INTRODUCTION: Obstructive sleep apnoea (OSA) is common in Singapore, with moderate to severe OSA affecting around 30% of residents. These consensus statements aim to provide scientifically grounded recommendations for the management of OSA, standar-dise the management of OSA in Singapore and promote multidisciplinary collaboration. METHOD: An expert panel, which was convened in 2024, identified several areas of OSA management that require guidance. The expert panel reviewed the current literature and developed consensus statements, which were later independently voted on using a 3-point Likert scale (agree, neutral or disagree). Consensus (total ratings of agree and neutral) was set a priori at ≥80% agreement. Any statement not reaching consensus was excluded. RESULTS: The final consensus included 49 statements that provide guidance on the screening, diagnosis and management of adults with OSA. Additionally, 23 statements on the screening, diagnosis and management of paediatric OSA achieved consensus. These 72 consensus statements considered not only the latest clinical evidence but also the benefits and harms, resource implications, feasibility, acceptability and equity impact of the recommendations. CONCLUSION The statements presented in this paper aim to guide clinicians based on the most updated evidence and collective expert opinion from sleep specialists in Singapore. These recommendations should augment clinical judgement rather than replace it. Management decisions should be individualised, taking into account the patient's clinical characteristics, as well as patient and caregiver concerns and preferences.
Humans ; Sleep Apnea, Obstructive/diagnosis* ; Singapore ; Consensus ; Adult

Objective:To identify the pathogenic gene in a family with cone-rod dystrophy (CRD).Methods:A pedigree study was conducted.Clinical data were collected from three generations of six people from a family with CRD who visited Henan Eye Hospital in December 2019, including one patient.After detailed collection of the patient's medical history, the proband and his family members underwent best-corrected visual acuity, slit-lamp microscope+ front-lens examination, optometry, non-mydriatic fundus photography, spectral-domain optical coherence tomography (SD-OCT), and full-field flash electroretinography (ff-ERG). Peripheral venous blood (5 ml) was collected from the proband, his parents and siblings, and the whole genome DNA was extracted.The proband's DNA was sequenced using whole exome sequencing.Hemizygous and potentially pathogenic mutations were verified by Sanger sequencing.Pathogenicity was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines.Tools such as SpliceAI and dbscSNV were used to predict the impact of mutations on mRNA splicing.This study strictly followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[15]). All subjects and guardians of minor subjects signed informed consent forms.Results:The proband (Ⅲ: 1), a 5-year-old boy, presented with recessive nystagmus in both eyes and a best corrected visual acuity of 0.2.Color vision examination revealed red-green color blindness without night blindness.SD-OCT showed the presence of neuroepithelial structures in both eyes, but the interdigitation zone was blurred in both eyes.ff-ERG showed a slight decrease in rod function and a moderate-severe decrease in cone function in the right eye, and a slight decrease in cone and rod function in the left eye.Gene sequencing results showed that the proband had the hemizygous splice site variant c. 1911-3C>A of the CACNA1F gene on the X chromosome.Sanger sequencing showed that neither his mother nor his younger sister carried the variant, suggesting it was novel.This variant site was not recorded in the normal population database (PM2). Bioinformatics tools SpliceAI and dbscSNV consistently predicted that this variation affects on splicing.According to the ACMG guidelines, this variation is pathogenic. Conclusions:A novel variant c. 1911-3C>A in the CACNA1F gene was found in a family with CRD, and this variant may be a pathogenic variant site in this CRD family.This discovery expands the spectrum of pathogenic variations in CRD.

Objective:To identify the pathogenic gene in a family with cone-rod dystrophy (CRD).Methods:A pedigree study was conducted.Clinical data were collected from three generations of six people from a family with CRD who visited Henan Eye Hospital in December 2019, including one patient.After detailed collection of the patient's medical history, the proband and his family members underwent best-corrected visual acuity, slit-lamp microscope+ front-lens examination, optometry, non-mydriatic fundus photography, spectral-domain optical coherence tomography (SD-OCT), and full-field flash electroretinography (ff-ERG). Peripheral venous blood (5 ml) was collected from the proband, his parents and siblings, and the whole genome DNA was extracted.The proband's DNA was sequenced using whole exome sequencing.Hemizygous and potentially pathogenic mutations were verified by Sanger sequencing.Pathogenicity was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines.Tools such as SpliceAI and dbscSNV were used to predict the impact of mutations on mRNA splicing.This study strictly followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[15]). All subjects and guardians of minor subjects signed informed consent forms.Results:The proband (Ⅲ: 1), a 5-year-old boy, presented with recessive nystagmus in both eyes and a best corrected visual acuity of 0.2.Color vision examination revealed red-green color blindness without night blindness.SD-OCT showed the presence of neuroepithelial structures in both eyes, but the interdigitation zone was blurred in both eyes.ff-ERG showed a slight decrease in rod function and a moderate-severe decrease in cone function in the right eye, and a slight decrease in cone and rod function in the left eye.Gene sequencing results showed that the proband had the hemizygous splice site variant c. 1911-3C>A of the CACNA1F gene on the X chromosome.Sanger sequencing showed that neither his mother nor his younger sister carried the variant, suggesting it was novel.This variant site was not recorded in the normal population database (PM2). Bioinformatics tools SpliceAI and dbscSNV consistently predicted that this variation affects on splicing.According to the ACMG guidelines, this variation is pathogenic. Conclusions:A novel variant c. 1911-3C>A in the CACNA1F gene was found in a family with CRD, and this variant may be a pathogenic variant site in this CRD family.This discovery expands the spectrum of pathogenic variations in CRD.

Objective To investigate the effect of total paeony glycoside(TPG)on cerebral ischemia-reperfusion injury(CI/RI)of rats.Methods The rats were randomly divided into sham surgery(sham)group,CI/RI model group(simple CI/RI group),positive control group(nimodipine group,5 mg/kg),low-dose TPG group(TPG-L group,27 mg/kg),a high-dose TPG group(TPG-H group,54 mg/kg)and a high-dose TPG+NOD-like receptor thermal protein domain associated protein 3(NLRP3)activator diethyl dithiocarbamate(DDC)group(TPG-H+DDC group,54 mg/kg TPG and 30 mg/kg DDC),with 18 rats in each,administered once a day for 7 consecutive days.After the administration,the neurological deficit score of the rats was evaluated.Nissl staining microscopy was applied to observe neuronal activity in brain tissue.2,3,5-triphenyltetrazolium chloride(TTC)staining microscopy was applied to detect the area of cerebral infarction in rats.The level of interleukin-1β and IL-18 in brain tissue was measured by ELISA method.Western blot was applied to detect the expression of purinergic receptor P2X ligand-gated ion channel 7(P2X7R)/NLRP3 signaling pathway related proteins and pyroptosis related proteins such as apoptosis associated speck like protein containing a CARD(ASC)and cysteine protease 1(caspase-1)proteins in brain tissue.Results Compared with the sham group,the neurological deficit score,infarct area,level of IL-1β and IL-18 in brain tissue and protein expression of P2X7R,NLRP3,ASC,and caspase-1 in brain tissue of rats in the simple CI/RI group were significantly increased(P<0.05),while the proportion of Nissl body positive cells in brain tissue was significantly reduced(P<0.05).The change in corresponding indicators of rats in the nimodipine group,TPG-L group,and TPG-H group was opposite to those in the simple CI/RI group(P<0.05).NLRP3 acti-vator DDC antagonized the inhibitory effect of TPG on cell pyroptosis in CI/RI rats.Conclusions TPG may inhibit brain injury in CI/RI rats by down-regulating the P2X7R/NLRP3 pathway.

OBJECTIVE: To assess the association of cytochrome P450 (CYP450) gene polymorphisms with the occurrence of ischemic stroke (IS). METHODS: From January 2020 to August 2022, 390 IS patients treated at the Zhengzhou Seventh People's Hospital were enrolled as the study group, and 410 healthy individuals undergoing physical examination during the same period were enrolled as the control group. Clinical data of all subjects were collected, which included age, sex, body mass index (BMI), smoking history and results of laboratory tests. Chi-square test and independent sample t test were used for comparing the clinical data. Multivariate logistic regression analysis was used to analyze the non-hereditary independent risk factors for IS. Fasting blood samples of the subjects were collected, and the genotypes of rs4244285, rs4986893, rs12248560 of the CYP2C19 gene and rs776746 of the CYP3A5 gene were determined by Sanger sequencing. The frequency of each genotype was calculated by using SNPStats online software. The association between the genotype and IS under the dominant, recessive and additive models was analyzed. RESULTS: The levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), apolipoprotein B (Apo-B) and homocysteine (Hcy) of the case group were significantly higher than those of the control group, whilst the levels of high density lipoprotein (HDL-C) and Apo-A1 (APO-A1) were significantly lower (P < 0.05). Multivariate Logistic regression analysis showed that TC (95%CI = 1.13-1.92, P = 0.02), LD-C (95%CI = 1.03-2.25, P = 0.03), Apo-A1 (95%CI = 1.05-2.08, P = 0.04), Apo-B (95%CI = 1.7-4.22, P < 0.01) and Hcy (95%CI = 1.12-1.83, P = 0.04) were non-genetic independent risk factors for the occurrence of IS. Analysis of the association between the genetic polymorphisms and the risk of IS showed that the AA genotype at rs4244285 of the CYP2C19 gene, the AG genotype and A allele at rs4986893 of the CYP2C19 gene, and the GG genotype and G allele at rs776746 of the CYP3A5 gene were significantly associated with IS. Under the recessive/additive model, dominant model and dominant/additive model, polymorphisms of the rs4244285, rs4986893 and rs776746 loci were also significantly associated with the IS. CONCLUSION TC, LDL-C, Apo-A1, Apo-B and Hcy can all affect the occurrence of IS, and CYP2C19 and CYP3A5 gene polymorphisms are closely associated with the IS. Above finding has confirmed that the CYP450 gene polymorphisms can increase the risk of IS, which may provide a reference for the clinical diagnosis.
Humans ; Cytochrome P-450 CYP3A/genetics* ; Cytochrome P-450 CYP2C19/genetics* ; Ischemic Stroke ; Cholesterol, LDL/genetics* ; Polymorphism, Single Nucleotide ; Genotype ; Apolipoproteins B/genetics* ; Gene Frequency

Objective:To evaluate the effect of hyperthermia on the apoptosis and the expression levels of cysteine-containing aspartate-specific protease-3 (Caspase-3) and phosphorylated protein kinase B (p-AKT) in laryngeal squamous cell carcinoma cells.Methods:A prospective study was conducted on 30 patients with laryngeal squamous cell carcinoma who were treated at the First Affiliated Hospital of Zhengzhou University from October, 2021 to October, 2022. Three times of hyperthermia were performed with a time interval of 24 h. The tumor tissue samples were collected from 30 patients before and after hyperthermia and divided into before hyperthermia group (group A ) and after hyperthermia group (group B). Self-control study mode was adopted for comrparative analysis. The cell apoptosis was detected by TUNEL assay. The expression levels of Caspase-3 and p-AKT in the tissues were detected by immunohistochemistry. Positive cell ratio and immunohistochemistry (IHC) score were recorded. Comparison between two groups was performed by paired t-test. The correlation between the degree of apoptosis and the changes of Caspase-3 and p-AKT molecules was assessed by Pearson correlation analysis. Results:No evident adverse reactions were observed in 30 patients after hyperthermia. The apoptosis index of laryngeal squamous cell carcinoma cells in group A was 2.37%±1.33%, and 4.27%±3.93% in group B ( P=0.006). In group A, the ratio of Caspase-3 positive cells in tumor tissues was 62.31%±19.49% and 80.79%±17.15% in group B ( P=0.001). The ratio of p-AKT positive cells in group A was 31.26%±19.30%, and 26.26%±15.86% in group B ( P=0.023). There was a positive correlation between the degree of apoptosis and the changes of Caspase-3 molecule ( r=0.544, P=0.002), but a negative correlation was noted between the degree of apoptosis and the changes of p-AKT molecule ( r=-0.434, P=0.017). Conclusion:Hyperthermia can promote the apoptosis of tumor cells in laryngeal squamous cell carcinoma, which may be related to Caspase-3 dependent apoptosis, and the inhibition of AKT phosphorylation is also involved in this process.

Objective:To investigate the effect of Mediterranean diet on blood glucose control and cardiovascular risk factors in patients with type 2 diabetes.Methods:As to December 2021, the PubMed, Cochrance Central Register of Controlled Trials and Cochrance Database, Cochranc Library, Embase, China National Knowledge Infrastructure and Wanfang Medical Network system were searched for clinical randomized controlled trials(RCTs) of Mediterranean diet in patients with type 2 diabetes to conduct Meta-analysis The main observation index were cardiovascular risk factors, and the mean difference and its 95% confidence interval were used to estimate the effect size.Results:There were six RCTs, and 1181 patients met the inclusion criteria and entered the Meta-analysis. Compared with the control group, the intervention group can significantly reduce the level of systolic blood pressure ( MD=-1.20, 95% CI-2.21 to -0.19) and diastolic blood pressure ( MD=-4.17, 95% CI-7.12 to -1.22) in patients with type 2 diabetes mellitus, but there were no significant difference in the level of TC ( MD=2.92, 95% CI-0.84 to-6.67), HDL ( MD=2.33, 95% CI-0.27 to -4.92) and LDL ( MD=-2.34, 95% CI-5.67 to -0.99) between the two groups (all P>0.05). Conclusions:The meta-analysis provided evidence the Mediterranean diet showed the beneficial improvements in blood pressure glycemic control, but the effect of Mediterranean diet on lipid profile was not significant, which needed further verification.

Objective:To determine the pathogenic gene mutation in a family with incomplete congenital quiescent night blindness (CSNB) of Schubert-Bornschein type.Methods:A retrospective clinical study. In February 2021, one patient and his parents and elder brother from a Han Chinese incomplete CSNB of Schubert-Bornschein type family diagnosed by clinical and genetic examination at Henan Provincial People's Hospital were included in the study. The patient’s medical history, family history were inquired; best corrected visual acuity (BCVA), color vision, fundus color photography, full-field electroretinogram (ERG), and frequency domain optical coherence tomography (OCT) were examined in detail. Five ml of the subject’s peripheral venous blood was collected and the whole genome DNA was extracted. The genomic DNA of the subject was library constructed, and all-exon probes were polymerized for capture. The suspected pathogenic mutation site was verified by Sanger, and the pathogenicity of the gene mutation site was determined by parallel bioinformatics analysis.Results:The BCVA of both eyes of the proband (Ⅱ2) was 0.4; the color vision test could not recognize the red color. Fundus examination showed no obvious abnormalities. The retina thickness in the macular area of both eyes was slightly thinned. ERG examination of the whole field showed that the amplitude of ERG b wave was significantly reduced under the stimulation of binocular dark adaptation 3.0 and showed a negative waveform. The mother of the proband (Ⅰ2) had normal BCVA, color vision, fundus color photography, and frequency domain OCT examination. The full-field ERG examination showed that the amplitude of each eye reaction was slightly reduced, and the amplitude of the dark adaptation shock potential was significantly reduced. Genetic testing showed that the proband (Ⅱ2) had a c.1761dupC hemizygous mutation in exon 14 of the voltage-dependent calcium channel α1F subunit gene ( CACNA1F gene). The results of protein sequence homology analysis showed that the site was highly conserved in multiple species; the results of bioinformatics analysis showed that the CACNA1F gene c.1761dupC (pY588fs) subsequently had a frameshift mutation and became a stop at position 10. Codons appear translational termination in the conserved regions of the protein. According to the standards and guidelines of the American College of Medical Genetics and Genomics, the mutation was judged to be a possible pathogenic variant. The mother of the proband (Ⅰ2) was a carrier of this site mutation. The clinical and genetic test results of the father and elder brother of the proband were not abnormal. Conclusion:CACNA1F gene c.1761dupC is the pathogenic mutation site of the Schubert-Bornschein type incomplete CSNB family.

Objective:To identify the pathogenic gene mutations in a family with early onset severe retinal dystrophy (EOSRD).Methods:A retrospective clinical study. One patient and three family members from a Han of EOSRD who were diagnosed at Henan Eye Hospital in August 2018 were included in the study. After the detailed history of the patients was collected, all participants underwent best corrected visual acuity (BCVA), slit-lamp, fundus biomicroscopy with the slit lamp, untra-widefield fundus color photography, spectral-domain optical coherence tomography (SD-OCT) and full-field electroretinography (ff-ERG). The subject’s peripheral venous blood of 5 ml was collected and the whole genome DNA was extracted. A genetic eye disease capture chip containing 441 disease-causing genes was used for targeted capture and enrichment of high-throughput sequencing, and Sanger sequencing was performed for the clear pathogenic mutation sites; the analysis software was used for bioinformatics analysis of the mutation sites.Results:A 6-year-old female proband developed poor night vision in both eyes after 1 year old. The BCVA of both eyes were 0.1. The color of the optic disc was slightly lighter; the diameter of the retinal vessels was slightly reduced, and extensive pigment changes can be seen in the retina outside the vascular arch. SD-OCT examination showed that the outer membrane, ellipsoid zone and chimera zone in the central fovea of both eyes were unclear and intermittent. The visual area outside the fovea was neuroepithelial outer plexiform layer, outer nuclear layer, outer membrane, ellipsoid zone. The chimera zone gradually disappeared, and the thickness of the pigment epithelial layer was not uniform. In ff-ERG examination, the functions of the binocular cone and rod system were severely decreased. The results of genetic testing showed that there were c.921C>A homozygous mutations in the Tubby-like protein (TULP1) gene of the proband, and c.3121C>T and c.3488G>A compound heterozygous mutations in the cyclic nucleotide gated channel beta 1 (CNGB1) gene. Amino acid conservation analysis results showed that the above three mutation sites were highly conserved in multiple species; bioinformatics analysis results showed that TULP1 gene c.921C>A (p.Cys307*) had translation termination in the protein conserved region, CNGB1 gene c.3121C>T (p.Arg1041Trp) and c.3488G>A (p.Gly1163Glu) had amino acid polarity changes in the protein conserved region, which led to major changes in the protein spatial structure.Conclusion:TULP1 gene c.921C>A homozygous mutation, CNGB1 gene c.3121C>T and c.3488G>A compound heterozygous mutation are the mutation sites of this EOSRD family.

Objective:To identify the pathogenic gene mutations in a family with Leber congenital amaurosis (LCA).Methods:In October 2018, 1 patient and 3 normal family members from a LCA family was enrolled in this retrospective study. Detailed medical history of proband was obtained and fixation test, cycloplegic refraction, slit-lamp, fundus color photography and full-field ERG were performed. And other family members underwent BCVA, refraction slit-lamp, fundus biomicroscopy with the slit lamp, fundus color photography and full-field ERG. The family was investigated with a specific hereditary eye disease enrichment panel which contained 441 known pathogenic genes and based on targeted exome capture technology first to indentify the potential pathogenic genes and mutations. Then the potential pathogenic mutations were conformed by Sanger sequencing. Finally, the results were analyzed via bioinformatics analysis.Results:The proband showed no trace object from childhood, but had obvious photophobia and nystagmus. No positive changes were found in the anterior segment, vitreous and retina in both eyes. Both cone and rod system function decreased significantly in full-field ERG in both eyes. Gene tests showed the proband carried both RPGRIP1 c.1635dupA and c.3565C> T, which composited a heterozygous mutation. Bioinformatics analysis showed RPGRIP1 c.1635dupA was a pathogenic mutation, and RPGRIP1 c.3565C> T which was a novel potential pathogenic mutation in LCA.Conclusion:The compound heterozygous mutation, c.1635dupA and c.3565C> T in RPGRIP1 may be responsible for the pathogenesis in this Chinese Han LCA pedigree.