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 explore the diagnosis and treatment of adolescence-onset methylenetetrahydrofolate reductase (MTHFR) deficiency.Methods:This was a retrospective case study. Nine patients with adolescence-onset MTHFR deficiency were diagnosed at Peking University First Hospital from January 2016 to December 2022, and followed up for more than 1 year. Their general information, clinical manifestations, laboratory tests, cranial images, MTHFR gene variants, diagnosis, treatment, and outcome were analyzed retrospectively.Results:The 9 patients came from 8 families. They had symptoms at age of 8.0 years to 17.0 years and diagnosed at 9.0 years to 17.5 years. Eight were male and 1 was female. Two patients were brothers, the elder brother developed abnormal gait at 17.0 years; and the younger brother was then diagnosed at 15.0 years of age and treated at the asymptomatic stage, who was 18.0 years old with normal condition during this study. The main manifestations of the 8 symptomatic patients included progressive dyskinesia and spastic paralysis of the lower limbs, with or without intellectual decline, cognitive impairment and behavioral abnormalities. Totally, 15 variants of MTHFR gene were identified in the 9 patients, including 8 novel variants. Five patients had brain image abnormalities. Increased plasma total homocysteine level (65-221 μmol/L) was found in all patients, and decreased to 20-70 μmol/L after treatment with betaine and calcium folinate. Besides, the 8 symptomatic patients had their behavior and cognitive problems significantly improved, with a legacy of lower limb motor disorders.Conclusions:Late-onset MTHFR deficiency can occur in adolescence. The diagnosis is usually delayed because of non-specific clinical symptoms. The test of blood total homocysteine could be used as a selective screening test. Eight novel varients of MTHFR gene were identified. Timely treatment can improve clinical condition significantly, and pre-symptomatic treatment may prevent brain damage.

Objective:To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies.Methods:This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months.Results:Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work.Conclusions:Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.

A liquid chromatography-quadrupole-time-of-flight mass spectrometer(LC-Q/TOF-MS) based urinary metabolomic approach was employed to assess the toxicity-alleviation effect of Huangqi oral solution(HOs) on cisplatin-exposed rats and explore its possible mechanisms. Rat toxicity model was developed by multiple intraperitoneal injection of low-dose cisplatin, while HOs was orally administrated to rats simultaneously for 16 consecutive days to attenuate or reduce the cisplatin-induced toxicity. 24-hour urine samples on day 18 were collected and analyzed using LC-Q/TOF-MS to obtain the dataset of urinary metabolites. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to assess the quality of the dataset and screen the potential toxicity-alleviation biomarkers. The serum level of rat creatinine and urea nitrogen on day 20 was determined, and the results showed that successive administration of HOs significantly reduced the cisplatin-induced increase of creatinine and urea nitrogen. PCA cluster analysis clearly demonstrated that HOs could partly improve the CDDP-induced abnormality of metabolic profiling. 35 urinary metabolites were finally screened as the potential biomarkers associated with the toxicity-attenuation effect of HOs, according to the combination of the analysis results of OPLS-DA, t-test and fold change analysis. Further metabolic pathway analysis revealed that HOs could restore the metabolic disorders of amino acid, energy and nucleotide, thereby exerted its toxicity-alleviation effect.

OBJECTIVE:To virtually screen potential α-glycosidase inhibitor ingredients from C. mori and F. mori,and to pro-vide reference for finding out new typeα-glycosidase inhibitor ingredient. METHODS:Surflex-Dock module of Sybyl-x 2.0 molecu-lar simulation software was used to perform the docking of small molecule compound,which was from the ingredients of C. mori and F. mori as ligand stated in literatures,with α-glycosidase. Total score of affinity scoring function was equal to 7 as the thresh-old value,to judge potential α-glycosidase inhibitor ingredient in C. mori and F. mori. RESULTS:After 70 small molecule com-pounds docked with α-glycosidase, 10 compounds showed binding activity (Total score≥7.00). Among them, moracin M-3′-O-β-D-glucopyranoside,5,7,2′-trihydroxyflavanone-4′-O-β-D-glucoside,mulberroside A,resveratrol-4,3′-di-O-β-D-gluco-pyranoside and 1,4-dideoxy-1,4-imino-(2-O-β-D-glucopyranosyl)-D-arabinitol had higher binding activity with α-glycosidase(Total score>8.00). CONCLUSIONS:Multi-constituents of C. mori and F. Mori show potential α-glycosidase inhibitory activity. The method is a kind of highly targeted,rapid and efficient approach to discover α-glycosidase inhibitor from traditional Chinese medi-cine.

Aim To establish a LC-MS/MS method for the determination of pirfenidone(BT)and its major metabolite 5-carboxy-pirfenidone(SBT)in human plasma.Methods Human plasma samples containing BT and SBT,as well as their corresponding deuterium-labeled internal standards pirfenidone-d5(dBT)and 5-carboxy-pirfenidone-d5(dSBT),were precipitated using methanol.Chromatographic separation was carried out on an Agilent ZORBAX SB C18(3.0 mm×100 mm,3.5 μm)column with the mobile phase of water(0.5％formic acid)and acetonitrile(50/50).The detection of analytes was performed on a tandem mass system equipped with an electrospray ionization source in positive ion mode using multiple-reaction monitoring.The MS/MS ion transitions monitored were m/z 185.958→77.1 for BT,m/z 215.944→77.0 for SBT,m/z 190.965→81.1 for dBT and m/z 220.948→99.1 for dSBT.Results There was no remarkable interference in blank solvent,plasma,and there was no mutual interference between analytes or internal standards.The proposed method showed good linearity over the concentration range of 0.020 59～25.14 mg·L-1 for BT and 0.016 73～20.42 mg·L-1 for SBT.The intra-batch and inter-batch precision and accuracy were proved to be acceptable.Human samples kept stable after 4 h at room temperature,the three freeze-thaw cycles and 10,29 and 52 days at-70 ℃,and the processed samples remained stable after 24 h in the autosampler.The average extraction recovery and matrix effect were precise,reproducible and acceptable.Conclusion Our current LC-MS/MS method is proved to be sensitive,accurate and convenient,and could be suitable for the clinical pharmacokinetic studies of BT-related preparations.

Objective:To explore the clinical characteristics,diagnosis,and treatments of adrenal insufficiency (AI) in the patients with acquired immune deficiency syndrome (AIDS),and to improve the clinician's understanding of the disease and provide evidences for its diagnosis and treatments.Methods:The clinical data of one patient with AIDS and AI were retrospectively analyzed and the diagnosis and treatments were summarized,and the relative literatures were reviewed.Results:The patient was clearly diagnosed as AIDS and AI after relevant examinations.The symptoms such as fatigue,nausea and vomiting of the patient were disappeared,the food intake of the patient was increased,and the electrolyte was normal after some treatments such as hormone replacement therapy (oral prednisone acetate 5.0 mg at 8:00 am.and 2.5 mg at 4:00 pm.) and symptomatic treatments.The patient died of a severe opportunistic infection when followed up for 37 d.Conclusion:The possibility of AI should be taken into account when the patients with AIDS have unexplained symptoms such as anorexia,nausea,weight loss and more characteristic manifestations such as orthostatic hypotension,hyponatremia or hyperkalemia.Early administration of glucocorticoid replacement therapy is feasible and effective.