A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

OBJECTIVES: Psoriasis is a chronic inflammatory skin disease often accompanied by comorbidities such as hyperglycemia, insulin resistance, and obesity. Acitretin, as a second-generation retinoid, is used in the treatment of psoriasis. This study aims to explore the role of acitretin on glucose and lipid metabolism in psoriasis. METHODS: HepG2 cells were treated with acitretin under high- or low-glucose conditions. mRNA and protein expression levels of glucose transport-related genes were evaluated using real-time reverse transcription PCR (real-time RT-PCR) and Western blotting. Glucose uptake was analyzed by flow cytometry, and intracellular lipid droplet formation was assessed via Oil Red O staining. Healthy adult female BALB/C mice were randomly divided into 3 groups: a control group, an imiquimod (IMQ)-induced psoriasis model group (IMQ group), and an acitretin treatment group. Skin lesions and inflammatory markers were examined, along with changes in body weight, plasma glucose/lipid levels, and transcription of metabolic genes. Islets were isolated from normal and psoriasis-induced mice, and the effect of acitretin on insulin secretion was evaluated in vitro. RESULTS: Acitretin treatment increased glucose uptake and lipid droplet synthesis of HepG2 in high-glucose environment, with elevated transcription levels of glucose transport-related genes GLUT1 and GLUT4. Transcription of gluconeogenesis-related gene G6pase decreased, while transcription levels of glycogen synthesis-related genes AKT1 and GSY2 increased (all P<0.05), while acitretin inhibits glucose uptake and promotes gluconeogenesis in low-glucose environment. In vivo experiments revealed that compared with the control group, the blood glucose level in the IMQ group was significantly decreased (P<0.05), while acitretin treatment partially restored glucose homeostasis and alleviated weight loss. Ex vivo culture of islets from psoriatic mice revealed that acitretin reduced elevated insulin secretion and downregulated PDX-1 expression, while upregulating glucose homeostasis gene SIRT1 and insulin sensitivity gene PPARγ (all P<0.05). These findings suggest that acitretin plays a critical role in improving islet function and restoring islet homeostasis. CONCLUSIONS Acitretin helps maintain the balance between hepatic glycogenesis and gluconeogenesis, enhances insulin sensitivity, and improves pancreatic islet function, thereby promoting systemic and cellular glucose homeostasis.
Acitretin/therapeutic use* ; Psoriasis/drug therapy* ; Animals ; Imiquimod ; Humans ; Glucose/metabolism* ; Homeostasis/drug effects* ; Mice ; Lipid Metabolism/drug effects* ; Mice, Inbred BALB C ; Female ; Hep G2 Cells ; Disease Models, Animal

Objective:To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China.Methods:The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia.Results:The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% ( HR=1.22, 95% CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% ( HR=0.67, 95% CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion:Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

Objective:To research the quality control and testing methods of polysomnography and to ensure its safe and effective performance.Methods:A quality control testing method was designed for the main indicators of EEG signal,EMG signal,ECG signal,and pulse oxygen saturation of polysomnography.In August 2023,two polysomnography instruments of the same brand and different models(marked as Test Equipment A and Test Equipment B)in clinical use in Daping Hospital,Army Medical University were selected.The quality control testing of polysomnography instrument was conducted by using electroencephalogram calibration instrument and vital sign simulator to evaluate the reliability of the performance of polysomnography.Results:A quality control testing method was developed for quality control testing of polysomnography aiming at the repeatability of the indicated values of EEG signals,EMG signals,ECG signals,and pulse oxygen saturation of polysomnography.Except for the output value of 2 mV of the voltage measurement simulator of test equipment B,the relative error of the recorded data was-11%,and the parameters were out of tolerance,and the rest of the test data of test equipment A and test equipment B met the maximum limit output value of the national metrology verification regulations and the technical requirements of the equipment manufacturer.Conclusion:The quality control detection method of polysomnography can evaluate the performance parameters of the selected testing equipment A and testing equipment B,and provide technical support for the quality control detection and safe use of such equipment.

Hepatic cholesterol accumulation is an important contributor to hypercholesterolemia, which results in atherosclerosis and cardiovascular disease (CVD). ATP-citrate lyase (ACLY) is a key lipogenic enzyme that converts cytosolic citrate derived from tricarboxylic acid cycle (TCA cycle) to acetyl-CoA in the cytoplasm. Therefore, ACLY represents a link between mitochondria oxidative phosphorylation and cytosolic de novo lipogenesis. In this study, we developed the small molecule 326E with an enedioic acid structural moiety as a novel ACLY inhibitor, and its CoA-conjugated form 326E-CoA inhibited ACLY activity with an IC₅₀ = 5.31 ± 1.2 μmol/L in vitro. 326E treatment reduced de novo lipogenesis, and increased cholesterol efflux in vitro and in vivo. 326E was rapidly absorbed after oral administration, exhibited a higher blood exposure than that of the approved ACLY inhibitor bempedoic acid (BA) used for hypercholesterolemia. Chronic 326E treatment in hamsters and rhesus monkeys resulted in remarkable improvement of hyperlipidemia. Once daily oral administration of 326E for 24 weeks prevented the occurrence of atherosclerosis in ApoE^-/- mice to a greater extent than that of BA treatment. Taken together, our data suggest that inhibition of ACLY by 326E represents a promising strategy for the treatment of hypercholesterolemia.

OBJECTIVE To evaluate the bioequivalence of a single oral administration of two palbociclib preparations in healthy subjects under fasting and fed conditions. METHODS Twenty-four healthy subjects （fasting test） and twenty healthy subjects （fed test） were enrolled and divided into two groups. A single-center， open-label， single-dose， two-formulation， two- period， two-sequence and crossover trial was designed. The subjects in the two groups were given the test preparation （domestic Palbociclib capsules） or the reference preparation （original Palbociclib capsules） orally under fasting or fed conditions respectively followed by a 14-day washout period. The blood samples were collected at different time points before and after treatment. After pretreatment， the mass concentration of palbociclib in vivo was determined by high-performance liquid chromatography-tandem mass spectrometry with palbociclib-d8 as the internal standard. SAS V9.4 software was used to calculate the pharmacokinetic parameters and evaluate the bioequivalence. RESULTS Under fasting condition， the cmax of the test preparation and the reference preparation were （71.4±18.1） and （73.8±19.0） ng/mL； AUC0－t were （1 754±412） and （1 793±448） h·ng/mL； AUC0－∞ were （1 851±456） and （1 887±478） h·ng/mL， respectively. Under fed condition， the cmax of the test preparation and the reference preparation were （78.4±18.3） and （81.9±21.7） ng/mL； AUC0－t were （1 905±375） and （1 932±318） h·ng/mL； AUC0－∞ were （2 027±411） and （2 050±342） h·ng/mL， respectively. The 90%CI of the geometric mean ratio of the above parameters was within the acceptable range （80.00%-125.00%）. Under fasting and fed conditions， there were 20 and 16 adverse events in 9 and 8 subjects， respectively， but no serious adverse event was observed. CONCLUSIONS Under the fasting and fed conditions， the test preparation and the reference preparation of Pibociclib capsules are bioequivalent and have comparable safety.

Blau syndrome is a rare genetic disorder characterized by the a mix of granulomatous arthritis, uveitis, and dermatitis. Patients typically manifest multisystem involvement, including ocular, skin, and skeletal abnormalities. Blau syndrome is extremely rare, with a global incidence of less than one in a million among children. In this multidisciplinary consultation, we present a case of a 21-year-old young female patient having multisystemic involvement since early childhood. She was presented with multiple joint swelling, skin lesions, increased eye discharge, and accompanied by hypertension and arterial abnormalities, and received a diagnosis of uveitis. The patient had been receiving steroid treatment since the age of 6 and has tried various medications, with some improvement in joint swelling and ocular symptoms. Through this rare disease multidisciplinary consultation, we aim to provide guidance in the molecular diagnosis of the patient, multisystem assessment, and the selection and formulation of treatment plans. Additionally, we hope that by reporting this case, clinical physicians can gain a better understanding of the diagnosis and comprehensive treatment strategies for Blau syndrome, thereby improving the management and treatment of rare diseases.

Objective    To systematically evaluate the clinical value of miRNA-1 in the diagnosis of acute myocardial infarction (AMI) patients. Methods    We searched PubMed, EMbase, Cochrane Library, CNKI, Wangfang, VIP, etc databases to identify literature about miRNA-1 in the diagnosis of AMI. Quality of the included literature was assessed by (quality assessment for diagnostic accuracy studies-2, QUADAS-2). The indices of pooled sensitivity (Sen), specificity (Spe), positivity likelihood ratio (PLR), negative likelihood ratio (NLR), diagnosis odds ratio (DOR), and the area under the summary receiver operating characteristic (SROC) curve were pooled using MetaDisc 1.4 software. Results    A total of 12 articles were included. According to the different populations of miRNA-1 to be tested, subgroup analysis of healthy people (7 articles) and non-AMI disease groups (5 articles) was conducted. The results showed that AMI compared with healthy people, the pooled Sen was 0.78 with 95%CI 0.73 to 0.82, Spe was 0.88 with 95%CI 0.83 to 0.91 of miRNA-1 in the diagnosis of AMI. AUC of SROC curve was 0.911 2. Comparison of AMI and non-AMI patients, the pooled Sen was 0.59 with 95%CI 0.54 to 0.64, Spe was 0.74 with 95%CI 0.68 to 0.79 of miRNA-1 in the diagnosis of AMI. AUC of SROC curve was 0.743 2. Conclusion    MiRNA-1 has a certain value in the diagnosis of AMI. It has an advantage in identifying AMI and patients with other systemic diseases, and can be combined with other biomarkers to  diagnose AMI.