Publications by authors named "Liming Zhao"

157 Publications

Gene-metabolite networks associated with impediment of bone fracture repair in spaceflight.

Comput Struct Biotechnol J 2021 8;19:3507-3520. Epub 2021 Jun 8.

Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.

Adverse effects of spaceflight on musculoskeletal health increase the risk of bone injury and impairment of fracture healing. Its yet elusive molecular comprehension warrants immediate attention, since space travel is becoming more frequent. Here we examined the effects of spaceflight on bone fracture healing using a 2 mm femoral segmental bone defect (SBD) model. Forty, 9-week-old, male C57BL/6J mice were randomized into 4 groups: 1) Sham surgery on Ground (G-Sham); 2) Sham surgery housed in Spaceflight (FLT-Sham); 3) SBD surgery on Ground (G-Surgery); and 4) SBD surgery housed in Spaceflight (FLT-Surgery). Surgery procedures occurred 4 days prior to launch; post-launch, the spaceflight mice were house in the rodent habitats on the International Space Station (ISS) for approximately 4 weeks before euthanasia. Mice remaining on the Earth were subjected to identical housing and experimental conditions. The right femur from half of the spaceflight and ground groups was investigated by micro-computed tomography (µCT). In the remaining mice, the callus regions from surgery groups and corresponding femoral segments in sham mice were probed by global transcriptomic and metabolomic assays. µCT confirmed escalated bone loss in FLT-Sham compared to G-Sham mice. Comparing to their respective on-ground counterparts, the morbidity gene-network signal was inhibited in sham spaceflight mice but activated in the spaceflight callus. µCT analyses of spaceflight callus revealed increased trabecular spacing and decreased trabecular connectivity. Activated apoptotic signals in spaceflight callus were synchronized with inhibited cell migration signals that potentially hindered the wound site to recruit growth factors. A major pro-apoptotic and anti-migration gene network, namely the RANK-NFκB axis, emerged as the central node in spaceflight callus. Concluding, spaceflight suppressed a unique biomolecular mechanism in callus tissue to facilitate a failed regeneration, which merits a customized intervention strategy.
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http://dx.doi.org/10.1016/j.csbj.2021.05.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220416PMC
June 2021

Cross-triggered and cascaded recycling amplification system for electrochemical detection of circulating microRNA in human serum.

Chem Commun (Camb) 2021 Jul;57(58):7116-7119

School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou 221116, China.

A cross-triggered and cascaded recycling amplification system was developed for electrochemical sensing of microRNA 122 based on the DNAzyme/multicomponent nucleic acid enzyme cleavage technique and a dumbbell-shaped probe. The linear range and detection limit were obtained to be 1 fM-100 pM and 0.34 fM, respectively. Compared with some reported studies, the proposed system can achieve the selective detection of endogenous miRNA in liver injury patients and healthy human serums with the advantages of high sensitivity, low cost, and easy manipulation, which are significant for disease diagnosis as well as the fundamental research of molecular biology.
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http://dx.doi.org/10.1039/d1cc02060aDOI Listing
July 2021

Application Fields, Positions, and Bioinformatic Mining of Non-active Sites: A Mini-Review.

Front Chem 2021 31;9:661008. Epub 2021 May 31.

School of Life Science, Shandong University of Technology, Zibo, China.

Active sites of enzymes play a vital role in catalysis, and researchhas been focused on the interactions between active sites and substrates to understand the biocatalytic process. However, the active sites distal to the catalytic cavity also participate in catalysis by maintaining the catalytic conformations. Therefore, some researchers have begun to investigate the roles of non-active sites in proteins, especially for enzyme families with different functions. In this mini-review, we focused on recent progress in research on non-active sites of enzymes. First, we outlined two major research methodswith non-active sites as direct targets, including understanding enzymatic mechanisms and enzyme engineering. Second, we classified the positions of reported non-active sites in enzyme structures and studied the molecular mechanisms underlying their functions, according to the literature on non-active sites. Finally, we summarized the results of bioinformatic analysisof mining non-active sites as targets for protein engineering.
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http://dx.doi.org/10.3389/fchem.2021.661008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201498PMC
May 2021

A Novel GH Family 20 β-N-acetylhexosaminidase With Both Chitosanase and Chitinase Activity From .

Front Mol Biosci 2021 19;8:684086. Epub 2021 May 19.

School of Biotechnology, State Key Laboratory of Bioreactor Engineering, R&D Center of Separation and Extraction Technology in Fermentation Industry, East China University of Science and Technology, Shanghai, China.

Aminooligosaccharides possess various biological activities and can exploit wide applications in food, pharmaceutical and cosmetic industries. Commercial aminooligosaccharides are often prepared by the hydrolysis of chitin and chitosan. In this study, a novel GH family 20 β-N-acetylhexosaminidases gene named AoNagase was cloned from and expressed in . The purified AoNagase had maximal activity at pH 5.5 and 65°C. It exhibited good pH stability in the range of pH 6.0-7.5 and at temperatures below 50°C. AoNagase was capable of hydrolyzing not only colloidal chitosan (508.26 U/mg) but also chitin (29.78 U/mg). The kinetic parameters ( and ) of AoNagase were 1.51 mM, 1106.02 U/mg for chitosan and 0.41 mM, 40.31 U/mg for colloidal chitin. To our knowledge, AoNagase is the first GH family 20 β-N-acetylhexosaminidase capable of hydrolyzing both chitosan and chitin. AoNagase is an endo-type β-N-acetylhexosaminidases and can potentially be used for the manufacturing of aminooligosaccharides.
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http://dx.doi.org/10.3389/fmolb.2021.684086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170477PMC
May 2021

Occlusion of the Anterior Cerebral Artery Mimicking a Cerebral Aneurysm: Clinical Presentation and Literature Review.

J Neurol Surg A Cent Eur Neurosurg 2021 May 24. Epub 2021 May 24.

Department of Neurosurgery, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Cerebrovascular Disease Hospital, Henan University People's Hospital, Zhengzhou, Henan, China.

Background:  Intracranial aneurysms may be misdiagnosed with other vascular lesions such as vascular loops, infundibulum, or the stump of an occluded artery (very rare and reported compromising only the middle cerebral artery and the posterior circulation territory). Our aim was to describe a unique case of occlusion of an anterior cerebral artery mimicking a cerebral aneurysm in a probable moyamoya disease patient, and to highlight its clinical presentation, diagnosis, and management, and to perform an extensive literature review.

Case:  A 67-year-old man suffering from recurrent dizziness for 3 months. Previous medical history was unremarkable. Brain magnetic resonance angiography (MRA) and digital subtraction angiography (DSA) demonstrated occlusion of the right middle cerebral artery (MCA) associated with a "probable moyamoya disease" and an aneurysm-like shadow protruding lesion at the anterior communicating artery (AcomA). Perfusion images showed ischemia along the right temporo-occipital lobe. Due to MCA occlusion with perfusion deficits and unspecific symptoms, we offered a right side encephalo-duro-myo-synangiosis (EDMS) and clipping of the AcomA aneurysm in one session. Intraoperatively, there was no evidence of the AcomA aneurysm; instead, this finding corresponded to the stump of the occluded right anterior cerebral artery (A1 segment). This segment appeared to be of yellowish color due to atherosclerosis and lacked blood flow. The patient underwent as previously planned a right side EDMS and the perioperative course was uneventful without the presence of additional ischemic attacks.

Conclusion:  Arterial branch occlusions can sometimes present atypical angiographic characteristics that can mimic a saccular intracranial aneurysm. It is relevant to consider this radiographic differential diagnosis, especially when aneurysm treatment is planned.
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http://dx.doi.org/10.1055/s-0040-1722272DOI Listing
May 2021

Whole-genome resequencing identified candidate genes associated with the number of ribs in Hu sheep.

Genomics 2021 Jul 11;113(4):2077-2084. Epub 2021 May 11.

College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, Gansu 730070, China. Electronic address:

The number of ribs is an important economic trait in the sheep industry when the sheep are raised for mutton. However, in sheep, the genetic mechanisms regulating rib number are poorly understood. In the present study, we aimed to identify important candidate genes that affect the increase in rib number in sheep. Whole-genome resequencing of 36 Hu sheep with an increased number of ribs (R14) and 36 sheep with normal (R13) rib numbers was carried out. Analysis using three methods (fixation index (F), Fisher's exact test, and Chi-squared test) showed that 219 single nucleotide polymorphism sites overlapped among the results of the three methods, which represented 206 genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that the genes were mainly associated with regulation of developmental process, inorganic anion transport, cellular biosynthetic process, tight junction, the oxytocin signaling pathway, and arrhythmogenic right ventricular cardiomyopathy. Four mutations were selected according to the significantly selected genomic regions and important pathways for genotyping and association analysis. The result demonstrated that three synonymous mutations correlated significantly with the rib number. Importantly, we revealed that the CPOX (encoding coproporphyrinogen oxidase), KCNH1 (encoding potassium voltage-gated channel subfamily H member 1), and CPQ (encoding carboxypeptidase Q) genes have a combined effect on rib number in Hu sheep. Our results identified candidate molecular markers for rib number in sheep breeding.
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http://dx.doi.org/10.1016/j.ygeno.2021.05.004DOI Listing
July 2021

Characterization of umami compounds in bone meal hydrolysate.

J Food Sci 2021 Jun 4;86(6):2264-2275. Epub 2021 May 4.

State Key Laboratory of Bioreactor Engineering, R&D Center of Separation and Extraction Technology in Fermentation Industry, East China University of Science and Technology, Shanghai, China.

The objective of this research was to identify and characterize the chemical compounds that exhibited monosodium glutamate (MSG)-like taste in the hydrolyzed bone meal produced by using flavourzyme. The free amino acids and peptides in the bone meal hydrolysate were analyzed. The results showed that the glutamic acid and the aspartic acid in the bone meal increased by 13.1 times and 14.2 times, respectively, after the flavourzyme hydrolysis. The peptides' isolation identified six MSG-like peptides in the hydrolysate, including APGPVGPAG, DAINWPTPGEIAH, FLGDEETVR, GVDEATIIEILTK, PAGPVGPVG, and VAPEEHPTL, which should contribute to the taste. The human sensory evaluation results indicated that the six peptides showed MSG-like taste, and the electronic tongue analysis indicated that the six peptides showed sourness, saltiness, bitterness, and astringency. The findings of this study demonstrated that the MSG-like taste of the bone meal hydrolysate should be attributed to the generation of MSG-like amino acids and peptides from the flavourzyme hydrolysis. PRACTICAL APPLICATION: The manuscript describes the umami compounds in the bone meal hydrolysate. The findings from this study should further confirm the feasibility of using bone meal to prepare meat-flavor essence and provide a better understanding of preparing bio-source flavoring peptides, which is very important to the artificial meat development and gene breeding.
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http://dx.doi.org/10.1111/1750-3841.15751DOI Listing
June 2021

Gradient Heating Effect Modulated by Hydrophobic/Hydrophilic Carbon Nanotube Network Structures for Ultrafast Solar Steam Generation.

ACS Appl Mater Interfaces 2021 Apr 14;13(16):19109-19116. Epub 2021 Apr 14.

School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei 230000, China.

The emerging interface solar-thermal water evaporation has been widely studied to solve fresh water shortage because of its high solar-thermal conversion efficiency, environmental friendliness, and low cost. However, traditional water evaporation systems inevitably lose heat to the environment, which not only greatly affects the water evaporation rate but also hinders their practical applications. In this work, an interface solar-thermal water evaporation system with enhanced heat localization, which is combined by a hydrophobic carbon nanotube (CNT) film (heating layer) and hydrophilic polyvinyl alcohol (PVA)/CNT foam (evaporating layer), is demonstrated. Under solar irradiation, the temperature of the hydrophobic CNT film is higher than that of the hydrophilic PVA/CNT foam due to the differences in wettability, so the thermal energy in the CNT film can be continuously transferred to the PVA/CNT foam evaporator, forming a gradient heating effect and greatly increasing the water evaporation rate. As a result, the water evaporation rate can reach 4.2 kg m h under a solar illumination of 1 kW m, which is among the highest water evaporation rate levels. More importantly, this water evaporation system structure is simple, can be easily scaled up, and has gradient applicability to other photothermal materials, which provides a route to improve the interfacial solar steam evaporation rate.
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http://dx.doi.org/10.1021/acsami.0c21831DOI Listing
April 2021

Lexical Planning in People Who Stutter: A Defect in Lexical Encoding or the Planning Scope?

Front Psychol 2021 23;12:581304. Epub 2021 Feb 23.

Faculty of Psychology, Tianjin Normal University, Tianjin, China.

Developmental stuttering is a widely discussed speech fluency disorder. Research on its mechanism has focused on an atypical interface between the planning (PLAN) and execution (EX) processes, known collectively as the EXPLAN model. However, it remains unclear how this atypical interface influences people who stutter. A straightforward assumption is that stuttering speakers adopt a smaller scope of speech planning, whereas a defect in word retrieval can be confounding. To shed light on this issue, we took the semantic blocking effect as an index to examine lexical planning in word and phrase production. In Experiment 1, for word production, pictures from the same semantic category were combined to form homogeneous blocks, and pictures from different categories were combined to form heterogeneous blocks. A typical effect of semantic blocking showing longer naming latencies for homogeneous blocks than heterogeneous ones was observed for both stuttering and fluent speakers. However, this effect was smaller for stuttering speakers, when it was subject to lexical defects in stuttering. In Experiment 2, for a conjoined noun phrase production task, the pictures referring to the first noun were manipulated into homogeneous and heterogeneous conditions. The semantic blocking effect was also much smaller for stuttering speakers, indicating a smaller scope of lexical planning. Therefore, the results provided more evidence in support of the EXPLAN model and indicated that a smaller scope of lexical planning rather than lexical defects causes the atypical interface for stuttering. Moreover, a comparison between these two tasks showed that the study findings have implications for syntactic defects in stuttering.
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http://dx.doi.org/10.3389/fpsyg.2021.581304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940678PMC
February 2021

Current innovations in nutraceuticals and functional foods for intervention of non-alcoholic fatty liver disease.

Pharmacol Res 2021 04 24;166:105517. Epub 2021 Feb 24.

School of Biotechnology, State Key Laboratory of Bioreactor Engineering, R&D Center of Separation and Extraction Technology in Fermentation Industry, East China University of Science and Technology, Shanghai 200237, China; School of Life Science, Shandong University of Technology, Zibo, Shandong 255000, China; Shanghai Collaborative Innovation Center for Biomanufacturing Technology (SCICBT), Shanghai 200237, China. Electronic address:

As innovations in global agricultural production and food trading systems lead to major dietary shifts, high morbidity rates from non-alcoholic fatty liver disease (NAFLD), accompanied by elevated risk of lipid metabolism-related complications, has emerged as a growing problem worldwide. Treatment and prevention of NAFLD and chronic liver disease depends on the availability of safe, effective, and diverse therapeutic agents, the development of which is urgently needed. Supported by a growing body of evidence, considerable attention is now focused on interventional approaches that combines nutraceuticals and functional foods. In this review, we summarize the pathological progression of NAFLD and discuss the beneficial effects of nutraceuticals and the active ingredients in functional foods. We also describe the underlying mechanisms of these compounds in the intervention of NAFLD, including their effects on regulation of lipid homeostasis, activation of signaling pathways, and their role in gut microbial community dynamics and the gut-liver axis. In order to identify novel targets for treatment of lipid metabolism-related diseases, this work broadly explores the molecular mechanism linking nutraceuticals and functional foods, host physiology, and gut microbiota. Additionally, the limitations in existing knowledge and promising research areas for development of active interventions and treatments against NAFLD are discussed.
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http://dx.doi.org/10.1016/j.phrs.2021.105517DOI Listing
April 2021

Prognostic nutritional index and the risk of mortality in patients with hypertrophic cardiomyopathy.

Int J Cardiol 2021 05 30;331:152-157. Epub 2021 Jan 30.

Department of Cardiology, West China Hospital of Sichuan University, Chengdu, China. Electronic address:

Aims: Nutritional status has been related to clinical outcomes in patients with cardiovascular diseases. The prognostic impact of poor nutritional status in hypertrophic cardiomyopathy (HCM) is not clearly understood. The aim of the present study is to investigate the prognostic value of prognostic nutritional index (PNI), calculated from serum albumin level and total lymphocyte count, in HCM patients.

Methods: A total of 393 HCM patients in a tertiary medical centre were enrolled. The primary and secondary endpoints were all-cause mortality and cardiovascular death. The association between PNI and endpoints was analysed.

Results: During a mean follow-up duration of 4.8 years, patients with high PNI values (PNI ≥ 48.8) had significantly lower incidence of all-cause mortality (9.3% vs. 33.1%, P < 0.001) and cardiovascular death (7.1% vs. 21.0%, P < 0.001). After adjusting for potential confounders, PNI was independently associated with all-cause mortality and cardiovascular death (hazard ratio per 1 SD increase: 0.46 [95% CI: 0.34-0.62, P < 0.001] and 0.44 [95% CI: 0.30-0.63, P < 0.001]). In subgroup analysis stratified by age, gender, New York Heart Association class, atrial fibrillation, estimated glomerular filtration rate, left ventricular ejection fraction or left ventricular outflow tract obstruction, PNI was consistently related to mortality.

Conclusions: PNI is an independent prognostic factor for mortality in patients with HCM.
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http://dx.doi.org/10.1016/j.ijcard.2021.01.023DOI Listing
May 2021

Triglyceride-glucose index as predictor for future type 2 diabetes mellitus in a Chinese population in southwest China: a 15-year prospective study.

Endocrine 2021 04 12;72(1):124-131. Epub 2021 Jan 12.

Department of Cardiology, West China Hospital of Sichuan University, Chengdu, China.

Purpose: Triglyceride-glucose (TyG) index is an emerging surrogate predictor of incident type 2 diabetes mellitus (T2DM). The study aimed to examine the association between TyG index and incident T2DM in a prospective Chinese cohort.

Methods: The data were collected in 1992 and recollected in 2007 from the same group of 687 participants. The association between TyG index and T2DM was analysed.

Results: During follow-up, 74 participants developed T2DM and the risk of T2DM increased with TyG index. The adjusted hazard ratio (HR) was 3.36 (95% CI: 1.52-7.39, P < 0.001) comparing the top TyG quartile to the bottom quartile. Smooth curve fitting revealed a nonlinear association and threshold effect between TyG index and incident T2DM with a nadir of risk when TyG index was around 8.51. For TyG ≤ 8.51, the risk of incident T2DM tended to decrease with per SD increase in TyG but no statistical significance was achieved (adjusted HR: 0.69, 95% CI: 0.43-1.12, P = 0.133). For TyG > 8.51, the risk of incident T2DM significantly increased by 38% with per SD increase in TyG (adjusted HR: 1.38, 95% CI: 1.14-1.67, P = 0.001). Time-dependent receiver operating curve suggested helpful discriminative power of TyG index for T2DM. It also significantly promoted the reclassification ability beyond the baseline risk model with net reclassification index of 0.159 (P = 0.020). Sensitivity analysis excluding participants with prediabetes demonstrated similar results.

Conclusions: The TyG index was a significant and independent predictor for future T2DM development. The shape of relationship will require further studies.
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http://dx.doi.org/10.1007/s12020-020-02589-7DOI Listing
April 2021

Relation between neutrophil-to-lymphocyte ratio and mortality in patients with hypertrophic cardiomyopathy.

Biomark Med 2020 12;14(18):1693-1701

Department of Cardiology, West China Hospital of Sichuan University, Chengdu, China.

We assessed the prognostic value of neutrophil-to-lymphocyte ratio (NLR) for all-cause mortality in patients with hypertrophic cardiomyopathy (HCM). A total of 354 HCM patients were enrolled. There were 44 all-cause mortality in total. Patients in the third tertile of NLR had the highest all-cause mortality rate of 5.2 per 100 person-years. Patients in tertile 3 had a significantly higher risk of all-cause mortality with adjusted hazard ratio of 2.4 (95% CI: 1.0-5.4; p = 0.040) when compared with that of patients in tertile 1. No significant interactions between NLR and other variables were observed during subgroup analysis. NLR was an independent risk factor for all-cause mortality in HCM patients.
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http://dx.doi.org/10.2217/bmm-2020-0463DOI Listing
December 2020

The Association between Socioeconomic Factors and Visual Function among Patients with Age-Related Cataracts.

J Ophthalmol 2020 30;2020:7236214. Epub 2020 Nov 30.

Department of Ophthalmology, Hebei Eye Hospital, 399 Quanbeidong Street, Xingtai 054001, Hebei, China.

Background: With the development of the economy, socioeconomic factors, such as inequalities in the status of regional economies and the subsequent effects on health systems, have influenced the status of health. We explored the association between age-related cataracts and socioeconomic indicators, including the regional economy, health systems, and energy industries.

Methods: This was a prospective, multicenter, Chinese population-based, cross-sectional study. A total of 830 participants from seven centers were enrolled. Data on the best-corrected visual acuity (BCVA), Lens Opacities Classification System III (LOCS III) score, Visual Function Index-14 (VF-14) score, total and subscale scores of the 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), per capita disposable income (PCDI), medical resource-related indicators, and investments in the energy industry were obtained. Associations among these parameters were analyzed.

Results: The PCDI ranking was correlated with the VF-14 score ( = -0.426, < 0.01), total score of NEI-VFQ-25 ( = -0.500, < 0.01), and BCVA ( = 0.278, < 0.01). The number of health agencies (1 = 0.267, 2 = -0.303, 3 = -0.291,), practicing or assistant practicing doctors (1 = -0.283, 2 = 0.427, 3 = 0.502,), registered nurses (1 = -0.289, 2 = 0.409, 3 = 0.469, < 0.01), and health technicians (1 = -0.278, 2 = 0.426, 3 = 0.500, < 0.01) per 10,000 of the population was each correlated with the BCVA, VF-14 score, and total score of NEI-VFQ-25, respectively. Health expenditure per capita was correlated with the VF-14 score ( = 0.287, < 0.01) and total score of NEI-VFQ-25 ( = 0.459, < 0.01). The LOCS III P score was correlated with investments in the energy industry ( = 0.485, < 0.001).

Conclusions: Patients in higher economic regions with greater medical resources show a greater demand to undergo cataract surgery at a better subjective and objective visual function. The energy industry has a significant effect on cataracts, especially the posterior subcapsular cataract, and thus more attention should be paid to people in regions with abundant energy industries.
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http://dx.doi.org/10.1155/2020/7236214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722637PMC
November 2020

Impact of blood pressure changes in cerebral blood perfusion of patients with ischemic Moyamoya disease evaluated by SPECT.

J Cereb Blood Flow Metab 2021 06 5;41(6):1472-1480. Epub 2020 Nov 5.

Department of Neurosurgery, Cerebrovascular Disease Hospital, Henan Provincial People's Hospital; Zhengzhou University, Zhengzhou, China.

Our aim was to determine the impact of targeted blood pressure modifications on cerebral blood flow in ischemic moyamoya disease patients assessed by single-photon emission computed tomography (SPECT). From March to September 2018, we prospectively collected data of 154 moyamoya disease patients and selected 40 patients with ischemic moyamoya disease. All patients underwent in-hospital blood pressure monitoring to determine the mean arterial pressure baseline values. The study cohort was subdivided into two subgroups: (1) Group A or relative high blood pressure (RHBP) with an induced mean arterial pressure 10-20% higher than baseline and (2) Group B or relative low blood pressure (RLBP) including patients with mean arterial pressure 10-20% lower than baseline. All patients underwent initial SPECT study on admission-day, and on the following day, every subgroup underwent a second SPECT study under their respective targeted blood pressure values. In general, RHBP patients showed an increment in perfusion of 10.13% (SD 2.94%), whereas RLBP patients showed a reduction of perfusion of 12.19% (SD 2.68%). Cerebral blood flow of moyamoya disease patients is susceptible to small blood pressure changes, and cerebral autoregulation might be affected due to short dynamic blood pressure modifications.
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http://dx.doi.org/10.1177/0271678X20967458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142135PMC
June 2021

Structure-function analysis of Gynuella sunshinyii chitosanase uncovers the mechanism of substrate binding in GH family 46 members.

Int J Biol Macromol 2020 Dec 17;165(Pt B):2038-2048. Epub 2020 Oct 17.

School of Biotechnology, State Key Laboratory of Bioreactor Engineering, R&D Center of Separation and Extraction Technology in Fermentation Industry, East China University of Science and Technology, Shanghai 200237, China; Shanghai Collaborative Innovation Center for Biomanufacturing Technology (SCICBT), Shanghai 200237, China. Electronic address:

Chitooligosaccharides (COS) is a kind of functional carbohydrates with great application potential as its various biological functions in food, cosmetics, and pharmaceutical fields. Exploring the relationship between structure and function of chitosanase is essential for the controllable preparation of chitooligosaccharides with the specific degree of polymerization (DP). GsCsn46A is a cold-adapted glycosyl hydrolase (GH) family 46 chitosanase with application potential for the controllable preparation of chitooligosaccharides. Here, we present two complex structures with substrate chitopentaose and chitotetraose of GsCsn46A, respectively. The overall structure of GsCsn46A contains nine α-helices and two β-strands that folds into two globular domains with the substrate between them. The unique binding positions of both chitopentaose and chitotetraose revealed two novel sugar residues in the negatively-numbered subsites of GH family 46 chitosanases. The structure-function analysis of GsCsn46A uncovers the substrate binding and catalysis mechanism of GH family 46 chitosanases. Structural basis mutagenesis in GsCsn46A indicated that altering interactions near +3 subsite would help produce hydrolysis products with higher DP. Specifically, the mutant N21W of GsCsn46A nearly eliminated the ability of hydrolyzing chitotetraose after long-time degradation.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.10.066DOI Listing
December 2020

Myocardial contraction fraction predicts mortality for patients with hypertrophic cardiomyopathy.

Sci Rep 2020 10 12;10(1):17026. Epub 2020 Oct 12.

Department of Cardiology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan Province, People's Republic of China.

The myocardial contraction fraction (MCF: stroke volume to myocardial volume) is a novel volumetric measure of left ventricular myocardial shortening. The purpose of the present study was to assess whether MCF could predict adverse outcomes for HCM patients. A retrospective cohort study of 438 HCM patients was conducted. The primary and secondary endpoints were all-cause mortality and HCM-related mortality. The association between MCF and endpoints was analysed. During a follow-up period of 1738.2 person-year, 76 patients (17.2%) reached primary endpoint and 50 patients (65.8%) reached secondary endpoint. Both all-cause mortality rate and HCM-related mortality rate decreased across MCF tertiles (24.7% vs. 17.9% vs. 9.5%, P trend = 0.003 for all-cause mortality; 16.4% vs. 9.7% vs. 6.1%, P trend = 0.021 for HCM-related mortality). Patients in the third tertile had a significantly lower risk of developing adverse outcomes than patients in the first tertile: all-cause mortality (adjusted HR: 0.26, 95% CI: 0.12-0.56, P = 0.001), HCM-related mortality (adjusted HR: 0.17, 95% CI: 0.07-0.42, P < 0.001). At 1-, 3-, and 5-year of follow-up, areas under curve were 0.699, 0.643, 0.618 for all-cause mortality and 0.749, 0.661, 0.613 for HCM-related mortality (all P value < 0.001), respectively. In HCM patients, MCF could independently predict all-cause mortality and HCM-related mortality, which should be considered for overall risk assessment in clinical practice.
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http://dx.doi.org/10.1038/s41598-020-72712-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552384PMC
October 2020

Extending nudged elastic band method to reaction pathways involving multiple spin states.

J Chem Phys 2020 Oct;153(13):134114

Institute for Catalysis, Hokkaido University, N21 W10 Kita-ku, Sapporo 001-0021, Hokkaido, Japan.

There are diverse reactions including spin-state crossing, especially the reactions catalyzed by transition metal compounds. To figure out the mechanisms of such reactions, the discussion of minimum energy intersystem crossing (MEISC) points cannot be avoided. These points may be the bottleneck of the reaction or inversely accelerate the reactions by providing a better pathway. It is of great importance to reveal their role in the reactions by computationally locating the position of the MEISC points together with the reaction pathway. However, providing a proper initial guess for the structure of the MEISC point is not as easy as that of the transition state. In this work, we extended the nudged elastic band (NEB) method for multiple spin systems, which is named the multiple spin-state NEB method, and it is successfully applied to find the MEISC points while optimizing the reaction pathway. For more precisely locating the MEISC point, a revised approach was adopted. Meanwhile, our examples also suggest that special attention should be paid to the criterion to define an image optimized as the MEISC point.
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http://dx.doi.org/10.1063/5.0021923DOI Listing
October 2020

KIAA0101 and UbcH10 interact to regulate non-small cell lung cancer cell proliferation by disrupting the function of the spindle assembly checkpoint.

BMC Cancer 2020 Oct 2;20(1):957. Epub 2020 Oct 2.

Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Pudong, Shanghai, 200120, P.R. China.

Background: Chromosome mis-segregation caused by spindle assembly checkpoint (SAC) dysfunction during mitosis is an important pathogenic factor in cancer, and modulating SAC function has emerged as a potential novel therapy for non-small cell lung cancer (NSCLC). UbcH10 is considered to be associated with SAC function and the pathological types and clinical grades of NSCLC. KIAA0101, which contains a highly conserved proliferating cell nuclear antigen (PCNA)-binding motif that is involved in DNA repair in cancer cells, plays an important role in the regulation of SAC function in NSCLC cells, and bioinformatics predictions showed that this regulatory role is related to UbcH10. We hypothesized KIAA0101 and UbcH10 interact to mediate SAC dysfunction and neoplastic transformation during the development of USCLC.

Methods: NSCLC cell lines were used to investigate the spatial-temporal correlation between UbcH10 and KIAA0101 expression and the downstream effects of modulating their expression were evaluated. Further immunoprecipitation assays were used to investigate the possible mechanism underlying the correlation between UbcH10 and KIAA0101. Eventually, the effect of modulating UbcH10 and KIAA010 on tumor growth and its possible mechanisms were explored through in vivo tumor-bearing models.

Results: In this study, we demonstrated that both UbcH10 and KIAA0101 were upregulated in NSCLC tissues and cells and that their expression levels were correlated in a spatial and temporal manner. Importantly, UbcH10 and KIAA0101 coordinated to mediate the premature degradation of various SAC components to cause further SAC dysfunction and neoplastic proliferation. Moreover, tumor growth in vivo was significantly inhibited by silencing UbcH10 and KIAA0101 expression.

Conclusions: KIAA0101 and UbcH10 interact to cause SAC dysfunction, chromosomal instability and malignant proliferation in NSCLC, suggesting that UbcH10 and KIAA0101 are potential therapeutic targets for the treatment of NSCLC by ameliorating SAC function.
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http://dx.doi.org/10.1186/s12885-020-07463-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532574PMC
October 2020

Analysis of lens epithelium telomere length in age-related cataract.

Exp Eye Res 2020 12 28;201:108279. Epub 2020 Sep 28.

Peking University Third Hospital, Beijing, China. Electronic address:

We aimed to investigate the associations among lens epithelium telomere length (LETL), cataract types, and systemic pro-senescence factors in patients with age-related cataract. In this prospective study, the general demographic factors, body mass index, smoking history, depression, hypertension, diabetes, various psychological measures, and uncorrected distant visual acuity of patients with age-related cataract were recorded. Lens Opacities Classification System III (LOCS III) scores and lens density measured by Scheimpflug imaging were used to evaluate the cataracts. LETL was measured by real-time polymerase chain reaction. Correlations among these parameters were analyzed. The LOCS III nuclear opalescence (NO) score was associated with age (β = 0.053, P < 0.001) and Patient Health Questionnaire-9 score (β = -0.042, P = 0.004). Smoking was identified as a risk factor affecting LOCS III NO score (odds ratio = 1.546, 95% confidence interval, 1.128-2.119), but not the LOCS III cortical or posterior subcapsular scores. LETLs showed a weak association with systemic factors and LOCS III scores, and a significantly moderate correlation with the average objective lens densities of different regions measured by Scheimpflug imaging (r values ranged from -0.278 to -0.523, P < 0.05). However, there was no correlation between the LETLs and the maximum lens densities. The groups with a relatively low lens density had longer LETLs. In Conclusion, being an age-related disease, cortical cataract was also associated with "aging of the lens epithelium." Notably, lens epithelium activity rarely showed systemic effects. Thus, future studies should emphasize the importance of the telomeric system in cataractous process and aging.
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http://dx.doi.org/10.1016/j.exer.2020.108279DOI Listing
December 2020

Validation and comparison of the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) and the Visual Function Index-14 (VF-14) in patients with cataracts: a multicentre study.

Acta Ophthalmol 2021 Jun 17;99(4):e480-e488. Epub 2020 Sep 17.

Peking University Third Hospital, Beijing, China.

Purpose: The present study aimed to investigate and compare the psychometric properties of the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) and the Visual Function Index-14 (VF-14) in a large sample of patients with cataracts.

Methods: A total of 1052 patients with bilateral age-related cataracts were recruited in the study. Patients with other comorbidities that severely impacted vision were excluded. Participants completed the two questionnaires in random order. Classical test theory and Rasch analyses were used to assess the psychometric properties of the questionnaires.

Results: Complete data were obtained from 899 patients. The mean overall index score on the NEI VFQ-25 was 76.1 ± 19.0, while that on the VF-14 was 46.5 ± 15.0. Cronbach's α-values for the NEI VFQ-25 and VF-14 were 0.89 and 0.95, respectively. Ceiling effects were observed on nine of the 12 subscales in the NEI VFQ-25. The correlation between total scores on the NEI VFQ-25 and VF-14 was moderate (r = 0.600; p < 0.001), and subscales of the NEI VFQ-25 were weakly or moderately correlated with the similar domains on the VF-14. Rasch analysis revealed ordered category thresholds and sufficient person separation for both instruments, while the two questionnaires had critical deficiencies in unidimensionality, targeting and differential item functioning.

Conclusion: Neither the NEI VFQ-25 nor VF-14 is optimal for the assessment of vision-related quality of life in typical Chinese patients with cataracts. The potential deficiencies of the questionnaires should be taken into consideration prior to application of the instruments or interpretation of the results.
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http://dx.doi.org/10.1111/aos.14606DOI Listing
June 2021

Effects of Metabolic Syndrome on Semen Quality and Circulating Sex Hormones: A Systematic Review and Meta-Analysis.

Front Endocrinol (Lausanne) 2020 11;11:428. Epub 2020 Aug 11.

Department of Urology, Linyi People's Hospital, Linyi, China.

Previous studies were controversial in the effects of metabolic syndrome (MetS) on semen quality and circulating sex hormones, and thus we conducted a systematic review and meta-analysis to clarify the association. A systematic search was conducted in public databases to identify all relevant studies, and study-specific standardized mean differences (SMD) and 95% confidence intervals (CI) were pooled using a random-effects model. Finally, 11 studies were identified with a total of 1,731 MetS cases and 11,740 controls. Compared with the controls, MetS cases had a statistically significant decrease of sperm total count (SMD: -0.96, 95% CI: -1.58 to -0.31), sperm concentration (SMD: -1.13, 95% CI: -1.85 to -0.41), sperm normal morphology (SMD: -0.61, 95% CI: -1.01 to -0.21), sperm progressive motility (SMD: -0.58, 95% CI: -1.00 to -0.17), sperm vitality (SMD: -0.83, 95% CI: -1.11 to -0.54), circulating follicle-stimulating hormone (SMD: -0.87, 95% CI: -1.53 to -0.21), testosterone (SMD: -5.61, 95% CI: -10.90 to -0.31), and inhibin B (SMD: -2.42, 95% CI: -4.52 to -0.32), and a statistically significant increase of sperm DNA fragmentation (SMD: 0.76, 95% CI: 0.45 to 1.06) and mitochondrial membrane potential (SMD: 0.89, 95% CI: 0.49 to 1.28). No significant difference was found in semen volume, sperm total motility, circulating luteinizing hormone (LH), estradiol, prolactin and anti-Müllerian hormone (AMH) ( > 0.05). In conclusion, this meta-analysis demonstrated the effects of MetS on almost all the semen parameters and part of the circulating sex hormones, and MetS tended to be a risk factor for male infertility. Further larger-scale prospective designed studies were needed to confirm our findings.
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http://dx.doi.org/10.3389/fendo.2020.00428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431460PMC
May 2021

Articular cartilage regeneration by activated skeletal stem cells.

Nat Med 2020 10 17;26(10):1583-1592. Epub 2020 Aug 17.

Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Osteoarthritis (OA) is a degenerative disease resulting in irreversible, progressive destruction of articular cartilage. The etiology of OA is complex and involves a variety of factors, including genetic predisposition, acute injury and chronic inflammation. Here we investigate the ability of resident skeletal stem-cell (SSC) populations to regenerate cartilage in relation to age, a possible contributor to the development of osteoarthritis. We demonstrate that aging is associated with progressive loss of SSCs and diminished chondrogenesis in the joints of both mice and humans. However, a local expansion of SSCs could still be triggered in the chondral surface of adult limb joints in mice by stimulating a regenerative response using microfracture (MF) surgery. Although MF-activated SSCs tended to form fibrous tissues, localized co-delivery of BMP2 and soluble VEGFR1 (sVEGFR1), a VEGF receptor antagonist, in a hydrogel skewed differentiation of MF-activated SSCs toward articular cartilage. These data indicate that following MF, a resident stem-cell population can be induced to generate cartilage for treatment of localized chondral disease in OA.
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http://dx.doi.org/10.1038/s41591-020-1013-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704061PMC
October 2020

Neutrophil-to-lymphocyte ratio predicts the clearance of SARS-CoV-2 RNA in mild COVID-19 patients - a retrospective analysis from Dongxihu Fangcang Hospital in Wuhan, China.

Clin Chem Lab Med 2020 08 1;58(9):e167-e170. Epub 2020 Jul 1.

Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, P.R. China.

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http://dx.doi.org/10.1515/cclm-2020-0733DOI Listing
August 2020

Chitooligosaccharides-modified PLGA nanoparticles enhance the antitumor efficacy of AZD9291 (Osimertinib) by promoting apoptosis.

Int J Biol Macromol 2020 Nov 20;162:262-272. Epub 2020 Jun 20.

State Key Laboratory of Bioreactor Engineering, R&D Center of Separation and Extraction Technology in Fermentation Industry, School of Biotechnology, East China University of Science and Technology, Shanghai 200237, China; Shanghai Collaborative Innovation Center for Biomanufacturing Technology (SCICBT), Shanghai 200237, China. Electronic address:

The nano drug delivery system (NDDS) has been extensively investigated for cancer treatment because of its ability to enhance drug efficacy. However, there are only a few studies attempting NDDS for AZD9291 (Osimertinib). Here, we encapsulated AZD9291 in chitooligosaccharides (COS)-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles. COS, a cationic polymer, was used to develop positively charged nanoparticles with good biological affinity. The prepared AZD-PLGA-COS NPs exhibited a smaller particle size (176.6 ± 0.4 nm), a positively charged surface (+18.65 ± 0.38 mV), and an increased cellular uptake. The IC of H1975 cells was reduced by 45.90%, and the expression of p-EGFR, PARP, Bak, caspase-9, Bax, and Bcl-2 was regulated to promote cellular apoptosis. Furthermore, COS was found to inhibit the expression of immune checkpoint PD-L1. This study suggests that COS-modified PLGA nanoparticles with low toxicity and high encapsulation efficiency (EE) could potentially enhance drug efficacy.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.06.154DOI Listing
November 2020

Geriatric fragility fractures are associated with a human skeletal stem cell defect.

Aging Cell 2020 07 14;19(7):e13164. Epub 2020 Jun 14.

Department of Surgery, Stanford Medicine, Stanford, CA, USA.

Fragility fractures have a limited capacity to regenerate, and impaired fracture healing is a leading cause of morbidity in the elderly. The recent identification of a highly purified bona fide human skeletal stem cell (hSSC) and its committed downstream progenitor cell populations provides an opportunity for understanding the mechanism of age-related compromised fracture healing from the stem cell perspective. In this study, we tested whether hSSCs isolated from geriatric fractures demonstrate intrinsic functional defects that drive impaired healing. Using flow cytometry, we analyzed and isolated hSSCs from callus tissue of five different skeletal sites (n = 61) of patients ranging from 13 to 94 years of age for functional and molecular studies. We observed that fracture-activated amplification of hSSC populations was comparable at all ages. However, functional analysis of isolated stem cells revealed that advanced age significantly correlated with reduced osteochondrogenic potential but was not associated with decreased in vitro clonogenicity. hSSCs derived from women displayed an exacerbated functional decline with age relative to those of aged men. Transcriptomic comparisons revealed downregulation of skeletogenic pathways such as WNT and upregulation of senescence-related pathways in young versus older hSSCs. Strikingly, loss of Sirtuin1 expression played a major role in hSSC dysfunction but re-activation by trans-resveratrol or a small molecule compound restored in vitro differentiation potential. These are the first findings that characterize age-related defects in purified hSSCs from geriatric fractures. Our results provide a foundation for future investigations into the mechanism and reversibility of skeletal stem cell aging in humans.
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http://dx.doi.org/10.1111/acel.13164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370785PMC
July 2020

Association between sleep-disordered breathing and lower extremity artery disease: a meta-analysis.

Sleep Breath 2021 Mar 12;25(1):227-236. Epub 2020 May 12.

Department of Neurosurgery, Liuzhou People's Hospital, No. 8 Wenchang Road, Liuzhou, 545006, China.

Objective: Previous studies suggest a relationship between sleep disordered breathing (SDB) and lower extremity artery disease (LEAD) though disagreements remain. This study was performed to assess the association between SDB and LEAD in a metaanalysis.

Methods: PubMed and Embase databases were searched for observational studies. A random-effects model incorporating between-study heterogeneity was used to pool the data.

Results: The search revealed 7 studies including 152,885 participants. Patients with SDB had higher odds of LEAD (risk ratio [RR] = 1.32, 95% confidence interval [CI] = 1.07 to 1.63, p = 0.01, I = 66%) compared to non-SDB participants. In subgroup analyses, SDB was related to higher odds of LEAD in patients with stroke or diabetes (RR = 3.28, p < 0.001) than in a community-derived population (RR = 1.17, p = 0.08; p for subgroup difference < 0.001). Furthermore, the odds of LEAD was increased in patients with moderate (RR = 1.34, 95% CI = 1.04 to 1.73, p = 0.02) or severe SDB (RR = 1.81, 95% CI = 1.08 to 3.03, p = 0.02), but not in those with mild SDB (RR = 0.94, 95% CI = 0.69 to 1.29, p = 0.71). Differences in study design or methods for LEAD diagnosis did not appear to affect the association between SDB and LEAD.

Conclusions: Patients with SDB have higher odds of LEAD compared to non-SDB participants.
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http://dx.doi.org/10.1007/s11325-020-02096-zDOI Listing
March 2021

Epidemiological features and medical care-seeking process of patients with COVID-19 in Wuhan, China.

ERJ Open Res 2020 Apr 27;6(2). Epub 2020 Apr 27.

Dept of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University, Shanghai, China.

Background: We aimed to investigate the epidemiological and clinical features, and medical care-seeking process of patients with the 2019 coronavirus disease (COVID-19) in Wuhan, China, to provide useful information to contain COVID-19 in other places with similar outbreaks of the virus.

Methods: We collected epidemiological and clinical information of patients with COVID-19 admitted to a makeshift Fangcang hospital between 7 and 26 February, 2020. The waiting time of each step during the medical care-seeking process was also analysed.

Results: Of the 205 patients with COVID-19 infection, 31% had presumed transmission from a family member. 10% of patients had hospital-related transmission. It took as long as a median of 6 days from the first medical visit to receive the COVID-19 nucleic acid test and 10 days from the first medical visit to hospital admission, indicating early recognition of COVID-19 was not achieved at the early stage of the outbreak, although these delays were shortened later. After clinical recovery from COVID-19, which took a mean of 21 days from illness onset, there was still a substantial proportion of patients who had persistent SARS-CoV-2 infection.

Conclusions: The diagnostic evaluation process of suspected patients needs to be accelerated at the epicentre of the outbreak and early isolation of infected patients in a healthcare setting rather than at home is urgently required to stop the spread of the virus. Clinical recovery is not an appropriate criterion to release isolated patients and as long as 4 weeks' isolation for patients with COVID-19 is not enough to prevent the spread of the virus.
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http://dx.doi.org/10.1183/23120541.00142-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184112PMC
April 2020

Time-Economical Radical Cascade Cyclization/Haloazidation of 1,6-Enynes: Construction of Highly Functional Succinimide Derivatives.

Org Lett 2020 Apr 7;22(8):2956-2960. Epub 2020 Apr 7.

School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116, P.R. China.

A "time-economical" radical cascade cyclization/haloazidation of 1,6-enynes provides a direct approach to access highly functional succinimide compounds. Moderate to excellent yields along with excellent / ratio were obtained under the reaction features of broad substrate scope, good functional group tolerance, and mild reaction conditions.
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http://dx.doi.org/10.1021/acs.orglett.0c00682DOI Listing
April 2020

Correlation among Lens Opacities Classification System III grading, the 25-item National Eye Institute Visual Functioning Questionnaire, and Visual Function Index-14 for age-related cataract assessment.

Int Ophthalmol 2020 Jul 5;40(7):1831-1839. Epub 2020 Apr 5.

Peking University Third Hospital, Beijing, China.

Purpose: To evaluate the relationship between cataract types and subjective visual function among patients with age-related cataract.

Methods: This was a prospective, multicenter, 831 Chinese patient-based, cross-sectional study. Patients were administered the Visual Function Index-14 (VF-14) and the 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) to evaluate their subjective visual function. Lens Opacities Classification System III (LOCS III) was used to evaluate the type of cataract. Relationships among these parameters were analyzed.

Results: LOCS III cortical (C) and posterior subcapsular scores are negatively associated with VF-14 (r = - 0.188, P < 0.01; r = - 0.146, P < 0.01) and total score of NEI-VFQ-25 (r = - 0.223, P < 0.01; r = - 0.160, P < 0.01), respectively; LOCS III nuclear opalescence (NO) score is positively associated with VF-14 (r = 0.087, P < 0.05) and total score of NEI-VFQ-25 (r = 0.097, P < 0.05). In multiple linear regression, a decrease in the LOCS III C score is a significant predictor for improvement of the total score of NEI-VFQ-25 (β = - 1.286, P < 0.05). In contrast, an increase in LOCS III NO score is a significant predictor for improvement of VF-14 (β = 3.826, P < 0.01) and total score of NEI-VFQ-25 (β = 4.618, P < 0.01). Patients with LOCS III C score ≤ 2 have higher VF-14 (49.38 versus 43.74, P < 0.01), total (80.73 versus 71.58, P < 0.01) and subscale scores of NEI-VFQ-25 than patients with LOCS III C score > 2.

Conclusion: Cortical cataract has adverse effects on subjective visual function, while mild-to-moderate nuclear cataract has positive effects. Furthermore, "LOCS III C score > 2" can be a potential cutoff as a reference for cataract surgery without self-assessing questionnaires.
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http://dx.doi.org/10.1007/s10792-020-01353-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308262PMC
July 2020
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