Publications by authors named "Xinhua Li"

215 Publications

Krüppel like factor 10 prevents intervertebral disc degeneration via TGF-β signaling pathway both and .

J Orthop Translat 2021 Jul 15;29:19-29. Epub 2021 May 15.

Department of Spine Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.

Background: Krüppel like factor 10 (KLF10), which is also known as TGF-β Inducible Early Gene-1 (TIEG1), plays a crucial role in regulating cell proliferation, cell apoptosis and inflammatory reaction in human carcinoma cells. Moreover, KLF10 knockout in mice leads to severe defects associated with muscle, skeleton and heart etc. However, the function of KLF10 in intervertebral disc degeneration (IVDD) has not been reported yet.

Methods: The relationship between KLF10 and IVDD were investigated in nucleus pulposus (NP) tissues from human and rats. The role of KLF10 in NP cells was explored via loss or gain of function experiments. IVDD rat models were constructed through needle puncture and the effects of KLF10 in IVDD model of rats were investigated via intradiscal injection of KLF10.

Results: We first found that KLF10 was lowly expressed in degenerative NP tissues and the level of KLF10 showed negative correlation with the disc grades of IVDD patients. Loss or gain of function experiments demonstrated that KLF10 could inhibit apoptosis and enhance migration and proliferation of IL-1β induced NP cells. And KLF10 overexpression reduced extracellular matrix (ECM) degeneration and enhanced ECM synthesis, whereas knockdown of KLF10 resulted in adverse effects. These positive effects of KLF10 could be reversed by the inhibition of TGF-β signaling pathway. , KLF10 overexpression alleviated IVDD.

Conclusions: This is the first study to reveal that KLF10 was dysregulated in IVDD and overexpressed KLF10 could alleviate IVDD by regulating TGF-β signaling pathway both and , which were involved in prohibiting apoptosis, promoting proliferation and migration of NP cells.The translational potential of this article: Overexpression of KLF10 might be an effective therapeutic strategy in the treatment of IVDD.
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http://dx.doi.org/10.1016/j.jot.2021.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141503PMC
July 2021

Fetal dose evaluation for body CT examinations of pregnant patients during all stages of pregnancy.

Eur J Radiol 2021 May 19;141:109780. Epub 2021 May 19.

Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.

Purpose: CTDI-to-fetal-dose coefficients from Monte Carlo simulations are useful for fetal dose evaluations, but the available data is limited to the fetus being completely inside the abdominopelvic scan range. Whereas in a chest examination, the fetus is completely outside the scan range. In an abdominal examination, the fetus after 16 gestational weeks is partly in the scan region, and an earlier fetus is completely outside of it. This work proposes a practical approach to evaluate fetal dose for pregnant patients undergoing body CT examinations, without using Monte Carlo simulation.

Methods: The proposed method was based on the z-axis dose profile computed for a CT examination, considering CTDI, scan range, mA, and maternal WED (water equivalent diameter) at the fetus centroid. Fetal average dose was calculated over the fetus z-axis coverage. For validation, we considered a reference dataset of 24 pregnant patients, each underwent two abdominopelvic examinations (fixed mA, tube current modulation). WED was 30.1 ± 3.3 (25.3-35.6) cm [mean(range)]. Gestational age was <5 weeks for one patient, and 20.3 ± 9.1 (5-35.9) weeks for the others. Fetal depth (from the anterior skin surface to the most anterior part of fetus) was 6.1 ± 2.1 (2.5-10.9) cm. We further considered three whole-body models of a pregnant patient (gestational age, 3, 6, 9 months; weight, 62-73 kg) undergoing chest, abdominal, and abdominopelvic examinations (fixed mA). For the patients and models, profile-based fetal dose calculations were compared with the results of Monte Carlo simulations. Statistical software (R, version 3.5.1) was used to determine the mean and 95th percentile.

Results: The fetal dose difference between profile-based evaluations and Monte Carlo simulations was (5.9 ± 3.8)% for 24 fixed-mA examinations, (5.8 ± 4.6)% for 24 tube current modulated examinations, and (8.8 ± 5.9)% for the whole-body models in three scan ranges.

Conclusions: Profile-based fetal dose calculations can be performed for patients in body CT, considering maternal size, fetus size and location, and whether fetus is completely inside, partly inside, or outside scan ranges.
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http://dx.doi.org/10.1016/j.ejrad.2021.109780DOI Listing
May 2021

Type II collagen-positive embryonic progenitors are the major contributors to spine and intervertebral disc development and repair.

Stem Cells Transl Med 2021 May 25. Epub 2021 May 25.

Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Type II collagen-positive embryonic progenitors are the major contributors to spine and intervertebral disc development and repair has been removed because it was published by mistake. The article will be published on October 1, 2021.
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http://dx.doi.org/10.1002/sctm.20-0424DOI Listing
May 2021

Expression Pattern and Prognostic Value of EPHA/EFNA in Breast Cancer by Bioinformatics Analysis: Revealing Its Importance in Chemotherapy.

Biomed Res Int 2021 22;2021:5575704. Epub 2021 Apr 22.

Department of Otorhinolaryngology, Tianjin Medical University General Hospital, Tianjin 300052, China.

The activities of the ephrin family in breast cancer (BrCa) are complex. Family A receptors (EPHA) and ligands (EFNA) can act as oncogenes or tumor suppressors and are implicated in chemoresistance. Here, we examined the expression pattern and prognostic value of the EPHA/EFNA family in patients with breast cancer, including patients with different subtypes or different chemotherapy cohorts. In the UALCAN database, the mRNA expression of EPHA1, EPHA10, EFNA1, EFNA3, and EFNA4 was significantly higher, whereas that of EPHA2, EPHA4, EPHA5, and EFNA5 was significantly lower in breast cancer tissues than in paracancerous tissues. The transcriptional levels of EPHA/EFNA family members were correlated with intrinsic subclasses of breast cancer. The relationship between EPHA/EFNA and the clinicopathological parameters of BrCa was analyzed using bc-GenExMiner V4.5. EPHA1, EPHA2, EPHA4, EPHA7, EFNA3, EFNA4, and EFNA5 were upregulated in estrogen receptor- (ER-) and progesterone receptor- (PR-) negative tumors, whereas EPHA3, EPHA6, and EFNA1 were upregulated in ER- and PR-positive tumors. EPHA1, EPHA2, EFNA3, and EFNA4 mRNA expression was significantly higher in human epidermal growth factor receptor 2- (HER2-) positive tumors than in HER2-negative tumors. Triple-negative status was positively correlated with EPHA1, EPHA2, EPHA4, EPHA7, EFNA3, EFNA4, and EFNA5 and negatively correlated with EPHA3 and EPHA10 mRNA expression. Genetic alterations of EPHA/EFNA in breast cancer varied from 1.1% to 10% for individual genes, as determined by the cBioPortal database. The Kaplan-Meier plotter indicated that high EphA7 mRNA expression was associated with poor overall survival (OS) and recurrence-free survival (RFS), especially in the HER2 and luminal A subtypes. EFNA4 was predicted to have poor OS and RFS in breast cancers, especially in luminal B, basal-like subtype, and patients treated with adjuvant chemotherapy. High EPHA3 expression was significantly associated with better OS and RFS, especially in the luminal A subtype, but with poor RFS in BrCa patients receiving chemotherapy. Our findings systematically elucidate the expression pattern and prognostic value of the EPHA/EFNA family in BrCa, which might provide potential prognostic factors and novel targets in BrCa patients, including those with different subtypes or treated with chemotherapy.
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http://dx.doi.org/10.1155/2021/5575704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087473PMC
April 2021

Effect of food processing on the antioxidant activity of flavones from (Mill.) Druce.

Open Life Sci 2021 29;16(1):92-101. Epub 2021 Jan 29.

College of Food Science and Engineering, Tonghua Normal University, Tonghua 134001, China.

(Mill.) Druce (POD) is a natural plant widely used for food and medicine, thanks to its rich content of a strong antioxidant agent called homoisoflavones. However, food processing methods could affect the stability of POD flavones, resulting in changes to their antioxidant activity. This study attempts to evaluate the antioxidant activity of POD flavones subject to different processing methods and determines which method could preserve the antioxidant activity of POD flavones. Therefore, flavones were extracted from POD samples, which had been treated separately with one of the four processing methods: extrusion, baking, high-pressure treatment, and yeast fermentation. After that, the antioxidant activity of the flavones was subject to tests in zebrafish embryos. The results show that yeast fermentation had the least disruption to the antioxidant activity of POD flavones, making it the most suitable food processing method for POD. By contrast, extrusion and high-pressure treatment both slightly weakened the antioxidant activity of the flavones and should be avoided in food processing. The research results provide a reference for the development and utilization of POD and the protection of its biological activity.
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http://dx.doi.org/10.1515/biol-2021-0010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874555PMC
January 2021

Cryptococcus neoformansInfected Macrophages Release Proinflammatory Extracellular Vesicles: Insight into Their Components by Multi-omics.

mBio 2021 03 30;12(2). Epub 2021 Mar 30.

Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland, USA

causes deadly mycosis in immunocompromised individuals. Macrophages are key cells fighting against microbes. Extracellular vesicles (EVs) are cell-to-cell communication mediators. The roles of EVs from infected host cells in the interaction with remain uninvestigated. Here, EVs from viable -infected macrophages reduced fungal burdens but led to shorter survival of infected mice. , EVs induced naive macrophages to an inflammatory phenotype. Transcriptome analysis showed that EVs from viable -infected macrophages activated immune-related pathways, including p53 in naive human and murine macrophages. Conserved analysis demonstrated that basic cell biological processes, including cell cycle and division, were activated by infection-derived EVs from both murine and human infected macrophages. Combined proteomics, lipidomics, and metabolomics of EVs from infected macrophages showed regulation of pathways such as extracellular matrix (ECM) receptors and phosphatidylcholine. This form of intermacrophage communication could serve to prepare cells at more distant sites of infection to resist infection. causes cryptococcal meningitis, which is frequent in patients with HIV/AIDS, especially in less-developed countries. The incidence of cryptococcal meningitis is close to 1 million each year globally. Macrophages are key cells that protect the body against microbes, including Extracellular vesicles are a group of membrane structures that are released from cells such as macrophages that modulate cell activities via the transfer of materials such as proteins, lipids, and RNAs. In this study, we found that -infected macrophages produce extracellular vesicles that enhance the inflammatory response in -infected mice. These -infected macrophage vesicles also showed higher fungicidal biological effects on inactivated macrophages. Using omics technology, unique protein and lipid signatures were identified in these extracellular vesicles. Transcriptome analysis showed that these vesicles activated immune-related pathways like p53 in naive macrophages. The understanding of this intermacrophage communication could provide potential targets for the design of therapeutic agents to fight this deadly mycosis.
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http://dx.doi.org/10.1128/mBio.00279-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092229PMC
March 2021

Increased angiogenesis and migration of dermal microvascular endothelial cells from patients with psoriasis.

Exp Dermatol 2021 Mar 22. Epub 2021 Mar 22.

Shanxi Key Laboratory of Stem Cell for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, China.

Psoriasis displays both increased angiogenesis and microvascular dilation in the skin, while human dermal microvascular endothelial cells (HDMECs) are involved in angiogenesis and microvascular dilation. Whether the functions of HDMECs are altered in psoriatic skin versus healthy skin remain unknown. Here, we isolated HDMECs from the skin of 10 patients with psoriasis and 10 healthy subjects and compared angiogenesis, proliferation, migration and cell metabolism between psoriatic HDMECs and normal HDMECs. We found that the morphology of primary HDMECs was comparable between psoriatic HDMECs and normal HDMECs. After passage, psoriatic HDMECs displayed larger cell size and wider intercellular space. In addition to DiI-Ac-LDL (DiI-labelled acetylated low-density lipoprotein) uptake, expression levels of CD31, vWF (von Willebrand factor) and LYVE-1 were comparable in psoriatic HDMECs versus normal HDMECs. However, psoriatic HDMECs exhibited increased tube formation (numbers of nodes and meshes, p < 0.05) and migration (numbers of migrated cells, p < 0.001) and reductions in proliferation (growth rates, p < 0.05) and energy metabolism (oxygen consumption rate and extracellular acidification rate, p < 0.05) compared with normal HDMECs. Therefore, psoriatic HDMECs display an increased angiogenesis and migration and decreased proliferation and metabolic activity, suggesting a pathogenic role of HDMECs in psoriasis.
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http://dx.doi.org/10.1111/exd.14329DOI Listing
March 2021

Syntheses, crystal structures, and biological evaluations of new dinuclear platinum(ii) complexes with 1,2,4-triazole derivatives as bridging ligands.

Dalton Trans 2021 Apr 16;50(13):4527-4538. Epub 2021 Mar 16.

Key Laboratory of Materials for Energy Conversion and Storage of Shanxi Province, Key Laboratory of Chemical Biology and Molecular Engineering of the Education Ministry, Institute of Molecular Science, Shanxi University, Taiyuan, 030006, Shanxi, P. R. China.

A series of new dinuclear platinum(ii) complexes with the general formula [Pt(μ-HL)] (1-4), where HL is 4-[(5-chloro-2-hydroxy-benzylidene)-amino]-3-R-1,2,4-triazole-5-thione: R = H (1), methyl (2), ethyl (3) and propyl (4), were synthesized and characterized. The X-ray crystal structures of 2, 3 and 4 reveal that the two platinum atoms form a paddlewheel core with four chelating triazole ligands as bridges, revealing a radically different structure than those of the traditional anticancer platinum(ii) complexes. These complexes show higher in vitro antiproliferative activity against human liver hepatocellular carcinoma (HepG2) and human breast adenocarcinoma (MCF7) than human lung cancer (A549) and human normal hepatocyte (HL-7702) cell lines. In particular, 3 exhibits antiproliferative activity (IC = 5.5 μM) against HepG2 cells comparable to that of cisplatin. Different from the traditional anticancer platinum(ii) complexes with high DNA affinity, 3 binds very weakly to DNA. Upon comparison, it exhibits potent inhibiting activity against protein tyrosine phosphatases 1B (PTP1B, IC = 16 μM) through possible binding to its active sites and its binding constant is 5.28 × 10 M. The results suggest that the antiproliferative mechanism of 3 against HepG2 cells may be different from that of cisplatin.
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http://dx.doi.org/10.1039/d0dt03285aDOI Listing
April 2021

Identification and validation of three core genes in p53 signaling pathway in hepatitis B virus-related hepatocellular carcinoma.

World J Surg Oncol 2021 Mar 8;19(1):66. Epub 2021 Mar 8.

Department of Infectious Diseases and Key Laboratory of Liver Disease of Guangdong Province, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, Guangdong Province, China.

Background: Hepatocellular carcinoma (HCC) is a common cancer and the leading cause is persistent hepatitis B virus (HBV) infection. We aimed to identify some core genes and pathways for HBV-related HCC.

Methods: Gene expression profiles of GSE62232, GSE121248, and GSE94660 were available from Gene Expression Omnibus (GEO). The GSE62232 and GSE121248 profiles were the analysis datasets and GSE94660 was the validation dataset. The GEO2R online tool and Venn diagram software were applied to analyze commonly differentially expressed genes between HBV-related HCC tissues and normal tissues. Then, functional enrichment analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Gene and Genome (KEGG) as well as the protein-protein interaction (PPI) network was conducted. The overall survival rates and the expression levels were detected by Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA). Next, gene set enrichment analysis (GSEA) was performed to verify the KEGG pathway analysis. Furthermore, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to validate the levels of these three core genes in tumor tissues and adjacent non-tumor liver tissues from 12 HBV related HCC patients, HBV-associated liver cancer cell lines and normal liver cell lines, and HepG2 with p53 knockdown or deletion, respectively.

Results: Fifteen highly expressed genes associated with significantly worse prognoses were selected and CCNB1, CDK1, and RRM2 in the p53 signaling pathway were identified as core genes. GSEA results showed that samples highly expressing three core genes were all enriched in the p53 signaling pathway in a validation dataset (P < 0.0001). The expression of these three core genes in tumor tissue samples was higher than that in relevant adjacent non-tumor liver tissues (P < 0.0001). Furthermore, we also found that the above genes were highly expressed in liver cancer cell lines compared with normal liver cells. In addition, we found that the expression of these three core genes in p53 knockdown or knockout HCC cell lines was lower than that in negative control HCC cell lines (P < 0.05).

Conclusions: CCNB1, CDK1, and RRM2 were enriched in the p53 signaling pathway and could be potential biomarkers and therapeutic targets for HBV-related HCC.
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http://dx.doi.org/10.1186/s12957-021-02174-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938465PMC
March 2021

Axl is related to inflammation in hemodialysis patients.

Mol Immunol 2021 05 2;133:146-153. Epub 2021 Mar 2.

Department of Nephrology & Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301, Middle Yanchang Road, Shanghai, 200072, China. Electronic address:

Background: Hemodialysis (HD) patients often develop chronic inflammation, which is associated with an increased risk of cardiovascular complications and mortality. Axl and its ligand, growth arrest 6 (Gas6), have been reported to play key roles in regulating the immune response. However, the function of Axl in HD patients has not been clarified.

Methods: In the present study, we enrolled 130 HD patients and 117 normal controls (NCs) and evaluated the levels of inflammatory markers, soluble Axl (sAxl), membrane Axl (mAxl), and Gas6 in all participants. The potential downstream cascades of Gas6-Axl signaling in HD patients were identified by quantitative real time polymerase chain reaction and western blotting.

Results: The levels of inflammatory cytokines-tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-plasma sAxl, and Gas6, were significantly increased in HD patients compared to NCs. Additionally, sAxl was positively associated with the inflammatory factor, interleukin-6 (IL-6), in HD patients. Moreover, we found that mAxl in CD14 mononuclear cells and CD19 B cells was increased upon HD. Furthermore, we discovered that the metalloproteinase ADAM17, also called TACE, contributed to the cleavage of mAxl into sAxl, and not ADAM10, in the peripheral blood mononuclear cells (PBMCs) of HD patients. The upregulation of Gas6-mAxl signaling caused the activation of the STAT1-SOCS3 pathway in the PBMCs of HD patients. After two years follow-up, patients with lower sAxl levels had longer survival time than those with higher sAxl levels.

Conclusion: Our results suggest that Axl may play a significant role in systemic inflammation in HD patients.
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http://dx.doi.org/10.1016/j.molimm.2021.02.024DOI Listing
May 2021

Dysregulated Dermal Mesenchymal Stem Cell Proliferation and Differentiation Interfered by Glucose Metabolism in Psoriasis.

Int J Stem Cells 2021 Feb;14(1):85-93

Shanxi Key Laboratory of Stem Cell for Immunological Dermatosis, Institute of Dermatology, Taiyuan City Centre Hospital of Shanxi Medical University, Taiyuan, China.

Background And Objectives: Psoriasis is a chronic inflammatory skin disease, which the mechanisms behind its initiation and development are related to many factors. DMSCs (dermal mesenchymal stem cells) represent an important member of the skin microenvironment and play an important role in the surrounding environment and in neighbouring cells, but they are also affected by the microenvironment. We studied the glucose metabolism of DMSCs in psoriasis patients and a control group to reveal the relationship among glucose metabolism, cell proliferation activity,and VEC (vascular endothelial cell) differentiation , we demonstrated the biological activity and molecular mechanisms of DMSCs in psoriasis.

Methods And Results: We found that the OCR of DMSCs in psoriatic lesions was higher than that in the control group, and mRNA of GLUT1 and HK2 were up-regulated compared with the control group. The proliferative activity of DMSCs in psoriasis was reduced at an early stage, and mRNA involved in proliferation, JUNB and FOS were expressed at lower levels than those in the control group. The number of blood vessels in psoriatic lesions was significantly higher than that in the control group (p<0.05), which the mRNA of VEC differentiation, CXCL12, CXCR7, HEYL and RGS5 tended to be increased in psoriatic lesions compared to the control group, in addition to Notch3.

Conclusions: We speculated that DMSCs affected local psoriatic blood vessels through glucose metabolism, and the differentiation of VECs, which resulted in the pathophysiological process of psoriasis.
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http://dx.doi.org/10.15283/ijsc20073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904530PMC
February 2021

Excess mortality in Wuhan city and other parts of China during the three months of the covid-19 outbreak: findings from nationwide mortality registries.

BMJ 2021 02 24;372:n415. Epub 2021 Feb 24.

The National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Xicheng District, 100050, Beijing, China

Objective: To assess excess all cause and cause specific mortality during the three months (1 January to 31 March 2020) of the coronavirus disease 2019 (covid-19) outbreak in Wuhan city and other parts of China.

Design: Nationwide mortality registries.

Setting: 605 urban districts and rural counties in China's nationally representative Disease Surveillance Point (DSP) system.

Participants: More than 300 million people of all ages.

Main Outcome Measures: Observed overall and weekly mortality rates from all cause and cause specific diseases for three months (1 January to 31 March 2020) of the covid-19 outbreak compared with the predicted (or mean rates for 2015-19) in different areas to yield rate ratio.

Results: The DSP system recorded 580 819 deaths from January to March 2020. In Wuhan DSP districts (n=3), the observed total mortality rate was 56% (rate ratio 1.56, 95% confidence interval 1.33 to 1.87) higher than the predicted rate (1147 735 per 100 000), chiefly as a result of an eightfold increase in deaths from pneumonia (n=1682; 275 33 per 100 000; 8.32, 5.19 to 17.02), mainly covid-19 related, but a more modest increase in deaths from certain other diseases, including cardiovascular disease (n=2347; 408 316 per 100 000; 1.29, 1.05 to 1.65) and diabetes (n=262; 46 25 per 100 000; 1.83, 1.08 to 4.37). In Wuhan city (n=13 districts), 5954 additional (4573 pneumonia) deaths occurred in 2020 compared with 2019, with excess risks greater in central than in suburban districts (50% 15%). In other parts of Hubei province (n=19 DSP areas), the observed mortality rates from pneumonia and chronic respiratory diseases were non-significantly 28% and 23% lower than the predicted rates, despite excess deaths from covid-19 related pneumonia. Outside Hubei (n=583 DSP areas), the observed total mortality rate was non-significantly lower than the predicted rate (675 715 per 100 000), with significantly lower death rates from pneumonia (0.53, 0.46 to 0.63), chronic respiratory diseases (0.82, 0.71 to 0.96), and road traffic incidents (0.77, 0.68 to 0.88).

Conclusions: Except in Wuhan, no increase in overall mortality was found during the three months of the covid-19 outbreak in other parts of China. The lower death rates from certain non-covid-19 related diseases might be attributable to the associated behaviour changes during lockdown.
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http://dx.doi.org/10.1136/bmj.n415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900645PMC
February 2021

Awareness and prevalence of e-cigarette use among Chinese adults: policy implications.

Tob Control 2021 Feb 19. Epub 2021 Feb 19.

Chinese Center for Disease Control and Prevention, Beijing, Beijing, China.

Objective: To assess the awareness and prevalence of electronic cigarettes (e-cigarettes) and associated factors among Chinese adults (15 years and older).

Method: This study examined data from Global Adults Tobacco Survey China Project, which was nationally representative and used stratified multiphase cluster randomised sampling design. Data were collected in 2018 through a household survey with in-person interviews using tablet computers. Complex sampling weighted analysis method was used.

Results: 48.5% of Chinese adults had heard of e-cigarettes. The proportions of Chinese adults who had ever used, had used in the last 12 months, and currently used e-cigarettes were 5.0%, 2.2% and 0.9%, respectively; people in the 15-24 years group showed the highest rates of ever use, last 12-month use and current use at 7.6%, 4.4%, and 1.5%, respectively. Among males, higher e-cigarette use was associated with 15-24 years age group, college/university or above education, and daily use of combustible cigarettes. Among all e-cigarette users, 90.6% also used combustible cigarettes. The most common reason for e-cigarette use was smoking cessation (46.2%) while among ever smokers, 9.5% of ever e-cigarette users had quit smoking and 21.8% of never e-cigarette users had quit smoking (adjusted OR 0.454, 95% CI 0.290 to 0.712).

Conclusion: Prevalence of e-cigarettes among Chinese adults had increased since 2015, especially among young people aged 15-24. The high level of dual use and lower quit rate among e-cigarette users indicated e-cigarettes had not shown cessation utility at the population level in China. Regulation of e-cigarettes is needed to protect youth and minimise health risks.
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http://dx.doi.org/10.1136/tobaccocontrol-2020-056114DOI Listing
February 2021

Experimental and numerical studies on kV scattered x-ray imaging for real-time image guidance in radiation therapy.

Phys Med Biol 2021 02 11;66(4):045022. Epub 2021 Feb 11.

Innovative Technology Of Radiotherapy Computations and Hardware (iTORCH) Laboratory, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, 75235, United States of America. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, 75235, United States of America.

Motion management is a critical component of image guided radiotherapy for lung cancer. We previously proposed a scheme using kV scattered x-ray photons for marker-less real-time image guidance in lung cancer radiotherapy. This study reports our recent progress using the photon counting detection technique to demonstrate potential feasibility of this method and using Monte Carlo (MC) simulations and ray-tracing calculations to characterize the performance. In our scheme, a thin slice of x-ray beam was directed to the target and we measured the outgoing scattered photons using a photon counting detector with a parallel-hole collimator to establish the correspondence between detector pixels and scatter positions. Image corrections of geometry, beam attenuation and scattering angle were performed to convert the raw image to the actual image of Compton attenuation coefficient. We set up a MC simulation system using an in-house developed GPU-based MC package modeling the image formation process. We also performed ray-tracing calculations to investigate the impacts of imaging system geometry on resulting image resolution. The experiment demonstrated feasibility of using a photon counting detector to measure scattered x-ray photons and generate the proposed scattered x-ray image. After correction, x-ray scattering image intensity and Compton scattering attenuation coefficient were linearly related, with R greater than 0.9. Contrast to noise ratios of different objects were improved and the values in experimental results and MC simulation results agreed with each other. Ray-tracing calculations revealed the dependence of image resolution on imaging geometry. The image resolution increases with reduced source to object distance and increased collimator height. The study demonstrated potential feasibility of using scattered x-ray imaging as a real-time image guidance method in radiation therapy.
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http://dx.doi.org/10.1088/1361-6560/abd66cDOI Listing
February 2021

E-cigarette use among adults in China: findings from repeated cross-sectional surveys in 2015-16 and 2018-19.

Lancet Public Health 2020 12;5(12):e639-e649

National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. Electronic address:

Background: The use of e-cigarettes among adults is increasing globally. Since 2018, policies in China have restricted e-cigarette use; however, little information is available on the national trend in e-cigarette use before regulations were implemented. Therefore, we sought to estimate the trend in e-cigarette use in China before policy implementation and explored associated factors.

Methods: We assessed two nationally representative cross-sectional datasets from the China Chronic Disease and Nutrition Surveillance (CCDNS) surveys initiated in 2015 (June, 2015, to May, 2016) and 2018 (August, 2018, to June, 2019). The surveys were done at 298 national disease surveillance points in 31 provinces in mainland China, and used a multistage, stratified, cluster-randomised sampling design, recruiting community-based Chinese adults aged 18 years and older. Within the standard CCDNS survey, face-to-face questionnaire interviews were used to collect self-report data on e-cigarette use in the preceding 30 days. E-cigarette users were those who self-reported e-cigarette use on 1 day or more in the past 30 days. Prevalence estimates of past 30-day e-cigarette use were weighted to represent the Chinese adult population accounting for the complex sampling design. Populations for the years 2015-16 and 2018-19 were standardised with the 2010 population census to gain comparable estimates. Multivariable logistic regression models adjusted for age, sex, urban or rural residence, household income, occupation, and education level were applied to identify factors associated with the likelihood of e-cigarette use among the total population, ever smokers (current and former), and never smokers across both surveys.

Findings: Our study included 189 306 Chinese adults from the 2015 survey (100 405 [53·0%] women; mean age 43·6 years [SD 14·6]) and 184 475 Chinese adults from the 2018 survey (102 373 [55·5%] women; mean age 43·4 years [13·9]). The weighted prevalence of past 30-day e-cigarette use among Chinese adults increased from 1·3% (95% CI 1·1-1·5%) in 2015-16 to 1·6% (95% CI 1·4-1·8%) in 2018-19 (an increase of 0·3% [95% CI 0·1-0·6]; Rao-Scott χ p=0·0086). Based on weighted proportion data, e-cigarette users were predominantly men (97·4% [95% CI 96·7-98·1] in 2015-16 and 97·0% [95·4-98·6] in 2018-19) and current conventional smokers (93·0% [90·7-95·2] in 2015-16 and 96·2% [95·1-97·3] in 2018-19). Across both surveys, the odds of e-cigarette use were significantly associated with obesity (odds ratio 1·6 [95% CI 1·3-2·1]; p=0·0007), awareness of smoking hazards (1·2 [1·0-1·4]; p=0·022), and smoking status (in current smokers, 135·2 [87·7-208·6]; and in former smokers, 33·5 [21·3-52·7]; p<0·0001). Among current smokers, the odds were increased with daily cigarette consumption (2·1 [1·5-2·8]; p<0·0001), smoking more than 20 cigarettes per day (1·8 [1·5-2·3]; p<0·0001), and an attempt to quit smoking (within the past 12 months, 1·9 [1·5-2·4]; and before the past 12 months, 1·5 [1·3-1·9]; p<0·0001). In never smokers, the odds were increased in those aware of the hazards of smoking (2·4 [1·2-4·7]; p=0·011).

Interpretation: E-cigarette use in China remains low but has increased substantially between 2015 and 2019. Our study identified increased e-cigarette use among subpopulations, and use patterns, that warrant further attention from public health policy makers in China.

Funding: Chinese Central Government, National Key Research and Development Program of China.
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http://dx.doi.org/10.1016/S2468-2667(20)30145-6DOI Listing
December 2020

Clinical experience with emergency endotracheal intubation in COVID-19 patients in the intensive care units: a single-centered, retrospective, descriptive study.

Am J Transl Res 2020 15;12(10):6655-6664. Epub 2020 Oct 15.

Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology 1095 Jiefang Avenue, Wuhan 430030, Hubei, China.

Few studies have reported the implications of performing endotracheal intubation for critically ill COVID-19 patients admitted to intensive care units (ICUs). Therefore, this study aimed to summarize the outcomes of COVID-19 patients in the ICU following endotracheal intubation and provide a clinical reference for the high-risk procedure. From February 1 to February 18, 2020, we enrolled 59 critically ill COVID-19 patients who received emergency endotracheal intubation in the ICUs of Tongji Hospital. We recorded demographic information, laboratory parameters, comorbidities, changes in vital signs pre- and post-intubation, the airway grade, intubation success rate using three types of laryngoscopes, and the experience of intubators. Follow-up evaluations were performed for all proceduralists to monitor nosocomial infections. The majority of the patients requiring intubation were elderly and had at least one comorbidity. Of the patients, 86.4% developed hypoxia before intubation. The first and second attempts of successful endotracheal intubation with the Macintosh laryngoscope (70.0% and 83.3%), Airtraq videolaryngoscope (93.5% and 80%), and UE videolaryngoscope (88.9% and 100%) were performed. Notably, SpO <93% and hypotension were observed 3 min after intubation in 32.2% and 39% patients, respectively. With the proper use of personal protective equipment (PPE), no nosocomial infections were observed among proceduralists. Full PPE increased the occurrence of fogging on goggles and myopia glasses. Overall, a higher success rate of intubation was achieved by senior intubators using a videolaryngoscope. Although inconvenient, appropriate ensembles of PPE could prevent nosocomial infections.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653591PMC
October 2020

Upper Respiratory Tract Viral Ribonucleic Acid Load at Hospital Admission Is Associated With Coronavirus Disease 2019 Disease Severity.

Open Forum Infect Dis 2020 Jul 5;7(7):ofaa282. Epub 2020 Jul 5.

Guangzhou Eighth People's Hospital, Guangzhou, China.

Background: The outbreak of coronavirus disease 2019 (COVID-19) has aroused global public health concerns. Multiple clinical features relating to host profile but not for virus have been identified as the risk factors for illness severity and/or the outcomes in COVID-19.

Methods: The clinical features obtained from a cohort of 195 laboratory-confirmed, nasopharynx-sampled patients with COVID-19 in Guangdong, China from January 13 to February 29, 2020 were enrolled to this study. The differences in clinical features among 4 groups (mild, moderate, severe, and critical) and between 2 groups (severe vs nonsevere) were compared using one-way analysis of variance and Student's test, respectively. Principal component analysis and correlation analysis were performed to identify the major factors that account for illness severity.

Results: In addition to the previously described clinical illness severity-related factors, including older age, underlying diseases, higher level of C-reactive protein, D-dimer and aspartate aminotransferase, longer fever days and higher maximum body temperature, larger number of white blood cells and neutrophils but relative less lymphocytes, and higher ratio of neutrophil to lymphocytes, we found that the initial viral load is an independent factor that accounts for illness severity in COVID-19 patients.

Conclusions: The initial viral load of severe acute respiratory syndrome coronavirus 2 is a novel virological predictor for illness severity of COVID-19.
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http://dx.doi.org/10.1093/ofid/ofaa282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454839PMC
July 2020

The regulation of dermal mesenchymal stem cells on keratinocytes apoptosis.

Cell Tissue Bank 2021 Mar 29;22(1):57-65. Epub 2020 Sep 29.

Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, No. 5 East Third Lane, Jiefang Road, Taiyuan, 030009, Shanxi, China.

Dermal mesenchymal stem cells (DMSCs) are progenitor cells with the capacity of self-renewal, multilineage differentiation, and immunomodulation, which were reported to induce the proliferation of keratinocytes, however the regulation on keratinocytes apoptosis was unknown. In this study, we isolated DMSCs from normal skin and co-cultured with keratinocytes, and then detected apoptosis of keratinocytes by flow cytometry and expression of apoptosis associated proteins by western blot. The mRNA expression profile of normal DMSCs was investigated by RNA sequencing. The results of our study presented that the DMSCs promoted HaCaT cells apoptosis both in early apoptotic state (13.8 vs. 2.9, p < 0.05) and late apoptotic state (4.2 vs. 0.7, p < 0.05). The expression of apoptosis associated proteins caspase-3 (3.51 vs. 1.99, p < 0.05) and lymphoid enhancer-binding factor 1 (3.10 vs. 0.83, p < 0.05) were upregulated. However, the cell cycle protein cyclin E1 was similar (9.38 vs. 9.05, p > 0.05). Moreover, 33 genes with the function of induced cell apoptosis were highly expressed in DMSCs, including insulin-like growth factor-binding protein 4 (2828.13), IGFBP7 (1805.69), cathepsin D (1694.34), cathepsin B (CTSB, 1641.40) and dickkopf WNT signaling pathway inhibitor 1 (DKK1, 384.79). This study suggested DMSCs induce the apoptosis of keratinocytes through non-G1/S phase blockade via highly expression of apoptosis inducer.
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http://dx.doi.org/10.1007/s10561-020-09865-wDOI Listing
March 2021

Twenty-Four-Hour Urinary Sodium and Potassium Excretion and Their Associations With Blood Pressure Among Adults in China: Baseline Survey of Action on Salt China.

Hypertension 2020 11 28;76(5):1580-1588. Epub 2020 Sep 28.

Chinese Center for Disease Control and Prevention, Beijing (Xinhua Li).

This study aimed to assess current level of sodium and potassium intake and their associations with blood pressure (BP) using the 24-hour urinary data in a large sample of China. Data from participants aged 18 to 75 years were collected as the baseline survey of Action on Salt China in 2018. Of 5454 adults, 5353 completed 24-hour urine collection. The average sodium, potassium excretion, and sodium-to-potassium molar ratio were 4318.1±1814.1 mg/d (equivalent to 11.0±4.6 g/d of salt), 1573.7±627.1 mg/d, and 5.0±2.1, respectively. After adjusting for potential confounding factors and correcting for regression dilution, each 1000-mg increase in sodium excretion was associated with increased systolic BP (1.32 mm Hg [95% CI, 0.92-1.81]) and diastolic BP (0.34 mm Hg [95% CI, 0.09-0.60]). Each 1000-mg increase in potassium excretion was inversely associated with systolic BP (-3.19 mm Hg [95% CI, -4.38 to -2.20]) and diastolic BP (-1.56 mm Hg [95% CI, -2.29 to -0.90]). Each unit increase in sodium-to-potassium molar ratio was associated with an increase of systolic BP by 1.21 mm Hg (95% CI, 0.91-1.60) and diastolic BP by 0.44 mm Hg (95% CI, 0.24-0.64). The relationships between sodium and BP mostly increase with the rise of BP quantiles. Potassium shows the opposite trend. The current sodium intake in Chinese adults remains high and potassium intake is low. Sodium and sodium-to-potassium ratio were positively associated with BP, whereas potassium was inversely associated with BP. Registration- URL: https://tinyurl.com/vdr8rpr; Unique identifier: ChiCTR1800017553. URL: https://tinyurl.com/w8c7x3w; Unique identifier: ChiCTR1800016804. URL: https://tinyurl.com/s3ajldw; Unique identifier: ChiCTR1800018119.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15238DOI Listing
November 2020

Increased Expression of Fibulin-1 Is Associated With Hepatocellular Carcinoma Progression by Regulating the Notch Signaling Pathway.

Front Cell Dev Biol 2020 16;8:478. Epub 2020 Jun 16.

Department of Infectious Diseases, Key Laboratory of Liver Disease of Guangdong Province, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Fibulin-1, a component of the extracellular matrix (ECM), its prognostic, pathophysiologic and diagnostic role in hepatocellular carcinoma (HCC) is still unexplored. We first found that either Fibulin-1 messenger RNA (mRNA) or protein level was highly elevated in HCC tissues compared with normal tissues. Fibulin-1 correlated with poor overall survival, and it was an independent prognostic predictor ( = 0.001). Furthermore, Overexpression or inhibition of Fibulin-1 reduced or sensitized HCC cells to apoptotic signals, and Fibulin-1 silencing suppressed the ability of HCC cells to form tumors . Moreover, Fibulin-1 inhibited apoptosis via the Notch pathway while Fibulin-1 silencing had no obvious effect on p-MAPK, p-c-jun and p-stat3 expression, and both Mcl-1 and Bcl-xL are targets of Fibulin-1. Furthermore, the stromal and immune score was elevated in high Fibulin-1 tissues, and FBLN1 expression was associated with increased infiltrating macrophages using xCell, TIMER and TISDIB tool based on TCGA HCC database. Importantly, the circulating cell-free RNA (cfRNA) level of Fibulin-1 in the serum were significantly increased in patients with HCC compared with those in healthy controls, individuals with chronic hepatitis B and patients with HBV-induced liver cirrhosis. The area under receiver operating characteristic curves (AUC) was 0.791 for Fibulin-1, 0.640 for α-fetoprotein and 0.868 for the combination of the two tumor markers. Our findings indicate that Fibulin-1 may be a potential prognostic indicator, a promising serum biomarker and a therapeutic target in patients with HCC.
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http://dx.doi.org/10.3389/fcell.2020.00478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308487PMC
June 2020

Performance Analysis of PCM Ceiling Coupling with Earth-Air Heat Exchanger for Building Cooling.

Materials (Basel) 2020 Jun 27;13(13). Epub 2020 Jun 27.

School of Energy and Environmental Engineering, Hebei University of Technology, Tianjin 300401, China.

In recent years, the systematic application of phase change materials (PCM) is continuously developing. In this paper, an innovative PCM ceiling coupled with earth-air heat exchanger (EAHE) cooling system was proposed for building cooling. The system aimed to combine the cooling capacity of soil and the energy storage capacity of PCM, thus improving the indoor thermal environment. Performance of the system was tested by experimental method while data analysis focused on the indoor side. To research the effect of cold storage time on the performance of the system, two different operation strategies were adopted for comparison: 8-h cold storage strategy and 12-h cold storage strategy. Moreover, a control group was set up to observe the performance of the system on indoor temperature under the same weather conditions. The result showed that the experimental room in which we installed this system could reduce peak temperature by 2.1 °C under 8-h timed cold storage strategy and 2.7 °C under 12-h timed cold storage strategy. What is more, under the two operation strategies, temperature and heat flux of the PCM ceiling had similar distribution characteristics. Different strategies mainly affected the sustainability of the system and phase transition efficiency of the PCM ceiling.
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http://dx.doi.org/10.3390/ma13132890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372354PMC
June 2020

LncRNA SNHG7 promotes cardiac remodeling by upregulating ROCK1 via sponging miR-34-5p.

Aging (Albany NY) 2020 06 6;12(11):10441-10456. Epub 2020 Jun 6.

Department of Critical Medicine, Aerospace Center Hospital, Peking University School of Clinical Medicine, Beijing 100049, China.

Previous studies have shown that lncRNA small nuclear RNA host gene 7 (lncRNA SNHG7) played an important role in cancer progression. However, the role of lncRNA SNHG7 in cardiac fibrosis is still poorly understood. In this study, the results of quantitative real time polymerase chain reaction (qRT-PCR) analysis showed that lncRNA SNHG7 was over expressed in the infarcted and peri-infarcted area in the left ventricle after MI in mice. Western blot analysis showed that knockdown of SNHG7 decreased the expression of collagen type 1 (Col1)and α-smooth muscle actin (α-SMA). Echocardiographic study suggested that inhibition of SNHG7 improved cardiac function after MI in mice. Luciferase assay indicated SNHG7 could act as a competing endogenous RNA (ceRNA) by sponging miR-34-5p. The MTT cell proliferation assay and 5-ethynyl-2'-deoxyuridine (EdU) labelling assay revealed that co-transfection of SNHG7 and miR-34-5p inhibited cell viability and proliferation of cardiac fibroblasts (CF). All the results indicated that lncRNA SNHG7 could promote cardiac fibrosis via targeting miR-34-5p through acting as a ceRNA in mice after MI. Silencing of SNHG7 could attenuate deposition of collagens and improve cardiac function. miR-34-5p could suppress the fibrogenesis of CF by targeting ROCK1 and abolish SNHG7-induced CF proliferation and fibroblast-to-myofibroblast transition.
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http://dx.doi.org/10.18632/aging.103269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346013PMC
June 2020

Radiation Effective Dose Above 100 mSv From Fluoroscopically Guided Intervention: Frequency and Patient Medical Condition.

AJR Am J Roentgenol 2020 08 6;215(2):433-440. Epub 2020 Jun 6.

Department of Radiology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114.

The purpose of this article was to investigate the medical condition of patients who received substantial cumulative effective dose (CED) in fluoroscopically guided interventional (FGI) procedures. We examined 25,253 patients (mean age, 58.2 years; 50.6% male) who underwent 46,491 FGI procedures at a tertiary care center in the United States from January 2010 to January 2019. Radiation dosage data were retrieved from an in-house semiautomated dose-tracking system. A cohort was identified as those who received a CED of 100 mSv or greater and was categorized by medical disorder from longitudinal medical records. Statistical software was used to determine mean value, five percentiles (10th, 25th, 50th, 75th, 95th), and interquartile range for age and dose. Among 1011 (4.0%) patients (30.4% female) with a CED of 100 mSv or more, the median number of procedures was 2.0, the median age at first procedure was 60.0 years old, and the median value of CED was 177.2 mSv. The patients' medical disorders included cancer (36.7%), chronic disease of the torso (30.0%), internal bleeding (24.8%), trauma (4.6%), organ transplant (3.2%) and cerebrovascular disease (0.7%). Eight-hundred (79.1%) patients underwent all of their procedures within 365 days. This is the first cohort study of the medical condition of patients receiving substantial cumulative doses from FGI procedures over a long period. In the critical care of patients with serious medical disorders, 4.0% of patients may be exposed to substantial radiation dose (CED ≥ 100 mSv). The risks associated with such a high level of radiation warrant continued attention.
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http://dx.doi.org/10.2214/AJR.19.22227DOI Listing
August 2020

Cross-sectional study reveals thatHLA-C*07:02 is a potential biomarker of early onset/lesion severityof psoriasis.

Exp Dermatol 2020 Jun 7. Epub 2020 Jun 7.

Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, No. 5 Dong San Dao Xiang, Jiefang Road, Taiyuan, 030009, China.

Psoriasis is a common chronic autoimmune skin disease, with T cells playing a predominant role in its pathogenesis.Here, we aimed to investigate the relation of T cell repertoires (TCR) and major histocompatibility complex (MHC) in psoriatic patients to further understand mechanisms in disease pathogenesis.We conducted a cross-sectional study involving 9 pairs of monozygotic twins with inconsistent psoriasis and examined the TCR diversity and MHC haplotype ofthe individuals using multiple-PCR and high-throughput sequencing. Additionally, 665 psoriatic patients were applied to validate the relation of human leukocyte antigen (HLA)-class I allele HLA-C*07:02 and early onset or lesion severity of psoriasis.The immune diversity was lower in psoriatic patients compared with unaffected individuals within the twin pairs, although the difference was not significant.The clonotypes of TCR significantly decreased in psoriatic patients with high PASI score and early onset. HLA-C*07:02, a haplotype associated with psoriasis, was positively correlated with the diversity of the TCRV gene. Moreover, HLA-C*07:02 clustered in patients with high PASI and early onset. In the replication stage, we found that the PASI and onset age in psoriasis with HLA-C*07:02 were significantly different from those without HLA-C*07:02 and without HLA-C*06:02. Our observations indicate that HLA-C*07:02 is positively correlated with the diversity of TCRV gene in psoriasis, and maybe a potential biomarker of early onset/severe lesions of psoriasis.
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http://dx.doi.org/10.1111/exd.14127DOI Listing
June 2020

Different epigenome regulation and transcriptome expression of CD4 and CD8 T cells from monozygotic twins discordant for psoriasis.

Australas J Dermatol 2020 Nov 21;61(4):e388-e394. Epub 2020 May 21.

Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, China.

Objectives: Psoriasis is an immunodeficient skin disorder, and its exact pathogenesis is unclear. Monozygotic twins are presumed to be genetically identical, and their phenotypic differences may be due to transcriptional regulation or epigenome factors. To explain the inconsistency between twins, we have collected 3 pairs of monozygotic twins who are discordant for psoriasis.

Methods: Reduced representation of bisulfite sequencing and RNA sequencing was conducted using the peripheral blood of the twins to find the genes playing important roles in psoriasis pathogenesis.

Results: As a result, we found methylation diversity in four genes (MAST3, MTOR, PM20D1 and ZNF99), and we also found 9 differentially expressed genes (PPAN-P2RY11, PIGV, RPS18, TMEM121, KIF21A, KCNH2, WNT10B, PRX and CDH24) by RNA sequencing. According to the conjoint analysis of methylation and the mRNA results, PTPN6, CCL5, NFATC1 and PRF1 were found to be closely related to psoriasis. We then annotated the genes to explore the associations between these genes and psoriasis.

Conclusions: These findings provide a better understanding of psoriasis that can improve the diagnosis and treatment of the disease.
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http://dx.doi.org/10.1111/ajd.13325DOI Listing
November 2020

Role of SPRED1 in keratinocyte proliferation in psoriasis.

J Dermatol 2020 Jul 12;47(7):735-742. Epub 2020 May 12.

Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, China.

Psoriasis is a recurrent inflammatory skin disease, affecting approximately 2% of the population. Previous studies have demonstrated that psoriatic dermal mesenchymal stem cells (DMSC) stimulated keratinocyte (KC) proliferation and that psoriasis exhibited missense SPRED1 mutations. To further investigate the molecular mechanism by which psoriatic DMSC stimulate KC proliferation, and the role of missense SPRED1 mutations in psoriasis, we assessed expression levels of miRNA, and both mRNA and protein of SPRED1 in normal human epidermal keratinocyte cells (NHEK) cocultured with either psoriatic or control DMSC. Expression levels of miRNA and mRNA were determined by RNA sequencing. Expression levels of spred1 protein were assessed using western blot analysis. Moreover, the variation in SPRED1 was also examined by whole-genome sequencing in 665 psoriatic patients, and verified by Sanger sequencing. Our results showed that coculture of NHEK with psoriatic DMSC induced 32 differentially expressed miRNA, in which expression levels of miR-1 increased approximately 16-fold over control DMSC-treated NHEK (P < 0.05). Likewise, expression levels of miR-21-3p increased over twofold (P < 0.05). Moreover, coculture of NHEK with psoriatic DMSC induced marked increase in expression levels of mRNA for MAPK3, CDC25B and CDC25C, while decreasing expression levels of SPRED1 mRNA and protein in comparison with control DMSC treatment (P < 0.05 for all between cocultured with control and psoriatic DMSC). Furthermore, psoriasis displayed non-synonymous mutation of SPRED1 enriched in exon 7: c.A881T:p.Y294F (chr15:38351210). These results suggest that dysregulation and mutations of SPRED1 may participate in the pathogenesis of psoriasis, including epidermal hyperproliferation.
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http://dx.doi.org/10.1111/1346-8138.15369DOI Listing
July 2020

Expression and functional regulation of gap junction protein connexin 43 in dermal mesenchymal stem cells from psoriasis patients.

Acta Histochem 2020 May 14;122(4):151550. Epub 2020 Apr 14.

Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, No. 5 Dong San Dao Xiang, Jiefang Road, Taiyuan, 030009, Shanxi Province, China. Electronic address:

Background: Psoriasis is a chronic recurrent inflammatory disease. Mesenchymal stem cells (MSCs) can regulate the inflammatory microenvironment, thereby controlling the proliferation, differentiation, and migration of immune cells. Connexin 43(Cx43), a key gap junction protein, has been shown to form gap junctions for communication between neighboring cells.

Objective: We investigated the expression of Cx43 in dermal mesenchymal stem cells (DMSCs) derived from psoriasis patients and explored the relationship between the Cx43-mediated gap junction intercellular communication (GJIC) and DMSCs.

Methods: Human DMSCs were isolated and propagated in adherent culture. Quantitative real-time reverse transcription PCR and western blot and immunofluorescence were used to detect the expression and localization of Cx43 in DMSCs. Fluorescence redistribution after photobleaching was performed to assess adjacent DMSCs GJIC. CCK8 was used to detect the proliferation of DMSCs before and after gap junction blocker (18α-glycyrrhetinic acid; AGA) treatment. Cell energy metabolism was analyzed with an energy metabolism analyzer.

Results: Cx43 was located in the cytoplasm and cytomembrane, as well as partially in the nucleus of DMSCs. The expression of Cx43 in psoriasis DMSCs was higher than that in control samples and the gap junction function was enhanced. In addition, the glycolysis and mitochondrial respiration of psoriasis DMSCs were also enhanced. However, AGA inhibited the expression of Cx43, attenuated GJIC function, and inhibited the proliferation of DMSCs.

Conclusions: Our results indicated that the expression of Cx43 in DMSCs from psoriasis lesions is increased and that the inhibition of Cx43 leads to the inhibition of both GJIC and DMSCs proliferation.
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http://dx.doi.org/10.1016/j.acthis.2020.151550DOI Listing
May 2020

Effect of cold stress on ovarian & uterine microcirculation in rats and the role of endothelin system.

Reprod Biol Endocrinol 2020 Apr 14;18(1):29. Epub 2020 Apr 14.

Hebei University of Chinese Medicine, No.326, Xinshi South Road, Qiaoxi District, Shijiazhuang, 050091, Hebei Province, China.

Background: Cold, an environmental factor, induces many reproductive diseases. It is known that endothelin (ET) is a potent vasoconstrictor, and cold stress can increase the expression of ET and its receptors. The cold stress rat model was developed to examine two parameters: (1) the effects of cold stress on ovarian and uterine morphology, function, and microvascular circulation and (2) possible mechanisms of ET and its receptors involved in cold stress-induced menstruation disorders.

Methods: The rat cold stress model was prepared with an ice water bath. The estrous cycle was observed by methylene blue and hematoxylin and eosin (H&E) staining. Serum estradiol 2 (E), testosterone (T), progesterone (P) were detected by radioimmunoassay. Hemorheology indices were measured. The real-time blood flow of auricle and uterine surfaces was measured. Expressions of CD34 and α-SMA in ovarian and uterine tissues were detected by immunohistochemistry. ET-1 contents in serum were tested, and expressions of ET-receptor types A and B (ET-AR and ET-BR) in ovarian tissues were detected via Western blotting.

Results: Cold stress extended the estrous cycle, thereby causing reproductive hormone disorder, imbalance of local endothelin/nitric oxide expression, and microcirculation disturbance. Cold-stress led to up-regulation of ET-AR expression and protein and down-regulation of ET-BR expression in rats.

Conclusions: This study suggests that the reason for cold stress-induced dysfunction in reproductive organs may be closely related to the imbalance of ET-1 and its receptor expressions, leading to microvascular circulation disorders in local tissues.
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http://dx.doi.org/10.1186/s12958-020-00584-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155299PMC
April 2020

Reducing Salt Intake in China with "Action on Salt China" (ASC): Protocol for Campaigns and Randomized Controlled Trials.

JMIR Res Protoc 2020 Apr 9;9(4):e15933. Epub 2020 Apr 9.

Chinese Center for Disease Control and Prevention, Beijing, China.

Background: Salt intake in China is over twice the maximum recommendation of the World Health Organization. Unlike most developed countries where salt intake is mainly derived from prepackaged foods, around 80% of the salt consumed in China is added during cooking.

Objective: Action on Salt China (ASC), initiated in 2017, aims to develop, implement, and evaluate a comprehensive and tailored salt reduction program for national scaling-up.

Methods: ASC consists of six programs working in synergy to increase salt awareness and to reduce the amount of salt used during cooking at home and in restaurants, as well as in processed foods. Since September 2018, two health campaigns on health education and processed foods have respectively started, in parallel with four open-label cluster randomized controlled trials (RCTs) in six provinces across China: (1) app-based intervention study (AIS), in which a mobile app is used to achieve and sustain salt reduction in school children and their families; (2) home cook-based intervention study (HIS), in which family cooks receive support in using less salt; (3) restaurant-based intervention study (RIS) targeting restaurant consumers, cooks, and managers; and (4) comprehensive intervention study (CIS), which is a real-world implementation and evaluation of all available interventions in the three other RCTs. To explore the barriers, facilitators, and effectiveness of delivering a comprehensive salt reduction intervention, these RCTs will last for 1 year (stage 1), followed by nationwide implementation (stage 2). In AIS, HIS, and CIS, the primary outcome of salt reduction will be evaluated by 24-hour urinary sodium excretion in 6030 participants, including 5436 adults and 594 school children around 8-9 years old. In RIS, the salt content of meals will be measured by laboratory food analysis of the 5 best-selling dishes from 192 restaurants. Secondary outcomes will include process evaluation; changes in knowledge, attitude, and practice on salt intake; and economic evaluation.

Results: All RCTs have been approved by Queen Mary Research Ethics Committee and the Institutional Review Boards of leading institutes in China. The research started in June 2017 and is expected to be completed around March 2021. The baseline investigations of the four RCTs were completed in May 2019.

Conclusions: The ASC project is progressing smoothly. The intervention packages and tailored components will be promoted for salt reduction in China, and could be adopted by other countries.

Trial Registration: Chinese Clinical Trial Registry. AIS: ChiCTR1800017553; https://tinyurl.com/vdr8rpr. HIS: ChiCTR1800016804; https://tinyurl.com/w8c7x3w. RIS: ChiCTR1800019694; https://tinyurl.com/uqkjgfw. CIS: ChiCTR1800018119; https://tinyurl.com/s3ajldw.

International Registered Report Identifier (irrid): DERR1-10.2196/15933.
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http://dx.doi.org/10.2196/15933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180507PMC
April 2020