This study aimed to investigate the effects of zidovudine (AZT) on high-fat diet (HFD)-induced metabolic disturbances in rats and its underlying mechanisms. The HFD rat model was established, and the animals were divided into the control group, the model group, and the AZT-treated group at low (25 mg/kg) and high (50 mg/kg) doses. Metabolic phenotype, hepatic lipid deposition, oxidative stress, mitochondrial function, and peroxisome proliferator-activated receptor (PPAR) signaling were evaluated. AZT treatment significantly mitigated HFD-induced body weight gain and reduced both the mass and adipocyte size of inguinal and epididymal white adipose tissues; it also enhanced metabolic flexibility and improved glucose tolerance without elevating blood lactate levels. High-dose AZT further lowered hepatic triglyceride accumulation, ameliorated steatosis, and additionally, attenuated hepatic oxidative stress by increasing superoxide dismutase (SOD) activity and decreasing malondialdehyde (MDA) levels. Western blot analysis revealed that AZT upregulated hepatic PPARα and carnitine palmitoyltransferase 1α (CPT1α), while downregulating PPARγ expression. In conclusion, AZT effectively ameliorates HFD-induced metabolic disorders without inducing mitochondrial toxicity, which may be related to the promotion of fatty acid oxidation, the reduction of oxidative stress, and the modulation of both the PPAR signaling pathway and pyrimidine metabolism.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Purpose: Rare diseases occur in <50 per 100000 people and require lifelong management. However, essential epidemiological data on such diseases are lacking, and a consecutive monitoring system across time and regions remains to be established. Standardized digital phenotypes are required to leverage an international data network for research on rare endocrine diseases. We developed digital phenotypes for rare endocrine diseases using the observational medical outcome partnership common data model. Materials and Methods: Digital phenotypes of three rare endocrine diseases (medullary thyroid cancer, hypoparathyroidism, pheochromocytoma/paraganglioma) were validated across three databases that use different vocabularies: Severance Hospital’s electronic health record from South Korea; IQVIA’s United Kingdom (UK) database for general practitioners; and IQVIA’s United States (US) hospital database for general hospitals. We estimated the performance of different digital phenotyping methods based on International Classification of Diseases (ICD)-10 in the UK and the US or systematized nomenclature of medicine clinical terms (SNOMED CT) in Korea. Results: The positive predictive value of digital phenotyping was higher using SNOMED CT-based phenotyping than ICD-10-based phenotyping for all three diseases in Korea (e.g., pheochromocytoma/paraganglioma: ICD-10, 58%–62%; SNOMED CT, 89%). Estimated incidence rates by digital phenotyping were as follows: medullary thyroid cancer, 0.34–2.07 (Korea), 0.13–0.30 (US); hypoparathyroidism, 0.40–1.20 (Korea), 0.59–1.01 (US), 0.00–1.78 (UK); and pheochromocytoma/paraganglioma, 0.95–1.67 (Korea), 0.35–0.77 (US), 0.00–0.49 (UK). Conclusion Our findings demonstrate the feasibility of developing digital phenotyping of rare endocrine diseases and highlight the importance of implementing SNOMED CT in routine clinical practice to provide granularity for research.

Purpose: Rare diseases occur in <50 per 100000 people and require lifelong management. However, essential epidemiological data on such diseases are lacking, and a consecutive monitoring system across time and regions remains to be established. Standardized digital phenotypes are required to leverage an international data network for research on rare endocrine diseases. We developed digital phenotypes for rare endocrine diseases using the observational medical outcome partnership common data model. Materials and Methods: Digital phenotypes of three rare endocrine diseases (medullary thyroid cancer, hypoparathyroidism, pheochromocytoma/paraganglioma) were validated across three databases that use different vocabularies: Severance Hospital’s electronic health record from South Korea; IQVIA’s United Kingdom (UK) database for general practitioners; and IQVIA’s United States (US) hospital database for general hospitals. We estimated the performance of different digital phenotyping methods based on International Classification of Diseases (ICD)-10 in the UK and the US or systematized nomenclature of medicine clinical terms (SNOMED CT) in Korea. Results: The positive predictive value of digital phenotyping was higher using SNOMED CT-based phenotyping than ICD-10-based phenotyping for all three diseases in Korea (e.g., pheochromocytoma/paraganglioma: ICD-10, 58%–62%; SNOMED CT, 89%). Estimated incidence rates by digital phenotyping were as follows: medullary thyroid cancer, 0.34–2.07 (Korea), 0.13–0.30 (US); hypoparathyroidism, 0.40–1.20 (Korea), 0.59–1.01 (US), 0.00–1.78 (UK); and pheochromocytoma/paraganglioma, 0.95–1.67 (Korea), 0.35–0.77 (US), 0.00–0.49 (UK). Conclusion Our findings demonstrate the feasibility of developing digital phenotyping of rare endocrine diseases and highlight the importance of implementing SNOMED CT in routine clinical practice to provide granularity for research.

Objective To explore the clinical characteristics of the patients with follicular cysts and menstrual disorders.Methods A total of 178 women with follicular cysts complicated by menstrual disorders were recruited,who were aged 23-53(38.62±6.35)years and came to the Department of Gynecological Endocrinology,Beijing Obstetrics and Gynecology Hospital between August 2022 and July 2024.The participants were divided into three groups according to the age,with 27 women in the age group of 21-30 years(Group 1),77 in the age group of 31-40 years(Group 2),and 74 in the age group of>40 years(Group 3).The age and menstruation of these patients were collected,the body height,weight,follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),progesterone(Po),total testosterone(TT),prolactin(PRL),anti-müllerian hormone(AMH)and thyroid function[blood routine and blood clotting for patients with abnormal uterine bleeding(AUB)]were measured,and the diameter of ovarian cyst and the thickness of endometrium were examined.The clinical characteristics of the patients with follicular cysts complicated by menstrual disorders were described and compared with each other among the three age groups.Results ① Among 178 patients,61(34.3%)patients presented with complaints of cessation of regular menstruation or amenorrhea and 117(65.7%)with complaints of AUB.Out of 178 patients,13(7.3%)patients developed anemia due to AUB,and all the patients were treated with medication.② Follicular cysts disappeared in 1 month for 124(69.7%)patients,disappeared in 2 months for 176(98.9%)patients,and disappeared in 3 months for 178(100%)patients.A total of 177(99.4%)patients had follicular cysts with a diameter less than 5 cm,and only 1(0.6%)patient had follicular cysts with a diameter≥5 cm.③ The overall prevalence of diminished ovarian reserve(DOR)in patients with follicular cysts complicated by menstrual disorders was 82.0%,and the prevalence of DOR was 70.2%for the patients under 40 years old.The prevalence of DOR in three age groups was 37.0%(10/27),81.8%(63/77),and 98.6%(73/74),respectively.The prevalence of DOR gradually increased with age.④ The median AMH values for Group 1,Group 2,and Group 3 were 1.55,0.51,and 0.15 ng/mL,respectively.The FSH level in Group 3 was significantly higher than that in Groups 1 and 2(adjusted P<0.05),while the AMH level was significantly lower than that in Groups 1 and 2(adjusted P<0.05).The AMH level in Group 2 was lower than that in Group 1(adjusted P<0.05).Conclusion Patients with follicular cysts complicated by menstrual disorders are recommended to receive medication treatment,rather than just expecting treatment.The prevalence of DOR in patients with follicular cysts complicated by menstrual disorders is significantly higher than that in normal women,even in women younger than 40 years old.Therefore,it is essential to evaluate the ovarian reserve of these patients while treating menstrual disorders,particularly for young women with fertility needs.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective To investigate the differences of condylar position in patients with temporomandibular disorders(TMD),and to further explore the effects of condylar position displacement and malocclusion factors on TMD.Methods According to the inclusion criteria,normal occlusion subjects without TMD(group A,n=10),normal occlusion subjects with TMD(group B,n=8),malocclu-sion subjects without TMD(group C,n=9)and malocclusion subjects with TMD(group D,n=20)were collected.Condylar position measurement(CPM)and Cadiax Ⅳ were used to locate the position of condyle in RP and ICP,and the displacement and direction of condyle in three-dimensional direction from RP to ICP were measured by vernier caliper.All the data were averaged three times and an-alyzed by SPSS26.0 statistical software.Results In the sagittal direction,the condylar displacement of group A and group B,group C and group D,and group A and group D had statistical differences(P＜0.01).The displacement of the right condyle in the vertical direc-tion of group D was greater than that of group A,and the difference was statistically significant(P＜0.05).The difference among other groups was not statistically significant.There was no significant difference in the lateral displacement of condyle between the four groups.In group A and group D,the largest proportion of condyle deviation was anterior up,while in group B and group C,the largest proportion of condyle deviation was posterior up.Conclusion RP-ICP condylar sagittal displacement is common in people with TMD.The condyle displacement of RP-ICP in malocclusion patients without TMD is not significantly different from that in normal occlusion patients without TMD.Patients with TMD malocclusion are more likely to have condylar displacement in sagittal direction and vertical direction than normal occlusion without TMD.

Streptococcus equinus is a zoonotic disease that can cause illness in various animals under specific environmental condi-tions.No reports have described isolation of this bacterium from the liver in affected sheep.This study successfully isolated and identi-fied a strain of Streptococcus equinus through bacterial isolation and culture,Gram staining,drug sensitivity testing,mouse sensitivity testing,bacterial biochemical testing,and whole genome sequencing.The strain was found to have pathogenicity toward Kunming white mice,and to be sensitive to four antibiotics(penicillin,ampicillin,ceftiofur sodium,and ceftriaxone sodium)but resistant to four antibiotics(streptomycin,amoxicillin,tetracycline,and gentamicin).On the basis of drug sensitivity testing,targeted treatment of the affected sheep flock with ceftiofur sodium effectively controlled the disease within 2 days,and no new cases occurred.This study provides a reference for biological characterization of ovine Streptococcus equinus;public health;and the investigation of disease pre-vention,control,and epidemiology.