ObjectiveTo study the mechanism of Huanglian Jiedutang （HLJDT） in treating mice with atherosclerosis （AS） by improving ferroptosis. MethodsA total of 10 SPF C57BL/6J mice were selected as a normal group， and 50 ApoE^-/- mice were randomly divided into five groups： model group， low-dose group of HLJDT， medium-dose group of HLJDT， high-dose group of HLJDT， and atorvastatin （ATV） group. ApoE^-/- mice were fed a high-fat diet for eight weeks to establish the AS model， and at the 9th week， they were given normal saline， low， medium， and high doses of HLJDT （3.9， 7.8， 15.6 g·kg^-1·d^-1）， and atorvastatin calcium tablets （0.01 g·kg^-1·d^-1）， respectively， for a total of eight weeks. The formation of aortic plaque in mice was observed by gross oil red O staining and Masson staining. The levels of total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， triglyceride （TG）， and high-density lipoprotein cholesterol （HDL-C） in blood fat were measured by the automatic biochemical analyzer， and the mitochondrial structure of the aorta was observed by transmission electron microscopy. The content of serum superoxide dismutase （SOD） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. The content of reduced glutathione （GSH） in serum was detected by the microplate method， and that of malondialdehyde （MDA） in serum was detected by the TBA method. The protein expression of nuclear factor E₂-associated factor 2 （Nrf2）/glutathione peroxidase 4 （GPX4） signaling pathway was detected by Western blot. ResultsCompared with those of the normal group， the contents of TC， LDL-C， TG， HDL-C， and MDA in the serum and the aortic vascular plaque deposition of the model group were significantly increased （P<0.01）， while the expression levels of SOD and GSH in serum， as well as Nrf2， solute carrier family 7 member 11 （SLC7A11）， and GPX4 in aorta were significantly decreased （P<0.01）. Mice in the model group appeared mitochondrial fragmentation and vacuolation in the aorta， volume atrophy， mitochondrial crista reduction， or a loose and disorganized form. Compared with those in the model group， the aortic vascular plaque deposition was significantly decreased in the low-dose， medium-dose， and high-dose groups of HLJDT and ATV group， and the contents of serum TC， LDL-C， TG， and MDA in serum were significantly decreased （P<0.05， P<0.01）. The contents of serum SOD and GSH and the expression levels of Nrf2， SLC7A11， and GPX4 in the aorta were increased （P<0.05， P<0.01）， and the symptoms of aortic mitochondrial vacuolation were alleviated. The number of cristae was increased， and they were ordered neatly. ConclusionHLJDT can reduce aortic vascular plaque deposition， decrease blood lipid and MDA expression， increase SOD and GSH expression， and ameliorate the pathological changes of ferroptosis， the mechanism of which is related to the Nrf2/GPX4 signaling pathway.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

The interleukin-10 （IL-10） family is expressed in various types of cells and has a wide range of biological functions， and it plays an important role in the development and progression of hepatic fibrosis. Hepatic fibrosis is a chronic liver disease characterized by abnormal repair of hepatic tissues after injury， activation of hepatic stellate cells， and excessive accumulation of extracellular matrix. The IL-10 family members include IL-10， IL-19， IL-20， IL-22， IL-24， IL-26， IL-28， IL-29， and IL-35， with similarities in structure and function， and changes in their expression levels are closely associated with the progression of hepatic fibrosis. Moderate upregulation of the expression of IL-10 family members can help maintain the quiescent state of hepatic stellate cells， promote the transformation of macrophages to anti-inflammatory phenotype， and regulate the activity of natural killer cells， thereby inhibiting inflammatory response， regulating cell apoptosis and autophagy， and finally reversing the progression of hepatic fibrosis. This article discusses the mechanism of action of IL-10 family members and their application in traditional Chinese medicine and Western medicine therapies， in order to provide new thoughts for the treatment of hepatic fibrosis.

In most types of erectile dysfunction, particularly in advanced stages, typical pathological features observed are reduced parenchymal cells coupled with increased tissue fibrosis. However, the current treatment methods have shown limited success in reversing these pathologic changes. Recent research has revealed that changes in autophagy levels, along with alterations in apoptosis and fibrosis-related proteins, are linked to the progression of erectile dysfunction, suggesting a significant association. Autophagy, known to significantly affect cell fate and tissue fibrosis, is currently being explored as a potential treatment modality for erectile dysfunction. However, these present studies are still in their nascent stage, and there are limited experimental data available. This review analyzes erectile dysfunction from a pathological perspective. It provides an in-depth overview of how autophagy is involved in the apoptotic processes of smooth muscle and endothelial cells and its role in the fibrotic processes occurring in the cavernosum. This study aimed to develop a theoretical framework for the potential effectiveness of autophagy in preventing and treating erectile dysfunction, thus encouraging further investigation among researchers in this area.
Male ; Humans ; Autophagy/physiology* ; Apoptosis/physiology* ; Erectile Dysfunction/physiopathology* ; Fibrosis ; Penis/pathology* ; Animals ; Endothelial Cells/pathology* ; Myocytes, Smooth Muscle/pathology*

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017-2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 10 6 (0.09 × 10 6 -0.27 × 10 6 ) ml and 12.21 × 10 6 (4.52 × 10 6 -19.91 × 10 6 ) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
Humans ; Male ; Adult ; Semen Analysis ; China ; Body Fat Distribution ; Longitudinal Studies ; Sperm Count ; Sperm Motility ; Body Mass Index ; Tissue Donors ; Obesity/complications* ; Spermatozoa ; Young Adult ; Middle Aged ; East Asian People

Objective To construct a targeted drug delivery system, Ang-BEVs@Dox, based on Angiopep-2 peptide-modified bacterial extracellular vesicles （BEVs） loaded with doxorubicin （Dox）, overcome the challenges of blood-brain barrier （BBB） penetration and systemic toxicity in chemotherapy for glioblastoma （GBM）, enhance drug targeting to brain tumors and reduce its toxic side effects. Methods BEVs derived from Escherichia coli were isolated using ultracentrifugation. The targeting ligand Angiopep-2, specific for the LRP-1 receptor, was conjugated onto the surface of BEVs to construct the targeted carrier （Ang-BEVs）. Dox was loaded into Ang-BEVs using low-frequency sonication to form Ang-BEVs@Dox. The physicochemical properties （morphology and size） of the carriers were characterized by transmission electron microscopy （TEM） and dynamic light scattering （DLS）. The BBB-penetrating capability, in vitro/in vivo anti-tumor efficacy, and biosafety of the system were evaluated using cellular uptake assays, 3D tumor spheroid models, and orthotopic tumor-bearing mouse models. Results ① Carrier characterization and in vitro efficacy: Ang-BEVs@Dox exhibited a particle size of approximately 100 nm and maintained structural stability after Dox loading. It significantly enhanced cellular uptake efficiency in U87MG cells and achieved deep penetration within 3D tumor spheroids. Cytotoxicity assays demonstrated synergistic anti-tumor effects between the BEVs and Dox in the Ang-BEVs@Dox system. ② In vivo targeting and anti-tumor efficacy: In orthotopic tumor-bearing mouse models, Ang-BEVs@Dox effectively penetrated the BBB and significantly inhibited tumor growth, extending the median survival time of tumor-bearing mice to 33.5 days （compared to 23.5 days in the blank control group, P<0.001）. Immunohistochemical analysis revealed significant suppression of the tumor cell proliferation marker Ki-67 and enhancement of the apoptosis marker TUNEL staining signals. ③ Biosafety: Major organs from mice in the Ang-BEVs@Dox treatment group showed no observable pathological damage, indicating good biosafety. Conclusion This study successfully constructed an Angiopep-2 peptide-modified engineered BEVs delivery system （Ang-BEVs@Dox）. Through Angiopep-2-mediated BBB penetration and tumor targeting, it significantly enhanced the accumulation and therapeutic efficacy of BEVs at the GBM site. This method combined efficient delivery, low systemic toxicity, and clinical translation potential, which provided an innovative solution to overcome the therapeutic bottleneck in GBM treatment.