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: Endometrial damage is a critical factor contributing to infertility, particularly in women with refractory thin endometrium or intrauterine adhesions. Therefore, developing innovative therapeutic strategies for endometrial regeneration is essential. This study evaluates the regenerative potential of endometrial stromal cell (EMSC) injection and EMSC-loaded patch application in a mouse model with ethanol-induced endometrial damage. METHODS: A mouse model of endometrial damage was established using ethanol injection into the uterine horn. EMSCs were isolated, cultured, and either HA-injected into the damaged endometrium or transplanted via a small intestinal submucosa (SIS)-based EMSC patch. Histological analyses were performed to assess endometrial thickness, gland regeneration, and fibrosis reduction. RESULTS: Both EMSC injection and SIS-based EMSC patch engraftment promoted endometrial regeneration. However, the SIS-based EMSC patch group exhibited significant improvements in endometrial thickness, gland formation, and fibrosis reduction compared to the EMSC injection group. CONCLUSIONS This study demonstrates the superior regenerative potential of an SIS-based EMSC patch over direct EMSC injection for endometrial repair. The findings suggest that scaffold-assisted cell therapy could be a promising approach for treating endometrial damage-related infertility. Further studies are required to optimize this strategy for clinical applications.

This study systematically examined the effects of atomization as a transdermal permeation enhancer on the transdermal delivery of active ingredients with different physicochemical properties and investigated the underlying mechanisms. Porcine ear skin served as an in vitro model, and skin permeation experiments were conducted using Franz diffusion cells. Receptor fluids were collected at specific time points, and samples of the stratum corneum and viable epidermis–dermis were separated and prepared. Quantitative and visualization methods, including high-performance liquid chromatography, fluorescence derivatization, and confocal laser scanning microscopy, were used to compare skin retention and transdermal permeation of adenosine (AD), tranexamic acid (TXA), calcein (CAL), and tocopheryl acetate (TA) under atomized and non-atomized conditions. Additionally, transepidermal water loss (TEWL) measurements and attenuated total reflectance–Fourier transform infrared spectroscopy (ATR-FTIR) were employed to analyze the mechanism behind the penetration enhancement caused by atomization. The findings showed that atomization increased skin retention within the stratum corneum and viable epidermis–dermis, as well as the transdermal permeation of all four active ingredients to varying degrees. The most significant enhancement was observed for TXA, which has a relatively low molecular weight and moderate lipophilicity, while the enhancement effects for highly hydrophilic AD and highly lipophilic TA were comparatively limited; however, atomization significantly increased the skin retention of TA. TEWL results indicated that skin permeability increased within 4 hours after atomization and largely recovered within 8 hours. ATR-FTIR analysis suggested that atomization may facilitate transdermal delivery by disrupting the lipid order and keratin conformation in the stratum corneum.This study provides theoretical support and experimental references for the advancement of atomization transdermal delivery technology, as well as the design and development of related atomization products.

Objective To establish an effective management mode, play the full role of DRGs in rational drug use, formulate the pharmaceutical clinical path, and intervene the prescription behavior of doctors, which could improve the level of rational drug use in the hospital through the management practice of rational drug use under the payment method of DRGs in a third-grade hospital. Methods A drug entering mechanism, a rational drug use supervision mechanism and an active and rational drug use data exposure mechanism based on DRGs were established, and the rational drug use indicators such as drug consumption index, average drug cost, and auxiliary drug use were accurately positioned based on the information platform, and the accurate and refined management of rational drug use was realized through the daily supervision of the office of the Pharmaceutical Affairs Committee. Results and Conclusion Under the multi-dimensional and multi-level rational drug use management based on DRGs, the effect of rational drug use was evaluated after the reform of DRGs payment method, and all the index of rational drug use in our hospital were continuously improved.

Objective To investigate the diagnostic value of cytokeratin 19 fragment(CYFRA21-1),squa-mous cell carcinoma antigen(SCC),neuron-specific enolase(NSE)combined with fibrinogen(FIB)in patho-logical type and lymph node metastasis of lung cancer.Methods A total of lung cancer patients admitted to Deyu Medical Maanshan General Hospital from September 2022 to March 2024 were selected as the lung canc-er group,including 14 cases of lung squamous cell carcinoma,36 cases of lung adenocarcinoma,8 cases of small cell lung cancer,39 cases of lymph node metastasis and 19 cases of no lymph node metastasis.In addition,45 patients with benign pulmonary lesions in Deyu Medical Ma'anshan General Hospital during the same period were selected as the control group.The levels of CYFRA21-1,SCC,NSE and FIB were compared between the two groups.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of CY-FRA21-1,SCC,NSE combined with FIB for pathological type and lymph node metastasis of lung cancer.Re-sults The levels of CYFRA21-1,NSE,SCC and FIB in lung cancer group were higher than those in control group(P<0.05).There were statistically significant differences in CYFRA21-1,NSE,SCC and FIB levels in patients with different pathological types of lung cancer(P<0.05).The levels of FIB and NSE levels in pa-tients with small cell lung cancer were higher than those in patients with lung squamous cell carcinoma and lung adenocarcinoma.The levels of CYFRA21-1 and SCC in patients with lung squamous cell carcinoma were higher than those in patients with lung adenocarcinoma and small cell lung cancer(P<0.05).The levels of CYFRA21-1,NSE,SCC and FIB in patients with lymph node metastasis were higher than those in patients without lymph node metastasis(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of CYFRA21-1,NSE,SCC and FIB alone and in combination were 0.795,0.620,0.672,0.757 and 0.812,re-spectively.The AUC of combined detection in the diagnosis of lung cancer,lung adenocarcinoma,lung squa-mous cell carcinoma,small cell lung cancer and lymph node metastasis were 0.812,0.837,0.786,0.922 and 0.875,respectively.Conclusion CYFRA21-1,SCC,NSE combined with FIB can improve the diagnostic value of pathological type and lymph node metastasis of lung cancer.

Multiple myeloma(MM)is a common hematological malignancy that is currently incurable.MM exhibits significant heterogeneity in its manifestations,genetics,and response to treatment.Although some traditional biomarkers and drug combination therapies used for MM diagnosis and evaluation have a-chieved certain results,the recurrence and mortality rates of the disease are still high,and the prognosis is poor.Therefore,it is crucial to explore more sensitive and effective diagnostic and prognostic biomarkers.This article focuses on introducing new biomarkers reported and studied in recent years,which may facilitate early diagnosis,prognostic stratification,and personalized treatment decisions for MM.

Objective To observe the clinical efficacy of Biyuan Tongqiao Granules combined with moxibustion in the treatment of allergic rhinitis(AR)of lung qi deficiency and cold type,and to explore its possible mechanism of action.Methods A total of 138 patients diagnosed with AR in the otolaryngology outpatient and inpatient departments of Linyi People's Hospital from November 2020 to November 2022 were selected as the study subjects.The patients were randomly divided into an observation group and a control group using a random number table,with 69 cases in each group.The control group was treated with Mometasone Furoate Nasal Spray,while the observation group received Biyuan Tongqiao Granules combined with moxibustion in addition to the control group's treatment.Both groups were treated for 4 weeks.After the ending of treatment,the clinical efficacy of the two groups was evaluated.Changes in traditional Chinese medicine(TCM)syndrome scores,serum levels of interleukin-6(IL-6),interleukin-8(IL-8),and C-reactive protein(CRP)were observed.The proportions of Treg cells and Th17 cells were compared before and after treatment,and the Treg/Th17 ratio,as well as levels of transforming growth factor β1(TGF-β1)and interleukin-17(IL-17)were calculated.The safety and incidence of adverse reactions in the two groups were evaluated.Six months after the end of treatment,the recurrence rate of patients was followed up and compared between the two groups.Results(1)After treatment,the TCM syndrome scores of both groups were significantly improved(P＜0.05),and the observation group showed significantly better improvement in TCM syndrome scores compared to the control group,with a statistically significant difference(P＜0.05).(2)After treatment,the serum levels of IL-6,CRP,and IL-8 in both groups were significantly improved(P＜0.05),and the observation group showed significantly better improvement in serum IL-6,CRP,and IL-8 levels compared to the control group,with a statistically significant difference(P＜0.05).(3)After treatment,the levels of Treg,Th17,Treg/Th17,TGF-β1,and IL-17 in both groups were significantly improved(P＜0.05),and the observation group showed significantly better improvement in these levels compared to the control group,with a statistically significant difference(P＜0.05).(4)The total effective rate in the observation group was 97.10%(67/69),while it was 76.81%(53/69)in the control group.The efficacy of the observation group was superior to that of the control group,with a statistically significant difference(P＜0.05).(5)At the 6-month follow-up,the recurrence rate in the observation group was 5.80%(4/69),while it was 24.64%(17/69)in the control group.The recurrence rate in the observation group was lower than that in the control group,with a statistically significant difference(P＜0.05).(6)There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Biyuan Tongqiao Granules combined with moxibustion in the treatment of AR of lung qi deficiency and cold type can significantly improve patients'clinical symptoms,help regulate the Treg/Th17 immune imbalance,improve inflammatory factor levels,and has a low recurrence rate,good safety,and significant efficacy.

Alzheimer's disease(AD),a major cause of dementia,is a common neurodegenerative disease,beginning with memory loss and difficulties with thinking,language and problem-solving skills.Intensification of population aging and the increasing incidence of AD have imposed a heavy burden on healthcare systems.Currently,the main pathological explanation remains the excessive accumulation of β-amyloid plaques,formation of neurofibrillary tangles and neuronal loss,but the true etiology and pathogenesis of AD remain unknown.The advances of research in AD,with respect to genetics,pathophysiological mechanism,imaging diagnosis and laboratory diagnosis,are reviewed in this article,aiming to provide references for relevant research and potential clinical applications.

Objective To reveal the development characteristics of fat percentage and muscle mass in three nomadic populations in the Hexi Corridor of Gansu.Methods Bioelectrical impedance analysis was used to determine the values of 13 indexes of fat percentage and muscle mass in 263 cases of Gansu Kazakhs,400 cases of Gansu Mongols,and 362 cases of Yugu adults.Results In the three nomadic populations of the Hexi Corridor,visceral fat level of males was significantly positively correlated with age,while total body muscle mass and estimated bone mass were significantly negatively correlated with age.In females,percent body fat,visceral fat grade,percent left and right upper limb fat,percent right lower limb fat and percent trunk fat were all significantly positively correlated with age,while trunk muscle mass was significantly negatively correlated with age.The result of principal component analysis showed that the three nomadic populations in the Hexi Corridor were close to each other in terms of fat percentage and muscle mass characteristics,with high visceral fat grades in males and normal visceral fat grade in females.Among the 13 populations,three nomadic groups in the Hexi Corridor had high fat percentage and muscle mass.Overall,the nomadic population had greater fat percentage and muscle mass than the semi-agricultural and semi-pastoral population,and even more significantly greater than the agrarian population.The long-term integration of the historical Hexi Corridor populations result ed in the relative proximity of the genetic structure of three nomadic populations,which was a genetic factor for the proximity of their fat percentage and muscle mass.Higher per capita disposable income was a socio-economic factor for high fat percentage and muscle mass among Gansu Kazakhs and Gansu Mongolians.Low average annual temperature was an environmental factor for high muscle mass among Gansu Kazakhs and Yugus.Conclusion Gansu Kazakhs,Gansu Mongols,and Yugus have the fat percentage and muscle mass characteristic of northern Chinese populations.

Objective To investigate the effects of miR-126 on myocardial remodeling and macrophage polarization after acute myocardial infarction(AMI).Methods(1)Twenty-one rats were divided into a sham operation group and an AMI group.The AMI group was further divided into postoperative days 1,3,5,7,9,and 11 days(AMI-1,AMI-3,AMI-5,AMI-7,AMI-9,AMI-11),with 3 rats in each group,and postoperative day 3 was selected for subsequent study.(2)Thirty rats were randomly divided into three groups:sham operation group,AMI group and miR-126 overexpression group,with 10 rats in each group.RT-qPCR was used to detect the expression levels of miR-126 mRNA.2,3,5-Triphenyltetrazole chloride(TTC)staining was used to detect the infarct size.Myocardial fibrosis was detected by Masson staining.The cross-sectional area of the myocardium was determined by H&E staining.Immunofluorescence staining was used to detect the protein levels of CD86 and CD206 in myocardial tissue.Western blotting was used to detect the protein levels of CD86 and CD206 in myocardial tissue.The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in serum were detected by ELISA kit.Results Compared with the sham operation group,the expression level of miR-126 mRNA in myocardial tissue of rats in the AMI group was significantly decreased on postoperative day 1(P<0.05),reached the lowest level on postoperative day 3.And then although it rose to a certain extent,it remained lower than that of the sham operation group on postoperative day 11(P<0.05),and postoperative day 3 was selected for further study.Compared with the sham operation group,the expression of miR-126 mRNA in myocardial tissue of the AMI group was decreased(P<0.05),and the myocardial fibrosis,infarct size and myocardial cross-sectional area were increased(P<0.05).The expression of CD86 protein in myocardial tissue was increased and the expression of CD206 protein was decreased(P<0.05).The serum levels of TNF-α,IL-6 and IL-1β were increased(P<0.05).Compared with the AMI group,the rats in the miR-126 overexpression group had a significant increase in the mRNA expression of miR-126 in myocardial tissue(P<0.05),a significant reduction in myocardial fibrosis,infarct size,and myocardial cross-sectional area(P<0.05),a significant reduction in the expression of CD86 protein in myocardial tissue,and a significant increase in the expression of CD206 protein(P<0.05).The serum levels of TNF-α,IL-6 and IL-1β were significantly decreased(P<0.05).Conclusion Over-expression of miR-126 can improve myocardial remodeling and promote M2 macrophage polarization in AMI rats.