ObjectiveTo construct a standardized diagnostic scale for Qi-Yin deficiency with blood stasis syndrome in diabetic macrovascular disease. MethodsLiterature related to Qi-Yin deficiency with blood stasis syndrome in diabetic macrovascular disease was retrieved from CNKI， VIP， and Wanfang databases. Diagnostic information from four diagnostic methods was extracted and standardized， with items having a frequency of ≥15 included in the item pool. A three-round Delphi expert consultation was conducted， screening items using support degree， mean score， rank sum， and coefficient of variation. Item weights were determined using analytic hierarchy process （AHP）， gactor analysis （FA）， and combined weighting method （CWM）. The optimal weighting method was selected by comparing the area under the receiver operating characteristic （ROC） curve （AUC）. The Youden index was calculated to establish the diagnostic cutoff value， which was proportionally scaled. ResultsA total of 102 studies were included. Thirty-five items were incorporated into the item pool. The authority coefficients for the three Delphi rounds were 0.82， 0.85， and 0.86， with coordination coefficients of 0.648， 0.538， and 0.506， respectively. Fifteen items were retained after screening. ROC curve analysis showed the AUC ranking as FA > CWM > AHP. The maximum Youden index was 0.814， corresponding to a diagnostic cutoff of 8.361 （scaled to 40 points）. The final scale adopted a structured diagnostic framework： the symptom dimension requires at least 2 items， and the tongue or pulse dimension requires at least 1 category. ConclusionThis study developed a standardized diagnostic scale for Qi-Yin deficiency with blood stasis syndrome in diabetic macrovascular disease. Core items were screened via the Delphi method， with factor analysis identified as the optimal weighting method through AUC comparison. The diagnostic threshold （40 points） and structured diagnostic framework provide a quantitatively clear， clinically practical tool.

ObjectiveTo explore the establishment of a rat model of diabetic macrovascular atherosclerosis （DMA） with Qi and Yin deficiency syndrome induced by high-fat diet， streptozotocin （STZ）， and Yin-depleting herbs， and to evaluate its biological characteristics. MethodsForty SD rats were randomly divided into a blank group （n=10） and a modeling group （n=30）. Except for the blank group， rats in the model group were fed a high-fat diet for 4 weeks， followed by intraperitoneal injection of STZ （30 mg·kg^-1） to establish a diabetic model. Twenty-four successfully modeled diabetic rats were randomly divided into a model group （n=7）， a Qi and Yin deficiency syndrome group （n=8）， and a counter-syndrome group （n=9）. Except for the model group， rats received intragastric administration of Yin-depleting herbs （1.2 g·kg^-1） for 8 weeks. The counter-syndrome group was further treated with Shenqi compound formula （1.69 g·kg^-1） for an additional 8 weeks. General condition and body weight were recorded， and syndrome-related indicators were assessed， including precordial temperature， skin moisture content， grip strength， open-field test performance， and tongue appearance. Serum levels of vascular endothelial growth factor （VEGF）， endothelin-1 （ET-1）， vascular cell adhesion molecule-1 （VCAM-1）， insulin-like growth factor-1 （IGF-1）， and monocyte chemotactic protein-1 （MCP-1） were measured by enzyme-linked immunosorbent assay （ELISA）. Fasting blood glucose， blood lipids， hemorheological parameters， and coagulation function were analyzed using an automatic biochemical analyzer. Vascular ultrasound and hematoxylin-eosin （HE） staining were used to evaluate vascular lesions. ResultsIn terms of syndrome manifestations， compared with the blank group， body weight increased rapidly during the first 5 weeks in the model， Qi and Yin deficiency， and counter-syndrome groups. After STZ injection combined with Yin-depleting herbal administration at week 5， body weight decreased significantly （P<0.01） and continued to decline until the end of the experiment. Rats exhibited decreased activity， irritability， coarse and yellowish fur with obvious shedding， polydipsia， polyphagia， frequent urination， and dry stools， which were most pronounced in the Qi and Yin deficiency group. Grip strength decreased， peak activity time occurred earlier， total distance in the open-field test was reduced， and residence time was prolonged. Precordial temperature decreased （P<0.01）， while paw temperature increased （P<0.05）， and skin moisture and oil content were reduced （P<0.05， P<0.01）. In terms of disease-related indicators， compared with the blank group， fasting blood glucose was significantly increased （>16.7 mmol·L^-1） in the model and Qi and Yin deficiency groups， and blood lipid levels were significantly elevated （P<0.05）. Vascular-related factors ET-1， MCP-1， VCAM-1， and VEGF were significantly increased （P<0.05，P<0.01）， while IGF-1 was significantly decreased （P<0.01）. Pathological examination of the aortic valve showed valvular thickening and structural disorganization. Carotid artery examination revealed discontinuity of the intima， foam cell accumulation beneath the intima， disordered smooth muscle arrangement， and widened intercellular spaces. Compared with the model group， ET-1， MCP-1， and VEGF levels were significantly decreased in both the Qi and Yin deficiency group and the counter-syndrome group. The reductions in ET-1 and MCP-1 were more pronounced in the Qi and Yin deficiency group （P<0.01）， while the decrease in VCAM-1 was more significant in the counter-syndrome group （P<0.05）. Compared with the blank group， the Qi and Yin deficiency group showed significantly prolonged activated partial thromboplastin time （APTT）， thrombin time （TT）， and prothrombin time （PT） （P<0.01）. The erythrocyte deformability index （TK）， erythrocyte sedimentation rate， erythrocyte electrophoresis index， and whole blood low-shear viscosity all showed increasing trends. Vascular ultrasound revealed reduced arterial blood flow velocity， increased vascular resistance， and intimal thickening without plaque formation. The aortic intima showed no obvious overall thickening， with only occasional localized thickening and foam cell presence， and carotid artery injury was observed. ConclusionA rat model of DMA with Qi and Yin deficiency syndrome was successfully established using high-fat diet feeding combined with STZ injection and Yin-depleting herbal administration. Shenqi compound formula effectively alleviated Qi and Yin deficiency syndrome， regulated glucose and lipid metabolism， improved hemorheological and coagulation function， reduced vascular lesion severity， and demonstrated potential for early prevention and treatment of DMA.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

This study aimed to introduce a modified Byars staged procedure and investigate its application value in patients with severe hypospadias. We retrospectively analyzed the clinical data of patients with severe hypospadias admitted to the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between October 2012 and October 2022. In total, 31 patients underwent the conventional Byars procedure (conventional group), and 45 patients underwent the modified Byars staged procedure (modified group). Our modified strategy was built upon the standard Byars procedure by incorporating glansplasty during the first stage and employing a Y-shaped flap in conjunction with a glandular tunnel for urethroplasty during the second stage. Notably, there were no statistically significant differences in the preoperative baseline characteristics, duration of surgery, amount of blood loss, or occurrence of postoperative complications, including urethral fistula, stricture and diverticulum, or penile curvature, between the conventional and modified groups. However, there was a significantly lower incidence of coronal sulcus fistula (0 vs 16.1%, P = 0.02) and glans dehiscence (0 vs 12.9%, P = 0.02) in the surgical group than that in the conventional group. In addition, the modified group exhibited a notably greater rate of normotopic urethral opening (100.0% vs 83.9%, P = 0.01) and a higher mean score on the Hypospadias Objective Penile Evaluation (HOPE; mean ± standard error of mean: 8.6 ± 0.2 vs 7.9 ± 0.3, P = 0.02) than did the conventional group. In conclusion, the modified Byars staged procedure significantly reduced the risks of glans dehiscence and coronal sulcus fistula. Consequently, it offers a promising approach for achieving favorable penile esthetics, thereby providing a reliable therapeutic option for severe hypospadias.
Humans ; Hypospadias/surgery* ; Male ; Retrospective Studies ; Urologic Surgical Procedures, Male/methods* ; Child, Preschool ; Child ; Postoperative Complications/etiology* ; Urethra/surgery* ; Plastic Surgery Procedures/methods* ; Surgical Flaps ; Penis/surgery* ; Treatment Outcome ; Infant

OBJECTIVES: To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard. METHODS: Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard. RESULTS: Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively. CONCLUSIONS SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies ; Treatment Outcome ; Double-Balloon Enteroscopy/statistics & numerical data* ; Single-Balloon Enteroscopy/statistics & numerical data* ; Humans ; Male ; Female ; Child ; Operative Time ; Tomography, X-Ray Computed/statistics & numerical data* ; Sensitivity and Specificity ; Intestine, Small/surgery* ; Intestinal Diseases/surgery*

OBJECTIVES: To evaluate and integrate evidence on the management of sleep disorders in children with attention deficit hyperactivity disorder (ADHD). METHODS: Literature was retrieved based on the 6S model, and evidence related to sleep disorder management in children with ADHD was extracted from the included references. RESULTS: A total of 17 studies were included, from which 16 pieces of evidence were extracted. Of these, 6 were classified as Level 1 evidence and 10 as Level 5. The evidence covered screening, assessment, non-pharmacological interventions, pharmacological interventions, follow-up, and multidisciplinary collaboration. CONCLUSIONS This study integrated evidence on the management of sleep disorders in children with ADHD using an evidence-based approach, providing an evidence-based foundation for managing sleep disorders in this population.
Humans ; Attention Deficit Disorder with Hyperactivity/complications* ; Sleep Wake Disorders/etiology* ; Child ; Evidence-Based Medicine

OBJECTIVES: To study the effect of prophylactic phenytoin (PHT) or levetiracetam (LEV) on busulfan (BU) blood concentration in children undergoing hematopoietic stem cell transplantation. METHODS: Pediatric patients conditioned with BU plus cyclophosphamide and fludarabine at the First People's Hospital of Chenzhou from September 2023 to February 2025 were retrospectively included. Patients were grouped by prophylactic antiepileptic regimen into PHT (n=24) and LEV (n=26). BU blood concentrations at the end of infusion (0 hour) and at 1, 2, and 4 hours post-infusion were compared between groups. RESULTS: At 0 hour post-infusion, BU blood concentrations did not differ significantly between groups (P>0.05). At 1, 2, and 4 hours post-infusion, BU blood concentrations were higher in the LEV group than in the PHT group (P<0.05). The area under the concentration-time curve from 0 to ∞ (AUC_0-∞) was greater in the LEV group (P<0.001), and the attainment rate of AUC_0-∞ was higher in the LEV group than in the PHT group (73% vs 21%, P<0.001). No significant differences were observed between groups in time to hematopoietic engraftment or in the incidence of BU-related adverse drug reactions (P>0.05). CONCLUSIONS Compared with PHT, LEV prophylaxis is associated with higher BU blood concentration and a higher AUC_0-∞ attainment rate. There is no observed difference in BU efficacy or safety between PHT and LEV.
Humans ; Levetiracetam/therapeutic use* ; Busulfan/pharmacokinetics* ; Hematopoietic Stem Cell Transplantation ; Male ; Female ; Child ; Child, Preschool ; Phenytoin/pharmacology* ; Infant ; Retrospective Studies ; Anticonvulsants/pharmacology* ; Adolescent

Non-small cell lung cancer (NSCLC) ranks among the most lethal malignancies worldwide. The clinical application of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have successfully revolutionized the treatment paradigm for EGFR-mutant NSCLC, significantly prolonging progression-free survival and establishing EGFR-TKIs as the standard first-line therapy for advanced lung adenocarcinoma. However, acquired resistance remains a major obstacle to sustained clinical benefit, with mechanisms that are highly heterogeneous. A phenomenon of "oxidative stress compensation" is commonly observed in EGFR-TKIs-resistant cells, where in redox homeostasis, through the precise regulation of reactive oxygen species (ROS) generation and elimination, plays a pivotal role in maintaining the balance between tumor cell proliferation and apoptosis. This review aims to innovatively construct a theoretical framework describing how dynamic redox regulation influences resistance to third-generation EGFR-TKIs. It focuses on the multifaceted roles of ROS in both EGFR-dependent and EGFR-independent resistance mechanisms, and further explores therapeutic strategies that target ROS kinetic thresholds and antioxidant systems. These insights not only propose an innovative "metabolic checkpoint" regulatory pathway to overcome acquired resistance to third-generation EGFR-TKIs, but also lay a molecular foundation for developing the redox biomarker-based dynamic therapeutic decision-making systems, thereby facilitating a shift in NSCLC therapy from single-target inhibition toward multi-dimensional metabolic remodeling in the context of precision medicine.
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Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Drug Resistance, Neoplasm/drug effects* ; Lung Neoplasms/genetics* ; Oxidation-Reduction/drug effects* ; Homeostasis/drug effects* ; Protein Kinase Inhibitors/therapeutic use* ; Reactive Oxygen Species/metabolism* ; Animals

OBJECTIVE To explore the correlation between serum matrix metalloproteinase-2(MMP-2),interleukin-25(IL-25)expression and mast cell infiltration in patients with recurrent chronic sinusitis with nasal polyps(CRSwNP).METHODS Sixty patients diagnosed with recurrent CRSwNP in our hospital from October 2022 to March 2023 were selected as the CRSwNP group,and 60 patients diagnosed with simple Nasal septal deviation(NSD)in our hospital during the same period were selected as the NSD group.Compare the clinical data,mast cell count,and serum MMP-2 and IL-25 expression levels between two groups of patients.Use local weighted regression(Lowess)to analyze the correlation between MMP-2,IL-25 levels and mast cell count.Apply multiple logistic regression analysis to investigate the independent correlation between MMP-2,IL-25 levels and the risk of CRSwNP recurrence.Establish a restricted cubic spline(RCS)model to analyze the dose-response relationship between serum MMP-2,IL-25 levels and the risk of CRSwNP recurrence.Analyze the interaction and type of interaction between MMP-2,IL-25,and mast cell count on the risk of CRSwNP recurrence using an interaction calculation table.RESULTS The Lund Kennedy endoscopic score,Lund Mackay CT score,total VAS score,peripheral eosinophils,peripheral basophils,inhaled allergens,total IgE levels,smoking,alcohol consumption,and incidence of asthma,mast cell count,serum MMP-2 and IL-25 levels in the CRSwNP group were significantly higher than those in the NSD group,and the differences were statistically significant(P<0.05).Lowess analysis showed that there was a nonlinear relationship between MMP-2,IL-25 and mast cell count.MMP-2 and IL-25 were independently correlated with the recurrence of crswnp.RCS model analysis showed that MMP-2 and IL-25 levels had a nonlinear dose-response relationship with the recurrence risk of crswnp(Pfor non linear=0.002,0.008).The recurrence rates of crswnp corresponding to MMP-2,IL-25 and mast cell count in high-level group were 5.26%,12.54%and 19.08%,respectively,which were significantly higher than those corresponding to MMP-2,IL-25 and mast cell count in low-level group(55.91%,70.83%and 68.05%),and the difference was statistically significant(P<0.05).The results of interaction analysis showed that MMP-2,IL-25 and mast cell count had interaction in the additive model and the multiplicative model,showing a synergistic effect.CONCLUSION The levels of serum MMP-2 and IL-25 in CRSwNP recurrent patients are positively correlated with the degree of mast cell infiltration in the tissue.The higher the levels of MMP-2,IL-25 and Mast cell count,the higher the recurrence rate of CRSwNP.There was an independent correlation between MMP-2,IL-25 and recurrence of CRSwNP,which was a risk factor for recurrence of CRSwNP.

Panax species are mostly valuable medicinal plants. While some species' seeds are sensitive to dehydration, the dehydration tolerance of seeds from other Panax species remains unclear. The phospholipase D(PLD) gene plays an important role in plant responses to dehydration stress. However, the characteristics of the PLD gene family and their mechanisms of response to dehydration stress in seeds of Panax species with different dehydration tolerances are not well understood. This study used seeds from eight Panax species to measure the germination rates and PLD activity after dehydration and to analyze the correlation between dehydration tolerance and seed traits. Bioinformatics analysis was also conducted to characterize the PnPLD and PvPLD gene families and to evaluate their expression patterns under dehydration stress. The dehydration tolerance of Panax seeds was ranked from high to low as follows: P. ginseng, P. zingiberensis, P. quinquefolius, P. vietnamensis var. fuscidiscus, P. japonicus var. angustifolius, P. japonicus, P. notoginseng, and P. stipuleanatus. A significant negative correlation was found between dehydration tolerance and seed shape(three-dimensional variance), with flatter seeds exhibiting stronger dehydration tolerance(r=-0.792). Eighteen and nineteen PLD members were identified in P. notoginseng and P. vietnamensis var. fuscidiscus, respectively. These members were classified into five isoforms: α, β, γ, δ, and ζ. The gene structures, subcellular localization, physicochemical properties, and other characteristics of PnPLD and PvPLD were similar. Both promoters contained regulatory elements associated with plant growth and development, hormone responses, and both abiotic and biotic stress. During dehydration, the PLD enzyme activity in P. notoginseng seeds gradually increased as the water content decreased, whereas in P. vietnamensis var. fuscidiscus, PLD activity first decreased and then increased. The expression of PLDα and PLDδ in P. notoginseng seeds initially increased and then decreased, whereas in P. vietnamensis var. fuscidiscus, the expression of PLDα and PLDδ consistently decreased. In conclusion, the dehydration tolerance of Panax seeds showed a significant negative correlation with seed shape. The dehydration tolerance in P. vietnamensis var. fuscidiscus and dehydration sensitivity of P. notoginseng seeds may be related to differences in PLD enzyme activity and the expression of PLDα and PLDδ genes. This study provided the first systematic comparison of dehydration tolerance in Panax seeds and analyzed the causes of tolerance differences and the optimal water content for long-term storage at ultra-low temperatures, thus providing a theoretical basis for the short-term and ultra-low temperature long-term storage of medicinal plant seeds with varying dehydration tolerances.
Seeds/metabolism* ; Panax/physiology* ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant ; Phospholipase D/metabolism* ; Plants, Medicinal/enzymology* ; Germination ; Multigene Family ; Water/metabolism* ; Dehydration ; Phylogeny