To evaluate the therapeutic effect of a modified Devine procedure with a subcutaneous sliding fixation method for the treatment of congenital concealed penis, we retrospectively selected 45 patients with congenital concealed penises who were admitted to General Hospital of Ningxia Medical University (Yinchuan, China) between September 2020 and November 2023. In all cases, the penis was observed to be short, and retracting the skin at the base revealed a normal penile body, which immediately returned to its original position upon release. All patients underwent the modified Devine procedure with subcutaneous sliding fixation and completed a 12-week postoperative follow-up. A statistically significant increase in penile length was observed postoperatively, with the median length increasing from 4.0 (interquartile range [IQR]: 3.5-4.8; 95% confidence interval [CI]: 3.9-4.4) cm to 8.0 (IQR: 7.8-8.0; 95% CI: 7.7-7.9) cm, with P < 0.001. The parents were satisfied with the outcomes, including increased penile length, improved hygiene, and enhanced esthetics. Except for mild foreskin edema in all cases, no complications (such as infections, skin necrosis, or penile retraction) were observed. The edema was resolved within 4 weeks after the operation. This study demonstrates that the modified Devine procedure utilizing the subcutaneous sliding fixation method yields excellent outcomes with minimal postoperative complications, reduced penile retraction, and high satisfaction rates among patients and their families.
Humans ; Male ; Penis/abnormalities* ; Retrospective Studies ; Urologic Surgical Procedures, Male/methods* ; Treatment Outcome ; Child ; Plastic Surgery Procedures/methods*

OBJECTIVE: The aim of this study is to analyze the clinical features and genetic etiology of a patient with multiple morphological abnormalities of the sperm flagella (MMAF) retrospectively. METHODS: A severely oligospermic patient from the Reproductive Center of the First Affiliated Hospital of Ningbo University was selected as the study subject. Clinical data and examination results were collected. High-throughput sequencing and bioinformatics were used to analyze the genetic etiology. And Sanger sequencing was employed to validate findings in the family. Transmission electron microscopy (TEM) was used to observe the sperm ultrastructure, and immunofluorescence analysis was performed to examine the localization of FSIP2 protein in the sperm. RESULTS: The patient presented with severe oligospermia, and sperm morphology displayed MMAF. TEM revealed fibrous sheath and 9+2 microtubule structural disruptions in the sperm. Sequencing identified compound heterozygous variants in the FSIP2 gene (c.17798C > T, c.5927T > G), inherited from the father and mother, respectively. According to the guidelines of the American College of Medical Genetics and Genomics, the variants were classified as pathogenic. The patient's spouse underwent intracytoplasmic single sperm injection, resulting in one embryo, but no clinical pregnancy occurred after embryo transfer. CONCLUSION This study reported the mutation of FSIP2 gene c.17798C > T, c.5927T > G in a patient with MMAF. These findings expand the mutational spectrum of the FSIP2 gene and provide insights for genetic and assisted reproductive counseling for patients with MMAF.
Humans ; Male ; Sperm Tail/pathology* ; Heterozygote ; Oligospermia/genetics* ; Spermatozoa ; Mutation ; Infertility, Male/genetics* ; Adult ; Pedigree ; Retrospective Studies ; Sperm Injections, Intracytoplasmic

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVES: To explore the mechanism by which astragaloside IV (AS-IV) alleviates D-galactose (D-GAL)-induced senescence in human umbilical vein endothelial cells (HUVECs). METHODS: Cultured HUVECs were treated with D-GAL (40 g/L), AS-IV (200 μmol/L), D-GAL+AS-IV, or D-GAL+AS-IV+MTK458 (a mitochondrial autophagy agonist, 25 μmol/L) for 48 h, and the changes in cell proliferation, migration, and angiogenesis capacity were evaluated. Cell apoptosis, reactive oxygen species (ROS) levels, mitochondrial membrane potential, and expressions of autophagy-related proteins (LC3-II/LC3-I) and PINK1/Parkin pathway proteins in the treated cells were detected. RESULTS: AS-IV treatment significantly reduced the inhibitory effect of D-GAL on HUVEC viability, effectively alleviated D-GAL-induced impairment of tube-forming ability, and promoted angiogenesis and migration ability of the cells. AS-IV also significantly reduced the rate of D-GAL-induced HUVECs positive for senescence-associated β-galactosidase (SA-β-Gal) staining and inhibited the expression of senescence-related genes P21 and P53. AS-IV restored mitochondrial membrane potential and reduced intracellular ROS levels in D-GAL-induced HUVECs, and inhibited the fusion of autophagosomes and lysosomes to prevent the completion of autophagic flux. In HUVECs treated with both D-GAL and AS-IV, the application MTK458 significantly increased the number of yellow spots and enhanced the expressions of P21, P53, PINK1, Parkin, LC3, and Beclin proteins. CONCLUSIONS AS-IV alleviates D-GAL-induced endothelial cell senescence by inhibiting the PINK1/Parkin pathway to regulate mitochondrial autophagy.
Humans ; Human Umbilical Vein Endothelial Cells/drug effects* ; Cellular Senescence/drug effects* ; Autophagy/drug effects* ; Saponins/pharmacology* ; Ubiquitin-Protein Ligases/metabolism* ; Mitochondria/drug effects* ; Triterpenes/pharmacology* ; Protein Kinases/metabolism* ; Galactose/pharmacology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects* ; Cells, Cultured ; Apoptosis/drug effects* ; Membrane Potential, Mitochondrial ; Cell Proliferation/drug effects*

Melanoma is characterized by high malignancy, ranking the third among skin malignancies, and is associated with lack of specific treatment options and poor prognosis. Therefore, the development of effective therapies for melanoma is imperative. A critical challenge in addressing subcutaneous disease lies in overcoming the skin barrier. In this study, we engineered a microneedle (MN) system that integrates chemotherapy, photothermal therapy (PTT), and targeted therapy to enhance anti-tumor efficacy while effectively penetrating the skin barrier. In vitro studies have demonstrated that the MN drug delivery system (DDS) can effectively penetrate the stratum corneum of the skin, deliver therapeutics to subcutaneous tumor sites, and establish a drug reservoir at these locations to exert anti-tumor effects. Cellular experiments indicated that the engineered PTT chemotherapy-targeted MNs can be internalized by tumor cells, exhibiting enhanced cytotoxicity against them. In vivo pharmacological investigations revealed that the combination of PTT and chemotherapy delivered via this MN DDS produced synergistic anti-tumor effects, achieving a tumor inhibition rate of up to 98.15%. This in situ DDS minimizes involvement with other organs, significantly reducing chemotherapy-related side effects. In summary, the PTT chemotherapy-targeted MNs developed in this study demonstrate promising application potential by enhancing anti-tumor efficacy while minimizing adverse effects.

Most tumor cells and healthy neurons are at rest during G0 phase.Once the cell cycle is abnormally re-entered under certain conditions,the proliferation of tumor cells and the degenerative necrosis of neurons can be initiated.From the perspective of the cell cycle,cancer and central nervous system diseases,two seemingly different disease types,have a common pathogenesis.This type of diseases is named aberrant cell cycle diseases.As a newly discovered microRNA(miR),miR-1976 is closely related to the regulation of the cell cycle.This review summarizes the progress in the research on miR-1976 in cancer and central nervous system diseases,aiming to provide a reference for the clinical application of miR-1976 in aberrant cell cycle diseases in the future.
MicroRNAs/genetics* ; Humans ; Cell Cycle/genetics* ; Neoplasms/genetics* ; Central Nervous System Diseases/genetics*

Atrial fibrillation(AF)is the most common arrhythmia in clinical practice,with over 37 million people affected worldwide.AF may have great impacts on patients'cardiac function,cognitive function,quality of life,increase the risk of stroke,and raise the cardiovascular mortality.Therefore,early prediction of AF is crucial for reducing the risk of AF-related complications,early intervention,and improving patient prognosis.With the rapid development of artificial intelligence(AI)technology,its application in the medical field,especially in cardiology,has increasingly attracted great attention.In recent years,numerous studies have utilized various AI tools to analyze vast amounts of medical data,including clinical information and imaging parameters,trying to predict the occurrence,progression,and complications of AF,thereby providing a basis for clinical decision-making.However,despite certain progress,current research still faces multiple challenges,such as data privacy,model interpretability,the accuracy and rationality of parameter selection,and the clinical operability and feasibility of data implementation.Therefore,we aim to review the latest researches of AI in AF prediction,analyze the current application status,and discuss the future development,in order to provide references and insights for further research in related fields.

The traditional medical quality management model has many problems,such as excessive reliance on experience,poor coordination among departments,and lagging supervision,innovating medical quality management models has become an essential issue for the high-quality development of hospitals.A tertiary Grade A general hospital built a"data element multiplier"ecological chain for medical quality management,and established a complete closed-loop management system for medical quality management under the"Internet plus"model.Finally,the mobile medical quality management platform was built.Jointly driven by"Internet plus"and"data element multiplier",the level of lean management has been significantly improved,providing practical reference for hospitals at the same level.

Objective:To explore the molecular mechanism by which adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) inhibit hypertrophic scars (HS), and to identify the key functional miRNA and its downstream signaling pathway.Methods:A mouse model of hypertrophic scars was established by subcutaneous injection of bleomycin. The dorsal fibrotic modeling area was intervened with human ADSC-Exos (ADSC-Exos group), while the control group was injected with the same volume of PBS. HE and Masson staining were used to evaluate the morphological changes and collagen deposition of skin scar tissue in the two groups. Immunohistochemistry was performed to detect the expression of collagen 1 (Col-1) and α-smooth muscle actin (α-SMA). Western blot was used to determine the expression levels of key proteins in the transforming growth factor-β1 (TGF-β1)/Smad pathway (p-Smad2/3, Smad2/3). RNA sequencing datasets from the public database (GEO) were downloaded to analyze and screen differentially expressed miRNAs after ADSC-Exos treatment. In vitro cultured human hypertrophic scar fibroblasts (HSF) were transfected with miR-376b-5p mimic or inhibitor on the basis of ADSC-Exos treatment, and the expression of fibrosis markers (Col-1, α-SMA) as well as p-Smad2/3 and Smad2/3 was detected.Results:In vivo experiments showed that ADSC-Exos treatment significantly improved the fibrotic phenotype of mouse scar tissue, reduced the expression of Col-1 and α-SMA, and decreased the phosphorylation of Smad2/3 protein. Bioinformatics analysis revealed that miR-376b-5p was one of the most significantly upregulated miRNAs after ADSC-Exos treatment. In vitro experiments confirmed that overexpression of miR-376b-5p could mimic the antifibrotic effect of ADSC-Exos, significantly inhibit the expression of Col-1 and α-SMA in HSF, and reduce the phosphorylation level of Smad2/3. Specific inhibition of miR-376b-5p could effectively reverse the inhibitory effect of ADSC-Exos on the fibrotic phenotype of HSF and the phosphorylation of Smad2/3.Conclusions:This study reveals that ADSC-Exos exert their antifibrotic effect by mediating miR-376b-5p to target and inhibit the activation of the TGF-β1/Smad signaling pathway. miR-376b-5p is a key functional molecule in ADSC-Exos, and this finding provides a new potential target for the treatment of HS.