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1.
BMC Ophthalmol ; 24(1): 210, 2024 May 13.
Article En | MEDLINE | ID: mdl-38741065

BACKGROUND: Parry-Romberg syndrome (PRS) is a rare progressive degenerative disorder of unknown etiology. Here we report a rare case of PRS combined with lens subluxation in Eye and ENT hospital of Fudan University, Shanghai. To our knowledge, it is the first reported case of PRS combined with lens subluxation that has been managed surgically with phacoemulsification and CTR placement and IOL implantation in Shanghai. CASE PRESENTATION: A 60-year-old woman was referred for "right visual blur for 2 years" and had persistent right facial paralysis of unknown etiology since the age 12. She had right facial muscle atrophy and paralysis. Eye examination also showed the right eyelid pseudoptosis, enophthalmos, age-related cataract combined with lens subluxation existed in the right eye. The patient was diagnosed as age-related cataract and lens subluxation in the right eye and progressive hemifacial atrophy (Parry-Romberg syndrome). We conducted a combined phacoemulsification, IOL and CTR implantation and pupilloplasty surgery for the patient under general anesthesia and the postoperative UCVA was 20/30 and remained for 1 year's follow up. CONCLUSIONS: Here we reported a rare case of PHA combined with lens subluxation in China. After appropriate eye surgery, the patient achieved satisfying vision result in the right eye.


Facial Hemiatrophy , Lens Subluxation , Phacoemulsification , Humans , Female , Facial Hemiatrophy/complications , Facial Hemiatrophy/diagnosis , Facial Hemiatrophy/surgery , Middle Aged , Lens Subluxation/surgery , Lens Subluxation/diagnosis , Lens Subluxation/etiology , Lens Implantation, Intraocular , Visual Acuity/physiology
2.
J Alzheimers Dis ; 98(3): 907-923, 2024.
Article En | MEDLINE | ID: mdl-38489180

Background: The hippocampus consists of histologically and functionally distinct subfields, which shows differential vulnerabilities to Alzheimer's disease (AD)-associated pathological changes. Objective: To investigate the atrophy patterns of the main hippocampal subfields in patients with mild cognitive impairment (MCI) and AD and the relationships among the hippocampal subfield volumes, plasma biomarkers and cognitive performance. Methods: This cross-sectional study included 119 patients stratified into three categories: normal cognition (CN; N = 40), MCI (N = 39), and AD (N = 40). AD-related plasma biomarkers were measured, including amyloid-ß (Aß)42, Aß40, Aß42/Aß40 ratio, p-tau181, and p-tau217, and the hippocampal subfield volumes were calculated using automated segmentation and volumetric procedures implemented in FreeSurfer. Results: The subiculum body, cornu ammonis (CA) 1-head, CA1-body, CA4-body, molecular_layer_HP-head, molecular_layer_HP-body, and GC-ML-DG-body volumes were smaller in the MCI group than in the CN group. The subiculum body and CA1-body volumes accurately distinguished MCI from CN (area under the curve [AUC] = 0.647-0.657). The subiculum-body, GC-ML-DG-body, CA4-body, and molecular_layer_HP-body volumes accurately distinguished AD from MCI (AUC = 0.822-0.833) and AD from CN (AUC = 0.903-0.905). The p-tau 217 level served as the best plasma indicator of AD and correlated with broader hippocampal subfield volumes. Moreover, mediation analysis demonstrated that the subiculum-body volume mediated the associations between the p-tau217 and p-tau181 levels, and the Montreal Cognitive Assessment and Auditory Verbal Learning Test recognition scores. Conclusions: Hippocampal subfields with distinctive atrophy patterns may mediate the effects of tau pathology on cognitive function. The subiculum-body may be the most clinically meaningful hippocampal subfield, which could be an effective target region for assessing disease progression.


Alzheimer Disease , Cognitive Dysfunction , Humans , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/pathology , Cross-Sectional Studies , Magnetic Resonance Imaging , Hippocampus/diagnostic imaging , Hippocampus/pathology , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/pathology , Atrophy/pathology , Biomarkers
3.
Asia Pac J Ophthalmol (Phila) ; 13(1): 100002, 2024.
Article En | MEDLINE | ID: mdl-38383074

PURPOSE: To investigate the current prevalence and causes of moderate and severe visual impairment (MSVI) and blindness in elderly people in suburban Shanghai, China. METHODS: A cross-sectional study based on the population was conducted, which involved 5846 individuals (11,692 eyes) aged 65 years or older. Thorough eye examinations were performed to assess the prevalence and leading factors of MSVI (BCVA <20/63 to ≥20/400) and blindness (BCVA <20/400). RESULTS: The standardized prevalence of bilateral MSVI and blindness was 3.3% and 0.6%, correspondingly. The standardized prevalence of monocular MSVI and blindness was 7.4% and 2.0%, correspondingly. Cataract (47.9% and 20.7%, correspondingly) and myopic macular degeneration (MMD, 25.7% and 31.1%, correspondingly) were the principal causes of bilateral MSVI and blindness. As for monocular MSVI, the primary causes were cataract (39.4%), age-related macular degeneration (AMD, 16.6%), and MMD (16.6%). The primary causes of monocular blindness were other posterior segment eye diseases (30.1%) and MMD (14.2%). In adults aged 65-74 years, MMD was the foremost factor causing bilateral vision impairment. Conversely, cataract was identified as the primary cause of bilateral and monocular vision impairment among adults aged ≥ 75 years. AMD accounts for a significant proportion of individuals across all age groups. CONCLUSIONS: The significant prevalence of MSVI and blindness among Chinese adults represents a critical public health issue. In addition to cataract, the vision impairment caused by MMD and AMD become an important issue in the elderly Chinese people.


Blindness , Cataract , East Asian People , Macular Degeneration , Vision Disorders , Vision, Low , Aged , Humans , Blindness/epidemiology , Blindness/etiology , Cataract/complications , Cataract/epidemiology , China/epidemiology , Cross-Sectional Studies , Macular Degeneration/complications , Macular Degeneration/epidemiology , Prevalence , Vision Disorders/epidemiology , Vision Disorders/etiology , Vision, Low/epidemiology , Vision, Low/etiology
4.
Brain Res ; 1827: 148757, 2024 03 15.
Article En | MEDLINE | ID: mdl-38215865

There is increasing recognition of gut microbial dysbiosis in cerebral small vessel disease (CSVD). The altered diversity in a single ecosystem - alpha diversity index of gut microbiota has attracted wide attention. Our study aims to determine whether the alpha diversity index differs among healthy control (HC), CSVD with and without cognitive impairment. Moreover, we investigate the correlation between the alpha diversity index, neuroimaging markers, and cognitive function. We recruited 40 HC, 43 CSVD patients without cognitive impairment (CSVD-NCI), and 35 CSVD patients with mild cognitive impairment (CSVD-MCI). Clinical and neuropsychological assessments, MRI scanning, and gut microbiota analysis were performed on all participants. The alpha diversity indexes Chao1 and Shannon were calculated to evaluate community richness and diversity in a sample, respectively. Individual neuroimaging markers of CSVD and the CSVD burden score were also evaluated. A significantly lower level of Chao 1 rather than the Shannon index was observed in the CSVD subgroups than in the HC group. The level of the Chao 1 index was negatively correlated with both CMB counts, a neuroimaging characteristic of CSVD, and CSVD burden score in patients with CSVD. Additionally, the Chao 1 index has been associated with general cognitive function, information processing speed, and language function in patients with CSVD. Remarkably, the increased CSVD burden score mediated the effects of decreased levels of Chao 1 on information processing speed and language function. Hence, the alterations in species richness may be associated with CSVD-related cognitive impairment and mediated by CSVD neuroimaging markers.


Cerebral Small Vessel Diseases , Gastrointestinal Microbiome , Humans , Ecosystem , Cognition , Neuroimaging , Cerebral Small Vessel Diseases/diagnostic imaging
5.
Heart Fail Rev ; 29(1): 113-123, 2024 Jan.
Article En | MEDLINE | ID: mdl-37823952

The progression of heart failure is reported to be strongly associated with homeostatic imbalance, such as mitochondrial dysfunction and abnormal autophagy, in the cardiomyocytes. Mitochondrial dysfunction triggers autophagic and cardiac dysfunction. In turn, abnormal autophagy impairs mitochondrial function and leads to apoptosis or autophagic cell death under certain circumstances. These events often occur concomitantly, forming a vicious cycle that exacerbates heart failure. However, the role of the crosstalk between mitochondrial dysfunction and abnormal autophagy in the development of heart failure remains obscure and the underlying mechanisms are mainly elusive. The potential role of the link between mitochondrial dysfunction and abnormal autophagy in heart failure progression has recently garnered attention. This review summarized recent advances of the interactions between mitochondria and autophagy during the development of heart failure.


Heart Failure , Mitochondrial Diseases , Humans , Heart Failure/metabolism , Autophagy/physiology , Mitochondria/metabolism , Myocytes, Cardiac/metabolism , Mitochondrial Diseases/metabolism
6.
J Cardiovasc Pharmacol ; (0)2023 Dec 15.
Article En | MEDLINE | ID: mdl-38113918

ABSTRACT: Studies have examined the therapeutic effect of levosimendan on cardiovascular diseases such as heart failure, perioperative cardiac surgery, and septic shock, but the specific mechanism in mice remains largely unknown. This study aimed to investigate the relaxation mechanism of levosimendan in the thoracic aorta smooth muscle of mice. Levosimendan-induced relaxation of isolated thoracic aortic rings that were precontracted with norepinephrine (NE) or KCl was recorded in an endothelium-independent manner. Vasodilatation by levosimendan was not associated with the production of the endothelial relaxation factors NO and PGI2. The voltage-dependent K+ channel (KV) blocker (4-aminopyridine) and selective KCa blocker (tetraethylammonium) had no effect on thoracic aortas treated with levosimendan, indicating that KV and KCa channels may not be involved in the levosimendan-induced relaxation mechanism. Although the inwardly rectifying K+ channel (Kir) blocker (barium chloride) and the KATP channel blocker (glibenclamide) significantly inhibited levosimendan-induced vasodilation in the isolated thoracic aorta, barium chloride had a much stronger inhibitory effect on levosimendan-induced vasodilation than glibenclamide, suggesting that levosimendan-induced vasodilation may be mediated by Kir channels. The vasodilation effect and expression of Kir 2.1 induced by levosimendan were further enhanced by the PKC inhibitor staurosporine. Extracellular calcium influx was inhibited by levosimendan without affecting intracellular Ca2+ levels in the isolated thoracic aorta. These results suggest that Kir channels play a more important role than KATP channels in regulating vascular tone in larger arteries and that the activity of the Kir channel is enhanced by the PKC pathway.

7.
Biochem Pharmacol ; 217: 115814, 2023 11.
Article En | MEDLINE | ID: mdl-37769713

Antimicrobial resistance (AMR) is a global health threat. The dramatic increase of Methicillin-resistant Staphylococcus aureus (MRSA) infections emphasizes the need to find new anti-infective agents with a novel mode of action. The Caseinolytic protease (ClpP) is a central virulence factor in stress survival, virulence, and antibiotic resistance of MRSA. Here, we found ayanin, a flavonoid isolated from Callicarpa nudiflora, was an inhibitor of MRSA ClpP with an IC50 of 19.63 µM. Using quantitative real-time PCR, ayanin reduced the virulence of Staphylococcus aureus (S. aureus) by down-regulating the level of some important virulence factors, including agrA, RNAⅢ, hla, pvl, psmα and spa. The results of cellular thermal shift assay and thermal shift assay revealed a binding between ayanin and ClpP. Molecular docking showed that ASP-168, ASN-173 and ARG-171 were the potential binding sites for ClpP binding to ayanin. ClpP mutagenesis study further indicated that ARG-171 and ASN-173 were the main active sites of ClpP. The affinity constant (KD) value of ayanin with ClpP was 3.15 × 10-5 M measured by surface plasmon resonance. In addition, ayanin exhibited a significant therapeutic effect on pneumonia infection induced by S. aureus in mice in vivo, especially in combination with vancomycin. This is the first report of ayanin with in vivo and in vitro efficacy against S. aureus infection. In conclusion, ayanin is a promising therapeutic agent to combat MRSA infections by targeting ClpP.


Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Animals , Mice , Staphylococcus aureus , Peptide Hydrolases/pharmacology , Molecular Docking Simulation , Flavonoids/pharmacology , Flavonoids/therapeutic use , Staphylococcal Infections/drug therapy , Virulence Factors , Endopeptidases , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Microbial Sensitivity Tests
8.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(4): 571-580, 2023 Aug.
Article Zh | MEDLINE | ID: mdl-37654137

Objective To investigate the changes in plasma amyloid-ß (Aß) level and their relationship with white matter microstructure in the patients with amnesic mild cognitive impairment(aMCI) and vascular mild cognitive impairment (vMCI).Methods A total of 36 aMCI patients,20 vMCI patients,and 34 sex and age matched healthy controls (HC) in the outpatient and inpatient departments of the First Affiliated Hospital of Anhui Medical University were enrolled in this study.Neuropsychological scales,including the Mini-Mental State Examination,the Montreal Cognitive Assessment,and the Activity of Daily Living Scale,were employed to assess the participants.Plasma samples of all the participants were collected for the measurement of Aß42 and Aß40 levels.All the participants underwent magnetic resonance scanning to obtain diffusion tensor imaging (DTI) data.The DTI indexes of 48 white matter regions of each individual were measured (based on the ICBM-DTI-81 white-matter labels atlas developed by Johns Hopkins University),including fractional anisotropy (FA) and mean diffusivity (MD).The cognitive function,plasma Aß42,Aß40,and Aß42/40 levels,and DTI index were compared among the three groups.The correlations between the plasma Aß42/40 levels and DTI index of aMCI and vMCI patients were analyzed.Results The Mini-Mental State Examination and the Montreal Cognitive Assessment scores of aMCI and vMCI groups were lower than those of the HC group (all P<0.001).There was no significant difference in the Activity of Daily Living Scale score among the three groups (P=0.654).The plasma Aß42 level showed no significant difference among the three groups (P=0.227).The plasma Aß40 level in the vMCI group was higher than that in the HC group (P=0.014),while it showed no significant difference between aMCI and HC groups (P=1.000).The plasma Aß42/40 levels in aMCI and vMCI groups showed no significant differences from that in the HC group (P=1.000,P=0.105),while the plasma Aß42/40 level was lower in the vMCI group than in the aMCI group (P=0.016).The FA value of the left anterior limb of internal capsule in the vMCI group was lower than those in HC and aMCI groups (all P=0.001).The MD values of the left superior corona radiata,left external capsule,left cingulum (cingulate gyrus),and left superior fronto-occipital fasciculus in the vMCI group were higher than those in HC (P=0.024,P=0.001,P=0.003,P<0.001) and aMCI (P=0.015,P=0.004,P=0.019,P=0.001) groups,while the MD values of the right posterior limb of internal capsule (P=0.005,P=0.001) and left cingulum (hippocampus) (P=0.017,P=0.031) in the aMCI and vMCI groups were higher than those in the HC group.In the aMCI group,plasma Aß42/40 level was positively correlated with FA of left posterior limb of internal capsule (r=0.403,P=0.015) and negatively correlated with MD of the right fonix (r=-0.395,P=0.017).In the vMCI group,plasma Aß42/40 level was positively correlated with FA of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=0.575,P=0.008;r=0.639,P=0.002),while it was negatively correlated with MD of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=-0.558,P=0.011;r=-0.626,P=0.003).Conclusions Plasma Aß levels vary differently in the patients with aMCI and vMCI.The white matter regions of impaired microstructural integrity differ in the patients with different dementia types in the early stage.The plasma Aß levels in the patients with aMCI and vMCI are associated with the structural integrity of white matter,and there is regional specificity between them.


Cognitive Dysfunction , White Matter , Humans , Diffusion Tensor Imaging , White Matter/diagnostic imaging , Outpatients , Cognition , Amyloid beta-Peptides
9.
Phenomics ; 3(3): 255-267, 2023 Jun.
Article En | MEDLINE | ID: mdl-37325711

High myopia has long been highly prevalent worldwide with a largely yet unexplained genetic contribution. To identify novel susceptibility genes for axial length (AL) in highly myopic eyes, a genome-wide association study (GWAS) was performed using the genomic dataset of 350 deep whole-genome sequencing data from highly myopic patients. Top single nucleotide polymorphisms (SNPs) were functionally annotated. Immunofluorescence staining, quantitative polymerase chain reaction, and western blot were performed using neural retina of form-deprived myopic mice. Enrichment analyses were further performed. We identified the four top SNPs and found that ADAM Metallopeptidase With Thrombospondin Type 1 Motif 16 (ADAMTS16) and Phosphatidylinositol Glycan Anchor Biosynthesis Class Z (PIGZ) had the potential of clinical significance. Animal experiments confirmed that PIGZ expression could be observed and showed higher expression level in form-deprived mice, especially in the ganglion cell layer. The messenger RNA (mRNA) levels of both ADAMTS16 and PIGZ were significantly higher in the neural retina of form-deprived eyes (p = 0.005 and 0.007 respectively), and both proteins showed significantly upregulated expression in the neural retina of deprived eyes (p = 0.004 and 0.042, respectively). Enrichment analysis revealed a significant role of cellular adhesion and signal transduction in AL, and also several AL-related pathways including circadian entrainment and inflammatory mediator regulation of transient receptor potential channels were proposed. In conclusion, the current study identified four novel SNPs associated with AL in highly myopic eyes and confirmed that the expression of ADAMTS16 and PIGZ was significantly upregulated in neural retina of deprived eyes. Enrichment analyses provided novel insight into the etiology of high myopia and opened avenues for future research interest. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-022-00082-x.

10.
Opt Lett ; 48(7): 1790-1793, 2023 Apr 01.
Article En | MEDLINE | ID: mdl-37221767

We report an all-fiber 2.8-µm ultra-short pulse master oscillator power amplifier (MOPA) system seeded by a soliton self-frequency shift from a mode-locked thulium-doped fiber laser. This all-fiber laser source delivers 2.8-µm pulses with an average power of 3.42 W, a pulse width of 115 fs, and a pulse energy of 45.4 nJ. We demonstrate, to the best of our knowledge, the first femtosecond watt-level all-fiber 2.8-µm laser system. A 2.8-µm pulse seed was obtained via the soliton self-frequency shift of 2-µm ultra-short pulses in a cascaded silica and passive fluoride fiber. A novel, to the best of our knowledge, high-efficiency and compact home-made end-pump silica-fluoride fiber combiner was fabricated and used in this MOPA system. Nonlinear amplification of the 2.8-µm pulse was realized, and soliton self-compression was observed accompanied by spectral broadening.

11.
J Alzheimers Dis ; 92(3): 1001-1013, 2023.
Article En | MEDLINE | ID: mdl-36847009

BACKGROUND: ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a key enzyme in the formation of amyloid-ß (Aß) protein. Increasing evidence suggests that BACE1 concentration is a potential biomarker for Alzheimer's disease (AD). OBJECTIVE: To evaluate the correlations between plasma BACE1 concentration, cognition, and hippocampal volume at different stages of the AD continuum. METHODS: Plasma BACE1 concentrations were measured in 32 patients with probable dementia due to AD (ADD), 48 patients with mild cognitive impairment (MCI) due to AD, and 40 cognitively unimpaired (CU) individuals. Memory function was evaluated using the auditory verbal learning test (AVLT), and voxel-based morphometry was used to analyze bilateral hippocampal volumes. Correlation and mediation analyses were performed to investigate the associations between plasma BACE1 concentration, cognition, and hippocampal atrophy. RESULTS: The MCI and ADD groups exhibited elevated BACE1 concentrations compared with the CU group after adjusting for age, sex, and apolipoprotein E (APOE) genotype. Increased BACE1 concentration was found in AD continuum patients who were APOE ɛ4 carriers (p < 0.05). BACE1 concentration was negatively associated with the scores of the subitems of the AVLT and hippocampal volume (p < 0.05, false discovery rate correction) in the MCI group. Moreover, bilateral hippocampal volume mediated the relationship between BACE1 concentration and recognition in the MCI group. CONCLUSION: BACE1 expression increased in the AD continuum, and bilateral hippocampal volume mediated the effect of BACE1 concentration on memory function in patients with MCI. Research has indicated that the plasma BACE1 concentration might be a biomarker at the early stage of AD.


Alzheimer Disease , Cognitive Dysfunction , Humans , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Cross-Sectional Studies , Amyloid Precursor Protein Secretases/metabolism , Aspartic Acid Endopeptidases/metabolism , Amyloid beta-Peptides/metabolism , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/genetics , Cognitive Dysfunction/metabolism , Apolipoproteins E/genetics , Biomarkers/metabolism , Hippocampus/diagnostic imaging , Hippocampus/metabolism
12.
J Alzheimers Dis ; 92(1): 81-93, 2023.
Article En | MEDLINE | ID: mdl-36710682

BACKGROUND: The primary manifestations of Alzheimer's disease (AD) include cognitive decline and brain gray matter volume (GMV) atrophy. Recent studies have found that plasma phosphorylated-tau (p-tau) concentrations perform better in diagnosing, differentiating, and monitoring the progression of AD. However, the correlation between plasma p-tau, GMV, and cognition remains unclear. OBJECTIVE: To investigate whether GMV plays a mediating role in the association between plasma p-tau concentrations and cognition. METHODS: In total, 99 participants (47 patients with AD and 52 cognitively unimpaired [CU] individuals) were included. All participants underwent neuropsychological assessments, laboratory examinations, and magnetic resonance imaging scans. Plasma p-tau217 and p-tau181 concentrations were measured using an enzyme-linked immunosorbent assay kit. Voxel-based morphometry was performed to assess participants' brain GMV. Partial correlation and mediation analyses were conducted in AD group. RESULTS: Plasma p-tau concentrations were significantly higher in the AD group than in the CU group. Patients with AD had significant brain GMV atrophy in the right hippocampus, bilateral middle temporal gyrus, and right inferior temporal gyrus. In the AD group, there were significant correlations between plasma p-tau217 concentrations, GMV, and Mini-Mental State Examination (MMSE) scores. Brain GMV of the right hippocampus mediated the association between plasma p-tau217 concentrations and MMSE scores. A significant correlation between plasma p-tau181 and MMSE scores was not identified. CONCLUSION: The findings indicate that p-tau217 is a promising biomarker for central processes affecting brain GMV and cognitive function. This may provide potential targets for future intervention and treatment of tau-targeting therapies in the early stages of AD.


Alzheimer Disease , Cognitive Dysfunction , Humans , Alzheimer Disease/pathology , Gray Matter/pathology , tau Proteins , Cognition , Cognitive Dysfunction/pathology , Magnetic Resonance Imaging , Biomarkers , Atrophy/pathology , Amyloid beta-Peptides , Brain/pathology
13.
Diabetes Obes Metab ; 25(3): 664-674, 2023 03.
Article En | MEDLINE | ID: mdl-36314246

AIM: To assess the efficacy and safety of liraglutide to reduce visceral and ectopic fat in adults with or without type 2 diabetes mellitus (T2DM). METHODS: Four databases were searched up to 6 May 2022 for randomized clinical trials assessing the effect of liraglutide on visceral and ectopic fat. The mean and standard deviation of the values of visceral fat, ectopic fat and body mass index were calculated. Subgroup analyses were performed based on the type of disease (T2DM or non-T2DM), duration of intervention, dosage of liraglutide and whether life interventions were added to liraglutide therapy. We extracted and integrated the safety assessments reported in each article. RESULTS: Sixteen randomized clinical trials with, in total, 845 participants were included in the meta-analysis. Liraglutide could significantly decrease visceral fat [standard mean difference (SMD) = -0.72, 95% confidence interval (CI; -1.12, -0.33)], liver fat [SMD = -0.78, 95% CI (-1.24, -0.32)] and body mass index [weighted mean difference = -1.44, 95% CI (-1.95, -0.92)] in adult patients with or without T2DM when compared with the control group. However, reduction of epicardial fat by liraglutide [SMD = -0.74, 95% CI (-1.82, 0.34)] was not statistically significant. Subgroup analysis revealed that an adequate dosage (≥1.8 mg/day) and appropriate duration of treatment (ranging from 16 to 40 weeks) were the decisive factors for liraglutide to reduce visceral fat effectively. Mild gastrointestinal reactions were the main adverse event of liraglutide. CONCLUSIONS: Liraglutide significantly and safely reduces visceral and ectopic liver fat irrespective of T2DM status, and reduces visceral fat provided adequate dosage and duration of therapy are ensured.


Diabetes Mellitus, Type 2 , Liraglutide , Adult , Humans , Liraglutide/adverse effects , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/chemically induced , Liver , Body Mass Index , Adipose Tissue , Hypoglycemic Agents/adverse effects , Randomized Controlled Trials as Topic
14.
Br J Ophthalmol ; 107(5): 683-689, 2023 05.
Article En | MEDLINE | ID: mdl-35086805

PURPOSE: To estimate the prevalence rates of cataract and cataract surgery in suburban Shanghai, China. METHODS: This population-based, cross-sectional study was carried out in Pujiang Town, Shanghai, China, using a random cluster sampling strategy. A total of 5846 participants (11,657 eyes) aged ≥65 years were enrolled. Detailed eye examinations included presenting visual acuity (VA), best-corrected VA, non-contact tonometry, measurement of ocular parameters using IOLMaster 700, slit-lamp assessment of lens opacities using the Lens Opacities Classification System III and dilated fundus evaluation. RESULTS: Cataract was present in 57.0% of participants (53.8% of eyes). Cortical, nuclear and posterior subcapsular cataract (PSC) were found in 41.3%, 41.0% and 12.6% of participants. Among participants with any cataract, VA was <20/40 in 32.5%. According to Global Burden of Disease Study visual impairment (VI) criteria, 52.5% of participants with PSC had VI, 4.9% were considered blind (VA <20/400) and 31.9% had moderate VI (VA ≥20/400 to <20/63). This rate was significantly greater than that in participants with cortical (32.0%) or nuclear (38.0%) cataract (P<0.05). Cataract surgery was performed in 8.1% of eyes (men, 3.1%; women, 5.0%) or 10.9% of participants (men, 4.2%; women, 6.7%). CONCLUSIONS: The Pujiang Cataract Cohort Study has revealed the prevalence rates of cataract and cataract surgery among elderly individuals in suburban Shanghai, China. Although the frequency of cataract surgery has increased in China in recent decades, the high prevalence of cataract-related VI among older people suggests further attention to primary eyecare and medical awareness is necessary.


Cataract Extraction , Cataract , Vision, Low , Aged , Male , Humans , Female , Cohort Studies , Prevalence , Cross-Sectional Studies , East Asian People , China/epidemiology , Cataract/epidemiology
15.
Redox Biol ; 56: 102446, 2022 10.
Article En | MEDLINE | ID: mdl-36057161

AIMS: Metabolic switching during heart development contributes to postnatal cardiomyocyte (CM) cell cycle exit and loss of regenerative capacity in the mammalian heart. Metabolic control has potential for developing effective CM proliferation strategies. We sought to determine whether lactate dehydrogenase A (LDHA) regulated CM proliferation by inducing metabolic reprogramming. METHODS AND RESULTS: LDHA expression was high in P1 hearts and significantly decreased during postnatal heart development. CM-specific LDHA knockout mice were generated using CRISPR/Cas9 technology. CM-specific LDHA knockout inhibited CM proliferation, leading to worse cardiac function and a lower survival rate in the neonatal apical resection model. In contrast, CM-specific overexpression of LDHA promoted CM proliferation and cardiac repair post-MI. The α-MHC-H2B-mCh/CAG-eGFP-anillin system was used to confirm the proliferative effect triggered by LDHA on P7 CMs and adult hearts. Metabolomics, proteomics and Co-IP experiments indicated that LDHA-mediated succinyl coenzyme A reduction inhibited succinylation-dependent ubiquitination of thioredoxin reductase 1 (Txnrd1), which alleviated ROS and thereby promoted CM proliferation. In addition, flow cytometry and western blotting showed that LDHA-driven lactate production created a beneficial cardiac regenerative microenvironment by inducing M2 macrophage polarization. CONCLUSIONS: LDHA-mediated metabolic reprogramming promoted CM proliferation by alleviating ROS and inducing M2 macrophage polarization, indicating that LDHA might be an effective target for promoting cardiac repair post-MI.


Myocardial Infarction , Myocytes, Cardiac , Animals , Cell Proliferation , Coenzyme A/pharmacology , Lactate Dehydrogenase 5 , Lactates/metabolism , Lactates/pharmacology , Macrophages/metabolism , Mammals , Mice , Mice, Knockout , Myocardial Infarction/metabolism , Myocytes, Cardiac/metabolism , Reactive Oxygen Species/metabolism , Thioredoxin Reductase 1/metabolism
16.
BMC Ophthalmol ; 22(1): 71, 2022 Feb 12.
Article En | MEDLINE | ID: mdl-35151265

BACKGROUND: To investigate the associations between anterior segment biometry and high axial myopia in cataractous eyes in the Chinese population. METHODS: Data on 3438 eyes from 3438 subjects were analyzed in this cross-sectional study. Anterior segment biometry, axial length measurements, and intraocular pressure evaluation were implemented using an Oculus Pentacam HR, a Zeiss IOLMaster 500, and a Nidek TonoRef II, respectively. A multivariate-adjusted logistic model and a multivariate-adjusted linear model were used for statistical analysis. RESULTS: The mean age of the subjects was 62.2 ± 10.6 years, and 56.4% were female. There were 2665 subjects with high axial myopia (axial length, ≥26.50 mm) and 773 without (axial length, < 26.50 mm). The characteristics independently associated with high axial myopia included lower total corneal refractive power, a more negative Q value, greater total corneal astigmatism, greater white-to-white corneal diameter, greater anterior chamber depth, and higher intraocular pressure (all P <  0.05). In addition, greater axial length correlated with a thicker temporal cornea and a thinner nasal cornea (both P <  0.001). CONCLUSIONS: For cataractous eyes, high axial myopia was associated with corneal flattening, increased total corneal astigmatism, anterior segment enlargement, and intraocular pressure elevation. The findings may inform the choice of intraocular lenses and the calculation of their power, help improve the surgical practice of refractive cataract procedures, and provide useful information on the centration and stability of intraocular lenses.


Biometry , Myopia , Aged , China/epidemiology , Cornea , Cross-Sectional Studies , Female , Humans , Middle Aged , Myopia/diagnosis , Myopia/epidemiology , Refraction, Ocular
17.
Phenomics ; 2(2): 136-144, 2022 Apr.
Article En | MEDLINE | ID: mdl-36939791

The ocular biometry characteristics are clinically significant for children with unilateral congenital cataracts, but there is a lack of data analysis concerning the preoperative measurements. The axial length (AL), mean keratometry (Km), corneal astigmatism (CA), and the anterior chamber depth (ACD) from both eyes before cataract surgery were obtained from 205 patients (410 eyes, 3-15 years of age) with unilateral congenital cataracts. In the congenital cataract eyes, shorter AL (22.44 ± 1.52 mm vs. 22.57 ± 1.04 mm, p = 0.036) and higher CA (- 1.89 ± 0.91 D vs. - 1.24 ± 0.67 D, p < 0.001) were found, and no significant difference was found in the Km and the ACD measurements compared to the contralateral normal eyes. Females had shorter AL and shallower ACD compared to males. However, the Km and CA in the females were significantly larger than that in males. Shorter AL, larger Km, higher CA, and shallower ACD were also found in females who had a binocular axial difference (the value obtained by subtraction of the contralateral normal eye from the congenital cataract eye) that less than zero. The preoperative ocular biometry of shorter AL, larger Km, higher CA, and shallower ACD should be considered in females with unilateral congenital cataracts. The age and the binocular axial differences had a statistically significant correlation (r = -0.192, p = 0.006). Therefore, changes in the binocular axial differences associated with aging may enhance the guidelines for intraocular lens selection and the management of congenital cataracts.

18.
Phenomics ; 2(4): 254-260, 2022 Aug.
Article En | MEDLINE | ID: mdl-36939803

Genetic alterations are a major cause of microphthalmos, while novel-related genes and mutations in microphthalmos have rarely been explored. To identify the underlying genetic defect responsible for microphthalmos eyes in two three-generation Chinese families, we screened 425 genes involved in common inherited non-syndromic eye diseases with next-generation sequencing-based target capture sequencing of the two probands of two three-generation Chinese families diagnosed with microphthalmos. Variants were filtered and analyzed to identify possible disease-causing variants before Sanger sequencing validation. We enrolled two families with microphthalmos (Family 1: microphthalmos with congenital ocular coloboma and Family 2: simple microphthalmos). Two novel heterozygous mutations, Peroxidasin (PXDN) c.3165C>T (p.Pro1055Pro) and PXDN c.2640C>G (p.Arg880Arg), were found in Family 1, and Crystallin Beta B2 (CRYBB2) c.481G>A (p.Gly161Arg) was found in Family 2, but none of the mutations were found in the unaffected individuals, who were phenotypically normal. Multiple orthologous sequence alignment (MSA) revealed that the CRYBB2 p.Gly161Arg mutation was a deleterious effect mutation. In conclusion, the three novel mutations found in our study extend our current understanding of the genetic basis of microphthalmos and provide early pre-symptomatic diagnosis and emphasize the significance of genetic diagnosis of microphthalmos.

19.
Front Med (Lausanne) ; 8: 736686, 2021.
Article En | MEDLINE | ID: mdl-34869429

Purpose: To analyze the anterior, posterior, and total corneal spherical aberrations (ASA, PSA, and TSA) in patients with Chinese bilateral ectopia lentis (EL). Methods: A cross-sectional study was conducted to evaluate corneal spherical aberration (CSA) using a Pentacam system at the 6-mm optical zone. Axial length, keratometry, astigmatism, and corneal asphericity were also determined. Results: This study included 247 patients (420 eyes) with a mean age of 18.1 years. The values of ASA, PSA, and TSA were 0.136 ± 0.100 µm, -0.118 ± 0.030 µm, and 0.095 ± 0.095 µm, respectively. In the EL patients with Marfan syndrome (MFS), ASA and TSA were significantly lower than in the non-MFS patients (0.126 ± 0.094 µm vs. 0.155 ± 0.107 µm, P = 0.004 for ASA; 0.085 ± 0.091 µm vs. 0.114 ± 0.099 µm, P = 0.003 for TSA), whereas PSA was not significantly different (P = 0.061). The values of ASA and TSA were significantly higher in the patients with EL aged ≥ 40 years old than in younger patients, whereas ASA and PSA were lower in patients aged <10 years old than in older patients (all P < 0.05). In the multiple linear regression analysis, age, keratometry, astigmatism, anterior asphericity, higher-order aberration (HOA), and lower-order aberration (LOA) were positively or negatively correlated with TSA in the patients with EL (r = 0.681, P < 0.001). Conclusions: Corneal spherical aberration was low in the patients with EL especially for MFS and tended to increase with aging. Preoperatively, individual measurement of CSA was necessary for bilateral EL patients with MFS.

20.
Molecules ; 26(17)2021 Aug 29.
Article En | MEDLINE | ID: mdl-34500671

Fumonisin B1 (FB1), belonging to the member of fumonisins, is one of the most toxic mycotoxins produced mainly by Fusarium proliferatum and Fusarium verticillioide. FB1 has caused extensive contamination worldwide, mainly in corn, rice, wheat, and their products, while it also poses a health risk and is toxic to animals and human. It has been shown to cause oxidative stress, endoplasmic reticulum stress, cellular autophagy, and apoptosis. This review focuses on the current stage of FB1 contamination, its toxic effects of acute toxicity, immunotoxicity, organ toxicity, and reproductive toxicity on animals and humans. The potential toxic mechanisms of FB1 are discussed. One of the main aims of the work is to provide a reliable reference strategy for understanding the occurrence and toxicity of FB1.


Fumonisins/analysis , Animals , Apoptosis/drug effects , Autophagy/drug effects , Fumonisins/pharmacology , Fusarium/chemistry , Humans
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