Publications by authors named "Fan Hu"

302 Publications

Label-free hairpin probe for the rapid detection of Hg(II) based on T-Hg(II)-T.

Anal Chim Acta 2022 Aug 23;1221:340113. Epub 2022 Jun 23.

Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, People's Republic of China. Electronic address:

A simple thymine-rich mercury-specific oligonucleotide (G9T24C9) was designed to quickly detect Hg(Ⅱ) via thymine-Hg(II)-thymine (T-Hg(Ⅱ)-T) coordination chemistry by using 4',6-diamidinyl-2-phenylindole (DAPI). When the stable GC-paired stem of the DNA hairpin occurred, DPAI could intercalate into the T-Hg(Ⅱ)-T base pairs as a fluorescent recognizer. As a result, the hairpin structure was able to promote the rapid formation of T-Hg(Ⅱ)-T mismatches in the presence of Hg(Ⅱ), trigger DAPI to recognize T-Hg(Ⅱ)-T as well as TA/AT base pairs and restore fluorescence; moreover, fluorescence increases were not observed when Hg(Ⅱ) was not introduced. This method represents a simple strategy to detect Hg(Ⅱ). Taking advantage of the hairpin structure, the fluorescence intensity of the G9T24C9 hairpin probe was positively correlated with the concentration of Hg(Ⅱ) from 2.87 to 1400 nM (R = 0.9968), and the limit of detection (3σ) was as low as 2.87 nM. Furthermore, this probe had high selectivity for Hg(Ⅱ) detection. The probe was applied to real samples of pond water for the detection of Hg(Ⅱ), and a recovery rate from 95.9% to 104.4% was obtained.
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http://dx.doi.org/10.1016/j.aca.2022.340113DOI Listing
August 2022

Melanin-Targeted PET Imaging Sheds Light on Pigment Epithelioma in Corpus Ciliare.

Clin Nucl Med 2022 Sep 12;47(9):839-840. Epub 2022 May 12.

Abstract: A 57-year-old woman had gradually decreased visual acuity in the left eye, accompanied by distension and pain. MRI demonstrated a small neoplasm in corpus ciliare, which promoted PET imaging for further assessment. 18F-FDG PET imaging found no obvious uptake in the lesion. However, melanin-targeted PET imaging demonstrated the lesion with avid 18F-PFPN (18F-N-(2-diethylaminoethyl)-4-(2-[2-ethoxy]-ethoxy)pyridine) accumulation (SUVmax, 7.1), which suggested it with melanin expression. Pigmented epithelial adenoma was further confirmed by pathology. Our case illustrated that pigmented epithelial adenoma is characterized by avid 18F-PFPN accumulations and can be detected even in a hidden location with a size of ≤5 mm.
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http://dx.doi.org/10.1097/RLU.0000000000004268DOI Listing
September 2022

PARP12 is required for mitochondrial function maintenance in thermogenic adipocytes.

Adipocyte 2022 Dec;11(1):379-388

Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, China.

PARP12 is a member of poly-ADP-ribosyl polymerase (PARPs), which has been characterized for its antiviral function. Yet its physiological implication in adipocytes remains unknown. Here, we report a central function of PARP12 in thermogenic adipocytes. We show that PARP12 is highly expressed in brown adipose tissue and is mainly localized to the mitochondria. Knockdown of PARP12 in vitro reduced UCP1 expression. In parallel, the deficiency of PARP12 reduced mitochondrial respiration in adipocytes, while overexpression of PARP12 reversed these effects.
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http://dx.doi.org/10.1080/21623945.2022.2091206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351573PMC
December 2022

Vinpocetine and coenzyme Q10 combination alleviates cognitive impairment caused by ionizing radiation by improving mitophagy.

Brain Res 2022 Jul 27;1792:148032. Epub 2022 Jul 27.

Department of Neurology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, Jiangxi, China. Electronic address:

Objective: This research was designed to ascertain the effect and mechanism of vinpocetine (VIN) and coenzyme Q10 (CoQ10) combination on cognitive impairment induced by ionizing radiation (IR).

Methods: Cognitive impairment in mice was induced by 9-Gy IR, and they were intraperitoneally injected with VIN, CoQ10, or VIN + CoQ10. Then novel object recognition and Morris water maze tests were used to detect cognitive function. The number of hippocampal neurons and BrdUDcx cells was observed by Nissl and immunofluorescence staining. Mitochondrial respiratory complex I, adenosine triphosphate (ATP), and mitochondrial membrane potential (MMP) were evaluated, as well as oxidative stress injury. Mitophagy in hippocampal neurons was evaluated by observing the ultrastructure of hippocampal neurons and assessing the expression of mitophagy-related proteins.

Results: IR reduced novel object discrimination index, the time for platform crossing, and the time spent in platform quadrant, in addition to neuron loss, downregulated levels of mitochondrial respiratory complex I, ATP, and MMP, aggravated oxidative stress injury, increased expression of LC3 II/I, Beclin1, PINK1, and parkin, and decreased P62 expression. VIN or CoQ10 treatment mitigated cognitive dysfunction, neurons loss, mitochondrial damage, and oxidative stress injury, and enhanced mitophagy in hippocampal neurons. VIN and CoQ10 combination further protected against IR-induced cognitive dysfunction than VIN or CoQ10 alone.

Conclusion: VIN combined with CoQ10 improved neuron damage, promoted mitophagy, and ameliorated cognitive impairment in IR mice.
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http://dx.doi.org/10.1016/j.brainres.2022.148032DOI Listing
July 2022

Case Report: Lung Adenocarcinoma Initially Presenting With Cutaneous and Subcutaneous Metastases.

Front Oncol 2022 12;12:925382. Epub 2022 Jul 12.

Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Cutaneous and subcutaneous soft tissue metastases are rare in lung adenocarcinoma and suggest poor prognosis. We report a patient with lung adenocarcinoma who initially presented with cutaneous and subcutaneous metastases to the abdomen that were initially presumed to be herpes zoster and an occult subcutaneous soft tissue mass. Because the lesions progressed over 3 weeks despite routine herpes zoster treatment, magnetic resonance imaging was performed and showed a presumed sarcoma; however, F-fluourodeoxyglucose positron emission tomography/computed tomography demonstrated pulmonary lesions. Biopsy of the abdominal lesion confirmed poorly differentiated lung adenocarcinoma. Early diagnosis of soft tissue metastasis can be difficult. Clinicians should suspect internal organ malignancy when a progressive cutaneous or subcutaneous soft tissue lesion is encountered.
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http://dx.doi.org/10.3389/fonc.2022.925382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316617PMC
July 2022

Correction: Cognitive Impairment in Idiopathic Normal Pressure Hydrocephalus.

Neurosci Bull 2022 Jul 25. Epub 2022 Jul 25.

Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China.

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http://dx.doi.org/10.1007/s12264-022-00922-wDOI Listing
July 2022

Nephroptosis Incidentally Found on 99mTc-DTPA Renal Dynamic Scan.

Clin Nucl Med 2022 Jul 19. Epub 2022 Jul 19.

Health Management Center.

Abstract: Nephroptosis is a significant descent (more than 5 cm or 2 vertebral bodies) of the kidney from supine to the upright position. The incidence of nephroptosis is probably more prevalent than reported, as few patients present with typical symptoms. A 55-year-old woman with intermittent abdominal pain was referred for a 99mTc-DTPA renal dynamic scan. She had a ureteric calculi history. The result showed that the right kidney was significantly lower than the position in the CT scan a week ago. It had been diagnosed as nephroptosis according to these "moving" images. She was considering elective surgery for intervention.
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http://dx.doi.org/10.1097/RLU.0000000000004346DOI Listing
July 2022

Social isolation reinforces aging-related behavioral inflexibility by promoting neuronal necroptosis in basolateral amygdala.

Mol Psychiatry 2022 Jul 15. Epub 2022 Jul 15.

Department of Pathophysiology, Key Lab of Neurological Disorder of Education Ministry, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Aging is characterized with a progressive decline in many cognitive functions, including behavioral flexibility, an important ability to respond appropriately to changing environmental contingencies. However, the underlying mechanisms of impaired behavioral flexibility in aging are not clear. In this study, we reported that necroptosis-induced reduction of neuronal activity in the basolateral amygdala (BLA) plays an important role in behavioral inflexibility in 5-month-old mice of the senescence-accelerated mice prone-8 (SAMP8) line, a well-established model with age-related phenotypes. Application of Nec-1s, a specific inhibitor of necroptosis, reversed the impairment of behavioral flexibility in SAMP8 mice. We further observed that the loss of glycogen synthase kinase 3α (GSK-3α) was strongly correlated with necroptosis in the BLA of aged mice and the amygdala of aged cynomolgus monkeys (Macaca fascicularis). Moreover, genetic deletion or knockdown of GSK-3α led to the activation of necroptosis and impaired behavioral flexibility in wild-type mice, while the restoration of GSK-3α expression in the BLA arrested necroptosis and behavioral inflexibility in aged mice. We further observed that GSK-3α loss resulted in the activation of mTORC1 signaling to promote RIPK3-dependent necroptosis. Importantly, we discovered that social isolation, a prevalent phenomenon in aged people, facilitated necroptosis and behavioral inflexibility in 4-month-old SAMP8 mice. Overall, our study not only revealed the molecular mechanisms of the dysfunction of behavioral flexibility in aged people but also identified a critical lifestyle risk factor and a possible intervention strategy.
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http://dx.doi.org/10.1038/s41380-022-01694-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284973PMC
July 2022

Vimentin binds to a novel tumor suppressor protein, GSPT1-238aa, encoded by circGSPT1 with a selective encoding priority to halt autophagy in gastric carcinoma.

Cancer Lett 2022 Jul 13;545:215826. Epub 2022 Jul 13.

Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention and Regional Immunity and Diseases, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong, 518060, PR China. Electronic address:

Circular RNAs (circRNAs) are covalently closed, endogenous molecules that are widespread in eukaryotes. Recent evidence indicates that circRNAs play important roles in carcinogenesis. Several circRNAs have been reported to comprise translatable RNA; however, whether circRNAs encode functional proteins remains unknown. In our study, circRNA sequencing was carried out using five pathologically diagnosed gastric carcinoma (GC) samples and their paired adjacent normal tissues, we characterized the circRNA GSPT1 (circGSPT1), which is expressed at low levels in GC. Antibody detections, and mass spectrometry were used to validate active circRNA translation. The spanning junction open reading frame in circGSPT1, driven by an internal ribosome entry site (IRES), encodes a functional peptide, termed GSPT1-238aa. Interestingly, GSPT1-238aa tends to select the start codon used to initiate translation. This is the first finding of selective translation driven by IRES. CircGSPT1 and GSPT1-238aa halted the proliferation, migration, and invasion in GC cells in vitro. We also confirmed that the vimentin/Beclin1/14-3-3 complex interacts with GSPT1-238aa and modulates autophagy via the PI3K/AKT/mTOR signaling pathway in GC cells. Our study reveals that GSPT1-238aa, a novel protein encoded by circGSPT1, halts GC tumorigenesis. We also provide insights into the function and underlying molecular mechanisms of GSPT1-238aa in GC and suggest that this protein represents a novel target for GC treatment.
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http://dx.doi.org/10.1016/j.canlet.2022.215826DOI Listing
July 2022

Lipid metabolism and mA RNA methylation are altered in lambs supplemented rumen-protected methionine and lysine in a low-protein diet.

J Anim Sci Biotechnol 2022 Jul 13;13(1):85. Epub 2022 Jul 13.

CAS Key Laboratory for Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, 410125, Hunan, China.

Background: Methionine or lysine has been reported to influence DNA methylation and fat metabolism, but their combined effects in N6-methyl-adenosine (mA) RNA methylation remain unclarified. The combined effects of rumen-protected methionine and lysine (RML) in a low-protein (LP) diet on lipid metabolism, mA RNA methylation, and fatty acid (FA) profiles in the liver and muscle of lambs were investigated. Sixty-three male lambs were divided into three treatment groups, three pens per group and seven lambs per pen. The lambs were fed a 14.5% crude protein (CP) diet (adequate protein [NP]), 12.5% CP diet (LP), and a LP diet plus RML (LP + RML) for 60 d.

Results: The results showed that the addition of RML in a LP diet tended to lower the concentrations of plasma leptin (P = 0.07), triglyceride (P = 0.05), and non-esterified FA (P = 0.08). Feeding a LP diet increased the enzyme activity or mRNA expression of lipogenic enzymes and decreased lipolytic enzymes compared with the NP diet. This effect was reversed by supplementation of RML with a LP diet. The inclusion of RML in a LP diet affected the polyunsaturated fatty acids (PUFA), n-3 PUFA, and n-6 PUFA in the liver but not in the muscle, which might be linked with altered expression of FA desaturase-1 (FADS1) and acetyl-CoA carboxylase (ACC). A LP diet supplemented with RML increased (P < 0.05) total mA levels in the liver and muscle and were accompanied by decreased expression of fat mass and obesity-associated protein (FTO) and alkB homologue 5 (ALKBH5). The mRNA expressions of methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14) in the LP + RML diet group were lower than those in the other two groups. Supplementation of RML with a LP diet affected only liver YTH domain family (YTHDF2) proteins (P < 0.05) and muscle YTHDF3 (P = 0.09), which can be explained by limited mA-binding proteins that were mediated in mRNA fate.

Conclusions: Our findings showed that the inclusion of RML in a LP diet could alter fat deposition through modulations of lipogenesis and lipolysis in the liver and muscle. These changes in fat metabolism may be associated with the modification of mA RNA methylation. A systematic graph illustrates the mechanism of dietary methionine and lysine influence on lipid metabolism and MA. The green arrow with triangular heads indicates as activation and brown-wine arrows with flat heads indicates as suppression.
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http://dx.doi.org/10.1186/s40104-022-00733-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277831PMC
July 2022

Blood lipids and all-cause mortality among old people: the Chinese Longitudinal Healthy Longevity Survey 2008-2018.

Epidemiol Health 2022 Jul 5:e2022054. Epub 2022 Jul 5.

School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objectives: Proper concentration of blood lipids is essential to the survival of seniors. Past studies on old people showed inconsistent relationships between blood lipids and all-cause mortality.

Methods: In this retrospective longitudinal study, 1067 Chinese elderly participants were enrolled from the Chinese Longitudinal Healthy Longevity Survey at baseline in 2008 and followed up until death or December 31, 2018. The outcome was all-cause mortality. Multivariate Cox regression analyses were used to estimate Hazard ratios and 95% confidence interval values and the participants were stratified into three groups (60-80, 80-100, or ≥100 years) for further analysis. The survival probability according to lipid profiles quartiles were calculated using the Kaplan-Meier curves, and the log-rank tests were performed.

Results: The mean age of the participants was 84.84 years old and 56.98% of them were female. 578 individuals died and 277 were lost to follow up in ten years. Mean TC, HDL-C and LDL-C were higher among those who died than those survived. Participants with the second quartile of HDL-C, the highest quartile of LDL-C and TG had a 28% higher risk, 23% and 49% lower risk of for all-cause mortality, respectively. After further adjustment, the association remained except for HDL-C, and an extra association between all-cause mortality and the third quartile of TC and LDL-C and the second quartile of TG appeared (HR = 1.44, 95% CI: 1.01-2.06; HR = 0.68, 95% CI: 0.49-0.94; HR = 0.79, 95% CI: 0.62-0.99).

Conclusion: Old people could pay attention to keep levels of LDL-C at 1.91-2.47 mmol/L for healthy aging while maintaining TG not less than 1.66 mmol/L may benefit for survival.
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http://dx.doi.org/10.4178/epih.e2022054DOI Listing
July 2022

Neuronavigation-Guided Transcortical-Transventricular Endoport-Assisted Endoscopic Resection for Thalamic Lesions: Preliminary Experience.

World Neurosurg 2022 Jun 27;166:19-27. Epub 2022 Jun 27.

Department of Neurosurgery, Zhongshan Hospital, Fudan University, Shanghai, China; Digital Medical Research Center, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Key Laboratory of Medical Image Computing and Computer-Assisted Intervention, Shanghai, China. Electronic address:

Background: Surgery for thalamic lesions is generally challenging because they are deep-seated lesions surrounded by vital neurovascular structures. Whether neuronavigation-guided transcortical-transventricular endoport-assisted endoscopic resection for thalamic lesions is feasible remains to be further evaluated.

Methods: A retrospective review of 8 who patients received neuronavigation-guided transcortical-transventricular endoport-assisted endoscopic resection for thalamic lesions was performed. Preoperative and tumor-related variables and postoperative outcomes were analyzed.

Results: All lesions were located in the medial part of the thalamus, and most of them expanded forward, downward, or backward. Median size of lesions was 31 mm (range, 16-52 mm). Final pathology results confirmed that 1 case was a cavernous malformation, 3 were pilocytic astrocytomas, and 4 were glioblastomas. None of the patients had postoperative seizures. Gross total resection and long-term postoperative survival were achieved in all patients with benign lesions, while near-total resection (>90%) was achieved in 3 of 4 patients (75%) with glioblastoma, and subtotal resection (<90%) was achieved in 1 patient (25%). Among patients with glioblastoma, 1 patient remained free of recurrence at 16 months of follow-up; the other 3 patients had worse Karnofsky performance scale scores after surgery and died within 6 months.

Conclusions: Combining the advantages of neuronavigation, endoscopy, and endoport techniques via the middle frontal gyrus approach can safely and effectively remove benign lesions in the medial part of the thalamus. This procedure can also be performed in well-selected cases of glioblastoma and likely confers a survival advantage for this rapidly and universally fatal disease.
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http://dx.doi.org/10.1016/j.wneu.2022.06.110DOI Listing
June 2022

The analysis of risk factors for diabetic kidney disease progression: a single-centre and cross-sectional experiment in Shanghai.

BMJ Open 2022 06 28;12(6):e060238. Epub 2022 Jun 28.

Tongren Hospital Shanghai Jiaotong University School of Medicine, Shanghai, China

Objective: To identify the risk factors for diabetic kidney disease (DKD) development, especially the difference between patients with different courses.

Patients And Methods: 791 patients were considered to be eligible and were enrolled in the cross-sectional study from Shanghai Tongren Hospital Inpatient Department. 36 variables were initially screened by univariate analysis. The risk factors affecting progression of DKD were determined by logistics regression analysis. Subgroups were grouped according to the course of diabetes disease, and multivariate logistics regression analysis was performed to find out the different risk factors in two subgroups. Finally, the receiver operating characteristics curve is used to verify the result.

Results: The logistic regression model indicated age (OR=1.020, p=0.017, 95% CI 1.004 to 1.040), systolic blood pressure (OR=1.013, p=0.006, 95% CI 1.004 to 1.022), waist circumference (OR=1.021, p=0.015, 95% CI 1.004 to 1.038), white blood cells (WBC, OR=1.185, p=0.001, 95% CI 1.085 to 1.295) and triglycerides (TG, OR=1.110, p=0.047, 95% CI 1.001 to 1.230) were risk factors for DKD, while free triiodothyronine (fT3, OR=0.711, p=0.011, 95% CI 0.547 to 0.926) was a protective factor for DKD in patients with type 2 diabetes mellitus (T2DM). Subgroup analysis revealed that in patients with a short duration of diabetes (<8 years), WBC (OR=1.306, p<0.001, 95% CI 1.157 to 1.475) and TG (OR=1.188, p=0.033, 95% CI 1.014 to 1.393) were risk factors for DKD,fT3 (OR=0.544, p=0.002, 95% CI 0.367 to 0.804) was a protective factor for DKD; whereas for patients with disease course more than 8 years, age (OR=1.026, Pp=0.012, 95%CI=95% CI[ 1.006- to 1.048]) was identified as the only risk factor for DKD and fT3 (OR=0.036, Pp=0.017, 95%CI=95% CI[ 0.439- to 0.922]) was a protective factor for DKD.

Conclusion: The focus of attention should especially be on patients with a prolonged course of T2DM, and those with comorbid hypertension and hypertriglyceridaemia waist phenotype. More potential clinical indexes such as thyroid function and inflammatory indicators might be considered as early warning factors for DKD in T2DM. Women should pay attention to controlling inflammation and TGs, and men should strictly control blood pressure. Avoiding abdominal obesity in both men and women will bring great benefits.
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http://dx.doi.org/10.1136/bmjopen-2021-060238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240884PMC
June 2022

Prophylactic Antitubercular Therapy Is Associated With Accelerated Disease Progression in Patients With Crohn's Disease Receiving Anti-TNF Therapy: A Retrospective Multicenter Study.

Clin Transl Gastroenterol 2022 Jun 1;13(6):e00493. Epub 2022 Jun 1.

Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Introduction: Prophylactic antitubercular therapy (ATT) is widely prescribed in patients with Crohn's disease (CD) receiving antitumor necrosis factor (anti-TNF) treatment. However, antitubercular agents have been demonstrated to possess profibrotic effects. We aimed to evaluate whether ATT accelerated disease progression in patients with CD receiving anti-TNF treatment.

Methods: A retrospective, multicenter study was performed in CD patients presented with inflammatory behavior (B1) and treated with anti-TNF agents. Disease progression was defined as the development of a stricturing (B2) or penetrating (B3) phenotype. ATT users were propensity score-matched with non-ATT users. Survival and multivariable Cox analyses were used to identify factors associated with disease progression.

Results: We enrolled 441 patients, including 295 ATT users and 146 non-ATT users, with a median follow-up of 3.15 years (interquartile range: 1.6-4.7). The cumulative rates of disease progression in the ATT group were constantly higher than those in the non-ATT group after 1-, 3-, 5-, and 10-year follow-ups, respectively (P = 0.031). Multivariable Cox analysis identified ATT as an independent risk factor for disease progression using both the whole (hazard ratio = 2.22; 95% confidence interval: 1.11-4.48; P = 0.025) and propensity score-matched cohorts (hazard ratio = 2.35; 95% confidence interval: 1.07-5.14; P = 0.033). In subgroup analysis, patients receiving ATT ≥4.5 months had a significantly higher rate of disease progression compared with patients receiving ATT <4.5 months (P = 0.005) and non-ATT treatment (P = 0.036).

Discussion: Prophylactic ATT with duration over 4.5 months was associated with disease progression in patients with CD receiving anti-TNF treatment.
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http://dx.doi.org/10.14309/ctg.0000000000000493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9236600PMC
June 2022

Intestinal strictures in Crohn's disease: a 2021 update.

Therap Adv Gastroenterol 2022 21;15:17562848221104951. Epub 2022 Jun 21.

Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2nd, Guangzhou 510080, People's Republic of China.

Intestinal strictures remain one of the most intractable and common complications of Crohn's disease (CD). Approximately 70% of CD patients will develop fibrotic strictures after 10 years of CD diagnosis. Since specific antifibrotic therapies are unavailable, endoscopic balloon dilation and surgery remain the mainstay treatments despite a high recurrence rate. Besides, there are no reliable methods for accurately evaluating intestinal fibrosis. This is largely due to the fact that the mechanisms of initiation and propagation of intestinal fibrosis are poorly understood. There is growing evidence implying that the pathogenesis of stricturing CD involves the intricate interplay of factors including aberrant immune and nonimmune responses, host-microbiome dysbiosis, and genetic susceptibility. Currently, the progress on intestinal strictures has been fueled by the advent of novel techniques, such as single-cell sequencing, multi-omics, and artificial intelligence. Here, we perform a timely and comprehensive review of the substantial advances in intestinal strictures in 2021, aiming to provide prompt information regarding fibrosis and set the stage for the improvement of diagnosis, treatment, and prognosis of intestinal strictures.
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http://dx.doi.org/10.1177/17562848221104951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218441PMC
June 2022

An Atypical Anomalous Aortic Origin of the Left Coronary Artery With Intra-Arterial Wall Course Pretending a Normal Migration on Imaging Screening: A Case Report.

Front Cardiovasc Med 2022 9;9:918832. Epub 2022 Jun 9.

Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Oral Diseases, Department of Pediatrics, National Clinical Research Center for Oral Diseases, West China Second University Hospital, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Background: An anomalous aortic origin of a coronary artery (AAOCA) has been considered as a dominant cause of sudden cardiac death (SCD) among young age children. Therefore, it is critical to identify AAOCA timely to avoid lethal events. Recently, accumulating cases of right or left coronary arteries originating from inappropriate locations at the sinus of Valsalva have been identified. Here, we report a rare case of AAOCA with an intra-arterial wall course pretending normal migration on imaging screening in a patient who suffered from syncope.

Case Summary: A 7-year-old male without a previous history of cardiovascular and cerebrovascular diseases suddenly suffered from sharp chest pain and syncope after intensive exercise. The electrocardiogram showed that the ST segment of multiple leads was depressed by more than 0.05 mV, and biomarkers indicated severe myocardial injuries. The left ventricular ejection fraction (LVEF) decreased dramatically to 23%. Fulminant myocarditis and cardiomyopathy were therefore excluded. However, a relatively normal coronary artery origin, which arose from the left coronary sinus, presented on echocardiography and cardiac CT angiography (CTA). It is difficult to draw an association between severe clinical manifestations and slight malformations on echocardiography and CTA. Furthermore, selective coronary angiography revealed that an anomalous left coronary artery arose from the superior margin of the inappropriate sinus, developed an intramural wall course and finally exits the left sinus of Valsalva and migrated between the aorta and the pulmonary artery, which induced severe myocardial infarction during exercise. Then, the patient received surgical correction with a modified unroofing procedure. After 2 months of intensive treatment, the patient was discharged and remained asymptomatic through 18 months of follow-up.

Conclusion: AAOCA, especially anomalous left coronary artery (ALCA), represents a major potential risk of SCD. We reported an atypical manifestation of ALCA arising from the inappropriate sinus of Valsalva and merging into the intra-arterial wall to develop a strange course and then sprout between the aorta and the pulmonary artery. The diversity of AAOCA might present as a relatively normal course under non-invasive radiological imaging scanning.
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http://dx.doi.org/10.3389/fcvm.2022.918832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9222707PMC
June 2022

CLSTN3 gene variant associates with obesity risk and contributes to dysfunction in white adipose tissue.

Mol Metab 2022 Jun 24;63:101531. Epub 2022 Jun 24.

Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China; Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China; Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Diabetes Institute, Shanghai, China. Electronic address:

Objective: White adipose tissue (WAT) possesses the remarkable remodeling capacity, and maladaptation of this ability contributes to the development of obesity and associated comorbidities. Calsyntenin-3 (CLSTN3) is a transmembrane protein that promotes synapse development in brain. Even though this gene has been reported to be associated with adipose tissue, its role in the regulation of WAT function is unknown yet. We aim to further assess the expression pattern of CLSTN3 gene in human adipose tissue, and investigate its regulatory impact on WAT function.

Methods: In our study, we observed the expression pattern of Clstn3/CLSTN3 gene in mouse and human WAT. Genetic association study and expression quantitative trait loci analysis were combined to identify the phenotypic effect of CLSTN3 gene variant in humans. This was followed by mouse experiments using adeno-associated virus-mediated human CLSTN3 overexpression in inguinal WAT. We investigated the effect of CLSTN3 on WAT function and overall metabolic homeostasis, as well as the possible underlying molecular mechanism.

Results: We observed that CLSTN3 gene was routinely expressed in human WAT and predominantly enriched in adipocyte fraction. Furthermore, we identified that the variant rs7296261 in the CLSTN3 locus was associated with a high risk of obesity, and its risk allele was linked to an increase in CLSTN3 expression in human WAT. Overexpression of CLSTN3 in inguinal WAT of mice resulted in diet-induced local dysfunctional expansion, liver steatosis, and systemic metabolic deficiency. In vivo and ex vivo lipolysis assays demonstrated that CLSTN3 overexpression attenuated catecholamine-stimulated lipolysis. Mechanistically, CLSTN3 could interact with amyloid precursor protein (APP) in WAT and increase APP accumulation in mitochondria, which in turn impaired adipose mitochondrial function and promoted obesity.

Conclusion: Taken together, we provide the evidence for a novel role of CLSTN3 in modulating WAT function, thereby reinforcing the fact that targeting CLSTN3 may be a potential approach for the treatment of obesity and associated metabolic diseases.
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http://dx.doi.org/10.1016/j.molmet.2022.101531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254126PMC
June 2022

Extracellular electron transfer-dependent Cr(VI)/sulfate reduction mediated by iron sulfide nanoparticles.

J Biosci Bioeng 2022 Aug 9;134(2):153-161. Epub 2022 Jun 9.

Ministry of Education Key Laboratory of Pollution Control and Ecological Remediation for Industrial Agglomeration Area, College of Environment and Energy, South China University of Technology, Guangzhou 510006, PR China. Electronic address:

The slow electron transfer rate is a bottleneck to the biological wastewater treatment. This study evaluated the concomitant biotransformation and nonenzymatic reduction of Cr(VI) mediated by sulfate reducing bacteria (SRB), especially for the reinforcing Cr(VI) reduction via accelerating the electron transfer by the in-situ biosynthesized iron sulfide nanoparticles (FeS NPs). The kinetic results showed that 10 mg/L Cr(VI) was completely removed by pre-cultured FeS NPs within 7 h with k of 2.6 × 10 s, one magnitude higher than that without FeS NPs. Despite its competing electron to postpone sulfate reduction, the reduction of Cr(VI) was markedly improved via nonenzymatic reactions by the sulfide, the product of sulfate reduction. In the reinforcing system (bio-FeS [email protected]), the bio-FeS NPs served as an electronic bypass conduit for CoQ could significantly amplify the electron flux, and switch the Cr(VI) reduction from intracellular space to extracellular environment, which had a great detoxification effect on the microorganisms, eventually markedly promoted electron transfer extracellularly and the reduction of Cr(VI). After the long-term acclimatization, Desulfovibrio became the dominant bacteria at the genus level and accounted for the relative abundance of 32%. This study provides an alternative to use biogenic FeS NPs for Cr(VI) remediation.
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http://dx.doi.org/10.1016/j.jbiosc.2022.05.005DOI Listing
August 2022

Cognitive Impairment in Idiopathic Normal Pressure Hydrocephalus.

Neurosci Bull 2022 May 15. Epub 2022 May 15.

Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China.

Idiopathic normal pressure hydrocephalus (iNPH) is a significant cause of the severe cognitive decline in the elderly population. There is no cure for iNPH, but cognitive symptoms can be partially alleviated through cerebrospinal fluid (CSF) diversion. In the early stages of iNPH, cognitive deficits occur primarily in the executive functions and working memory supported by frontostriatal circuits. As the disease progresses, cognition declines continuously and globally, leading to poor quality of life and daily functioning. In this review, we present recent advances in understanding the neurobiological mechanisms of cognitive impairment in iNPH, focusing on (1) abnormal CSF dynamics, (2) dysfunction of frontostriatal and entorhinal-hippocampal circuits and the default mode network, (3) abnormal neuromodulation, and (4) the presence of amyloid-β and tau pathologies.
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http://dx.doi.org/10.1007/s12264-022-00873-2DOI Listing
May 2022

Diagnostic Accuracy of Interferon-Gamma Release Assays for Tuberculous Meningitis: A Systematic Review and Meta-Analysis.

Front Cell Infect Microbiol 2022 22;12:788692. Epub 2022 Apr 22.

Department of Neurology, Jiangxi Provincial People's Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, China.

Background: In this study, we evaluated and compared the accuracy of blood and cerebrospinal fluid (CSF) interferon release tests [interferon-gamma release assays (IGRAs)] in the diagnosis of tuberculous meningitis (TBM) by a meta-analysis of the relevant literature.

Methods: We searched for studies published before 2021 in Medline, Embase, the Cochrane database, and Chinese databases. All studies used the QuantiFERON-TB Gold In-Tube and/or T-SPOT.TB method. Blood and/or CSF tests that met the guidelines for the quality assessment of studies with diagnostic accuracy were included. We used the revised diagnostic accuracy study quality assessment to assess the quality of the included studies. Begg's funnel plots were used to assess publication bias in the meta-analysis of the diagnostic studies, and statistical analyses were performed by using Stata (Version 12) software.

Results: A total of 12 blood and/or CSF IGRA studies were included in this meta-analysis, with 376 patients and 493 controls. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve (SROC) of the blood IGRAs in the pooled data from 12 studies were 74% (95% CI: 0.65-0.82), 78% (95% CI: 0.68-0.86), 3.38 (95% CI 2.26-5.06), 0.33 (95% CI: 0.23-0.46), 10.25 (95% CI: 5.46-19.25), and 0.83 (95% CI: 0.79-0.86), respectively. For CSF IGRAs, these values for the pooled data from the 10 studies included were 79% (95% CI: 0.71-0.85), 95% (95% CI: 0.88-0.98), 16.30 (95% CI 6.5-40.83), 0.22 (95% CI: 0.16-0.31), 57.93 (95% CI: 22.56-148.78), and 0.91 (95% CI: 0.88-0.93), respectively.

Conclusion: CSF IGRAs exhibited a better diagnostic accuracy than blood IGRAs in diagnosing TBM.
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http://dx.doi.org/10.3389/fcimb.2022.788692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9072785PMC
April 2022

Case Report: F-FDG PET/CT Demonstrating Malignant Spread of a Pulmonary Epithelioid Hemangioendothelioma.

Front Med (Lausanne) 2022 4;9:862690. Epub 2022 Apr 4.

Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Pulmonary epithelioid hemangioendothelioma (EHE) is a rare vascular malignancy that is typically low-to-intermediate grade. We report a 47-year-old man with a rapidly progressive pulmonary EHE who initially presented with asymptomatic pulmonary nodules. One nodule was mildly hypermetabolic on initial F-FDG PET/CT. 10 months later, the patient developed severe bone pain and night sweats. Repeat imaging revealed several lung lesions, diffuse pleural thickening, and multiple skeletal metastases with considerably increased tracer uptake. The patient underwent vertebral, pleural, and pulmonary biopsies and a diagnosis of advanced pulmonary EHE was made. His disease progressed despite four courses of antineoplastic therapy, after which he began palliative care. Pulmonary EHE can be aggressive and spread rapidly. Biopsy of hypermetabolic lung lesions using PET/CT guidance might enable early definitive diagnosis.
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http://dx.doi.org/10.3389/fmed.2022.862690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9013896PMC
April 2022

A New Scoring System to Differentially Diagnose and Distinguish Tuberculous Meningitis and Bacterial Meningitis in South China.

Front Neurol 2022 30;13:830969. Epub 2022 Mar 30.

Department of Pediatrics, Jiangxi Provincial People's Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, China.

Background: Tuberculous meningitis (TBM) is the most serious form of extrapulmonary tuberculosis caused by , and is characterized by high morbidity and mortality. Unfortunately, it is difficult to distinguish TBM from bacterial meningitis (BM) based on clinical features alone. The latest diagnostic tests and neuroimaging methods are still not available in many developing countries. This study aimed to develop a simple diagnostic algorithm based on clinical and laboratory test results as an early predictor of TBM in South China.

Methods: A retrospective study was conducted to compare the clinical and laboratory characteristics of 114 patients with TBM and 47 with BM. Multivariate logistic regression analysis was performed on the characteristics of independently predicted TBM to develop a new diagnostic rule.

Results: Five characteristics were predictive of a diagnosis of TBM: duration of symptoms before admission; tuberculous symptoms; white blood cell (WBC) count, total cerebrospinal fluid WBC count, and cerebrospinal fluid chloride concentration. The sensitivity and specificity of the new scoring system developed in this study were 81.6 and 93.6%, respectively.

Conclusion: The new scoring system proposed in this study can help physicians empirically diagnose TBM and can be used in countries and regions with limited microbial and radiological resources.
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http://dx.doi.org/10.3389/fneur.2022.830969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006614PMC
March 2022

Preparation of poly(ionic liquid)/multi-walled carbon nanotube fillers using divinylbenzene as a linker to enhance the impact resistance of polyurethane elastomers.

RSC Adv 2022 Jan 12;12(3):1777-1787. Epub 2022 Jan 12.

School of Materials Science and Engineering, Xiangtan University Xiangtan 411105 P. R. China

The brittle fracture of polyurethane elastomer (PUE) under high-speed impact limits its application in high-speed impact protection. Here, based on the principle of free radical polymerization and π-π conjugation, composite nanoparticles (C-MWCNTs) are prepared by copolymerization of epoxy group ionic liquid (GVIMBr) and divinylbenzene (DVB) on MWCNTs using DVB as a linker. C-MWCNTs participate in the curing process of PUE through epoxy groups to form crosslinked C-MWCNTs/PUE, which improves the energy absorption and high-speed impact properties of PUE. Compared with neat PUE, the maximum compressive strength and energy absorbed by C-MWCNTs/PUE are increased by 46.3% and 23.6%, respectively. By observing the microsurface and fracture morphology of C-MWCNTs/PUE, the relationship between macroscopic mechanical properties and microstructure is constructed. The improvement of the mechanical properties of the C-MWCNTs/PUE is attributed to the interfacial interaction and homogeneous dispersion of the C-MWCNTs in the PUE matrix. These microscopic effects are caused by the good compatibility between GVIMBr and PUE matrix and the synergistic enhancement between GVIMBr and MWCNTs.
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http://dx.doi.org/10.1039/d1ra07174bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8979035PMC
January 2022

Genkwanin Alleviates Mitochondrial Dysfunction and Oxidative Stress in a Murine Model of Experimental Colitis: The Participation of Sirt1.

Ann Clin Lab Sci 2022 Mar;52(2):301-313

Graduate School, Hunan University of Chinese Medicine.

Objective: Genkwanin is a biologically active O-methylated flavone extracted from . An increasing number of studies have described the modulatory effects of genkwanin on human diseases, including antitumor, anti-inflammatory, and antioxidant activities. However, little is known about whether genkwanin might be a therapeutic agent for inflammatory bowel disease or its possible underlying mechanisms.

Materials And Methods: Forty C57BL/6 male mice were orally administered dextran sulfate sodium (DSS) to generate the colitis model, and genkwanin was orally administered at the indicated concentrations. Body weight, disease activity index, colon length, and H&E staining were used to evaluate colitis. Oxidative stress and antioxidant levels were measured by detecting ROS generation and malondialdehyde, superoxide dismutase and glutathione levels. The levels of proinflammatory cytokines (TNF-α, IL-1β, IFNγ and IL-6) were measured using ELISAs. Cell viability was determined using the CCK-8 assay. Mitochondrial function was evaluated by measuring the oxygen consumption rate, mtDNA content, and activities of electron transfer chain (ETC) complexes I, II, and IV. The expression of SIRT1, Nrf2 and its target genes was determined using qRT-PCR and western blotting. SIRT1 was depleted by lentivirus-mediated knockdown.

Results: In this study, oral administration of genkwanin alleviated colitis induced by oral administration of DSS in mice, as evidenced by reduced weight loss, colon length shortening and histopathology scores. Furthermore, genkwanin relieved oxidative stress and reduced the production of proinflammatory cytokines. assays revealed that genkwanin administration inhibited reactive oxygen species (ROS) production and improved mitochondrial function in human intestinal epithelial cells. Genkwanin also upregulated the expression of SIRT1, and lentivirus-mediated SIRT1 knockdown partially abrogated the protective effect of genkwanin on oxidative stress and mitochondrial dysfunction.

Conclusions: Findings from our murine model and cell culture experiments provide a promising basis for genkwanin to be studied as a treatment for IBD in clinical trials.
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March 2022

Elevated I-MIBG activity in adrenocortical adenoma-what other imaging options do we have?

Quant Imaging Med Surg 2022 Apr;12(4):2591-2595

Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.21037/qims-21-904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923844PMC
April 2022

Paeoniflorin Inhibits ASK1-TF Axis by Up-Regulating SOCS3 to Alleviate Radiation Enteritis.

Front Pharmacol 2022 14;13:743708. Epub 2022 Mar 14.

The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.

Radiation enteritis is one of the main adverse effects of radiotherapy, presenting with a poorly understood etiology and limited options for therapy. Intestinal inflammation and ischemia are the core mechanisms of radiation enteritis. Suppressor of cytokine signaling 3 (SOCS3) is an endogenous "inflammation brake." We hypothesized that paeoniflorin, a pinane monoterpene bitter glycoside, could increase SOCS3 expression to reduce inflammation and ischemia and improve enteritis in mice. Laser Doppler flowmetry was used to detect changes in intestinal blood flow. RAW264.7 and human umbilical vein endothelial cells were used to investigate the mechanism of action of paeoniflorin. It was observed that radiation caused high mortality, intestinal inflammatory responses, and low blood flow in mice. Paeoniflorin effectively alleviated intestinal atrophy, prevented thrombosis, improved radiation enteritis, and reduced mortality in mice undergoing radiotherapy. In addition, paeoniflorin increased the release of growth arrest-specific gene 6 (Gas6) and phosphorylation of the Axl receptor, subsequently inducing the expression of SOCS3 and inhibiting the expression of p-apoptosis signal-regulating kinase 1 and tissue factor and . Based on our findings, we suggest that paeoniflorin is potentially effective in alleviating radiation enteritis the activation of the Gas6/Axl/SOCS3 axis and subsequent reduction in intestinal inflammation and ischemia.
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http://dx.doi.org/10.3389/fphar.2022.743708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964139PMC
March 2022

Impact of TOF on Brain PET With Short-Lived C-Labeled Tracers Among Suspected Patients With AD/PD: Using Hybrid PET/MRI.

Front Med (Lausanne) 2022 2;9:823292. Epub 2022 Mar 2.

Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objective: To explore the impact of the time-of-flight (TOF) reconstruction on brain PET with short-lived C-labeled tracers in PET magnetic resonance (PET/MR) brain images among suspected patients with Alzheimer's and Parkinson's disease (AD/PD).

Methods: Patients who underwent C-2-ß-carbomethoxy-3-b-(4-fluorophenyl) tropane (C-CFT) and 2-(4-N-[C] methylaminophenyl)-6-hydroxybenzothiazole (C-PiB) PET/MRI were retrospectively included in the study. Each PET LIST mode data were reconstructed with and without the TOF reconstruction algorithm. Standard uptake values (SUVs) of Caudate Nucleus (CN), Putamen (PU), and Whole-brain (WB) were measured. TOF and non-TOF SUVs were assessed by using paired -test. Standard formulas were applied to measure contrast, signal-to-noise ratio (SNR), and percentage relative average difference of SUVs (%RAD-SUVs).

Results: Total 75 patients were included with the median age (years) and body mass index (BMI-kg/m) of 60.2 ± 10.9 years and 23.9 ± 3.7 kg/m in C-CFT ( = 41) and 62.2 ± 6.8 years and 24.7 ± 2.9 kg/m in C-PiB ( = 34), respectively. Higher average SUVs and positive %RAD-SUVs were observed in CN and PU in TOF compared with non-TOF reconstructions for the two C-labeled radiotracers. Differences of SUV were significant ( < 0.05) in CN and PU for both C-labeled radiotracers. SUV was enhanced significantly in CN and PU for C-CFT and CN for C-PiB, but not in PU. Significant contrast enhancement was observed in PU for both C-labeled radiotracers, whereas SNR gain was significant in PU, only for C-PiB in TOF reconstruction.

Conclusion: Time-of-flight leads to a better signal vs. noise trade-off than non-TOF in C-labeled tracers between CN and PU, improving the SUVs, contrast, and SNR, which were valuable for reducing injected radiation dose. Improved timing resolution aided the rapid decay rate of short-lived C-labeled tracers, and it shortened the scan time, increasing the patient comfort, and reducing the motion artifact among patients with AD/PD. However, one should adopt the combined TOF algorithm with caution for the quantitative analysis because it has different effects on the SUV, contrast, and SNR of different brain regions.
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http://dx.doi.org/10.3389/fmed.2022.823292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8926006PMC
March 2022

Predicting Distant Metastasis in Young-Onset Colorectal Cancer After Surgery: A Retrospective Study.

Front Oncol 2022 24;12:804038. Epub 2022 Feb 24.

Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Background: Although overall colorectal cancer (CRC) cases have been declining worldwide, there has been an increase in the incidence of the CRC among individuals younger than 50 years old, which is associated with distant metastasis (DM) and poor prognosis.

Methods: Young-onset CRC patients' postoperative data were collected from the Surveillance, Epidemiology, and End Results (SEER) database between January 2010 and December 2015. Data from the SEER database were divided into early stage and advanced stage according to whether chemoradiotherapy was recommended in the guidelines. Independent risk factors for DM were explored by using univariate and multivariate logistic regression separately. A predictive model was established and presented as nomogram in the training set of advanced stage. The model was internally verified in testing set and externally validated in a cohort of 145 patients from Zhongnan Hospital of Wuhan University. The accuracy, reliability, and clinical application value were assessed using the receiver operating characteristic curve (ROC), the area under the curve (AUC), calibration curve, and decision curve analysis (DCA), respectively. Different risk subgroups of DM were classified according to the scores of the nomogram in the training set of advanced stage.

Results: A total of 5,584 patients were eligible and enrolled in our study in which 1,277 were in early stage and 4,307 in advanced stage. Preoperative CEA positive was found to be an independent predictor of DM in early stage. Multivariate logistic regression analysis showed that tumor size, degree of differentiation, T stage, N stage, preoperative CEA, and whether radiation or chemotherapy performed were independent risk factors for DM (all,  < 0.05) in advanced stage. Great accuracies were achieved in our nomogram with AUC of 0.801 in training set, 0.811 in testing set, and 0.791 in the validation cohort, respectively. Calibration curves and DCA in internal validation and external validation both showed good stability and clinical utility values.

Conclusions: Preoperative CEA positive was a significant predictor of DM for young-onset CRC patients. A novel nomogram containing clinical and pathological features was established for predicting DM of advanced CRC in patients younger than 50 years old. This tool may serve as an early alert for clinicians to DM and make better clinical treatment regimens.
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http://dx.doi.org/10.3389/fonc.2022.804038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8907263PMC
February 2022

F-PFPN PET: a new and attractive imaging modality for patients with malignant melanoma.

J Nucl Med 2022 Feb 3. Epub 2022 Feb 3.

Union Hospital, Tongji Medical College, Huazhong University of Science & Technology.

F-FDG PET has limited diagnostic applications in malignant melanoma (MM). F-PFPN is a novel PET probe with high affinity and selectivity for melanin. We conducted a clinical study with two aims, firstly to investigate the biodistribution and radiation dosimetry of F-PFPN in healthy volunteers, and secondly, to examine the diagnostic utility of F-PFPN PET imaging in patients with MM. F-PFPN was synthesized through a fluoro-for-tosyl exchange reaction. Five healthy volunteers were enrolled to investigate the biodistribution, pharmacokinetics, radiation dosimetry, and safety of the tracer. Subsequently, a total of 21 patients with clinically suspected or confirmed MM underwent both F-PFPN PET/MR and F-FDG PET/CT scans. Normalized maximum standardized uptake values of selected lesions were determined for both tracers and compared in patient- and lesion-based analyses. F-PFPN has elevated radiochemical yield and was highly stable in vivo. In healthy volunteers, F-PFPN was safe and well-tolerated and its effective absorbed dose was comparable to that of F-FDG. In patient-based analysis, F-PFPN uptake was higher than F-FDG for both primary tumors and nodal metastases. In lesion-based analysis,F-PFPN PET imaging could detect 365 metastases that were missed on F-FDG PET. Additionally, F-PFPN PET imaging had clinical value in distinguishing false-positive lesions on F-FDG PET. F-PFPN is a safe and well-tolerated melanin PET tracer. In a pilot clinical study, F-PFPN PET imaging outperformed traditional F-FDG PET in identifying both primary MM and its distant spread.
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http://dx.doi.org/10.2967/jnumed.121.263179DOI Listing
February 2022

Survivin is essential for thermogenic program and metabolic homeostasis in mice.

Mol Metab 2022 04 31;58:101446. Epub 2022 Jan 31.

Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China; Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China; Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Diabetes Institute, Shanghai, China. Electronic address:

Objective: Survivin is a member of the inhibitor of apoptosis family. Our previous study showed that survivin expression could be strongly induced by long-term, high-fat diet (HFD) exposure in vivo. It could also be induced by insulin through the PI3K/mTOR signaling pathway in vitro. Therefore, we hypothesized that under certain conditions, survivin expression might be required for adipocyte function. In the current study, we aim to further investigate the regulation of survivin expression in mature adipocytes upon various nutritional stimuli and the role of survivin using adipocyte-specific survivin knockout (SKO) mice.

Methods: SKO mice were obtained by crossing survivin mice with Adiponectin-Cre mice. The overall metabolic phenotype was observed under chow diet (CD) and HFD feeding conditions. The thermogenic program of mice was detected upon cold exposure. The inguinal white adipose tissue (iWAT) and brown adipose tissue (BAT) stromal vascular fraction cells were isolated and differentiated into mature adipocytes, and the effects of survivin deletion on mature adipocyte function were detected in vitro.

Results: Survivin expression in adipose tissue and adipocytes was regulated by short-term nutritional stress both in vivo and in vitro. The postnatal development of BAT was impaired in SKO mice, which resulted in drastically reduced BAT mass and decreased expression of the thermogenic protein Ucp1 in 24-week-old mice fed with CD. After HFD feeding, the iWAT and BAT mass of SKO mice were significantly decreased, causing ectopic lipid accumulation in the liver, which was associated with insulin resistance and glucose intolerance. Upon cold exposure, the expression of thermogenic genes and proteins was markedly reduced in BAT and iWAT of SKO mice, accompanied by abnormal mitochondrial structure and induced autophagy. Consistently, thermogenic program and mitochondrial oxidative phosphorylation were reduced in survivin-depleted brown and beige adipocytes in vitro.

Conclusions: Our findings showed that survivin could be regulated by nutritional stress in adipocytes and revealed a new role of survivin in maintaining normal BAT mass and positively regulating the thermogenic program and mitochondrial oxidative phosphorylation.
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http://dx.doi.org/10.1016/j.molmet.2022.101446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866150PMC
April 2022
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