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*

The rare-earth-elements-doped upconversion nanoparticles NaYF4:Yb3+,Er3+were synthesized by solvothermal method,and NaYF4:Yb3+,Er3+@SiO2 were prepared by coating SiO2 on the surface of NaYF4:Yb3+,Er3+by inverse microemulsion method in this work.Based on the fluorescence quenching principle between NaYF4∶Yb3+,Er3+@SiO2 and SQA-Fe3+,a NaYF4∶Yb3+,Er3+@SiO2-SQA-Fe3+fluorescence nanosensor was constructed for detection of trace hydrogen peroxide(H2O2).Under optimal conditions,the linear range of this method for detecting H2O2 was 1.8?84.0 μmol/L,with detection limit(3σ)of 0.47 μmol/L.The recoveries of H2O2 spiked in milk were 98.4%?99.7%.This method could be used for detection of H2O2 residue in milk samples,with advantages such as low detection limit,good stability and strong anti-interference ability.

A purified polysaccharide with a galactose backbone(SPR-1,Mw 3,622 Da)was isolated from processed Polygonati Rhizoma with black beans(PRWB)and characterized its chemical properties.The backbone of SPR-1 consisted of[(4)-β-D-Galp-(1]9→ 4,6)-β-D-Galp-(1 → 4)-α-D-GalpA-(1 → 4)-α-D-GalpA-(1 →4)-α-D-Glcp-(1 → 4,6)-α-D-Glcp-(1 → 4)-α/β-D-Glcp,with a branch chain of R1:β-D-Galp-(1 → 3)-β-D-Galp-(1 → connected to the →4,6)-β-D-Galp-(1 → via O-6,and a branch chain of R2:α-D-Glcp-(1 →6)-α-D-Glcp-(1 → connected to the →4,6)-α-D-Glcp-(1 → via O-6.Immunomodulatory assays showed that the SPR-1 significantly activated macrophages,and increased secretion of NO and cytokines(i.e.,IL-1β and TNF-α),as well as promoted the phagocytic activities of cells.Furthermore,isothermal titration calorimetry(ITC)analysis and molecular docking results indicated high-affinity binding between SPR-1 and MD2 with the equilibrium dissociation constant(KD)of 18.8 μM.It was suggested that SPR-1 activated the immune response through Toll-like receptor 4(TLR4)signaling and downstream responses.Our research demon-strated that the SPR-1 has a promising candidate from PRWB for the TLR4 agonist to induce immune response,and also provided an easily accessible way that can be used for PR deep processing.

OBJECTIVE: To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI). METHODS: Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO₁₅) and Shen (CO₁₀), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores. RESULTS: The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036). CONCLUSION The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.
Humans ; Depression/therapy* ; Magnetic Resonance Imaging/methods* ; Vagus Nerve Stimulation/methods* ; Brain/diagnostic imaging* ; Transcutaneous Electric Nerve Stimulation/methods* ; Vagus Nerve

OBJECTIVES: To find a method to distinguish exogenous gamma-hydroxybutyrate (GHB) from endogenous GHB by establishing ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) based on exosome for quantitative detection of GHB in the rat blood. METHODS: Adult male SD rats were divided into 1 h, 5 h, 10 h administration group and control group. After 1 h, 5 h and 10 h of single precursor of GHB gamma-butyrolactone (GBL) intraperitoneal injection in administration groups, 5 mL blood was collected from the abdominal aorta. Meanwhile, the control group was given a same dose of normal saline, and 5 mL blood was collected at 1 h. Among the 5 mL blood, 0.5 mL was directly detected by HPLC-MS after pretreatment, and exosomes were extracted from the remaining blood by differential centrifugation and detected. RESULTS: The concentration of GHB in the control group was (87.36±33.48) ng/mL, and the concentration with administration at 1 h, 5 h and 10 h was (110 400.00±1 766.35) ng/mL, (1 479.00±687.01) ng/mL and (133.60±12.17) ng/mL, respectively. The results of exosome detection showed that no peak GHB signal was detected in the control group and the 10 h administration group, and the concentrations of GHB at 1 h and 5 h administration groups were (91.47±33.44) ng/mL and (49.43±7.05) ng/mL, respectively. CONCLUSIONS GHB was detected in blood exosome by UPLC-MS, which indicated that exogenous GHB could be detected in plasma exosomes, while endogenous GHB could not be detected, suggesting that this method may be used as a basis to determine whether there is exogenous drug intake.
4-Butyrolactone/chemistry* ; Animals ; Chromatography, Liquid ; Exosomes/chemistry* ; Hydroxybutyrates/chemistry* ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium Oxybate/analysis* ; Tandem Mass Spectrometry/methods*

The purpose of this study is to analyze the family's clinical data of 22 children who were given an intended clinical diagnosis of Duchenne muscular dystrophy (DMD), and to explore the clinical value of next-generation sequencing (NGS) in the molecular diagnosis of DMD. The probands were simultaneously tested by NGS for a gene panel associated with hereditary neuromuscular disease and multiplex ligation-dependent probe amplification (MLPA) for the Dystrophin gene. The exon deletion/repetition mutations of the Dystrophin gene determined by both methods were compared and the point mutations of the Dystrophin gene were verified by Sanger sequencing. Dystrophin gene mutations were found in all the 22 probands, including 14 exon deletion/repetition mutations and 8 point mutations/minor variations. The results of MLPA detection were consistent with those of NGS. The results of Sanger sequencing showed that the point mutations and minor variations determined by NGS were correct. One missense mutation (c.6290G>T), 1 nonsense mutation (c.3487C>T) and 4 minor deletion-induced frameshift mutations (c.1208delG, c.7497_7506delGGTGGGTGAC, c.9421_9422delAA and c.8910_8913delTCTC) had not been reported in the Human Gene Mutation Database, and thus were considered as novel mutations of the Dystrophin gene. The results of this study showed that NGS can detect variations in the Dystrophin gene, including exon deletion/repetition, point mutation, minor deletion and intron mutation. Therefore, NGS is of certain clinical value in the molecular diagnosis of DMD and is worthy of recommendation.
Dystrophin ; Exons ; High-Throughput Nucleotide Sequencing ; Humans ; Muscular Dystrophy, Duchenne ; Mutation

Objective To understand the potential risk of schistosomiasis transmission in Xiuzhou District of Jiaxing City, so as to provide the scientific evidence for consolidating schistosomiasis control achievements. Methods Fixed and mobile surveillance sites were set up in Xiuzhou District of Jiaxing City from 2013 to 2015. Oncomelania hupensis snails was surveyed historical snail habitats, current snail habitats, and suspected snail habitats. The schistosome infections were identified using serological and parasitological testing among local residents and mobile populations. In addition, the survival and reproduction of snails imported into Xiuzhou District was observed, and the schistosome infection in wild reservoir hosts was detected. Results A total of 540.14 hm² of settings were surveyed in Xiuzhou District, Jiaxing City from 2013 to 2015, and 1.65 hm² of snail habitats were identified. The snail habitats were mainly located in dry lands, and no infected snails or importation of snails were found. During the period from 2013 to 2015, a total of 7 668 local residents and mobile populations were examined in Xiuzhou District, and no new local infections were detected; however, three imported schistosomiasis cases were identified. Field simulation experiment showed that the imported snails laid eggs and reproduced in Xiuzhou District, and no schistosome infections were found in wild animals. Conclusion There are still residual Oncomelania snails and imported schistosomiasis patients in Xiuzhou District of Jiaxing City; therefore, the surveillance and management of local Oncomelania snails and imported schistosomiasis should be intensified to reduce the risk of schistosomiasis transmission.

Emerging evidence indicates that microglia activation plays an important role in spinal cord injury (SCI) caused by trauma. Studies have found that inhibiting the Rho/Rho-associated protein kinase (ROCK) signaling pathway can reduce inflammatory cytokine production by microglia. In this study, Western blotting was conducted to detect ROCK2 expression after the SCI; the ROCK Activity Assay kit was used for assay of ROCK pathway activity; microglia morphology was examined using the CD11b antibody; electron microscopy was used to detect microglia phagocytosis; TUNEL was used to detect tissue cell apoptosis; myelin staining was performed using an antibody against myelin basic protein (MBP); behavioral outcomes were evaluated according to the methods of Basso, Beattie, and Bresnahan (BBB). We observed an increase in ROCK activity and microglial activation after SCI. The microglia became larger and rounder and contained myelin-like substances. Furthermore, treatment with fasudil inhibited neuronal cells apoptosis, alleviated demyelination and the formation of cavities, and improved motor recovery. The experimental evidence reveals that the ROCK inhibitor fasudil can regulate microglial activation, promote cell phagocytosis, and improve the SCI microenvironment to promote SCI repair. Thus, fasudil may be useful for the treatment of SCI.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ; analogs & derivatives ; pharmacology ; therapeutic use ; Animals ; Apoptosis ; Male ; Microglia ; drug effects ; metabolism ; Myelin Basic Protein ; metabolism ; Myelin Sheath ; metabolism ; Phagocytosis ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; drug therapy ; rho-Associated Kinases ; antagonists & inhibitors ; metabolism

INTRODUCTIONPatients with metastatic nasopharyngeal carcinoma (NPC) have variable survival outcomes. We have previously shown that an elevated peripheral blood lymphocyte-to-monocyte ratio (LMR) is associated with an increased metastatic risk in patients with primary NPC. The present study aimed to investigate the prognostic value of pretreatment LMR in a large cohort of metastatic NPC patients.

METHODSClinical data of 672 patients with metastatic NPC diagnosed between January 2003 and December 2009 were analyzed. The peripheral lymphocyte and monocyte counts were retrieved, and LMR was calculated. Receiver operating characteristic (ROC) curve analysis and univariate and multivariate COX proportional hazards analyses were performed to evaluate the association of LMR with overall survival (OS).

RESULTSUnivariate analysis revealed that an elevated absolute lymphocyte count (≥1.390×10(9)/L) and LMR (≥2.475) as well as a decreased monocyte count (<0.665×10(9)/L) were significantly associated with prolonged OS. Multivariate Cox proportional hazard analysis showed that LMR (hazard ratio [HR]=0.50, 95% confidence interval [CI]=0.41-0.60, P<0.001), absolute lymphocyte count (HR=0.77, 95% CI=0.64-0.93, P=0.007), and monocyte count (HR=1.98, 95% CI=1.63-2.41, P<0.001) were independent prognostic factors. By stratification analyses, only LMR remained a significant predictor of prognosis.

CONCLUSIONWe identified pretreatment LMR as an independent prognostic factor for patients with metastatic NPC. Independent validation of our findings is needed.

Introduction:Patients with metastatic nasopharyngeal carcinoma (NPC) have variable survival outcomes. We have previously shown that an elevated peripheral blood lymphocyte-to-monocyte ratio (LMR) is associated with an increased metastatic risk in patients with primary NPC. The present study aimed to investigate the prognostic value of pretreatment LMR in a large cohort of metastatic NPC patients. Methods:Clinical data of 672 patients with metastatic NPC diagnosed between January 2003 and December 2009 were analyzed. The peripheral lymphocyte and monocyte counts were retrieved, and LMR was calculated. Receiver operating characteristic (ROC) curve analysis and univariate and multivariate COX proportional hazards analyses were performed to evaluate the association of LMR with overall survival (OS). Results:Univariate analysis revealed that an elevated absolute lymphocyte count (≥1.390 × 109/L) and LMR (≥2.475) as well as a decreased monocyte count (<0.665 × 109/L) were significantly associated with prolonged OS. Multivariate Cox proportional hazard analysis showed that LMR (hazard ratio [HR]=0.50, 95%confidence interval [CI]=0.41–0.60, P<0.001), absolute lymphocyte count (HR=0.77, 95%CI=0.64–0.93, P=0.007), and monocyte count (HR=1.98, 95%CI=1.63–2.41, P<0.001) were independent prognostic factors. By stratification analyses, only LMR remained a significant predictor of prognosis. Conclusion:We identified pretreatment LMR as an independent prognostic factor for patients with metastatic NPC. Independent validation of our findings is needed.