Background: Aspiration pneumonia (AP), which can be caused by gastric content inhalation into the lower airways, causes acute lung injury (ALI) through complex mechanisms, including inflammation, oxidative stress, and apoptosis. Here, we evaluated the efficacy of exosomes derived from human placental mesenchymal stem cells (hpMSCs) in mitigating ALI in a murine model of AP. We also investigated the role of hsa-let-7i-5p, the most abundant miRNA in hpMSC-derived exosomes, in this respect. Methods: Adult male C57BL/6 mouse AP models were administered hpMSC-derived exosomes (APExo group) or phosphate-buffered saline (AP group) intra-tracheally. After 48 h, the mice were euthanized and evaluated. The effects of hsa-let-7i-5p were assessed by specific inhibition or overexpression. Results: Compared with the APExo group, the AP group exhibited significantly greater ALI, as evidenced by histological damage, increased lung injury scores, impaired lung function, increased leukocyte infiltration, and elevated tissue edema (all P < 0.05). The untreated AP group also showed more inflammation, characterized by nuclear factor-κB upregulation, macrophage M1 polarization, and cytokine level elevation (tumor necrosis factor-α, interleukin-1β, and interleukin-6), as well as increased oxidation and activation of the apoptosis pathway (all P < 0.05). Notably, the therapeutic effects of hpMSC-derived exosomes were compromised by specific inhibition of hsa-let-7i-5p. Furthermore, engineered exosomes derived from genetically modified RAW264.7 overexpressing hsa-let-7i-5p demonstrated therapeutic effects against AP similar to those obtained with hpMSC-derived exosomes. Conclusions In a murine AP model, intra-tracheal administration of hpMSC-derived exosomes has ALI-mitigating effects, involving inflammation, oxidation, and apoptosis modulation, with hsa-let-7i-5p playing a pivotal mediating role.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

PURPOSE: The secondary damage of spinal cord injury (SCI) starts from the collapse of the blood spinal cord barrier (BSCB) to chronic and devastating neurological deficits. Thereby, the retention of the integrity and permeability of BSCB is well-recognized as one of the major therapies to promote functional recovery after SCI. Previous studies have demonstrated that activation of hypoxia inducible factor-1α (HIF-1α) provides anti-apoptosis and neuroprotection in SCI. Endogenous HIF-1α, rapidly degraded by prolylhydroxylase, is insufficient for promoting functional recovery. Dimethyloxalylglycine (DMOG), a highly selective inhibitor of prolylhydroxylase, has been reported to have a positive effect on axon regeneration. However, the roles and underlying mechanisms of DMOG in BSCB restoration remain unclear. Herein, we aim to investigate pathological changes of BSCB restoration in rats with SCI treated by DOMG and evaluate the therapeutic effects of DMOG. METHODS: The work was performed from 2022 to 2023. In this study, Allen's impact model and human umbilical vein endothelial cells were employed to explore the mechanism of DMOG. In the phenotypic validation experiment, the rats were randomly divided into 3 groups: sham group, SCI group, and SCI + DMOG group (10 rats for each). Histological analysis via Nissl staining, Basso-Beattie-Bresnahan scale, and footprint analysis was used to evaluate the functional recovery after SCI. Western blotting, TUNEL assay, and immunofluorescence staining were employed to exhibit levels of tight junction and adhesion junction of BSCB, HIF-1α, cell apoptosis, and endoplasmic reticulum (ER) stress. The one-way ANOVA test was used for statistical analysis. The difference was considered statistically significant at p < 0.05. RESULTS: In this study, we observed the expression of HIF-1α reduced in the SCI model. DMOG treatment remarkably augmented HIF-1α level, alleviated endothelial cells apoptosis and disruption of BSCB, and enhanced functional recovery post-SCI. Besides, the administration of DMOG offset the activation of ER stress induced by SCI, but this phenomenon was blocked by tunicamycin (an ER stress activator). Finally, we disclosed that DMOG maintained the integrity and permeability of BSCB by inhibiting ER stress, and inhibition of HIF-1α erased the protection from DMOG. CONCLUSIONS Our findings illustrate that the administration of DMOG alleviates the devastation of BSCB and HIF-1α-induced inhibition of ER stress.
Spinal Cord Injuries/pathology* ; Animals ; Apoptosis/drug effects* ; Amino Acids, Dicarboxylic/therapeutic use* ; Recovery of Function/drug effects* ; Rats ; Rats, Sprague-Dawley ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Male ; Spinal Cord/blood supply*

Erectile dysfunction (ED) is prevalent among men, but its relationship with dietary habits is uncertain. The aim of our study was to assess whether dietary patterns enhance erectile function by reviewing the literature published before August 1, 2022, via PubMed, Web of Science, and EMBASE databases. The data compiled included author details; publication dates, countries, treatments, patient numbers, ages, follow-ups, and clinical trial outcomes, such as ED cases, odds ratios (ORs), confidence intervals (CIs), and International Index of Erectile Function-5 (IIEF-5) scores with means and standard deviations. An analysis of 14 studies with 27 389 participants revealed that plant-based diets (OR = 0.71, 95% CI: 0.66-0.75; P < 0.00001), low-fat diets (OR = 0.27, 95% CI: 0.13-0.53; P = 0.0002), and alternative diets such as intermittent fasting and organic diets (OR = 0.54, 95% CI: 0.36-0.80; P = 0.002) significantly reduced ED risk. High-protein low-fat diets (hazard ratio [HR] = 1.38, 95% CI: 1.12-1.64; P < 0.00001) and high-carb low-fat diets (HR = 0.79, 95% CI: 0.55-1.04; P < 0.00001) improved IIEF-5 scores. Combined diet and exercise interventions decreased the likelihood of ED (OR = 0.49, 95% CI: 0.28-0.85; P = 0.01) and increased the IIEF-5 score (OR = 3.40, 95% CI: 1.69-5.11; P < 0.0001). Diets abundant in fruits and vegetables (OR = 0.97, 95% CI: 0.96-0.98; P < 0.00001) and nuts (OR = 0.54, 95% CI: 0.37-0.80; P = 0.002) were also correlated with lower ED risk. Our meta-analysis underscores a strong dietary-ED association, suggesting that low-fat/Mediterranean diets rich in produce and nuts could benefit ED management.
Humans ; Male ; Erectile Dysfunction/epidemiology* ; Diet ; Diet, Fat-Restricted ; Feeding Behavior ; Penile Erection/physiology* ; Diet, Vegetarian

OBJECTIVE: To investigate the whole-genome differential methylation profile of patients with high-altitude polycythemia (HAPC). METHODS: In this study, a total of 20 adult male patients with HAPC were included, including 10 Tibetan and 10 Han patients. The control group consisted of 20 healthy adult males, including 10 Tibetan and 10 Han patients. Peripheral blood was collected from each group for DNA extraction and quality inspection, and DNA libraries were constructed. The differential methylation regions (DMRs) between groups were detected using reduced representation bisulfite sequencing, with enriched regions compared to those of the control group. The differential enrichment regions were selected, and the intersection of the enriched regions was associated with genes. The methylation enrichment regions that differed significantly between groups were filtered based on the number of enriched samples in the enriched regions between the groups. GO, KEGG functional, and pathway analysis were performed on the differentially associated gene sets to reveal significant differences between the patients and control groups at the functional and pathway levels. RESULTS: In comparison with the control group, 17 152 sites with more than 25% difference and 15 558 sites with less than -25% difference were identified in Tibetan patients. The top 5 genes with the largest methylation differences between the two groups were MCCC2, RP3-399L15.3, ZNF621, RP11-394A14.2 and SLC39A10. The top significantly different pathways annotated in the differentially expressed genes pathway was serotonergic synapse. In comparison with the control group, 2 687 CpG sites with a greater than 25% difference and 2 602 CpG sites with a less than -25% difference were identified in Han patients. The top 5 genes with the largest methylation differences between the two groups were NAA25, CORO2B, PDC, ZNF853, and MLLT10. The top significantly different pathways annotated in the differentially expressed genes pathway were glutamatergic synapse, retrograde endocannabinoid signaling, Rap1 signaling pathway and cholinergic synapse. In comparison with the control group, 3 895 CpG sites with a greater than 25% difference and 3 969 CpG sites with a less than -25% difference were identified in HAPC patients. The maximum methylation difference between the two groups could reach 78.1%, while the minimum was -42.6%. The top 5 genes with the largest methylation differences between the two groups were MCCC2, ARSJ, CTNNA3, SLC39A10, and SWAP70. The top significantly different pathways annotated in the differentially expressed genes pathway was signaling pathways regulating pluripotency of stem cells. CONCLUSION The occurrence of HAPC may be related to abnormal changes in DNA methylation, and methylation sites may be helpful for the early diagnosis of HAPC.
Humans ; DNA Methylation ; Altitude ; Polycythemia/genetics* ; Male ; Adult ; CpG Islands

Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.
Dermatitis, Atopic/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Integrative Medicine ; Drugs, Chinese Herbal/therapeutic use* ; Practice Guidelines as Topic

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective:To investigate the clinical significance of monitoring SIL::TAL1 fusion transcripts in the evaluation of treatment response and prognosis of children with T-acute lymphoblastic leukemia (T-ALL).Methods:A retrospective cohort study was conducted to analyze the clinical data of 46 newly diagnosed pediatric T-ALL with SIL::TAL1 fusion transcripts treated at Beijing Children′s Hospital Capital Medical University from November 2004 to December 2022. The SIL::TAL1 fusion transcripts were quantitatively detected at the initial diagnosis (TP0) and early stage of induction therapy (TP1), at the end of induction remission therapy (TP2), before consolidation therapy (TP3) and subsequent treatment. Patients were divided into negative and positive groups on SIL::TAL1 fusion transcripts level, differences of clinical features and survival among groups at TP0 to TP3 were analyzed. The χ2 test or Fisher exact test or Mann-Whitney U test was used to compare the clinical difference. Survival analysis was estimated by Kaplan-Meier method with Log-Rank testing. Multivariate analysis was conducted by Cox proportional hazards models. Results:Among the 46 children with SIL::TAL1 fusion transcripts, 36 were males and 10 were females, with the onset age of 6.8 (3.4, 9.5) years. The negative rates of SIL::TAL1 fusion transcripts for TP1,TP2, TP3, before delayed intensification Ⅰ treatment (TP4), before maintenance therapy (TP5) were 36% (13/36), 78% (32/41), 76% (32/42), 15/16, and 12/12, respectively. No significant difference was found on clinical features and prednisone response between groups at TP0-TP3 (all P>0.05). The 5-year events free survival (EFS) rate of patients classified as negative (32 cases) and positive (9 cases) groups at TP2 was (78±8)% and (33±16)%, respectively ( χ2=9.86, P=0.002), the 5-year overall survival (OS) rate was (81±7)% and (44±17)%, respectively ( χ2=6.40, P=0.011). The 5-year EFS rate of patients classified as negative (32 cases) and positive (10 cases) groups at TP3 was (78±8)% and (30±15)%, respectively ( χ2=13.04, P<0.001) and the 5-year OS rate was (84±6)% and (30±15)%, respectively ( χ2=15.95, P<0.001). Cox multivariate regression showed that positive of SIL::TAL1 transcript at TP3 was adverse independent prognostic factors for EFS and OS (EFS: HR=6.70, 95% CI 2.01-22.35, P=0.002; OS: HR=10.73, 95% CI 2.50-46.09, P=0.001). Conclusions:Monitoring SIL::TAL1 fusion transcripts can reflect the clinical treatment response. The level of SIL::TAL1 fusion transcripts at early period can predict long-term outcomes of these patients.

Objective:To evaluate the effect of an electronic balance aid in balance rehabilitation training for patients with acute peripheral vestibular injury by comparing the outcomes of medication-only treatment and medication combined with vestibular rehabilitation using an electronic balance aid.Methods:This was a randomized controlled trial. The study subjects included 98 patients (40 males and 58 females, aged 25-69 years) diagnosed with idiopathic sudden sensorineural hearing loss (ISSNHL) with vertigo or vestibular neuritis, who were treated in the Department of Otorhinolaryngology-Head and Neck Surgery of Tianjin First Central Hospital from November 2022 to November 2023. All patients were randomly divided into the experimental group and the control group at a 1∶1 ratio using the sealed envelope method. Control group (conventional drug treatment): Patients received medication treatment for 2 weeks, including betahistine mesilate tablets, vitamin B1 tablets, methylcobalamin tablets, ginkgo biloba tablets, diphenhydramine hydrochloride injection (within 3 days of onset), metoclopramide hydrochloride injection, and glucocorticoids. Experimental group (conventional drug treatment+device training): On the basis of the same medication treatment as the control group, patients received vestibular rehabilitation training using an electronic balance aid (20 minutes per session, once a day,≥5 days per week, for a total of 2 weeks). SPSS software was used to compare the total scores of the Dizziness Handicap Inventory (DHI), the total scores of the Sensory Organization Test (SOT), and sensory analysis indicators between the two groups before and after treatment.Results:After treatment, vertigo symptoms significantly improved in both groups. DHI: The total DHI score in the control group decreased from 77.9±1.8 before treatment to 20.2±2.3 after treatment ( P<0.001). In the experimental group, the total DHI score decreased from 73.5±2.1 before treatment to 8.6±0.9 after treatment ( P<0.001). The difference in total DHI scores between the two groups after treatment was statistically significant, with the experimental group showing a lower score ( t=-4.616, P<0.001). The improvement in DHI scores was also more pronounced in the experimental group compared to the control group ( t=2.004, P=0.048). SOT: The total SOT score in the control group increased from 52.90±0.95 before treatment to 73.3±1.1 after treatment ( P<0.001). In the experimental group, the total SOT score increased from 54.9±0.8 before treatment to 83.5±0.9 after treatment ( P<0.001). The difference in total SOT scores between the two groups after treatment was statistically significant, with the experimental group showing a higher score ( t=7.104, P<0.001). The improvement in SOT scores was also more pronounced in the experimental group compared to the control group ( t=6.532, P<0.001). Sensory Analysis Indicators Proprioception (SOM): In the experimental group, the proprioception score significantly increased after treatment compared with before treatment ( t=-2.338, P=0.029), while, there was no statistically significant difference in the proprioception score of the control group before and after treatment ( P=0.537). Before treatment, there were no statistically significant differences in visual, vestibular, or visual dependence scores between the two groups (all P>0.05). After treatment, the visual, vestibular, and visual dependence scores of both groups significantly increased compared with those before treatment (all P<0.05); moreover, the post-treatment visual, vestibular, and visual dependence scores of the experimental group were significantly higher than those of the control group (all P<0.05). Conclusion:Compared with medication-only treatment, the combination of an electronic balance aid and medication for the treatment and rehabilitation training of patients with acute peripheral vestibular injury can significantly improve the therapeutic effect in the short term.