Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide, affecting approximately 32%-38% of the adult population and posing a growing public health burden. MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), progressive hepatic fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC). The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis, characterized by an imbalance among de novo lipogenesis, fatty acid β-oxidation, and very-low-density lipoprotein (VLDL)-mediated lipid export. This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression. Among the multiple regulatory pathways involved, thyroid hormone (TH) signaling has emerged as a central regulator of hepatic metabolic homeostasis. The liver is a major peripheral target organ of TH action, where TH predominantly exerts its metabolic effects through thyroid hormone receptor β (TRβ). Large-scale epidemiological studies and meta-analyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence, more severe histological injury, and advanced hepatic fibrosis, suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum. At the molecular level, TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis, enhancement of mitochondrial fatty acid oxidation, and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβ axis and non-genomic signaling pathways. Across different stages of MASLD, TH signaling exerts stage-dependent protective effects. In the steatosis stage, TH improves metabolic flexibility by modulating insulin sensitivity, glucose metabolism, and lipid droplet clearance, thereby alleviating early lipotoxic stress. During progression to MASH, TH attenuates inflammatory amplification by improving mitochondrial homeostasis, suppressing activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and modulating the gut-liver axis microenvironment. In advanced stages, TH signaling influences hepatic stellate cell activation and extracellular matrix deposition, partly through interaction with the transforming growth factor-β (TGF-β)/SMAD pathway, while alterations in intrahepatic TH availability, mediated by dynamic changes in iodothyronine deiodinase 1 (DIO1), contribute to fibrosis progression and hepatocellular dedifferentiation. In hepatocellular carcinoma, coordinated downregulation of TRβ and DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression. The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom, a liver-targeted TRβ‑selective agonist, for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis (F2-F3). This approval represents a landmark transition from mechanistic understanding to metabolism-centered precision therapy in MASLD. Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints, including MASH resolution and fibrosis regression, but also favorably modulates atherogenic lipid profiles, highlighting the therapeutic potential of selectively targeting hepatic TH pathways. This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of TH-based interventions, aiming to inform future mechanistic research and optimize clinical management strategies.

Diagnosis-related groups (DRG) payment is an important component of deepening the reform of medical insurance payment methods. In June 2023, a tertiary hospital launched an intelligent DRG grouping audit system to enhance grouping accuracy. By establishing a multi departmental collaborative organizational structure, building a standardized knowledge base and a rule base covering five categories (diagnosis, fees, testing, nursing, and pathology), and integrating electronic medical records, medical orders, testing, and imaging data throughout the entire diagnosis and treatment process, the intelligent DRG grouping audit system with data collection, identification, extraction, comparison, and output modules was constructed to achieve intelligent audit. At the same time, it was formed a closed-loop management system for pre reporting quality control, in-process group entry control, and post data analysis and assessment, which would prevent the risk of differentiated behaviors such as high coding and high sets, and ensure the reasonable use of medical insurance funds. By January 2024, the system had covered 89 ADRG groups, and improved the efficiency and quality of DRG grouping audit. Compared with February to May 2023, the monthly average rejection rate of medical records on the first page decreased by 9.4% after the system was put into operation (June to December 2023), and core medical indicators such as the number of DRG groups, medical insurance settlement cases, and time consumption index continued to improve. The practical experience could provide reference and inspiration for other hospitals in China.

Objective:To analyze the human immunodeficiency virus (HIV) screening status and the resulting residual risk (RR) among blood donors across 17 provincial blood centers in China.Methods:This study used a cross-sectional study. Data on HIV infection markers per 100 000 first-time donors (FD) and repeat donors (RD) from January 2015 to December 2024 were extracted from the National Blood Establishment Performance Comparison Information Management System. Questionnaires were used to collect each center′s HIV screening strategy, algorithm, serological test (ST) kit manufacturers, gray-zone setting for ST, and nucleic acid test (NAT) modality, method, and platform. The incidence-window-period model was used to calculate the residual risk for first-time donors (RR FD), repeat donors (RR RD), and total donors (RR TD) at each center. Horizontal and vertical analysis of RR FD, RR RD, and RR TD across centers and years were performed. Results:All 17 centers applied the same HIV screening strategy which was two rounds of ST followed by one round of NAT. Eight of them operated a single screening algorithm, six employed two algorithms and three used three. Eleven centers used both imported and domestic ST kits, five relied on domestic ST kits only, and one used imported ST kits only, while four centers never set a grey zone for ST throughout the decade. For NAT modalities, eight centers adopted both individual nucleic acid test (ID-NAT) and minipool nucleic acid test (MP-NAT), eight used MP-NAT only and one used ID-NAT only. Seven centers combined transcription mediated amplification (TMA) and polymerase chain reaction (PCR), nine used PCR only and one used TMA only, and fourteen centers ran both imported and domestic NAT systems, two used imported systems only and one used a domestic system only. Over the ten-year period, the mean RR FD across the centers ranged from 2.22 to 12.33 per 10 6 person-years, RR RD from 0.83 to 3.29 per 10 6 person-years and RR TD from 1.59 to 9.29 per 10 6 person-years, with center Z4 consistently showing the lowest values for all three metrics and center U4 recording the highest RR FD and RR TD, while center D2 had the highest RR RD. In 2024 compared with 2015, eleven centers achieved a lower RR FD and ten centers achieved lower RR RD and RR TD. The RR FD and RR TD of centers W2 and U4 displayed pronounced fluctuations and an upward trend in recent years. Conclusions:The 17 provincial blood centers maintain consistent HIV screening strategies, while demonstrating variations in screening algorithm, ST kit manufacturers, NAT modalities, methods, and platform. And the RR FD, RR RD, and RR TD differ across centers. Although most centers show declining trend in RR over the ten-year period, some centers exhibite data fluctuations with a rising trend, suggesting potential for further optimization of HIV screening protocols.

BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

The present study aimed to explore whether hydrogen sulfide (H₂S) improved hypoxic pulmonary hypertension (HPH) in rats by inhibiting aerobic glycolysis-pyroptosis. Male Sprague-Dawley (SD) rats were randomly divided into normal group, normal+NaHS group, hypoxia group, and hypoxia+NaHS group, with 6 rats in each group. The control group rats were placed in a normoxic (21% O₂) environment and received daily intraperitoneal injections of an equal volume of normal saline. The normal+NaHS group rats were placed in a normoxic environment and intraperitoneally injected with 14 μmol/kg NaHS daily. The hypoxia group rats were placed in a hypoxia chamber, and the oxygen controller inside the chamber maintained the oxygen concentration at 9% to 10% by controlling the N₂ flow rate. An equal volume of normal saline was injected intraperitoneally every day. The hypoxia+NaHS group rats were also placed in an hypoxia chamber and intraperitoneally injected with 14 μmol/kg NaHS daily. After the completion of the four-week modeling, the mean pulmonary artery pressure (mPAP) of each group was measured using right heart catheterization technique, and the right ventricular hypertrophy index (RVHI) was weighed and calculated. HE staining was used to observe pathological changes in lung tissue, Masson staining was used to observe fibrosis of lung tissue, and Western blot was used to detect protein expression levels of hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate kinase isozyme type M2 (PKM2), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), GSDMD-N-terminal domain (GSDMD-N), Caspase-1, interleukin-1β (IL-1β) and IL-18 in lung tissue. ELISA was used to detect contents of IL-1β and IL-18 in lung tissue. The results showed that, compared with the normal control group, there were no significant changes in all indexes in the normal+NaHS group, while the hypoxia group exhibited significantly increased mPAP and RVHI, thickened pulmonary vascular wall, narrowed lumen, increased collagen fibers, up-regulated expression levels of aerobic glycolysis-related proteins (HK2 and PKM2), up-regulated expression levels of pyroptosis-related proteins (NLRP3, GSDMD-N, Caspase-1, IL-1β, and IL-18), and increased contents of IL-1β and IL-18. These changes of the above indexes in the hypoxia group were significantly reversed by NaHS. These results suggest that H₂S can improve rat HPH by inhibiting aerobic glycolysis-pyroptosis.
Animals ; Rats, Sprague-Dawley ; Male ; Hypertension, Pulmonary/metabolism* ; Glycolysis/drug effects* ; Hydrogen Sulfide/therapeutic use* ; Hypoxia/complications* ; Rats ; Pyroptosis/drug effects*

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.

Objective:To investigate the clinical value of dynamic AI ultrasonic intelligent assisted diagnosis system for preoperative evaluation of thyroid nodules with diameter ≤1.0 cm.Methods:From Apr. 1, 2023, to Dec. 30, 2023, 742 thyroid nodules with diameter ≤1.0 cm were removed from 532 patients with thyroid nodule disease who received surgical treatment in the Department of Thyroid (hernia) of the First Medical Center of the Chinese People’s Liberation Army General Hospital. Among them, 423 were d≤0.5 cm. 319 cases (235 males and 507 females) with 0.5

Objective:To analyze the perioperative risks and prognosis in patients with differentiated thyroid cancer (DTC) complicated by Graves' disease (GD) .Methods:Clinical data of 880 DTC patients who underwent radical thyroidectomy at the Department of General Surgery, the First Medical Center of Chinese PLA General Hospital between Jan. 2016 and Dec. 2022 was retrospectively collected. The cohort included 119 DTC patients with GD (hyperthyroid group) and 761 DTC patients with normal thyroid function without GD (normal group) . Use propensity score matching (PSM) was used to obtain cohorts with balanced baseline characteristics between the hyperthyroid and normal groups. Perioperative risks and prognos were compared between the two groups.Results:For perioperative risk comparison, after 1∶2 matching, 116 patients were included in the hyperthyroid group and 232 patients in the normal group. The operation time was longer in the hyperthyroid group compared to normal group ([107.26±30.27]min vs. [96.45±32.51]min, P=0.003) . There were no statistical differences between the two groups in intraoperative blood loss, postoperative drainage volume or postoperative hospital stay ( P>0.05) . There were no statistical difference in the incidence of complications such as temporary or permanent hypoparathyroidism, temporary or permanent recurrent laryngeal nerve injury, and lymphatic leakage between the two groups. For prognostic comparison, after 1∶2 matching, 117 cases were included in the hyperthyroid group and 234 cases in the normal group. During follow-up period, 16 patients experienced DTC recurrence, including 5 cases in the hyperthyroid group and 11 cases in the normal group. There was no statistical difference in reccurence-free survival rates between the two groups (5-year RFS: 95.7% vs. 95.3%, P=0.907) . Multivariate Cox regression analysis revealed GD was not the risk factor for DTC recurrence. Conclusions:With standardized and adequate preoperative preparation, the perioperative risks of DTC patients complicated by GD were not increased compared to patients without GD. Additionally, GD does not increase the risk of postoperative tumor recurrence in DTC patients.

Objective:In order to effectively educate students on tooth defect diseases and restoration techniques, the teaching and research team at the School of Stomatology of Qingdao University developed an integrated course operative dentistry. This course is specifically designed to align with the undergraduate curriculum reform requirements of "Three Early, Two Multiple and One Integration".Methods:The teaching practice of operative dentistry was conducted with the stomatology undergraduates of grade 2020 and 2021. The course group redesigned the curriculum by reorganizing teaching content, rebuilding teaching resources, reconstructing teaching mode, and reshaping the evaluation system. Evaluation of the curriculum design included test scores, satisfaction questionnaires, and teacher self-evaluation. Statistical analysis was performed using SPSS 27.0 software, including independent sample t-tests for numerical variables and Fisher's exact test or Wilcoxon rank sum test for categorical variables. Results:Through the integrated course learning, 92.68% (38/41) of the students of grade 2020 and 97.44% (38/39) of the students of grade 2021 can basically or completely master various dental defect repair schemes and understand the importance of preserving natural tooth. 82.93% (34/41) of the students of grade 2020 and 100.00% (39/39) of the students of grade 2021 could basically or completely master the key points of various dental defect restorations.Conclusions:Through the practice of teaching, it has been confirmed that the integrated course of operative dentistry is beneficial to students' mastering the knowledge and skills of dental defect diseases and their restoration in a more comprehensive way, and is conducive to the cultivation of clinical thinking, hands-on ability and the patient-centered, comprehensive problem-solving thinking, which is in line with the guidance on the innovation and development of medical education.

Objective To investigate the in vitro anti-hepatitis B virus(HBV)effects of icariside Ⅱ(ICS Ⅱ)and its impact on mitochondrial fission.Methods HBV-positive hepatocellular carcinoma HepAD38 cells were used as the cellular model.The cytotoxicity of ICS Ⅱ was assessed via CCK8 assay.The secretion levels of HBV surface antigen(HBsAg)and HBV e antigen(HBeAg),as well as HBV DNA copy numbers,were measured by ELISA and qPCR after treatment with ICS Ⅱ alone or ICS Ⅱ in combination with entecavir(ENT).The effects of ICS Ⅱ on mitochondrial morphology and motility were observed using confocal laser scanning microscopy and transmission electron microscopy(TEM).After ICS Ⅱ treatment,Western blot was performed to analyze the expression levels of key proteins involved in mitochondrial dynamics.Additionally,intracellular reactive oxygen species(ROS)production was evaluated via fluorescence staining.Results The CCK8 assay results showed that ICS Ⅱ treatment at 25 μmol/L had no significant effect on cell proliferation after 72 h.ICS Ⅱ significantly inhibited the secretion levels of HBsAg and HBeAg,with the respective inhibition rates reaching 54.90％and 39.65％(P＜0.05).Additionally,ICS Ⅱ alone reduced HBV DNA copy numbers by 15.19％,while ENT alone achieved a 34.11％inhibition rate.Notably,ICS Ⅱ in combination with ENT reduced HBV DNA copy numbers by 55.81％(P＜0.05).Furthermore,ICS Ⅱ induced mitochondrial shortening and enhanced mitochondrial motility in HepAD38 cells(P＜0.05).ICS Ⅱ significantly increased the expression levels of mitochondrial motility-related proteins,including Mfn1,Fis1,and phosphorylated Drp1(ser 616)(P＜0.05),while no significant changes were observed in the expression levels of Mfn2,total Drp1,or Drp1(ser 637)(P＞0.05).Additionally,ICS Ⅱ significantly suppressed the production of intracellular ROS in HepAD38 cells(P＜0.05).Conclusion ICS Ⅱ inhibits HBV replication in HepAD38 cells,and the underlying mechanism may be associated with the promotion of mitochondrial fission and suppression of ROS production.