Objectives: . This study aimed to explore the role of the Pcdh15 gene in hearing maintenance and to examine the effects of its deficiency on cochlear structure, cochlear function, and hearing loss in mice. Methods: . CRISPR/Cas9 technology was used to generate Pcdh15 knockout (KO) mice. Auditory function was evaluated using hearing tests, while histological approaches were employed to assess morphological changes in cochlear hair cells and spiral ganglion neurons (SGNs). RNA sequencing (RNA-seq) was performed on cochlear tissue from postnatal day 18 (P18) wild-type (WT) and Pcdh15 KO mice to identify differentially expressed genes (DEGs). These DEGs were subjected to functional annotation and pathway analysis, with particular emphasis on oxidative phosphorylation (OXPHOS). Reactive oxygen species (ROS) levels were quantified using flow cytometry and DCFH-DA assays. Results: . Pcdh15 KO mice exhibited progressive sensorineural hearing loss, which worsened to profound deafness by P18. Notably, cochlear hair cells and SGNs showed substantial loss and pronounced morphological abnormalities, particularly within the basal high-frequency region. RNA-seq analysis identified 1,359 DEGs, including 1,024 downregulated and 335 upregulated genes. Pathway analysis indicated that Pcdh15 deficiency was associated with inhibition of the OXPHOS pathway, potentially disrupting mitochondrial respiratory chain complexes I, III, IV, and V and thereby impairing energy production and ATP metabolism. In addition, early-stage cochleae from KO mice demonstrated elevated ROS levels and increased oxidative stress, suggesting that redox imbalance may contribute to hearing damage. Conclusion . Pcdh15 plays a critical role in hearing maintenance. Its deficiency is associated with severe hearing loss and marked cochlear abnormalities, which are linked to inhibition of OXPHOS, disruption of energy metabolism, and exacerbation of oxidative stress. Together, these findings provide new insights into the mechanisms underlying hearing loss and suggest potential targets for therapeutic intervention.

Objective To explore the application effect of a standardized management method based on failure mode and effect analysis （FMEA） in optimizing the whole-process quality control system of the intravenous admixture service （PIVAS）. Methods The quality control management system of the PIVAS was optimized by establishing six quality control groups led by the head nurse, with full participation of pharmacy, nursing, and logistical staff, ensuring comprehensive coverage and traceability of all quality control links. Each group conducted risk priority number （RPN） scoring for potential failure modes in their respective quality control processes, and targeted improvement measures were formulated based on the scoring results. The RPN values of failure modes and quality control-related evaluation indicators before and after implementation were compared to achieve closed-loop management. Results After one year of management, the RPN values of the six major failure modes significantly decreased compared to those before implementation （P<0.05）. The compounding error rate dropped to 0.13%, the dispensing error rate decreased to 0.95%, the compounding efficiency increased to 98%, the delivery time was shortened by 0.45 h per batch, the intervention rate for irrational prescriptions rose to 94.87%, satisfaction improved to 96.78%, and the participation rate of quality control personnel reached 95.36% （P<0.05）. Conclusion FMEA-based identification of potential failure modes in the whole-process quality control system of the IVAS, combined with risk quantification and targeted interventions, significantly reduced high-risk failure modes, improved compounding accuracy and efficiency, and ensured the safety of clinical intravenous medication and the effectiveness of healthcare quality management.

Objective To explore the application effect of a standardized management method based on failure mode and effect analysis （FMEA） in optimizing the whole-process quality control system of the intravenous admixture service （PIVAS）. Methods The quality control management system of the PIVAS was optimized by establishing six quality control groups led by the head nurse, with full participation of pharmacy, nursing, and logistical staff, ensuring comprehensive coverage and traceability of all quality control links. Each group conducted risk priority number （RPN） scoring for potential failure modes in their respective quality control processes, and targeted improvement measures were formulated based on the scoring results. The RPN values of failure modes and quality control-related evaluation indicators before and after implementation were compared to achieve closed-loop management. Results After one year of management, the RPN values of the six major failure modes significantly decreased compared to those before implementation （P<0.05）. The compounding error rate dropped to 0.13%, the dispensing error rate decreased to 0.95%, the compounding efficiency increased to 98%, the delivery time was shortened by 0.45 h per batch, the intervention rate for irrational prescriptions rose to 94.87%, satisfaction improved to 96.78%, and the participation rate of quality control personnel reached 95.36% （P<0.05）. Conclusion FMEA-based identification of potential failure modes in the whole-process quality control system of the IVAS, combined with risk quantification and targeted interventions, significantly reduced high-risk failure modes, improved compounding accuracy and efficiency, and ensured the safety of clinical intravenous medication and the effectiveness of healthcare quality management.

Hemoglobin (Hb) concentration is a key clinical biomarker for diagnosing and managing anemia, ischemic stroke, perioperative blood loss, and chronic diseases such as renal failure. Traditional venous blood sampling remains the gold standard due to its high accuracy, but its invasive nature limits frequent testing, real time monitoring, and large scale screening. This has driven growing interest in non-invasive Hb detection technologies over the past decade. Among these, optical methods are the most promising because of their safety, potential for continuous monitoring, and compatibility with portable or wearable devices. This paper systematically reviews major advances in optical non invasive Hb detection from the last ten years. We focus on near-infrared spectroscopy branches—photoplethysmography (PPG) and dynamic spectrum (DS)—and also cover color analysis/RGB imaging, Raman spectroscopy, and photoacoustic spectroscopy. For each technology, we explain its detection principles, analyze advantages and limitations, and summarize optimization strategies reported in recent literature. PPG, based on pulsatile blood volume changes, underpins many commercial continuous monitors. However, its accuracy is constrained by motion artifacts, individual physiological variations (e.g., skin tone, tissue thickness), and low AC signal to noise ratio. In contrast, DS—an advanced derivative of PPG—uses a differential principle to extract absorbance changes between systolic and diastolic peaks. This theoretically eliminates interference from static tissues (skin, bone, venous blood) and common mode noise (e.g., ambient light), positioning DS as a more robust framework for high precision Hb quantification. Beyond spectral methods, color analysis/RGB imaging offers a hardware minimalist approach. By analyzing images of vascular rich, thin tissues (e.g., conjunctiva, nail beds, palms), it enables Hb estimation using smartphone cameras. Recent advances have shifted from manual RGB feature extraction to deep learning models and spectral super resolution that reconstruct hyperspectral data from RGB inputs, significantly improving screening accuracy. Our academic perspective emphasizes critical and integrative analysis. We highlight persistent challenges that hinder clinical translation: profound individual biological variability (skin optics, microvascular architecture), sensitivity to measurement conditions (pressure, ambient light), and a lack of standardized validation protocols and multi center trials. A central thesis is that no single optical method is universally superior; each involves trade offs between accuracy, complexity, cost, and practicality. Looking forward, we posit that the next performance leap will come from multimodal information fusion—combining PPG, electrocardiogram (ECG), bioimpedance, or different optical modalities to compensate for individual differences and environmental noise. AI and deep learning are essential not only for image analysis but also for automated, end to end feature extraction from complex waveforms like PPG sequences. Advancing hardware (tunable lasers, quantum dot LEDs, novel sensor designs) is crucial to improve signal fidelity and portability. Finally, we advocate for clinical scenario specific optimization and rigorous standardized evaluation frameworks to gain regulatory approval (e.g., FDA, NMPA) and achieve widespread clinical acceptance. In conclusion, this review synthesizes a decade of progress. Optical non-invasive Hb detection has evolved from proof of concept studies to emerging products and validated screening tools, but the journey toward reliable, clinic ready quantitative devices continues. The convergence of smarter algorithms, fused sensing modalities, and focused clinical validation offers the most promising path to transform this potential into routine medical practice, ultimately enabling personalized, continuous, and accessible hematological management.

With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.

BACKGROUND:The regulation of intestinal flora by exercise is closely related to human health,but intestinal flora involves many factors.Existing studies have lacked consistent evidence on the effect of exercise on the intestinal flora of college students. OBJECTIVE:To explore the effects of exercise on intestinal flora diversity and species composition of college students. METHODS:Through systematic search of PubMed,Web of Science,Embase,Medline,Cochrane Library,CNKI,WanFang Database and VIP database,eight empirical studies were selected and included,and semi-quantitative analysis was performed on them. RESULTS AND CONCLUSION:In terms of the species diversity of the intestinal flora,both high-intensity interval training and Tai Chi exercise significantly enhance the species diversity of intestinal flora in college students,while aerobic exercise does not have a significant effect on the enhancement of intestinal flora diversity in college students.In terms of the species composition of the intestinal flora,all three exercise modalities significantly alter the compositional structure of the intestinal flora in college students,which can increase the abundance of beneficial bacteria such as Ruminalococcus,Faecalis prevotelli,Blautia,and decrease the abundance of harmful bacteria such as Escherichia spp.Compared with high-intensity interval training,aerobic and Tai Chi exercise causes more elevated abundance of beneficial bacteria.In addition to changes in intestinal flora characteristics,exercise improves body composition,cardiorespiratory function,and executive function in college students,and these health benefits are closely linked to exercise-induced changes in intestinal flora that can produce health benefits for the body through metabolic regulation,barrier function,and neuromodulation.Although studies have confirmed the association between exercise and intestinal flora,the mechanism by which exercise affects intestinal flora has not yet been clarified,and at the same time,localizing the flora related to the host health is the key to targeting intestinal flora as a therapeutic target in the future,all of which are worthy of further attention and investigation.

OBJECTIVES: To investigate the relationship between the polygenic risks for various psychiatric disorders and clinical and neuropsychological characteristics in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Using a cross-sectional design, 285 children with ADHD and 107 healthy controls were assessed using the Child Behavior Checklist, the Behavior Rating Inventory of Executive Function for parents, the Wechsler Intelligence Scale for Children, Fourth Edition, and the Cambridge Neuropsychological Test Automated Battery. Blood samples were collected for genetic data. Polygenic risk scores (PRSs) for various psychiatric disorders were calculated using the PRSice-2 software. RESULTS: Compared with the healthy controls, the children with ADHD displayed significantly higher PRSs for ADHD, major depressive disorder, anxiety disorder, and obsessive-compulsive disorder (P<0.05). In terms of daily-life executive function, ADHD-related PRS was significantly correlated with the working memory factor; panic disorder-related PRS was significantly correlated with the initiation factor; bipolar disorder-related PRS was significantly correlated with the shift factor; schizophrenia-related PRS was significantly correlated with the inhibition, emotional control, initiation, working memory, planning, organization, and monitoring factors (P<0.05). The PRS related to anxiety disorders was negatively correlated with total IQ and processing speed index (P<0.05). The PRS related to obsessive-compulsive disorder was negatively correlated with the processing speed index and positively correlated with the stop-signal reaction time index of the stop-signal task (P<0.05). CONCLUSIONS PRSs for various psychiatric disorders are closely correlated with the behavioral and cognitive characteristics in children with ADHD, which provides more insights into the heterogeneity of ADHD.
Humans ; Attention Deficit Disorder with Hyperactivity/genetics* ; Child ; Male ; Female ; Cross-Sectional Studies ; Neuropsychological Tests ; Multifactorial Inheritance ; Adolescent ; Mental Disorders/etiology* ; Executive Function ; Genetic Risk Score

OBJECTIVE: To investigate the common mechanisms among collagen-induced arthritis (CIA), bleomycin (BLM)-induced pulmonary fibrosis, and CIA+BLM to evaluate the therapeutic effect of triptolide (TP) on CIA+BLM. METHODS: Thirty-six male Sprague-Dawley rats were randomly assigned to 6 groups according to a random number table (n=6 per group): normal control (NC), CIA, BLM, combined CIA+BLM model, TP low-dose (TP-L, 0.0931 mg/kg), and TP high-dose (TP-H, 0.1862 mg/kg) groups. The CIA model was induced by intradermal injection at the base of the tail with emulsion of bovine type II collagen and incomplete Freund's adjuvant (1:1), with 200 µL administered on day 0 and a booster of 100 µL on day 7. Pulmonary fibrosis was induced via a single intratracheal injection of BLM (5 mg/kg). The CIA+BLM model combined both protocols, and TP was administered orally from day 14 to 35. After successful modeling, arthritis scores were recorded every 3 days, and pulmonary function was assessed once at the end of the treatment period. Lung tissues were collected for histological analysis (hematoxylin eosin and Masson staining), immunohistochemistry, measurement of hydroxyproline (HYP) content, and calculation of lung coefficient. In addition, HE staining was performed on the ankle joint. Total RNA was extracted from lung tissues for transcriptomic analysis. Differentially expressed genes (DEGs) were compared with those from the RA-associated interstitial lung diseases patient dataset GSE199152 to identify overlapping genes, which were then used to construct a protein-protein interaction network. Hub genes were identified using multiple topological algorithms. RESULTS: The successfully established CIA+BLM rat model exhibited significantly increased arthritis scores and severe pulmonary fibrosis (P<0.01). By intersecting the DEGs obtained from transcriptomic analysis of lung tissues in CIA, BLM, and CIA+BLM rats with DEGs from rheumatoid arthritis-interstitial lung disease patients (GSE199152 dataset), 50 upregulated and 44 downregulated genes were identified. Through integrated PPI network analysis using multiple topological algorithms, IGF1 was identified as a central hub gene. TP intervention significantly improved pulmonary function by increasing peak inspiratory flow (P<0.01), and reduced lung index and HYP content (P<0.01). Histopathological analysis showed that TP alleviated alveolar collapse, interstitial thickening, and collagen deposition in the lung tissues (P<0.01). Moreover, TP treatment reduced the expression of collagen type I and α-SMA and increased E-cadherin levels (P<0.01). TP also significantly reduced arthritis scores and ameliorated synovial inflammation (P<0.05). Both transcriptomic and immunohistochemical analyses confirmed that IGF1 expression was elevated in the CIA+BLM group and downregulated following TP treatment (P<0.05). CONCLUSION TP exerts protective effects in the CIA+BLM model by alleviating arthritis and pulmonary fibrosis through the inhibition of IGF1-mediated EMT.
Animals ; Pulmonary Fibrosis/complications* ; Bleomycin/adverse effects* ; Phenanthrenes/pharmacology* ; Male ; Rats, Sprague-Dawley ; Diterpenes/pharmacology* ; Epoxy Compounds/therapeutic use* ; Arthritis, Experimental/complications* ; Insulin-Like Growth Factor I/metabolism* ; Rats ; Lung/physiopathology*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.