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.

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.

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.

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 formulate refined management strategies to improve the operation quality and protective effect of medical X-ray diagnosis equipment based on the risk analysis of the correlation of medical X-ray diagnostic equipment.Methods:The used 41 medical X-ray diagnosis equipment in Fuwai Hospital,Chinese Academy of Medical Sciences from January 2022 to December 2023 were selected.According to different management modes for equipment,they were managed respectively by the conventional management mode(20 units)and the management mode with risk analysis of the correlation(21 units).The risk grades of correlation of management mode with risk analysis of the correlation were classified on the basis of the probability of risk and the degree of harm in medical X-ray diagnosis equipment.The protection management of equipment was conducted from three aspects included the location of equipment,the staffs and subjects.A self-made questionnaire was used to investigate the satisfactions of engineers of using management for equipment,operators,and staffs of operating and maintaining equipment for the two kinds of management modes.The protection quality,failure rate of equipment,and qualification rate of protection of medical X-ray diagnosis equipment under different management modes were compared.Results:The quality scores of operation safety,regular inspection,maintenance and repair,and shielding protection for radiation of medical X-ray diagnosis equipment that adopted the management mode with risk analysis of the correlation were respectively(92.14±3.36),(91.47±2.41),(92.54±3.32)and(91.69±3.57)points,all of which were higher than those of the conventional management mode,and the differences of them were statistically significant(t=16.396,17.368,19.688,14.401,P<0.05).The failure rate of the 21 medical X-ray diagnosis equipment that adopted the management mode with risk analysis of correlation was 0,which was lower than 20.00%of the conventional management mode.The qualified rate of protection was 95.23%,which was higher than 70.00%of the conventional management mode,and the differences of them were statistically significant(x2=4.654,4.608,P<0.05).The satisfaction scores of engineers of using equipment,operators and staffs of operating and maintaining equipment for the protective effect of adopting the management mode with risk analysis of correlation were respectively(94.69±4.02),(93.21±4.36)and(92.54±3.47)points,all of which were higher than those of the conventional management mode,and the differences were statistically significant(t=16.902,11.291,12.020,P<0.05).Conclusion:The process-based protection management strategy on the basis of risk analysis of correlation for medical X-ray diagnosis equipment can prevent risks of medical X-ray diagnostic equipment,and improve the operation quality of the equipment,and reduce the operation risks of the equipment,and maximize the enhancement for management quality of medical X-ray diagnosis equipment.

Tracheal intubation in emergency and complex scenarios is difficult for critical care medicine residents.Virtual reality(VR)technology has not been used in the training of tracheal intubation in critical care scenarios in China.This project team has developed an emergency tracheal intubation training system for the intensive care unit(ICU)based on virtual simulation technology,and has obtained the computer software copyright registration certificate from the National Copyright Administration(registration number:2024SR1139484).This system uses a case script of acute respiratory distress syndrome(ARDS)secondary to severe acute pancreatitis,sets the roles of patients,family members,nurses and residents,collects digital resources of ICU rescue scenes,computer-aided design(CAD)drawings,instrument models and equipment photos,models instruments and equipment,and uses PICO 4 Pro VR helmets to display the ICU environment in the virtual scene.The key points of skill assessment include tracheal intubation operation,the ability to interpret laboratory results,the ability to judge diseases and the ability to work in teams.The user center contains 3 submodules,namely,the score center,skill analysis and user management.There are 3 user roles in the system,namely,residents,teachers and administrators.The system can track and record the entire operation process,including video recording and playback,and score and comprehensively evaluate each step,thereby realizing an objective and quantitative training and assessment system.By simulating the three-dimensional clinical operation environment of the ICU,the entire process of real tracheal intubation is fully reproduced.Resident doctors are placed in the ICU rescue scene,focusing on training tracheal intubation skills,the ability of doctor-patient communication,on-the-spot response,and teamwork,which is expected to become an important type of standardized teaching in critical care medicine.

AIM To investigate the effect of Fuzheng Hefu Zhiyang Formula(FZHFZY)on psoriasis-like skin lesions and immune regulation in mice.METHODS In the in vivo experiment,30 BALB/c mice were randomly divided into the blank group,the model group,the dexamethasone group(1.5 g/kg of compound dexamethasone acetate cream),and the low-dose(2.5 g/kg)and high-dose(5 g/kg)FZHFZY groups,with six mice in each group.The experiment groups were treated with respective FZHFZY and dexamethasone,and the other groups were given normal saline for 10 consecutive days,during which psoriatic skin lesions were induced with imiquimod cream for 7 consecutive days.The mice had their area and severity of psoriasis assessed by PASI score;their histological changes of skin lesions.observed with Hematoxylin-eosin(HE)staining;their F4/80 ratio of skin lesions observed with immunohistochemical(IHC)staining;their protein expressions of P38,p-P38,Erk,p-Erk,P65 and p-P65 detected by Western blot;and their mRNA expressions of tumor necrosis factor-α(TNF-α),IL-17,IL-23 and IL-1β detected by RT-qPCR.In the in vitro research,the cultured RAW264.7 cells were divided into the blank group,the LPS group,and the FZHFZY groups(1 200,600,300,150 μg/mL).The cells had their protein expressions of P38,p-P38,Erk,p-Erk,P65 and p-P65 detected with Western blot;and their mRNA expressions of IL-6,TNF-α,IL-23 and IL-8 detected by RT-qPCR.RESULTS The in vivo experiment showed that compared to the model group,the FZHFZY groups demonstrated decreased PASI score(P＜0.01);improved epidermal thickening and parakeratosis of skin lesions as revealed by HE staining result and increased expression of F4/80 in IHC staining sections;decreased protein expression ratios of p-P38/P38,p-ERK/Erk and p-P65/P65 in skin(P＜0.05,P＜0.01);and reduced mRNA expressions of TNF-α,IL-17,IL-23 and IL-1β in the skin(P＜0.01).FZHFZY(0～2 400 μg/mL)showed no significant cytotoxicity towards RAW264.7 cells in vitro(P＞0.05).Compared to those of the LPS group,the cells exposed to FZHFZ at concentrations of 1 200 and 600 μg/mL demonstrated decreased protein expression ratios of p-P38/P38,p-ERK/Erk,and p-P65/P65(P＜0.05,P＜0.01);and significantly decreased mRNA expressions of TNF-α,IL-17,IL-23 and IL-1β(P＜0.01).CONCLUSION FZHFZY alleviates imiquimod-induced psoriatic lesions in mice and suppresses inflammatory response in LPS-stimulated RAW264.7 cells by inhibiting P38/Erk/NF-κB signaling pathway.

Objective To explore the effectiveness of a tracheal intubation training system based on virtual reality(VR)technology in cultivating the clinical practice abilities of resident physicians.Methods Twenty-five first-year resident physicians who were enrolled in the residency programme at Peking University Third Hospital from August 2024 to February 2025 were recruited for this study.All participants completed a questionnaire after receiving VR-based intensive care unit(ICU)emergency tracheal intubation training,to share their experiences with the VR technology-based ICU emergency tracheal intubation training and the shortcomings encountered during the process.Results ① General information:a total of 25 resident physician questionnaires were distributed in this study and received 25 valid responses(response rate 100%).Among the 25 residents,there were 15 males(60%)and 10 females(40%),with an average age of(25.3±0.8)years.Clinical experience was categorised as≤1 year 4 residents(16%),>1-3 years 8 residents(32%),>3-<5 years 5 residents(20%)and≥5 years 8 residents(32%).Among them,3 residents(12%)had no prior tracheal intubation experience,while 11(44%)had performed>10 intubations.Prior to this training,3 residents(12%)had received other forms of virtual tracheal intubation training,whereas 22(88%)had not.During traditional tracheal intubation training,18 residents(72%)reported that they monitored heart rate and blood pressure,whereas 7(28%)did not.In real-world emergency tracheal intubation scenarios,21 residents(84%)experienced role confusion.Additionally,23 residents(92%)believed that opportunities for tracheal intubation practice were too limited,17(68%)thought traditional training provided more guidance from instructors,and 15(60%)valued practical operation opportunities more in tracheal intubation training.②VR-based ICU emergency tracheal intubation training experience:23 residents(92%)considered the VR-based ICU emergency tracheal intubation training effective,with 13(52%)believing it to be more effective than traditional training.Furthermore,23 residents(92%)felt that the VR-based training created a more relaxed learning atmosphere,heightened their interest in learning tracheal intubation,and had better future prospects;22 residents(88%)believed that VR technology facilitated a better understanding of the laryngeal structure;24 residents(96%)thought that VR-based training reduced practical operation risks and better simulated real-world conditions;16 residents(64%)were highly satisfied with the VR-based ICU emergency tracheal intubation operating system;24 residents(96%)considered the case scenarios in the VR-based training reasonable.17 residents(68%)believed that VR-based training offered more learning opportunities,and 19 residents(76%)thought it reduced anxiety during the intubation process.③ Disadvantages of VR-based ICU emergency tracheal intubation:9 residents(36%)tended to overlook obtaining family consent before emergency tracheal intubation prior to the training.Regarding interactivity,5 residents(20%)rated it as excellent,9(36%)as average,and 11 residents(44%)believe that the interactivity was poor;22 residents(88%)felt a lack of tactile feedback during practical operations;20 residents(80%)recommended adding more simulated scenarios;11 residents(44%)believed that,compared to traditional training,VR training lacked practical operation opportunities.Additionally,17 residents(68%)experienced discomfort such as dizziness during the operation.Conclusion VR-based intubation training effectively enhances technical proficiency and psychological preparedness in ICU clinicians,particularly in anatomical visualization and risk-controlled rehearsal.