Publications by authors named "Lijun Jiang"

113 Publications

Prevalence of depressive disorders and treatment in China: a cross-sectional epidemiological study.

Lancet Psychiatry 2021 Sep 21. Epub 2021 Sep 21.

Mental Health Centre, West China Hospital, Sichuan University, Chengdu, China.

Background: In China, depressive disorders have been estimated to be the second leading cause of years lived with disability. However, nationally representative epidemiological data for depressive disorders, in particular use of mental health services by adults with these disorders, are unavailable in China. The present study, part of the China Mental Health Survey, 2012-15, aims to describe the socioeconomic characteristics and the use of mental health services in people with depressive disorders in China.

Methods: The China Mental Health Survey was a cross-sectional epidemiological survey of mental disorders in a multistage clustered-area probability sample of adults of Chinese nationality (≥18 years) from 157 nationwide representative population-based disease surveillance points in 31 provinces across China. Trained investigators interviewed the participants with the Composite International Diagnostic Interview 3.0 to ascertain the presence of lifetime and 12-month depressive disorders according to DSM-IV criteria, including major depressive disorder, dysthymic disorder, and depressive disorder not otherwise specified. Participants with 12-month depressive disorders were asked whether they received any treatment for their emotional problems during the past 12 months and, if so, the specific types of treatment providers. The Sheehan Disability Scale (SDS) was used to assess impairments associated with 12-month depressive symptoms. Data-quality control procedures included logic check by computers, sequential recording check, and phone-call check by the quality controllers, and reinterview check by the psychiatrists. Data were weighted according to the age-sex-residence distribution data from China's 2010 census population survey to adjust for differential probabilities of selection and differential response, as well as to post-stratify the sample to match the population distribution.

Findings: 28 140 respondents (12 537 [44·6%] men and 15 603 [55·4%] women) completed the survey between July 22, 2013, and March 5, 2015. Ethnicity data (Han or non-Han) were collected for only a subsample. Prevalence of any depressive disorders was higher in women than men (lifetime prevalence odds ratio [OR] 1·44 [95% CI 1·20-1·72] and 12-month prevalence OR 1·41 [1·12-1·78]), in unemployed people than employed people (lifetime OR 2·38 [95% CI 1·68-3·38] and 12-month OR 2·80 [95% CI 1·88-4·18]), and in people who were separated, widowed, or divorced compared with those who were married or cohabiting (lifetime OR 1·87 [95% CI 1·39-2·51] and 12-month OR 1·85 [95% CI 1·40-2·46]). Overall, 574 (weighted % 75·9%) of 744 people with 12-month depressive disorders had role impairment of any SDS domain: 439 (83·6%) of 534 respondents with major depressive disorder, 207 (79·8%) of 254 respondents with dysthymic disorder, and 122 (59·9%) of 189 respondents with depressive disorder not otherwise specified. Only an estimated 84 (weighted % 9·5%) of 1007 participants with 12-month depressive disorders were treated in any treatment sector: 38 (3·6%) in speciality mental health, 20 (1·5%) in general medical, two (0·3%) in human services, and 21 (2·7%) in complementary and alternative medicine. Only 12 (0·5%) of 1007 participants with depressive disorders were treated adequately.

Interpretation: Depressive disorders in China were more prevalent in women than men, unemployed people than employed, and those who were separated, widowed, or divorced than people who were married or cohabiting. Most people with depressive disorders reported social impairment. Treatment rates were very low, and few people received adequate treatment. National programmes are needed to remove barriers to availability, accessibility, and acceptability of care for depression in China.

Funding: National Health Commission and Ministry of Science and Technology of People's Republic of China.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2215-0366(21)00251-0DOI Listing
September 2021

Lanthanide-Based Peptide-Directed Visible/Near-Infrared Imaging and Inhibition of LMP1.

JACS Au 2021 Jul 20;1(7):1034-1043. Epub 2021 Jun 20.

Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China.

A lanthanide-based peptide-directed bioprobe (Ln = Eu or Yb) is designed as an impressive example of a small molecule-based dual-functional probe for the EBV oncoprotein LMP1. The peptide (Pra-KAhx-K-LDLALK-FWLY-K-IVMSDKW-K-RrRK) is designed to selectively bind to LMP1 by mimicking its TM1 region during oligomerization in lipid rafts while signal transduction is significantly suppressed. Immunofluorescence imaging and Western blotting results reveal that can effectively inactivate the oncogenic cellular pathway nuclear factor κB (NF-κB) and contribute to a selective cytotoxic effect on LMP1-positive cells. By conjugation with cyclen-based europium(III) and ytterbium(III) complexes, and were constructed to offer visible and near-infrared LMP1-targeted imaging and cancer monitoring. In addition to the ability to target and inhibit LMP1 and to selective inhibit LMP1-positive cells, selective growth inhibition toward the LMP1-positive tumor by is also demonstrated.
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http://dx.doi.org/10.1021/jacsau.1c00187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395644PMC
July 2021

Mahjong Playing and Leisure Physical Activity Alleviate Cognitive Symptoms in Older Community Residents.

J Aging Phys Act 2021 Aug 13:1-9. Epub 2021 Aug 13.

Leisure activities, particularly physically and cognitively stimulating leisure activities, mitigate cognitive decline. The present study aimed to examine the relationship between mahjong playing, leisure physical activity, and mild cognitive impairment (MCI). Older adults with and without MCI were recruited (n = 489, healthy group; and n = 187, MCI group). The regression results showed that years of mahjong playing (odds ratio = 0.595, 95% confidence interval [0.376, 0.961], p = .032) and physical activity (odds ratio = 0.572, 95% confidence interval [0.381, 0.849], p = .012) were associated with reduced odds of having MCI after adjusting for a series of covariates. Leisure physical activity and mahjong playing interacted with each other and produced combined effects on the odds of having MCI. Combined cognitive and physical interventions may produce larger benefits on cognition than either intervention alone.
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http://dx.doi.org/10.1123/japa.2020-0383DOI Listing
August 2021

A fluorescent probe for the discrimination of oxidation states of palladium.

Chem Sci 2021 Jul 24;12(29):9977-9982. Epub 2021 Jun 24.

Department of Chemistry, Imperial College London MSRH Building, White City Campus London W12 0BZ UK

Palladium-based catalysts are widely used in pharmaceutical industries, which can sometimes cause palladium contamination in pharmaceutical drug manufacture. It is important to separately quantify the different oxidation states of palladium (Pd and Pd) in pharmaceuticals as they react with scavengers differently. Although palladium sensors have been under intense investigation, oxidation state differentiators are very rare. Here, we report a simple porphyrin-coumarin conjugate, , that can selectively discriminate between the oxidation states of palladium. The reaction of with Pd showed a 24-fold fluorescence increase of the coumarin emission, meanwhile, the presence of Pd led to a 98% quenching of the porphyrin emission. Fluorescent responses of towards Pd and Pd are specific, and its sensitivity towards both palladium species is significantly increased with a detection limit of 75 nM and 382 nM for Pd and Pd respectively.
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http://dx.doi.org/10.1039/d1sc01616dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317638PMC
July 2021

The PI3K/mTOR Inhibitor Ompalisib Suppresses Nonhomologous End Joining and Sensitizes Cancer Cells to Radio- and Chemotherapy.

Mol Cancer Res 2021 Jul 30. Epub 2021 Jul 30.

Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.

As the predominant pathway for the repair of DNA double-strand breaks (DSB), non-homologous end joining (NHEJ) attenuates the efficacy of cancer treatment which relies on the introduction of DSBs, such as radiotherapy and genotoxic drugs. Identifying novel NHEJ inhibitors is of great importance for improving the therapeutic efficiency of radio- or chemotherapy. Here we miniaturized our recently developed NHEJ detecting system into a 96-well plate-based format and interrogated an FDA approved drug library containing 1732 compounds. A collection of novel hits were considered to be potential DSB repair inhibitors at the noncytotoxic concentration. We identified omipalisib as an efficient sensitizer for DNA damage-induced cell death . Furthermore, analysis uncovered the repressive effect of omipalisib on the phosphorylation of DNA-dependent protein kinase catalytic subunit induced by ionizing radiation and doxorubicin, which led to the suppression of NHEJ pathway. IMPLICATIONS: In summary, our findings suggested the possibility for repurposing these candidates as radio- or chemosensitizers, which might extend their clinical application in cancer therapy.
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http://dx.doi.org/10.1158/1541-7786.MCR-21-0301DOI Listing
July 2021

Complete resolution of chylothorax with ibrutinib in chronic lymphocytic leukemia: a case report.

Ann Palliat Med 2021 Jul 21. Epub 2021 Jul 21.

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Chylothorax is an infrequent pleural effusion often caused by traumatic or nontraumatic injury to the thoracic duct. Nontraumatic chylothorax caused by chronic lymphocytic leukemia (CLL) is rarely reported. Previous experience has implied that the main factor affecting the treatment of chylothorax is whether the anti-cancer treatment is effective. The patient diagnosed with chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL) before the hospital admission, and not received any treatment. After four months, he had progressive dyspnea. Chest computed tomography (CT) scan showed bilateral pleural effusion with progressive lymphadenopathy, and massive chylous pleural effusion was drained by closed thoracic drainage. After a course of chemotherapy including fludarabine, cyclophosphamide and rituximab (FCR), the patient developed agranulocytosis and his pleural effusion was still abundant. After careful consideration, the patient refused to receive following chemotherapy and chose to take ibrutinib orally. Two months after oral ibrutinib, ultrasound examination showed that pleural effusion completely disappeared. In the next one year, the patient had a routine follow-up and was in good condition. To our knowledge, this is the first report of ibrutinib in the treatment of chylothorax associated with CLL. Ibrutinib provides a more palliative treatment for elderly CLL patients with chylothorax.
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http://dx.doi.org/10.21037/apm-21-989DOI Listing
July 2021

Phosphatidylinositol 3,4,5-Trisphosphate-Dependent Rac Exchanger 2 Protein Facilitates Glioma Progression via Akt and Stat3 Signaling.

J Mol Neurosci 2021 Aug 28;71(8):1674-1682. Epub 2021 Jul 28.

Department of Neurosurgery, Cangzhou Central Hospital, Xinhua West Road, Cangzhou, 061000, Hebei, China.

Glioblastoma multiforme (GBM) is the recognized as the most aggressive brain tumor with poor prognosis and low 1-year and 5-year survival rate. The treatment methods for GBM are limited and inefficient, and novel strategies for GBM treatment are urgently warranted. MiR-338-3p is described as a tumor suppressor in a variety of malignancies, including GBM. However, its role in GBM is not fully understood. The mRNA or protein levels of targets in cells or tissues were determined by quantitative reverse transcription PCR (RT-qPCR) or Western blot, respectively. The GBM cell growth rate in vitro or in vivo was measured by Cell Counting Kit-8 or bioluminescence imaging, respectively. Upregulation of hsa-miR-338-3p and downregulation of phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 protein (Prex2) were observed in GBM tissues compared to normal brain tissues. We further confirmed that murine Prex2 was a target of mmu-miR-338-3p in GBM. Mmu-miR-338-3p exerted profound inhibition effects on GBM cell growth in vitro or in vivo through targeting Prex2, leading to attenuation of (Protein kinase B) AKT/Signal transducer and activator of transcription 3 (STAT3) signaling activation. Restoration of mmu-miR-338-3p or inhibition of Prex2 may facilitate the development of innovative therapies for GBM treatment.
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http://dx.doi.org/10.1007/s12031-021-01883-xDOI Listing
August 2021

Cardiac Glycoside Ouabain Exerts Anticancer Activity Downregulation of STAT3.

Front Oncol 2021 30;11:684316. Epub 2021 Jun 30.

Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.

Cardiac glycosides are plant-derived steroid-like compounds which have been used for the treatment of cardiovascular diseases. Ouabain, a cardiotonic steroid and specific Na/K-ATPase inhibitor, has been rediscovered for its potential use in the treatment of cancer. However, the cellular targets and anticancer mechanism of ouabain in various cancers remain largely unexplored. In this study, we confirmed the cytotoxic effects of ouabain on several cancer cell lines. Further examination revealed the increase of apoptosis, intracellular ROS generation and DNA double-strand breaks induced by ouabain treatment. Besides, ouabain effectively suppressed STAT3 expression as well as phosphorylation in addition to block STAT3-mediated transcription and downstream target proteins. Interestingly, these inhibitory activities seemed to be independent of the Na/K-ATPase. Furthermore, we found that ouabain inhibited protein synthesis through regulation of the eukaryotic initiation factor 4E (eIF4E) and eIF4E binding protein 1 (4EBP1). Taken together, our study provided a novel molecular insight of anticancer activities of ouabain in human cancer cells, which could raise the hope of using cardiac glycosides for cancer therapeutics more rational.
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http://dx.doi.org/10.3389/fonc.2021.684316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279743PMC
June 2021

Action Video Gaming Experience Related to Altered Resting-State EEG Temporal and Spatial Complexity.

Front Hum Neurosci 2021 29;15:640329. Epub 2021 Jun 29.

MOE Key Lab for Neuroinformation, The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China, Chengdu, China.

Action video gaming (AVG) places sustained cognitive load on various behavioral systems, thus offering new insights into learning-related neural plasticity. This study aims to determine whether AVG experience is associated with resting-state electroencephalogram (rs-EEG) temporal and spatial complexity, and if so, whether this effect is observable across AVG subgenres. Two AVG games - League of Legends (LOL) and Player Unknown's Battle Grounds (PUBG) that represent two major AVG subgenres - were examined. We compared rs-EEG microstate and omega complexity between LOL experts and non-experts (Experiment 1) and between PUBG experts and non-experts (Experiment 2). We found that the experts and non-experts had different rs-EEG activities in both experiments, thus revealing the adaptive effect of AVG experience on brain development. Furthermore, we also found certain subgenre-specific complexity changes, supporting the recent proposal that AVG should be categorized based on the gaming mechanics of a specific game rather than a generic genre designation.
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http://dx.doi.org/10.3389/fnhum.2021.640329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275975PMC
June 2021

Clinical and genetic features of Epstein-Barr virus-triggered late-onset primary hemophagocytic lymphohistiocytosis: Ten pedigrees study.

Clin Transl Med 2021 06;11(6):e393

Department of Hematology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

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http://dx.doi.org/10.1002/ctm2.393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161514PMC
June 2021

Caseous calcification of the mitral annulus mimicking benign cardiac tumour of the mitral valve.

Cardiovasc J Afr 2021 Jul-Aug 23;32(4):224-227. Epub 2021 May 7.

Echocardiography and Vascular Ultrasound Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Email:

Caseous calcification of the mitral annulus (CCMA) is a rare subtype of mitral annular calcification. It usually appears as a large, round, mass-like calcification with an echolucent core, which may be misdiagnosed as an intracardiac mass, cyst, thrombus or abscess of the mitral valve. We present a case report of CCMA that was misdiagnosed by echocardiography as a benign tumour due to its atypical imaging. The mitral valve mass was resected and it was pathologically confirmed to be a myxoid change with calcification. Echocardiography is the preferred initial diagnostic tool. Myocardial contrast echocardiography (MCE) is used to evaluate the vascularity of intracardiac masses or mass-like lesions, but neither echocardiography nor MCE is reliable for identifying atypical lesions. Cardiac computed tomography is helpful in establishing a diagnosis by showing dense calcifications, while cardiac magnetic resonance imaging is used primarily as a credible tool. We therefore recommend that a diagnosis should be made based on various imaging modalities, if necessary, and operators should be skilled to avoid misdiagnosis.
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http://dx.doi.org/10.5830/CVJA-2021-007DOI Listing
May 2021

Optimizing Safe Dental Practice During the COVID-19 Pandemic: Recommendations Based on a Guide Developed for Dental Practices in China.

Front Med (Lausanne) 2021 26;8:619357. Epub 2021 May 26.

Department of Periodontology and Oral Implantology, Stomatological Hospital, Southern Medical University, Guangzhou, China.

The current global coronavirus disease 2019 (COVID-19) outbreak is still exerting severe global implications, and its development in various regions is complex and variable. The high risk of cross-infection poses a great challenge to the dental practice environment; it is therefore urgent to develop a set of pandemic prevention measures to ensure dental practice safety during the COVID-19 outbreak. Therefore, we combined the epidemiological characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), public emergency measures for COVID-19, characteristics of dental practice, and relevant literature reports to develop a set of dynamic practice measures for dental practices in high-, medium-, and low-risk areas affected by COVID-19. This will help dental practices to achieve standard prevention and ensure their safe and smooth operation during the pandemic. It is hoped that these measures will provide a reference basis for dental hospitals and dental clinics in their care and pandemic prevention work.
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http://dx.doi.org/10.3389/fmed.2021.619357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187590PMC
May 2021

MicroRNA-370 carried by M2 macrophage-derived exosomes alleviates asthma progression through inhibiting the FGF1/MAPK/STAT1 axis.

Int J Biol Sci 2021 23;17(7):1795-1807. Epub 2021 Apr 23.

Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.

Emerging evidence has suggested the functions of exosomes in allergic diseases including asthma. By using a mouse model with asthma induced by ovalbumin (OVA), we explored the roles of M2 macrophage-derived exosomes (M2Φ-Exos) in asthma progression. M2Φ-Exos significantly alleviated OVA-induced fibrosis and inflammatory responses in mouse lung tissues, as well as inhibited abnormal proliferation, invasion, and fibrosis-related protein production in platelet derived growth factor (PDGF-BB) treated primary mouse airway smooth muscle cells (ASMCs). The OVA administration in mice or the PDGF-BB treatment in ASMCs reduced the expression of miR-370, which was detected in M2Φ-Exos by miRNA sequencing. However, treating the mice or ASMCs with M2Φ-Exos reversed the inhibitory effect of OVA or PDGF-BB on miR-370 expression. We identified that the target of miR-370 was fibroblast growth factor 1 (). Downregulation of miR-370 by Lv-miR-370 inhibitor or overexpression of FGF1 by Lv-FGF1 blocked the protective roles of M2Φ-Exos in asthma-like mouse and cell models. M2Φ-Exos were found to inactivate the MAPK signaling pathway, which was recovered by miR-370 inhibition or FGF1 overexpression. Collectively, we conclude that M2Φ-Exos carry miR-370 to alleviate asthma progression through downregulating FGF1 expression and the MAPK/STAT1 signaling pathway. Our study may offer a novel insight into asthma treatment.
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http://dx.doi.org/10.7150/ijbs.59715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120458PMC
April 2021

Influence of emulsifiers and enzymes on dough rheological properties and quality characteristics of steamed bread enriched with potato pulp.

Food Chem 2021 Oct 6;360:130015. Epub 2021 May 6.

School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo, Shandong 255000, China. Electronic address:

The aim of this study was to evaluate whether processing characteristics of steamed bread enriched with potato pulp could be improved through the addition of different emulsifiers (soy lecithin-Soy L, sodium stearoyl lactate and diacetyl tartaric esters of monoglyceride) and enzymes (glucose oxidase-GOX and transglutaminase). Results showed that separate addition of each emulsifier at 1% concentration or each enzyme at 1.5 U/g could increase the viscoelasticity and strength of potato pulp dough due to enhancement of gluten network. Fermentation properties of dough showed that Soy L and GOX significantly (P < 0.05) increased the maximum dough height and the gas retention capacity during fermentation which promoting dough expansion. Moreover, Soy L and GOX increased specific volume and improved crumb structure and softness of steamed bread, which were consistent with the results of sensory analysis. In conclusion, Soy L and GOX could be used as improvers of potato pulp steamed bread.
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http://dx.doi.org/10.1016/j.foodchem.2021.130015DOI Listing
October 2021

A phase I study of anti-BCMA CAR T cell therapy in relapsed/refractory multiple myeloma and plasma cell leukemia.

Clin Transl Med 2021 03;11(3):e346

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Background: Relapsed/refractory (R/R) multiple myeloma (MM) patients and primary plasma cell leukemia (PCL) have an unfavorable prognosis and no effective treatment. This study was designed to assess the safety and preliminary efficacy of a novel anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell in R/R MM and PCL.

Methods: Between February 22, 2017, and June 25, 2018, 28 R/R and two R/R primary PCL patients received a median dose of 11.2 × 10 CAR+ cells/kg. The subjects were refractory to a proteasome inhibitor and/or an immunomodulatory agent. Fludarabine and cyclophosphamide were given as lymphodepletion chemotherapy.

Results: Results for these 30 consecutive patients who received an anti-BCMA CAR T cell infusion are reported. The patients had received a median of four prior lines of therapy. A total of 44 different types of adverse events were recorded, and hematologic toxic effects were the most common events of any grade during treatment. Hematologic toxic effects were also the most common events of grade 3 or higher. A total of 29 patients (96.7%) had cytokine release syndrome, which was of grade 1 or 2 in 24 patients (80%) and grade 3 in five patients (16.7%). Neurologic toxic effects only occurred in one patient (3.3%) and were of grade 1. The objective response rate was 90%, and the complete response rate was 43.3%. With a median follow-up of 12.6 months, the median progression-free survival (PFS) and overall survival were 5.2 months and 14.0 months. One of the two primary PCL achieved a complete response with a PFS of 307 days. The other patients achieved a very good partial response with a PFS of 117 days.

Conclusions: Anti-BCMA CAR T cell treatment is safe and highly active in R/R multiple myeloma.
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http://dx.doi.org/10.1002/ctm2.346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943908PMC
March 2021

A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer's dementia.

Alzheimers Res Ther 2021 03 17;13(1):62. Epub 2021 Mar 17.

Department of Geriatric psychiatry, Wuxi Mental Health Center, Wuxi, China.

Background: New therapies are urgently needed for Alzheimer's disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China.

Methods: We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored.

Results: A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was - 2.15 points (95% confidence interval, - 3.07 to - 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group.

Conclusions: GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated.

Trial Registration: ClinicalTrials.gov, NCT0229391 5. Registered on November 19, 2014.
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http://dx.doi.org/10.1186/s13195-021-00795-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967962PMC
March 2021

Ultrasensitive assays for detection of plasma tau and phosphorylated tau 181 in Alzheimer's disease: a systematic review and meta-analysis.

Transl Neurodegener 2021 03 12;10(1):10. Epub 2021 Mar 12.

Department of Neurology and State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, China.

A lack of convenient and reliable biomarkers for diagnosis and prognosis is a common challenge for neurodegenerative diseases such as Alzheimer's disease (AD). Recent advancement in ultrasensitive protein assays has allowed the quantification of tau and phosphorylated tau proteins in peripheral plasma. Here we identified 66 eligible studies reporting quantification of plasma tau and phosphorylated tau 181 (ptau181) using four ultrasensitive methods. Meta-analysis of these studies confirmed that the AD patients had significantly higher plasma tau and ptau181 levels compared with controls, and that the plasma tau and ptau181 could predict AD with high-accuracy area under curve of the Receiver Operating Characteristic. Therefore, plasma tau and plasma ptau181 can be considered as biomarkers for AD diagnosis.
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http://dx.doi.org/10.1186/s40035-021-00234-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953695PMC
March 2021

A phase 1 study of a novel fully human BCMA-targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma.

Blood 2021 May;137(21):2890-2901

Department of Hematology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies have shown efficacy in relapsed/refractory multiple myeloma (RRMM). Because the non-human originated antigen-targeting domain may limit clinical efficacy, we developed a fully human BCMA-specific CAR, CT103A, and report its safety and efficacy in a phase 1 trial. Eighteen consecutive patients with RRMM, including 4 with prior murine BCMA CAR exposures, were enrolled. CT103A was administered at 1, 3, and 6 × 106 CAR-positive T cells/kg in the dose-escalation phase, and 1 × 106 CAR-positive T cells/kg in the expansion cohort. The overall response rate was 100%, with 72.2% of the patients achieving complete response or stringent complete response. For the 4 murine BCMA CAR-exposed patients, 3 achieved stringent complete response, and 1 achieved a very good partial response. At 1 year, the progression-free survival rate was 58.3% for all cohorts and 79.1% for the patients without extramedullary myeloma. Hematologic toxicities were the most common adverse events; 70.6% of the patients experienced grade 1 or 2 cytokine release syndromes. No immune effector cell-associated neurotoxicity syndrome was observed. To the cutoff date, CAR transgenes were detectable in 77.8% of the patients. The median CAR transgene persistence was 307.5 days. Only 1 patient was positive for the anti-drug antibody. Altogether, CT103A is safe and highly active in patients with RRMM and can be developed as a promising therapy for RRMM. Patients who relapsed from prior murine BCMA CAR T-cell therapy may still benefit from CT103A. This trial was registered at http://www.chictr.org.cn as #ChiCTR1800018137.
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http://dx.doi.org/10.1182/blood.2020008936DOI Listing
May 2021

Biomimetic Anti-PD-1 Peptide-Loaded 2D FePSe Nanosheets for Efficient Photothermal and Enhanced Immune Therapy with Multimodal MR/PA/Thermal Imaging.

Adv Sci (Weinh) 2021 Jan 25;8(2):2003041. Epub 2020 Nov 25.

Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic University Hong Kong SAR P. R. China.

Metal phosphorous trichalcogenides (MPX) are novel 2D nanomaterials that have recently been exploited as efficient photothermal-chemodynamic agents for cancer therapy. As a representative MPX, FePSe has the potential to be developed as magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) agents due to the composition of Fe and the previously revealed PA signal. Here, a FePSe-based theranostic agent, [email protected]@CCM, loaded with anti-PD-1 peptide (APP) as the inner component and CT26 cancer cell membrane (CCM) as the outer shell is reported, which acts as a multifunctional agent for MR and PA imaging and photothermal and immunotherapy against cancer. [email protected]@CCM induces highly efficient tumor ablation and suppresses tumor growth by photothermal therapy under near-infrared laser excitation, which further activates immune responses. Moreover, APP blocks the PD-1/PD-L1 pathway to activate cytotoxic T cells, causing strong anticancer immunity. The combined therapy significantly prolongs the lifespan of experimental mice. The multimodal imaging and synergistic therapeutic effects of PTT and its triggered immune responses and APP-related immunotherapy are clearly demonstrated by in vitro and in vivo experiments. This work demonstrates the potential of MPX-based biomaterials as novel theranostic agents.
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http://dx.doi.org/10.1002/advs.202003041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816711PMC
January 2021

Erratum to: Discovery of Chrysoeriol, a PI3K-AKT-mTOR Pathway Inhibitor with Potent Antitumor Activity against Human Multiple Myeloma Cells In Vitro.

Curr Med Sci 2020 Dec;40(6):1203

Department of Hematology, Tongji Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

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http://dx.doi.org/10.1007/s11596-020-2309-7DOI Listing
December 2020

IFI27 may predict and evaluate the severity of respiratory syncytial virus infection in preterm infants.

Hereditas 2021 Jan 2;158(1). Epub 2021 Jan 2.

Department of Neonatology, Children's Hospital of Soochow University, NO.92 Zhongnan Street, Industrial Park, Suzhou, 215025, Jiangsu, China.

Background: Preterm infants are a special population that vulnerable to respiratory syncytial virus (RSV) infection and the lower respiratory tract infections (LRTIs) caused by RSV could be severe and even life-threating. The purpose of the present study was to identify candidate genes of preterm infants who are susceptible to RSV infection and provide a new insight into the pathogenesis of RSV infection.

Methods: Three datasets (GSE77087, GSE69606 and GSE41374) containing 183 blood samples of RSV infected patients and 33 blood samples of healthy controls from Gene Expression Omnibus (GEO) database were downloaded and the differentially expressed genes (DEGs) were screened out. The function and pathway enrichments were analyzed through Database for Annotation, Visualization and Integrated Discovery (DAVID) website. The protein-protein interaction (PPI) network for DEGs was constructed through Search Tool for the Retrieval of Interacting Genes (STRING). The module analysis was performed by Cytoscape software and hub genes were identified. Clinical verification was employed to verify the expression level of top five hub genes among 72 infants including 50 RSV infected patients and 22 non-RSV-infected patients hospitalized in our center. Further, the RSV infected infants with high-expression IFI27 and those with low-expression IFI27 were compared (defined as higher or lower than the median mRNA level). Finally, the gene set enrichment analysis (GSEA) focusing on IFI27 was carried out.

Results: Totally, 4028 DEGs were screened out and among which, 131 most significant DEGs were selected. Subsequently, 13 hub genes were identified, and function and pathway enrichments of hub genes mainly were: response to virus, defense response to virus, regulation of viral genome replication and regulation of viral life cycle. Furthermore, IFI27 was confirmed to be the most significantly expressed in clinical verification. Gene sets associated with calcium signaling pathway, arachidonic acid metabolism, extracellular matrix receptor interaction and so on were significantly enriched when IFI27 was highly expressed. Moreover, high-expression IFI27 was associated with more severe cases (p = 0.041), more requirements of mechanical ventilation (p = 0.034), more frequent hospitalization (p < 0.001) and longer cumulative hospital stay (p = 0.012).

Conclusion: IFI27 might serve to predict RSV infection and evaluate the severity of RSV infection in preterm infants.
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http://dx.doi.org/10.1186/s41065-020-00167-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778825PMC
January 2021

CD74, a novel predictor for bronchopulmonary dysplasia in preterm infants.

Medicine (Baltimore) 2020 Nov;99(48):e23477

Department of Neonatology, Children's Hospital of Soochow University, Suzhou, Jiangsu.

Bronchopulmonary dysplasia (BPD) remains a major complication and accounts for high morbidity and mortality of preterm infants. The present study aimed to identify the key genes in the development of BPD and to provide some new insights into the pathogenesis of BPD. The GSE108754 dataset was downloaded from Gene Expression Omnibus database containing 5 samples of BPD patients and 6 of non-BPD infants. The differentially expressed genes (DEGs) between BPD and non-BPD patients were identified by R software. The pathway and function enrichment analyses were performed through Database for Annotation Visualization and Integrated Discovery website. The protein-protein interaction network for DEGs was established by Cytoscape software and the most highly connected module was selected through MCODE plugin. Furthermore, the clinical sample verification among 25 BPD patients and 10 non-BPD infants was carried out in our center. Finally, based on the results above, the gene set enrichment analysis focusing on CD74 upregulated status was employed. Totally, 189 DEGs including 147 upregulated genes and 42 downregulated genes between BPD and non-BPD patients were screened out. The pathway and function enrichments revealed these DEGs were mainly enriched in asthma, intestinal immune network for IgA production, antigen processing and presentation and immune response. Thirteen DEGs (CD74, HLA-DMA, HLA-DRA, HLA-DMB, HLA-DOB, HLA-DQA1, HLA-DRB5, HLA-DPA1, HLA-DOA, HLA-DPB1, HLA-DQB2, HLA-DQA2, and HLA-DQB1) were determined as hub genes. The mRNA expression levels of the 13 hub genes were tested by quantitative real-time polymerase chain reaction among our clinical samples. Eventually, CD74 was confirmed to be the most significant highly expressed in BPD samples (P < .001) and its expression level was negatively correlated with gestational age (r = -0.653) and birth weight (r = -0.675). The gene set enrichment analysis results showed the gene sets associated with lupus erythematosus, viral myocarditis, immune network for IgA production, graft versus host disease, cell adhesion molecules and so no were differentially enriched with the phenotype of high-expression CD74. In conclusion, CD74 may serve to predict the BPD development and provide a new therapeutic target for BPD.
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http://dx.doi.org/10.1097/MD.0000000000023477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710202PMC
November 2020

Safety and feasibility of umbilical cord mesenchymal stem cells in patients with COVID-19 pneumonia: A pilot study.

Cell Prolif 2020 Dec 17;53(12):e12947. Epub 2020 Nov 17.

Wuhan Leishenshan Hospital, Wuhan, China.

Objectives: We aim to explore the safety and feasibility of umbilical cord mesenchymal stem cells (UC-MSCs) transplantation in patients with severe and critically severe coronavirus disease-2019 (COVID-19).

Methods: We conducted a small sample, single arm, pilot trial. In addition to standard therapy, we performed four rounds of transplantation of UC-MSCs in sixteen patients with severe and critically severe COVID-19. We recorded adverse events from enrolment to Day 28. We evaluated the oxygenation index, inflammatory biomarkers, radiological presentations of the disease and lymphocyte subsets count on the 7th day (D7 ± 1 day), the 14th day (D14 ± 1 day) and the 28th day (D28 ± 3 days).

Results: There were no infusion-related or allergic reactions. The oxygenation index was improved after transplantation. The mortality of enrolled patients was 6.25%, whereas the historical mortality rate was 45.4%. The level of cytokines estimated varied in the normal range, the radiological presentations (ground glass opacity) were improved and the lymphocyte count and lymphocyte subsets (CD4 T cells, CD8 T cells and NK cells) count showed recovery after transplantation.

Conclusions: Intravenous transplantation of UC-MSCs was safe and feasible for treatment of patients with severe and critically severe COVID-19 pneumonia.
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http://dx.doi.org/10.1111/cpr.12947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705911PMC
December 2020

Simultaneous detection of anions and carbohydrates in cyanobacteria by two-dimensional ion chromatography.

J AOAC Int 2020 Nov 17. Epub 2020 Nov 17.

CAS Key Laboratory of Bio-based Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, China.

Background: The simultaneous analysis of several anions and carbohydrates by one-dimensional chromatography with a single detector is often complicated by the presence of overlapping peaks. To overcome this problem, analytes are usually analysed separately making analysis long and tedious.

Objective: A method combining two-dimensional ion chromatography (2 D-IC) and valve switching was developed for the simultaneous determination of anions (F-, Cl-, NO2-, SO42-, NO3-, and PO43-) and carbohydrates (glycerinum, glucosyl glycerol, trehalose, mannose, glucose, galactose, fructose, ribose, and sucrose) in cyanobacteria.

Methods: Interfering color compounds were removed by first passing the sample through graphitized carbom solid phase extraction (SPE) cartridges. Samples were applied to an AS11-HC column, which was used to separate the anions followed by quantification using a conductance detector. Carbohydrates eluted from the AS11-HC column were trapped and separated on a MA1 column and simultaneously quantified using electrochemical detection in the second dimension with valve switching.

Results: The following parameters were established: LOD, 0.001-0.030 (mg/L); LOQ, 0.001-0.010 (mg/L); linearity (r), 0.9940; repeatability, 0.39%-3.02%; and spiked recovery, 90.1%-107%.

Conclusion: The proposed method is adequately linear, accurate, and repeatable. The 2 D-IC method provides fast, high resolution, and completely automated procedure for the simultaneous determination of anions and carbohydrates without co-elution compared to the one dimension ion chromatography method. This study provides application perspectives for use in biotechnology and other research fields.

Highlights: An accurate and effective 2 D-IC method was developed for determining anions and carbohydrates in cyanobacteria. The method includes pre-treating samples with graphitized carbon SPE cartridges.
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http://dx.doi.org/10.1093/jaoacint/qsaa153DOI Listing
November 2020

Efficacy of light therapy for a college student sample with non-seasonal subthreshold depression: An RCT study.

J Affect Disord 2020 12 26;277:443-449. Epub 2020 Aug 26.

Department of Public Health and Preventive Medicine, School of Basic Medicine, Jinan University, Guangzhou 510632, China; Division of Medical Psychology and Behavior Science, School of Basic Medicine, Jinan University, Guangzhou 510632, China; Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong-Macao Greater Bay Area, Guangzhou 510515, China. Electronic address:

Background: Light therapy has been successfully used to treat seasonal and non-seasonal depression, but there is limited evidence for its efficacy in subthreshold depression. This study examines the efficacy of light therapy for symptoms of depression and anxiety in non-seasonal subthreshold depression.

Methods: College students with non-seasonal subthreshold depression were recruited. The participants were randomly allocated to one of the three conditions: high- (LT-5000 lux) and low-intensity (LT-500 lux) light therapy conditions and a waiting-list control condition (WLC). The primary outcome was Hamilton Depression Rating Scale (HAMD), and secondary outcomes were Beck Depression Inventory-II (BDI-II) and state anxiety inventory (SAI), which were assessed at baseline (Week 0), during the trial (Week 4), and after completion of the light therapy (Week 8).

Results: A total of 142 participants completed the trial. The LT-5000 (effect size [d] = 1.56, 95% CI: 1.15 to 1.98) and LT-500 conditions (d = 0.84, 95% CI: 0.43 to 1.26) were significantly superior to the WLC condition. For the LT-5000, LT-500, and WLC conditions by the end of the 8-week trial, a response on the HAMD was achieved by 70.0%, 42.0% and 19.0% of the participants, and remission was achieved by 76.0%, 54.0%, and 19.0%, respectively.

Limitations: The subjects were not followed up regularly after completion of the trial.

Conclusion: Light therapy, both at high- and low-intensity, was efficacious in the treatment of college students with non-seasonal subthreshold depression. High-intensity light therapy was superior to low-intensity light therapy by the end of an 8-week trial.
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http://dx.doi.org/10.1016/j.jad.2020.08.055DOI Listing
December 2020

TAK‑242 exerts a neuroprotective effect via suppression of the TLR4/MyD88/TRIF/NF‑κB signaling pathway in a neonatal hypoxic‑ischemic encephalopathy rat model.

Mol Med Rep 2020 Aug 11;22(2):1440-1448. Epub 2020 Jun 11.

Department of Neonatology, Affiliated Children's Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.

Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the main causes of death and nervous system damage in neonates. The aim of the present study was to investigate the effect of the Toll‑like receptor 4 (TLR4) antagonist TAK‑242 on HIE. The Rice‑Vannucci method was used for ligation of the left common carotid artery, followed by hypoxic treatment for 2.5 h to establish a neonatal HIE rat model. Rats were intraperitoneally injected with 7.5 ml/kg TAK‑242 after hypoxia‑ischemia. It was demonstrated that TAK‑242 significantly reduced the infarct volume and cerebral edema content of neonatal rats after HIE, alleviating neuronal damage and neurobehavioral function deficits. Furthermore, TAK‑242 decreased the protein expression levels of TLR4, MyD88, TIR‑domain‑containing adapter‑inducing interferon‑β (TRIF), NF‑κB, tumor necrosis factor α (TNF‑α) and interleukin‑1β in the hippocampus. The present results suggested that TAK‑242 may exert a neuroprotective effect after HIE by inhibiting the TLR4/MyD88/TRIF/NF‑κB signaling pathway, and reducing the release of downstream inflammatory cytokines.
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http://dx.doi.org/10.3892/mmr.2020.11220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339810PMC
August 2020

Hematoma Resolution In Vivo Is Directed by Activating Transcription Factor 1.

Circ Res 2020 09 1;127(7):928-944. Epub 2020 Jul 1.

From the National Heart and Lung Institute (A.S., Y.H., E.W., E.R.H.W., L.C., J.C.M., D.O.H., J.J.B.), Imperial College London Hammersmith Campus.

Rationale: The efficient resolution of tissue hemorrhage is an important homeostatic function. In human macrophages in vitro, heme activates an AMPK (AMP-activated protein kinase)/ATF1 (activating transcription factor-1) pathway that directs Mhem macrophages through coregulation of HO-1 (heme oxygenase-1; ) and lipid homeostasis genes.

Objective: We asked whether this pathway had an in vivo role in mice.

Methods And Results: Perifemoral hematomas were used as a model of hematoma resolution. In mouse bone marrow-derived macrophages, heme induced HO-1, lipid regulatory genes including LXR (lipid X receptor), the growth factor IGF1 (insulin-like growth factor-1), and the splenic red pulp macrophage gene . This response was lost in bone marrow-derived macrophages from mice deficient in AMPK () or ATF1 (). In vivo, femoral hematomas resolved completely between days 8 and 9 in littermate control mice (n=12), but were still present at day 9 in mice deficient in either AMPK () or ATF1 (; n=6 each). Residual hematomas were accompanied by increased macrophage infiltration, inflammatory activation and oxidative stress. We also found that fluorescent lipids and a fluorescent iron-analog were trafficked to lipid-laden and iron-laden macrophages respectively. Moreover erythrocyte iron and lipid abnormally colocalized in the same macrophages in mice. Therefore, iron-lipid separation was -dependent.

Conclusions: Taken together, these data demonstrate that both AMPK and ATF1 are required for normal hematoma resolution. Graphic Abstract: An online graphic abstract is available for this article.
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http://dx.doi.org/10.1161/CIRCRESAHA.119.315528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478221PMC
September 2020

Contemporary trends in mitral valve surgery in East China: a 10-year experience.

Asian Cardiovasc Thorac Ann 2020 Sep 9;28(7):404-412. Epub 2020 Jun 9.

Department of Cardiovascular Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: Contemporary nationwide data from mainland China on trends in mitral valve surgery are scarce. The purpose of the present study was to review a single-center experience with mitral valve surgery over a 10-year period in East China.

Methods: Between July 2009 and June 2019, 3238 consecutive patients who underwent mitral valve surgery in our center were retrospectively reviewed. The patients were evenly divided into three periods: July 2009 to October 2012 (period I), November 2012 to February 2016 (period II), March 2016 to June 2019 (period III).

Results: The 3238 patients included 536 (16.6%) who had mitral valve repair and 2702 (83.4%) who had mitral valve replacement. Early mortalities for mitral valve repair and mitral valve replacement were 0.2% and 0.9%, respectively. There were trends towards a higher proportion of degenerative valve lesions (24.6%, 35.8%, 54.7% in periods I, II, and III, respectively) and a lower proportion of rheumatic valve lesions (71.0%, 62.6%, 38.0%) in more recent years. The proportions of minimally invasive surgery (0.7%, 2.1%, 30.2%), mitral valve repair (8.3%, 15.4%, 27.5%), use of a bioprosthesis (10.1%, 17.0%, 23.1%), and concomitant tricuspid valve procedures (13.2%, 28.5%, 46.0%) increased dramatically, while early mortality remained constant during the 10-year period (1.0%, 0.3%, 0.9%).

Conclusions: In the past 10 years, the spectrum of mitral valve disease experienced a trend towards more degenerative valve lesions and less rheumatic valve lesions in East China. Mitral valve repair, bioprostheses, tricuspid valve repair, and minimally invasive surgery have been more often applied in recent years.
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http://dx.doi.org/10.1177/0218492320932743DOI Listing
September 2020

Characterization of sustained-release chitosan film loaded with rutin-β-cyclodextrin complex and glucoamylase.

J Food Sci Technol 2020 Feb 17;57(2):734-744. Epub 2019 Sep 17.

School of Agricultural Engineering and Food Science, Shandong University of Technology, Zhangdian District, No. 12, Zhangzhou Road, Zibo, Shandong Province, China.

Abstract: Edible chitosan film incorporated with rutin-β-cyclodextrin was developed and characterized. The delivery of rutin was improved via the hydrolyzation function of glucoamylase, and the antioxidant activity of the chitosan film was enhanced by the addition of rutin. Sodium bicarbonate solution at different pHs (pH-adjusting reagent) was employed to afford the mild condition for the incorporated glucoamylase. The enzyme exhibited its hydrolyzation function to improve the release rate of rutin by destabilizing the rutin-β-cyclodextrin complex (RCC) in chitosan film. The optimum pH of glucoamylase was achieved with 5 mL addition amount of 0.5 mol/L sodium bicarbonate solution, and the glucoamylase improved the radical scavenging ratio of chitosan film. The yellowness of chitosan film was enhanced with the addition of RCC solution. The films prepared without water demonstrated coarse and rough surface, while the water-based films had smoother and even surface as examined by scanning electron microscopy. In contrast, these observations disappeared in the water immersion groups. X-ray diffraction suggested that the hydrolyzation of β-cyclodextrin and the interlinkage between β-cyclodextrin and the chitosan chain exerted a negative function on maintaining the crystal structure of pure chitosan film. Further, the destabilization of RCC complex with the glucoamylase activity was evidenced by the absence of peak associated with β-cyclodextrin as observed from Fourier transform infrared spectra. The enzyme improved the release of rutin and the addition of RCC successfully endowed antioxidant activity to the chitosan film.

Graphic Abstract:
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http://dx.doi.org/10.1007/s13197-019-04106-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016053PMC
February 2020

Efficacy and toxicity for CD22/CD19 chimeric antigen receptor T-cell therapy in patients with relapsed/refractory aggressive B-cell lymphoma involving the gastrointestinal tract.

Cytotherapy 2020 03 13;22(3):166-171. Epub 2020 Feb 13.

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Gastrointestinal (GI) tract is the most common site of extranodal involvement in non-Hodgkin lymphoma. Life-threatening complications of GI may occur because of tumor or chemotherapy. Chimeric antigen receptor (CAR) T-cell therapy has been successfully used to treat refractory/relapse B-cell lymphoma, however, little is known about the efficacy and safety of CAR-T cell therapy for GI lymphoma. Here, we reported the efficacy and safety of CAR-T cell therapy in 14 patients with relapsed/refractory aggressive B-cell lymphoma involving the GI tract. After a sequential anti-CD22/anti-CD19 CAR-T therapy, 10 patients achieved an objective response, and seven patients achieved a complete response. CAR transgene and B-cell aplasia persisted in the majority of patients irrespective of response status. Six patients with partial response or stable disease developed progressive disease; two patients lost target antigens. Cytokine release syndrome (CRS) and GI adverse events were generally mild and manageable. The most common GI adverse events were diarrhea (4/14), vomiting (3/14) and hemorrhage (2/14). No perforation occurred during follow-up. Infection is a severe complication in GI lymphoma. Two patients were infected with bacteria that are able to colonize at GI; one died of sepsis early after CAR-T cells infusion. In conclusion, our study showed promising efficacy and safety of CAR-T cell therapy in refractory/relapsed B-cell lymphoma involving the GI tract. However, the characteristics of CAR-T-related infection in GI lymphoma should be further clarified to prevent and control infection.
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http://dx.doi.org/10.1016/j.jcyt.2020.01.008DOI Listing
March 2020
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