Publications by authors named "Jie Hong"

277 Publications

Germline mutations in a DNA repair pathway are associated with familial colorectal cancer.

JCI Insight 2021 Sep 22;6(18). Epub 2021 Sep 22.

State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease.

Aiming to identify rare high-penetrance mutations in new genes for the underlying predisposition in familial colorectal cancer (CRC), we performed whole-exome sequencing in 24 familial CRCs. Mutations in genes that regulate DNA repair (RMI1, PALB2, FANCI) were identified that were related to the Fanconi anemia DNA repair pathway. In one pedigree, we found a nonsense mutation in CHEK2. CHEK2 played an essential role in cell cycle and DNA damage repair. Somatic mutation analysis in CHEK2 variant carriers showed mutations in TP53, APC, and FBXW7. Loss of heterozygosity was found in carcinoma of CHEK2 variant carrier, and IHC showed loss of Chk2 expression in cancer tissue. We identified a second variant in CHEK2 in 126 sporadic CRCs. A KO cellular model for CHEK2 (CHEK2KO) was generated by CRISPR/Cas9. Functional experiments demonstrated that CHEK2KO cells showed defective cell cycle arrest and apoptosis, as well as reduced p53 phosphorylation, upon DNA damage. We associated germline mutations in genes that regulate the DNA repair pathway with the development of CRC. We identified CHEK2 as a regulator of DNA damage response and perhaps as a gene involved in CRC germline predisposition. These findings link CRC predisposition to the DNA repair pathway, supporting the connection between genome integrity and cancer risk.
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http://dx.doi.org/10.1172/jci.insight.148931DOI Listing
September 2021

Enterotoxigenic Bacteroidesfragilis Promotes Intestinal Inflammation and Malignancy by Inhibiting Exosome-Packaged miR-149-3pf.

Gastroenterology 2021 Aug 8. Epub 2021 Aug 8.

State Key Laboratory for Oncogenes and Related Genes, Shanghai, China; Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai, China; Division of Gastroenterology and Hepatology, Shanghai Cancer Institute, Shanghai, China; Shanghai Institute of Digestive Disease, Shanghai, China; Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Background & Aims: Enterotoxigenic Bacteroides fragilis (ETBF) is strongly associated with the occurrence of inflammatory bowel disease (IBD), colitis-associated colorectal cancer, and colorectal cancer (CRC). However, the mechanism of ETBF-induced intestinal inflammation and tumorigenesis remains unclear.

Methods: microRNA sequencing was used to detect the differentially expressed microRNAs in both ETBF-treated cells and exosomes derived from ETBF-inoculated cells. Cell Counting Kit 8 assays were used to evaluate the effect of ETBF and exosomes on CRC cell proliferation. The biological role and mechanism of ETBF-mediated miR-149-3p in colitis and colon carcinogenesis were determined both in vitro and in vivo.

Results: ETBF promoted CRC cell proliferation by down-regulating miR-149-3p both in vitro and in vivo. ETBF-down-regulated miR-149-3p depended on METTL14-mediated mA methylation. As the target gene of miR-149-3p, PHF5A transactivated SOD2 through regulating KAT2A messenger RNA alternative splicing after ETBF treatment in CRC cells. miR-149-3p could be released in exosomes and mediated intercellular communication by modulating T-helper type 17 cell differentiation. The level of plasma exosomal miR-149-3p was gradually decreased from healthy control individuals to patients with IBD and CRC. miR-149-3p, existing in plasma exosomes, negatively correlated with the abundance of ETBF in patients with IBD and CRC.

Conclusions: Exosomal miR-149-3p derived from ETBF-treated cells facilitated T-helper type 17 cell differentiation. ETBF-induced colorectal carcinogenesis depended on down-regulating miR-149-3p and further promoting PHF5A-mediated RNA alternative splicing of KAT2A in CRC cells. Targeting the ETBF/miR-149-3p pathway presents a promising approach to treat patients with intestinal inflammation and CRC with a high amount of ETBF.
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http://dx.doi.org/10.1053/j.gastro.2021.08.003DOI Listing
August 2021

Co/MoC Nanoparticles Embedded in Carbon Nanoboxes as Robust Trifunctional Electrocatalysts for a Zn-Air Battery and Water Electrocatalysis.

ACS Nano 2021 Aug 4. Epub 2021 Aug 4.

Institute for Ecological Research and Pollution Control of Plateau Lakes, School of Ecology and Environmental Science, Yunnan University, Kunming, Yunnan 650504, P. R. China.

To meet the application needs of rechargeable Zn-air battery and electrocatalytic overall water splitting (EOWS), developing high-efficiency, cost-effective, and durable trifunctional catalysts for the hydrogen evolution reaction (HER), oxygen evolution, and reduction reaction (OER and ORR) is extremely paramount yet challenging. Herein, the interface engineering concept and nanoscale hollowing design were proposed to fabricate N-doping carbon nanoboxes confined with Co/MoC nanoparticles. Uniform zeolitic imidazolate framework nanocube was employed as the starting material to construct the trifunctional electrocatalyst through the conformal polydopamine-Mo layer coating and the subsequent pyrolysis treatment. The [email protected]/[email protected] catalyst displayed superior electrochemical ORR performances with a positive half-wave potential of 0.875 V and a high limiting current density of 5.89 mA/cm. When practically employed as an electrocatalyst in regenerative Zn-air battery, a high specific capacity of 728 mAh/g, a large peak power density of 221 mW/cm, a high open-circuit voltage of 1.482 V, and a low charge/discharge voltage gap of 0.41 V were obtained. Moreover, its practicability was further exploited by overall water splitting, affording low overpotentials of 277 and 68 mV at 10 mA/cm for the OER and HER in 1 M KOH solution, respectively, and a decent operating potential of 1.57 V for EOWS. Ultraviolet photoelectron spectroscopy and density functional theory calculation revealed that the Co/MoC interface synergistically facilitated the charge-transfer, thereby contributing to the enhancements of electrocatalytic ORR/OER/HER processes. More importantly, this catalyst design concept can offer some interesting prospects for the construction of outstanding trifunctional catalysts toward various energy conversion and storage devices.
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http://dx.doi.org/10.1021/acsnano.1c03766DOI Listing
August 2021

Deciphering CT texture features of human visceral fat to evaluate metabolic disorders and surgery-induced weight loss effects.

EBioMedicine 2021 Jul 3;69:103471. Epub 2021 Jul 3.

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Background: Metabolic syndrome (MetS) is highly related to the excessive accumulation of visceral adipose tissue (VAT). Quantitative measurements of VAT are commonly applied in clinical practice for measurement of metabolic risks; however, it remains largely unknown whether the texture of VAT can evaluate visceral adiposity, stratify MetS and predict surgery-induced weight loss effects.

Methods: 675 Chinese adult volunteers and 63 obese patients (with bariatric surgery) were enrolled. Texture features were extracted from VATs of the computed tomography (CT) scans and machine learning was applied to identify significant imaging biomarkers associated with metabolic-related traits.

Findings: Combined with sex, ten VAT texture features achieved areas under the curve (AUCs) of 0.872, 0.888, 0.961, and 0.947 for predicting the prevalence of insulin resistance, MetS, central obesity, and visceral obesity, respectively. A novel imaging biomarker, RunEntropy, was identified to be significantly associated with major metabolic outcomes and a 3.5-year follow-up in 338 volunteers demonstrated its long-term effectiveness. More importantly, the preoperative imaging biomarkers yielded high AUCs and accuracies for estimation of surgery responses, including the percentage of excess weight loss (%EWL) (0.867 and 74.6%), postoperative BMI group (0.930 and 76.1%), postoperative insulin resistance (0.947 and 88.9%), and excess visceral fat loss (the proportion of visceral fat reduced over 50%; 0.928 and 84.1%).

Interpretation: This study shows that the texture features of VAT have significant clinical implications in evaluating metabolic disorders and predicting surgery-induced weight loss effects.

Funding: The complete list of funders can be found in the Acknowledgement section.
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http://dx.doi.org/10.1016/j.ebiom.2021.103471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264112PMC
July 2021

Development of a miniature protein mass spectrometer capable of analyzing native proteins.

Talanta 2021 Oct 1;233:122580. Epub 2021 Jun 1.

School of Life Science, Beijing Institute of Technology, Beijing, 100081, China. Electronic address:

Current miniature mass spectrometers were usually designed for the detection of small and medium size molecules, including volatile (semi-volatile) compounds, drugs and lipids. In this study, a miniature protein mass spectrometer was developed in this work, which could serve as a biosensor for the rapid identification of proteins as well as their conformations. A linear ion trap with a field radius of 2.5 mm was designed to extend mass range of the instrument to over 6500 Th. Mass resolution and sensitivity of the instrument were also optimized for protein ions by increasing the buffer gas pressure and using a high-gain Faraday detector. It is then demonstrated that the mass spectra of native proteins, such as IgG1, could be acquired by coupling the instrument with a soft electrospray ionization source. As a proof-of-concept demonstration, results suggest that the current instrument could be used to identify target proteins and probe/distinguish their conformations in solutions.
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http://dx.doi.org/10.1016/j.talanta.2021.122580DOI Listing
October 2021

Association of night-time sleep and day napping with the prevalence of MOSH in young obese men.

Andrology 2021 Jul 1. Epub 2021 Jul 1.

Department of Endocrine and Metabolic Diseases, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China.

Background: Obesity in men is also shown to be associated with reduced reproductive potential, and this particular subtype was described as male obesity-associated secondary hypogonadism (MOSH). Recent studies showing the influence of sleep disorders on testosterone levels suggested a potential role of sleep disorders in determining the development of MOSH.

Objectives: To assess the association between night-time sleep duration and day napping and the prevalence of MOSH.

Materials And Methods: In this cross-sectional study, 226 obese male participants aged 18-30 years were enrolled. Daytime napping and night-time sleep duration data were collected using a standardized self-reported Chinese-language questionnaire. MOSH was defined as obese men (BMI ≥ 30 kg/m ) with hypogonadal symptoms and decreased total testosterone level and/or free testosterone level, excluding other causes of hypogonadism.

Results: The overall prevalence of MOSH was 48.2% in this study. An inverse association was observed between night sleep duration and the risk of prevalent MOSH. Men who reported fewer than 6 h of night-time sleep had reduced total testosterone and free testosterone levels and an increased risk of MOSH. Further regression analysis revealed that after adjustment for potential confounders, the odds ratio of MOSH for the short night-time sleep group (<6 h vs. 6-8 h) was 6.17 (p = 0.040). No significant association was observed between day napping status and prevalence of MOSH.

Discussion And Conclusion: Short night sleep duration was associated with an increased risk of MOSH in the young obese Chinese population. Chronic sleep curtailment has a negative effect on obese men's health in terms of hypogonadism.
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http://dx.doi.org/10.1111/andr.13074DOI Listing
July 2021

The safety and feasibility of the screening for retinopathy of prematurity assisted by telemedicine network during COVID-19 pandemic in Wuhan, China.

BMC Ophthalmol 2021 Jun 11;21(1):258. Epub 2021 Jun 11.

Department of Ophthalmology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Medical College, Huazhong University of Science & Technology, Wuhan, 430016, China.

Background: During the coronavirus disease 2019 (COVID-19) epidemic, due to the traffic blockade and the shortage of medical resources, more and more premature infants could not receive timely and effective ROP screening, which delayed treatment and even caused children blindness. Therefore, how to carry out ROP screening safely and effectively during the epidemic was very important and urgent. This study aimed to evaluate the safety and feasibility of ROP screening assisted by telemedicine network during COVID-19 outbreak.

Methods: This retrospective study was conducted at Wuhan Children's hospital in Wuhan, China, from January to October, 2020. The measures which were performed to make the ROP screening more safe and effective were summarized and the comparison between ROP screening assisted by telemedicine network in 2020 and usual screening in 2019 were analyzed.

Results: A total of 267 outpatient infants completed ROP screening. The median gestational age was 32 weeks (30w to 34w) and the median birth weight was 1780 g (1460 g to 2100 g). Meanwhile, 149 (55.8%) out of 267 infants were males. During January to May in 2020, 86 screening appointments were received, among which 67 (77.9%) were from telemedicine platform online. The completing percentage of total online ROP appointments was higher than that of total face-to-face appointments (58.1% VS 22. 1%, P = 0.018). As for the number of infants screened between 2020 and 2019 from Februaryto October, 54 infants completed ROP screening in 2020, which was higher than that (51participants) in 2019 on September. Furthermore, compared with the usual screening in 2019, ROP screening assisted by telemedicine network in 2020 had smaller gestational age (32w VS 33w, p<0.001) and lower birth weight (1780 g VS 1900 g, p = 0.001). However, of the 267 infants screened, 18(6.7%) had ROP while the percentage of ROP screened in 2019 was the same (44[6.7%]). During follow-up, none of medical staffs was infected and no adverse reaction was reported.

Conclusions: The screening for retinopathy of prematurity assisted by telemedicine network was safe and feasible during the COVID-19 pandemic. Preventive measures before and after screening were very necessary, which could effectively avoid cross infection.
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http://dx.doi.org/10.1186/s12886-021-02018-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192130PMC
June 2021

The Application of Tissue Glue in Eyelid Laceration Repair in Children During the Coronavirus Disease 2019 Pandemic Lockdown in Wuhan.

Clin Cosmet Investig Dermatol 2021 20;14:541-546. Epub 2021 May 20.

Department of Ophthalmology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430016, People's Republic of China.

Objective: To discuss a rapid and effective treatment used for children with eyelid lacerations during the COVID-19 lockdown in Wuhan to limit the risk of cross-infection.

Methods: A comparative study was conducted of forty-five patients with eyelid lacerations who attended the Ophthalmology Department of Wuhan Children's Hospital between January 23, 2020 and March 6, 2020. The tissue glue Histoacryl was used to bond the wounds in 24 cases, while the traditional suture method was used for 21 cases. The wound healing time, complications, treatment satisfaction, and number of visits of the two groups were compared.

Results: The two groups had similar baseline characteristics. The wound healing time (from wound disinfection to wound dressing) was shorter in the tissue glue group (4.35 ± 0.47min versus 11.71 ± 1.85 min, < 0.01). There was 1 case of wound dehiscence in the tissue glue group. Twenty-two cases in the tissue glue group were satisfied, 2 cases were basically satisfied, and 0 were dissatisfied. Eleven cases in the traditional suture group were satisfied, 9 cases were basically satisfied, and 1 case was dissatisfied. The difference was statistically significant ( < 0.05). In terms of the number of visits, the tissue glue group visited (1.54 ± 0.88) times, while the traditional suture group visited (2.38 ± 0.59) times. The difference between the two groups was statistically significant ( < 0.01). The real-time reverse transcriptase polymerase chain tests for severe acute respiratory syndrome coronavirus 2 of all medical staff in the ophthalmology emergency room were negative.

Conclusion: Compared with the traditional suture method, tissue glue used in eyelid laceration in children has the advantages of painlessness, shorter operation duration, higher safety and satisfaction, greater ease of care, and fewer hospital visits. Tissue glue can be widely used to reduce the risk of cross-infection.
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http://dx.doi.org/10.2147/CCID.S308092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146746PMC
May 2021

Reversal of Functional Brain Activity Related to Gut Microbiome and Hormones After VSG Surgery in Patients With Obesity.

J Clin Endocrinol Metab 2021 Aug;106(9):e3619-e3633

Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of Chinese Health Commission, Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025, China.

Context: Vertical sleeve gastrectomy (VSG) is becoming a prioritized surgical intervention for obese individuals; however, the brain circuits that mediate its effective control of food intake and predict surgical outcome remain largely unclear.

Objective: We investigated VSG-correlated alterations of the gut-brain axis.

Methods: In this observational cohort study, 80 patients with obesity were screened. A total of 36 patients together with 26 normal-weight subjects were enrolled and evaluated using the 21-item Three-Factor Eating Questionnaire (TFEQ), MRI scanning, plasma intestinal hormone analysis, and fecal sample sequencing. Thirty-two patients underwent VSG treatment and 19 subjects completed an average of 4-month follow-up evaluation. Data-driven regional homogeneity (ReHo) coupled with seed-based connectivity analysis were used to quantify VSG-related brain activity. Longitudinal alterations of body weight, eating behavior, brain activity, gastrointestinal hormones, and gut microbiota were detected and subjected to repeated measures correlation analysis.

Results: VSG induced significant functional changes in the right putamen (PUT.R) and left supplementary motor area, both of which correlated with weight loss and TFEQ scores. Moreover, postprandial levels of active glucagon-like peptide-1 (aGLP-1) and Ghrelin were associated with ReHo of PUT.R; meanwhile, relative abundance of Clostridia increased by VSG was associated with improvements in aGLP-1 secretion, PUT.R activity, and weight loss. Importantly, VSG normalized excessive functional connectivities with PUT.R, among which baseline connectivity between PUT.R and right orbitofrontal cortex was related to postoperative weight loss.

Conclusion: VSG causes correlated alterations of gut-brain axis, including Clostridia, postprandial aGLP-1, PUT.R activity, and eating habits. Preoperative connectivity of PUT.R may represent a potential predictive marker of surgical outcome in patients with obesity.
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http://dx.doi.org/10.1210/clinem/dgab297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372652PMC
August 2021

ZFP90 drives the initiation of colitis-associated colorectal cancer via a microbiota-dependent strategy.

Gut Microbes 2021 Jan-Dec;13(1):1-20

State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Chronic inflammation and gut microbiota dysbiosis are risk factors for colorectal cancer. In clinical practice, patients with inflammatory bowel disease (IBD) have a greatly increased risk of developing colitis-associated colorectal cancer (CAC). However, the underlying mechanism of the initiation of CAC remains unknown. Systematic analyses using an existing genome-wide association study (GWAS) and conditional deletion of (encoding zinc finger protein 90 homolog) in a CAC mouse model indicated that is a putative oncogene in CAC development.Strikingly, depletion of the gut microbiota eliminated the tumorigenic effect of in the CAC mouse model. Moreover, fecal microbiota transplantation demonstrated that promoted CAC dependent on the gut microbiota. Analysis of 16s rDNA sequences in fecal specimens from the CAC mouse model allowed us to speculate that a -defined microbiota might mediate the oncogenic role of in the development of CAC. Mechanistic studies revealed accelerated CAC development through the TLR4-PI3K-AKT-NF-κB pathway. Our findings revealed the crucial role of the -microbiota-NF-κB axis in creating a tumor-promoting environment and suggested therapeutic targets for CAC prevention and treatment.
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http://dx.doi.org/10.1080/19490976.2021.1917269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115455PMC
May 2021

The tryptic peptides of hemoglobin for diagnosis of type 2 diabetes mellitus using label-free and standard-free LC-ESI-DMRM.

Redox Biol 2021 07 22;43:101985. Epub 2021 Apr 22.

School of Life Science, Beijing Institute of Technology, Beijing, 100081, China.

N-1-(deoxyfructosyl) valine of β-hemoglobin, commonly referred to as HbA1c, is the "gold standard" for clinical detection of diabetes. Instead of quantifying the full-length HbA1c glycated protein, in the present study, we proposed the peptide-based strategy to quantify the depletion of the tryptic peptides of hemoglobin for the diagnosis of type 2 diabetes mellitus (T2DM). The peptides were discovered and validated as T2DM biomarkers by label-free LC-ESI-DMRM method without reference material. The glucose could react with hemoglobin's free amino group of N-terminus and ϵ-amino group of lysine residues and leave the modification on the hemoglobin tryptic peptides. Thus, there are two types of peptides in the hemoglobin: sensitive peptides and insensitive peptides to glucose due to the differential sensitivity of lysine residues to glycation. To discover two types of peptides of hemoglobin, we first developed the assay of liquid chromatography-electrospray ionization mass spectrometry coupled with dynamic multiple reaction monitoring. The protein coverage reaches 94.2%. Moreover, the hemoglobin was incubated with the 500 mmol/L glucose for 20 days, 40 days and 60 days in vitro to screen the sensitive peptides and insensitive peptides to glucose. A total of 14 sensitive peptides and 4 insensitive peptides were discovered. Furthermore, the LC-ESI-DMRM method was also utilized to validated the glucose-sensitive peptides by 40 clinical samples with healthy control individuals (n = 20) and type 2 diabetes mellitus patients (n = 20). Three putative sensitive peptides (LLGNVLVCVLAHHFGK, VVAGVANALAHKYH, LRVDPVNFK) from the hemoglobin showed excellent sensitivity and specificity based on receiver operating characteristic analysis and were verified as the promising biomarkers for the diagnosis of diabetes mellitus. And one peptide (LLVVYPWTQR) was found as glucose-insensitive peptide. Taken together, the findings of this study suggest that quantification of hemoglobin tryptic peptides using label-free and standard-free LC-ESI-DMRM is an alternative method for the diagnosis of T2DM, which could be combined with other MS-based blood biomarkers for diagnosis of multiple diseases in MS single shot.
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http://dx.doi.org/10.1016/j.redox.2021.101985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102995PMC
July 2021

Stronger association of triglyceride glucose index than the HOMA-IR with arterial stiffness in patients with type 2 diabetes: a real-world single-centre study.

Cardiovasc Diabetol 2021 04 22;20(1):82. Epub 2021 Apr 22.

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: The triglyceride-glucose index (TyG index) has been proposed as a simple and reliable alternative insulin resistance (IR) marker, while the homeostasis model assessment for IR (HOMA-IR) is the most frequently used index. Few studies have evaluated the role of IR assessed by the TyG index and HOMA-IR on arterial stiffness in a type 2 diabetes (T2D) population with a high risk of increased arterial stiffness. We aimed to investigate the association of the TyG index and HOMA-IR with arterial stiffness in patients with T2D.

Methods: We recruited 3185 patients with T2D, who underwent brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness, but without previous cardiovascular disease. Increased arterial stiffness was defined as a baPWV value greater than the 75th percentile (18.15 m/s) in the present study. The TyG index was determined as ln(fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2), and the HOMA-IR was calculated as (fasting insulin [μIU/mL] × fasting glucose [mmol/L])/22.5.

Results: The mean age of the study participants was 54.6 ± 12.0 years, and 1954 (61.4%) were men. Seemingly unrelated regression estimation analysis demonstrated that the TyG index had stronger associations with baPWV than the HOMA-IR (all P < 0.001). In the multivariable logistic analyses, each one-unit increase in the TyG index was associated with a 1.40-fold (95% CI 1.16-1.70, P < 0.001) higher prevalence of increased arterial stiffness, but the prominent association of the HOMA-IR with the prevalence of increased arterial stiffness was not observed. Subgroup analyses showed that a more significant association between the TyG index and the prevalence of increased arterial stiffness was detected in older patients with a longer duration of diabetes and poor glycaemic control (all P < 0.05).

Conclusions: Compared with the HOMA-IR, the TyG index is independently and more strongly associated with arterial stiffness in patients with T2D.
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http://dx.doi.org/10.1186/s12933-021-01274-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063289PMC
April 2021

Meteorological conditions are heterogeneous factors for COVID-19 risk in China.

Environ Res 2021 07 16;198:111182. Epub 2021 Apr 16.

Department of Epidemiology and Health Statistics, Fudan University, China. Electronic address:

Whether meteorological factors influence COVID-19 transmission is an issue of major public health concern, but available evidence remains unclear and limited for several reasons, including the use of report date which can lag date of symptom onset by a considerable period. We aimed to generate reliable and robust evidence of this relationship based on date of onset of symptoms. We evaluated important meteorological factors associated with daily COVID-19 counts and effective reproduction number (R) in China using a two-stage approach with overdispersed generalized additive models and random-effects meta-analysis. Spatial heterogeneity and stratified analyses by sex and age groups were quantified and potential effect modification was analyzed. Nationwide, there was no evidence that temperature and relative humidity affected COVID-19 incidence and R. However, there were heterogeneous impacts on COVID-19 risk across different regions. Importantly, there was a negative association between relative humidity and COVID-19 incidence in Central China: a 1% increase in relative humidity was associated with a 3.92% (95% CI, 1.98%-5.82%) decrease in daily counts. Older population appeared to be more sensitive to meteorological conditions, but there was no obvious difference between sexes. Linear relationships were found between meteorological variables and COVID-19 incidence. Sensitivity analysis confirmed the robustness of the association and the results based on report date were biased. Meteorological factors play heterogenous roles on COVID-19 transmission, increasing the possibility of seasonality and suggesting the epidemic is far from over. Considering potential climatic associations, we should maintain, not ease, current control measures and surveillance.
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http://dx.doi.org/10.1016/j.envres.2021.111182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050398PMC
July 2021

Association of Metabolic Syndrome With Prevalence of Obstructive Sleep Apnea and Remission After Sleeve Gastrectomy.

Front Physiol 2021 31;12:650260. Epub 2021 Mar 31.

Department of Endocrine and Metabolic Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Obesity is an important risk factor for metabolic syndrome and obstructive sleep apnea (OSA). Bariatric surgery has been shown to effectively reduce weight and obesity-related comorbidities. However, the prevalence and severity of OSA in obese patients with different baseline metabolic states and the improvements of OSA after bariatric surgery remain unknown. The main aims of this study were to ascertain the prevalence of OSA in young Chinese obese patients with different metabolic states and to evaluate their respective OSA remission after laparoscopic sleeve gastrectomy. We first performed a cross-sectional study involving 123 metabolically healthy obese patients and 200 metabolically unhealthy obese patients (who had the same age and BMI ranges) to estimate the prevalence of OSA at baseline. Then we performed a retrospective study, which was registered at ClinicalTrials.gov (ref. NCT02653430) of 67 patients who underwent laparoscopic sleeve gastrectomy to evaluate the remission of OSA. Metabolically healthy and unhealthy obese patients had similar apnea-hypopnea index levels (16.6 ± 22.0 vs. 16.7 ± 18.7 events/h, = 0.512) and prevalence of OSA (66.7% vs. 69.0%, = 0.662). Male sex, age, waist circumference and lower liver-to-spleen ratio were independent risk factors for OSA. After laparoscopic sleeve gastrectomy, no difference was found in the decrease in body mass index (BMI) change (10.8 ± 4.8 vs. 10.8 ± 3.0 kg/m, = 0.996) or the decrease in the apnea-hypopnea index (18.9 ± 24.6 vs. 17.0 ± 24.0 events/h, = 0.800). The remission of moderate-to-severe OSA was observed in the MHO (36.3%; 54.5-18.2%, = 0.125) and MUO (32.2%; 66.1-33.9%, = 0.001) patients. These results suggest that, in patients with obesity, metabolic syndrome does not add extra risk for the prevalence or severity of OSA. Both metabolically healthy and unhealthy obese patients could benefit equally from laparoscopic sleeve gastrectomy in terms of weight loss and obstructive sleep apnea remission.
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http://dx.doi.org/10.3389/fphys.2021.650260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044302PMC
March 2021

Decreased Functional Connectivity of the Primary Visual Cortex and the Correlation With Clinical Features in Patients With Intermittent Exotropia.

Front Neurol 2021 26;12:638402. Epub 2021 Mar 26.

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

The purpose of this study is to investigate characteristic alterations of functional connectivity (FC) patterns in the primary visual area (V1) in patients with intermittent exotropia (IXT) using resting-state functional magnetic resonance imaging (rs-fMRI) and how they relate to clinical features. Twenty-six IXT patients and 21 age-, sex-, handedness-, and education-matched healthy controls (HCs) underwent rs-fMRI. We performed FC analyses between bilateral V1 and other brain areas and compared FC strength between two groups. A Pearson correlation analysis was used to evaluate the correlation between the FC differences and clinical features. Compared with HCs, patients with IXT showed significantly lower FC of the right V1 with the right calcarine sulcus and right superior occipital gyrus, and the left V1 with right cuneus and right postcentral gyrus. The Newcastle Control Test score was positively correlated with mean FC values between the left inferior parietal lobule and bilateral V1, and between the left supramarginal gyrus and left V1. The duration of IXT was positively correlated with mean FC values between the right inferior occipital gyrus and right V1. Reduced FC between the V1 and various brain regions involved in vision and eye movement processes may be associated with the underlying neural mechanisms of impaired visual function in patients with IXT.
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http://dx.doi.org/10.3389/fneur.2021.638402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032987PMC
March 2021

CXCL11 Correlates With Antitumor Immunity and an Improved Prognosis in Colon Cancer.

Front Cell Dev Biol 2021 11;9:646252. Epub 2021 Mar 11.

Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou Medical University, Xuzhou, China.

The chemokine ligand C-X-C motif chemokine ligand 11 (CXCL11) is involved in the progression of various cancers, but its biological roles in colorectal cancer (CRC) remain confused. Therefore, the prognostic value and underlying mechanism of CXCL11 in CRC were preliminarily evaluated. Three independent datasets were used for mRNA-related analysis: one dataset from the Cancer Genome Atlas (TCGA, = 451) and two single-cell RNA sequencing (scRNA-seq) datasets from Gene Expression Omnibus (GEO): GSE146771 and GSE132465. In addition, a colon adenocarcinoma (COAD) patient cohort (the Yijishan Hospital cohort, YJSHC, = 108) was utilized for analysis of cell infiltration by immunohistochemistry. We determined the distribution of CXCL11 in tumor tissue across all TCGA cancers and found that CXCL11 expression was significantly upregulated in both COAD and rectal adenocarcinoma (READ). However, the upregulation of CXCL11 mRNA was associated with a better prognosis in COAD, but not in READ. Within the YJSHC, the patients with a high abundance of intratumoral CXCL11 cells had prolonged survival ( = 0.001). Furthermore, we found that the high CXCL11 expression group had a higher proportion of antitumor immune cells, and a lower proportion of protumor immune cells. Additionally, we discovered the changes of gene expression and enriched immune pathway network mediated by CXCL11. Interestingly, both cytotoxic genes (IFNG, GZMA, GZMB, GZMK, GZMM, and PRF1) and immunosuppressive molecules, including PD-L1, were positively correlated with CXCL11 expression. CXCL11, which promoted antitumor immunity to benefit survival, was identified as an independent prognostic biomarker in patients with COAD.
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http://dx.doi.org/10.3389/fcell.2021.646252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991085PMC
March 2021

Overexpression Enhances Expression .

Front Endocrinol (Lausanne) 2021 10;12:634191. Epub 2021 Mar 10.

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: The Iroquois homeobox 3 () gene was recently reported to be a functional downstream target of a common polymorphism in the gene, which encodes an obesity-associated protein; however, the role of in energy expenditure remains unclear. Studies have revealed that the overexpression of a dominant-negative form of IRX3 in the mouse hypothalamus and adipose tissue promoted energy expenditure by enhancing brown/browning activities. Meanwhile, we and others recently demonstrated that knockdown impaired the browning program of primary preadipocytes . In this study, we aimed to further clarify the effects of overexpressing human (h) on brown/beige adipose tissues .

Methods: Brown/beige adipocyte-specific h-overexpressing mice were generated and the browning program of white adipose tissues was induced by both chronic cold stimulation and CL316,243 injection. Body weight, fat mass, lean mass, and energy expenditure were measured, while morphological changes and the expression of thermogenesis-related genes in adipose tissue were analyzed. Moreover, the browning capacity of primary preadipocytes derived from h-overexpressing mice was assessed. RNA sequencing was also employed to investigate the effect of h on the expression of thermogenesis-related genes.

Results: h overexpression in embryonic brown/beige adipose tissues ( ;Cre) led to increased energy expenditure, decreased fat mass, and a lean body phenotype. After acute cold exposure or CL316,243 stimulation, brown/beige tissue h-overexpressing mice showed an increase in expression. Consistent with this, induced h overexpression in adult mice ( ;Cre) also promoted a moderate increase in expression. experiments further revealed that h overexpression induced by -driven Cre recombinase activity upregulated brown/beige adipocytes expression and oxygen consumption rate (OCR). RNA sequencing analyses indicated that h overexpression in brown adipocytes enhanced brown fat cell differentiation, glycolysis, and gluconeogenesis.

Conclusion: Consistent with the findings, brown/beige adipocyte-specific overexpression of h promoted expression and thermogenesis, while reducing fat mass.
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http://dx.doi.org/10.3389/fendo.2021.634191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988233PMC
March 2021

CCMAlnc Promotes the Malignance of Colorectal Cancer by Modulating the Interaction Between miR-5001-5p and Its Target mRNA.

Front Cell Dev Biol 2020 16;8:566932. Epub 2020 Dec 16.

State Key Laboratory of Oncogenes and Related Genes, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objective: Colorectal cancer (CRC) is highly malignant and cancer metastasis remains the predominant cause of CRC death. The potential molecular mechanism of long non-coding RNA (lncRNAs) in CRC malignance is still poorly elucidated.

Methods: CCMAlnc expression was analyzed by using the Sequence ReadArchive (SRA) database. Target gene expression was examined by real-time PCR and Western blotting. The biological function of CCMAlnc and miR-5001-5p was detected by cell invasion, CCK8 proliferation, and colony formation assays in loss of function and gain of function experiments . A luciferase assay was performed to validate the target site of miR-5001-5p on the 3'-UTR of HES6 mRNA.

Results: CCMAlnc was identified as a novel functional lncRNA in CRC. Elevated CCMAlnc was detected in CRC cells as well as in clinical CRC tissue samples, and the expression of this lncRNA positively correlated with the poor prognosis of CRC patients. Functional validation assays revealed that downregulation of CCMAlnc impaired CRC cell proliferation and invasion , but upregulation of CCMAlnc reversed this effect. Moreover, CCMAlnc was validated to act as a competing endogenous RNA (ceRNA) that stabilizes the expression of HES6 by downregulating miR-5001-5p.

Conclusion: CCMAlnc/miR-5001-5p/HES6 signaling is strongly activated to promote CRC malignance. CCMAlnc is defined as a potential candidate biomarker for metastasis prediction in CRC patients and as a potential therapeutic target for CRC treatment.
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http://dx.doi.org/10.3389/fcell.2020.566932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931267PMC
December 2020

Quantitative proteomic analysis of ahpC/F and katE and katG knockout Escherichia coli-a useful model to study endogenous oxidative stress.

Appl Microbiol Biotechnol 2021 Mar 25;105(6):2399-2410. Epub 2021 Feb 25.

School of Life Science, Beijing Institute of Technology, No. 5 Zhongguancun South Street, Beijing, 100081, People's Republic of China.

Alkyl hydroperoxide reductase (AhP), catalase G (KatG), and catalase E (KatE) are the main enzymes to scavenge the excessive hydrogen peroxide in E. coli. It was found the concentration of endogenous HO was submicromolar in a mutant strain E. coli MG1655/ΔAhpΔKatEΔKatG, which was enough to cause damage to DNA and proteins as well as concomitant cell growth and metabolism. However, few studies explored how submicromolar intracellular hydrogen peroxide alters protein function and regulates the signaling pathways at the proteome level. In order to study the effect of endogenous oxidative stress caused by submicromolar hydrogen peroxide, this study first constructed a mutant strain E. coli MG1655/ΔAhpΔKatEΔKatG. Then, label-free quantitative proteomic analysis was used to quantify the differentially expressed proteins between the wild-type strain and the mutant strain. A total of 265 proteins were observed as differentially expressed proteins including 108 upregulated proteins and 157 downregulated proteins. Among them, three differentially expressed proteins were also validated by parallel reaction monitoring (PRM) methodology. The 265 differentially expressed proteins are not only involved with many metabolism pathways including the TCA cycle, the pentose phosphate pathway, and the glyoxylic acid cycle, but also activated the DNA repair and cellular antioxidant signaling pathway. These findings not only demonstrated that ahp, katE, and katG played the critical role in aerobic growth but also delineated proteins network and pathway regulated by submicromolar intracellular hydrogen peroxide, which allowed a deeper understanding of oxidative signaling in E. coli. The findings of this study also demonstrate that the mutant E. coli may serve as a cell model to investigate the effect of endogenous oxidative stress and downstream signaling pathways. KEY POINTS: • The mutant strain E. coli MG1655/ΔAhpΔKatEΔKatG was constructed to study the effect of endogenous oxidative stress in E. coli. • A total of 265 differentially expressed proteins were quantified and enriched in metabolic pathways and antioxidant systems by using label-free proteomics analysis. • The findings of this study demonstrate that the mutant E. coli may serve as an effective tool to investigate the endogenous oxidative stress.
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http://dx.doi.org/10.1007/s00253-021-11169-2DOI Listing
March 2021

Risk SNP-induced lncRNA-SLCC1 drives colorectal cancer through activating glycolysis signaling.

Signal Transduct Target Ther 2021 Feb 19;6(1):70. Epub 2021 Feb 19.

State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Cancer Institute; Shanghai Institute of Digestive Disease; Renji Hospital, Shanghai Jiao Tong University School of Medicine, 145 Middle Shandong Road, 200001, Shanghai, China.

Long non-coding RNAs (lncRNAs) play key roles in colorectal carcinogenesis. Here, we aimed to identify the risk SNP-induced lncRNAs and to investigate their roles in colorectal carcinogenesis. First, we identified rs6695584 as the causative SNP in 1q41 locus. The A>G mutation of rs6695584 created a protein-binding motif of BATF, altered the enhancer activity, and subsequently activated lncSLCC1 expression. Further validation in two independent CRC cohorts confirmed the upregulation of lncSLCC1 in CRC tissues, and revealed that increased lncSLCC1 expression was associated with poor survival in CRC patients. Mechanistically, lncRNA-SLCC1 interacted with AHR and transcriptionally activated HK2 expression, the crucial enzyme in glucose metabolism, thereby driving the glycolysis pathway and accelerating CRC tumor growth. The functional assays revealed that lncSLCC1 induced glycolysis activation and tumor growth in CRC mediated by HK2. In addition, HK2 was upregulated in colorectal cancer tissues and positively correlated with lncSLCC1 expression and patient survival. Taken together, our findings reveal a risk SNP-mediated oncogene lncRNA-SLCC1 promotes CRC through activating the glycolysis pathway.
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http://dx.doi.org/10.1038/s41392-020-00446-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892549PMC
February 2021

A tumor microenvironment-specific gene expression signature predicts chemotherapy resistance in colorectal cancer patients.

NPJ Precis Oncol 2021 Feb 12;5(1). Epub 2021 Feb 12.

State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Studies have shown that tumor microenvironment (TME) might affect drug sensitivity and the classification of colorectal cancer (CRC). Using TME-specific gene signature to identify CRC subtypes with distinctive clinical relevance has not yet been tested. A total of 18 "bulk" RNA-seq datasets (total n = 2269) and four single-cell RNA-seq datasets were included in this study. We constructed a "Signature associated with FOLFIRI resistant and Microenvironment" (SFM) that could discriminate both TME and drug sensitivity. Further, SFM subtypes were identified using K-means clustering and verified in three independent cohorts. Nearest template prediction algorithm was used to predict drug response. TME estimation was performed by CIBERSORT and microenvironment cell populations-counter (MCP-counter) methods. We identified six SFM subtypes based on SFM signature that discriminated both TME and drug sensitivity. The SFM subtypes were associated with distinct clinicopathological, molecular and phenotypic characteristics, specific enrichments of gene signatures, signaling pathways, prognosis, gut microbiome patterns, and tumor lymphocytes infiltration. Among them, SFM-C and -F were immune suppressive. SFM-F had higher stromal fraction with epithelial-to-mesenchymal transition phenotype, while SFM-C was characterized as microsatellite instability phenotype which was responsive to immunotherapy. SFM-D, -E, and -F were sensitive to FOLFIRI and FOLFOX, while SFM-A, -B, and -C were responsive to EGFR inhibitors. Finally, SFM subtypes had strong prognostic value in which SFM-E and -F had worse survival than other subtypes. SFM subtypes enable the stratification of CRC with potential chemotherapy response thereby providing more precise therapeutic options for these patients.
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http://dx.doi.org/10.1038/s41698-021-00142-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881244PMC
February 2021

targets lncRNA ENO1-IT1 to promote glycolysis and oncogenesis in colorectal cancer.

Gut 2020 Dec 14. Epub 2020 Dec 14.

State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Cancer Institute; Shanghai Institute of Digestive Disease, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Objective: Microbiota disorder promotes chronic inflammation and carcinogenesis. High glycolysis is associated with poor prognosis in patients with colorectal cancer (CRC). However, the potential correlation between the gut microbiota and glucose metabolism is unknown in CRC.

Design: F-FDG (F-fluorodeoxyglucose) PET (positron emission tomography)/CT image scanning data and microbiota PCR analysis were performed to measure the correlation between metabolic alterations and microbiota disorder in 33 patients with CRC. Multiple colorectal cancer models, metabolic analysis and Seahorse assay were established to assess the role of long non-coding RNA (lncRNA) enolase1-intronic transcript 1 (ENO1-IT1) in -induced glucose metabolism and colorectal carcinogenesis. RNA immunoprecipitation and chromatin immunoprecipitation sequencing were conducted to identify potential targets of lncRNA ENO1-IT1.

Results: We have found . abundance correlated with high glucose metabolism in patients with CRC. Furthermore, supported carcinogenesis via increasing CRC cell glucose metabolism. Mechanistically, activated lncRNA ENO1-IT1 transcription via upregulating the binding efficiency of transcription factor SP1 to the promoter region of lncRNA ENO1-IT1. Elevated ENO1-IT behaved as a guider modular for KAT7 histone acetyltransferase, specifying the histone modification pattern on its target genes, including ENO1, and consequently altering CRC biological function.

Conclusion: and glucose metabolism are mechanistically, biologically and clinically connected to CRC. Targeting ENO1 pathway may be meaningful in treating patients with CRC with elevated .
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http://dx.doi.org/10.1136/gutjnl-2020-322780DOI Listing
December 2020

Dynamic pneumatic rails enabled microdroplet manipulation.

Lab Chip 2021 01;21(1):105-112

Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, 29 Zhongguancun East Road, Haidu District, Beijing 10019, China.

This study presented a convenient method of gathering, splitting, merging, and sorting microdroplets by dynamic pneumatic rails in double-layered microfluidic devices. In these devices, the pneumatic rails were placed below the droplet channel, with a thin elastic polydimethylsiloxane (PDMS) film between them. The PDMS film would sag down to the rail channel, forming a groove pattern at the bottom of the droplet channel, when the fluid pressure in the droplet channel was higher than the air pressure in the rail channel. The groove could capture the flattened droplets and guide the flow path of them due to the lowered surface energy when they extended into the groove. We have designed different components consisting of pneumatic rails to split, merge and sort droplets, and demonstrated that the components maintained good performance in manipulating droplets only by controlling the air pressure. Furthermore, a pneumatic rail-based sorter has been successfully used to sort out single-cell droplets. The pneumatic rail can be integrated into pneumatic valve-based microfluidic devices to be a flexible tool for droplet-based biological and chemical analysis.
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http://dx.doi.org/10.1039/d0lc00805bDOI Listing
January 2021

Changed transmission epidemiology of COVID-19 at early stage: A nationwide population-based piecewise mathematical modelling study.

Travel Med Infect Dis 2021 Jan-Feb;39:101918. Epub 2020 Nov 13.

Department of Epidemiology and Health Statistics, School of Public Health, Fudan University, Shanghai, 200032, China; Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, 200032, China. Electronic address:

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http://dx.doi.org/10.1016/j.tmaid.2020.101918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661920PMC
March 2021

Breath-, air- and surface-borne SARS-CoV-2 in hospitals.

J Aerosol Sci 2021 Feb 15;152:105693. Epub 2020 Oct 15.

College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, China.

The COVID-19 pandemic has brought an unprecedented crisis to the global health sector. When discharging COVID-19 patients in accordance with throat or nasal swab protocols using RT-PCR, the potential risk of reintroducing the infection source to humans and the environment must be resolved. Here, 14 patients including 10 COVID-19 subjects were recruited; exhaled breath condensate (EBC), air samples and surface swabs were collected and analyzed for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) in four hospitals with applied natural ventilation and disinfection practices in Wuhan. Here we discovered that 22.2% of COVID-19 patients (n = 9), who were ready for hospital discharge based on current guidelines, had SARS-CoV-2 in their exhaled breath (~10 RNA copies/m). Although fewer surface swabs (3.1%, n = 318) tested positive, medical equipment such as face shield frequently contacted/used by healthcare workers and the work shift floor were contaminated by SARS-CoV-2 (3-8 viruses/cm). Three of the air samples (n = 44) including those collected using a robot-assisted sampler were detected positive by a digital PCR with a concentration level of 9-219 viruses/m. RT-PCR diagnosis using throat swab specimens had a failure rate of more than 22% in safely discharging COVID-19 patients who were otherwise still exhaling the SARS-CoV-2 by a rate of estimated ~1400 RNA copies per minute into the air. Direct surface contact might not represent a major transmission route, and lower positive rate of air sample (6.8%) was likely due to natural ventilation (1.6-3.3 m/s) and regular disinfection practices. While there is a critical need for strengthening hospital discharge standards in preventing re-emergence of COVID-19 spread, use of breath sample as a supplement specimen could further guard the hospital discharge to ensure the safety of the public and minimize the pandemic re-emergence risk.
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http://dx.doi.org/10.1016/j.jaerosci.2020.105693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557302PMC
February 2021

Sex-influenced association between free triiodothyronine levels and poor glycemic control in euthyroid patients with type 2 diabetes mellitus.

J Diabetes Complications 2020 11 31;34(11):107701. Epub 2020 Jul 31.

Shanghai National Clinical Research Center for Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Objective: The study investigated the association between free triiodothyronine (FT3) and poor glycemic control with different definitions in euthyroid patients with type 2 diabetes mellitus (T2DM).

Methods: This was a cross-sectional study which included 2172 patients from National Metabolic Management Center in Ruijin Hospital. The association between thyroid function and glycated hemoglobin A1c (HbA1c) was determined by multiple liner regression models. The association between FT3 and poor glycemic control was further determined by binary logistic regression models. Two definitions of poor glycemic control (HbA1c ≥ 7% and HbA1c ≥ 8%) were applied when we analyzed the association.

Results: Prevalence of HbA1c ≥ 7% and HbA1c ≥ 8% were 63.8% and 39.3%, respectively. After adjusting for confounding factors, FT3, rather than free tetraiodothyronine (FT4) or thyroid stimulating hormone (TSH), was independently associated with HbA1c (β = -0.104, P = 0.002). Further analysis after gender stratification showed that the association was only found in males (β = -0.164, P < 0.001). We further analyzed the association between FT3 quartiles and poor glycemic control. FT3 quartiles were not significantly associated with the risk of HbA1c ≥ 7% before and after adjusting for confounding factors in both genders. FT3 quartiles were negatively associated with the risk of HbA1c ≥ 8% only in males, independent of traditional risk factors for poor glycemic control (P for trend = 0.030).

Conclusions: FT3 in the reference range was significantly associated with reduced risk of HbA1c ≥ 8% in males, independent of traditional risk factors for poor glycemic control.
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http://dx.doi.org/10.1016/j.jdiacomp.2020.107701DOI Listing
November 2020

Single cell transcriptome revealed SARS-CoV-2 entry genes enriched in colon tissues and associated with coronavirus infection and cytokine production.

Signal Transduct Target Ther 2020 07 8;5(1):121. Epub 2020 Jul 8.

State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai, 200001, China.

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http://dx.doi.org/10.1038/s41392-020-00237-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340775PMC
July 2020

ALKBH4 Functions as a Suppressor of Colorectal Cancer Metastasis via Competitively Binding to WDR5.

Front Cell Dev Biol 2020 14;8:293. Epub 2020 May 14.

State Key Laboratory of Oncogenes and Related Genes, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Epithelial-Mesenchymal Transition (EMT) is a major process in the initiation of tumor metastasis, where cancer cells lose sessile epithelial potential and gain mesenchymal phenotype. Large-scale cell identity shifts are often orchestrated on an epigenetic level and the interplay between epigenetic factors and EMT progression was still largely unknown. In this study, we tried to identify candidate epigenetic factors that involved in EMT progression.

Methods: Colorectal cancer (CRC) cells were transfected with an arrayed shRNA library targeting 384 genes involved in epigenetic modification. Candidate genes were identified by real-time PCR. Western blot, RNA-seq and gene set enrichment analysis were conducted to confirm the suppressive role of ALKBH4 in EMT. The clinical relevance of ALKBH4 in CRC was investigated in two independent Renji Cohorts and a microarray dataset (GSE21510) from GEO database. transwell assay and metastatic tumor model were performed to explore the biological function of ALKBH4 in the metastasis of CRC. Co-IP (Co-Immunoprecipitation) and ChIP (Chromatin Immunoprecipitation) assays were employed to uncover the mechanism.

Results: We screened for candidate epigenetic factors that affected EMT process and identified ALKBH4 as a candidate EMT suppressor gene, which was significantly downregulated in CRC patients. Decreased level of ALKBH4 was associated with metastasis and predicted poor prognosis of CRC patients. Follow-up functional experiments illustrated overexpression of ALKBH4 inhibited the invasion ability of CRC cells , as well as their metastatic capability . Mechanistically, CO-IP and ChIP assays indicated that ALKBH4 competitively bound WDR5 (a key component of histone methyltransferase complex) and decreased H3K4me3 histone modification on the target genes including .

Conclusions: This study illustrated that ALKBH4 may function as a novel metastasis suppressor of CRC, and inhibits H3K4me3 modification through binding WDR5 during EMT.
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http://dx.doi.org/10.3389/fcell.2020.00293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240015PMC
May 2020

Liquid-Phase Ion Trap for Ion Trapping, Transfer, and Sequential Ejection in Solutions.

Anal Chem 2020 07 14;92(13):9065-9071. Epub 2020 Jun 14.

School of Life Science, Beijing Institute of Technology, Beijing 100081, China.

In this study, a new method/mechanism to manipulate ions in solution was developed, based on which liquid-phase ion trap was built. In this liquid-phase ion trap, ion manipulations conventionally performed in a quadrupole ion trap or in a trapped ion mobility spectrometer placed in a vacuum were achieved in solutions. Through theoretical derivation and numerical simulation, it is found that ions have different motional characteristics than those in vacuum. Instead of a radio frequency quadrupole electric field, tunable DC electric fields together with a constant liquid flow were applied to control ion motions in solution. Different ions could be trapped and focused in a potential well, and ion densities could be increased by over 100-fold. By adjusting the DC electric field of the potential well, trapped ions could be transferred into another trapping region or sequentially released for detection. Ions released from the liquid-phase ion trap were then detected by a mass spectrometer interfaced with an electrospray ionization source. Since the ion manipulation mechanism in solution is different and complementary to that in vacuum, the use of a liquid-phase ion trap could also boost detection sensitivity and the mixture analysis capability of a mass spectrometer.
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http://dx.doi.org/10.1021/acs.analchem.0c01261DOI Listing
July 2020

Prevalence of heterophoria in a population of school children in central China: the Anyang Childhood Eye Study.

Int J Ophthalmol 2020 18;13(5):801-805. Epub 2020 May 18.

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University; Beijing Ophthalmology and Visual Science Key Laboratory, Beijing 100730, China.

Aim: To investigate the prevalence of heterophoria and the relationship between heterophoria and refractive error in a school-based study conducted in central China.

Methods: A total of 2363 7-grade children were recruited into the cross-sectional school-based Anyang Childhood Eye Study (ACES) by cluster sampling method. Heterophoria was examined using alternate cover and cover-uncover testing. The Maddox rod and prism test were conducted at 33 cm and 6 m distance fixation. Uncorrected viual acuity (UCVA) and best-corrected viual acuity (BCVA) were recorded as logarithm of the minimum angle of resolution (logMAR) with cycloplegic autorefraction by administrating of Mydrin-P and 1.0% cyclopentolate. Hyperopia was defined as the spherical equivalent (SE) refraction of +0.50 D or greater, and higher hyperopia was defined as +2.00 D or greater. Emmetropia was defined as the SE refraction in the range of -0.49 to +0.49 D, and myopia was in the SE refraction range from -0.50 D to less.

Results: Totally 2260 students in grade 7 were examined. Response rate among eligible children was 95.64%. Totally 486 children, 22.66% of the population, were diagnosed with heterophoria in which 479 were diagnosed with exophoria at near distance, and 6 with esophoria. Totally 89 (4.15%) children were diagnosed with heterophoria in which 82 had exophoria, and 7 had esophoria at far distance. Exophoria was common at near fixation (22.33%). Myopia was examined to be related to exophoria at near distance (OR 3.03, 95%CI 2.33-3.95) and far distance fixation (OR 1.90, 95%CI 1.09-3.32).

Conclusion: Exophoria is a predominant heterophoria for 7-grade junior school in central China. Significant associations are discovered between heterophoria and refractive error. Hyperopia is associated with esophoria, and myopia is associated with exophoria.
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http://dx.doi.org/10.18240/ijo.2020.05.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201350PMC
May 2020
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