in the study. Through standardized questionnaires, we obtained their general demographic information (such as gender, age, education, etc.), disease-related information (hypertension and diabetes) and physical exercise information (such as whether they did physical exercise and the frequency of physical exercise, etc.). The mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess their overall cognitive function, while the Wechsler block diagram was used to assess their executive function. Moreover, 164 healthy, randomly selected older adults also underwent brain MRI scans at the same time, and the target brain regions included hippocampus, gray matter, and cerebellar cortex.ResultsBy using stepwise multiple logistics regression analysis, we found that physical exercise was associated with both MCI (p = 0.001*, OR = 0.689, 95%CI: 0.553–0.859) and dementia (p &lt; 0.001*, OR = 0.501, 95%CI: 0.354–0.709), independent of gender, age, education, and other factors. The results of ROC curve showed that the area under the curve of physical exercise in predicting MCI and dementia was 0.551 (p &lt; 0.001*, 95%CI: 0.525–0.577) and 0.628 (p = 0.001*, 95%CI: 0.585–0.671), respectively. The results of partial correlation analysis showed that physical exercise was associated with left cerebellar cortex (r = 0.163, p = 0.023), right cerebellar cortex (r = 0.175, p = 0.015) and Wechsler block diagram score (r = 0.235, p = 0.011). Moreover, the results of linear regression analysis mediation model showed that physical exercise may affect Wechsler block diagram score through influencing the thickness of right cerebellum cortex, and the latter may play a partial mediation effect (indirect B = 0.001, p = 0.045).ConclusionPhysical exercise might be a protective factor for mild cognitive impairment and dementia among the Chinese elderly, and there might be an association among physical exercise, executive function, and the thickness of the cerebellar cortex.
Fewer neurocognitive deficits and less brain atrophy by third ventricle measurement in PLWH treated with modern ART: A prospective analysis
Authors: Kaddu-Mulindwa Dominic , Heit Matthias , Wagenpfeil Gudrun , Bewarder Moritz , Fassbender Klaus , Behnke Stefanie , Yilmaz Umut , Fousse Mathias 
Published: August 2022

BackgroundDespite antiretroviral therapy, cognitive dysfunction seems to remain a major issue for people living with human immunodeficiency virus (PLWH). Previous studies showed a correlation between the width of the third ventricle (WTV) and neurocognitive disorders in PLWH.Patients and methodsWe investigated prevalence and correlation of neuropsychological disorders using WTV as a brain atrophy marker examined by transcranial sonography and MRI in PLWH and healthy age- and gender-matched controls. We used Becks Depression Inventory (BDI) for depression screening, the questionnaires Fatigue Severity Scale (FSS) for fatigue and Short-Form-36 (SF36) for quality of life (QoL) evaluation and Consortium to establish a registry for Alzheimer's disease (CERAD-PLUS) as neuropsychological test battery.Results52 PLWH (47 males) and 28 non-infected controls (23 males) with a median age of 52 years (24–78 years) and 51 years (22–79) were analyzed. WTV correlated significantly with age (p &lt; 0.01) but showed no significantly difference in PLWH (median = 3.4 mm) compared to healthy controls (median = 2.8 mm) (p = 0.085). PLWH had both significantly higher BDI-Scores (p = 0.005) and FSS-Scores (p = 0.012). Controls reported higher QoL (SF-36) with significant differences in most items. However, the overall cognitive performance (CERAD total score) showed no significant difference. The WTV of all subjects correlated with neurocognitive performance measured as CERAD total score (p = 0.009) and trail making tests A (p &lt; 0.001) and B (p = 0.018). There was no correlation between the scores of BDI, FSS, SF-36, and CERAD-PLUS items and WTV.ConclusionWTV is considered as a predictor of cognitive deficits in neurodegenerative diseases. Nevertheless, we found no significant difference in WTV or overall cognitive performance between PLWH and controls. PLWH suffer more often from depression and fatigue and report reduced QoL when compared to healthy controls.
Dynamic changes of amplitude of low-frequency in systemic lupus erythematosus patients with cognitive impairment
Authors: Yang Yifan , Zhao Ruotong , Zhang Fengrui , Bai Ru , Li Shu , Cui Ruomei , Liu Shuang , Xu Jian 
Published: August 2022

BackgroundCognitive dysfunction (CI) is frequently reported in patients with systemic lupus erythematosus (SLE), but the identification and assessment of SLE-related CI remain challenging. Previous studies have focused on changes in static brain activity, and no studies have investigated the characteristics of dynamic brain activity in SLE patients with CI.ObjectsWe calculated the dynamic amplitude of low-frequency fluctuation (dALFF) by combining the ALFF with a sliding window method to assess the temporal variability of brain functional activity in SLE patients with and without CI.MethodsThirty-eight SLE with CI, thirty-eight SLE without CI, and thirty-eight healthy controls (HCs) were recruited. By comparing static ALFF (sALFF) and dALFF among the three groups, changes in brain activity intensity and its temporal variability were assessed in patients with SLE with or without CI. Spearman correlation coefficients were calculated between the brain function indicator and Mini-mental State Examination (MMSE) scores of SLE with CI.ResultsSubjects among the three groups exhibited significant sALFF differences in the right parahippocampal gyrus, left caudate nucleus, right putamen, and left cuneus. Compared to the SLE without CI, the right parahippocampal gyrus exhibited higher sALFF in the SLE with CI group. Compared to the HCs, the left caudate nucleus exhibited increased sALFF in the SLE with CI group. Participants in the three groups exhibited significant dALFF variability in the right parahippocampal gyrus, right lingual gyrus, and bilateral inferior occipital gyrus. Compared to the HCs, the right lingual gyrus exhibited reduced dALFF in the SLE without CI group. Compared to the HCs, the right parahippocampal gyrus exhibited increased dALFF, left calcarine fissure, and the surrounding cortex exhibited reduced dALFF in the SLE with CI group. There was no significant correlation between the MMSE score, sALFF, and dALFF in the SLE with CI group.ConclusionSLE patients with CI have abnormal brain activity intensity and stability. By analyzing the dynamics of intrinsic brain activity, it provides a new idea for evaluating SLE-related CI. However, more research and validation with multiple metrics are needed to determine the link between the severity of cognitive impairment (CI) and brain activity in patients with SLE.
Mind-body-medicine and comprehensive lifestyle-modification in patients with Crohn's disease—Feasibility of a randomized controlled trial under pandemic circumstances
Authors: Bauer Nina , Löffler Claudia , Öznur Özlem , Uecker Christine , Keil Thomas , Langhorst Jost 
Published: August 2022

IntroductionMind-body medicine (MBM) focuses on stress reduction and lifestyle changes. The primary objective of this pilot trial was to test study feasibility of a complex integrative MBM program for patients with Crohn's disease (CD), especially in rural regions, and under pandemic conditions.MethodsPatients were stratified and randomized to the intervention group (IG) or the control group (CG). The intervention included a weekly 6-h session for 10 weeks. The CG (waiting list) received an initial 90-min workshop and started the intervention 9 months later. The primary outcome for study feasibility was recruitment and retention rates, as well as reasons for drop-out. The trial took place in Bamberg, Germany (September 2020 to December 2021).ResultsTotally 700 members of the German Crohn's and Colitis Organization—DCCV—were contacted. A total of 15% (102/700; 95% CI 12–17%) expressed interest to participate. Following screening, 41% (95% CI 32–50) were randomized to IG (n = 22) and CG (n = 20). The patients were on average (±standard deviation) 48 ± 13 years old, 67% were female, and have been suffering from CD for 20 ± 12 years. Patients traveled 71.5 ± 48.7 km (range: 9–227 km) to the intervention with no differences between IG and CG. At the 6-month follow-up, 36/42 (86%, 95% CI 74–95%) participants completed final assessment and 19/22 (86%, 95% CI 70–100%) the intervention. The most important reasons for non-responding were work-related (12/60; 20%) and for or drop-out pandemic-related anxiety (3/6). No patient and staff member became infected with SARS-CoV-2 during the study.ConclusionThe feasibility of the MBM study was confirmed in terms of predefined recruitment and retention criteria, both despite difficult conditions (including the rural setting) and patients' fears associated with the pandemic. It was crucial to develop appropriate hygiene and safety concepts that enable chronically ill patients to participate in helpful group-based interventions even under pandemic conditions.Clinical trial registrationClinicalTrials.gov, identifier: NCT05182645.
Molecular subtyping of CD5+ diffuse large B-cell lymphoma based on DNA-targeted sequencing and Lymph2Cx
Authors: Ma Dongshen , Ma Yuhan , Ma Yuanyuan , Liu Jia , Gu Ying , Liu Nian , Xiang Chenxi , Liu Hui , Sang Wei 
Published: August 2022

BackgroundCD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) showed poor prognosis in the rituximab era, with limited research on its genetic characteristics and cell of origin (COO). We aimed to demonstrate the molecular characteristics of CD5+ DLBCL and to discover potential prognostic factors.MethodsWe included 24 cases of CD5+ DLBCL and 23 CD5-negative (CD5-) counterparts and collected their clinicopathological features. Targeted DNA sequencing of 475 lymphoma-related genes was performed, and all cases were assigned to distinct genetic subtypes using the LymphGen tool. The COO was determined by the Lymph2Cx assay. The Kaplan–Meier method and Cox proportional hazards model were applied to identify the possible prognostic factors.ResultsCompared with their CD5- counterparts, patients with CD5+ DLBCL tended to have a worse prognosis and a higher incidence of MYD88L265P and CD79B double mutation (MCD) subtype (54.17%, P = 0.005) and activated B cell-like (ABC) subtype (62.5%, P = 00017), as determined by next-generation sequencing and Lymph2Cx, respectively. Moreover, PIM1, MYD88, and KMT2D mutations were detected more frequently in CD5+ DLBCL cases (P &lt; 0.05). According to multivariate analysis, MYC/BCL2 double expression and ABC subtype were correlated with unfavorable overall survival (OS). High mRNA expression of SERPINA9 and MME showed a significant correlation with a better OS, and high expression of MME showed a significant correlation with better progression-free survival in CD5+ DLBCL.ConclusionThe genetic profile of CD5+ DLBCL is characterized by PIM1, MYD88, and KMT2D mutations, with a higher incidence of MCD and ABC subtypes. MYC/BCL2 double expression, ABC subtype, and mRNA expression of SERPINA9 and MME are independently predictive of the prognosis of CD5+ DLBCL.
The Application of Pearls in Traditional Medicine of China and Their Chemical Constituents, Pharmacology, Toxicology, and Clinical Research
Authors: Song Yinglian , Chen Wanyue , Fu Ke , Wang Zhang 
Published: August 2022

Although pearls are well known by most people, their medicinal value has not been popularized. This article collates the medicinal history of pearls over 2,000 years in China, including the application of pearls in the traditional medicine of China and their various preparations, as well as the progress of their chemical constituents, pharmacology, toxicology, and clinical research. Pearls from three different sources are used as medical materiel by 9 nationalities and 251 prescription preparations in China. In addition, pearls contain various inorganic constituents, such as calcium carbonate, trace elements, and water, and organic constituents, such as amino acids. In terms of pharmacology, pearls have many effects such as calming, improving cognitive ability, being anti-epileptic, promoting bone growth and regeneration, promoting the proliferation and migration of human microvascular endothelial cells, protecting the heart, anti-hemolysis, and anti-oxidation. In terms of toxicology, pearls are safe to take for a long time without exerting obvious adverse reactions. In terms of clinical application, pearls have been used to treat many diseases and conditions, such as convulsions, epilepsy, palpitations, eye diseases, ulcer diseases, skin diseases, or skin lesions. This article provides a reference for the application and research of pearls in the future.
The add-on effects of Danhong injection among patients with ischemic stroke receiving Western medicines: A systematic review and meta-analysis
Authors: Ma Yu , Deng Ke , Liu Jiali , Ma Bin , Mei Fan , Hui Wen , Luo Xiaochao , Yao Minghong , Liu Yanmei , Qin Xuan , Zhou Xu , Zou Kang , Li Ling , Sun Xin 
Published: August 2022

Background: Danhong injection is widely used for treating ischemic stroke in China. However, its effects on ischemic stroke patients when given along with Western medicines (i.e., the add-on effect) were not well-established.Methods: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and three Chinese databases from inception to 20 July 2020 to identify randomized controlled trials (RCTs) that assessed the effects of Danhong injection as add-on therapy in patients with ischemic stroke. Pairs of trained reviewers independently screened for eligible studies, assessed risk of bias, and extracted the data. The outcomes were the National Institutes of Health Stroke Scale Score (NIHSS), Barthel index, activities of daily living (ADL), total cholesterol, and homocysteine (Hcy).Results: Sixty-seven RCTs of 6594 patients with varying risk of bias were included. Compared with Western medicine alone, the addition of Danhong injection to Western medicine significantly lowered the NIHSS score (45 RCTs with 4565 patients; MD −4.21, 95% CI −4.96 to −3.46), total cholesterol (10 trials with 1019 patients; MD −1.14 mmol/L, 95% CI −1.57 to −0.72), and Hcy (four trials with 392 patients; MD −3.54 μmol/L, 95% CI −4.38 to −2.07). The addition of Danhong also increased the Barthel index (14 trials with 1270 patients; MD 8.71, 95% CI 3.68–13.74) and ADL (12 trials with 1114 patients; MD 14.48, 95% CI 9.04–19.92) scores. Subgroup analyses showed differential effects in the average cerebral blood flow rate by mean age of patients (&lt;60 years: MD 0.74 cm/s, 95% CI 0.29–1.19; ≥60 years: MD 4.09 cm/s, 95% CI 2.02–6.16; interaction p = 0.002) and the NIHSS score by type of baseline Western medicines (interaction p &lt; 0.00001).Conclusion: The addition of Danhong injection to Western medicine may improve neurological function, self-care ability, and blood lipid level of ischemic stroke patients. However, given most included trials with unclear risk of bias, current evidence is not definitive, and more carefully designed and conducted trials are warranted to confirm our findings.Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022298628].
Corporate social responsibility of pharmaceutical industry in Korea
Authors: Bae Green , Ahn Jeong-Hoon , Lim Kyung-Min , Bae SeungJin 
Published: August 2022

Background: Global pharmaceutical companies in Korea argue that the development of innovative drugs should be recognized as a social contribution, yet it has been countered by various stakeholders. The need to distinguish between philanthropic activities and Corporate Social Responsibility (CSR) of pharmaceutical companies and reaching consensus in the Korean context has been raised. We sought to evaluate the CSR status of Korean pharmaceutical companies and collect the stakeholders’ opinions to define philanthropic activities and CSR related to pharmaceutical companies in Korea.Methods: We conducted a literature review on the definition of CSR of pharmaceutical companies, and the CSR activities of the domestic pharmaceutical companies were compared with those of global pharmaceutical companies operating in Korea. The opinions of stakeholder groups (patient advocate groups, consumer organizations, and domestic/global pharmaceutical companies) were collected using focus group interviews (FGI) and written surveys.Results: Literature review suggested that CSR is categorized as “must do” (economic and legal responsibilities), “ought to do” (ethical responsibilities), and “can do” (philanthropic responsibilities), whereas contributions beyond the economic, legal, or ethical responsibilities can be defined as “can do” (philanthropic responsibilities). Domestic pharmaceutical companies simply adopted systems for ethical and ESG (Environmental, Social, and Governance) management, which are at the “ought to do” level (ethical responsibility), whereas the headquarters of these global pharmaceutical companies established the CSR team and systematically reported on the CSR activity, including ESG management reports, which is at the “ought to do” level and further moving to the “can do” level, but the Korean branch rarely has CSR teams, and the CSR activities in Korea were also insufficient. At the FGI, the global pharmaceutical companies argued that CSR activities, such as innovative drug development, should be recognized as similar to philanthropic activities, yet stakeholders besides them suggested that those activities are “can do” rather than being philanthropic.Discussion: We found that the pharmaceutical companies in Korea are attempting to achieve the “ought to do” level (ethical responsibilities) while complying with the “must do” level (legal and economic responsibilities) yet not philanthropic activities. A social consensus regarding the philanthropic responsibilities of pharmaceutical companies in Korea was not reached.
A randomized, double-blind, parallel control study to evaluate the biosimilarity of QL1209 with Perjeta® in healthy male subjects
Authors: Sun Yuanyuan , Yang Heng , Yang Xiaoyan , Yang Shuang , Guo Can , Chen Honghui , Cui Chang , Xiang Yuxia , Yang Guoping , Huang Jie 
Published: August 2022

Purpose: This is the first study to compare the pharmacokinetics, safety and, immunogenicity of QL1209, a biosimilar of Perjeta®.Methods: This study was a randomized, double-blind, parallel-controlled clinical trial evaluating the biosimilarity between QL1209 (specification: 420 mg:14 ml, single use via, manufacturer: Qilu Pharmaceutical Co., Ltd., batch number: 201808001KJL) and Perjeta® (specification: 420 mg: 14 ml, single use via, manufacturer: Roche Pharma AG, batch number: H0309H02). The trial period was 99 days (blood samples for PK were collected 99 days after infusion). Serum concentrations were determined using a validated assay. PK parameters were calculated using a non-compartmental model and analyzed statistically. Anti-drug antibody (ADA)-positive samples were further tested for the presence of neutralization antibody detection (NAb).Results: A total of 137 healthy subjects were administrated. The subjects were randomized 1:1 to receive QL1209 or Perjeta® 420 mg intravenously. The geometric mean ratio (GMRs) for QL1209 versus Perjeta® are 104.14%, 104.09%, and 110.59% for Cmax, AUC0-t, and AUC0-∞, respectively, and their 90% confidence interval (CIs) all fell within the predefined bioequivalence margin 80.00–125%. The incidence of drug-related adverse events was 95.6% and 95.5% in the QL1209 and Perjeta® groups, respectively, also comparable between the two groups.Conclusion: The results of this comparative clinical pharmacology study demonstrated the PK similarity of QL1209 (420 mg: 14 ml) and Perjeta® (420 mg: 14 ml) and there was no significant difference in safety and immunogenicity between QL1209 and Perjeta® manufactured by Roche Pharma AG.