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*

Aim To investigate the mechanism by which sufentanil(Suf)improved hypoxia-reoxygen-ation(H/R)-induced myocardial cell injury by regula-ting hypoxia inducible factor-1α(HIF-1α)and KC-NQ1 opposite strand/antisense transcript 1(Kcnq1ot1).Methods Bioinformatics analysis was conducted to predict the interaction between HIF-1αand Kcnq1ot1.Subsequently,H9c2 cells were divided into multiple treatment groups:Ctrl group,H/R group,and Suf group.Further grouping was based on different transfection conditions,including oe-HIF-1α group,oe-HIF-1α+Suf group,sh-HIF-1α group,and sh-HIF-1α+Kcnq1ot1 group.Cell viability was detected u-sing the MTT assay,cell apoptosis was detected using the TUNEL assay,and the concentrations of CK-MB and HBDH in cell supernatants were measured using ELISA.HIF-1α protein expression in cellswas deter-mined by Western blot,and the mRNA expression level of Kcnq1ot1 was measured by reverse transcription quantitative PCR(RT-qPCR).Additionally,a rat model of myocardial is chemia reperfusion was con-structed to evaluate the therapeutic potential of Suf for myocardial ischemia reperfusion injury in vivo.Results The results of bioinformatics analysis showed a direct interaction between HIF-1α and Kcnq1ot1.Compared with the Ctrl group,the H/R group showed significantly reduced H9c2 cell viability,increased cell apoptosis,and significantly upregulated concentrations of CK-MB and HBDH,along with significantly enhanced expres-sion of HIF-1α and Kcnq1ot1(all P＜0.05).When H9c2 cells were transfected with oe-HIF-1 α,cell via-bility further decreased,apoptosis was worsened,and CK-MB and HBDH concentrations further increased(all P＜0.05);however,these adverse effects were significantly inhibited when combined with Suf inter-vention(all P＜0.05).Additionally,compared with the H/R group,the sh-HIF-1α group showed signifi-cantly improved cell viability,reduced apoptosis and decreased CK-MB and HBDH concentrations(all P＜0.05);however,these improvements were partially re-versed upon transfection with Kcnq1ot1(all P＜0.05).Animal experiments confirmed that Suf could improve myocardial ischemia-reperfusion injury in myo-cardial ischemia-reperfusion injury rats.Conclusions Suf improves myocardial H/R injury by inhibiting the HIF-1α-Kcnq1ot1.

Objective: To investigate the efficacy of therapeutic plasma exchange and rituximab in the treatment of passenger lymphocyte syndrome (PLS) after ABO incompatible liver transplantation. Methods: PLS diagnosis was performed on the transplant patient using immunohematology testing techniques such as direct anti human globulin test (DAT), red blood cell elution test, and blood type antibody titer detection, combined with changes in hemolysis laboratory indicators; Severe immune hemolysis caused by PLS treated with red blood cell transfusion, therapeutic plasma exchange, and rituximab. Results: The patient was diagnosed with PLS 9 days after transplantation, and hemolysis caused by PLS continued until 20 days after transplantation; After three rounds of therapeutic plasma exchange and treatment with 100 mg rituximab, the titer of the patient's immune blood type antibody (IgG anti-B) decreased from 128 to 8 and was maintained until 27 days after transplantation. The patient's hemolytic symptoms improved and were discharged 32 days after transplantation. Conclusion: This case explores the application of therapeutic plasma exchange and rituximab in the treatment of severe hemolysis in PLS after transplantation, providing a reference for establishing standardized management of PLS after solid organ transplantation.

Objective: To explore the effects of Cldn14 gene knockout on renal metabolism and stone formation in rats，so as to provide reference for research in the field of urinary calium metabolism and stone formation. Methods: Cldn14 gene knockout homozygous rats and wild-type rats of the same age were randomly divided into 4 groups：wild-type control (WC) group，wild-type ethylene glycol (WE) group，gene knockout control (KC) group and gene knockout ethylene glycol (KE) group，with 10 rats in each group.The WE and KE groups were induced with ethylene glycol + ammonium chloride to form kidney stones，while the WC and KC groups received normal saline gavage.After 4 weeks of standard maintenance feeding，the urine samples were collected to detect the venous blood.The kidneys were collected for HE，Pizzolatto's staining and transmission electron microscopy.The protein in renal tissues was extracted to detect the expressions of Claudin16 and Claudin19. Results: Crystal deposition was observed in the renal tubular lumen of the WE and the KE groups，and more crystals were detected in the KE group.The WE group had a large number of intracytoplasmic black crystalline inclusions observed in renal tubular epithelial cells under transmission electron microscope，followed by the KE and KC groups.Compared with WC and WE groups，KC and KE groups had significantly decreased serum calcium and magnesium levels but significantly increased urinary calcium level.In addition，the urinary calcium level was higher in the WE group than in the WC group and higher in the KE group than in the KC group.The KE group had lower level of Claudin16，but there was no significant difference in the level of Claudin19 among the 4 groups(P>0.05). Conclusion: Knockout of Cldn14 gene alone cannot effectively reduce urinary calcium excretion or reduce the risk of stone formation in rats，which may be related to the decrease of Claudin16 level.

Age-related macular degeneration (AMD) represents a predominant cause of blindness among older adults, with limited therapeutic options currently available. Oxidative stress, inflammation, and retinal pigment epithelium injury are recognized as key contributors to the pathogenesis of AMD. Regulated cell death plays a pivotal role in mediating cellular responses to stress, maintaining tissue homeostasis, and contributing to disease progression. Recent research has elucidated several regulated cell death pathways-such as apoptosis, ferroptosis, pyroptosis, necroptosis, and autophagy-that may contribute to the progression of AMD owing to cell death in the retinal pigment epithelium. These discoveries open new avenues for therapeutic interventions in patients with AMD. In this review, we provide a comprehensive summary and analysis of the latest advancements regarding the relationship between regulated cell death and AMD. Moreover, we examined the therapeutic potential of targeting regulated cell death pathways for the treatment and prevention of AMD, highlighting their roles as promising targets for future therapeutic strategies.

Objective To explore the mechanism by which electroacupuncture(EA)improves postherpetic neuralgia(PHN)by affecting the activation of microglia through the high mobility group box 1(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor kappa-B(NF-κB)signaling pathway.Methods Fifty SPF-grade SD rats were divided into the following groups:control(Vehicle)group,model(RTX)group,sham electroacupuncture(Sham-EA)group,electroacupuncture(EA)group,and electroacu-puncture+pathway inhibitor(EA+Gly)group.Behavioral tests in rats were conducted using mechanical withdrawal threshold testing,hot foot reflex latency testing,and tilt board testing.Hematoxylin-eosin(HE)staining was used to detect pathological morphological changes in the spinal dorsal horn tissue.TUNEL assay was used to detect cell apoptosis in the spinal dorsal horn tissue.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of pain-sensitive substances:prostaglandin E2(PGE2),substance P(SP),neurokinin 1(NK-1),and inflammatory factors:interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor α(TNF-α).Immunofluorescence was used to detect the expression of Iba1.Western blot was used to detect the expression of proteins involved in the HMGB1/TLR4/NF-κB pathway.Results Compared with Vehicle group,RTX group showed decreased mechanical withdrawal threshold,shortened hot foot reflex latency,reduced angle of balance on the tilt board,structural damage,disordered arrangement of nerve fibers,inflammatory cell infiltration,increased cell apoptosis rate,increased activation of microglia,and increased levels of PGE2,SP,NK-1,IL-6,IL-1β,TNF-α in the spinal dorsal horn tissue,with upregu-lated expression of HMGB1,TLR4,NF-κB p65 proteins(all P＜0.01).Compared with RTX group,no significant difference was observed in Sham-EA group(P＞0.05),while EA group showed increased mechanical withdrawal threshold,prolonged hot foot reflex latency,increased angle of balance on the tilt board,relieved morphological damage of nerve cells,more orderly arrangement,reduced in-flammatory cell infiltration,reduced cell apoptosis rate,reduced activation of microglia,and decreased levels of PGE2,SP,NK-1,IL-6,IL-1β,TNF-α in the spinal dorsal horn tissue,with downregulated expression of HMGB1,TLR4,NF-κB p65 proteins(all P＜0.01).Com-pared with EA group,EA+Gly group showed increased mechanical withdrawal threshold,prolonged hot foot reflex latency,increased angle of balance on the tilt board,reduced degree of morphological damage and disorder of nerve cells,reduced cell apoptosis rate,re-duced activation of microglia,and decreased levels of PGE2,SP,NK-1,IL-6,IL-1β,TNF-α in the spinal dorsal horn tissue,with down-regulated expression of HMGB1,TLR4,NF-κB p65 proteins(all P＜0.05).Conclusion EA exerts its therapeutic effect on PHN by in-hibition of HMGB1/TLR4/NF-κB signaling pathway and activation of microglia.

Objective To explore the mechanism by which electroacupuncture(EA)affects postherpetic neuralgia(PHN)through the cyclic cGMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)pathway in microglia-mediated processes.Methods Fifty rats were randomly divided into the following groups,with 10 rats in each group:Vehicle group,resiniferatoxin(RTX)group,RTX+EA group,RTX+cGAS inhibitor(RU.521)group,and RTX+STING inhibitor(C-176)group.Behavioral assessments were conducted on rats in each group using the hot plate test,inclined plane test,tail suspension test,and mechanical withdrawal threshold test.The ELISA method was used to detect the levels of substance P(SP),neurokinin 1(NK-1),tumor necrosis factor-α(TNF-α),inducible nitric oxide synthase(iNOS),interleukin-10(IL-10),and arginase 1(Arg1).TUNEL staining was used to detect cell apoptosis,and immunofluores-cence staining was used to detect the levels of Iba1,cGAS,and STING in the spinal dorsal horn tissues.Furthermore,Western blotting was used to detect the expression of cGAS-STING pathway-related factors.Results Compared with the Vehicle group,rats in the RTX group exhibited increased anxious behavior,decreased motor function,exacerbated depression,and reduced mechanical withdrawal thresholds.Additionally,there was an increase in the levels of pain-related neurotransmitters,enhanced cellular apoptosis,activation and M1 polar-ization of microglia in the spinal dorsal horn tissue,and activation of the cGAS-STING pathway.EA or cGAS-STING inhibitors partially reversed the above results and induced M2 polarization of microglia(all P＜0.05).Conclusion EA may exert therapeutic effects on PHN by inhibiting the cGAS-STING pathway in microglia.

Aim To investigate the mechanism by which sufentanil(Suf)improved hypoxia-reoxygen-ation(H/R)-induced myocardial cell injury by regula-ting hypoxia inducible factor-1α(HIF-1α)and KC-NQ1 opposite strand/antisense transcript 1(Kcnq1ot1).Methods Bioinformatics analysis was conducted to predict the interaction between HIF-1αand Kcnq1ot1.Subsequently,H9c2 cells were divided into multiple treatment groups:Ctrl group,H/R group,and Suf group.Further grouping was based on different transfection conditions,including oe-HIF-1α group,oe-HIF-1α+Suf group,sh-HIF-1α group,and sh-HIF-1α+Kcnq1ot1 group.Cell viability was detected u-sing the MTT assay,cell apoptosis was detected using the TUNEL assay,and the concentrations of CK-MB and HBDH in cell supernatants were measured using ELISA.HIF-1α protein expression in cellswas deter-mined by Western blot,and the mRNA expression level of Kcnq1ot1 was measured by reverse transcription quantitative PCR(RT-qPCR).Additionally,a rat model of myocardial is chemia reperfusion was con-structed to evaluate the therapeutic potential of Suf for myocardial ischemia reperfusion injury in vivo.Results The results of bioinformatics analysis showed a direct interaction between HIF-1α and Kcnq1ot1.Compared with the Ctrl group,the H/R group showed significantly reduced H9c2 cell viability,increased cell apoptosis,and significantly upregulated concentrations of CK-MB and HBDH,along with significantly enhanced expres-sion of HIF-1α and Kcnq1ot1(all P＜0.05).When H9c2 cells were transfected with oe-HIF-1 α,cell via-bility further decreased,apoptosis was worsened,and CK-MB and HBDH concentrations further increased(all P＜0.05);however,these adverse effects were significantly inhibited when combined with Suf inter-vention(all P＜0.05).Additionally,compared with the H/R group,the sh-HIF-1α group showed signifi-cantly improved cell viability,reduced apoptosis and decreased CK-MB and HBDH concentrations(all P＜0.05);however,these improvements were partially re-versed upon transfection with Kcnq1ot1(all P＜0.05).Animal experiments confirmed that Suf could improve myocardial ischemia-reperfusion injury in myo-cardial ischemia-reperfusion injury rats.Conclusions Suf improves myocardial H/R injury by inhibiting the HIF-1α-Kcnq1ot1.

Objective To explore the mechanism by which electroacupuncture(EA)improves postherpetic neuralgia(PHN)by affecting the activation of microglia through the high mobility group box 1(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor kappa-B(NF-κB)signaling pathway.Methods Fifty SPF-grade SD rats were divided into the following groups:control(Vehicle)group,model(RTX)group,sham electroacupuncture(Sham-EA)group,electroacupuncture(EA)group,and electroacu-puncture+pathway inhibitor(EA+Gly)group.Behavioral tests in rats were conducted using mechanical withdrawal threshold testing,hot foot reflex latency testing,and tilt board testing.Hematoxylin-eosin(HE)staining was used to detect pathological morphological changes in the spinal dorsal horn tissue.TUNEL assay was used to detect cell apoptosis in the spinal dorsal horn tissue.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of pain-sensitive substances:prostaglandin E2(PGE2),substance P(SP),neurokinin 1(NK-1),and inflammatory factors:interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor α(TNF-α).Immunofluorescence was used to detect the expression of Iba1.Western blot was used to detect the expression of proteins involved in the HMGB1/TLR4/NF-κB pathway.Results Compared with Vehicle group,RTX group showed decreased mechanical withdrawal threshold,shortened hot foot reflex latency,reduced angle of balance on the tilt board,structural damage,disordered arrangement of nerve fibers,inflammatory cell infiltration,increased cell apoptosis rate,increased activation of microglia,and increased levels of PGE2,SP,NK-1,IL-6,IL-1β,TNF-α in the spinal dorsal horn tissue,with upregu-lated expression of HMGB1,TLR4,NF-κB p65 proteins(all P＜0.01).Compared with RTX group,no significant difference was observed in Sham-EA group(P＞0.05),while EA group showed increased mechanical withdrawal threshold,prolonged hot foot reflex latency,increased angle of balance on the tilt board,relieved morphological damage of nerve cells,more orderly arrangement,reduced in-flammatory cell infiltration,reduced cell apoptosis rate,reduced activation of microglia,and decreased levels of PGE2,SP,NK-1,IL-6,IL-1β,TNF-α in the spinal dorsal horn tissue,with downregulated expression of HMGB1,TLR4,NF-κB p65 proteins(all P＜0.01).Com-pared with EA group,EA+Gly group showed increased mechanical withdrawal threshold,prolonged hot foot reflex latency,increased angle of balance on the tilt board,reduced degree of morphological damage and disorder of nerve cells,reduced cell apoptosis rate,re-duced activation of microglia,and decreased levels of PGE2,SP,NK-1,IL-6,IL-1β,TNF-α in the spinal dorsal horn tissue,with down-regulated expression of HMGB1,TLR4,NF-κB p65 proteins(all P＜0.05).Conclusion EA exerts its therapeutic effect on PHN by in-hibition of HMGB1/TLR4/NF-κB signaling pathway and activation of microglia.

Objective To explore the mechanism by which electroacupuncture(EA)affects postherpetic neuralgia(PHN)through the cyclic cGMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)pathway in microglia-mediated processes.Methods Fifty rats were randomly divided into the following groups,with 10 rats in each group:Vehicle group,resiniferatoxin(RTX)group,RTX+EA group,RTX+cGAS inhibitor(RU.521)group,and RTX+STING inhibitor(C-176)group.Behavioral assessments were conducted on rats in each group using the hot plate test,inclined plane test,tail suspension test,and mechanical withdrawal threshold test.The ELISA method was used to detect the levels of substance P(SP),neurokinin 1(NK-1),tumor necrosis factor-α(TNF-α),inducible nitric oxide synthase(iNOS),interleukin-10(IL-10),and arginase 1(Arg1).TUNEL staining was used to detect cell apoptosis,and immunofluores-cence staining was used to detect the levels of Iba1,cGAS,and STING in the spinal dorsal horn tissues.Furthermore,Western blotting was used to detect the expression of cGAS-STING pathway-related factors.Results Compared with the Vehicle group,rats in the RTX group exhibited increased anxious behavior,decreased motor function,exacerbated depression,and reduced mechanical withdrawal thresholds.Additionally,there was an increase in the levels of pain-related neurotransmitters,enhanced cellular apoptosis,activation and M1 polar-ization of microglia in the spinal dorsal horn tissue,and activation of the cGAS-STING pathway.EA or cGAS-STING inhibitors partially reversed the above results and induced M2 polarization of microglia(all P＜0.05).Conclusion EA may exert therapeutic effects on PHN by inhibiting the cGAS-STING pathway in microglia.