To investigate the impact of preoperative serum follicle-stimulating hormone (FSH) levels on the probability of testicular sperm retrieval, we conducted a study of nonobstructive azoospermic (NOA) men with different testicular volumes (TVs) who underwent microdissection testicular sperm extraction (micro-TESE). A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital, Shenzhen, China) were retrospectively reviewed. The subjects were divided into four groups based on average TV quartiles. Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups. Overall sperm retrieval rate was 57.6%. FSH levels (median [interquartile range]) were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was <5 ml (first quartile [Q1: TV <3 ml]: 43.32 [17.92] IU l -1 vs 32.95 [18.56] IU l -1 , P = 0.048; second quartile [Q2: 3 ml ≤ TV <5 ml]: 31.31 [15.37] IU l -1 vs 25.59 [18.40] IU l -1 , P = 0.042). Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were <5 ml (adjusted odds ratio [OR]: 1.06 per unit increase; 95% confidence interval [CI]: 1.01-1.11; P = 0.011). In men with TVs ≥5 ml, larger TVs were associated with lower odds of sperm retrieval (adjusted OR: 0.84 per 1 ml increase; 95% CI: 0.71-0.98; P = 0.029). In conclusion, elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs <5 ml. In men with TV ≥5 ml, increases in average TVs were associated with lower odds of sperm retrieval.
Humans ; Male ; Azoospermia/surgery* ; Sperm Retrieval/statistics & numerical data* ; Adult ; Follicle Stimulating Hormone/blood* ; Retrospective Studies ; Testis/pathology* ; Microdissection ; Organ Size

The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Objective To discuss the effect of interleukin-17A(IL-17A)and transforming growth factor-β1(TGF-β1)on the benign tracheal stenosis after tracheal injury in experimental dogs.Methods The trachea stenosis model of healthy Beagle dogs was established by burning the middle part of trachea with electric snare under bronchoscopy guidance.A total of 21 dogs were divided into normal group(n=3,receiving normal feeding),molding group(n=12,after airway modeling every 3 dogs were sacrificed each week for 4 weeks),IL-17A suppression group(n=3,receiving Secukinumab after airway modeling),and IL-17A inhibitor+TGF-β1 inhibitor group(n=3,receiving Secukinumab and SB43154 after airway modeling).Bronchoscopy and CT scan were performed once a week,and the stenosis degree was calculated.RT-qPCR,immunohistochemistry,and HE staining of the obtained tracheal tissues were performed.Results Within 1-4 weeks after molding,in module-making dogs the degree of stenosis of the injured trachea gradually increased,and the expressions of ECM-related proteins,TGF-β1 and IL-17A were up-regulated.After treatment with IL-17A inhibitors,the inflammatory infiltration and granulation tissue hyperplasia were reduced and the early tracheal stenosis was improved(P＜0.05).The combination use of IL-17A inhibitor and TGF-β1 inhibitor had a better remission effect(P＜0.05).Conclusion IL-17A and TGF-β1 may synergistically affect the formation of tracheal stenosis.

The efficient,precise,and rapid detection of trace copper ions(Cu2+)is of paramount importance in the realms of food safety,environmental monitoring,and medical health.By ingeniously utilizing the chemical properties of benzotriazole compounds in copper protection,and introducing an electrochemical reduction strategy,a silver nanoparticle composite structure supported by a nickel foam substrate was developed as an active platform for surface-enhanced Raman scattering(SERS)detection.This platform employed benzotriazole-5-carboxylic acid(BTAC)as a specific SERS probe molecule to achieve sensitive analysis of metal ion concentrations.The detection mechanism revealed a highly selective coordination between the Cu2+and the nitrogen atom in the triazole ring of BTAC,triggering subtle structural changes in the triazole ring.This was manifested by a significant and quantifiable shift in the characteristic peak of the SERS spectrum(particularly at 1001 cm-1),with a maximum shift of up to 30 cm-1.This phenomenon not only addressed the issue of reproducibility in quantitative analysis caused by the non-uniformity of SERS substrate materials but also significantly broadened the application boundaries of SERS technology for trace metal ion detection.It enabled ultra-sensitive detection of Cu2+concentrations ranging from 1×10-6 to 1×10-11 mol/L,with a detection limit as low as 1×10-11 mol/L,significantly enhancing detection sensitivity and accuracy.This work provided a novel and efficient strategy for rapid detection of trace Cu2+and enriched the application potential of SERS technology in food safety,environmental monitoring and biomedical analysis.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To evaluate the feasibility of using the domestic ArcherQA system for fast and simplified independent verification of CyberKnife (CK) stereotactic radiotherapy (SRT) plans.Methods:SRT plans of 57 patients treated with CK at Tianjin Medical University Cancer Institute and Hospital from August 2021 to August 2022 were retrospectively analyzed, including 15 intracranial, 30 pulmonary, and 12 abdominal tumors cases. Point-dose and planar-dose verifications were performed using an ionization chamber and radiochromic films embedded in a homogeneous phantom, and the results were compared with those calculated by the treatment planning system (TPS). The localization CT images and corresponding SRT plans were imported into the ArcherQA system for independent dose verification and analysis. The correlation between ArcherQA results and phantom measurements was analyzed, with comparisons of target mean dose differences and γ pass rates.Results:Phantom measurement results showed, the measured point-dose differences for intracranial, lung, and abdominal plans were -0.94% ± 3.22%, 1.92% ± 2.05%, and 2.12% ± 0.77%, respectively. The mean dose differences in target dose calculation between ArcherQA and TPS: intracranial in the gross tumor volume (GTV) regions were 0.34% ± 2.21%, lung tumor GTV were -2.47% ± 2.46%, and abdominal tumor GTV were 0.80% ± 2.61%, respectively. Among them, the abdominal GTV region showed the highest correlation between ArcherQA and measured results ( r=0.78). The average two-dimensional γ pass rates (2 mm/2%, threshold=10%) measured using phantom films were 95.92% ± 2.35% for intracranial, 95.70% ± 2.74% for lung, and 96.74% ± 3.41% for abdominal tumors plans, respectively. The three-dimensional ArcherQA results showed comparable γ pass rates (1 mm/2%, threshold=10%) for lung and abdominal GTV and PTV regions, with similar medians and data dispersion to film measurements. Conclusions:The ArcherQA system enables rapid and efficient independent dose verification of CK SRT plans without the need for additional hardware. The verification results show good correlation with phantom measurements, supporting its potential as an auxiliary quality assurance tool in clinical CK SRT implementation.

Objective:To investigate effect and mechanism of hydroxysafflor yellow A(HSYA)activating neuronal autophagy on cerebral ischemia-reperfusion injury through a combination of in vitro and in vivo experiments.Methods:SD rat MCAO/R model was established by improved suture method.Rats were randomly divided into sham surgery(Sham)group,MCAO/R group and MCAO/R+HSYA group,following indicators were detected to determine extent of cerebral ischemia-reperfusion nerve damage:Z-Longa neu-rological function score was detected,TTC staining to measure cerebral infarction area,and TUNEL staining to measure cell apopto-sis;Western blot was used to detect protein expressions of autophagy related markers LC3,Beclin1,P62 and SIRT1 in rat brain tis-sue;immunofluorescence staining was used to observe expression of LC3 co-localization with neurons.OGD/R injury model of SH-SY5Y cells was established and randomly divided into Normal group,OGD/R group,OGD/R+HSYA group,OGD/R+SIRT1 inhibitor(EX-527)group and OGD/R+EX-527+HSYA group.Western blot was used to detect protein expressions of LC3,Beclin1,P62 and SIRT1.Results:Compared with Sham group,model group rats showed impaired neurological function,significantly increased neu-robehavioral scores,widespread cerebral infarction,significantly increased neuronal cell apoptosis,significantly increased autophagy related protein Beclin1 expression and LC3-Ⅱ/LC3-Ⅰ,significantly decreased P62 expression,significantly increased LC3/NeuN co-stained cells,and decreased SIRT1 expression;compared with model group,HSYA intervention group showed a significant decrease in neurological functional scores,a significant reduction in cerebral infarction area,a significant decrease in neuronal cell apoptosis,a further increase in Beclin1 expression and LC3-Ⅱ/LC3-Ⅰ,a further decrease in P62 expression,number of LC3/NeuN and P62/NeuN co-stained cells also increased,and SIRT1 expression significantly increased.Expression trends of Beclin1,LC3-Ⅱ/LC3-Ⅰ,P62 and SIRT1 of cells between normal group,model group and HSYA intervention group were same as animal experiment;compared with model group,expressions of SIRT1,Beclin1 and LC3-Ⅱ/LC3-Ⅰ in OGD/R+EX-527 group were significantly reduced,while expression of P62 was significantly increased;compared with OGD/R+EX-527 group,there was no significant change in SIRT1 expression in OGD/R+EX-527+HSYA group,LC3-Ⅱ/LC3-Ⅰ and Beclin1 expression were significantly increased,and P62 expres-sion was significantly decreased.Conclusion:HSYA can significantly improve neurological deficits in rats after cerebral ischemia-reperfusion,reduce cerebral infarction area,and decrease neuronal cell apoptosis rate,whose neuroprotective effect may be related to its activation of SIRT1,which significantly enhances neuronal autophagy.

Objective To investigate the mechanism of Naringenin(NGN)in the treatment of steroid(glucosteroid)-induced osteonecrosis of the femoral head(SONFH).Methods A SONFH rat model was established using Methylprednisolone(MPS)treatment,followed by intervention with NGN and zinc protoporphyrin(ZnPP).Micro-CT was used to analyze the morphological changes in femoral head tissues,and the levels of osteocalcin(OCN)in rat serum as well as heme oxygenase-1(HO-1)and hypoxia-inducible factor-1α(HIF-1α)in femoral bone tissue were measured.A cellular model was constructed by treating MC3T3-E1 cells with Dexamethasone(DEX),followed by NGN intervention.Bioinformatics analysis combined with molecular docking technology was used to predict the target of NGN,and the Pulldown experiment was performed for validation.The expression of HO-1 was knocked down through cell transfection,to analyze the viability,proliferation,apoptosis,and migration of MC3T3-E1 cells,and angiogenesis assays were conducted to evaluate the angiogenic potential of human umbilical vein endothelial cells(HUVECs).Results Micro-CT analysis revealed that,compared with the control group,the trabecular thickness and trabecular number were significantly reduced in the MPS group,while the bone surface area/bone volume ratio and trabecular separation were significantly increased(P<0.001).In vitro experimental results indicated that DEX inhibited the proliferation of MC3T3-E1 cells,promoted cell apoptosis,and increased reactive oxygen species generation(P<0.01),and that DEX suppressed the formation of mineralized nodules,a key indicator of osteogenic differentiation,and downregulated the expression of osteogenesis-related genes(Runt-related transcription factor 2,osteopontin,osteocalcin)(P<0.01).However,NGN treatment partially reversed these effects.DEX significantly inhibited the migration of HUVECs,angiogenesis,and the expression of angiogenesis-related markers(platelet endothelial cell adhesion molecule-1,vascular endothelial growth factor,and von Willebrand factor)(P<0.01).In contrast,NGN treatment did not significantly affect the aforementioned effects,but the treatment with NGN conditioned medium[CM(NGN)]partially reversed these effects(P<0.01).Bioinformatics analysis combined with Pulldown assay results indicated that HO-1 was the target of NGN.DEX treatment significantly downregulated the expression of HO-1,while NGN intervention partially counteracted the inhibitory effect induced by DEX(P<0.01);knockdown of HO-1 negated the therapeutic effects of NGN(P<0.01).Compared with MPS administration alone,the combined administration of NGN and MPS upregulated the expression of HO-1 and HIF-1α in rat femoral head tissues.However,the HO-1 inhibitor ZnPP further upregulated the expression of HO-1 but downregulated the protein level of hypoxia-inducible factor-α(HIF-1α)(P<0.01).Conclusion NGN exerts its therapeutic effects on SONFH by activating the expression and activity of HO-1,which regulates the HIF-1α/VEGF pathway to promote osteoblast differentiation,bone formation,and angiogenesis.

Objective To investigate the mechanism of Naringenin(NGN)in the treatment of steroid(glucosteroid)-induced osteonecrosis of the femoral head(SONFH).Methods A SONFH rat model was established using Methylprednisolone(MPS)treatment,followed by intervention with NGN and zinc protoporphyrin(ZnPP).Micro-CT was used to analyze the morphological changes in femoral head tissues,and the levels of osteocalcin(OCN)in rat serum as well as heme oxygenase-1(HO-1)and hypoxia-inducible factor-1α(HIF-1α)in femoral bone tissue were measured.A cellular model was constructed by treating MC3T3-E1 cells with Dexamethasone(DEX),followed by NGN intervention.Bioinformatics analysis combined with molecular docking technology was used to predict the target of NGN,and the Pulldown experiment was performed for validation.The expression of HO-1 was knocked down through cell transfection,to analyze the viability,proliferation,apoptosis,and migration of MC3T3-E1 cells,and angiogenesis assays were conducted to evaluate the angiogenic potential of human umbilical vein endothelial cells(HUVECs).Results Micro-CT analysis revealed that,compared with the control group,the trabecular thickness and trabecular number were significantly reduced in the MPS group,while the bone surface area/bone volume ratio and trabecular separation were significantly increased(P<0.001).In vitro experimental results indicated that DEX inhibited the proliferation of MC3T3-E1 cells,promoted cell apoptosis,and increased reactive oxygen species generation(P<0.01),and that DEX suppressed the formation of mineralized nodules,a key indicator of osteogenic differentiation,and downregulated the expression of osteogenesis-related genes(Runt-related transcription factor 2,osteopontin,osteocalcin)(P<0.01).However,NGN treatment partially reversed these effects.DEX significantly inhibited the migration of HUVECs,angiogenesis,and the expression of angiogenesis-related markers(platelet endothelial cell adhesion molecule-1,vascular endothelial growth factor,and von Willebrand factor)(P<0.01).In contrast,NGN treatment did not significantly affect the aforementioned effects,but the treatment with NGN conditioned medium[CM(NGN)]partially reversed these effects(P<0.01).Bioinformatics analysis combined with Pulldown assay results indicated that HO-1 was the target of NGN.DEX treatment significantly downregulated the expression of HO-1,while NGN intervention partially counteracted the inhibitory effect induced by DEX(P<0.01);knockdown of HO-1 negated the therapeutic effects of NGN(P<0.01).Compared with MPS administration alone,the combined administration of NGN and MPS upregulated the expression of HO-1 and HIF-1α in rat femoral head tissues.However,the HO-1 inhibitor ZnPP further upregulated the expression of HO-1 but downregulated the protein level of hypoxia-inducible factor-α(HIF-1α)(P<0.01).Conclusion NGN exerts its therapeutic effects on SONFH by activating the expression and activity of HO-1,which regulates the HIF-1α/VEGF pathway to promote osteoblast differentiation,bone formation,and angiogenesis.