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.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Type 1 diabetes mellitus is a chronic autoimmune disease caused by the destruction of pancreatic islet β cells. Pancreatic islet transplantation provides a treatment method for patients with type 1 diabetes mellitus to restore endogenous insulin secretion. However, some problems limit the widespread application of islet transplantation, such as the shortage of donors and post-transplantation rejection damage. Mesenchymal stem cell-derived exosome (MSC-Exo) has become a potential tool for islet transplantation therapy due to their immunomodulatory and tissue repair capabilities. MSC-Exo shows great promise for application, because of low immunogenicity, easily being stored and transported, and the potential as drug delivery vehicles. However, challenges such as preparation, purification, standardization and safety verification need to be overcome before converting MSC-Exo into clinical practice. Therefore, this article reviews the application and potential advantages of MSC-Exo in islet transplantation, aiming to providing more effective and safer treatment options for patients with type 1 diabetes mellitus.

Objective:To analyze the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with main splenic artery embolization in the treatment of patients with portal hypertension upper gastrointestinal bleeding complicated with extensive portal vein thrombosis (PVT).Methods:This study was a prospective, single-center, open-label, single-arm clinical trial. In the first phase, 81 patients with portal hypertension upper gastrointestinal bleeding who were admitted to Beijing Shijitan Hospital, Capital Medical University from January 2018 to December 2018 were consecutively enrolled, including 57 males and 24 females, with the age of (51.3±10.4) years. During TIPS surgery, the pressure of the portal vein before and after the balloon blocking the splenic artery was measured to clarify the contribution of the splenic artery to portal hypertension. In the second stage, from January 2019 to December 2022, 104 patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT were re-enrolled, including 71 males and 33 females, with the age of (50.9±12.5) years. TIPS combined with main splenic artery embolization was performed, and portal vein pressure was measured before and after embolization. Follow up on the postoperative esophageal and gastric varices of the patients in the second stage.Results:The portal vein pressures before and after the first stage of balloon occlusion of the splenic artery were (35.2±8.4) mmHg (1 mmHg=0.133 kPa) and (24.2±6.3) mmHg, respectively. The pressure after occlusion was lower than that before occlusion, and the difference was statistically significant ( t=10.54, P<0.001). The portal vein pressures before and after the second stage embolization were (36.1±9.5) mmHg and (21.1±4.7) mmHg respectively. The pressure after embolization was lower than that before embolization, and the difference was statistically significant ( t=13.47, P<0.001). In the second stage, among the 104 patients, the proportion of those whose varicose veins disappeared or improved 6 months after the operation was 43.3%(45/104) and 51.0%(53/104), respectively. There were no patients with aggravation or rebleeding due to rupture. One year later, 8 patients (7.7%) had aggravated or ruptured esophageal and gastric varices with bleeding. Two years later, 12 patients (11.5%) had aggravated or bleeding. Conclusion:TIPS combined with main splenic artery embolization can effectively reduce the portal vein pressure in patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT, improve the degree of esophageal and gastric varices, and reduce the risk of gastrointestinal bleeding.

Objective This study aims to investigate the current status and determinants of compassion fatigue symptoms among orthopedic nurses,and to analyze the interrelationships among these determinants to provide references for targeted intervention development.Methods From May to June 2024,a convenience sampling method was employed to recruit orthopedic nurses from 20 tertiary hospitals across 14 provinces and cities in China.The survey instruments encompassed the general demographic information sheet,the Compassion Fatigue Scale,the Social Support Rating Scale,the Nurses' Psychological Capital Questionnaire,and the Professional Identity Questionnaire.The data were analyzed using univariate analysis,Spearman correlation analysis,and multiple linear regression analysis.A structured equation model was also developed.Results Totally 1 397 valid questionnaires were collected,and the effective response rate was 96.94％(1 397/1 441).The average score of compassion fatigue symptoms was 47.41±12.16.The multiple linear regression analysis indicated that professional identity,social support,psychological capital,length of service,and frequency of night shifts per week were independent determinants of compassion fatigue symptoms(P＜0.05).The path analysis demonstrated a good fit with the specified indicators.Psychological capital exhibited a direct mediating effect on compassion fatigue symptoms(β=-0.15,P＜0.05).Furthermore,professional identity(β=1.46,P＜0.001;β=-0.38,P＜0.001)and social support(β=0.14,P＜0.001;β=-0.99,P＜0.001)served as mediators in the relationship between psychological capital and compassion fatigue symptoms.Conclusion The compassion fatigue symptoms among orthopedic nurses are relatively severe.It is imperative for nursing managers to address associated factors of compassion fatigue symptoms among orthopedic nurses and implement effective preventive strategies to mitigate its level.

Objective:To explore the complement deposition levels on blood cell surfaces in patients with paroxysmal nocturnal hemoglobinuria (PNH) and evaluate their association with clinical manifestations.Methods:This study enrolled patients with PNH, who had not been treated with complement inhibitors and appeared at Peking Union Medical College Hospital from February 2021 to February 2023. The clinical information of participants was retrospectively recorded, and peripheral blood samples were collected. Gender- and age-matched normal controls (NC) were recruited accordingly. C5b-9, C3, C4b, and factor B (FB) deposition levels on peripheral red blood cells, white blood cells, and platelets were detected with flow cytometry. The correlation between complement deposition levels and clinical symptoms was analyzed.Results:This study involved 73 patients with PNH, including 42 (57.5%) males, with a median age of 36 (range: 14-76) years. 16 matched NC were collected. Among patients with PNH, 36 (49.3%) had classical PNH and 37 (50.7%) had aplastic anemia-PNH syndrome. Thromboembolic events (TEE) occurred in 18 (24.7%) patients. The median HGB, absolute reticulocyte count (Ret), and lactate dehydrogenase of PNH patients were 76 (37-116) g/L, 181.0 (45.9-495.8) ×10 9/L, and 1 875 (377 - 5 509) U/L, respectively. The median number of Flaer-negative white blood cells was 94.0% (13.0% - 99.9%) ; the median CD59 negative red blood cells was 46.7% (9.0% - 93.0%). The deposition of C5b-9, C3, C4b, and FB on red blood cells, white blood cells, and platelets in patients with PNH was significantly higher than that in NC (all P<0.05). C5b-9 deposition level was significantly higher than that of C3, C4b, and FB on all three blood cell lineages in PNH patients (all P<0.01). The deposition of all complement fragments on red blood cells was significantly lower than that on white blood cells and platelets (all P<0.01). C5b-9 deposition on red blood cells was positively correlated with Ret in PNH patients ( P=0.005). C3 ( P=0.001) and C4b ( P=0.017) deposition levels on white blood cells and C3 deposition on platelets ( P=0.002) in patients with TEE history were lower than those without. Conclusions:C5b-9, C3, C4b, and FB deposition levels on all three blood cells in patients with PNH were higher than NC. Increased C5b-9 on red blood cells may indicate active hemolysis. Reduced C3 and C4b levels on white blood cells and low C3 deposition on platelets may indicate TEE risk.

This retrospective analysis included 10 patients with relapsed/refractory warm autoimmune hemolytic anemia (wAIHA) who received zanubrutinib (treatment course: 3-6 months) and completed at least 3 months of follow-up at Peking Union Medical College Hospital from July 2022 to January 2024. The cohort included two male and eight female patients with a median age of 63 years (range: 36-76), who had received a median of 9 months (range: 3-22) of previous therapies. At 1-month, 3-month, and final follow-up (median 7 months), the overall response (OR) rates were 30%, 60%, and 60%, with corresponding complete response (CR) rates of 20%, 40%, and 40%, respectively. The median time to achieve a response was 2 months (range: 1-2) among the responders. No disease relapse or clonal progression was documented during follow-up. Treatment-related adverse events occurred in 30% of the patients (all grade 1-2 reversible events). One responder died of infectious multiple organ failure at 8 months after treatment initiation. Our results indicate that zanubrutinib provides rapid amelioration of anemia with manageable short-term safety in patients with relapsed/refractory wAIHA.

Objective:To evaluate the efficacy and safety of luspatercept combined with roxadustat in patients with refractory low-risk myelodysplastic neoplasms with ring sideroblasts (MDS-RS) patients.Methods:In this single-center, prospective, randomized controlled trial, patients with refractory MDS-RS were randomly assigned in a 1:2 ratio to receive either combination therapy (luspatercept + roxadustat) or luspatercept monotherapy. The primary endpoint was erythroid response at 12 weeks, while secondary endpoints included erythroid response at 24 weeks, achievement of transfusion independence ≥8 weeks within the first 12 weeks, and other hematologic indicators.Results:The combination therapy and monotherapy groups included 16 and 32 patients, respectively. Baseline demographic characteristics, laboratory tests, IPSS-R risk classification, transfusion burden, EPO levels, and previous treatment history were comparable between the two groups ( P>0.05). With similar doses of luspatercept and follow-up durations, no significant differences were observed between the groups at either 12 or 24 weeks in terms of erythroid response, transfusion independence, or other clinical indicators (all P-values>0.05). The incidence of adverse events was similar in both groups (all P-values>0.05) . Conclusion:Luspatercept combined with roxadustat shows comparable efficacy and safety to luspatercept monotherapy in the treatment of refractory low-risk MDS-RS. Clinical trial register: Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing (K3697)

This study retrospectively analyzed data from 25 patients with paroxysmal nocturnal hemoglobinuria (PNH) admitted to Peking Union Medical College Hospital and Dongfang Hospital of Beijing University of Chinese Medicine from January 2023 to June 2024. Patients receiving sufficient eculizumab treatment for at least 3 months and who completed hemolytic complex (CH50) level testing pre- and post-treatment for 3 and 6 months were selected. Blood routine, biochemistry, and the 50% CH50-related indicators were monitored pre- and post-treatment. Among these patients, 24 completed 6 months of treatment and CH50 testing. After 3 and 6 months of eculizumab treatment, all patients with PNH showed significant improvement in symptoms, with lactate dehydrogenase (LDH) levels decreasing from a baseline of (1 814.4 ± 924.8) U/L to (248.5 ± 61.0) U/L and (239.3 ± 44.8) U/L. Hemoglobin levels increased from a baseline of (73.9±14.4) g/L to (99.9 ± 21.3) g/L and (99.6 ± 19.8) g/L. The baseline CH50 level was (32.4±14.7) %, which decreased to 2.0% (1.0% –8.0% ) and 1.0% (1.0% –4.0% ) at 3 and 6 months posttreatment, respectively. At baseline, a linear correlation was found between CH50 and LDH levels ( P<0.001), and the trend of CH50 changes was significantly lower than LDH at 3 and 6 months post-treatment with eculizumab, with similar trends. However, no linear correlation was observed between CH50 and LDH levels or other parameters at 3 and 6 months of medication. Our case demonstrates that eculizumab is effective for PNH hemolysis treatment. The serum CH50 level may be a biomarker for complement blockade induced by eculizumab, which can, to some extent, reflect the intravascular hemolysis of PNH and the efficacy of eculizumab.

This study retrospectively analyzed 12 patients with transfusion-dependent, non-severe aplastic anemia (TD-NSAA) refractory to cyclosporine A (CsA) , who were treated with lusutrombopag monotherapy. These patients either had a variety of chronic comorbidities or medication-related risks, or they were unresponsive to or intolerant of other thrombopoietin receptor agonists (TPO-RA) . The median treatment duration with lusutrombopag was 4 months (range: 3-11 months) , while the median follow-up period was 8 months (range: 6-11 months) . The overall response (OR) rates at months 3, 6, and the end of follow-up were 50.0%, 58.3%, and 50.0%, respectively, with a median time to OR of 2 months (range: 1-4 months) . Complete response (CR) rates were 8.3%, 16.7%, and 16.7% at the same time points, with a median time to CR of 4 months (range: 2-5 months) . Adverse events were all Grade 1, with an incidence rate of 25.0%. During follow-up, one patient experienced a loss of OR after discontinuing treatment, with a relapse rate of 14.3%; no clonal evolution or mortality was observed. These findings suggest that lusutrombopag is both effective and well-tolerated in CsA-refractory TD-NSAA patients and represents a promising therapeutic option for those with poor treatment tolerability.