OBJECTIVE To provide reference for medical institutions to establish the record management mode and review rules of off-label use of 5-aminolevulinic acid （ALA） in photodynamic therapy based on the level of evidence. METHODS All ALA-containing outpatient prescriptions in the rational drug use system in our hospital from January 1， 2024 to December 31， 2025 were retrospectively collected. Based on the drug instructions， the current status of off-label use of ALA in photodynamic therapy was identified . The relevant studies in Micromedex， PubMed， CNKI， Wanfang Data and other databases were systematically searched as the relevant evidence-based evidence of ALA off-label use. According to the Off-label Drug Use Filing Standard of the hospital，the evidence-based evaluation method was used to evaluate the evidence-based evidence of ALA off-label use and carry out hierarchical management. RESULTS A total of 1 803 effective prescriptions were included， of which 676 （37.49%） were off-label use， distributed in the dermatology department （564 prescriptions，83.43%） and the plastic surgery department （112 prescriptions，16.57%）. All 676 prescriptions were off-indications medication， involving ten types of skin diseases， primarily including moderate to severe acne （39.94%）， skin warts （25.44%）， Bowen’s disease （11.98%）， and others. According to evidence-based evidence，off-label uses such as moderate to severe acne， actinic keratosis， and Bowen’s disease were managed according to the evidence categoryⅠ orⅡ.The uses of extramammary Paget’s disease and rosacea were managed according to the evidence category Ⅲ.The uses of lichen sclerosus and keloids were managed according to the evidence category Ⅳ.The results of evidence-based evaluation showed that 92.01% of off-label use in our hospital had high-level evidence-based support （ evidence category was gradeⅠ-Ⅱ）. CONCLUSIONS Off-label uses supported by high-level evidence， such as moderate to severe acne， skin warts， and Bowen’s disease， can be managed under filing category Ⅰ or Ⅱ. For the use of lichen sclerosus and keloids， evidence-based evidence is insufficient and should be strictly restricted.The vast majority of ALA off-label use in our hospital has sufficient evidence-based basis.

Fibrosis, the pathological scarring of vital organs, is a severe and often irreversible condition that leads to progressive organ dysfunction. It is particularly pronounced in organs like the liver, kidneys, lungs, and heart. Despite its clinical significance, the full understanding of its etiology and complex pathogenesis remains incomplete, posing substantial challenges to diagnosing, treating, and preventing the progression of fibrosis. Among the various molecular players involved, platelet-derived growth factor-C (PDGF-C) has emerged as a crucial factor in fibrotic diseases, contributing to the pathological transformation of tissues in several key organs. PDGF-C is a member of the PDGFs family of growth factors and is synthesized and secreted by various cell types, including fibroblasts, smooth muscle cells, and endothelial cells. It acts through both autocrine and paracrine mechanisms, exerting its biological effects by binding to and activating the PDGF receptors (PDGFRs), specifically PDGFRα and PDGFRβ. This binding triggers multiple intracellular signaling pathways, such as JAK/STAT, PI3K/AKT and Ras-MAPK pathways. which are integral to the regulation of cell proliferation, survival, migration, and fibrosis. Notably, PDGF-C has been shown to promote the proliferation and migration of fibroblasts, key effector cells in the fibrotic process, thus accelerating the accumulation of extracellular matrix components and the formation of fibrotic tissue. Numerous studies have documented an upregulation of PDGF-C expression in various fibrotic diseases, suggesting its significant role in the initiation and progression of fibrosis. For instance, in liver fibrosis, PDGF-C stimulates hepatic stellate cell activation, contributing to the excessive deposition of collagen and other extracellular matrix proteins. Similarly, in pulmonary fibrosis, PDGF-C enhances the migration of fibroblasts into the damaged areas of lungs, thereby worsening the pathological process. Such findings highlight the pivotal role of PDGF-C in fibrotic diseases and underscore its potential as a therapeutic target for these conditions. Given its central role in the pathogenesis of fibrosis, PDGF-C has become an attractive target for therapeutic intervention. Several studies have focused on developing inhibitors that block the PDGF-C/PDGFR signaling pathway. These inhibitors aim to reduce fibroblast activation, prevent the excessive accumulation of extracellular matrix components, and halt the progression of fibrosis. Preclinical studies have demonstrated the efficacy of such inhibitors in animal models of liver, kidney, and lung fibrosis, with promising results in reducing fibrotic lesions and improving organ function. Furthermore, several clinical inhibitors, such as Olaratumab and Seralutinib, are ongoing to assess the safety and efficacy of these inhibitors in human patients, offering hope for novel therapeutic options in the treatment of fibrotic diseases. In conclusion, PDGF-C plays a critical role in the development and progression of fibrosis in vital organs. Its ability to regulate fibroblast activity and influence key signaling pathways makes it a promising target for therapeutic strategies aiming at combating fibrosis. Ongoing research into the regulation of PDGF-C expression and the development of PDGF-C/PDGFR inhibitors holds the potential to offer new insights and approaches for the diagnosis, treatment, and prevention of fibrotic diseases. Ultimately, these efforts may lead to the development of more effective and targeted therapies that can mitigate the impact of fibrosis and improve patient outcomes.

Objective: Accurate evaluation of inflammation severity in ulcerative colitis (UC) can guide treatment strategy selection. The potential value of the pericolic fat attenuation index (FAI) on CT as an indicator of disease severity remains unknown.This study aimed to assess the diagnostic accuracy of pericolic FAI in predicting UC severity. Materials and Methods: This retrospective study enrolled 148 patients (mean age 48 years; 87 males). The fat attenuation on CT was measured in four different locations: the mesocolic vascular side (MS) and opposite side of MS (OMS) around the most severe bowel lesion, the retroperitoneal space (RS), and the subcutaneous area. The fat attenuation indices (FAI MS, FAI OMS, and FAI RS) were calculated as the fat attenuation measured in MS, OMS, and RS, respectively, minus that of the subcutaneous area, and were obtained in the non-enhanced, arterial, and delayed phases. Correlations between the FAI and UC Endoscopic Index of Severity (UCEIS) were assessed using Spearman’s correlation. Predictors of severe UC (UCEIS ≥7) were selected by univariable analysis. The performance of FAI in predicting severe UC was evaluated using the area under the receiver operating characteristic curve (AUC). Results: The FAIMS and FAI OMS scores were significantly higher than FAI RS in three phases (all P < 0.001). The FAIMS and FAI OMS scores moderately correlated with the UCEIS score (r = 0.474–0.649 among the three phases). Additionally, FAI MS and FAI OMS identified severe UC, with AUC varying from 0.77 to 0.85. Conclusion Increased CT attenuation of pericolic adipose tissue could serve as a noninvasive marker for evaluating UC severity. FAI MS and FAI OMS of three phases showed similar prediction accuracies for severe UC identification.

Objective: Accurate evaluation of inflammation severity in ulcerative colitis (UC) can guide treatment strategy selection. The potential value of the pericolic fat attenuation index (FAI) on CT as an indicator of disease severity remains unknown.This study aimed to assess the diagnostic accuracy of pericolic FAI in predicting UC severity. Materials and Methods: This retrospective study enrolled 148 patients (mean age 48 years; 87 males). The fat attenuation on CT was measured in four different locations: the mesocolic vascular side (MS) and opposite side of MS (OMS) around the most severe bowel lesion, the retroperitoneal space (RS), and the subcutaneous area. The fat attenuation indices (FAI MS, FAI OMS, and FAI RS) were calculated as the fat attenuation measured in MS, OMS, and RS, respectively, minus that of the subcutaneous area, and were obtained in the non-enhanced, arterial, and delayed phases. Correlations between the FAI and UC Endoscopic Index of Severity (UCEIS) were assessed using Spearman’s correlation. Predictors of severe UC (UCEIS ≥7) were selected by univariable analysis. The performance of FAI in predicting severe UC was evaluated using the area under the receiver operating characteristic curve (AUC). Results: The FAIMS and FAI OMS scores were significantly higher than FAI RS in three phases (all P < 0.001). The FAIMS and FAI OMS scores moderately correlated with the UCEIS score (r = 0.474–0.649 among the three phases). Additionally, FAI MS and FAI OMS identified severe UC, with AUC varying from 0.77 to 0.85. Conclusion Increased CT attenuation of pericolic adipose tissue could serve as a noninvasive marker for evaluating UC severity. FAI MS and FAI OMS of three phases showed similar prediction accuracies for severe UC identification.

Objective: To establish a prediction model for high-risk cardiovascular disease (CVD) among residents aged 35 to 75 years, so as to provide the basis for improving CVD prevention and control measures. Methods: Permanent residents aged 35 to 75 years were selected from Dongcheng District, Beijing Municipality using the stratified random sampling method from 2018 to 2023. Demographic information, lifestyle, waist circumference and blood biochemical indicators were collected through questionnaire surveys, physical examinations and laboratory tests. Influencing factors for high-risk CVD among residents aged 35 to 75 years were identified using a multivariable logistic regression model, and a prediction model for high-risk CVD was established. The predictive effect was evaluated using the receiver operating characteristic (ROC) curve. Results: A total of 6 968 individuals were surveyed, including 2 821 males (40.49%) and 4 147 females (59.51%), and had a mean age of (59.92±9.33) years. There were 1 155 high-risk CVD population, with a detection rate of 16.58%. Multivariable logistic regression analysis showed that gender, age, smoking, central obesity, systolic blood pressure, fasting blood glucose, triglyceride and low-density lipoprotein cholesterol were influencing factors for high-risk CVD among residents aged 35 to 75 years (all P<0.05). The area under the ROC curve of the established prediction model was 0.849 (95%CI: 0.834-0.863), with a sensitivity of 0.693 and a specificity of 0.863, indicating good discrimination. Conclusion The model constructed by eight factors including demographic characteristics, lifestyle and blood biochemical indicators has good predictive value for high-risk CVD among residents aged 35 to 75 years.

OBJECTIVES: Urinary calculi are characterized by a high recurrence rate, and patients' adherence to self-management after discharge directly affects health outcomes. Traditional offline follow-up models often face problems such as poor compliance and uneven allocation of medical resources, making it difficult to meet individualized health management needs. Remote follow-up provides a novel solution to optimize long-term management, improve health literacy, and enhance clinical outcomes. This study aims to evaluate the effect of remote follow-up under an intelligent medical collaborative model on quality of life and health-promoting lifestyle in patients with urinary calculi, and to assess its short-term impact on clinical outcomes. METHODS: A total of 118 patients with urinary calculi admitted to a tertiary hospital in Hunan Province between August and November 2024 were recruited and randomly assigned to a control group (n=59) or an intervention group (n=59). The control group received routine departmental follow-up, while the intervention group underwent remote follow-up based on an intelligent medical collaborative model for one month. Assessments were conducted before discharge (T0), 15 days after discharge (T1), and one month after discharge (T2), using the Wisconsin Stone Quality of Life Questionnaire and the Health-Promoting Lifestyle Profile. At T2, the incidence of forgotten ureteral stents (FUS), ureteral stent-related complications, unplanned readmissions, and patient satisfaction were evaluated. RESULTS: No significant differences were observed between groups at T0 in baseline characteristics or outcome measures (all P>0.05). At T1 and T2, the intervention group had significantly higher health-related quality of life scores than the control group (P<0.05). Generalized estimating equation (GEE) analysis showed significant between-group effects (Wald's χ²=22.961, P<0.001), time effects (Wald's χ²=23.065, P<0.001), and interaction effects (Wald's χ²=6.930, P<0.05). Similarly, at T1 and T2, the intervention group scored significantly higher on health-promoting lifestyle than the control group (P<0.05), with significant between-group effects (Wald's χ²=22.936, P<0.001), time effects (Wald's χ²=10.694, P<0.001), and interaction effects (Wald's χ²=18.921, P<0.05). No significant differences were found between groups in the incidence of FUS, ureteral stent-related complications, or unplanned readmissions (all P>0.05). Patient satisfaction was significantly higher in the intervention group (t=4.089, P<0.001). CONCLUSIONS Remote follow-up under an intelligent medical collaborative model helps improve quality of life, promote health-oriented lifestyles, and enhance patient satisfaction among individuals with urinary calculi.
Humans ; Quality of Life ; Male ; Female ; Urinary Calculi/therapy* ; Health Promotion/methods* ; Middle Aged ; Adult ; Follow-Up Studies ; Treatment Outcome

Objective To investigate the application value of peripheral blood soluble human leukocyte antigen-G(sHLA-G)combined with immune cytokines in the differential diagnosis of renal transplant rejection.Methods This case-control study retrospectively analyzed 81 renal transplant patients hospitalized in the Department of Organ Transplantation,the Second Affiliated Hospital of Naval Medical University from April 2020 to December 2023,due to elevated serum creatinine.Among them,32 patients were diagnosed with acute rejection(acute rejection group),29 with chronic rejection(chronic rejection group),and 20 with elevated creatinine due to non-rejection causes(non-rejection group).Fifty renal transplant inpatients and outpatients with normal and stable serum creatinine were selected as control group during the same period.Clinical data such as gender,age,serum creatinine,estimated glomerular filtration rate(eGFR),and urine protein positive rate,etc.were collected.Peripheral blood of patients was sampled to measure the levels of plasma sHLA-G and immune cytokines[interferon-γ(IFN-γ),tumor necrosis factor-β(TNF-β),interleukin(IL)-2,IL-4,IL-10,IL-5,IL-6,IL-17]using enzyme-linked immunosorbent assay(ELISA).Stratify and compare the differences in sHLA-G levels among different groups and all renal transplant inpatients by gender.Results Compared with control group,serum creatinine levels and urine protein positive rate were significantly higher in acute rejection group,chronic rejection group,and non-rejection group,while eGFR was significantly lower,serum creatinine levels in chronic rejection group and non-rejection group were higher than those in acute rejection group,while eGFR was lower than that in acute rejection group,with statistically significant differences(P<0.05).No statistically significant differences were observed in gender,age,blood type,body mass index,transplantation duration,and immunosuppressive agent use among acute rejection,chronic rejection,non-rejection,and control groups(P>0.05).Plasma sHLA-G levels in acute rejection and chronic rejection groups were significantly lower than those in control group[(19.665±11.233)U/ml vs.(24.785±21.668)U/ml vs.(44.918±39.898)U/ml,P<0.05].The sHLA-G/IL-2 ratio in chronic rejection group was significantly higher than that in acute rejection group(5.844±6.248 vs.1.825±1.574,P<0.05),and the sHLA-G/IFN-γ ratio in non-rejection group was significantly higher than that in chronic rejection group(3.452±3.283 vs.1.543±2.030,P<0.05).Among 131 renal transplant inpatients,female sHLA-G levels were significantly higher than male(P<0.05).Within each group,female sHLA-G levels in chronic rejection group were significantly higher than male(P<0.05).Although female sHLA-G levels in acute rejection,non-rejection,and control groups were higher than those of male,the gender difference was not statistically significant(P>0.05).Conclusions Peripheral blood sHLA-G levels are correlated with renal transplantation rejection.The application of sHLA-G/IL-2 and sHLA-G/IFN-γ ratios has potential value in the diagnosis and differentiation of elevated creatinine caused by acute/chronic rejection,chronic rejection and non-rejection causes,respectively.

Objective To explore the molecular mechanism by which SOS Ras/Rac guanine nucleotide exchange factor 1-intronic transcript 1(SOS1-IT1)affects enhancer of zeste homolog 2(EZH2)protein expression in endometrial cancer cells Ishikawa and RL95-2.Methods Lentiviral transfection of short hairpin RNA(shRNA)and overexpression plasmid were used in Ishikawa and RL95-2 cell lines to knock down and overexpress SOS1-IT1.The mechanism of EZH2 expression regulation was studied using Real-time PCR,Western blotting,and chromatin immunoprecipitation.Results The expression of SOS1-IT1 and EZH2 genes was positively correlated in endometrial cancer tissues.Knocking down SOS1-IT1 significantly reduces the expression of EZH2,inhibited the proliferation and migration of Ishikawa and RL95-2 cells,and could reduced the acetylation of histone H3 at position 27(H3K27)and the enrichment of CREB binding protein(CBP)in the EZH2 gene promoter region.Overexpression of SOS1-IT1 could increased the expression of EZH2 and enhance the acetylation of H3K27 and the enrichment of CBP.CBP could bind to SOS1-IT1 RNA,and this binding ability was weakened when CBP was knocked down.Conclusion SOS1-IT1 can promote the expression level of EZH2 in endometrial cancer cells Ishikawa and RL95-2 by regulating the acetylation modification level of the EZH2 gene promoter region,thereby affecting the proliferation and migration ability of endometrial cancer cells.

Objective To investigate the mechanism by which artesunate(ART)attenuates intestinal mucosal barrier damage in acute graft-versus-host disease(aGVHD)and the synergistic effect of ART in combination with dexamethasone(DXM)in the treatment of aGVHD mice.Methods The aGVHD mouse model was established by bone marrow haematopoietic stem cell transplantation.The mice were divided into 9 groups,including normal mice control(Ctrl),aGVHD mice(aGVHD),normal mice receiving ART[30 mg/(kg·d)],aGVHD mice receiving low-dose ART[10 mg/(kg·d)],aGVHD mice receiving medium-dose ART[30 mg/(kg·d)],aGVHD mice receiving high-dose ART[50 mg/(kg·d)],aGVHD mice receiving DXM[20 mg/(kg·d)],aGVHD mice receiving ART[30 mg/(kg·d)]and DXM[20 mg/(kg·d)],and aGVHD mice receiving ART[30 mg/(kg·d)]and halved DXM[10 mg/(kg·d)].Survival rate and clinical parameters were assessed.HE staining and Alcian blue-periodic acid-Schiff(AB-PAS)staining were used to observe the histopathological changes in the intestinal mucosa of the mice;Real-time PCR,Western blotting and immunohistochemistry were used to detect the structure of the intestinal mucosal barrier,the T cell differentiation related transcription factors and cytokines,and the key enzymes of energy metabolism.Flow cytometry was used to detect the T helper cell 17(Th17)and regulatory T cells(Treg).Results After 30 days of ART treatment,aGVHD mice showed significant relief of systemic symptoms and increase in survival rate.In aGVHD mice treated with ART,the intestinal mucosal barrier structure was restored,and the intestinal mucosal permeability was reduced.The activity of AMP-activated protein kinase(AMPK)/mTOR pathway was inhibited,and the energy metabolism pattern of T cells was dominated by fatty acid synthesis.The balance of Th17/Treg was restored due to the decrease of Th 17 and the increase of Treg.The effect of ART+DXM treatment on aGVHD mice was comparable to that of DXM treatment alone,and the survival rate of mice was higher.In particular,the recovery of the intestinal mucosal barrier function was most obvious in the mice treated with ART+half-dose DXM.Conclusion ART reduces the immune injury of allo-T cells to the intestinal mucosal barrier by recovering the Th17/Treg balance,thus maintaining the integrity of the intestinal mucosal barrier function.The synergistic effect of ART and DXM combination treatment in aGVHD mice can reduce the incidence of DXM side effects by decreasing the dosage of DXM.

Objective To explore the mechanism of abnormal metastable dynamics in Alzheimer disease(AD)using brain network dynamic model based on MRI.Methods Data of MR T1WI diffusion tensor imaging(DTI)and resting-state functional MRI(rs-fMRI)of 25 AD patients(AD group)38 mild cognitive impairment(MCI)patients(MCI group)and 37 healthy controls(HC group)in AD Neuroimaging Initiative(ADNI)database were collected.Based on abnormal brain structural connectivity and cortical atrophy characteristics of AD group the structural virtual injury brain network model was constructed and the mechanism of abnormal metastable dynamics in AD was explored.Results The abnormal functional connectivity of white matter in AD group was concentrated in visual network(VIS)default mode network(DMN)frontoparietal network(FPN)and limbic network(LIM).The overall metastable state of AD group in sensorimotor network(SMN)dorsal attention network(DAN)&ventral attention network(VAN)(i.e.attention network[AN])and DMN specific perturbation models were all significantly lower than that in HC group and MCI group respectively(all P＜0.001).In AD group local circuits abnormality could be seen in posterior right superior temporal gyrus precentral gyrus caudal anterior cingulate gyrus and isthmus of the cingulate gyrus leading to decrease in global metastability.The structural connection damage of DMN and AN as well as cortical atrophy of FPN had significant impact on metastable dynamics in AD patients.Conclusion Multimodal MRI brain network dynamic model revealed the core factors of mechanism of metastable dynamic decline in AD included DMN AN and FPN abnormalities.