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.

The concept of holism is the core idea of traditional Chinese medicine （TCM）. Various organs and tissues coordinate with each other to maintain the body's life activities， with a close and mutual influence between the spleen， stomach， and the central nervous system （brain）. The gut-brain axis plays an important bridging role between the digestive system and the central nervous system， achieving bidirectional information exchange between the brain and the gastrointestinal tract through complex neuroendocrine and immune mechanisms. The theory of cross-organ interaction involves the mutual influence， coordination， and integration between different organs and systems； multimodality， on the other hand， utilizes multiple sensory modalities， such as vision， hearing， and touch， to convey information. By combining TCM theory with the gut-brain axis theory， a cross-organ multimodal characterization system is established to explore its mechanism and application value in refractory diseases such as functional gastrointestinal disorders， precancerous gastrointestinal diseases， Alzheimer's disease， Parkinson's syndrome， type 2 diabetes， and depression.

OBJECTIVES: The American Heart Association (AHA) recently defined cardiovascular-kidney-metabolic (CKM) syndrome to better characterize the associations among cardiovascular, kidney, and metabolic diseases. Although about 9 in 10 United States adults have at least 1 risk factor for CKM syndrome, its prevalence in other populations is less understood. To fill this gap, we examined the prevalence of CKM syndrome in Korea and its association with demographic and socioeconomic status (SES). METHODS: Using data from the Korean National Health and Nutrition Examination Survey between 2011 and 2021, we calculated the prevalence of CKM syndrome across the following stages: stage 0 (no risk factors), stage 1 (excess or dysfunctional adiposity), stage 2 (other metabolic risk factors or chronic kidney disease), and stages 3-4 (subclinical/clinical cardiovascular diseases) among adults aged ≥20 years. Weighted analyses were used to estimate prevalence and 95% confidence intervals (CIs) for each CKM syndrome stage, stratified by age, gender, and SES factors. RESULTS: Among 54,994 Korean adults, the prevalence of CKM syndrome was as follows: stage 0 (25.2%; 95% CI, 24.7 to 25.8), stage 1 (19.3%; 95% CI, 18.9 to 19.7), stage 2 (51.6%; 95% CI, 51.1 to 52.2), and stages 3-4 (3.9%; 95% CI, 3.7 to 4.0). The prevalence of stages 2 and 3-4 was higher in men than in women. In addition, stages 3-4 were more prevalent among rural residents and those with lower education or income. CONCLUSIONS About 3 out of 4 Koreans are at risk for CKM syndrome. These findings highlight that CKM syndrome is a global health problem and that interventions are urgently needed to prevent further progression.

Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from Lactobacillus rhamnosus, has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness.Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as OCT4 and SOX2, along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.

OBJECTIVE: To investigate the short-term clinical effect of closed reduction single arm external fixator combined with percutaneous needle fixation in the treatment of C1 distal radius fracture in elderly patients. METHODS: Between December 2022 and December 2023, a total of 60 elderly patients diagnosed with type C1 distal radius fractures were treated, comprising 9 males and 51 females. The age ranged from 65 to 84 years old, with an average of (72.69±8.14) years old. Among them, there were 18 cases on the left side and 42 cases on the right side. There were 55 cases of falling injury and 5 cases of traffic accident injury. According to the different surgical methods, the patients were divided into observation group and control group, with 30 cases in each group. The control group underwent manual reduction and unilateral external fixator fixation, consisting of 4 males and 26 females. The mean age was (72.54±8.67) years old. The body mass index (BMI) was (20.61±2.17) kg·m^-2. There were 10 cases on the left side and 20 cases on the right side. Among them, there were 27 cases of falling injury and 3 cases of traffic accident injury. The observation group was treated with manual reduction and unilateral external fixator combined with percutaneous Kirschner wire fixation, including 5 males and 25 females. The mean age was (72.76±7.23) years old. BMI (20.82±2.03) kg·m^-2. The left side was involved in 8 cases and the right side in 22 cases. There were 28 cases of falling injury and 2 cases of traffic accident injury. The changes in radial height, ulnar declination, palmar inclination angle parameters and patient-rated wrist evaluation (PRWE) were assessed on X-ray films before surgery, 2 days after surgery, and 12 weeks after surgery between the two groups. RESULTS: All surgical procedures were successfully completed in both groups without any significant complications. All patients were followed up for a duration from 12 to 20 weeks with an average of(14.50±2.78) weeks. The two groups exhibited significant differences in radial height, palmar inclination angle, and ulnar deviation angle at 2 days and 12 weeks post-operation (P<0.05). However, there was no statistically significant difference observed in radial height, palmar inclination, and ulnar deviation between the two groups at 2 days after the operation (P>0.05). There were significant differences in radial height, palmar inclination angle, and ulnar deviation between the two groups at 12 weeks after operation (P<0.05). At 2 days and 12 weeks after the operation, there were significant differences in PRWE scores of the two groups compared with preoperative scores(P<0.05). At 2 days after the operation, there was no significant difference in PRWE score between the two groups (P>0.05). The PRWE score showed a significant difference between the two groups at 12 weeks post-operation(P<0.05). CONCLUSION The combination of closed reduction and unilateral external fixator, along with percutaneous pin fixation provides move stable fixation for type C1 distal radius fractures. Gradual removal of external fixator further facilitatse the recovery of wrist joint function.
Humans ; Male ; Female ; Radius Fractures/surgery* ; External Fixators ; Aged ; Aged, 80 and over ; Bone Wires ; Fracture Fixation/instrumentation* ; Wrist Fractures

PURPOSE: End-stage knee osteoarthritis (OA) patients are the primary candidates for total knee arthroplasty (TKA). However, most morphological refinements of TKA prosthesis are based on anatomical data from the knees of healthy individuals. This study aimed to determine whether differences exist in key bony morphological characteristics of the distal femur and proximal tibia between osteoarthritic knees and healthy knees. METHODS: This was a retrospective cross-sectional observational study with a case-control design. Patients who were aged ≥ 50 years, had no history of trauma, fracture, or surgery in the studied knee, and had no obvious knee flexion contracture were included in this study by CT scans. Patients who met the American College of Rheumatology clinical criteria for knee OA were included in the study group. Kellgren-Lawrence grade III or IV knees were studied (for bilateral cases, the more severely affected knee was chosen). Patients who presented with unilateral knee pain or trauma were included in the control group, with CT scans from the opposite (asymptomatic) knee used for analyzing. The studied knee had a Kellgren-Lawrence grade of 0 or I and showed no abnormalities upon physical examination. Archived knee CT scans from 160 patients were divided into 2 groups: the study group (80 moderate-to-severe OA knees) and the control group (80 healthy knees). After 3-dimensional reconstruction and virtual cutting using a CT workstation, 13 morphological parameters of the distal femur and proximal tibia were compared between the 2 groups using independent-samples t-tests. RESULTS: No significant group differences in the femoral anteroposterior dimension (p = 0.797), height of the lateral femoral condyle (p = 0.268), posterior condylar angle (p = 0.240), tibial anteroposterior dimension (p = 0.536), or tibial lateral anteroposterior dimension (p = 0.702) were observed. However, the femoral mediolateral dimension (p = 0.002), distal femoral aspect ratio (femoral mediolateral dimension/femoral anteroposterior dimension) (p < 0.001), height of the femoral trochlear groove (p < 0.001), height of the medial femoral condyle (p < 0.001), tibial mediolateral dimension (p = 0.001), proximal tibial aspect ratio (tibial mediolateral dimension/tibial anteroposterior dimension) (p = 0.004), tibial medial anteroposterior dimension (p = 0.005), and tibial asymmetry ratio (tibial medial anteroposterior dimension/tibial lateral anteroposterior dimension) (p = 0.006) were all significantly greater in the study group. CONCLUSION Knees with moderate-to-severe OA are significantly wider than healthy knees, and OA is a risk factor for increased tibial platform asymmetry. When refining the morphological parameters of TKA prostheses, the specific bony morphological characteristics of OA knees should be taken into account to reduce the potential risk of femoral or tibial component underhang and facilitate optimal balance between tibial component fit and rotational alignment.
Humans ; Osteoarthritis, Knee/pathology* ; Male ; Female ; Cross-Sectional Studies ; Retrospective Studies ; Arthroplasty, Replacement, Knee ; Middle Aged ; Aged ; Case-Control Studies ; Prosthesis Design ; Knee Prosthesis ; Femur/anatomy & histology* ; Tibia/anatomy & histology* ; Tomography, X-Ray Computed ; Knee Joint/diagnostic imaging*

Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 10 6 cells, 5 × 10 6 cells, and 1 × 10 7 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1 st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
Male ; Animals ; Erectile Dysfunction/metabolism* ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods* ; Rats ; Penis/pathology* ; Humans ; Disease Models, Animal ; Umbilical Cord/cytology* ; Peripheral Nerve Injuries/complications* ; Mesenchymal Stem Cells ; Nitric Oxide Synthase Type III/metabolism* ; Actins/metabolism* ; Nitric Oxide Synthase Type I/metabolism*