Publications by authors named "Chao Zhang"

3,404 Publications

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A multi-omics investigation of the composition and function of extracellular vesicles along the temporal trajectory of COVID-19.

Nat Metab 2021 Jun 22. Epub 2021 Jun 22.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.

Exosomes represent a subtype of extracellular vesicle that is released through retrograde transport and fusion of multivesicular bodies with the plasma membrane. Although no perfect methodologies currently exist for the high-throughput, unbiased isolation of pure plasma exosomes, investigation of exosome-enriched plasma fractions of extracellular vesicles can confer a glimpse into the endocytic pathway on a systems level. Here we conduct high-coverage lipidomics with an emphasis on sterols and oxysterols, and proteomic analyses of exosome-enriched extracellular vesicles (EVs hereafter) from patients at different temporal stages of COVID-19, including the presymptomatic, hyperinflammatory, resolution and convalescent phases. Our study highlights dysregulated raft lipid metabolism that underlies changes in EV lipid membrane anisotropy that alter the exosomal localization of presenilin-1 (PS-1) in the hyperinflammatory phase. We also show in vitro that EVs from different temporal phases trigger distinct metabolic and transcriptional responses in recipient cells, including in alveolar epithelial cells, which denote the primary site of infection, and liver hepatocytes, which represent a distal secondary site. In comparison to the hyperinflammatory phase, EVs from the resolution phase induce opposing effects on eukaryotic translation and Notch signalling. Our results provide insights into cellular lipid metabolism and inter-tissue crosstalk at different stages of COVID-19 and are a resource to increase our understanding of metabolic dysregulation in COVID-19.
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http://dx.doi.org/10.1038/s42255-021-00425-4DOI Listing
June 2021

Application of a targeted and quantificational foraminoplasty device in percutaneous transforaminal endoscopic discectomy for L5-S1 disc herniation: preliminary clinical outcomes.

J Orthop Surg Res 2021 Jun 22;16(1):398. Epub 2021 Jun 22.

Department of Spine Surgery, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.

Objective: Percutaneous transforaminal endoscopic discectomy (PTED) is minimally invasive and has been widely used to treat patients with lumbar disc herniation (LDH) due to its safety and efficiency. However, due to the unique anatomy of the L5-S1 level, the PTED procedure is often difficult to perform in the region. ZESSYS, a targeted and quantificational foraminoplasty device, may help to overcome these anatomical limitations. In this study, we assessed the efficiency and the short-term effects of PTED with ZESSYS at the L5-S1 level.

Methods: Between January and August of 2018, fifty-six patients with lumbar disc herniation at the single level of L5-S1 and who underwent percutaneous transforaminal endoscopic discectomy were enrolled in this retrospective cohort study. They were segregated into the transforaminal endoscopic surgical system (TESSYS) group and the ZESSYS group. The puncture time, foraminoplasty time, decompression time, and fluoroscopy time were evaluated for operation efficiency. Clinical outcomes were assessed by the visual analog scale (VAS) score and Oswestry Disability Index (ODI) score. The MacNab criteria were used to evaluate patient subjective satisfaction at 12-month follow-up postoperatively.

Results: The average puncture time (5.29 ± 2.05 min), foraminoplasty time (12.82 ± 2.52 min), and fluoroscopy time (26.29 ± 5.96 s) were all significantly shorter in the ZESSYS group than in the TESSYS group (average puncture time 8.07 ± 3.13 min, p < 0.01; foraminoplasty time, 17.18 ± 2.92 min, p < 0.01; fluoroscopy time, 34.73 ± 6.86 s; p < 0.01). No significant differences were observed between the 2 groups in the decompression time (p = 0.057). The VAS score of low back pain and leg pain, as well as the ODI score, improved at all time points postoperatively compared with preoperative, in both the TESSYS group and the ZESSYS group (P < 0.05). There were no significant differences in the VAS score of low back pain, VAS score of leg pain, and ODI score between the TESSYS group and the ZESSYS group at the same time points (P > 0.05). According to the MacNab criteria, the excellent and good rate at 12-month follow-up postoperatively was 85.7% in the TESSYS group and 89.3% in the ZESSYS group (P > 0.05).

Conclusion: The targeted and quantificational foraminoplasty device named ZESSYS was more efficient in the puncture and foraminoplasty procedures, effectively protecting the exiting nerve and minimizing the level of radiation exposure. The device is efficient and safe for PTED in treating lumbar disc herniation at the L5-S1 level.
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http://dx.doi.org/10.1186/s13018-021-02533-zDOI Listing
June 2021

Neural networks underlying hyperkinetic seizures: A quantitative PET and SEEG study.

Epilepsy Behav 2021 Jun 18;122:108130. Epub 2021 Jun 18.

Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China; Stereotactic and Functional Neurosurgery Laboratory, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; Beijing Key Laboratory of Neurostimulation, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China. Electronic address:

Objective: Hyperkinetic seizures (HKS) are characterized by complex movements that commonly occur during seizures arising from diverse cortical structures. A common semiology network may exist and analyzing the anatomo-electrical mechanisms would facilitate presurgical evaluation. Here, quantitative positron emission tomography (PET) and stereoelectroencephalography (SEEG) analysis was used to explore the underlying mechanism of HKS.

Methods: We retrospectively collected patients with epilepsy with HKS between 2014 and 2019. The interictal PET data of patients with epilepsy with HKS were compared with those of 25 healthy subjects using statistical parametric mapping to identify regions with significant hypometabolism. Then, regions of interest (ROI) for SEEG analysis were identified based on the results of PET analysis. Patients in which the ROIs were covered by intracerebral electrodes were selected for further analysis. Stereoelectroencephalography -clinical correlations with latency measurements were analyzed, and we also performed coherence analysis among ROIs both before and during HKS.

Results: Based on the inclusion criteria, 27 patients were analyzed. In the PET analysis, significant hypometabolism was observed in the ipsilateral dorsoanterior insular lobe, bilateral mesial frontal lobes (supplementary motor area/middle cingulate cortex, SMA/MCC), and the bilateral heads of the caudate nuclei in patients with HKS compared with the control group (p < 0.001). We selected dorsoanterior insula and SMA/MCC as ROIs for SEEG analysis. Eight patients with 23 HKS events were selected for further analysis. There was a linear correlation between the ictal involvement of both the dorsoanterior insula and SMA/MCC with the onset of HKS. Stereoelectroencephalography analysis indicated alpha range activity seemed more often associated with dorsoanterior insula and SMA/MCC involvement during HKS.

Conclusions: The dorsoanterior insular lobe, mesial frontal lobes (SMA/MCC), and the bilateral heads of the caudate nuclei were probably involved in the generation of HKS. The SEEG analysis further indicated that the occurrence of HKS might be partly associated with synchronized rhythmical alpha activity between dorsoanterior insula and SMA/MCC.
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http://dx.doi.org/10.1016/j.yebeh.2021.108130DOI Listing
June 2021

Material Flow Patterns of the Global Waste Paper Trade and Potential Impacts of China's Import Ban.

Environ Sci Technol 2021 Jun 21. Epub 2021 Jun 21.

Department of Ecology and Conservation Biology, Texas A&M University, College Station, Texas 77843, United States.

Waste paper, an essential substitute for wood and other plant-based fibers in paper making, is an indispensable part of the circular economy; yet, the impacts of China's ban on global waste paper cycles have not been well understood. We modeled the evolution of the global waste paper trade network during 1995-2019. We found that the cumulative trade volume of global waste paper reached 1010 million tons in the last 25 years and showed a downward trend since 2015. The global import center of waste paper experienced a transfer from Europe to East Asia and then to Southeast Asia. The ban has stimulated some developed countries to reduce the exports of unsorted waste paper since 2017, but for many major importers their changes in waste paper trade patterns were related to waste paperboard, which was not banned by China, suggesting that this import change trend may be inevitable and irrespective of China's ban. Besides, India has replaced China to become a new import hub of unsorted waste paper. Our results lay a foundation for exploring the evolution of the future global solid waste cycle under the background of zero import of solid waste increasingly implemented by China and many other developing countries.
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http://dx.doi.org/10.1021/acs.est.1c00642DOI Listing
June 2021

Observation of Negative Terahertz Photoconductivity in Large Area Type-II Dirac Semimetal PtTe_{2}.

Phys Rev Lett 2021 Jun;126(22):227402

Department of Physics, Shanghai University, Shanghai 200444, China.

As a newly emergent type-II Dirac semimetal, platinum telluride (PtTe_{2}) stands out from other two dimensional noble-transition-metal dichalcogenides for the unique band structure and novel physical properties, and has been studied extensively. However, the ultrafast response of low energy quasiparticle excitation in terahertz frequency remains nearly unexplored yet. Herein, we employ optical pump-terahertz probe (OPTP) spectroscopy to systematically study the photocarrier dynamics of PtTe_{2} thin films with varying pump fluence, temperature, and film thickness. Upon photoexcitation the terahertz photoconductivity (PC) of PtTe_{2} films shows abrupt increase initially, while the terahertz PC changes into negative value in a subpicosecond timescale, followed by a prolonged recovery process that lasted a few nanoseconds. The magnitude of both positive and negative terahertz PC response shows strongly pump fluence dependence. We assign the unusual negative terahertz PC to the formation of small polaron due to the strong electron-phonon (e-ph) coupling, which is further substantiated by temperature and film thickness dependent measurements. Moreover, our investigations give a subpicosecond timescale of simultaneous carrier cooling and polaron formation. The present study provides deep insights into the underlying dynamics evolution mechanisms of photocarrier in type-II Dirac semimetal upon photoexcitation, which is of crucial importance for designing PtTe_{2}-based optoelectronic devices.
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http://dx.doi.org/10.1103/PhysRevLett.126.227402DOI Listing
June 2021

Anti-inflammatory activity of different isolated sites of in complete Freund's adjuvant-induced arthritic rats.

Exp Ther Med 2021 Aug 8;22(2):848. Epub 2021 Jun 8.

Pharmacy Teaching and Research Department, College of Pharmacy, Wannan Medical College, Wuhu, Anhui 241002, P.R. China.

is a traditional Chinese medicine for treating arthritis and bruises. The aim of the present study was to investigate the anti-arthritic activities and possible associated mechanisms of different isolated sites of (DISC) in adjuvant-induced arthritis (AA) rats. The therapeutic effects of the extracts were assessed through changes in body weights, swelling rates, arthritis indexes (AI) and organ indexes. The levels of nitric oxide (NO), malondialdehyde and superoxide dismutase were determined using one-step method, TBA method and hydroxylamine method, respectively; the levels of TNF-α, IL-1β, IL-6, prostaglandin E, macrophage inhibitor factor-1, VEGF, immunoglobulin (Ig) G, IgM and IFN-γ in serum were determined using ELISA. Pathological changes and positive expression of VEGF in the ankle joints were investigated using hematoxylin-eosin staining and immunohistochemical staining, respectively. DISC treatment increased the weight gains and thymus indexes, and decreased the swelling rates, spleen indexes and AI in AA rats. The water isolated site (WA) and ethyl acetate isolated site (EA) significantly reversed complete Freund's adjuvant (CFA)-induced changes in the levels of NO, IL-6, TNF-α, IgG and IFN-γ, while the n-butanol isolated site (NB) only reversed the changes in IL-6 and IgG contents. Some changes in the chloroform isolated site group showed the same trend as those in the model group. The extracts relieved synovial hyperplasia, inflammatory cell infiltration and articular surface defects, and reduced the positive expression rate of VEGF in the synovial tissues of the AA rats to varying degrees. The WA exhibited the most marked effects, followed by the EA and NB, indicating that WA had optimal therapeutic effects on CFA-induced arthritic rats, which may be mediated by the oxidative stress and inhibition of inflammatory factors. may serve as a potential candidate for the treatment of rheumatoid arthritis.
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http://dx.doi.org/10.3892/etm.2021.10280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210295PMC
August 2021

Discovery of hydroxytyrosol as thioredoxin reductase 1 inhibitor to induce apoptosis and G/S cell cycle arrest in human colorectal cancer cells via ROS generation.

Exp Ther Med 2021 Aug 3;22(2):829. Epub 2021 Jun 3.

School of Pharmacy, Wannan Medical College, Wuhu, Anhui 241000, P.R. China.

Colorectal cancer (CRC) is one of the most common cancer types and a leading cause of cancer-associated mortality in China. Increased thioredoxin reductase 1 (TrxR1) levels have been previously identified as possible target for CRC. The present study revealed that the natural product hydroxytyrosol (HT), which exhibits a polyphenol scaffold, is a potent inhibitor of TrxR1. Inhibition of TrxR1 was indicated to result in accumulation of reactive oxygen species, inhibit proliferation and induce apoptosis and G/S cell cycle arrest of CRC cells. Using a C-terminal mutant TrxR1 enzyme activity assay, TrxR1 RNA interference assay and HT binding model assay, the present study demonstrated the core character of the selenocysteine residue in the interaction between HT and TrxR1. HT can serve as polyphenol scaffold to develop novel TrxR1 inhibitors for CRC treatment in the future.
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http://dx.doi.org/10.3892/etm.2021.10261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200807PMC
August 2021

Corrigendum: Learning Curve for Endovascular Treatment of Anterior Circulation Large Vessel Occlusion at a Single Center.

Front Neurol 2021 2;12:703055. Epub 2021 Jun 2.

Department of Neurology, Stroke Center, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China.

[This corrects the article DOI: 10.3389/fneur.2020.587409.].
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http://dx.doi.org/10.3389/fneur.2021.703055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207507PMC
June 2021

Stabilising Cobalt Sulphide Nanocapsules with Nitrogen-Doped Carbon for High-Performance Sodium-Ion Storage.

Nanomicro Lett 2020 Feb 12;12(1):48. Epub 2020 Feb 12.

School of Chemical Engineering, The University of Queensland, St Lucia, Brisbane, QLD, 4072, Australia.

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http://dx.doi.org/10.1007/s40820-020-0391-9DOI Listing
February 2020

Cultivating Scenedesmus dimorphus in lactic acid wastewater for cost-effective biodiesel production.

Sci Total Environ 2021 Jun 16;792:148428. Epub 2021 Jun 16.

School of Municipal and Environmental Engineering, Shandong Jianzhu University, JiNan 250101, China; Co-Innovation Center of Green Building, JiNan 250101, China.

The combination of lactic acid production wastewater and oil-producing microalgal culture could not only achieve harmless treatment of wastewater but also provided nutrients and significant amounts of water for microalgal culture. Thus the effects of different nutrients on the biomass yield, lipid yield of Scenedesmus dimorphus with lactic acid wastewater were investigated. Although lactic acid wastewater was very suitable for the cultivation of oil-producing microalgae, some nutrients were still needed. So 0.79 g/L NaNO, 14 mg/L MgSO·7HO, 4 mg/L KHPO·3HO, and trace elements needed to be added in the microalgal culture with lactic acid wastewater. In the optimized wastewater medium, the lipid yield could reach 1.54 ± 0.04 g/L, which was 48.1% higher than the level of 1.04 ± 0.06 g/L in the BG11 medium. Microalgae cells had high absorption capacity for nitrogen and phosphorus. The nitrogen, phosphorus removal rate of wastewater reached 96.31% and 90.78%, respectively, after 10 days of culture. And the treated wastewater could be used for lactic acid production for four times. These investigations laid a foundation for reducing the pollution of lactic acid wastewater, exploring a late-model for oleaginous microalgae cleaner production.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148428DOI Listing
June 2021

BET Bromodomain Inhibition Blocks an AR-Repressed, E2F1-Activated Treatment-Emergent Neuroendocrine Prostate Cancer Lineage Plasticity Program.

Clin Cancer Res 2021 Jun 18. Epub 2021 Jun 18.

Zenith Epigenetics Ltd.

Purpose: Lineage plasticity in prostate cancer-most commonly exemplified by loss of androgen receptor (AR) signaling and a switch from a luminal to alternate differentiation program-is now recognized as a treatment resistance mechanism. Lineage plasticity is a spectrum, but neuroendocrine prostate cancer (NEPC) is the most virulent example. Currently there are limited treatments for NEPC. Moreover, the incidence of treatment-emergent NEPC (t-NEPC) is increasing in the era of novel AR inhibitors. In contradistinction to de novo NEPC, t-NEPC tumors often express the AR, but AR's functional role in t-NEPC is unknown. Furthermore, targetable factors that promote t-NEPC lineage plasticity are also unclear.

Experimental Design: Using an integrative systems biology approach, we investigated enzalutamide-resistant t-NEPC cell lines and their parental, enzalutamide-sensitive adenocarcinoma cell lines. The AR is still expressed in these t-NEPC cells, enabling us to determine the role of the AR and other key factors in regulating t-NEPC lineage plasticity.

Results: AR inhibition accentuates lineage plasticity in t-NEPC cells-an effect not observed in parental enzalutamide-sensitive adenocarcinoma cells. Induction of an AR-repressed, lineage plasticity program is dependent on activation of the transcription factor E2F1 in concert with the BET bromodomain chromatin reader BRD4. BET inhibition (BETi) blocks this E2F1/BRD4-regulated program and decreases growth of t-NEPC tumor models and a subset of t-NEPC patient tumors with high activity of this program in a BETi clinical trial.

Conclusions: E2F1 and BRD4 are critical for activating an AR-repressed t-NEPC lineage plasticity program. BETi is a promising approach to block this program.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4968DOI Listing
June 2021

The impact of marital status on stage at diagnosis and survival of female patients with breast and gynecologic cancers: A meta-analysis.

Gynecol Oncol 2021 Jun 14. Epub 2021 Jun 14.

Department of Gynecology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address:

The aim of this meta-analysis is to evaluate the effect of marital status on the stage at diagnosis and survival of female patients with breast and gynecologic cancers. A systematic literature search was conducted on electronic databases (PubMed, Cochrane and EMBASE) till December 31, 2020. Publications investigating the association of marital status with stage at diagnosis and/or cancer-specific mortality (CSM) and/or overall survival (OS) in female patients with breast or gynecologic cancers were retrieved. After studies were selected according to inclusion criteria, data extraction, quality assessment and data analysis were performed. 55 articles were eligible for inclusion, consisting of 1,195,773 female cancer patients with breast, vulvar, cervical, endometrial and ovarian cancers. Unmarried female cancer patients had higher odds of being diagnosed at later stage [odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.22-1.36)] and worse survival outcomes in CSM [hazard ratio (HR) = 1.22, 95% CI: 1.16-1.28] and OS (HR = 1.20, 95% CI: 1.14-1.25). This estimate did not vary by level of social support, number of adjustment factors, or between America and Europe. Being married is associated with timely diagnosis and favorable prognosis in most women's cancers. Unmarried female cancer patients have a higher risk of late-stage diagnosis and worse survival outcomes than the married. Greater concern shall be demonstrated towards unmarried female cancer patients. Furthermore, the impact of lacking economic and emotional support on survival outcomes in unmarried female cancer patients deserves particular attention.
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http://dx.doi.org/10.1016/j.ygyno.2021.06.008DOI Listing
June 2021

Mangiferin attenuates cigarette smoke-induced chronic obstructive pulmonary disease in male albino rats.

Microvasc Res 2021 Jun 14:104208. Epub 2021 Jun 14.

Department of the sixth health care, the second Medical Center, Chinese PLA General Hospital, Beijing, China, 100048. Electronic address:

We analyzed the ability of mangiferin to suppress cigarette smoke-induced chronic obstructive pulmonary disease. Control rats showed a marked decrease in the ratio of the forced expiratory volume at 0.1 s to forced vital capacity. The decreases in the peak expiratory flow and maximal mid-expiratory flow indicated airway remodeling and enlargement. The expression levels of superoxide dismutase (SOD), heme oxygenase-1 (HO-1), γ-glutamylcysteine synthetase, nuclear factor erythroid 2-related factor 2, and activating transcription factor 4 were increased in the control rats. The levels of oxidative stress, malondialdehyde, and reactive oxygen species peaked after 24 weeks, whereas the SOD and HO-1 levels and the total antioxidant capacity were reduced in control rats. Mangiferin restored the levels of reactive oxygen species, malondialdehyde, SOD, HO-1, and T-AOC to near normal. Increased numbers of infiltrating inflammatory cells were observed in control rats but were significantly reduced by mangiferin. In addition, edema and airway inflammation were reduced by mangiferin.
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http://dx.doi.org/10.1016/j.mvr.2021.104208DOI Listing
June 2021

Surgical Disparities of Parathyroid Carcinoma: Long-Term Outcomes and Deep Excavation Based on a Large Database.

J Oncol 2021 27;2021:8898926. Epub 2021 May 27.

Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

Purpose: Parathyroid carcinoma (PC) is an uncommon endocrine disease, and surgery is considered the only potential cure. PC does not have a mature staging system because of the small number of PC patients. Our aim is to further investigate the prognostic factors associated with PC and explore the optimal extent of resection for PC patients.

Methods: Univariate and multivariate Cox regression analyses were conducted to explore the influence of relevant factors on cancer-specific survival (CSS) and overall survival (OS). Survival curves were generated using the Kaplan-Meier method and analyzed using the log-rank test. The mortality rates per 1,000 person-years were calculated to evaluate patients' follow-up data. We also performed subgroup analysis based on the extent of resection.

Results: The extent of resection was related to both CSS and OS, whereas race and extent of disease had a significant positive correlation with OS (all < 0.05). Patients who underwent parathyroidectomy had remarkably better CSS and OS than patients who did not undergo definitive treatment.

Conclusion: The extent of resection is related to CSS and OS in patients with PC. No significant difference in prognosis was observed between patients who underwent parathyroidectomy and those who underwent en bloc resection, which may provide useful parameters for the treatment of PC.
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http://dx.doi.org/10.1155/2021/8898926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178016PMC
May 2021

Perinatal low-dose bisphenol AF exposure impairs synaptic plasticity and cognitive function of adult offspring in a sex-dependent manner.

Sci Total Environ 2021 Sep 21;788:147918. Epub 2021 May 21.

Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China. Electronic address:

Bisphenol AF (BPAF), a kind of the ideal substitutes of Bisphenol A (BPA), has frequently been detected in environmental media and biological samples. Numerous studies have focused on the reproductive toxicity, cardiotoxicity and endocrine disrupting toxicity of BPAF. However, little evidence is available on neurodevelopmental toxicity of BPAF. Here, our study is to evaluate the effect of perinatal BPAF exposure (0, 0.34, 3.4 and 34 mg/kg body weight/day, correspond to Ctrl, low-, medium- and high-dose groups) on the cognitive function of adult mouse offspring. This study firstly found that perinatal BPAF exposure caused cognitive impairments of mouse offspring, in which male offspring was more sensitive than female offspring in low- and medium-dose BPAF groups. Furthermore, the dendritic arborization and complexity of hippocampal CA1 and DG neurons in male offspring were impaired in all BPAF groups, and these effects were only found in high-dose BPAF group for female offspring. The damage of BPAF to dendritic spines, and the structural basis of learning and memory, was found in male offspring but not in females. Correspondingly, perinatal BPAF exposure significantly downregulated the expressions of hippocampal PSD-95 and Synapsin-1 proteins, and male offspring was more vulnerable than female offspring. Meanwhile, we explored the alteration of hippocampal estrogen receptors (ERs) to explain the sex specific impairment of cognitive function in low- and medium-dose BPAF groups. The results showed that perinatal BPAF exposure significantly decreased the expression of ERα in male offspring in a dose-dependent manner, but not in female offspring. In addition, we found that perinatal BPAF exposure can disordered the balance of oxidation and antioxidation in hippocampus of male offspring. In summary, perinatal low-dose bisphenol AF exposure impairs synaptic plasticity and cognitive function of adult offspring in a sex-dependent manner. The present results provide a pierce of potential mechanism of BPAF-caused neurodevelopmental toxicity.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147918DOI Listing
September 2021

Mechanical property characterization of partially crystalline Poly-Ether-Ether-Ketone.

J Mech Behav Biomed Mater 2021 Jun 1;121:104600. Epub 2021 Jun 1.

CAS Key Laboratory for Mechanical Behavior and Design of Materials, Department of Modern Mechanics. University of Science and Technology of China, Hefei, Anhui, 230027, China.

The present study investigates the mechanical properties of partially crystalline Poly-Ether-Ether-Ketone between the glass transition and the cold crystallization. Biaxial tension, uniaxial tension, and DMA experiments were conducted to investigate the influence of temperature-induced crystallization on mechanical properties, and three stiffening behaviors are observed. Firstly, a 'U' type mechanical property is observed for all three experiments with first softening and then significant stiffening behavior with increasing temperature. Secondly, stiffening also occurs during low strain rate tests but not in higher strain rate tests. Thirdly, the stiffening behavior of the anisotropic film shows orientation dependence. Crystallinity evolution is predicted by the Nakaruma non-isothermal crystallization kinetics with optimized parameters, with which we demonstrate and explain that the stiffening behaviors are connected to the onset of crystallization. Therefore, the conclusion provides a new tool to approach and distinguish extrinsic and intrinsic properties during characterization, promoting future implementation for constitutive modeling and corresponding simulation that could replicate the influence of temperature-induced crystallization.
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http://dx.doi.org/10.1016/j.jmbbm.2021.104600DOI Listing
June 2021

Dietary Intake of Vegetables and Cooking Oil Was Associated With Drug-Induced Liver Injury During Tuberculosis Treatment: A Preliminary Cohort Study.

Front Nutr 2021 24;8:652311. Epub 2021 May 24.

Institute of Nutrition and Health, School of Public Health, Qingdao University, Qingdao, China.

Drug-induced liver injury is challenging during tuberculosis treatment. There is no epidemiological data investigating the relation between dietary intake and the risk of drug-induced liver injury during tuberculosis treatment. The aim of this study is to investigate the association of food and nutrient intake with the incidence of tuberculosis-drug-induced liver injury. A cohort study was conducted in two city-level tuberculosis-specialized hospitals in Linyi City and Qingdao City, China from January 2011 to December 2013. The dietary intake was assessed by a 3-day 24-h food recall survey and a standard food-frequency questionnaire. The liver functions including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were monitored throughout the 6-month tuberculosis therapy. Liver injury was defined as ALT or AST higher than two times of the upper limit of normal (ULN). Liver dysfunction was defined as ALT or AST higher than the ULN. The ULN for ALT and AST is 40 U/L. Multivariate logistic regression analyses were performed to determine the dietary factors associated with the incidence of liver injury and liver dysfunction. A total of 605 patients were included in the analysis. During the treatment, 8.1% patients exhibited liver injury and 23.3% patients exhibited liver dysfunction. A lower intake of vegetables was associated with a higher risk of liver injury [OR (95% CI): 3.50 (1.52-8.08), = 0.003) and liver dysfunction [OR (95% CI): 2.37 (1.31-4.29), = 0.004], while a lower intake of cooking oil was associated with a lower risk of liver injury [OR (95% CI): 0.44 (0.20-0.96), = 0.040)] and liver dysfunction [OR (95% CI): 0.51 (0.31-0.85), = 0.009]. The current study indicated that the higher risks of tuberculosis-drug-induced liver injury and liver dysfunction were statistically associated with decreased vegetable intake and increased cooking oil intake.
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http://dx.doi.org/10.3389/fnut.2021.652311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180911PMC
May 2021

LogPar: Logistic PARAFAC2 Factorization for Temporal Binary Data with Missing Values.

KDD 2020 Aug;2020:1625-1635

University of Illinois, Urbana-Champaign.

Binary data with one-class missing values are ubiquitous in real-world applications. They can be represented by irregular tensors with varying sizes in one dimension, where value one means presence of a feature while zero means unknown (i.e., either presence or absence of a feature). Learning accurate low-rank approximations from such binary irregular tensors is a challenging task. However, none of the existing models developed for factorizing irregular tensors take the missing values into account, and they assume Gaussian distributions, resulting in a distribution mismatch when applied to binary data. In this paper, we propose Logistic PARAFAC2 (LogPar) by modeling the binary irregular tensor with Bernoulli distribution parameterized by an underlying real-valued tensor. Then we approximate the underlying tensor with a positive-unlabeled learning loss function to account for the missing values. We also incorporate uniqueness and temporal smoothness regularization to enhance the interpretability. Extensive experiments using large-scale real-world datasets show that LogPar outperforms all baselines in both irregular tensor completion and downstream predictive tasks. For the irregular tensor completion, LogPar achieves up to 26% relative improvement compared to the best baseline. Besides, LogPar obtains relative improvement of 13.2% for heart failure prediction and 14% for mortality prediction on average compared to the state-of-the-art PARAFAC2 models.
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http://dx.doi.org/10.1145/3394486.3403213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186437PMC
August 2020

Cluster phenomenon of vertebral refractures after posterior pedicle screw fixation in a patient with glucocorticosteroid-induced Kümmell's disease: a treatment dilemma.

Arch Osteoporos 2021 Jun 8;16(1):93. Epub 2021 Jun 8.

Department of Orthopaedic Surgery, The Sixth Medical Center, General Hospital of PLA, 6# Fucheng Road, Haidian District, Beijing, 100048, China.

Introduction: Surgical treatments are usually preferred in patients with Kümmell's disease since it represents a failure of conservative treatment for osteoporotic vertebral compression fracture without evidence of spontaneous healing. However, the risk of postoperative refractures is much higher in patients with glucocorticosteroid-induced osteoporosis (GIOP) than in those with primary osteoporosis, possessing a therapeutic challenge and dilemma to orthopaedic surgeons.

Case Report: We described a rare cluster phenomenon of vertebral refractures in a patient with GIOP subsequent to segmental internal fixation for the initial management of glucocorticosteroid-induced Kümmell's disease, and a review of the literature.

Conclusion: Our patient illustrates that clinicians should be aware of the significant management dilemma and possible disastrous outcome after surgical interventions for glucocorticosteroid-induced Kümmell's disease and, thus, pay much more attention to comprehensive perioperative antiosteoporotic medications for patients with GIOP in current medical treatment.
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http://dx.doi.org/10.1007/s11657-021-00941-6DOI Listing
June 2021

Development and External Validation a Novel Inflammation-Based Score for Acute Kidney Injury and Prognosis in Intensive Care Unit Patients.

Int J Gen Med 2021 2;14:2215-2226. Epub 2021 Jun 2.

Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People's Republic of China.

Purpose: We aimed to evaluate the predictive ability of an integrated score based on several inflammatory indices of acute kidney injury (AKI) in patients in the intensive care unit (ICU).

Patients And Methods: In this observational study, 2555 patients from the Medical Information Mart for Intensive Care III database were randomly assigned to the test set (n=1599) and internal validation set (n=656). Moreover, 412 coronary care unit patients from Zhongnan Hospital, Wuhan University were also included in the external validation set. The AKI-specific inflammatory index (ASII) was created using various inflammatory indices significantly associated with AKI. We further developed and validated two nomograms based on the ASII and other informative clinical features of AKI and prognosis.

Results: The ASII was calculated as 2.317×MLR+0.417×GPS+0.007×ALRI. In the training set, patients with a high ASII had a higher risk of incident AKI (odds ratio [OR], 5.33; 95% confidence index [CI], 3.60-7.88; P<0.001) than those with a low ASII with or without pre-existing chronic kidney disease. The nomograms for AKI and prognosis based on the ASII and other significant clinical characteristics had high predictive value in the prediction of AKI and prognosis in patients in the ICU. Moreover, the results in the internal validation set and in the external validation cohort were almost consistent with those in the training set.

Conclusion: The ASII is an AKI-specific tool based on the combination of available inflammatory indices. A high ASII is a strong predictor of a higher risk of AKI and worse survival outcomes in patients in the ICU.
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http://dx.doi.org/10.2147/IJGM.S311021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180284PMC
June 2021

Dynamics of HIV reservoir decay and naïve CD4 T-cell recovery between immune non-responders and complete responders on long-term antiretroviral treatment.

Clin Immunol 2021 Jun 6;229:108773. Epub 2021 Jun 6.

Treatment and Research Center for Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. Electronic address:

Background: The dynamics of viral reservoir decay and naïve CD4 T-cell recovery between immunological non-responders (INR) and complete responders (CR) during long-term antiretroviral treatment (ART) are not fully known.

Methods: Twenty-eight chronic HIV-infected individuals on 5-year ART were divided into two groups: INR (CD4 counts ≤350 cells/μL, n = 13) and CR (CD4 counts ≥500 cells/μL, n = 15). The levels of HIV DNA and cell-associated HIV RNA (CA-RNA), CD4 counts, naïve CD4 counts and their correlations were analyzed at baseline, years 1, 3 and 5 of ART between the two groups. Expression of PD-1 on CD4 T-cells was quantified by flow cytometry. Linear mixed effect models were used to estimate the change procession in repeated measurements over 5 years. Slopes of the above-mentioned indicators were estimated using participant-specific linear regressions, respectively.

Results: INR maintained higher levels of HIV DNA and CA-RNA with higher percentages of PD-1CD4 T-cells compared with CR during 5-year ART, concurrent with lower naïve CD4 T-cells. However, the rates of HIV DNA and CA-RNA decay in INR were not different from that in CR over time, and INR had higher rates of naïve CD4 T-cell percentage recovery. The baseline levels of HIV DNA were positively associated with the 5-year levels of HIV DNA, but negatively associated with the 5-year naïve CD4 counts.

Conclusions: INR maintained significantly higher viral reservoir and lower naïve CD4 T-cells compared with CR during 5-year ART, however, the rates of reservoir decay and naïve CD4 T-cell percentage growth within INR were not lower than that in CR over time.
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http://dx.doi.org/10.1016/j.clim.2021.108773DOI Listing
June 2021

Impact and barriers of a pharmacist-led practice with computerized reminders on intravenous to oral antibiotic conversion for community-acquired pneumonia inpatients.

J Clin Pharm Ther 2021 Jun 7. Epub 2021 Jun 7.

Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

What Is Known And Objective: Intravenous to oral (IV-PO) antibiotic conversion, one of the critical elements in antimicrobial stewardship (AMS), is not well implemented in China. Studies on the strategy to apply the IV-PO conversion are needed. Our objective was to evaluate the impact and its barriers of a pharmacist-led practice with computerized reminders on IV-PO antibiotic conversion for community-acquired pneumonia (CAP) inpatients.

Method: This was a retrospective, observational pre- and post-intervention study. Interventions were introduced in 2 sequential 12-month phases: Phase 1: pharmacists implemented the conventional practice of reviewing patient charts and medication records every 24 h and verbally informed the prescribers on eligible IV-PO conversions; Phase 2: pharmacists implemented a new intervention practice to inform the prescribers with a computerized reminder in electronic medical record system on eligible IV-PO conversions.

Main Outcome Measures: The primary outcome was the proportion of patients who converted to oral therapy on the day patients were eligible for the conversion. The secondary outcomes were length of IV antibiotic therapy days, total length of antibiotic therapy days and length of hospital stay.

Results: A total of 524 patients were studied (256 in phase 1 and 268 in phase 2). The proportion of patients who converted to oral therapy on the day patients were eligible for the conversion was significantly increased from 34.77% (89/256) in phase 1 to 62.69% (168/268) in phase 2 (p < 0.05). Length of IV antibiotic therapy days in phase 2 was shortened by 1.23 days, which was 5.52 days compared to 6.75 days in phase 1 (p < 0.05). Total length of antibiotic therapy days was 12.05 days in Phase 1, compared to 10.75 days in phase 2 (p > 0.05). Length of hospital stay for patients in phase 2 was significantly shorter, with a difference of 1.38 days (6.02 days vs. 7.40 days, p < 0.05). The most common barrier of not converting IV-PO was the presence of co-morbidity.

Conclusion: The pharmacist-led IV-PO antibiotic conversion practice with computerized reminders was successful and feasible in Chinese hospitals. More IV-PO intervention studies in patients with other infections are needed in the future.
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http://dx.doi.org/10.1111/jcpt.13397DOI Listing
June 2021

MET amplification attenuates lung tumor response to immunotherapy by inhibiting STING.

Cancer Discov 2021 Jun 7. Epub 2021 Jun 7.

Hubei Cancer Hospital.

Immune checkpoint blockade (ICB) has revolutionized cancer therapy. However, the response of patients to ICB is difficult to predict. Here, we examined 81 lung cancer patients under ICB treatment and found that patients with MET amplification were resistant to ICB and had a poor progress-free survival. Tumors with MET amplifications had significantly decreased STING levels and antitumor T cell infiltration. Furthermore, we performed deep single-cell RNA sequencing on more than 20000 single immune cells and identified an immunosuppressive signature with increased subsets of XIST- and CD96-positive exhausted NK cells and decreased CD8+ T cell and NK cell populations in patients with MET-amplification. Mechanistically, we found that oncogenic MET signaling induces phosphorylation of UPF1 and downregulates tumor cell STING expression via modulation of the 3'-UTR length of STING by UPF1. Decreased efficiency of ICB by MET amplification can be overcome by inhibiting MET.
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http://dx.doi.org/10.1158/2159-8290.CD-20-1500DOI Listing
June 2021

LncRNA LINC00473 is involved in the progression of invasive pituitary adenoma by upregulating KMT5A via ceRNA-mediated miR-502-3p evasion.

Cell Death Dis 2021 Jun 5;12(6):580. Epub 2021 Jun 5.

Department of Neurosurgery, 1st Affiliated Hospital of Kunming Medical University, Kunming, China.

Long noncoding RNAs (lncRNAs) and their crosstalks with other RNAs have been revealed to be closely related to tumorigenesis and development, but their role in invasive pituitary adenoma (IPA) remains largely unclear. In our study, LINC00473 was identified as the most upregulated lncRNA in IPA by whole transcriptome RNA sequencing (RNA-Seq). Further, its related signaling pathway LINC00473/miR-502-3p/KMT5A was obtained by constructing a competing endogenous RNA (ceRNA) regulatory network. Their expression in IPA and non-invasive pituitary adenoma (NIPA) tissues was verified by qRT-PCR. Then the effects and mechanisms of LINC00473 and its ceRNA network on the proliferation of pituitary adenoma (PA) cells were confirmed by gene overexpression or silencing techniques combined with CCK-8 assay, EdU staining, flow cytometry assay, and double luciferase reporter gene assay in PA cell lines AtT-20 and GT1-1 in vitro and in a xenograft model in vivo. LINC00473 is overexpressed in IPA and can promote PA cells proliferation. Mechanistically, overexpression of LINC00473 restricts miR-502-3p through the ceRNA mechanism, upregulates KMT5A expression, and promotes the expression of cyclin D1 and CDK2, which is conducive to the cell cycle process, thereby promoting the proliferation of PA cells, involving IPA progression.
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http://dx.doi.org/10.1038/s41419-021-03861-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179925PMC
June 2021

Extraction, structure, pharmacological activities and drug carrier applications of Angelica sinensis polysaccharide.

Int J Biol Macromol 2021 Jun 6;183:2337-2353. Epub 2021 Jun 6.

College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China. Electronic address:

Angelica sinensis polysaccharide (ASP) is one of the main active components of Angelica sinensis (AS) that is widely used in traditional Chinese medicine. ASP is water-soluble polysaccharides, and it is mainly composed of glucose (Glc), galactose (Gal), arabinose (Ara), rhamnose (Rha), fucose (Fuc), xylose (Xyl) and galacturonic acid (GalUA). The extraction methods of ASP include hot water extraction and ultrasonic wave extraction, and different extraction methods can affect the yield of ASP. ASP has a variety of pharmacological activities, including hematopoietic activity, promoting immunity, antitumor, anti-inflammatory, antioxidant, anti-aging, anti-virus, liver protection, and so on. As a kind of natural polysaccharide, ASP has potential application as drug carriers. This review provides a comprehensive summary of the latest extraction and purification methods of ASP, the strategies used for monosaccharide compositional analysis plus polysaccharide structural characterization, pharmacological activities and drug carrier applications, and it can provide a basis for further study on ASP.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.213DOI Listing
June 2021

Inhibition of histone deacetylase 1 suppresses pseudorabies virus infection through cGAS-STING antiviral innate immunity.

Mol Immunol 2021 Jun 1;136:55-64. Epub 2021 Jun 1.

College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs of the People's Republic of China, PR China; International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou, Henan Province, PR China. Electronic address:

Pseudorabies virus (PRV) is an enveloped double-stranded DNA virus that is the etiological agent of Aujeszky's disease in pigs. Vaccination is currently available to prevent PRV infection, but there is still an urgent need for new strategies to control this infectious disease. Histone deacetylases (HDACs) are epigenetic regulators that regulate the histone tail, chromatin conformation, protein-DNA interaction and even transcription. Viral transcription and protein activities are intimately linked to regulation by histone acetyltransferases and HDACs that remodel chromatin and regulate gene expression. We reported here that genetic and pharmacological inhibition of HDAC1 significantly influenced PRV replication. Moreover, we demonstrated that inhibition of HDAC1 induced a DNA damage response and antiviral innate immunity. Mechanistically, the HDAC1 inhibition-induced DNA damage response resulted in the release of double-strand DNA into the cytosol to activate cyclic GMP-AMP synthase and the downstream STING/TBK1/IRF3 innate immune signaling pathway. Our results demonstrate that an HDAC1 inhibitor may be used as a new strategy to prevent Aujeszky's disease in pigs.
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http://dx.doi.org/10.1016/j.molimm.2021.05.012DOI Listing
June 2021

The feasibility of non-contrast-enhanced zero echo time magnetic resonance angiography for characterization of intracranial atherosclerotic disease.

Quant Imaging Med Surg 2021 Jun;11(6):2442-2452

Department of Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Background: Accurate and non-invasive assessment of intracranial atherosclerotic disease (ICAD) is important because of its effect on treatment planning. The aim of this study is to investigate if zero echo time (zTE) magnetic resonance angiography (zTE-MRA) is feasible in the characterization of ICAD.

Methods: A total of 175 patients with ICAD were recruited. ZTE-MRA and time-of-flight (TOF)-MRA sequences were conducted for all participants using a 3T clinical MR system. Forty-one patients also underwent digital subtraction angiography (DSA), and were confirmed to have intracranial arterial stenosis (ICAS). Weighted kappa (κ) statistics were used to assess the inter-observer agreement and diagnostic consistency of both zTE- and TOF-MRA, using DSA as a reference. The Wilcoxon signed-rank test was used to evaluate differences in image quality between zTE- and TOF-MRA images. The nonparametric test of multiple paired samples was used to compare the results of vascular stenosis diagnosis between zTE-, TOF-MRA and DSA.

Results: Supported by high inter-observer agreement (weighted κ=0.78), zTE-MRA generated significantly higher scores than TOF-MRA for susceptibility artifact signal (mean: 3.03±0.98 2.72±1.09; P=0.017) and flow signal in parent artery (mean: 3.63±0.49 3.07±0.82; P<0.001). Additionally, zTE-MRA showed more robust diagnostic performance than TOF-MRA for patients with ICAD and degree of vascular stenosis (P<0.05), and was highly consistent with reference DSA images (weighted κ=0.80).

Conclusions: ZTE-MRA has potential for use as a routine clinical method for patients with ICAD.
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http://dx.doi.org/10.21037/qims-20-696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107310PMC
June 2021

Cell Type-Specific Differentiation Between and Rice Root Tip Responses to Different Environments Based on Single-Cell RNA Sequencing.

Front Genet 2021 17;12:659500. Epub 2021 May 17.

Shanghai Key Laboratory of Signaling and Disease Research, Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Shanghai East Hospital, Tongji University, Shanghai, China.

As ssp. and ssp. are the two major subspecies of Asian cultivated rice, the adaptative evolution of these varieties in divergent environments is an important topic in both theoretical and practical studies. However, the cell type-specific differentiation between and rice varieties in response to divergent habitat environments, which facilitates an understanding of the genetic basis underlying differentiation and environmental adaptation between rice subspecies at the cellular level, is little known. We analyzed a published single-cell RNA sequencing dataset to explore the differentially expressed genes between and rice varieties in each cell type. To estimate the relationship between cell type-specific differentiation and environmental adaptation, we focused on genes in the WRKY, NAC, and BZIP transcription factor families, which are closely related to abiotic stress responses. In addition, we integrated five bulk RNA sequencing datasets obtained under conditions of abiotic stress, including cold, drought and salinity, in this study. Furthermore, we analyzed quiescent center cells in rice root tips based on orthologous markers in . We found differentially expressed genes between and rice varieties with cell type-specific patterns, which were enriched in the pathways related to root development and stress reposes. Some of these genes were members of the WRKY, NAC, and BZIP transcription factor families and were differentially expressed under cold, drought or salinity stress. In addition, _, _, _, and _ may be potential markers of quiescent center cells in rice root tips. These results identified cell type-specific differentially expressed genes between - rice varieties that were related to various environmental stresses and provided putative markers of quiescent center cells. This study provides new clues for understanding the development and physiology of plants during the process of adaptative divergence, in addition to identifying potential target genes for the improvement of stress tolerance in rice breeding applications.
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http://dx.doi.org/10.3389/fgene.2021.659500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166412PMC
May 2021

Remifentanil protects against myocardial ischemia/reperfusion injury via miR-205-mediated regulation of PINK1.

J Toxicol Sci 2021 ;46(6):263-271

Department of Cardiovascular Internal Medicine, Central People's Hospital of Zhanjiang, China.

Myocardial ischemia/reperfusion (I/R) injury could lead to severe cardiovascular ischemic disease, including myocardial infarction and contractile dysfunction. Remifentanil demonstrated protective effect on myocardial I/R injury. The underlying pathophysiological mechanism was then investigated in this study. In the current study, primary cardiomyocytes were isolated from rats, and then preconditioned with remifentanil. Rats, tail vein injected with miR-205 antagomir, were subjected to infusion of remifentanil, and then subjected to regional ischemia followed by reperfusion. The results demonstrated that cell viability of hypoxia/reoxygenation-induced cardiomyocytes was increased post remifentanil, while the apoptosis was decreased accompanied with reduced cleaved caspase-3 expression. Hypoxia/reoxygenation treatment increased miR-205 and decreased PINK1 (PTEN induced putative kinase 1) expression. However, preconditioning with remifentanil reduced miR-205 and enhanced PINK1. Moreover, over-expression of miR-205 decreased PINK1 expression and counteracted the effects of remifentanil-induced increase of cell viability and decrease of cell apoptosis in hypoxia/reoxygenation-induced cardiomyocytes. Injection with miR-205 antagomir improved remifentanil-induced decrease of infarct size and LDH (lactic acid dehydrogenase) activity in rat model with I/R injury. In conclusion, miR-205 might participate in the protective effect of remifentanil in rat myocardial I/R injury via regulation of PINK1, providing a potential target for amelioration of cardiovascular ischemic disease.
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http://dx.doi.org/10.2131/jts.46.263DOI Listing
January 2021

Differential efficacy of mycophenolate mofetil in adults with relapsing myelin oligodendrocyte glycoprotein antibody-associated disorders.

Mult Scler Relat Disord 2021 May 24;53:103035. Epub 2021 May 24.

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China. Electronic address:

Background: Myelin oligodendrocyte glycoprotein-immunoglobulin (MOG-IgG) associated disorder (MOGAD) has been recognized as a distinct disease entity with recurrent attacks. But the standard therapeutic approach to reduce relapses is unknown. Different doses of mycophenolate mofetil (MMF) are frequently used in MOGAD. We aimed to investigate the response to stratified doses of MMF in adult patients with MOGAD.

Methods: We determined the frequency of relapses in patients receiving various doses of MMF treatment for MOGAD. Patients were reviewed for relapses before and during long-term treatment. Cox proportional hazards models were used to analyze the correlation between the MMF dosage and the annualized relapse rate (ARR) as well as clinical features.

Results: 22 patients receiving low-dose MMF (< 1000 mg/day), 19 patients receiving moderate-dose MMF (1000 mg/day ≤ MMF dose < 2000 mg/day) and 21 patients receiving high-dose MMF (≥ 2000 mg/day) were collected in our cohort. Cox regression analysis showed that high-dose MMF treatment significantly reduced the risk of relapses (HR 0.501 [95% CI 0.268-0.934], p = 0.030) compared with low-dose and moderate-dose of MMF treatment, after adjusted by age, gender, disease duration and prednisone therapy. Patients (13/62) concomitant with autoimmune diseases, had a higher proportion of relapses (76.92%) compared with those without autoimmune diseases (18.37%) (HR = 5.96, 95% CI 1.73-20.48, p < 0.001). The overall median ARR reduced from 1.13 to 0.32 under high-dose MMF treatment (p = 0.004). However, there was no significant reduction in ARR either in patients with low-dose or those with moderate-dose of MMF.

Conclusion: This study suggests that high-dose of MMF treatment may reduce recurrent demyelinating attacks, with the lowest ARR. Randomized controlled studies are required to validate the effective therapeutic regimen.
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http://dx.doi.org/10.1016/j.msard.2021.103035DOI Listing
May 2021