摘要 目的 肝豆状核变性（又称Wilson病，WD）是由ATP7B基因突变引起的铜代谢紊乱疾病，常累及肝脏和中枢神经系统，严重者可致死。目前关于WD患者死亡原因及危险因素的系统研究较少。本研究旨在探讨WD患者的常见死亡原因及其危险因素。方法 回顾性分析2011年1月—2022年1月间安徽中医药大学神经病学研究所附属医院87例死亡WD患者和113例存活WD患者的临床资料，分析死亡原因，并通过Cox回归分析死亡危险因素。结果 死亡组年龄中位数为32.00（27.00，41.00）岁、病程中位数为144.00（72.00，228.00）个月，存活组年龄中位数为31.00（25.00，37.00）岁、病程中位数为132.00（72.00，214.00）个月。主要死亡原因包括肝衰竭（33例）、感染（23例）、猝死（8例）、消化道出血（8例）及肝癌（4例）等。死亡组与存活组在性别、起病形式、低铜饮食、肝脏B超分型、脾脏切除、临床分型、治疗方案及多项实验室指标（如白细胞计数、TB、Alb等）上差异有统计学意义（P<0.05）。多因素Cox回归显示，基线尿铜每增加100 μg/24 h（HR=1.22， 95%CI 1.11~1.34）与肝硬化（HR=2.55，95%CI 1.02~6.36）使死亡风险增加。结论 WD患者的主要死亡原因为肝衰竭，高水平基线尿铜和肝硬化显著增加死亡风险。尿铜水平达400 μg/24 h（参考值<100 μg/24 h）的患者死亡风险较基线增加3.8倍（HR=3.8，P<0.001）。研究结果为WD患者的预后评估和临床干预提供了重要依据。 Abstract Objective Hepatolenticular degeneration（also know as Wilson disease ，WD） is a copper metabolic disorder caused by ATP7B gene mutation， often involving the liver and the central nervous system and leading to death in severe cases. At present， there is a lack of systematic studies on the cause of death and related risk factors in WD patients. Therefore， this study aims to investigate the common causes of death and related risk factors in WD patients. Methods A retrospective analysis was performed for the clinical data of 87 WD patients who died and 113 WD patients who survived in our hospital from January 2011 to January 2022. The common causes of death in WD patients were analyzed， and the Cox proportional-hazards regression model analysis was used to investigate the risk factors for death. Results The death group had a median age of 32.00 （27.00，41.00） years and a median course of disease of 144.00 （72.00，228.00） months， and the survival group had a median age of 31.00 （25.00，37.00） years and a median course of disease of 132.00 （72.00，214.00） months. The main causes of death included liver failure （33 patients）， infection （23 patients）， sudden death （8 patients）， gastrointestinal bleeding （8 patients）， and liver cancer （4 patients）. There were significant differences between the death group and the survival group in sex， pattern of disease onset， low copper diet， liver ultrasound classification， splenectomy， clinical classification， treatment regimens， and various laboratory markers （such as white blood cell count， total bilirubin， and albumin）（P<0.05）. The multivariate Cox regression analysis showed that the risk of death was doubled for every 100 μg/24 h increase in urinary copper at baseline （HR=1.22，95%CI 1.11-1.34） and the presence of liver cirrhosis （HR=2.55，95%CI 1.02-6.36）. Conclusion Liver failure is the main cause of death in WD patients， and a high level of urinary copper at baseline and the presence of liver cirrhosis significantly increase the risk of death. The risk of death in patients with a urinary copper level of 400 μg/24 h （reference value<100 μg/24 h） was increased by 3.8 times compared with the value at baseline （HR=3.8，P<0.001）.The results of this study provide an important basis for the prognosis evaluation and clinical intervention of WD patients.

BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

Objective To investigate the features of surface electromyography （sEMG） signals in patients with lower limb dystonia and hepatolenticular degeneration， also known as Wilson disease （WD）， as well as the feasibility of sEMG as an assessment tool for lower limb dystonia in WD. Methods A total of 36 WD patients with lower limb dystonia （observation group） and 20 WD patients without lower limb dystonia （control group） were enrolled， and 20 normal subjects were enrolled as healthy group. The sEMG technique was used to measure the AEMG， MF， MPF， and iEMG values of the anterior tibial muscle， the gastrocnemius muscle， and the rectus femoris muscle in the walking state， and a Spearman’s rank correlation analysis was used to investigate the correlation of the iEMG value of the rectus femoris muscle in both lower limbs with Activities of Daily Living （ADL）， the neurological subscale of Unified Wilson’s Disease Rating Scale （UWDRS-I）， the Burke-Fahn-Marsden Dystonia Rating Scale （BFMDRS）， the Modified Ashworth Scale， and 10-meter walking time. The observation group and the healthy group were compared in terms of the symmetry index （SI） of the same-named muscles on both sides， and the correlation of SI value with scale scores and walking time was analyzed for the observation group. Results There were significant differences in iEMG values and all electromyography values of the rectus femoris muscle between the three groups （P<0.05）. In the observation group， the iEMG value of the rectus femoris muscle was negatively correlated with the ADL scale and was positively correlated with dystonia-related scales and 10-meter walking time， suggesting that the iEMG value of the rectus femoris muscle could reflect the severity of lower limb dystonia in WD. Meanwhile， there were significant differences in the SI values of bilateral muscles between the observation group and the healthy group （P<0.05）， and for the observation group， the SI values of the muscles were negatively correlated with the ADL scale and were positively correlated with other variables， suggesting that lower limb dystonia in WD was asymmetric， and the degree of asymmetry was positively correlated with the degree of dystonia. Conclusion This study shows that sEMG has a certain application value in assessing lower limb dystonia in WD patients and can be used as an assessment tool for lower limb dystonia in WD.
Dystonia

Hepatolenticular degeneration （HLD），also known as Wilson disease (WD) is an uncommon hereditary disorder of the nervous system， characterized by hepatic impairment， extrapyramidal manifestations， psychiatric symptoms， and renal dysfunction， while impaired vision is a rare comorbidity. This article conducts a retrospective analysis of visual acuity changes， treatment， and prognosis of a female patient， aged 22 years， who were diagnosed with HLD complicated by bilateral neuritis in an affiliated hospital of Anhui University of Chinese Medicine in 2022， and a literature review was performed. The findings suggest that impaired vision is a rare manifestation of HLD. Ophthalmologists should consider the possibility of HLD in patients with optic atrophy and optic neuritis， and early intravenous administration of methylprednisolone may help to improve prognosis.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

In order to seek a patient friendly and low-cost intestinal examination method, a structurally simple pneumatic soft intestinal robot inspired by inchworms is designed and manufactured. The intestinal robot was consisted of two radially expanding cylindrical rubber film airbags for anchoring and one low density polyethylene film airbag for axial elongation, which achieved movement in the intestine by mimicking the crawling of inchworms. Theoretical derivation was conducted on the relationship between the internal air pressure of the anchored airbag and the free deformation size after expansion, and it pointed out that the uneven deformation of the airbag was a phenomenon of expansion instability caused by large deformation of the rubber material. The motion performance of the intestinal robot was validated in different sizes of hard tubes and ex vivo pig small intestine. The running speed in the ex vivo pig small intestine was 4.87 mm/s, with an anchoring force of 2.33 N when stationary, and could smoothly pass through a 90 ° bend. This work expects to provide patients with a new method of low pain and low-cost intestinal examination.
Animals ; Swine ; Robotics/instrumentation* ; Equipment Design ; Intestine, Small/physiology* ; Intestines/physiology* ; Humans

Objective To establish a three-dimensional finite element model of knee joint in patients with mild knee osteoarthritis in the absence of CT and MRI with thin layer thickness,and to analyze the stress distributions of the tibial plateau.Methods A female patient with mild knee osteoarthritis was selected as the study object,and received serial CT scan from pelvis to distal tibia of fibula.The obtained files in DICOM format were imported into Mimics software for extracting the bony structures of knee joint through threshold segmentation,and then optimizing the extracted structures with Edit Masks,Cavity Fill and Region Grow.The generated model of bony structures was imported into 3-matic for smoothing and wrapping,and Geomagic Wrap was used for bony structure processing with mesh doctor inspection,surface defect repair and surface fitting.The cartilages,meniscus and ligaments were established by contour extension,and assembled with bony structures in SolidWorks in the way of origin coincidence.After defining material properties and contact relationships,meshing,and setting constraints and loads in ANSYS software,the stress distributions of the tibial plateau when standing with both legs were analyzed.Results A complete knee joint model including bony structure,cartilage and ligament was successfully established.When standing with two legs,the peak value of contact stress was about 1.21 MPa,and the maximum stress was 0.72 MPa at the medial middle of tibial plateau and lateral tibial plateau.The 62.7%and 37.3%of the total load were borne by the inner and outer compartments.Conclusion The model of the total knee joint is established with CT extraction and software rendering,and the finite element analysis results meet clinical expectations,indicating that the model established by the proposed method is reliable and can be used for follow-up research.

Objective To investigate the role and potential mechanisms of tumor necrosis factor alpha-inducible protein 8-like molecule 1(TNFAIP8L1)in acute liver injury in mice.Methods The second generation of C57BL/6J male wild-type(WT)mice and the C57BL/6J female TNFAIP8L1+/-mice and WT mice were selected to further self-breed the third generation of male TNFAIP8L1-/-mice and the third generation of WT male mice.Five normal third-generation male WT mice and five normal third-generation male TNFAIP8L1-/-mice were selected.The serum alanine aminotransferase(ALT)levels of the two types of normal mice were measured and compared.The infiltration of inflammatory cells and cell necrosis in the liver tissues of the two types of normal mice were observed after hematoxylin & eosin(HE)staining.Flow cytometry was used to detect the percentages of neutrophils(Neu),eosinophils(EOS),dendritic cells(DC),bone marrow-derived macrophages(BMDMs),and bone marrow-derived mononuclear cell(BMNCs)in the liver myeloid cell subsets of the two types of normal mice.Another 5 third-generation male WT mice and 4 third-generation male TNFAIP8L1-/-mice were selected to induce acute liver injury mouse models using lipopolysaccharide(LPS)/D-galactosamine(D-Gal).After 24 hours,the serum ALT levels of the two types of acute liver injury mice were detected and compared,the infiltration of inflammatory cells and cell necrosis in the liver tissues of the two types of acute liver injury mice were observed,and the percentages of Neu,EOS,DC,BMDMs and BMNCs in the liver myeloid cell subsets of the two types of acute liver injury mice were measured by using the above methods.Results There was no significant difference in the percentages of Neu,EOS,DC,BMDMs and BMNCs,and serum ALT levels in the livermyeloid cell subsets of normal WT mice and TNFAIP8L1-/-mice(P＞0.05).HE staining results of liver tissues in normal WT mice and TNFAIP8L1/mice showed that hepatic lobules were structurally complete and clear,hepatocytes were morphologically normal and arranged neatly,and there was no obvious inflammatory cell infiltration or cell necrosis.Twenty-four hours after acute liver injury,the percentages of Neu and BMNCs in the liver myeloid cell subsets and the serum ALT levels in the liver tissues of TNFAIP8L1-/-mice were significantly higher than those of WT mice(P＜0.05);there was no significant difference in the percentages of EOS,DC and BMDMs in the liver myeloid cell subsets of mice between the two groups(P＞0.05).In the liver tissues of WT mice with acute liver injury,hepatic lobules were structurally blurred,hepatocytes were swollen with scattered vacuolated steatosis,and a small amount of inflammatory cells were infiltrated.In the liver tissues of TNFAIP8L1/mice with acute liver injury,hepatic lobules were structurally non-existent,and hepatocytes were severely damaged and extensively necrotic,with a large amount of inflammatory cell infiltration.Conclusion The deficiency of the TNFAIP8L1 gene in mice does not affect the development of liver myeloid cells and the homeostasis of the liver.TNFAIP8L1 plays an inhibitory role in the occurrence and development of acute liver injury.TNFAIP8L1 gene deficiency aggravates LPS/D-Gal-induced acute liver injury,possibly by increasing Neu and BMNCs infiltration and recruiting other types of immune cells to infiltrate liver tissues,thereby exacerbating liver cell necrosis.

Objective:To investigate the eye movement characteristics of non-emotional pictures and emotion-al pictures in college students with different self-rating levels of depression.Methods:The Baker Depression Ques-tionnaire(BDI-2)was used to select 20 college students in high score group(BDI-2 score≥ 18 points)and 20 col-lege students in low score group(BDI-2 score ≤2 points).In experiment 1 the different finding tasks were used to investigate the difference of eye movement features between the two groups when viewing non-emotional pic-tures.In experiment 2 the expression recognition tasks were used to investigate the difference of the eye movement features between the two groups when viewing emotional pictures.Results:The results of experiment 1 showed that when completing the judgment task,the fixation times of each interest area of non-emotional images was smaller in the high score group than in the low score group(P＜0.01).The results of experiment 2 showed that the reaction time was longer to sad faces than to happy faces in the high score group(P＜0.05),and the correct rate to sad faces was higher in the high score group than in the low score group(P＜0.05).For the eye interest area,the first fixation arrival time was earlier in the high score group than in the low score group(P＜0.001),and the first fixa-tion time and total fixation time were shorter in the high score group than in the low score group(Ps＜0.01).Con-clusion:College students with high self-rating level of depression show a decrease of interest when viewing non-e-motional pictures,and show an advantage in processing negative emotional information and avoiding eye gaze when viewing emotional pictures.