Publications by authors named "Liming Chen"

301 Publications

Value of M2BP in predicting in-stent restenosis in patients after coronary drug-eluting stent implantation.

Clin Cardiol 2022 Jan 15. Epub 2022 Jan 15.

Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

Objective: We evaluated the association between plasma levels of mac-2 binding protein (M2BP) with the risk of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI).

Methods: Plasma M2BP levels were compared between 258 patients who experienced ISR at 12-months post-PCI and 258 patients, matched for age and sex, without angiographic evidence of ISR.

Results: The plasma M2BP level was significantly higher in the ISR than in the non-ISR group. On multivariate analysis, adjusted for potential clinical, biochemical, and angiography characteristics, M2BP remained as an independent significant predictor of ISR.

Conclusions: M2BP may be an important predictive biomarker of ISR and may be useful in identifying at-risk patients.
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http://dx.doi.org/10.1002/clc.23775DOI Listing
January 2022

Primary Breast Lymphoma Detected by 18F-FDG and 68Ga-DOTA-FAPI-04 PET/CT.

Clin Nucl Med 2022 Jan 11. Epub 2022 Jan 11.

From the Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province Department of Radiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.

Abstract: Primary breast lymphoma is a rare form of extranodal lymphoma. We report 18F-FDG and 68Ga-DOTA-FAPI-04 PET/CT findings of breast lymphoma in a 60-year-old woman. Both breast ultrasound and mammogram showed a mass in the right breast and suggested that the mass might be a malignant tumor. She was referred for an 18F-FDG PET/CT scan and subsequently recruited in our 68Ga-DOTA-FAPI-04 PET/CT trial. Both scans revealed the breast mass with intense tracer uptake. Biopsy and immunohistochemical examinations of the mass confirmed the diagnosis of diffuse large B-cell lymphoma.
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http://dx.doi.org/10.1097/RLU.0000000000003961DOI Listing
January 2022

The Value of Meteorological Data in Optimizing the Pattern of Physical Load-A Forecast Model of Rowing Pacing Strategy.

Int J Environ Res Public Health 2021 Dec 29;19(1). Epub 2021 Dec 29.

Division of Sports Science and Physical Education, Tangshan Polytechnic College, Tangshan 063299, China.

Mastering the information of arena environment is the premise for athletes to optimize their patterns of physical load. Therefore, improving the forecast accuracy of the arena conditions is an urgent task in competitive sports. This paper excavates the meteorological features that have great influence on outdoor events such as rowing and their influence on the pacing strategy. We selected the meteorological data of Tokyo from 1979 to 2020 to forecast the meteorology during the Tokyo 2021 Olympic Games, analyzed the athletes' pacing choice under different temperatures, humidity and sports levels, and then recommend the best pacing strategy for rowing teams of China. The model proposed in this paper complements the absence of meteorological features in the arena environment assessment and provides an algorithm basis for improving the forecast performance of pacing strategies in outdoor sports.
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http://dx.doi.org/10.3390/ijerph19010320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750911PMC
December 2021

Effects of Overexpression of Fibroblast Growth Factor 15/19 on Hepatic Drug Metabolizing Enzymes.

Drug Metab Dispos 2021 Dec 29. Epub 2021 Dec 29.

Pharmacology and Toxicology, Rutgers University, United States

Fibroblast growth factor 15/19 (FGF15/19) are endocrine growth factors that play an important role in bile acid homeostasis. FGF15/19 based therapies are currently being tested in clinical trials for the treatment of non-alcoholic steatohepatitis and cholestatic liver diseases. To determine the physiological impact of long-term elevations of FGF15/19, we developed a transgenic mouse model to overexpress ( Tg). In the current study, RNA-seq analysis revealed elevations of the expression of several genes encoding phase I drug metabolizing enzymes, including and , in Tg mice. We found that the induction of several isoforms resulted in increased function of CYP2B in microsomal metabolism and pharmacokinetics studies. Because CYP2B family is known to be induced by constitutive androstane receptor (CAR), to determine the role of CAR in the observed inductions, we crossed Tg mice with CAR knockout mice and found that CAR played a minor role in the observed alterations in drug metabolizing enzyme expression. Interestingly, we found that the overexpression of resulted in a phenotypical switch from a male hepatic expression pattern of drug metabolizing enzymes in wild type mice to a female expression pattern in Tg mice. Growth hormone differences between males and females is known to drive sexually dimorphic expression patterns in the livers of rodents in a STAT5b dependent manner. We found that male Tg mice presented with many features similar to wild type female mice, including lowered body length and weight, and expression, and STAT5 signaling. The overexpression of in mice causes an alteration in DMEs at the mRNA, protein, and functional levels, which is not entirely due to CAR activation but associated with lower GH signaling.
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http://dx.doi.org/10.1124/dmd.121.000416DOI Listing
December 2021

PACS-2 attenuates diabetic kidney disease via the enhancement of mitochondria-associated endoplasmic reticulum membrane formation.

Cell Death Dis 2021 11 26;12(12):1107. Epub 2021 Nov 26.

NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300134, Tianjin, China.

The altered homeostasis of mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) was closely associated with the pathological process of nervous system diseases and insulin resistance. Here, the exact implication of phosphofurin acidic cluster sorting protein 2 (PCAS-2), an anchor protein in the MAM interface, in diabetic kidney disease was investigated. In the kidneys of type 1 and type 2 diabetes mice and HG-induced HK-2 cells, a notable disruption of ER-mitochondria interactions, accompanied by a decreased PACS-2 expression in all subcellular fractions. Furthermore, PACS-2 knockout mice with diabetes displayed accelerated development of proteinuria, deterioration of kidney function, and aggravated disruption of MAM area, ER stress, mitochondrial dysfunction, renal apoptosis, and fibrosis. However, overexpression of PACS-2 effectively protected diabetic kidneys and HG-treated HK-2 cells from renal tubular impairments. Importantly, experimental uncoupling of ER-mitochondria contacts reversed the protective effects of PACS-2 restoration on HK-2 cells under HG conditions. In summary, our data indicate a pivotal role of PACS-2 in the development of diabetic renal tubular injury via the stabilization of MAM.
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http://dx.doi.org/10.1038/s41419-021-04408-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626491PMC
November 2021

Sensor-Based Fall Risk Assessment: A Survey.

Healthcare (Basel) 2021 Oct 27;9(11). Epub 2021 Oct 27.

School of Computer and Communication Engineering, University of Science and Technology Beijing, Beijing 100089, China.

Fall is a major problem leading to serious injuries in geriatric populations. Sensor-based fall risk assessment is one of the emerging technologies to identify people with high fall risk by sensors, so as to implement fall prevention measures. Research on this domain has recently made great progress, attracting the growing attention of researchers from medicine and engineering. However, there is a lack of studies on this topic which elaborate the state of the art. This paper presents a comprehensive survey to discuss the development and current status of various aspects of sensor-based fall risk assessment. Firstly, we present the principles of fall risk assessment. Secondly, we show knowledge of fall risk monitoring techniques, including wearable sensor based and non-wearable sensor based. After that we discuss features which are extracted from sensors in fall risk assessment. Then we review the major methods of fall risk modeling and assessment. We also discuss some challenges and promising directions in this field at last.
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http://dx.doi.org/10.3390/healthcare9111448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624006PMC
October 2021

Ocular Biometry of Primary Angle-Closure Disease in Younger Patients.

Front Med (Lausanne) 2021 3;8:772578. Epub 2021 Nov 3.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

The purpose of this study was to analyze the ocular biometric parameters of primary angle-closure disease (PACD) in younger patients and compare them with those of elderly patients. This clinic-based, cross-sectional study included 154 eyes of 154 patients with PACD, consisting of 77 eyes of patients aged 40 years or younger and 77 eyes of patients older than 40. The PACD case definition was compatible with the ISGEO definition. Anterior segment parameters were measured by ultrasound biomicroscopy, axial length (AL) and lens thickness (LT) were measured by A-scan ultrasonography measurements, and the thickness of the retina and choroid were measured by optical coherence tomography. The differences in ocular biometric parameters between different age groups were compared by independent sample tests or Mann-Whitney tests, and the correlation between the parameters and age was analyzed. Compared to older PACD patients, the lens vault(LV),LV/LT and subfoveal choroidal thickness (SFCT) of younger patients were larger, while the peripheral and mean iris thickness (IT), trabecular-ciliary angle (TCA), ciliary body thickness (CBT), AL and LT were smaller (all < 0.01). There was no significant difference in anterior chamber depth, anterior chamber width, pupil diameter, angle opening distance at 500 μm from the scleral spur, anterior chamber angle and iris convexity between the two groups (all > 0.05). AL, LT, IT, TCA and CBT were positively associated with age (all < 0.001), while LV and SFCT were negatively associated with age ( = 0.027 and < 0.001, respectively). Compared with elderly patients, younger PACD patients had more anteriorly positioned lenses, thinner and more anteriorly rotated ciliary bodies, thicker choroids, and shorter axial length. These characteristics might be important anatomical bases for the earlier onset of PACD and the higher risk of malignant glaucoma after filtering surgery.
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http://dx.doi.org/10.3389/fmed.2021.772578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595477PMC
November 2021

The association between serum ferritin levels and malignant intraductal papillary mucinous neoplasms.

BMC Cancer 2021 Nov 20;21(1):1253. Epub 2021 Nov 20.

Department of Radiology, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun road, Hangzhou, 310003, China.

Background: Serum ferritin levels are elevated in many malignancies. In this study, we showed the performance of serum ferritin in identifying malignant intraductal papillary mucinous neoplasms (IPMNs).

Methods: A total of 151 patients with pathologically confirmed IPMNs were enrolled. Serum tumor biomarker (carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA)) levels and serum ferritin levels were recorded. Lesion location, tumor size, diameter of the main pancreatic duct (MPD), mural nodule, and IPMN type, were collected from imaging examinations. IPMNs with high grade dysplasia and associated invasive carcinoma were considered malignant IPMNs.

Results: Serum ferritin levels in patients with malignant IPMNs were higher than those in patients with nonmalignant IPMNs (p <  0.05). Serum ferritin was an independent factor for the occurrence of malignant IPMNs (odds ratio (OR) = 1.18, 95% confidence interval (CI):1.01-1.39). A similar trend was found between high serum ferritin (> 149 ng/ml) and malignant IPMNs (OR = 5.64, 95% CI:1.78-17.92). The area under the curve (AUC) of serum ferritin was higher than that of CEA and CA19-9 in identifying malignant IPMNs (AUC = 0.67 vs. AUC = 0.58, 0.65). The combination of serum ferritin with IPMN type showed a similar performance to MPD diameter and the combination of serum CA19-9 with IPMN types in identifying malignant IPMNs (AUC = 0.78 vs. AUC = 0.79, 0.77) and invasive carcinoma (AUC = 0.77 vs. AUC = 0.79, 0.79).

Conclusions: Elevated serum ferritin is a factor associated with malignant IPMNs. Serum ferritin may be a useful marker for identifying malignancy in IPMNs.
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http://dx.doi.org/10.1186/s12885-021-08986-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606075PMC
November 2021

CD44 promotes hepatocellular carcinoma progression via upregulation of YAP.

Exp Hematol Oncol 2021 Nov 19;10(1):54. Epub 2021 Nov 19.

School of Life Sciences, Nanjing Normal University, Nanjing, China.

Hepatocellular carcinoma (HCC) is a common malignancy in human. CD44 is a transmembrane glycoprotein which is frequently overexpressed in cancer of various origins. The function and mechanism of CD44 in HCC remains elusive. In this study, we reported that CD44 was overexpressed in HCC to promote the proliferation and migration of HCC cells via oncogenic YAP, which is the key downstream regulator in Hippo pathway. These findings suggest that CD44-YAP is a probable important axis in pathogenesis of HCC, providing an insight in to HCC pathogenesis as well as potential targets for the intervention of HCC.
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http://dx.doi.org/10.1186/s40164-021-00247-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8603576PMC
November 2021

Clinical and Ultrasound Biomicroscopic Characteristics of Congenital Fibrovascular Pupillary Membrane-Induced Secondary Glaucoma.

Front Med (Lausanne) 2021 28;8:763137. Epub 2021 Oct 28.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

The purpose of this study was to describe and summarize the clinical features of congenital fibrovascular pupillary membrane-induced secondary glaucoma (CFPMSG). Cross-sectional case series. Eyes of 32 patients with CFPMSG were enrolled. Demographic data, including gender, laterality, age at presentation, and age at onset of glaucoma were collected. Patients underwent comprehensive ophthalmic examinations and ultrasound biomicroscopy (UBM). CFPMSG eyes were classified into three groups based on UBM findings and intergroup analysis was performed using ANOVA. The average age at presentation was 2.4 ± 4.6 months (mean ± SD) and at glaucoma onset was 3.8 ± 4.5 months. Compared to normal fellow eyes, all affected eyes had increased intraocular pressure (IOP), axial length, corneal diameter, and central corneal thickness, and decreased anterior chamber depth (ACD) (all ≤ 0.001). Twenty-two affected eyes (68.8%) had evidence of glaucomatous optic neuropathy. Based on iris configuration on UBM, eyes were classified as 53% type I ("U" shape), 34% type II ("Y" shape), and 13% type III (no anterior chamber). IOP in types II (33.8 ± 5.9 mmHg) and III (35.2 ± 5.9 mmHg) was significantly higher than in type I eyes (26.5 ± 5.1 mmHg). The ACD was shallower in type II compared to type I ( = 0.045). Congenital fibrovascular pupillary membrane-induced secondary glaucoma is characterized by ocular hypertension, corneal enlargement and edema, axial length elongation, and glaucomatous optic neuropathy. Glaucoma in this condition is secondary to pupillary block and angle-closure. UBM provides important information for the diagnosis and classification of CFPMSG. This novel classification system demonstrated varying levels of severity and may guide on management of this disease.
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http://dx.doi.org/10.3389/fmed.2021.763137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581037PMC
October 2021

Empagliflozin Induces White Adipocyte Browning and Modulates Mitochondrial Dynamics in KK Cg-Ay/J Mice and Mouse Adipocytes.

Front Physiol 2021 27;12:745058. Epub 2021 Oct 27.

NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin, China.

White adipose tissue (WAT) browning is a promising target for obesity prevention and treatment. Empagliflozin has emerged as an agent with weight-loss potential in clinical and studies, but the mechanisms underlying its effect are not fully understood. Here, we investigated whether empagliflozin could induce WAT browning and mitochondrial alterations in KK Cg-Ay/J (KKAy) mice, and explored the mechanisms of its effects. Eight-week-old male KKAy mice were administered empagliflozin or saline for 8 weeks and compared with control C57BL/6J mice. Mature 3T3-L1 adipocytes were treated in the presence or absence of empagliflozin. Mitochondrial biosynthesis, dynamics, and function were evaluated by gene expression analyses, fluorescence microscopy, and enzymatic assays. The roles of adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-γ coactivator-1-alpha (PGC-1α) were determined through AICAR (5-Aminoimidazole-4-carboxamide1-β-D-ribofuranoside)/Compound C and RNA interference, respectively. Empagliflozin substantially reduced the bodyweight of KKAy mice. Mice treated with empagliflozin exhibited elevated cold-induced thermogenesis and higher expression levels of uncoupling protein 1 (UCP1) and other brown adipose tissue signature proteins in epididymal and perirenal WAT, which was an indication of browning in these WAT depots. At the same time, empagliflozin enhanced fusion protein mitofusin 2 (MFN2) expression, while decreasing the levels of the fission marker phosphorylated dynamin-related protein 1 (Ser616) [p-DRP1 (Ser616)] in epididymal and perirenal WAT. Empagliflozin also increased mitochondrial biogenesis and fusion, improved mitochondrial integrity and function, and promoted browning of 3T3-L1 adipocytes. Further, we found that AMPK signaling activity played an indispensable role in empagliflozin-induced browning and mitochondrial biogenesis, and that PGC-1α was required for empagliflozin-induced fusion. Whether empagliflozin activates AMPK by inhibition of SGLT2 or by independent mechanisms remains to be tested. Our results suggest that empagliflozin is a promising anti-obesity treatment, which can immediately induce WAT browning mitochondrial biogenesis, and regulate mitochondrial dynamics.
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http://dx.doi.org/10.3389/fphys.2021.745058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578598PMC
October 2021

Characteristic phenotype of Chinese patients with adult-onset diabetes who are autoantibody positive by 3-Screen ICA™ ELISA.

Acta Diabetol 2021 Sep 17. Epub 2021 Sep 17.

NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.

Aims: To assess the prevalence of diabetes-associated autoantibodies in Chinese patients recently diagnosed with adult-onset diabetes and to evaluate the potential role of the autoantibody markers for characterization of disease phenotype in the patient population.

Methods: The study included 1273 recent-onset adult patients with phenotypic type 2 diabetes mellitus (T2DM). Serum samples were tested using the 3-Screen ICA™ ELISA (3-Screen) designed for combined measurement of GADAb and/or IA-2Ab and/or ZnT8Ab. 3-Screen positive samples were then tested for individual diabetes-associated and other organ-specific autoantibodies. Clinical characteristics of patients positive and negative in 3-Screen were analysed.

Results: Forty-four (3.5%) of the T2DM patients were positive in 3-Screen, and 38 (86%) of these were also positive for at least one of GADAb, IA-2Ab and ZnT8Ab in assays for the individual autoantibodies. 3-Screen positive patients had lower BMI, higher HbA1c, lower fasting insulin levels and lower fasting C-peptide levels compared to 3-Screen negative patients. Analysis using a homeostatic model assessment (HOMA2) indicated that HOMA2-β-cell function was significantly lower for the forty-four 3-Screen positive patients compared to 3-Screen negative patients. Twenty (45%) 3-Screen positive patients were also positive for at least one thyroid autoantibody.

Conclusions: The 3-Screen ELISA has been used successfully for the first time in China to detect diabetes autoantibodies in patients with phenotypic T2DM. 3-Screen positive patients presented with poorer β cell function.
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http://dx.doi.org/10.1007/s00592-021-01778-8DOI Listing
September 2021

Development and Validation of a Prevalence Model for Latent Autoimmune Diabetes in Adults (LADA) Among Patients First Diagnosed with Type 2 Diabetes Mellitus (T2DM).

Med Sci Monit 2021 Sep 15;27:e932725. Epub 2021 Sep 15.

Aging Research Center, Department Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Sweden, Sweden.

BACKGROUND We designed this study to develop and validate a prevalence model for latent autoimmune diabetes in adults (LADA) among people initially diagnosed with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS The study recruited 930 patients aged ≥18 years who were diagnosed with T2DM within the past year. Demographic information, medical history, and clinical biochemistry records were collected. Logistic regression was used to develop a regression model to distinguish LADA from T2DM. Predictors of LADA were identified in a subgroup of patients (n=632) by univariate logistic regression analysis. From this we developed a prediction model using multivariate logistic regression analysis and tested its sensitivity and specificity among the remaining patients (n=298). RESULTS Among 930 recruited patients, 880 had T2DM (96.4%) and 50 had LADA (5.4%). Compared to T2DM patients, LADA patients had fewer surviving b cells and reduced insulin production. We identified age, ketosis, history of tobacco smoking, 1-hour plasma glucose (1hPG-AUC), and 2-hour C-peptide (2hCP-AUC) as the main predictive factors for LADA (P<0.05). Based on this, we developed a multivariable logistic regression model: Y=-8.249-0.035(X1)+1.755(X2)+1.008(X3)+0.321(X4)-0.126(X5), where Y is diabetes status (0=T2DM, 1=LADA), X1 is age, X2 is ketosis (1=no, 2=yes), X3 is history of tobacco smoking (1=no, 2=yes), X4 is 1hPG-AUC, and X5 is 2hCP-AUC. The model has high sensitivity (78.57%) and selectivity (67.96%). CONCLUSIONS This model can be applied to people newly diagnosed with T2DM. When Y ≥0.0472, total autoantibody screening is recommended to assess LADA.
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http://dx.doi.org/10.12659/MSM.932725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8451248PMC
September 2021

Analysis of Primary Iris and Ciliary Body Cysts in Chinese Patients With Primary Angle Closure Disease.

Front Med (Lausanne) 2021 26;8:704200. Epub 2021 Aug 26.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

To investigate the incidence and clinical features of primary iris and ciliary body cysts in Chinese primary angle closure disease (PACD). Patients were evaluated by measuring and analyzing the cysts with an ultrasound biomicroscope (UBM). The data of patients diagnosed with PACD were reviewed. Demographic data were collected, and the cyst number, size, location, and trabecular-iris angle (TIA) were measured, with the size including the longest diameter (LD) and its corresponding vertical diameter (CVD). A total of 1,334 cases (2,317 eyes) were reviewed, and 409 cysts were found in 131 cases (168 eyes), with an average of 2.43 ± 3.14 cysts per eye. The ages of the patients with cysts ranged from 25 to 80 years, with an average age of 55.24 ± 12.22 years. The detection rate was 7.3%, and the majority of cysts were located in the iridociliary sulcus. Among the 131 patients, 94 had monocular cysts, while binocular cysts occurred in 37 patients. The locations of the cysts in both eyes were mainly in the inferior and temporal quadrants (42.5 and 34.0%, respectively). The cysts were mainly of medium size (49.9%), followed by small cysts (33.3%), large cysts (14.7%) and giant cysts (2.2%). The average LD was 0.68 ± 0.33 mm, and the average CVD was 0.45 ± 0.23 mm. There were no statistically significant differences in the TIA between the cyst area and unaffected area. The incidence of cysts is 7.3% in the PACD population. The cysts are mainly monocular, medium in size, and located in the iridociliary sulcus. Additionally, the cysts were located mainly in the inferior and temporal quadrants. These cysts have little effect on the anterior chamber angle.
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http://dx.doi.org/10.3389/fmed.2021.704200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426632PMC
August 2021

Coherent confocal light scattering spectroscopic microscopy evaluates cancer progression and aggressiveness in live cells and tissue.

ACS Photonics 2021 Jul 20;8(7):2050-2059. Epub 2021 Jun 20.

Center for Advanced Biomedical Imaging and Photonics, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University.

The observation of biological structures in live cells beyond the diffraction limit with super-resolution fluorescence microscopy is limited by the ability of fluorescence probes to permeate live cells and the effect of these probes, which are often toxic, on cellular behavior. Here we present a coherent confocal light scattering and absorption spectroscopic microscopy that for the first time enables the use of large numerical aperture optics to characterize structures in live cells down to 10 nm spatial scales, well beyond the diffraction limit. Not only does this new capability allow high resolution microscopy with light scattering contrast, but it can also be used with almost any light scattering spectroscopic application which employs lenses. We demonstrate that the coherent light scattering contrast based technique allows continuous temporal tracking of the transition from non-cancerous to an early cancerous state in live cells, without exogenous markers. We also use the technique to sense differences in the aggressiveness of cancer in live cells and for label free identification of different grades of cancer in resected tumor tissues.
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http://dx.doi.org/10.1021/acsphotonics.1c00217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411902PMC
July 2021

Typhoon-induced turbulence redistributed microplastics in coastal areas and reformed plastisphere community.

Water Res 2021 Oct 19;204:117580. Epub 2021 Aug 19.

School of Environmental Science and Engineering, College of Engineering, Southern University of Science and Technology, Shenzhen 518055, China; State Environmental Protection Key Laboratory of Integrated Surface Water-Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China; Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China. Electronic address:

The increasing microplastic pollution together with the plastisphere-associated ecological threats in coastal areas have aroused global concern. Tropical cyclones have been increased in both frequency and intensity under global warming, causing intense impact on the microplastics distribution and the structure of coastal ecosystems. However, until most currently, the extent to which typhoon impacts the microplastics and plastisphere community remains poorly known. This study analyzed the effects of Typhoon Wipha (Code: 1907) on microplastics abundance and composition in surface water and sediment crossed coastal areas of Shenzhen. Here we found a significant typhoon-induced increase in microplastics abundance in surface water, whereas an opposite trend was observed in sediment. Despite the evident transportation of microplastics from sediment to surface water by agitation, a possible microplastics influx was introduced by typhoon as evidenced by the large attribution of unknown force in source tracking analysis. Furthermore, typhoon had adeptly uniformed the plastisphere community in the sediment along the 190 km costal line overnight. A significant increase of nitrogen fixer, Bradyrhizobiaceae, was observed ubiquitously after typhoon, which might alter the nitrogen cycling and increase eutrophic condition of the coastal ecological system. Together, this study expanded the knowledge about the impact of typhoon-induced influx of the microplastics on coastal biogeochemical cycling. Moreover, the microplastics and the plastisphere compositional pattern revealed here will underpin future studies on adsorption behavior, interfacial processes and ecotoxicity of the coastal microplastic pollution.
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http://dx.doi.org/10.1016/j.watres.2021.117580DOI Listing
October 2021

Predictive Equation for Angle Opening Distance at 750 μm After Laser Peripheral Iridotomy in Primary Angle Closure Suspects.

Front Med (Lausanne) 2021 12;8:715747. Epub 2021 Aug 12.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

The aim of this study was to investigate the changes in anterior segment parameters as assessed by ultrasound biomicroscopy (UBM) after laser peripheral iridotomy (LPI) and to propose a prediction equation for the width of the angle after LPI. This was a prospective study. The participants included 100 subjects with primary angle closure suspect (PACS). Anterior segment UBM parameters were measured, whereas AOD750 was chosen to indicate the width of the angle associated with gonioscopic angle closure, as found in a prior study. Angle parameters, iris parameters, anterior chamber parameters and ciliary body parameters. All angle parameters increased after LPI, including the mean angle opening distance at 750 μm (AOD750), mean angle opening distance at 500 μm from the scleral spur (AOD500), mean angle opening distance at 750 μm from the scleral spur (AOD750), and mean angle recess area at 750 μm from the scleral spur (ARA750). Among iris parameters and ciliary body parameters, the iris thickness at 2,000 μm (IT2000), iris curvature (IC), and trabecular-ciliary process distance (ICPD) were reduced after LPI. The final equation consisted of four parameters: anterior chamber depth (ACD), iris thickness at 750 μm from the scleral spur (IT750), AOD750, and lens vault (LV). This equation explained 42.7% of the variability in the angle opening indicator AOD750 after LPI, whereas in the plateau iris configuration subgroup, the accuracy of the prediction equation reached the highest a maximum of 68.6%. There was an increase in angle opening and iris flattening after LPI. An equation involving four angle parameters was constructed, this equation which could explained 42.7% of the variability in the angle opening indicator AOD750 after LPI whereas in the plateau iris configuration subgroup, the accuracy of the prediction equation reached a maximum of 68.6%.
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http://dx.doi.org/10.3389/fmed.2021.715747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387715PMC
August 2021

Interaction of Hepatitis B Virus X Protein with the Pregnane X Receptor Enhances the Synergistic Effects of Aflatoxin B1 and Hepatitis B Virus on Promoting Hepatocarcinogenesis.

J Clin Transl Hepatol 2021 Aug 19;9(4):466-476. Epub 2021 Apr 19.

Department of Pharmacology, Shantou University Medical College, Shantou, Guangdong, China.

Background And Aims: Hepatitis B virus (HBV) infection has been found to increase hepatocellular sensitivity to carcinogenic xenobiotics, by unknown mechanisms, in the generation of hepatocellular carcinoma. The pregnane X receptor (PXR) is a key regulator of the body's defense against xenobiotics, including xenobiotic carcinogens and clinical drugs. In this study, we aimed to investigate the molecular mechanisms of HBV X protein (HBx)-PXR signaling in the synergistic effects of chemical carcinogens in HBV-associated hepatocarcinogenesis.

Methods: The expression profile of PXR-cytochrome p450 3A4 (CYP3A4) signaling was determined by PCR, western blotting, and tissue microarray. Cell viability and aflatoxin B1 (AFB1) cytotoxicity were measured using the cell counting kit-8 assay. Target gene expression was evaluated using transient transfection and real time-PCR. The genotoxicity of AFB1 was assessed in newborn mice with a single dose of AFB1.

Results: HBx enhanced the hepatotoxicity of AFB1 by activating CYP3A4 and reducing glutathione S-transferase Mu 1 (GSTM1) in cell lines. Activation of PXR by pregnenolone 16α-carbonitrile increased AFB1-induced liver tumor incidence by up-regulating oncogenic KRAS to enhance interleukin (IL)-11:IL-11 receptor subunit alpha-1 (IL11RA-1)-mediated inflammation in an HBx transgenic model.

Conclusions: Our finding regarding AFB1 toxicity enhancement by an HBx-PXR-CYP3A4/ GSTM1-KRAS-IL11:IL11RA signaling axis provides a rational explanation for the synergistic effects of chemical carcinogens in HBV infection-associated hepatocarcinogenesis.
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http://dx.doi.org/10.14218/JCTH.2021.00036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369009PMC
August 2021

Spectroscopic label-free microscopy of changes in live cell chromatin and biochemical composition in transplantable organoids.

Sci Adv 2021 Aug 18;7(34). Epub 2021 Aug 18.

Center for Advanced Biomedical Imaging and Photonics, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA.

Organoids formed from human induced pluripotent stem cells (hiPSCs) could be a limitless source of functional tissue for transplantations in many organs. Unfortunately, fine-tuning differentiation protocols to form large quantities of hiPSC organoids in a controlled, scalable, and reproducible manner is quite difficult and often takes a very long time. Recently, we introduced a new approach of rapid organoid formation from dissociated hiPSCs and endothelial cells using microfabricated cell-repellent microwell arrays. This approach, when combined with real-time label-free Raman spectroscopy of biochemical composition changes and confocal light scattering spectroscopic microscopy of chromatin transition, allows for monitoring live differentiating organoids without the need to sacrifice a sample, substantially shortening the time of protocol fine-tuning. We used this approach to both culture and monitor homogeneous liver organoids that have the main functional features of the human liver and which could be used for cell transplantation liver therapy in humans.
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http://dx.doi.org/10.1126/sciadv.abj2800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373132PMC
August 2021

Ultrasound Biomicroscopy Might Predict the Outcome of Phacoemulsification-Visco Dissection in Medically Controlled Primary Angle-Closure Glaucoma Eye With Extensive Peripheral Anterior Synechia.

Front Med (Lausanne) 2021 19;8:705864. Epub 2021 Jul 19.

State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

The treatment procedures of primary angle-closure glaucoma (PACG) with extensive peripheral anterior synechia (PAS) is a subject of debate. This study is to investigate the clinical features of phacoemulsification (Phaco)-visco dissection in medically controlled PACG patients with PAS > 180° and evaluate the predictability of Ultrasound Biomicroscopy (UBM) parameters on postoperative intraocular pressure (IOP). 48 eyes (48 patients) with acute angle-closure glaucoma (AACG) and 30 eyes (30 patients) with chronic angle-closure glaucoma (CACG) were prospectively included. All patients underwent phaco-viscogoniolysis and foldable lens implantation and were followed for 1 year after surgery. We analyzed preoperative and postoperative IOP, the numbers of anti-glaucoma medicine, the visual field value, the extent of PAS, and UBM parameters alterations, and evaluated the correlation between preoperative UBM parameters and one-year postoperative IOP. IOP reduced significantly from 16.24 ± 4.33 to 14.49 ± 3.69 mmHg in AACG group and from 16.16 ± 3.69 mmHg to 14.31 ± 4.12 mmHg in CACG group, and PAS decreased significantly from 270 ± 60.33 to 171 ± 56.44° in AACG group and from 285 ± 70.46 to 168 ± 61.32° in CACG group, and the number of anti-glaucoma drugs decreased significantly in both groups. Several UBM parameters, including anterior chamber depth, trabecular iris angle, and peripheral iris thickness 500 increased while iris convex reduced considerably in the two groups, and angle opening distance 500 and trabecular-meshwork ciliary process angle increased significantly only in AACG group. One-year postoperative IOP correlated with preoperative angle opening distance 500 and trabecular iris angle negatively and iris convex positively. Phaco-visco dissection can effectively reduce IOP, the numbers of glaucomatous medications, and PAS in medically controlled PACG patients with extensive PAS. UBM parameters might be valuable for analyzing postoperative anterior segment structure and predicting postoperative IOP of Phaco-visco dissection in PACG patients with extensive PAS.
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http://dx.doi.org/10.3389/fmed.2021.705864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326522PMC
July 2021

Cost-Effectiveness Analysis of a Mobile-Based Intervention for Patients with Type 2 Diabetes Mellitus.

Int J Endocrinol 2021 1;2021:8827629. Epub 2021 Jul 1.

National Health Commission Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, No 6, Huanruibei Road, Beichen District, Tianjin 300134, China.

Objective: The aim of this study was to evaluate the cost effectiveness of a mobile-based intervention for patients with type 2 diabetes mellitus (T2DM) and compare it with the usual management mode.

Method: A total of 215 patients with T2DM in a tertiary-care hospital specific to diabetes were selected as the study population. This study was conducted from January 1, 2019 to January 1, 2020. Of the 215 patients, 130 were randomly assigned to the mHealth group and 85 were assigned to the usual care group. IBM SPSS 25.0 software was used for descriptive statistics, tests, chi-square tests, and correlation analyses. Haemoglobin A1c (HbA1c) was the effectiveness parameter adopted. Cost-effectiveness analyses were performed, and incremental cost-effectiveness ratios (ICERs) were calculated.

Results: Of the 215 patients with T2DM, the proportion of male patients was 66.0%. The mean age of the patients was 47.2 (SD 9.95). Differences in baseline information were not statistically significant between the two groups ( > 0.05). At the 3-, 6-, and 12-month follow-ups, the mHealth group reported higher control rates of HbA1c than the usual care group, 67.9% versus 46.2% ( < 0.001), 72.4% versus 45.4% ( < 0.001), and 74.6% versus 47.1% ( < 0.001), respectively. The value of HbA1c was positively related to total patient cost, material fee, Western medicine fee, and hospitalization expenses ( < 0.05), with correlation coefficients of 0.202, 0.200, 0.172, and 0.183, respectively. The costs of the mHealth group and usual care group were CNY¥ 1169.76 and CNY¥ 1775.44 per patient/year, respectively. The incremental cost of the mHealth intervention was CNY¥ -605.68 per patient/year. The ICER was CNY¥ -22.02 per patient/year.

Conclusion: Compared with the usual care mode, the mHealth management model for patients with T2DM improved the control rate of HbA1c, and the mHealth management mode had better cost effectiveness.
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http://dx.doi.org/10.1155/2021/8827629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266460PMC
July 2021

Prostaglandin F2α protects against pericyte apoptosis by inhibiting the PI3K/Akt/GSK3β/β-catenin signaling pathway.

Ann Transl Med 2021 Jun;9(12):1021

NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.

Background: Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the main cause of non-traumatic blindness in adults. Pericyte loss is known to be an early pathological change of DR. Our group's previous research indicated that prostaglandin F2α (PGF2α) acts as an eicosanoidal protector against non-proliferative DR that can regulate the mobility of pericytes in a RhoA-mediated manner. However, the effect of PGF2α on pericyte apoptosis has yet to be described.

Methods: Two animal models were constructed: a high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetes mouse model and a spontaneous type 2 diabetes db/db mouse model. We analyzed pathological changes, and performed TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining and western blot to detect apoptosis in the retinas of diabetic mice. For our experiments, we selected human retinal pericytes and subjected them to high-glucose (HG), PGF2α, and AL8810 (an antagonist of the PGF2α receptor) treatment. Subsequently, apoptosis and the levels of PI3K/Akt/GSK3β/β-catenin pathway-related proteins were detected by TUNEL staining and western blot, respectively.

Results: The levels of apoptosis were increased in the retinas of diabetic mice in both T2DM models. , HG treatment increased apoptosis and inhibited PI3K/Akt/GSK3β/β-catenin signaling in pericytes. In contrast, PGF2α treatment inhibited pericyte apoptosis while increasing the levels of the PI3K, p-Akt/t-Akt, p-GSK3β/t-GSK3β, and β-catenin proteins; however, these PGF2α-induced effects were eliminated by ALL80.

Conclusions: PGF2α may make a key contribution to reducing pericyte apoptosis and protecting against DR via its inhibition of the PI3K/Akt/GSK3β/β-catenin signaling pathway.
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http://dx.doi.org/10.21037/atm-21-2717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267281PMC
June 2021

Can Mandatory Disclosure Policies Promote Corporate Environmental Responsibility?-Quasi-Natural Experimental Research on China.

Int J Environ Res Public Health 2021 06 3;18(11). Epub 2021 Jun 3.

School of Finance and Statistics, Hunan University, Changsha 410079, China.

Corporate environmental responsibility (CER) is an important component of the corporate social responsibility (CSR) report, and an important carrier for enterprises to disclose environmental protection information. Based on the corporate micro data, this paper evaluates the effect of a mandatory CSR disclosure policy on the fulfillment of corporate environmental responsibility by adopting the difference-in-differences model (DID) with the release of a mandatory disclosure policy of China in 2008 as a quasi-natural experiment. The study draws the following conclusions: First, a mandatory CSR disclosure policy can promote the fulfillment of CER. Second, after the implementation of a mandatory CSR disclosure policy, enterprises can improve their CER level through two channels: improving the quality of environmental management disclosure and increasing the number of patents. Third, the heterogeneity of the impacts of mandatory CSR disclosure on CER is reflected in three aspects: different CER levels, different corporate scales and a different property rights structure. In terms of the CER level, there is an inverted U-shaped relationship between the CER level and mandatory CSR disclosure effect. In terms of the corporate scale, mandatory disclosure of CSR plays a greater role in large-scale enterprises. In terms of the structure of property rights, mandatory CSR disclosure has a greater effect on non-state-owned enterprises.
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http://dx.doi.org/10.3390/ijerph18116033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199984PMC
June 2021

Effects of Age and Rice Straw Inclusion Levels in the Diet of Yiling Cull Cows on Growth Performance, Meat Quality, and Antioxidant Status of Tissues.

Animals (Basel) 2021 Jun 10;11(6). Epub 2021 Jun 10.

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.

The objectives of this study were to investigate the effects of age and dietary straw levels on growth performance, carcass and meat traits, as well as tissue antioxidant status of Yiling cull cows. Twenty-four Yiling cull cows were arranged in a 2 × 2 factorial design: two age classes consisting of younger cull cows (YCC; appearing with three or four pairs of permanent teeth) and older cull cows (OCC; worn out teeth); two dietary treatments consisting of lower and higher rice straw levels (LRS and HRS; providing 0.7 kg/d and 1.2 kg/d rice straw per head based on air-dry basis, respectively). Cows were fed twice a day. Straw was offered at half of the predetermined weight each meal; concentrate was separately supplied ad libitum. After 300 d of feeding, final body weight (BW), total BW gain, average daily gain and gain:feed intake were higher ( < 0.01) in the YCC group than in the OCC group. Total dry matter intake was higher ( = 0.03) in the HRS group than in the LRS group, but neutral detergent fiber apparent digestibility was negatively affected ( = 0.01) by increased straw levels. Decreased C15:0, C17:0, C20:5n3c, and saturated fatty acids (SFAs) proportion as well as increased C18:1n9c and monounsaturated fatty acids (MUFAs) proportion in meat from YCC with HRS diet were observed as compared to that in meat from YCC with LRS diet ( < 0.05). Meat from HRS group had higher ( = 0.04) C18:3n3c proportion than meat from LRS group. No significant differences ( > 0.05) were found for meat quality attributes except for cooking loss, which was higher ( = 0.02) in the HRS group than in the LRS group. Both YCC group and HRS group had higher ( < 0.05) cold carcass weight compared to OCC group and LRS group. Moreover, catalase activity of liver tissue was higher ( = 0.045) in YCC than in OCC, while superoxide dismutase activity of muscle tissue was higher ( = 0.01) in LRS than in HRS. Based on results, we concluded that younger age and feeding high-level straw can improve the finishing performance of Yiling cull cows.
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http://dx.doi.org/10.3390/ani11061732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229695PMC
June 2021

Differences in the reaction of hyperlipidemia on different endothelial progenitor cells based on sex.

Biomed Rep 2021 Aug 7;15(2):64. Epub 2021 Jun 7.

Department of Cardiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, P.R. China.

The sex of a patient can affect the outcomes of several cardiovascular diseases, and men generally tend to experience earlier episodes of cardiovascular diseases compared with women. The progression of atherosclerosis during hyperlipidemia can be induced by reactive oxygen species (ROS) and oxidized-low-density lipoprotein (ox-LDL). By contrast, bone marrow (BM)-derived endothelial progenitor cells (EPCs) have been reported to serve a protective role against atherosclerosis. The aim of the present was to compare the effects of sex under conditions of hyperlipidemia on different populations of EPCs, and to identify the potential underlying mechanisms. EPC numbers and ROS levels in the blood and BM were measured using fluorescence activated cell sorting in male and female LDL receptor knock-out C57BL/6 mice maintained on a high-fat diet for 6 months, and in male and female wild type C57BL/6 mice following ox-LDL injection for 3 days. Female hyperlipidemic mice exhibited lower levels of plasma lipids, atherosclerotic plaque formation, intracellular EPC ROS formation and inflammatory cytokine levels. Furthermore, BM CD34/ fetal liver kinase-1 (Flk-1), CD34/CD133 and stem cell antigen-1/Flk-1, as well as all circulating EPCs, were maintained at higher levels in female hyperlipidemic mice. In addition, similar changes with regards to BM CD34/Flk-1, CD34/CD133, c-Kit/CD31 and circulating CD34/Flk1 and CD34/CD133 EPCs were observed in female mice following ox-LDL treatment. These sustained higher levels of BM and circulating EPCs in female mice with hyperlipidemia may be associated with reduced levels of ox-LDL as a result of reduced intracellular ROS formation in EPCs and decreased inflammatory cytokine production.
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http://dx.doi.org/10.3892/br.2021.1440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212447PMC
August 2021

Serum concentrations of per-/polyfluoroalkyl substances and risk of type 2 diabetes: A case-control study.

Sci Total Environ 2021 Sep 30;787:147476. Epub 2021 Apr 30.

Tianjin Medical University Metabolic Diseases Hospital, Tianjin, China.

Per-/polyfluoroalkyl substances (PFASs), as a group of synthetic chemicals, have been extensively detected in human samples. Recently, epidemiological investigations have reported relationships between exposure to PFASs with risk of type 2 diabetes mellitus (T2DM), but with contradictory results. In this study, a case-control study was conducted to explore associations between serum PFASs and T2DM risk among 252 T2DM cases and 252 controls, who were both diagnosed according to fasting glucose and glycosylated hemoglobin levels. Besides, dose-response relationships were analyzed to clarify effects of PFAS exposure on T2DM risk at different exposure levels. Multivariable logistic regression models showed that compared to the lowest tertiles, elevated odds of T2DM risk were observed in the middle tertiles of perfluorohexane sulfonic acid (PFHxS) [odds ratio (OR): 4.09; 95% confidence interval (CI): 2.23, 7.50; p < 0.01] and perfluorohexane sulfonic acid (PFHpA) (OR: 1.87; 95% CI: 1.06, 3.29; p = 0.03), but not in the highest tertiles, and the restricted cubic spline regression models presented inverted U-shaped dose-response relationships for exposure to PFHxS and PFHpA with T2DM risk, indicating non-monotonic dose-response effect and low-dose effect. Most other PFASs were inversely associated with risk of T2DM, especially at higher exposure levels. Our findings suggested that there are associations between exposure to PFASs and risk of T2DM. Further mechanism research is worthy to be conducted to elucidate the mode of action of different PFASs on T2DM at different exposure levels.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147476DOI Listing
September 2021

Perturbation of serum metabolome in relation to type 2 diabetes mellitus and urinary levels of phthalate metabolites and bisphenols.

Environ Int 2021 10 6;155:106609. Epub 2021 May 6.

Tianjin Medical University Metabolic Diseases Hospital, Tianjin, China. Electronic address:

Background: Emerging evidence has proved the associations between exposure to phthalates (PAEs) and bisphenols and type 2 diabetes mellitus (T2DM), but the underlying mechanisms for these associations are poorly understood. Metabolomics is a powerful tool to identify differential metabolites and metabolic pathways related to diseases and chemical exposure, which may reveal underlying mechanisms. However, little is known about the roles of metabolism in the associations for PAE and bisphenol exposure with T2DM.

Objectives: The purpose of the study was to investigate the roles of metabolism in the associations for exposure to PAEs and bisphenols with T2DM.

Methods: In this study, 60 T2DM cases and 60 controls, who were matched in age, sex, and body mass index (BMI), were selected from the total study population in our previous studies. Fasting blood and spot urine samples of the volunteers were used for non-targeted metabolomics analysis and determination of phthalate metabolites (mPAEs) and bisphenols, respectively. The associations of urinary mPAEs and bisphenols with screened metabolic biomarkers in metabolomics analysis were analyzed using multiple linear regression models.

Results: Based on non-targeted metabolomics, 19 serum metabolic biomarkers were screened between T2DM cases and controls, mostly related to galactose metabolism, amino acid metabolism, and pyrimidine metabolism. More than half of mPAEs were mostly positively associated with up-regulated metabolic biomarkers and negatively associated with down-regulated biomarkers. Different from PAEs, no evident results suggested the roles of metabolism in the associations between bisphenol exposure and T2DM.

Conclusions: Combined with the positive associations between most urinary mPAEs and T2DM in our previous study, our findings indicated that PAE exposure may contribute to T2DM risk through disturbing galactose metabolism, amino acid metabolism (especially arginine biosynthesis and alanine, aspartate and glutamate metabolism), and pyrimidine metabolism.
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http://dx.doi.org/10.1016/j.envint.2021.106609DOI Listing
October 2021

Protective Effects of ACEI/ARB on Left Ventricular Function in Anthracycline-Induced Chronic Cardiotoxicity: A Meta-Analysis of Randomized Controlled Trials.

Cardiology 2021;146(4):469-480. Epub 2021 May 4.

Department of Oncology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.

Purpose: Cardiotoxicity is an important side effect of anthracycline. Cardioprotective drugs for anthracycline remain inconclusive. We attempted to determine the role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) in the prevention of anthracycline-induced cardiotoxicity.

Hypothesis: Prophylactic use of ACEI/ARB reduces the clinical or subclinical cardiotoxicity of anthracycline.

Methods: Randomized controlled trials (RCTs) of ACEI/ARB in the prevention of anthracycline-induced cardiotoxicity were obtained by searching Pubmed, Embase, Web of Science, and Cochrane databases. 7 studies were finally included. A meta-analysis was performed on the 7 studies. The end points were changes in left ventricle ejection fraction (LVEF), early and late diastolic peak velocity ratio (E/A), and occurrence of hypotensive events.

Results: Prophylactic use of ACEI/ARB has potential benefits for anthracycline-induced cardiotoxicity. LVEF was better preserved in the experimental group than in the control group (weighted mean difference [WMD] -3.16%, 95% confidence interval [CI] [-5.78, -0.54], p = 0.02). Follow-up time, tumor type, drug type, and geographical region did not affect the results. There was no significant benefit of E/A in the experimental group (WMD 0.02, 95% CI [-0.06, 0.11], p = 0.58), and no increase in the incidence of hypotension (risk ratio 3.79, 95% CI [0.44, 32.89], p = 0.23).

Conclusions: We found that prophylactic use of ACEI/ARB reduced the clinical or subclinical cardiotoxicity of anthracycline, and the increase in hypotensive events was not significant. Due to the relatively small number of clinical studies and participants, more related studies are necessary to further verify our results.
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http://dx.doi.org/10.1159/000512848DOI Listing
August 2021

Low-Temperature Tunneling Electroresistance in Ferromagnetic Metal/Ferroelectric/Semiconductor Tunnel Junctions.

ACS Appl Mater Interfaces 2021 May 4;13(19):23282-23288. Epub 2021 May 4.

Jiangsu Provincial Key Laboratory of Advanced Photonic and Electronic Materials, School of Electronic Science and Engineering, Nanjing University, Nanjing 210093, P. R. China.

Ferroelectric tunnel junctions (FTJs) as artificial synaptic devices are promising candidates for the building block of nonvolatile data storage devices. However, a small ON/OFF ratio of FTJs limits their application in low-temperature operations. In this work, the influence of quantum interference effects on tunneling electroresistance in the LaSrMnO/BaTiO/Nb:SrTiO (ferromagnetic metal/ferroelectric/semiconductor) FTJ at low temperatures is investigated. The Current-voltage curves are observed in the tunnel junction from 300 to 10 K with a six-unit-cell thick BaTiO film by the ferroelectric polarization effect. First, the ON/OFF current ratio increases from 300 to 30 K due to the increase of polarization in the ferroelectric barrier, and then, it gradually decreases when the temperature drops below 30 K. An anomalous ON/OFF current ratio of ∼10 is obtained at 30 K. The low-temperature tunneling properties in the FTJ are associated with a low-temperature resistivity minimum in the ferromagnetic metal layer by the electron-electron interaction, which increases the LaSrMnO/BaTiO interface resistance, leading to a higher resistance state and lower for the OFF state. As a result, the ON/OFF current ratio is abruptly enhanced at 30 K. Our results emphasize the crucial role of transport properties of LaSrMnO in FTJs and pave the way for the design and application of FTJs at low temperatures.
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http://dx.doi.org/10.1021/acsami.1c05366DOI Listing
May 2021
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