Publications by authors named "Han Yang"

789 Publications

Effect of spatial distribution of boron and oxygen concentration on DNA damage induced from boron neutron capture therapy using Monte Carlo simulations.

Int J Radiat Biol 2021 May 10:1-36. Epub 2021 May 10.

Department of Radiation Physics, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

This paper aims to investigate how the spatial distribution of boron in cells and oxygen concentration affect the DNA damage induced by charged particles in boron neutron capture therapy (BNCT) by Monte Carlo simulations, and further to evaluate the relative biological effectiveness (RBE) of DNA double-strand breaks (DSBs) induction in BNCT. The DNA damage induced by all charged particles in BNCT was evaluated by combining Geant4 and Monte Carlo Damage Simulation software (MCDS 3.10A). The kinetic energy spectra of α, Li particles in BNCT arriving at the nucleus surface were obtained from GEANT4 Monte Carlo simulation (Geant4 10.05.p01). Recoil protons were produced by hydrogen atoms capturing fast neutrons, whose spectrum was calculated by irradiating the cylindrical tissue equivalent material with a BNCT neutron source. The DNA damage caused by all charged particles in BNCT with the energy spectra calculated above was then evaluated using MCDS. Finally, the RBE of DSB induction in BNCT was determined with the Cs photons as the reference radiation. When α or Li particles were distributed in the cytomembrane or cytoplasm, the difference in the percentage of different types of DNA damage was less than 0.5%, simple damages and more complex damages had opposite trends in these two distributions. When the oxygen concentration varied from 0% to 50%, the DSB induced by recoil protons was increased by about 50%, whereas it was increased by about 85% by 0.54 MeV protons, that were generated from the capture of the thermal neutrons by nitrogen atoms. The calculated RBE for both kinds of protons decreased from 5 to 2. In BNCT, the effect of oxygen concentration on DNA damage induced by protons and recoil protons was more significant, the RBE of all charged particles in BNCT decreased gradually with the increase of oxygen concentration, this trend was reasonable consistent with the previous experimental data. This work indicated that the RBE of different radiation particles of BNCT might be affected by many factors, which should be paid attention to in theoretical research or clinical application.
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http://dx.doi.org/10.1080/09553002.2021.1928785DOI Listing
May 2021

The Cell Origin and Role of Osteoclastogenesis and Osteoblastogenesis in Vascular Calcification.

Front Cardiovasc Med 2021 23;8:639740. Epub 2021 Apr 23.

Department of Vascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Arterial calcification refers to the abnormal deposition of calcium salts in the arterial wall, which results in vessel lumen stenosis and vascular remodeling. Studies increasingly show that arterial calcification is a cell mediated, reversible and active regulated process similar to physiological bone mineralization. The osteoblasts and chondrocytes-like cells are present in large numbers in the calcified lesions, and express osteogenic transcription factor and bone matrix proteins that are known to initiate and promote arterial calcification. In addition, osteoclast-like cells have also been detected in calcified arterial walls wherein they possibly inhibit vascular calcification, similar to the catabolic process of bone mineral resorption. Therefore, tilting the balance between osteoblast-like and osteoclast-like cells to the latter maybe a promising therapeutic strategy against vascular calcification. In this review, we have summarized the current findings on the origin and functions of osteoblast-like and osteoclast-like cells in the development and progression of vascular progression, and explored novel therapeutic possibilities.
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http://dx.doi.org/10.3389/fcvm.2021.639740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102685PMC
April 2021

Protein corona precoating on redox-responsive chitosan-based nano-carriers for improving the therapeutic effect of nucleic acid drugs.

Carbohydr Polym 2021 Aug 16;265:118071. Epub 2021 Apr 16.

School of Pharmacy, Nantong University, No. 19 Qixiu Road, Nantong, 226001, China. Electronic address:

Spontaneous formation of protein corona on chitosan-based nano-carriers is inevitable once they enter the blood, which is considered to be an important factor that weakens the delivery efficiency and therapeutic effect of nucleic acid drugs. For this, cyclic RGDyK peptide (cRGD) modified bovine serum albumin (BSA) was designed as a corona to precoat on redox-responsive chitosan-based nano-carriers (TsR NPs) before administration. The effects of the precoating corona on the pharmaceutical properties and delivery efficiency of the nano-carriers and the therapeutic effect of model siRNA (siVEGF) were investigated. The results showed that BSA-cRGD formed steady corona around TsR NPs, which enhanced targeting ability to cancer cells and reduced serum proteins adsorption. The Bc corona improved the stability and biocompatibility of TsR NPs, increased the intracellular uptake, facilitated the lysosomal escape and maintained their redox-sensitive responsiveness, resulting in enhanced gene silencing efficiency and anti-tumor proliferation effects both in vitro and in vivo.
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http://dx.doi.org/10.1016/j.carbpol.2021.118071DOI Listing
August 2021

Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 infection.

Nat Commun 2021 05 4;12(1):2506. Epub 2021 May 4.

Institute of Immunology, PLA, Third Military Medical University, Chongqing, P. R. China.

It is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect human kidney, thus leading to acute kidney injury (AKI). Here, we perform a retrospective analysis of clinical parameters from 85 patients with laboratory-confirmed coronavirus disease 2019 (COVID-19); moreover, kidney histopathology from six additional COVID-19 patients with post-mortem examinations was performed. We find that 27% (23/85) of patients exhibited AKI. The elderly patients and cases with comorbidities (hypertension and heart failure) are more prone to develop AKI. Haematoxylin & eosin staining shows that the kidneys from COVID-19 autopsies have moderate to severe tubular damage. In situ hybridization assays illustrate that viral RNA accumulates in tubules. Immunohistochemistry shows nucleocapsid and spike protein deposits in the tubules, and immunofluorescence double staining shows that both antigens are restricted to the angiotensin converting enzyme-II-positive tubules. SARS-CoV-2 infection triggers the expression of hypoxic damage-associated molecules, including DP2 and prostaglandin D synthase in infected tubules. Moreover, it enhances CD68+ macrophages infiltration into the tubulointerstitium, and complement C5b-9 deposition on tubules is also observed. These results suggest that SARS-CoV-2 directly infects human kidney to mediate tubular pathogenesis and AKI.
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http://dx.doi.org/10.1038/s41467-021-22781-1DOI Listing
May 2021

Noninvasive papillary urothelial carcinoma with pathological features in between low and high grades: A case report.

Medicine (Baltimore) 2021 Apr;100(17):e25693

Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.

Rationale: Urinary bladder urothelial carcinoma is the most common malignant tumor in the urinary system, and noninvasive papillary urothelial carcinoma (NIPUC) comprises most bladder malignancies. NIPUC grading is important for therapeutic and clinical protocol selection. Here, we report a case of NIPUC with pathological features in between low (LG-NIPUC) and high (HG-NIPUC) grades NIPUC.

Patient Concerns: A 72-year-old male, presenting with a 20-year history of hypertension and 5 months of hematuria.

Diagnoses: Computed tomography examination revealed a tumor in the urinary bladder neck. Microscopic investigation revealed that most tumor tissue samples had a branching papillary architecture, with well-developed fibrous-vascular cores. Tumor cells were slightly crowded, with somewhat altered cell polarity and cell adhesion. Immunohistochemistry showed positive Ki67 staining, mostly in the basal layer, while p53 staining was rarely positive. These samples were diagnosed as LG-NIPUC. However, a few tumor tissue samples presented mildly fused papillary architectures without cell polarity or adhesion. Most nuclei stained intensely and were pleomorphic. All epithelial tissue layers were ki67 positive, and the p53 positive rate was higher than that in the LG samples. Therefore, these were classified as HG-NIPUC.

Interventions: The tumor was completely resected during lithotomy postural surgery.

Outcomes: The patient is alive with a good recovery during 3 months after the surgery.

Lessons: We diagnosed this patient as having LG-NIPUC with local HG-NIPUC components. HG- and LG-HIPUC have different outcomes. This case is a new challenge for the pathological grading of NIPUC. An intermediate HIPUC grade might need to be added to the original NIPUC grading system.
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http://dx.doi.org/10.1097/MD.0000000000025693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084004PMC
April 2021

The Role of non-coding RNAs in colorectal cancer, with a focus on its autophagy.

Pharmacol Ther 2021 Apr 23;226:107868. Epub 2021 Apr 23.

State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. Electronic address:

Colorectal cancer (CRC) is one of malignant afflictions burdening people worldwide, mainly caused by shortages of effective medical intervention and poorly mechanistic understanding of the pathogenesis of CRC. Non-coding RNAs (ncRNAs) are a type of heterogeneous transcripts without the capability of coding protein, but have the potency of regulating protein-coding gene expression. Autophagy is an evolutionarily conserved catabolic process in which cytoplasmic contents are delivered to cellular lysosomes for degradation, resulting in the turnover of cellular components and producing energy for cell functions. A growing body of evidence reveals that ncRNAs, autophagy, and the crosstalks of ncRNAs and autophagy play intricate roles in the initiation, progression, metastasis, recurrence and therapeutic resistance of CRC, which confer ncRNAs and autophagy to serve as clinical biomarkers and therapeutic targets for CRC. In this review, we sought to delineate the complicated roles of ncRNAs, mainly including miRNAs, lncRNAs and circRNAs, in the pathogenesis of CRC, particularly focus on the regulatory role of ncRNAs in CRC-related autophagy, attempting to shed light on the complex pathological mechanisms, involving ncRNAs and autophagy, responsible for CRC tumorigenesis and development, so as to underpin the ncRNAs- and autophagy-based therapeutic strategies for CRC in clinical setting.
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http://dx.doi.org/10.1016/j.pharmthera.2021.107868DOI Listing
April 2021

Advances in Research on the Cardiovascular Complications of Acromegaly.

Front Oncol 2021 2;11:640999. Epub 2021 Apr 2.

Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China.

Cardiovascular-related complications are one of the most common complications in patients with acromegaly, and can lead to an increased risk of death. Hypertension and cardiomyopathy are the main cardiovascular complications. The characteristics of acromegalic cardiomyopathy are concentric biventricular hypertrophy and diastolic dysfunction. In addition, arrhythmia and heart valve disease are common cardiac complications in acromegaly. Although the underlying pathophysiology has not been fully elucidated, the spontaneous overproduction of GH and IGF-1, increasing age, prolonged duration of disease and the coexistence of other cardiovascular risk factors are crucial to cardiac complications in patients with acromegaly. Early diagnosis and appropriate treatment of acromegaly might be beneficial for the prevention of cardiomyopathy and premature death.
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http://dx.doi.org/10.3389/fonc.2021.640999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050332PMC
April 2021

Acupuncture Treatment for Cough-Variant Asthma: A Meta-Analysis.

Evid Based Complement Alternat Med 2021 2;2021:6694936. Epub 2021 Apr 2.

Chengdu University of Traditional Chinese Medicine, Chengdu 6100752, Sichuan, China.

Background: In recent years, there have been many clinical reports on acupuncture treatment of cough-variant asthma, but no researcher has objectively analysed and evaluated the efficacy and safety of acupuncture treatment of cough-variant asthma from the perspective of evidence-based medicine.

Objective: To systematically evaluate the clinical efficacy and safety of acupuncture in treating cough-variant asthma and to provide reference values for clinical decision-making.

Methods: The comprehensive computer retrieval Chinese journal full-text database (CNKI), Chinese science and technology periodical database (VIP), ten thousand data knowledge service platform (WanFang Data), PubMed, Embase, and the Cochrane Library were used to collect literature for relevant randomized controlled trials (RCT) of acupuncture treatment of cough-variant asthma, as well as to retrieve papers and add reference retrieval after literature review, in accordance with the standard of literature filtering, data extraction, and quality evaluation. The data were meta-analysed using ReviewManager5.3 software recommended by Cochrane.

Results: A total of 11 randomized controlled clinical studies were screened and included, comprising 929 patients. The results of the meta-analysis showed that, compared with the control group, acupuncture intervention on CVA could enhance the total clinical effectiveness rate, reduce the relapse rate of drug withdrawal, relieve symptoms of cough, phlegm, and diaphragmatic congestion, and improve lung function-related indicators and immune inflammation indicators. There were statistically significant differences in all efficacy evaluation criteria.

Conclusion: The clinical curative effect of acupuncture treatment for cough-variant asthma is precise and has certain advantages in relieving symptoms and reducing the recurrence rate. However, the low quality of the evaluation in the RCT research literature is a problem, and more high-quality clinical randomized controlled trials are needed to further verify the comprehensive clinical efficacy and safety of this treatment. Registration number: PROSPERO (no. CRD42020155244) (https://www.crd.york.ac.uk/prospero/).
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http://dx.doi.org/10.1155/2021/6694936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034997PMC
April 2021

Clinicopathologic features and treatment of thymic lymphoepithelioma-like carcinoma: two case reports and literature review.

Am J Transl Res 2021 15;13(3):1896-1903. Epub 2021 Mar 15.

Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University No. 155 Nanjing North Street, Heping District, Shenyang 110001, Liaoning, China.

Lymphoepithelioma-like carcinoma (LELC) is rare in the thymus, and easily misdiagnosed. To improve its clinicopathologic knowledge, we describe two cases of thymic LELC, and investigate their microscopic and immunohistochemical features, treatment, and follow-up with a review of previously published cases. Two patients in the First Affiliated Hospital of China Medical University underwent complete surgical resection for thymic LELC. They were treated with chemotherapy or radiotherapy after operation. Histologically, tumor cells exhibited nest patterns or showed stripe-shaped infiltration in fibrous tissue containing lymphocytes. Tumor was diffusely positive for pan-cytokeratin (CK), CK19, cluster of differentiation 5 (CD5), CD117, epithelial membrane antigen (EMA), and p63, and negative for TdT. Recent follow-up showed that the two patients were alive with no signs of recurrence. We report two cases of thymic LELC with a review of previously published cases to summarize knowledge of their clinicopathological characteristics, which is necessary for accurate diagnosis and clinical treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014405PMC
March 2021

Identification and evolution analysis of the JAZ gene family in maize.

Authors:
Yang Han Dawn Luthe

BMC Genomics 2021 Apr 10;22(1):256. Epub 2021 Apr 10.

The Pennsylvania State University, Plant Science, University Park, PA, USA.

Background: Jasmonates (JAs) are important for plants to coordinate growth, reproduction, and defense responses. In JA signaling, jasmonate ZIM-domain (JAZ) proteins serve as master regulators at the initial stage of herbivores attacks. Although discovered in many plant species, little in-depth characterization of JAZ gene expression has been reported in the agronomically important crop, maize (Zea mays L.).

Results: In this study 16 JAZ genes from the maize genome were identified and classified. Phylogenetic analyses were performed from maize, rice, sorghum, Brachypodium, and Arabidopsis using deduced protein sequences, total six clades were proposed and conservation was observed in each group, such as similar gene exon/intron structures. Synteny analysis across four monocots indicated these JAZ gene families had a common ancestor, and duplication events in maize genome may drive the expansion of JAZ gene family, including genome-wide duplication (GWD), transposon, and/or tandem duplication. Strong purifying selection acted on all JAZ genes except those in group 4, which were under neutral selection. Further, we cloned three paralogous JAZ gene pairs from two maize inbreds differing in JA levels and insect resistance, and gene polymorphisms were observed between two inbreds.

Conclusions: Here we analyzed the composition and evolution of JAZ genes in maize with three other monocot plants. Extensive phylogenetic and synteny analysis revealed the expansion and selection fate of maize JAZ. This is the first study comparing the difference between two inbreds, and we propose genotype-specific JAZ gene expression might be present in maize plants. Since genetic redundancy in JAZ gene family hampers our understanding of their role in response to specific elicitors, we hope this research could be pertinent to elucidating the defensive responses in plants.
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http://dx.doi.org/10.1186/s12864-021-07522-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037931PMC
April 2021

Association between intake of sweetened beverages with all-cause and cause-specific mortality: a systematic review and meta-analysis.

J Public Health (Oxf) 2021 Apr 9. Epub 2021 Apr 9.

General Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University; Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis; Henan Engineering Research Center for Critical Care Medicine, Zhengzhou 450052, China.

Background: Conclusions remain controversial between the consumption of sugar and artificially sweetened beverages (SSBs and ASBs) and mortality.

Methods: We systematically searched the PubMed, Embase, Cochrane Library and Web of Science databases from their inception date to 1st January 2020, prospective cohort studies researching the mortality risk and SSBs or ASBs consumption were included. Random effects meta-analyses and dose-response analyses were performed to measure the association. Subgroup analyses and sensitivity analyses were further performed to explore the source of heterogeneity. Publication bias was assessed by Funnel plots and Egger's regression test.

Results: Across all 15 cohorts, 1211 470 participants were included. High SSB consumption was associated with a higher risk of all-cause mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.06-1.19, P < 0.001; and cardiovascular disease [CVD] mortality [HR 1.20, 95% CI, 1.05-1.38, P < 0.001]), and high ASBs consumption showed similar result (HR 1.12, 95% CI, 1.04-1.21, P = 0.001 for all-cause mortality and HR 1.23, 95% CI, 1.00-1.50, P = 0.049 for CVD mortality), both showed a linear dose-response relationship.

Conclusions: High consumption of both ASBs and SSBs showed significant associations with a higher risk of CVD mortality and all-cause mortality. This information may provide ideas for decreasing the global burden of diseases by reducing sweetened beverage intake.
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http://dx.doi.org/10.1093/pubmed/fdab069DOI Listing
April 2021

[Investigation and analysis of children's choice of environment in oral clinics].

Hua Xi Kou Qiang Yi Xue Za Zhi 2021 Apr;39(2):182-187

Dept. of Pediatric Dentistry, Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao 266001, China.

Objectives: To investigate and analyze children,s choice of environment in oral clinics so as to provide evidence for improving the oral clinic environment.

Methods: A total of 110 children in the Pediatric Dentistry of Qingdao Stomatological Hospital Affiliated to Qingdao University were selected as the research subjects from September to December 2019 to conduct a questionnaire survey, and the results were statistically analyzed by using a Chi-square test.

Results: A total of 107 effective questionnaires were collected. The children surveyed liked the room with pink and blue walls (61.68%), cartoon murals (57.94%), and arranged toys (61.68%). Most of them did not dislike the special smell in the room (62.62%) and liked the smell of orange essential oil (52.34%). During treatment, the children liked watching cartoons the best (61.68%), expected doctors to be dressed in white (51.40%), and expected doctors to be treated by female doctors (68.22%). Most children wanted to be accompanied by family members during treatment (62.62%). The Chi-square test showed statistically significant differences in seven questions between preschool and school-age children: the environment of the clinic room, the color of the walls, the clinic decoration, the entertainment during treatment, color of the doctors' dress and gender, and company of the family members during treatment (<0.05). The difference of children's choice of color of the wall and clinic decoration during the first and subsequent visit was statistically significant (<0.05). However, no significant difference was observed in the choice of clinic environment between different genders (>0.05).

Conclusions: Children have their own preferences for the environment in the oral clinic. For preschool children, we need to create a soothing and warm atmosphere with warm colors liked by children. For school-age children, a calm and relaxed clinic atmosphere with cold colors should be created.
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http://dx.doi.org/10.7518/hxkq.2021.02.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055774PMC
April 2021

Tumor suppressor DCAF15 inhibits epithelial-mesenchymal transition by targeting ZEB1 for proteasomal degradation in hepatocellular carcinoma.

Aging (Albany NY) 2021 Apr 4;13(7):10603-10618. Epub 2021 Apr 4.

Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

Epithelial-mesenchymal transition (EMT) is an evolutionarily conserved developmental program that has been implicated in tumorigenesis and confers metastatic properties upon cancer cells. ZEB1 is a master transcription factor that activates the EMT process in various cancers. ZEB1 is reportedly degraded through the ubiquitin proteasome pathway, but the underlying molecular mechanism of this process remains largely unknown in hepatocellular carcinoma (HCC). Here, we identified ZEB1 as a substrate of the CRL4-DCAF15 (DDB1 and CUL4 associated factor 15) E3 ubiquitin ligase complex. DCAF15 acts as an adaptor that specifically recognizes the N-terminal zinc finger domain of ZEB1, then triggers its degradation via the ubiquitin-proteasome pathway. DCAF15 knockdown led to upregulation of ZEB1 and activation of EMT, whereas overexpression of DCAF15 suppressed ZEB1 and inhibited EMT. DCAF15 knockdown also promoted HCC cell proliferation and invasion in a ZEB1-dependent manner. In HCC patients, low DCAF15 expression was predictive of an unfavorable prognosis. These findings reveal the distinct molecular mechanism by which DCAF15 suppresses HCC malignancy and provides insight into the relationship between the CUL4-DCAF15 E3 ubiquitin ligase complex and ZEB1 in HCC.
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http://dx.doi.org/10.18632/aging.202823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064142PMC
April 2021

Corrigendum: High-Dose Intravenous Immunoglobulin in Severe Coronavirus Disease 2019: A Multicenter Retrospective Study in China.

Front Immunol 2021 22;12:671443. Epub 2021 Mar 22.

Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

[This corrects the article DOI: 10.3389/fimmu.2021.627844/full.].
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http://dx.doi.org/10.3389/fimmu.2021.671443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020904PMC
March 2021

Colorectal Cancer, Gut Microbiota and Traditional Chinese Medicine: A Systematic Review.

Am J Chin Med 2021 6;49(4):805-828. Epub 2021 Apr 6.

State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

Based on the study and research on the pathogenesis of colorectal cancer, the types and functions of gut microbiota, and its role in guiding and regulating the occurrence and development of diseases, we have explored the mechanism of traditional Chinese medicine in the treatment of colorectal cancer by regulating the gut microbiota. Genetic variation, abnormal responses of innate and adaptive immunity, mucosal barrier dysfunction, imbalance of intestinal microbial colonization, personal and environmental risk factors are the main pathogenesis of colorectal cancer. The gut microbiota mainly includes (including , , and ) and (including and ), which have biological antagonism, nutrition for the organism, metabolic abilities, immune stimulation, and ability to shape cancer genes functions to body. The gut microbiota can be related to the health of the host. Current studies have shown that Chinese herbal compound, single medicinal materials, and monomer components can treat colorectal cancer by regulating the gut microbiota, such as Xiaoyaosan can increase the abundance of , , and and decrease the abundance of and . Therefore, studying the regulation and mechanism of gut microbiota on colorectal cancer is of great benefit to disease treatment.
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http://dx.doi.org/10.1142/S0192415X21500385DOI Listing
April 2021

Tuning Molecular Superlattice by Charge-Density-Wave Patterns in Two-Dimensional Monolayer Crystals.

J Phys Chem Lett 2021 Apr 5;12(14):3545-3551. Epub 2021 Apr 5.

MIIT Key Laboratory for Low-Dimensional Quantum Structure and Devices, School of Information and Electronics, Beijing Institute of Technology, Beijing 100081, China.

Charge density wave (CDW) in two-dimensional (2D) crystals plays a vital role in tuning the interface structures and properties. However, how the CDW tunes the self-assembled molecular superlattice still remains unclear. In this study, we investigated the self-assembled manganese phthalocyanine (MnPc) molecular superlattice on single-layered 1T- and 2H-NbSe crystals under regulation by distinct CDW patterns. We observe that, in low coverage, MnPc molecules preferentially adsorb on 2H-NbSe compared to 1T-NbSe. With increasing coverage, MnPc can form a highly ordered superlattice on 2H-NbSe; however, it is randomly distributed on 1T-NbSe. We reveal a perfect geometric commensurability between the molecular superlattice and intrinsic CDW pattern in 2H-NbSe and a poor commensurability for that of 1T-NbSe. We believe that the subtly different geometric commensurability dominates the different adsorption and arrangement of the molecular superlattices on 2D CDW patterns. Our study provides a pioneering approach for tuning the molecular superlattices using the CDW patterns.
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http://dx.doi.org/10.1021/acs.jpclett.1c00230DOI Listing
April 2021

[Mechanism of ursolic acid in regulating colorectal cancer cell HCT116 autophagy through hedgehog signaling pathway].

Zhongguo Zhong Yao Za Zhi 2021 Mar;46(5):1217-1223

Department of Pharmacology,School of Pharmacy,Chengdu University of Traditional Chinese Medicine Chengdu 611137,China.

To prove that ursolic acid(UA)could activate the autophagy of colorectal cancer HCT116 cells by inhibiting hedgehog signaling pathway. The effect of UA on the viability of HCT116 cells was determined by MTT assay. The effect of UA on the proliferation and migration of HCT116 cells was detected by crystal violet staining and scratch test. In the study on autophagy, the time points were screened out first: the autophagy fluorescence intensity of UA acting on HCT116 at different time points were detected by Cell Meter~(TM) Autophagy Assay Kit; Western blot was used to detect the expression of autophagy protein P62 at different time points. Then, Cell Meter~(TM) Autophagy Assay Kit was used to detect the effect of UA on autophagy fluorescence intensity of HCT116 cells. The effect of different doses of UA on the expressions of LC3Ⅱ and P62 proteins in HCT116 cells were detected by Western blot. Further, AdPlus-mCherry-GFP-LC3 B adenovirus transfection was used to detect the effects of UA on autophagy flux of HCT116 cells; UA combined with autophagy inhibitor chloroquine(CQ) was used to detect the expression of LC3Ⅱ by Western blot. In terms of mechanism, the effect of UA on hedgehog signaling pathway-related proteins in HCT116 cells was detected by Western blot. The results showed that UA inhibited the activity, proliferation and migration of HCT116 cells. UA enhanced the fluorescence intensity of autophagy in HCT116 cells, while promoting the expression of LC3Ⅱ and inhibiting the expression of P62, in a time and dose dependent manner. UA activated the autophagy in HCT116 cells, which manifested that UA resulted in the accumulation of fluorescence spots and strengthened the fluorescence intensity of autophagosomes; compared with UA alone, UA combined with autophagy inhibitor CQ promoted the expression of LC3Ⅱ. UA reduced the expressions of PTCH1, GLI1, SMO, SHH and c-Myc in hedgehog signaling pathway, while increased the expression of Sufu. In conclusion, our study showed that UA activated autophagy in colorectal cancer HCT116 cells, which was related to the mechanism in inhibiting hedgehog signaling pathway activity.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201207.403DOI Listing
March 2021

Direct identification of Mott Hubbard band pattern beyond charge density wave superlattice in monolayer 1T-NbSe.

Nat Commun 2021 Mar 30;12(1):1978. Epub 2021 Mar 30.

School of Information and Electronics, MIIT Key Laboratory for Low-Dimensional Quantum Structure and Devices, Beijing Institute of Technology, Beijing, China.

Understanding Mott insulators and charge density waves (CDW) is critical for both fundamental physics and future device applications. However, the relationship between these two phenomena remains unclear, particularly in systems close to two-dimensional (2D) limit. In this study, we utilize scanning tunneling microscopy/spectroscopy to investigate monolayer 1T-NbSe to elucidate the energy of the Mott upper Hubbard band (UHB), and reveal that the spin-polarized UHB is spatially distributed away from the dz orbital at the center of the CDW unit. Moreover, the UHB shows a √3 × √3 R30° periodicity in addition to the typically observed CDW pattern. Furthermore, a pattern similar to the CDW order is visible deep in the Mott gap, exhibiting CDW without contribution of the Mott Hubbard band. Based on these findings in monolayer 1T-NbSe, we provide novel insights into the relation between the correlated and collective electronic structures in monolayer 2D systems.
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http://dx.doi.org/10.1038/s41467-021-22233-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010100PMC
March 2021

Expanding the scope of plant genome engineering with Cas12a orthologs and highly multiplexable editing systems.

Nat Commun 2021 03 29;12(1):1944. Epub 2021 Mar 29.

Department of Plant Science and Landscape Architecture, University of Maryland, College Park, MD, USA.

CRISPR-Cas12a is a promising genome editing system for targeting AT-rich genomic regions. Comprehensive genome engineering requires simultaneous targeting of multiple genes at defined locations. Here, to expand the targeting scope of Cas12a, we screen nine Cas12a orthologs that have not been demonstrated in plants, and identify six, ErCas12a, Lb5Cas12a, BsCas12a, Mb2Cas12a, TsCas12a and MbCas12a, that possess high editing activity in rice. Among them, Mb2Cas12a stands out with high editing efficiency and tolerance to low temperature. An engineered Mb2Cas12a-RVRR variant enables editing with more relaxed PAM requirements in rice, yielding two times higher genome coverage than the wild type SpCas9. To enable large-scale genome engineering, we compare 12 multiplexed Cas12a systems and identify a potent system that exhibits nearly 100% biallelic editing efficiency with the ability to target as many as 16 sites in rice. This is the highest level of multiplex edits in plants to date using Cas12a. Two compact single transcript unit CRISPR-Cas12a interference systems are also developed for multi-gene repression in rice and Arabidopsis. This study greatly expands the targeting scope of Cas12a for crop genome engineering.
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http://dx.doi.org/10.1038/s41467-021-22330-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007695PMC
March 2021

Diversity of actinobacteria in sediments of Qaidam Lake and Qinghai Lake, China.

Arch Microbiol 2021 Mar 22. Epub 2021 Mar 22.

College of Food and Biological Engineering, Xihua University, Chengdu, 610039, P. R. China.

Using 16S rRNA gene analysis and high-throughput, the diversity and community structure of actinobacteria in the sediments of Qaidam Lake and Qinghai Lake with different salinity and alkalinity in Qinghai-Xizang Plateau were studied, and the differences of actinobacteria community structure and their relationship with environmental factors were discussed. A total of 77 genera belonging to actinobacteria were found in the samples, of which 31 genera were found in the sediment samples of Qaidam Lake with 19 genera being dominant genera, such as Actinomycetes, Corynebacterium, Morella, Bifidobacterium, and 69 genera were found in the sediment samples of Qinghai Lake with 17 genera becoming dominant, such as Ilumattalaer, Actinotalea, Aquihaans and so on. The correlation analysis of environmental factors and community showed that the community structure of the two salt lakes was mainly affected by total salinity, total organic carbon) (TOC) and CO, among which TOC was the most influential factor. The functional differences of metabolic pathway enrichment analysis (KEGG) showed that there was a high abundance of metabolic-related functions in the two salt lakes. There were significant differences in the biosynthesis of energy metabolism and other secondary metabolites between the two salt lakes, which may be the main reason for the difference of actinomycete community. The results show that the actinobacteria diversity was rich in the plateau salt lakes, and affected by a variety of physicochemical factors. In addition, there were a large number of unculturable actinobacteria in the sediment, which provides a theoretical basis for the excavation and utilization of actinobacteria resources in salt lakes.
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http://dx.doi.org/10.1007/s00203-021-02277-8DOI Listing
March 2021

Broad phenotypic alterations and potential dysfunction of lymphocytes in individuals clinically recovered from COVID-19.

J Mol Cell Biol 2021 Mar 5. Epub 2021 Mar 5.

Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.

Although millions of patients have clinically recovered from COVID-19, little is known about the immune status of lymphocytes in these individuals. In this study, the peripheral blood mononuclear cells (PBMCs) of a clinically recovered (CR) cohort were comparatively analyzed with those of an age- and sex-matched healthy donor (HD) cohort. We found that CD8+ T cells in the CR cohort had higher numbers of effector T cells and effector memory T cells but lower Tc1 (IFN-γ+), Tc2 (IL-4+), and Tc17 (IL-17A+) cell frequencies. The CD4+ T cells of the CR cohort were decreased in frequency, especially the central memory T cell subset. Moreover, CD4+ T cells in the CR cohort showed lower PD-1 expression and had lower frequencies of Th1 (IFN-γ+), Th2 (IL-4+), Th17 (IL-17A+), and circulating follicular helper T (CXCR5+PD-1+) cells. Accordingly, the proportion of isotype-switched memory B cells (IgM-CD20hi) among B cells in the CR cohort showed a significantly lower proportion, although the level of the activation marker CD71 was elevated. For CD3-HLA-DR- lymphocytes in the CR cohort, in addition to lower levels of IFN-γ, granzyme B, and T-bet, the correlation between T-bet and IFN-γ was not observed. Additionally, by taking into account the number of days after discharge, all the phenotypes associated with reduced function did not show a tendency toward recovery within 4‒11 weeks. The remarkable phenotypic alterations in lymphocytes in the CR cohort suggest that SARS-CoV-2 infection profoundly affects lymphocytes and potentially results in dysfunction even after clinical recovery.
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http://dx.doi.org/10.1093/jmcb/mjab014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989217PMC
March 2021

Rab26 suppresses migration and invasion of breast cancer cells through mediating autophagic degradation of phosphorylated Src.

Cell Death Dis 2021 Mar 17;12(4):284. Epub 2021 Mar 17.

School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, 361005, Fujian, China.

Rab proteins play crucial roles in membrane trafficking. Some Rab proteins are implicated in cancer development through regulating protein sorting or degradation. In this study, we found that the expression of Rab26 is suppressed in the aggressive breast cancer cells as compared to the levels in non-invasive breast cancer cells. Over-expression of Rab26 inhibits cell migration and invasion, while Rab26 knockdown significantly promotes the migration and invasion of breast cancer cells. Rab26 reduces focal adhesion association of Src kinase and induces endosomal translocation of Src. Further experiments revealed that Rab26 mediates the autophagic degradation of phosphorylated Src through interacting with ATG16L1, consequently, resulting in the suppression of the migration and invasion ability of breast cancer cells.
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http://dx.doi.org/10.1038/s41419-021-03561-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969620PMC
March 2021

What Do You Mean by Community Resilience? More Assets or Better Prepared?

Disaster Med Public Health Prep 2021 Mar 17:1-8. Epub 2021 Mar 17.

Shenzhen Institute for Advanced Study & School of Public Affairs and Administration, University of Electronic Science and Technology of China, Chengdu, China.

Objectives: Understanding people's perception of community resilience to disaster is important. This study explores the correlations of household livelihood assets, the adopted household disaster preparedness activities, and individuals' assessment of community resilience.

Methods: The data was collected in 2018 by surveying a group of survivors affected by the 2008 Wenchuan earthquake in China. The CART (Community Advancing Resilience Toolkit) was used to measure individuals' perception of community resilience, while the livelihood assets included financial, physical, natural, human, and social capitals owned by the family, and the preparedness contained 13 activities. Ordinary least squares (OLS) regression models were used to test our hypotheses.

Results: Social capital is consistently and positively associated with the overall individuals' perceived community resilience, while the natural, human, and financial capitals' effects are not significant. The awareness and participation preparedness activities are positively correlated with the perceived community resilience, but the material preparedness activities are not.

Conclusions: Social capital and disaster preparedness activities are critical in building community resilience. Community resilience can be achieved by making the community more connected and by providing disaster preparedness interventions.
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http://dx.doi.org/10.1017/dmp.2020.466DOI Listing
March 2021

Characteristics of T-cell responses in COVID-19 patients with prolonged SARS-CoV-2 positivity - a cohort study.

Clin Transl Immunology 2021 4;10(3):e1259. Epub 2021 Mar 4.

Shanghai Public Health Clinical Center Fudan University Shanghai China.

Objective: SARS-CoV-2 has caused a worldwide pandemic of COVID-19. The existence of prolonged SARS-CoV-2 positivity (PP) has further increased the burden on the health system. Since T cells are vital for viral control, we aimed to evaluate the characteristics of T-cell responses associated with PP.

Methods: We established a PP cohort and two age- and sex-matched control cohorts: a regular clinical recovery (CR) cohort and a healthy donor (HD) cohort. The mean time for RNA negativity conversion in the PP cohort was markedly longer than that in the CR cohort (66.2 vs 25.3 days), while the time from illness onset to sampling was not significantly different. T-cell responses in the PP cohort were assayed, analysed and compared with those in the CR and HD cohorts by flow cytometry and ELISpot analysis of peripheral blood mononuclear cells.

Results: Compared with the CR cohort, the proliferation, activation and functional potential of CD8 and CD4 T cells in the PP cohort were not significantly different. However, the frequencies and counts of Teff and Tem in CD8 but not in CD4 T cells of the PP cohort were prominently lower. Moreover, a weaker SARS-CoV-2 N protein-specific IFN-γ T-cell response and a higher frequency of Tregs were detected in the PP cohort.

Conclusion: Suppressed CD8 T-cell differentiation is associated with PP and may be an indicator for the prediction of prolonged SARS-CoV-2 positivity in COVID-19 patients. The association between suppressed CD8 T-cell differentiation and elevated Tregs warrants studies in the future.
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http://dx.doi.org/10.1002/cti2.1259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932004PMC
March 2021

Ultra-compact silicon-microcap based improved Michelson interferometer high-temperature sensor.

Opt Express 2021 Mar;29(5):6703-6713

An ultra-short high-temperature fiber-optic sensor based on a silicon-microcap created by a single-mode fiber (SMF) and simple fusion splicing technology is proposed and experimentally demonstrated. A section of the SMF with a silicon-microcap at one end is connected to the "peanut" structure to build the microcap-based optical fiber improved Michelson interferometer (MI). The optimal discharge parameters of microcap and length of SMF has been investigated to achieve the best extinction ratio of 6.61 dB. The size of this microcap-based improved MI sensor is 560 µm and about 18 times shorter compared to the current fiber tip interferometers (about 10 mm). Meanwhile, it showed good robustness during the two heating-cooling cycles and the duration period stability test at 900 °C. This microcap-based improved MI sensor with the smaller size, simple fabrication, low cost, high reliability, and good linearity within a large dynamic range is beneficial to practical temperature measurement and massive production.
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http://dx.doi.org/10.1364/OE.419260DOI Listing
March 2021

A large real-world cohort study of examined lymph node standards for adequate nodal staging in early non-small cell lung cancer.

Transl Lung Cancer Res 2021 Feb;10(2):815-825

Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Background: The current National Comprehensive Cancer Network (NCCN) guidelines for non-small cell lung cancer (NSCLC) recommend that surgeons sample is not clear. We aimed to define a minimal number of examined lymph nodes for removal or sampling for optimized nodal staging recommendation, with a focus on TNM patients.

Methods: A total of 55,101 consecutive patients were selected, including 52,099 patients with US Surveillance, Epidemiology, and End Results (SEER) data and 3,002 patients in a Chinese multicenter database from 11 thoracic referral centers, who underwent complete resection plus lymph node dissection or sampling for stage TNM NSCLC. Propensity score-matching analysis was performed with R software, and a cut-off value was calculated using X-tile software. Survival was evaluated using the Kaplan-Meier method and Cox proportional hazard models.

Results: Five-year survival rates with respect to total examined lymph nodes numbers (examined lymph nodes <10 examined lymph nodes ≥10) were 69% and 64% (group A), 66% and 63% (group B), 62% and 58% (group C), 81% and 75% (group D). There were significant differences between examined lymph nodes <10 and examined lymph nodes >10 in each group (P<0.001).

Conclusions: A minimum of 10 examined lymph nodes would significantly improve TNM NSCLC prognosis and patients' survival rates if implemented as a minimum standard for lymphadenectomy. Therefore, we recommended a minimum of 10 examined lymph nodes for TNM patients.
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http://dx.doi.org/10.21037/tlcr-20-1024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947406PMC
February 2021

Comparative transcriptomics highlights convergent evolution of energy metabolic pathways in group-living spiders.

Zool Res 2021 Mar;42(2):195-206

Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

Although widely thought to be aggressive, solitary, and potentially cannibalistic, some spider species have evolved group-living behaviors. The distinct transition provides the framework to uncover group-living evolution. Here, we conducted a comparative transcriptomic study and examined patterns of molecular evolution in two independently evolved group-living spiders and twelve solitary species. We report that positively selected genes among group-living spider lineages are significantly enriched in nutrient metabolism and autophagy pathways. We also show that nutrient-related genes of group-living spiders convergently experience amino acid substitutions and accelerated relative evolutionary rates. These results indicate adaptive convergence of nutrient metabolism that may ensure energy supply in group-living spiders. The decelerated evolutionary rate of autophagy-related genes in group-living lineages is consistent with an increased constraint on energy homeostasis as would be required in a group-living environment. Together, the results show that energy metabolic pathways play an important role in the transition to group-living in spiders.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2020.281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995277PMC
March 2021

Single cell capture, isolation, and long-term in-situ imaging using quantitative self-interference spectroscopy.

Cytometry A 2021 Mar 11. Epub 2021 Mar 11.

Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China.

Single cell research with microfluidic chip is of vital importance in biomedical studies and clinical medicine. Simultaneous microfluidic cell manipulations and long-term cell monitoring needs further investigations due to the lack of label-free quantitative imaging techniques and systems. In this work, single cell capture, isolation and long-term in-situ monitoring was realized with a microfluidic cell chip, compact cell incubator and quantitative self-interference spectroscopy. The proposed imaging method could obtain quantitative and dynamic refractive index distribution in living cells. And the designed microfluidic chip could capture and isolate single cells. The customized incubator could support cell growth conditions when single cell was captured in microfluidic chip. According to the results, single cells could be trapped, transferred and pushed into the culture chamber with the microfluidic chip. The incubator could culture single cells in the chip for 120 h. The refractive index sensitivity of the proposed quantitative imaging method was 0.0282 and the relative error was merely 0.04%.
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http://dx.doi.org/10.1002/cyto.a.24333DOI Listing
March 2021

Mutation analysis using cell-free DNA for endocrine therapy in patients with HR+ metastatic breast cancer.

Sci Rep 2021 Mar 10;11(1):5566. Epub 2021 Mar 10.

Translational Cancer Research Branch, Research Institute, National Cancer Center, Goyang, Republic of Korea.

We prospectively evaluated the utility of ESR1 and PIK3CA mutation analysis with cell-free DNA (cfDNA) using droplet digital PCR (ddPCR) for the efficacy of endocrine therapy (ET) in hormone receptive positive (HR+) metastatic breast cancer (MBC) patients. CfDNA was analyzed just before the start of ET for MBC. E380Q, Y537N, Y537S, and D538G were assessed for ESR1 mutations and H1047R, E545K, and E542K were assessed for PIK3CA mutations. A total of 75 patients were enrolled. Of those, 31 (41.3%) received letrozole with palbociclib, and 28 (37.3%) received exemestane and everolimus (EverX). ESR1 mutations were found in 36 (48.0%) patients, of which 16 (21.3%) had more than one variant. Seventeen (23.6%) patients had one PIK3CA mutation and 8 (11.1%) had two. In the total population, time to progression of the first ET after enrollment (TTP1) decreased significantly as the number of ESR1 mutations increased (p < 0.001). PIK3CA mutations were also significantly associated with shorter TTP1 (median TTP1: 16.2 months vs. 10.9 months, p = 0.03). In contrast, PIK3CA mutations were significantly associated with longer TTP in patients receiving EverX treatment (median TTP of EverX: 15.9 months vs. 5.2 months, p = 0.01) and remained a significant factor in multivariable analysis for TTP of EverX in this subgroup (hazard ratio = 0.2, 95% CI = 0.1- 0.8, p = 0.03). ESR1 and PIK3CA mutations in cfDNA were associated with clinical efficacies of ET in HR+ MBC patients.
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http://dx.doi.org/10.1038/s41598-021-84999-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946916PMC
March 2021

High-Dose Intravenous Immunoglobulin in Severe Coronavirus Disease 2019: A Multicenter Retrospective Study in China.

Front Immunol 2021;12:627844. Epub 2021 Feb 19.

Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Background: The effective treatment of coronavirus disease 2019 (COVID-19) remains unclear. We reported successful use of high-dose intravenous immunoglobulin (IVIg) in cases of severe COVID-19, but evidence from larger case series is still lacking.

Methods: A multi-center retrospective study was conducted to evaluate the effectiveness of IVIg administered within two weeks of disease onset at a total dose of 2 g/kg body weight, in addition to standard care. The primary endpoint was 28-day mortality. Efficacy of high-dose IVIg was assessed by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) analysis, and IPTW after multiple imputation (MI) analysis.

Results: Overall, 26 patients who received high-dose IVIg with standard therapy and 89 patients who received standard therapy only were enrolled in this study. The IVIg group was associated with a lower 28-day mortality rate and less time to normalization of inflammatory markers including IL-6, IL-10, and ferritin compared with the control. The adjusted HR of 28-day mortality in high-dose IVIg group was 0.24 (95% CI 0.06-0.99, p<0.001) in IPTW model, and 0.27 (95% CI 0.10-0.57, p=0.031) in IPTW-MI model. In subgroup analysis, patients with no comorbidities or treated in the first week of disease were associated with more benefit from high-dose IVIg.

Conclusions: High-dose IVIg administered in severe COVID-19 patients within 14 days of onset was linked to reduced 28-day mortality, more prominent with those having no comorbidities or treated at earlier stage.
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http://dx.doi.org/10.3389/fimmu.2021.627844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933558PMC
March 2021