OBJECTIVE To investigate the effects of Tripterygium wilfordii multiglycoside （TWM） on renal injury in diabetic nephropathy （DN） rats through tumor protein p53/microRNA-214 （miR-214）/UNC-51-like kinase 1 （ULK1） axis. METHODS Male SD rats were randomly divided into normal group （n＝6） and modeling group （n＝28）； the modeling group was fed with high fat and high glucose plus intraperitoneal injection of streptozotocin to establish DN model. The modeled rats were randomly divided into model group， valsartan group [8.33 mg/（kg·d）] and TWM group[6.25 mg/（kg·d）]， with 8 rats in each group. Rats in each group were gavaged with the corresponding medication or normal saline， once a day， for 6 consecutive weeks. After the last medication， liver and renal function indexes [24 h urinary total protein （24 h-UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， albumin （ALB）， alanine transaminase （ALT）]， blood lipid indexes （triglycerides， total cholesterol） and blood glucose index （fasting blood glucose） in urine/blood sample of rats were detected in each group. Renal pathologic change was observed， protein and mRNA expressions of p53， ULK1， Beclin-1 and microtubule-associated protein 1 light chain 3 （LC3）， and expression of miR-214 in renal tissue were also determined. RESULTS Compared with the normal group， the renal tubular epithelium of rats in the model group showed obvious edema， cell swelling， accompanied by lymphocyte infiltration； the levels of 24h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 in rats in the model group and administration groups were significantly increased or up-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1， Beclin-1 protein and mRNA were significantly decreased or down-regulated （P＜0.01）. Compared with the model group， the histopathological damage of the kidney in rats was improved in administration groups； the levels of 24 h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 were all significantly decreased or down-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1 and Beclin-1 protein and mRNA were significantly increased or up-regulated （P＜0.01）. CONCLUSIONS TG can alleviate renal damage in DN rats， and improve their liver and renal function， as well as glucose and lipid levels. These effects may be related to the regulation of the p53/miR-214/ULK1 axis and the restoration of cellular autophagy.

ObjectiveTo explore the effects of Kaixuan Jiedu core prescription （KXJD） on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions. MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups： healthy control （n=11）， model （n=11）， methotrexate （MTX， n=5）， low-dose （15.21 g·kg^-1） KXJD （n=5）， and high-dose （30.42 g·kg^-1） KXJD （n=5）. Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX， respectively， by gavage daily， while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment， back skin lesions were collected. Firstly， healthy control and model mice were selected for tandem mass tag （TMT） quantitative proteomics （control vs model=3 vs 3） and targeted lipid metabolomics （control vs model=11 vs 11）. Then， the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally， an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate （S1P）， and Western blot was employed to determine the expression levels of sphingosine kinase 2 （SPHK2） and monocyte chemotactic protein-1 （MCP-1）. ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin， and key proteases ［serine palmitoyltransferase， long chain base subunit 2 （SPTLC2）， SPHK2， delta（4）-desaturase sphingolipid 1 （Degs1）， and ceramide synthase 4 （CerS4）］ and 8 sphingolipid metabolites （including ceramides， sphingol， sphingomyelin， and glycosphingolipid） expressed abnormally （P<0.05） compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components （quercetin， kaempferol， and luteolin） in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol^-1. Further experimental verification showed elevated expression levels of SPHK2， S1P， and MCP-1 in psoriatic skin compared with healthy skin （P<0.05）， and KXJD down-regulated the expression levels of SPHK2， S1P， and MCP-1 compared with the model group （P<0.05）. ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.

ObjectiveTo explore the effects of Kaixuan Jiedu core prescription （KXJD） on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions. MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups： healthy control （n=11）， model （n=11）， methotrexate （MTX， n=5）， low-dose （15.21 g·kg^-1） KXJD （n=5）， and high-dose （30.42 g·kg^-1） KXJD （n=5）. Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX， respectively， by gavage daily， while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment， back skin lesions were collected. Firstly， healthy control and model mice were selected for tandem mass tag （TMT） quantitative proteomics （control vs model=3 vs 3） and targeted lipid metabolomics （control vs model=11 vs 11）. Then， the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally， an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate （S1P）， and Western blot was employed to determine the expression levels of sphingosine kinase 2 （SPHK2） and monocyte chemotactic protein-1 （MCP-1）. ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin， and key proteases ［serine palmitoyltransferase， long chain base subunit 2 （SPTLC2）， SPHK2， delta（4）-desaturase sphingolipid 1 （Degs1）， and ceramide synthase 4 （CerS4）］ and 8 sphingolipid metabolites （including ceramides， sphingol， sphingomyelin， and glycosphingolipid） expressed abnormally （P<0.05） compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components （quercetin， kaempferol， and luteolin） in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol^-1. Further experimental verification showed elevated expression levels of SPHK2， S1P， and MCP-1 in psoriatic skin compared with healthy skin （P<0.05）， and KXJD down-regulated the expression levels of SPHK2， S1P， and MCP-1 compared with the model group （P<0.05）. ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.

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

This study aims to explore the protective effect of Chaihu Jia Longgu Muli Decoction on rats with heart failure after myocardial infarction, and to clarify its possible mechanisms, providing a new basis for basic research on the mechanism of classic Chinese medicinal formula-mediated inflammatory response in preventing and treating heart failure induced by apoptosis after myocardial infarction. A heart failure model after myocardial infarction was established in rats by coronary artery ligation. The rats were divided into sham group, model group, and low, medium, and high-dose groups of Chaihu Jia Longgu Muli Decoction, with 10 rats in each group. The low-dose, medium-dose, and high-dose groups of Chaihu Jia Longgu Muli Decoction were given 6.3, 12.6, and 25.2 g·kg~(-1) doses by gavage, respectively. The sham group and model group were given an equal volume of distilled water by gavage once daily for four consecutive weeks. Cardiac function was assessed using color Doppler echocardiography. Myocardial pathology was detected by hematoxylin-eosin(HE) staining, apoptosis was measured by TUNEL assay, and mitophagy was observed by transmission electron microscopy. The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and N-terminal pro-B-type natriuretic peptide(NT-proBNP) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), and cleaved caspase-3 was detected by Western blot. Additionally, the expression of phosphorylated nuclear transcription factor-κB(NF-κB) p65(p-NF-κB p65)(upstream) and nuclear factor kappa B inhibitor alpha(IκBα)(downstream) in the NF-κB signaling pathway was assessed by Western blot. The results showed that compared with the sham group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) in the model group were significantly reduced, while left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) increased significantly. Myocardial tissue damage was severe, with widened intercellular spaces and disorganized cell arrangement. The apoptosis rate was increased, and mitochondria were enlarged with increased vacuoles. Levels of TNF-α, IL-1β, and NT-proBNP were elevated, indicating an obvious inflammatory response. The expression of pro-apoptotic factors Bax and cleaved caspase-3 increased, while the anti-apoptotic factor Bcl-2 decreased. The expression of p-NF-κB p65 was upregulated, and the expression of IκBα was downregulated. In contrast, the Chaihu Jia Longgu Muli Decoction groups showed significantly improved of LVEF, LVFS and decreased LVEDD, LVESD compared to the model group. Myocardial tissue damage was alleviated, and intercellular spaces were reduced. The apoptosis rate decreased, mitochondrial volume decreased, and the levels of TNF-α, IL-1β, and NT-proBNP were lower. The expression of pro-apoptotic factors Bax and cleaved caspase-3 decreased, while the expression of the anti-apoptotic factor Bcl-2 increased. Additionally, the expression of p-NF-κB p65 decreased, while IκBα expression increased. In summary, this experimental study shows that Chaihu Jia Longgu Muli Decoction can reduce the inflammatory response and apoptosis rate in rats with heart failure after myocardial infarction, which may be related to the regulation of the IκBα/NF-κB signaling pathway.
Animals ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Myocardial Infarction/physiopathology* ; Male ; NF-kappa B/genetics* ; Heart Failure/etiology* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; NF-KappaB Inhibitor alpha/genetics* ; Humans ; Tumor Necrosis Factor-alpha/genetics*

OBJECTIVES: This study aimed to investigate the clinical characteristics of deciduous fused teeth and their inherited permanent-tooth performance type by using panoramic radiographs. METHODS: A total of 14 404 panoramic radiographs of 3- to 6-year-old children with deciduous dentition were collected from January 2023 to July 2024. The incidence of deciduous fused teeth was observed, and the abnormality of permanent teeth was recorded. SPSS 24.0 software was used for statistical analysis. RESULTS: The incidence of deciduous fused teeth was 3.06% (441/14 404). The order of dental position was as follows: mandibular deciduous incisors and cusp teeth fused (58.18%) > mandibular deciduous central and lateral incisors fused (30.91%) > maxillary deciduous central and lateral incisors fused (8.89%) > deciduous incisors and supernumerary teeth fused (2.02%). Deciduous fused teeth were found in 226 boys and 215 girls, with no significant difference between the sexes (P>0.05). We observed one pair (87.76%, 387/441) and two pairs (12.24%, 54/441) of fused teeth (54/441), respectively. A total of 287 pairs of fusion teeth on the right side more than 208 pairs on the left side, and the difference between them was statistically significant (P<0.01). More fusion teeth existed in mandibular deciduous teeth (443 pairs) than in maxillary ones (54 pairs), and the difference between them was statistically significant (P<0.01). More unilateral deciduous teeth (387 subjects) were found than bilateral ones (54 subjects), and the difference between them was statistically significant (P<0.01). Three types of deciduous fused teeth with inherited permanent teeth were observed as follows: 1) 49.49% (245/495) of inherited permanent teeth was absent, 2) 46.67% (231/495) of inherited permanent teeth was not absent, and 3) the number of fused permanent teeth accounted for 3.84% (19/495). CONCLUSIONS The incidence of deciduous fused teeth was 3.06%, mostly occurring in the lower anterior teeth region, with no gender difference. One pair of fused teeth is commonly observed, more often on the right than the left. These fusions occur more frequently in the mandible than the maxillary, and unilateral cases are more common than bilateral ones. Deciduous fused teeth had a certain impact on inherited permanent teeth. Pediatric dentists should pay attention to and closely observe whether any abnormality exists in the permanent dentition for early detection to prevent the harm caused by deciduous fused teeth.
Humans ; Tooth, Deciduous/abnormalities* ; Male ; Child ; Female ; Child, Preschool ; Dentition, Permanent ; Radiography, Panoramic ; Fused Teeth/diagnostic imaging* ; Incisor/diagnostic imaging* ; Tooth, Supernumerary/diagnostic imaging* ; Incidence ; Mandible

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Objective To explore the distribution of traditional Chinese medicine(TCM)syndrome elements in patients with multi-drug resistant bacteria-infected pneumonia.Methods Clinical data of 126 patients with multi-drug resistant bacteria-infected pneumonia admitted to the intensive care unit of Lung Disease Centre of Qingdao Hospital of Traditional Chinese Medicine from May 2020 to July 2022 were retrospectively collected.The clinical data included the patients'gender,age,underlying diseases,history of bad additions of smoking and alcohol,multi-drug resistant bacteria,and the information of four diagnostic methods of TCM,etc.The disease-nature syndrome elements in patients with drug-resistance to various strains of drug-resistant bacteria were extracted,and then deficiency-excess syndrome differentiation was carried out.Results(1)A total of 201 strains of multi-drug resistant bacteria were detected in 126 patients with multi-drug resistant bacterial pneumonia.The main pathogenic species were Gram-negative bacteria,and the proportion accounted for 95.52%(192/201),which was significantly higher than that of Gram-positive bacteria[4.48%(9/201)],with a statistically significant difference(χ2 = 166.612,P＜0.001).Klebsiella pneumoniae accounted for the highest percentage of 23.38%in the gram-negative bacterium.(2)A total of 12 syndrome elements were extracted from the 126 patients.The excess syndrome elements were predominated by phlegm and heat,and the deficiency syndrome elements were predominated by yin deficiency.There was no statistically significant difference in the distribution of yin deficiency,blood deficiency,heat,phlegm,fluid-retention and damp syndrome elements among patients with different strains of drug-resistant bacterial infection(P＞0.05).(3)Of the 126 patients,62 cases(49.21%)had simple excess syndrome,one case(0.79%)had simple deficiency syndrome,and 63 cases(50.00%)had concurrent deficiency-excess syndrome.Among the 126 patients,there were 19 cases of single syndrome element,41 cases of concurrent two-syndrome element,49 cases of concurrent three-syndrome element,16 cases of concurrent four-syndrome element,and one case of concurrent five-syndrome element.And the combined syndrome element of phlegm-heat-yin deficiency occurred most frequently for 26 times.Conclusion Gram-negative bacteria are the primary infectious pathogens for the patients with multi-drug resistant bacterial infections,and the TCM syndrome elements of the patients are characterized by the concurrence of deficiency and excess and simple excess syndrome,mainly manifesting as phlegm,heat,and yin deficiency.

Huangqitang comes from the Taiping Huimin Hejiju Fang of the Song dynasty. It consists of four medicinal materials: Astragalus membranaceus var. mongholicus, Citrμs reticμlata， Cannabis sativa， and Apis cerana. It is a classic prescription for treating constipation in the elderly. This study systematically collated the literature records about Huangqitang in ancient Chinese medicine books and combined it with the current status of modern clinical applications to conduct in-depth analysis and research on the origin，composition， dosage, processing, preparation and administration, drug base, main symptoms， and other key information of the formula, so as to provide a strong reference for the development and clinical application of the classic Huangqitang compound preparation. Through systematic combing and textual research on the previous literature of Huangqitang， it can be seen that the formula of Huangqitang was first recorded in the Taiping Huimin Hejiju Fang， and the medical books of the past dynasties mostly adopted this formula. In terms of drug base， the dried roots of the leguminous plant Astragalus membranaceus var. mongholicus are used， and for tangerine， the dried outer peel of the Rutaceae plant Citrus reticμlata and its cultivated varieties are used. The Moraceae plant Cannabis sativa with the peel removed is selected, and the Apis cerana is selected from the honey brewed by Apis cerana， an insect of the Apidae family. In terms of dosage， although the dosage of some drugs changed during the Ming and Qing dynasties, the dosage records basically followed the original prescriptions from the Song dynasty. In terms of processing, preparation, and usage， although the drug processing， preparation， and usage of Huangqitang in the medical books of the past dynasties have changed slightly， they are basically the same as the original prescription of the Song dynasty. In terms of main symptoms, Huangqitang is designed to treat constipation in the elderly. From the Song dynasty to the Qing dynasty， it was mostly used to treat constipation， secret congestion, asthenia， etc. in the elderly. In modern times， it is clinically used to treat constipation due to Qi deficiency， functional constipation， irritable bowel syndrome， and other diseases in the elderly. No adverse reactions have been found yet. In the subsequent research and development， it is necessary to carry out mass spectrometry analysis of Huangqitang， in-depth exploration of its prescription efficacy and mechanism of action， and other multi-omics scientific research. At the same time， it is important to establish quality control standards to provide a reliable scientific basis for the research and development, clinical treatment， and drug supervision of Huangqitang compound preparations.