LncRNA-XR_002792574.1-mediated ceRNA network reveals potential biomarkers in myopia-induced retinal ganglion cell damage.

BACKGROUND: Long noncoding RNAs (lncRNAs) play a key role in the occurrence and progression of myopia. However, the function of lncRNAs in retinal ganglion cells (RGCs) in the pathogenesis of myopia is still unknown. The aim of our study was to explore the lncRNA-mediated competing endogenous RNA (ceRNA) network in RGCs during the development of myopia. METHODS: RNA sequencing was performed to analyze lncRNA and mRNA expression profiles in RGCs between guinea pigs with form-deprived myopia (FDM) and normal control guinea pigs, and related ceRNA networks were constructed. Then, potentially important genes in ceRNA networks were verified by qRT‒PCR, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore biological functions in the RGCs of FDM guinea pigs. The important genes and related signaling pathways were further verified by qRT‒PCR, immunohistochemistry, immunofluorescence and Western blot in myopia in FDM guinea pigs, FDM mice, and highly myopic adults. RESULTS: The distribution of RGCs was uneven, the number of RGCs was decreased, and RGC apoptosis was increased in FDM guinea pigs. In total, 873 lncRNAs and 2480 mRNAs were determined to be differentially expressed genes in RGCs from normal control and FDM guinea pigs. Via lncRNA-mediated ceRNA network construction and PCR verification, we found that lncRNA-XR_002792574.1 may be involved in the development of myopia through the miR-760-3p/Adcy1 pathway in RGCs. Further verification in FDM guinea pigs, FDM mice, and highly myopic adults demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to cGMP/PKG, the apelin signaling pathway and scleral remodeling. CONCLUSION: We demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to myopia. On the one hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis might inhibit the cGMP/PKG and apelin signaling pathways in RGCs, thereby causing RGC damage in myopia. On the other hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis may cause myopic scleral remodeling through the ERK-MMP-2 pathway. These findings may reveal novel potential targets in myopia and provide reference value for exploration and development of gene editing therapeutics for hereditary myopia.

Intensive topical steroid regimen for enhanced very early recovery after small incision lenticule extraction.

OBJECTIVE: This study aims to investigate the topical steroid regimen after small incision lenticule extraction (SMILE) for its effect on very early restoration of visual quality. METHODS: A total of 180 patients (360 eyes) who underwent SMILE were enrolled. These patients were randomly assigned to three groups, with 60 patients in each group. The only difference among these three groups was the administration of 0.1% fluorometholone (FML) eye drops within two hours after SMILE: no FML in group A, 0.1% FML once every hour in group B and 0.1% FML once every half hour in group C. The corrected distance visual acuity (CDVA), objective scattering index (OSI), modulation transfer function (MTF) cut-off, Strehl ratio (SR) and incidence of subjective symptoms were evaluated preoperatively, at 2, 4 and 24 h and one week after SMILE. RESULTS: The CDVA, MTF cut-off and SR values were significantly higher in group C, when compared to the other two groups, at 2 and 4 h after SMILE (p < 0.05). Furthermore, the OSI and incidence of subjective symptoms were significantly lower in group C, when compared to the other two groups, at 2 and 4 h after SMILE (p < 0.05). However, no significant differences in CDVA, MTF cut-off, SR, OSI and the incidence of subjective symptoms were detected among the three groups at 24 h and one week after SMILE (p > 0.05). CONCLUSION: The administration of 0.1% FML eye drops every half hour within two hours after SMILE accelerates the restoration of visual and optical quality, and reduces the incidence of subjective symptoms during the very early phase after surgery.

New splice site mutations in MYO7A causing Usher syndrome type 1: a study on a Chinese consanguineous family.

PURPOSE: This study investigated the new splice site mutations of Myosin VIIA (MYO7A) in patients with Usher syndrome type 1 (USH1) from a three-generation Chinese consanguineous family. METHODS: All subjects underwent comprehensive ophthalmic examinations and an audiometric test. Demographic data, family history, and peripheral blood leukocytes were collected. We performed whole exome sequencing (WES) to analyze the genomic DNA of the family. DNA sequence and restriction fragment length polymorphism (RFLP) analyses were also done. The identified genetic variants were validated by conducting polymerase chain reaction (PCR) in 100 healthy control subjects and comparing with the NCBI VARIANT database and the 1000 Genomes Project. The functional consequences were further analyzed. RESULTS: WES identified two new splice site mutations (c.5648G > A(rs111033215) and c.6238-1G > C) in MYO7A in two patients with USH1, i.e., the proband and her elder brother. DNA sequence and RFLP analyses showed that other members without USH1 carried only one of the two mutations. In the analysis of healthy controls, neither mutation existed. Both mutations were predicted to be damaging and were most likely associated with USH1. CONCLUSION: In the three-generation Chinese consanguineous family with USH1, c.5648G > A(rs111033215) and c.6238-1G > C mutations in MYO7A are most likely associated with the disease. Our findings expand the mutational spectrum of MYO7A, which will enhance the understanding of the genetic abnormalities in USH1 and provide more evidence for future investigations on therapeutic strategies such as precise gene replacement or gene editing.

Epidemiology of gaming disorder and its effect on anxiety and insomnia in Chinese ethnic minority adolescents.

BACKGROUND: The growing popularity and frequency of online game use have resulted in a large number of studies reporting various mental problems associated with game abuse in adolescents. In this article, we examined the prevalence of gaming disorder (GD) and explored the associations of GD with anxiety and insomnia symptoms in minority youth in China. METHODS: A total of 1494 students completed the Problematic Online Gaming Questionnaire Short-Form (POGQ-SF), the Generalized Anxiety Disorder 7-item questionnaire (GAD-7), and Athens Insomnia Scale (AIS). Chi-square and binary logistic regression analyses were used to explore the associations between gaming disorder and anxiety/insomnia. RESULTS: A total of 356 (23.83%) respondents reported that they had gaming disorder. Chi-square analysis showed that gender, grade, marital status of parents and exercise situation were significantly associated with GD. Binary logistic regression analysis showed that those who had GD were at significantly higher risk for anxiety and insomnia than those without GD. CONCLUSION: We found a high incidence of GD and a positive association among anxiety, insomnia and GD. Thus, special attention should be paid to those who have suffered from GD. It is worth addressing the adverse effects of GD on anxiety and insomnia.

Early outcomes of anterior segment parameters after implantable collamer lens V4c implantation.

BACKGROUND: This study investigated the early outcomes of anterior segment parameters after implanting an implantable collamer lens with a central hole (ICL V4c) in patients with myopia and determined the earliest follow-up time for detecting potential complications. METHODS: Sixty-two patients were included, and the following parameters were measured at baseline (preoperative), 1 day, 1 week, and 1, 3, and 6 months after the operation: intraocular pressure (IOP), endothelial cell density (ECD), central anterior chamber depth (CACD), anterior chamber volume (ACV), nasal and temporal anterior chamber angle (n-ACA and t-ACA), horizontal corneal diameter (white-to-white, WTW), and axial length (AL). The vault was measured at each post-operative timepoint. RESULTS: The postoperative IOP and ECD at the 6 months were both statistically similar to the baseline. The post-operative CACD and ACV were significantly less at all timepoints compared with the baseline (P < 0.001) and stayed stable from 1 day and 1 month after the operation, respectively. Postoperative n-ACA and t-ACA decreased significantly at 1 day and 1 week compared with the baseline (P < 0.001), while tended to stabilization at 1, 3, and 6 months. The vault kept decreasing significantly at 1 day, 1 week, and 1 month, but stayed stable at 3 and 6 months. The postoperative n-ACA and t-ACA positively correlated with the baseline ACA, CACD, and ACV. CONCLUSIONS: The anterior chamber parameters tended to stabilization early after the operation. Thus, it is essential to evaluate patients' anterior segment status at earlier timepoints and prevent complications with prompt and non-invasive intervention.

Effect of white-to-white corneal diameter on biomechanical indices assessed by Pentacam Scheimpflug corneal tomography and corneal visualization Scheimpflug technology.

PURPOSE: To provide evidence for more accurate evaluation of refractive surgery candidates in clinics, this retrospective study investigated the effect of corneal diameter on the biomechanical indices assessed by Pentacam Scheimpflug cornea tomography (Pentacam) and corneal visualization Scheimpflug technology (Corvis ST). METHODS: The relevant data were collected of 132 eyes from 132 participants with moderate myopia who were candidates for refractive surgery. Eligible participants were apportioned to 2 groups based on the white-to-white (WTW) corneal diameter: Group A, ≤ 11.5 mm, and Group B, ≥ 11.6 mm. A single clinician performed Pentacam and Corvis ST imaging on each subject for 3 consecutive measurements, and the means were used for statistical analyses. RESULTS: Each group comprised 66 eyes. As measured by Pentacam, the 2 groups were comparable regarding Df and Da. For other measurements, Group A had significantly higher K1, K2, Db, Dp, Dt, Do, PPImin, PPImax, PPIavg, while Group B had significantly higher CCT, BFSf, BFSb, and ARTmax. Corvis ST data included DA ratio, SPA1, CBI, TBI, and ARTh. Only the latter showed a significant difference, with ARTh of group A (437.04 ± 76.60) larger than group B (470.46 ± 103.36, p = 0.04). CONCLUSION: In a Chinese population, WTW corneal diameter showed effect on biomechanical indices assessed by Pentacam and Corvis ST. Personalized evaluation of these measurements based on corneal diameter should improve the sensitivity and specificity for screening of keratoconus by these devices.

Mutational screening of EFNA5 in Chinese age-related cataract patients.

BACKGROUND/AIM: In the past few years, Ephrin-A5 (EFNA5) had been identified to be associated with lens development, but so far no sequence variation in EFNA5 has been reported in humans. Therefore, we conduct this study to investigate the EFNA5 genetic variations in Chinese age-related cataract (ARC) patients. METHODS: Sequencing of EFNA5 was performed in 140 sporadic ARC patients and 142 random unrelated healthy subjects. Genomic DNA was extracted from peripheral blood leukocytes. All exons of EFNA5 were sequenced after being amplified by polymerase chain reaction. The functional consequences of the variations were analyzed using PolyPhen2. RESULTS: Three single nucleotide polymorphisms in EFNA5, c.668C>T (rs201008479), c.102C>T (rs199980747) and c.-27C>G (rs200187971), were found in the patients, and none of them presented in the normal controls. Using PolyPhen2, c.668C>T in EFNA5 is predicted to be possibly damaging. CONCLUSIONS: The genetic variations c.668C>T (rs201008479), c.102C>T (rs199980747) and c.-27C>G (rs200187971) may present an additional genetic risk factor for ARC in the Chinese population. This study shows the first cases of these genetic variations in EFNA5 in human beings.

Variants in the ZNF469 gene in families with Brittle cornea syndrome and keratoconus.

Background: Brittle cornea syndrome 1 (BCS1) is a rare autosomal recessive disorder characterized by corneal and sclera thinning and fragility that is caused by zinc finger protein 469 (ZNF469) gene mutation. Keratoconus is another disease related to corneal thinning. Several reports have linked ZNF469 variants and keratoconus. We recruited a four-generation BCS1 family and two keratoconus families to explore pathogenic ZNF469 variants. Methods: This study included 11 members from a family with BCS1, 2 families with keratoconus, 368 sporadic keratoconus patients and 325 unrelated healthy controls. Whole exome sequencing of DNA from peripheral blood and cross species conservation analysis was used to investigate and verify ZNF469 variants. Results: A new homozygous frameshift mutation c. 6727del (p.Asp2243Thr fs*8) in ZNF469 was detected in the BSC1 family. Two ZNF469 heterozygous variants g.88494671G > A (c.793G > A, p.G265S, rs754776767) were detected in keratoconus family 1 and a heterozygous missense variant g.88498262G > A (c.4384G > A, p.D1462 N, rs577890057) was found in keratoconus family 2. Based on the American College of Medical Genetics and Genomics guidelines, rs577890057 and rs754776767 were predicted to be variants of uncertain significance. c. 6727del (p. Asp2243Thr fs*8) in ZNF469 was identified to be pathogenic. Conclusions: We identified a new homozygous frameshift mutation and two heterozygous missense variations in ZNF469 in the three families. Our findings extend the spectrum of ZNF469 variants associated with keratoconus.

Genetic investigation in a four-generation Chinese family with congenital fibrosis of extraocular muscles and keratoconus.

Here, we have reported the genetic and clinical characteristics of four generations of a family patient from China with congenital fibrosis of extraocular muscles 1 (CFEOM1) and keratoconus (KC). The history of diseases, clinical observations, and blood samples of all family members were collected. A total of 100 healthy participants were recruited as normal controls. The whole exome sequencing of the genomic DNA and polymerase chain reaction were performed on samples obtained from the controls and their family members to verify the gene variants. The functional analyses of the variants were performed by using different software. Two single nucleotide polymorphisms were detected in the proband and other patients in his families, including a heterozygous missense variation, g.39726207C > T (c.2860C > T, p.R954W, rs121912585), in the third highly conserved coiled-coil domain of KIF21A, and a heterozygous missense variant, g.30664732A > C (c.136A > C, p.S46R, rs200111443) in TGFBR2. The variant p.R954W in KIF21A was predicted to be pathogenic using software, whereas p.S46R in TGFBR2 was predicted to be of uncertain significance (VUS). Thus, KC might have occurred in the proband and his daughter because of a combination of genetic mutations and involuntary eye rubbing induced by CFEOM1. This is the first case of concomitant KC in a family having CFEOM1. Thus, the study provides new information about patients with KC having CFEOM1. Furthermore, the study suggests that attention should be paid to the early detection and diagnosis of KC in patients with CFEOM1.

A novel variant in the keratin 12 gene in a four-generation Chinese family with high myopia.

BACKGROUND: High myopia is a major cause of visual impairment, and genetic factors play crucial roles in the pathogenesis. We performed this study to identify candidate genes for the development of high myopia in a four-generation Chinese family with myopia. METHODS: All family members with myopia and 100 healthy participants were included in this study. Data were obtained on demographics, disease history, and ocular examination results. We performed whole exome sequencing of the genomic DNA and Sanger sequencing to verify the variants. Functional analyses of the variant were performed using software programmes. RESULTS: Nine of thirteen family members were found to have high myopia, amongst which two members were also diagnosed keratoconus. A missense variant in the keratin 12 gene (KRT12, p.Val410Gly) was detected in all high myopia cases but not in other family members without high myopia or the controls. The variant was predicted to be benign by online software programmes. However, modelling of the three-dimensional structure of the protein clearly revealed conformational changes caused by the mutation. CONCLUSIONS: A missense mutation in the KRT12 gene was identified in this Chinese family, which may be associated with the pathogenesis of high myopia.

A genetic investigation in five Chinese families with keratoconus.

Background: This study investigated the genetic characteristics of five Chinese families with keratoconus (KC). Methods: In the five families affected by KC, medical records, clinical observations, and blood samples were collected from all individuals. All KC family members (n = 20) underwent both whole exome sequencing of genomic DNA and Sanger sequencing to confirm the variants. Online software was utilized to analyze all variants, and the online server I-TASSER was employed for in silico predictions of the three-dimensional protein structures of the variants. The newly discovered variants and single nucleotide polymorphisms were further examined in 322 sporadic KC patients. Results: The Pentacam tomographic composite index in those affected first-degree family members of the probands showed a pathological change. Five new variants were detected in the five probands and other affected members in their families: a heterozygous missense variant g.19043832C>T (p.Ser145Asn) in the homer scaffolding protein 3 (HOMER3) gene; a heterozygous missense variant g.99452113G>A (p.Gly483Arg) in the insulin-like growth factor 1 receptor (IGF1R) gene; a heterozygous missense variant g.55118280G>T (p.Trp843Leu) in the echinoderm microtubule-associated protein like 6 (EML6) gene; a heterozygous frameshift variant c. 1226_1227del (p.Gln410Glufs*17) in the DOP1 leucine zipper-like protein B (DOP1B) gene; and a heterozygous splice-site variant c.7776+2T>A in the neurobeachin-like protein 2 (NBEAL2) gene. These variations were predicted to be potentially pathogenic and associated with KC. Conclusion: Five novel variants in HOMER3, IGF1R, EML6, DOP1B, and NBEAL2 genes were identified in this study and may be associated with the pathogenesis of KC. This study provides new information about the gene variants and their protein changes in KC patients. The findings should be explored further and could potentially be applied to the early diagnosis of KC before clinical onset.

Genetic variations and polymorphisms in the ezrin gene are associated with age-related cataract.

PURPOSE: Age-related cataract (ARC) is a complex multifactorial disorder, including genetic and environmental factors. Ezrin (EZR), a member of the ezrin/radixin/moesin (ERM) protein family, plays a crucial role in the development of the lens as a plasma membrane-cytoskeleton linker. We conducted this study to investigate the role of genetic variations of ezrin and the relationship between single nucleotide polymorphisms (SNPs) in EZR and susceptibility to ARC in a Chinese population. METHODS: A total of 205 sporadic age-related cataract patients and 218 unrelated random healthy controls participated in our study. Genomic DNA was extracted from peripheral blood leukocytes. All exons of EZR were sequenced after being amplified with polymerase chain reaction. The functional consequences of the mutations were analyzed using PolyPhen2. SNP statistical analysis was performed using SNPstats. RESULTS: We found three novel variations in 205 patients. None presented in the 218 controls, including c.441C>G, c.924G>C, and c.1503G>A. PolyPhen2 predicted that the c.924G>C mutation probably had pathogenicity. Compared with the healthy controls, the rs5881286 -/GT genotype and - allele frequencies (p=0.0012; odds ratio [OR]=3.37; 95% confidence interval [CI]=1.70-6.70; p=3.96e-5; χ(2)=18.98, respectively), rs2242318 T/C genotype and C allele frequencies (p=0.0045; OR=3.40; 95% CI=1.70-6.79; p=8.82e-6; χ(2)=21.86, respectively), and rs144581330 A/G genotype and G allele frequencies (p=0.0472; OR=14.46; 95% CI=1.29-162.43; p=0.0244, χ(2)=6.99, respectively) were higher in the patients with age-related cataract. SNP rs144581330 in exon 2 was also predicted to be probably damaging by PolyPhen2. Haplotype association including the - allele of rs5881286, C allele of rs2242318, and A allele of rs144581330 exhibited significantly higher distribution in the patients with ARC (p=8.0e-4; OR=3.38; 95% CI=1.66-6.87). CONCLUSIONS: This study suggests that the genetic variations and SNPs in the gene EZR possibly contribute to the development of age-related cataracts in the Chinese population.

Identification of genetic variants in two families with Keratoconus.

BACKGROUND: This research investigated the genetic characteristic of two Chinese families with keratoconus (KC). METHODS: For all people in the two families with KC, their history, clinical data, and peripheral blood were collected. One hundred healthy participants without KC and 112 sporadic KC patients were recruited as the controls. Whole exome sequencing of the genomic DNA and polymerase chain reaction were conducted for all the controls and family members to verify the variants. Functional analyses of the variants was performed using the software programs. RESULTS: A missense tuberous sclerosis 1 (TSC1) variant g.135797247A > G (c.622A > G, p.Ser208Gly) was detected in family 1. A single nucleotide polymorphism (SNP) rs761232139 (p.Gly235Arg) in aldehyde dehydrogenase 3 family member A1 (ALDH3A1) gene was detected in family 2. The variant c.622A > G in TSC1 and the SNP rs761232139 in ALDH3A1 were predicted as being probably damaging. CONCLUSIONS: Novel variant c.622A > G in TSC1 and SNP rs761232139 in ALDH3A1 have been detected in families with KC. These two findings may play a role in the pathogenesis of KC.

The role of mip in the development of lens in zebrafish.

Major intrinsic protein (MIP) functions as a water channel and a cell-junction molecule in the vertebrate eye lens. The pathogenic mechanism behind the loss of MIP function in the lens, which leads to degraded optical quality and cataract formation, is still unclear. In this study, a zebrafish model with the mipb mutant was produced. The expression of mipb mRNA and protein was dramatically reduced in the mutant. Immunological analysis reveals that loss function of mip leads to the diffuse distribution of ZL-1 in the mutant lens. Furthermore, in situ hybridization reveals that mip knockout results in a decrease in the transcripts of beaded filament structural protein 2 (Bfsp2) in the lens. Histology study shows that lens fibers in the mutants are less uniform in shape and the fiber arrangement is disrupted. The presented data provides evidence for the essential role of mipb in the development of lens fibers. The absence of mipb during lens formation is likely to result in aberrant lens fiber formation and impaired lens function.

Flexible Quantum Dot Light-Emitting Device for Emerging Multifunctional and Smart Applications.

Quantum dot light-emitting diodes (QLEDs), owing to their exceptional performances in device efficiency, color purity/tunability in the visible region and solution-processing ability on various substrates, become a potential candidate for flexible and ultrathin electroluminescent (EL) lighting and display. Moreover, beyond the lighting and display, flexible QLEDs are enabled with endless possibilities in the era of the internet of things and artificial intelligence by acting as input/output ports in wearable integrated systems. Challenges remain in the development of flexible QLEDs with the goals for high performance, excellent flexibility/even stretchability, and emerging applications. In this paper, the recent developments of QLEDs including quantum dot materials, working mechanism, flexible/stretchable strategies and patterning strategies, and highlight its emerging multifunctional integrations and smart applications covering wearable optical medical devices, pressure-sensing EL devices, and neural smart EL devices, are reviewed. The remaining challenges are also summarized and an outlook on the future development of flexible QLEDs made. The review is expected to offer a systematic understanding and valuable inspiration for flexible QLEDs to simultaneously satisfy optoelectronic and flexible properties for emerging applications.

A novel variant in TGFBI causes keratoconus in a two-generation Chinese family.

BACKGROUND: This study aims to investigate the genetic abnormalities in a two-generation Chinese family affected by keratoconus (KC). A two-generation Chinese family affected by KC was studied. MATERIALS AND METHODS: A total of 118 unrelated healthy individuals without KC were recruited as controls. The family history, clinical data, and peripheral blood leukocytes were collected from all subjects. Whole exome sequencing was performed using the genomic DNA of the proband (II.2) and the other two affected family members (I.1 and II.3). Afterwards, polymerase chain reaction was performed for the other enrolled subjects to verify the variants identified in family members with KC. The PolyPhen2, SIFT, PROVEIN and Mutation Taster software programs were applied to analyze the functional consequences of the variants. RESULTS: A single nucleotide polymorphism (VARIANT) (c.1406 G > A [rs759370852]) in the transforming growth factor beta-induced (TGFBI) gene was identified in all affected family members, which resulted in a p.R469H amino acid change. This variant was not detected in the controls. The variant c.1406 G > A in TGFBI was predicted as probably damaging with software programs. CONCLUSION: A novel variant c.1406 G > A in TGFBI has been identified, and probably contributes to the pathogenesis of KC.

Complex impacts of gallstone disease on metabolic syndrome and nonalcoholic fatty liver disease.

Background: Patients with gallstone disease (GSD) often have highly co-occurrence with metabolic syndrome (MetS) and Nonalcoholic fatty liver disease (NAFLD) both associated with insulin resistance (IR). Meanwhile, highly prevalence of NAFLD was found in patients who received cholecystectomy. However, the associations of GSD with MetS, NAFLD is inconsistent in the published literature. And risk of cholecystectomy on NAFLD is unclear. Methods: We searched the Medline EMBASE and WOS databases for literature that met our study topic. To be specific, studies with focus on associations between GSD and MetS/NAFLD, and risk evaluation on cholecystectomy and NAFLD incidence were enrolled for further analysis. The random effect model was used to calculate the combined relative ratio (RR) and odds ratio (OR)and 95% confidence interval (CI). Results: Seven and six papers with focus on connections between GSD and NAFLD/MetS prevalence. Correspondingly, seven papers with focus on risk of cholecystectomy on NAFLD occurrence were also enrolled into meta-analysis. After pooling the results from individual study, patients with GSD had higher risk of MetS (OR:1.45, 95%CI: 1.23-1.67, I2 = 41.1%, P=0.165). Risk of GSD was increased by 52% in NAFLD patients (pooled OR:1.52, 95%CI:1.24-1.80). And about 32% of increment on NAFLD prevalence was observed in patients with GSD (pooled OR: 1.32, 95%CI:1.14-1.50). With regard to individual MetS components, patients with higher systolic blood pressure were more prone to develop GSD, with combined SMD of 0.29 (96%CI: 0.24-0.34, P<0.05). Dose-response analysis found the GSD incidence was significantly associated with increased body mass index (BMI) (pooled OR: 1.02, 95%CI:1.01-1.03) in linear trends. Patients who received cholecystectomy had a higher risk of post-operative NAFLD (OR:2.14, 95%CI: 1.43-2.85), P<0.05). And this impact was amplified in obese patients (OR: 2.51, 95%CI: 1.95-3.06, P<0.05). Conclusion: Our results confirmed that controls on weight and blood pressure might be candidate therapeutic strategy for GSD prevention. And concerns should be raised on de-novo NAFLD after cholecystectomy.

Progress on SARS-CoV-2 3CLpro Inhibitors: Inspiration from SARS-CoV 3CLpro Peptidomimetics and Small-Molecule Anti-Inflammatory Compounds.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently poses a threat to human health. 3C-like proteinase (3CLpro) plays an important role in the viral life cycle. Hence, it is considered an attractive antiviral target protein. Whole-genome sequencing showed that the sequence homology between SARS-CoV-2 3CLpro and SARS-CoV 3CLpro is 96.08%, with high similarity in the substrate-binding region. Thus, assessing peptidomimetic inhibitors of SARS-CoV 3CLpro could accelerate the development of peptidomimetic inhibitors for SARS-CoV-2 3CLpro. Accordingly, we herein discuss progress on SARS-CoV-2 3CLpro peptidomimetic inhibitors. Inflammation plays a major role in the pathophysiological process of COVID-19. Small-molecule compounds targeting 3CLpro with both antiviral and anti-inflammatory effects are also briefly discussed in this paper.

Epidemiology of childhood trauma and its association with insomnia and psychotic-like experiences in Chinese Zhuang adolescents.

Background: Adolescents who have experienced childhood trauma are more likely to have insomnia and psychotic-like experiences (PLEs) than adolescents from other ethnic groups. However, little is known about the youth of ethnic minorities. This study aimed to investigate the epidemiology of childhood trauma and its relationship with insomnia and PLEs in Chinese Zhuang adolescents, focusing on the role of a specific type of trauma and accumulation. Methods: A questionnaire of Childhood Trauma Questionnaire-Short Form (CTQ-SF), Athens Insomnia Scale (AIS), and Chinese Version Community assessment psychic experiences-8 (CCAPE- 8) were all completed by 1,493 Chinese Zhuang adolescents. Chi-square and multivariate logistic regression analyses examined the association between childhood trauma and insomnia/PLEs. Results: The incidences of emotional abuse (EA), physical abuse (PA), sexual abuse (SA), emotional neglect (EN), and physical neglect (PN) occurred at rates of 5.63, 5.02, 6.56, 23.98, and 33.15%, respectively. EA, SA, EN, and PN were all positively related to insomnia (OR: 1.314-7.720, all p < 0.05). EA and SA were positively associated with PLEs (OR: 2.131-3.202, all p < 0.001). Adolescents who had experienced three or more types of traumas were more likely to have insomnia (OR = 6.961, p < 0.001) and PLEs (OR = 3.558, p < 0.001). Conclusion: The most common type of childhood trauma is PN. Childhood trauma has the primary effect on insomnia/PLE. A significant dose-response relationship was found between Childhood trauma and insomnia/ PLEs. This association varied depending on the type and accumulation of exposure.

The relationship between childhood trauma and depressive symptom among Zhuang adolescents: Mediating and moderating effects of cognitive emotion regulation strategies.

Background: Not all adolescents who have endured childhood trauma will develop depressive symptom, nor will they all experience the same level of depressive symptom. According to previous research, cognitive emotion regulation strategies may explain a portion of the variance. Observe the connection between childhood trauma and depressive symptom and investigate whether cognitive emotion regulation strategies mediate or moderate this association. Methods: In October 2019, a cross-sectional study measuring childhood trauma, cognitive emotion regulation strategies, and depressive symptom among Zhuang adolescents was done in one senior high school and two junior highs in Chongzuo, Guangxi, China, using a self-report questionnaire. To examine the hypothesis of mediating and moderating effects, SPSS PROCESS was utilized. Results: In this study, there was a positive relationship between childhood trauma and depressive symptom, whereas there were positive correlations between expressive suppression and childhood trauma and depressive symptom (r = 0.380, 0.246, and 0.089, respectively, p < 0.01). The 5,000-sample bootstrap procedure revealed that the indirect relationship between the independent variable (childhood trauma or emotional abuse) and the dependent variable (depressive symptom) was statistically significant (ß = 0.0154 95% CI: 0.0019, 0.0165, ß = 0.0442 95% CI: 0.0008, 0.0117). The statistical significance of the interaction effect enhanced the R-square value of the moderating effect when the independent variable was the total childhood trauma score (ΔR2 = 0.0044, 0.0089). Conclusions: Our findings corroborated the conclusion of prior research that cognitive emotion regulation strategies mediate and moderate the development of depressive symptom. Although we demonstrate that cognitive emotion regulation strategies play a mediating and moderating role in the relationships between childhood trauma and depressive symptom, the mediating effects on the relationships between the other types of childhood traumas, including physical abuse and neglect, sexual abuse, emotional neglect, and depressive symptom, did not emerge.