The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective:To establish a detection method for fatty acid composition and methoxylaniline value in pharmaceutical excipient castor oil.Methods:The detection of fatty acid composition involves pre-test of the sam-ple using the methanol sodium methylation method,followed by direct injection analysis using gas chromatography,and finally calculating the content of each fatty acid composition using the area normalization method with correction factors.The detection of methoxylaniline value is achieved by dissolving and diluting the sample with isooctane:isopropanol(8∶2,volume ratio),reacting with 4-methoxylaniline,measuring the absorbance at a wavelength of 350 nm,and calculating the methoxylaniline value.Results:Under the composition of fatty acids,the 8 kinds of fatty acids have good separation degree.The methyl ricinoleate and methyl stearate have good linear relationship in the range of 0.1-5.0 mg·mL-1.The repeatabilityand intermediate precision(RSD)ofthe determination results of each fatty acid in the sample are all less than 5%.It is also found that only α-type of linolenic acid is present in castor oil,without γ-type.In the determination of methoxyaniline value,the blank solvent does not interfere with the determination of the sample,and the repeatability RSD is 3.6%.Conclusion:The detection method for fatty acid composition and meth-oxylaniline value established in this article is accurate and reliable,and can be used for the detection of fatty acid composition and methoxylaniline value in pharmaceutical excipient castor oil.

Objective:This study aimed to analyze the expression of B-cell maturation antigen (CD269) on myeloma cells in patients with newly diagnosed multiple myeloma (NDMM) and evaluate its prognostic value.Methods:The retrospective analysis was conducted on the clinical data of 154 NDMM patients admitted to the outpatient clinics and wards of Beijing Chaoyang Hospital, Capital Medical University from October 23, 2018 to December 25, 2023, including 90 males and 64 females, aged 60(55,66) years old. CD269 phenotype was analyzed using flow cytometry (FCM). Specifically, patients were divided into CD269 positive group (expression>20%, n=103) and CD269 negative group (expression≤20%, n=51) based on the flow cytometry prior to treatment. Initially, we assessed the effect of CD269 expression on progression-free survival (PFS) in patients with NDMM and compared the two groups. Through a cross-sectional analysis, we examined the basic clinical characteristics, 32 laboratory indicators, and 5 cytogenetic indicators. We identified differences between the two groups and analyzed the impact of various indicators on the PFS of patients in both the CD269 positive and negative groups. Furthermore, we employed the Cox proportional hazards regression model to evaluate the influence of CD269 expression and other disease-related indicators on patients′ PFS. Results:Among 154 NDMM patients, 103 were identified as CD269 positive (66.9%), while 51 were CD269 negative (33.1%). No statistically significant differences in clinical indicators were observed between the two groups. The PFS for CD269 positive group was significantly lower than it in the CD269 negative group [28.0(18.0,41.0) months vs 35.0 (27.0, -) months, HR=2.012, 95% CI 1.059-3.824, χ 2=4.554, P=0.033]. Cox proportional hazards regression analysis indicated that CD269 positivity and non-IgG subtypes were independent risk factors influencing PFS in NDMM patients( HR=2.395,95% CI 1.152-4.979, P=0.019; HR=0.425,95% CI 0.223-0.810, P=0.009). In the CD269 positive group, progression-free survival (PFS) was significantly shortened in patients with>65 years, non-IgG subtypes, International Staging System (ISS) stage Ⅲ, β2-microglobulin (β2-MG) levels≥5.5 mg/L, abnormal t(11;14) or ≥3 cytogenetic abnormalities. Conclusion:CD269 positivity serves as an independent risk factor influencing PFS in NDMM patients. Among the factors examined, older age, non-IgG subtype, ISS stage Ⅲ, elevated serum β2-MG, the presence of an abnormal t(11;14) translocation and≥3cytogenetic abnormalities, significantly impact the PFS of CD269 positive patients.

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

Arsenic is a semi-metal,and lipid-soluble arsenic compounds are one of the widespread forms in the environment and food chain,but there is a lack of standards for lipid-soluble arsenic compounds,which is one of the bottlenecks in the current analytical detection and toxicological studies of organic arsenic.In this study,four saturated arsenic-containing hydrocarbons,AsHC 318,AsHC 332,AsHC 346,and AsHC 374(The number is relative molecular mass),were successfully synthesized in three steps by using dimethylarsinic acid,potassium iodide,sodium hydroxide,and four brominated alkanes(1-Bromotetradecane,1-bromopentadecane,1-bromohexadecane,and 1-bromooctadecane)as raw materials.The structures of these four saturated arsenic-containing hydrocarbons were characterized by proton nuclear magnetic resonance(1H NMR)spectroscopy,13C nuclear magnetic resonance(13C NMR)spectroscopy,and high-resolution mass spectrometry(HR-MS).The yields of the method were 8%-10%,and the synthesized compounds could be used in subsequent toxicity evaluation experiments to assess the toxic effects and mechanisms of action of arsenic-containing hydrocarbons.This study provided an effective method for synthesis of arsenic-containing hydrocarbons,enriching the synthesis methods of arsenic-containing hydrocarbons,and provided raw materials for the subsequent toxicological studies of arsenic-containing hydrocarbons.

Objective To analyze the imaging features of cerebral small vessel disease in patients with type 2 diabetes mellitus by multimodal MRI.Methods The clinical data of 160 patients with cerebral small vessel disease admitted to our hospital from January to December 2020 were retrospectively analyzed.According to whether they were complicated with type 2 diabetes mellitus,they were divided into the diabetic group and the non-diabetic group,with 80 cases in each group.Both groups underwent multimodal MRI scans.And the severity of lacunar infarction,the severity of subcortical and periventricular white matter lesions,white matter integral and cerebral microbleeds of patients in the two groups were compared.Results The severity of lacunar infarction(χ2=34.076,P=0.001),subcortical white matter lesions(χ2=25.000,P=0.001),periventricular white matter lesions(χ2=22.895,P=0.001)and white matter integral(t=12.370,P=0.001)of patients in the diabetic group were significantly higher than those in the non-diabetic group.No cerebral microbleeds were detected in either group of patients.Conclusion Patients with cerebral small vessel disease and type 2 diabetes mellitus show characteristic multimodal MRI changes.The increase in the number of lacunar infarction lesions and the aggravation of white matter lesions can be used as the characteristic imaging basis for the diagnosis of type 2 diabetes mellitus related cerebral small vessel disease.