Hepatolenticular degeneration （HLD） is an autosomal recessive genetic disorder characterized by copper metabolism impairment， and it is one of the few treatable neurogenetic diseases. A retrospective analysis was performed for the clinical data of four patients with HLD who attended Beijing Ditan Hospital， Capital Medical University， from November 2023 to October 2024， and the genetic testing results of three patients were analyzed， along with a literature review. Among the four patients， there was one female patient and three male patients. All patients had the initial symptoms of dysarthria and limb tremors， and physical examination showed positive K-F rings， normal liver enzyme levels， a reduction in serum ceruloplasmin， and an increase in 24-hour urinary copper excretion. Three patients underwent ATP7B genetic testing， among whom two had compound heterozygous mutations， and one had a heterozygous mutation. In addition， two patients underwent cranial magnetic resonance imaging， and the results showed symmetrical long T1 and long T2 signals. All four patients received copper-chelating therapy and achieved a good outcome. This article reports the diagnosis and treatment of four patients with HLD and identifies a case of HLD resulting from a rare heterozygous mutation site， thereby expanding the variation spectrum of the ATP7B gene.

Objective: To analyze the characteristics and key risk factors of abnormal blood disposal throughout the 2024-2025 blood collection and supply process based on nationwide multi-site monitoring data, develop a comprehensive prevention and control strategy across the entire chain, reduce preventable blood waste, and ensure clinical blood safety. Methods: According to the Guidelines for Haemovigilance (T/CSBT 001-2026), we extracted 74 cases of abnormal blood disposal events reported by the China Blood Transfusion Association′s Blood Safety Monitoring System from January 1 2024, to December 31 2025, and conducted descriptive statistical analysis on the distribution of events, types of deviations, root causes, and classifications of disposal manifestations. Results: A total of 664 adverse events related to blood collection and supply were reported over two years, with 74 cases involving discarded abnormal blood units, accounting for 11.1% of the total. Among these, blood component preparation (40.5%) and blood collection (37.8%) remained traditional high-risk stages. The proportion of blood waste occurring during storage, distribution, and transportation increased from 7.7% in 2024 to 34.3% in 2025. Deviations from standard operating procedures (SOP) by personnel were the primary cause, accounting for 74.3% of cases. Discarded blood units were categorized into four types: compromised closed blood bag systems (40 cases), mainly due to inadequate heat sealing, physical damage, or dropped bags; blood out of the cold chain (12 cases), primarily resulting from blood being left at work sites; imbalanced proportion of preservation solution (10 cases), mostly caused by blood collection volumes exceeding the standard capacity of blood bags; and other causes (12 cases). Conclusion: Human operational errors are the core cause of abnormal blood waste. The collection and preparation stages have long been at high-risk, and the risks in the storage and transportation stages have been increasing year by year. We should focus on standardizing personnel management, improving specialized operation norms such as heat sealing, transportation, and storage, establishing a full-process intelligent cold chain monitoring and multi-node visual verification mechanism, and systematically reducing the occurrence rate of abnormal blood waste through a closed-loop quality intervention system, thereby improving the utilization efficiency of voluntary blood donation resources.

ObjectiveTo investigate the effect of proprioceptive stimulation combined with shoulder strength training on cervical muscle morphology, vertebral artery hemodynamics, proprioception and motor function in healthy young men. MethodsThirty healthy young men recruited from Beijing Bo'ai Hospital between January, 2022 and June, 2024 were randomly divided into a proprioceptive stimulation (PS) group, a strength training (ST) group and a combined training (CT) group, with ten participants in each group. PS group received proprioceptive stimulation using suspension vibration, ST group received isometric contraction of the right shoulder joint in six directions, and CT group received both interventions concurrently, for four weeks. Before and after intervention, the cross-sectional area (CSA) of the right cervical multifidus, the end diastolic velocity (EDV) and peak systolic velocity (PSV) of the vertebral artery, cervical range of motion (ROM), isometric peak torque (IPT) and cervical joint position error (CJPE) were measured. ResultsAll 30 subjects completed the study, and no serious adverse events were reported. The time-by-group interaction in CSA was significant (F = 10.183, P = 0.001, partial η² = 0.430); CSA was higher in CT group than in PS group and ST group (P < 0.05). The time-by-group interactions in EDV and PSV were significant (F > 4.036, P < 0.05, partial η² > 0.230); PSV was significantly higher in CT group than in PS group and ST group (P < 0.001). The time-by-group interaction in extension ROM was significant (F = 54.277, P < 0.001, partial η² = 0.801); extension ROM was significantly higher in CT group than in PS group and ST group (P < 0.001). The time-by-group interactions in flexion, extension and lateral flexion IPT were significant (F > 14.251, P < 0.001; partial η² > 0.514); flexion IPT was higher in CT group than in PS group and ST group (P < 0.05). ConclusionIn healthy young men, proprioceptive stimulation combined with shoulder strength training can improve neck muscle strength, blood flow and motor function.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

Objective To compare and analyze the epidemiological characteristics of the adverse events following immunization (AEFI) with measles containing vaccine (MCV) in Zibo City from 2018-2022, and to provide reference data for evaluating the safety of the immunization strategy adjustment. Methods AEFI surveillance data related to MCV in Zibo City from 2018 to 2022 were collected from the China Disease Prevention and Control Information System Immunization Planning System and Shandong Provincial Vaccination Information System. The AEFI reports and epidemic characteristics after adjusting the immunization strategy about MCV were compared. Results Before adjusting immunization strategy of MCV in Zibo City (January 1, 2018 to May 31, 2020), 114 cases of AEFI were reported in the first dose of measles and rubella combined attenuated live vaccine (MR), with a reported incidence rate of 131.50/100 000. After adjusting the immunization strategy (June 1, 2020- December 31, 2022), 156 cases of AEFI were reported in the first dose of MMR, with a reported incidence of 162.97/100,000. There was no statistically significant difference in the reported incidence of AEFI (χ²=3.049, P=0.081). AEFI cases were mainly characterized by general reactions, and the reported incidence rate of MR (88.82/100,000) was lower than that of MMR (137.90/100,000) (χ²=9.576, P=0.002). Their most common clinical manifestation was fever, with 71 cases reported (81.90/100 000) and 114 cases reported (119.10/100 000), respectively. The reported incidence of abnormal reactions in MR (42.68/100 000) was higher than that in MMR (22.98/100,000) (χ²=5.458, P=0.019). Among them, allergic rash was the most common, with 16 and 11 cases reported, respectively, and the reported incidence rates were 18.46/100 000 and 11.49/100 000, respectively. The proportion of reported cases in the age group ≥ 1 year old was higher in MMR than in MR (χ²=41.089, P<0.001). The proportion of reported cases in the first quarter was higher in MR than in MMR (29.82%, 17.95%), while the proportion in the third quarter was higher in MMR than in MR (34.64%, 17.54%) (χ²=14.197, P=0.003). Conclusion After adjusting the MCV immunization strategy in Zibo City, the report on AEFI is within the expected range, and no adverse changes have been found in the epidemic characteristics of MCV related AEFI.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

OBJECTIVES: To investigate the expression of parathyroid hormone-like hormone (PTHLH) in hepatocellular carcinoma (HCC) and analyze its correlation with clinical prognosis, its regulatory effects on HCC cell behaviors, and the signaling pathways mediating its effects. METHODS: We analyzed the differential expression of PTHLH in HCC and adjacent tissues and its association with patient prognosis based on data from TCGA and GEO databases and from 70 HCC patients treated in our hospital. The effects of PTHLH knockdown and overexpression on proliferation, migration, and invasion of cultured HCC cells were investigated using CCK-8 assay, colony formation assay, Transwell migration and invasion assays, and the signaling pathways activated by PTHLH were detected using Western blotting. RESULTS: TCGA and GEO database analysis showed significant overexpression of PTHLH mRNA in HCC tissues, which was associated with poor prognosis of the patients (P<0.05). High PTHLH mRNA expression was a probable independent prognostic risk factor for HCC (P<0.05). In the clinical samples, PTHLH mRNA and protein expressions were significantly higher in HCC tissues than in the adjacent tissues (P<0.001 or 0.01). Univariate and multivariate Cox regression analyses suggested that high PTHLH mRNA expression was an independent risk factor to affect postoperative disease-free survival of HCC patients (P<0.05). The prognostic prediction model based on PTHLH mRNA expression showed an improved accuracy for predicting the risk of postoperative recurrence in HCC patients. In cultured HCC cells, PTHLH overexpression significantly promoted cell proliferation, colony formation, migration and invasion, and caused activation of the ERK/JNK signaling pathway in Huh7 and Hep3B cells. CONCLUSIONS High PTHLH expression promotes HCC progression and is associated with poor patient prognosis. Its pro-tumor effects may be mediated by activation of the ERK/JNK signaling pathway.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Prognosis ; Cell Proliferation ; Parathyroid Hormone-Related Protein/genetics* ; Cell Line, Tumor ; Cell Movement ; Disease Progression ; Signal Transduction ; Male ; RNA, Messenger/genetics* ; Female

Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

ObjectiveThis study aims to analyze animal models of anxiety disorder based on the clinical characteristics of anxiety disorder in traditional Chinese and Western medicine， systematically assess the clinical compatibility， and provide suggestions for the construction of animal models with a high degree of clinical compatibility between traditional Chinese and Western medicine. MethodsRelevant literature on animal models of anxiety disorder was retrieved from global databases. Scoring scales were developed according to the etiology， pathogenesis， and diagnostic criteria of anxiety disorder in both traditional Chinese and Western medicine. The animal models of anxiety disorder in the literature were analyzed， and their clinical compatibility was systematically assessed to identify reference-worthy models. ResultsThe average clinical compatibility of existing animal models of anxiety disorder was 42.13% for traditional Chinese medicine and 50.94% for Western medicine. Among these， the chronic unpredictable mild stress （CUMS） model had the highest compatibility with both traditional Chinese and Western medicine. However， current models rarely reflect the clinical syndromes of traditional Chinese medicine in depth， and show limitations in syndrome differentiation. ConclusionThe existing animal models of anxiety disorder are mostly established using single-factor approaches， which fail to comprehensively simulate the onset process and physiopathological characteristics of anxiety disorder. These models also neglect the syndrome-based indicators emphasized in traditional Chinese medicine. In the future， the model development should incorporate the clinical characteristics of syndromes in both traditional Chinese and Western medicine， establish standardized evaluation criteria for anxiety disorder models， and utilize multifactorial approaches to enhance the representativeness of animal models in traditional Chinese medicine.

ObjectiveWe reviewed the existing experimental studies about renal injury-inducing Chinese medicine and systematically analyzed the toxicity mechanisms， toxic components， toxicity attenuation measures， and modern evaluation methods of renal injury-inducing Chinese medicine. The results are expected to provide new ideas for the modern research on kidney injury-inducing Chinese medicine， offer new breakthrough points for the toxicity attenuation of Chinese medicine by compatibility and processing， and give insights into the future research of Chinese medicine toxicology on the basis of ensuring the safety and scientific application of Chinese medicine. MethodsThe animal， cell， and clinical studies of kidney injury-inducing Chinese medicine were retrieved from CNKI， Wanfang Data， VIP， PubMed， and Web of Science. The names and toxic components of renal injury-inducing Chinese medicine， renal injury sites， toxicity mechanisms， toxicity attenuation measures， and related evaluation methods were summarized. ResultsThe toxicity mechanisms of kidney injury-inducing Chinese medicine mainly involved oxidative stress， endoplasmic reticulum stress， inflammatory cell infiltration， and organic anion transporters. Processing and compatibility were the main toxicity attenuation measures. The evaluation methods encompassed animal experiments， cell models， network pharmacology， metabolomics， toxicology genomics， and fluorescent probe technology. ConclusionAt present， the toxicological verification of kidney injury-inducing Chinese medicine starts from toxic components and combines various experimental methods， which is more comprehensive and systematic than the previous studies based on only animal experiments. According to the classical theories of traditional Chinese medicine， the toxicity of kidney injury-inducing Chinese medicine is mainly attenuated by decocting in water， steaming， and frying. With the progress of science and technology， new processing methods for toxicity attenuation are emerging， and structural transformation， fermentation， and microwave methods are the key research directions of toxicity attenuation of Chinese medicine in recent years.