OBJECTIVE: To investigate the correlation of seminal plasma oxidation reduction potential (ORP), normalized oxidation-reduction potential (nORP) and sperm DNA fragmentation index (DFI) to sperm motion parameters, and their clinical predictive value for oligoasthenozoospermia (OAZ). METHODS: This study included 433 male subjects visiting the Clinic of Andrology in our hospital from March to May 2024. According to sperm concentration and the percentage of progressively motile sperm (PMS), we divided them into a normal control (n = 119), an oligozoospermia (OZ, n = 118), an athenozoospermia (AZ, n = 119) and an OAZ group (n = 77). Using the electrode method, we measured the seminal plasma ORP, calculated nORP=ORP/sperm concentration (mV/［10⁶/ml］), and determined DFI and high DNA chromatin sperm (HDS) by flow cytometry based on sperm chromatin structure assay (SCSA), followed by comparison among the four groups in age, abstinence days, semen volume, total sperm count, sperm concentration, PMS, non-progressively motile sperm (NPMS), immotile sperm (IMS), curvilinear velocity (VCL), straight line velocity (VSL), average path velocity (VAP), linearity (LIN), straightness(STR), wobble (WOB), DFI, HDS, ORP and nORP. Using the receiver operating characteristic (ROC) curve, we assessed the predictive value of DFI, ORP and nORP for OAZ, and analyzed the correlation of DFI, ORP and nORP to sperm motion parameters by Pearson and Spearman analyses. RESULTS: Statistical analysis revealed statistically significant differences among the four groups in semen volume, abstinence days, total sperm count, sperm concentration, PMS, NPMS, IMS, total sperm motility, VCL, VSL, VAP, STR, DFI, HDS, ORP and nORP (P < 0.05), but not in age, LIN and WOB (P > 0.05). The area under the ROC curve (AUC) for the predictive value of DFI for OAZ was 0.880, with the critical value of 8.920, sensitivity of 74.8% and specificity of 88.2%; that of ORP for AZ was 0.698, with the critical value of 155.375, sensitivity of 70.6% and specificity of 64.7%; and that of nORP for OZ was 0.999, with the critical value of 9.844, sensitivity of 98.3% and specificity of 99.2%. Pearson and Spearman correlation analyses showed that DFI was correlated positively with age, abstinence days, semen volume, IMS, HDS and ORP, but negatively with PMS, NPMS, total sperm motility, VCL, VSL, VAP and STR; ORP positively with abstinence days, semen volume, IMS, DFI and nORP, but negatively with PMS, NPMS, total sperm motility, VSL, LIN and STR; and nORP positively with HDS, but negatively with abstinence days, total sperm count, sperm concentration, PMS and NPMS. CONCLUSION Oxidative stress (OS) may be an important pathological factor for elevated ORP, increased DFI and changes of routine sperm motion parameters, consequently leading to OAZ. As OS markers, DFI and ORP have a high predictive value for OS-induced OAZ.
Male ; Humans ; DNA Fragmentation ; Semen/metabolism* ; Sperm Motility ; Spermatozoa ; Oxidation-Reduction ; Adult ; Oligospermia ; Sperm Count ; Semen Analysis ; Asthenozoospermia

Objective:To analyze the operation efficiency of community health centers with inpatient beds in Chaoyang District,Beijing,providing evidence-based support for optimizing community health centers health resource allocation under the hierarchical medical system.Methods:Data on health resource inputsand service outputs were collected from all 10 eligible community health centers in Chaoyang District(2018-2023).Static efficiency was evaluated using the DEA-BCC model,while dynamic efficiency was assessed via the Malmquist index model.Results:Human capital input showed a year-on-year increase.Inpatient beds,outpatient visits,and inpatient discharges exhibited a fluctuating upward trend overall,with 2020 as a turning point.Static efficiency analysis revealed that mean technical efficiency first increased then decreased.The proportion of institutions exhibiting decreasing returns to scale decreased from 60%(2018)to 20%(2023).Dynamic efficiency analysis indicated that total factor productivity(TFP)fluctuated in a"rise → decline → rise → decline → rise"pattern,with a marginal overall decrease(mean:0.998).Conclusion:The technological change index was identified as the core driver of TFP changes in the sample community health centers during 2018 and 2023.Given the continuous increase in human capital input,future efforts to optimize health resource allocation should prioritize enhancing technical efficiency and technological advancement.

BACKGROUND:The asymmetrical biomechanical environment of adolescent idiopathic scoliosis can lead to further wedge deformation of the vertebral body,which may affect cardiopulmonary function and compress nerves in severe cases.Adolescent idiopathic scoliosis with different degrees of scoliosis should be treated with exercise,bracing,and surgery.However,the mechanical mechanism of selecting an orthopedic approach remains unclear due to the individual variability of patients.OBJECTIVE:To investigate the biomechanical mechanism of different orthopedic modalities for the treatment of adolescent idiopathic scoliosis to provide a basis for clinical selection of treatment modalities based on the spine model of adolescent idiopathic scoliosis patients.METHODS:Based on the CT images of an adolescent idiopathic scoliosis patient,a scoliosis model(C7-L5)was reconstructed in Mimics software in three dimensions,and lateral thrust force was applied at the T8/T9 thorax and vertical distraction force was applied over the C7 vertebra with the magnitude of 20,40,60,80,100,and 120 N.The intervertebral disc stress and vertebral displacement in concave and convex sides,and Cobb angle of the spine were analyzed under two orthopedic modalities.RESULTS AND CONCLUSION:(1)With lateral thrust,there was no significant change in the C7T1-T7T8 intervertebral disc.The concave and convex stress of T7T8-L4L5 segment decreased first and then increased with the increase of lateral thrust force.The correction effect of lateral thrust on the segment near T8T9 was obvious and weakened with the extension of the segment to the cephalic and caudal ends.At 120 N of lateral thrust,the thoracic Cobb angle changed from 53.2° to 32.5° and the lumbar Cobb angle changed from 50.2° to 43.9°.(2)With the vertical distraction,the thoracic intervertebral disc stresses first decreased and then increased,and all the lumbar disc stresses decreased.The C7 displacement was the most obvious,and the correction effect gradually diminished with the segment extended to the caudal end.At a vertical distraction force of 120 N,the thoracic Cobb angle changed from 53.2° to 39.4° and the lumbar Cobb angle changed from 50.2° to 47.6°.(3)It is concluded that both orthopedic modalities provide improvement in the degree of scoliosis,with the thoracic correction being greater than the lumbar correction.Also,the asymmetric stress distribution on the concave and convex sides is improved,which contributes to normal bone growth.A vertical distraction approach is appropriate for larger Cobb angles,and a lateral thrust approach is appropriate for smaller Cobb angles.The results of this study help to understand the mechanism of spinal orthosis and provide a theoretical basis for the choice of orthopedic approach.

Objective:To construct a medical education metaverse based on cloudytization virtual reality (VR) technique,so as to resolve various issues encountered with conventional VR devices in use process,and enhance the user's experience and teaching effect of virtual space education. Methods:The technical architecture of the medical education metaverse was conducted from the perspectives included the underlying technique layer,learning interface layer,teaching activity space and knowledge layer. The medical education mateverse,which based on cloudytization VR technique,was constructed,and the system performance and user's experience were optimized from a supporting environment included the content layer,platform layer,cloud computing layer,network layer and terminal layer. Results:The medical students could conduct practical operation in virtual environment at any time and any place by the deployment approach on cloudy terminal and lightweight devices. The efficient and convenient cross-disciplinary collaborative learning was convenient for students to acquire knowledge from multiple perspectives,to better response complex medical environments. The real-time interactive remote medical approach expanded the boundaries of medical education,and ensured equity and inclusivity in medical education. Conclusion:The application of medical education metaverse based on cloudytization VR technique in medical teaching can effectively reduce the application threshold of medical education metaverse,and expand the coverage of educational resources of high quality,and enhance the use experience of teaching of the virtual space of medical education based on VR,and meet the demands of medical teaching for diverse application scenarios.

Objective:To investigate the differences in clinical characteristics and antibiotic resistance of neonatal sepsis（NS）caused by different Gram-staining pathogens.Methods:A retrospective study was conducted on confirmed NS cases admitted to the Neonatal Ward of the Pediatric Department at The First Affiliated Hospital of Dali University，from June 1，2014，to May 31，2024.Patients were divided into Gram-positive and Gram-negative groups based on blood or cerebrospinal fluid（CSF）culture results.Clinical characteristics，pathogen distribution，and antibiotic resistance were compared between the two groups.Results:A total of 98 cases were included，with 81 in the Gram-positive group and 17 in the Gram-negative group.Multivariate logistic regression analysis revealed that NS cases with a high neutrophil percentage（ OR=0.933，95% CI：0.899-0.969）or hemorrhagic symptoms/signs（ OR=0.059，95% CI：0.008-0.458）were less likely to have Gram-positive pathogens detected in blood or CSF cultures（ P<0.05）.Common Gram-positive pathogens included Staphylococcus epidermidis with 35 strains（33.65%）and Staphylococcus hominis with 22 strains（21.15%）.The predominant Gram-negative pathogen was Escherichia coli with 14 strains（13.46%）.Gram-positive pathogens exhibited high resistance to oxacillin（91.30%），erythromycin（90.91%），and penicillin G（90.00%），but low resistance to tigecycline（0），linezolid（0），and vancomycin（0）.Gram-negative pathogens showed high resistance to ampicillin（92.31%），cefazolin（90.00%），and ampicillin/sulbactam（75.00%），but low resistance to amikacin（6.25%），latamoxef（0），and ertapenem（0）.The incidence of concurrent purulent meningitis was lower in the Gram-positive group than in the Gram-negative group（9.88% vs.47.06%， χ2=11.628， P<0.05），and there was significant difference. Conclusion:NS cases with high neutrophil percentages or hemorrhagic symptoms/signs are less likely to be caused by Gram-positive pathogens.Staphylococcus epidermidis and Staphylococcus hominis are common Gram-positive pathogens，while Escherichia coli is the predominant Gram-negative pathogen in NS.Both Gram-positive and Gram-negative pathogens exhibit resistance to specific antibiotics.NS caused by Gram-positive pathogens is less likely to be complicated by purulent meningitis compared to those caused by Gram-negative pathogens.

Computational approaches, encompassing both physics-based and machine learning (ML) methodologies, have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities. The human dopamine (DA) transporter (hDAT) is the primary therapeutic target of numerous psychiatric medications. However, traditional hDAT-targeting drugs, which interact with the primary binding site, encounter significant limitations, including addictive potential and stimulant effects. In this study, we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape (WHALES) descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs. Initially, WHALES descriptors facilitated a similarity search, employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates. Consequently, from a compound library of 4,921 marketed and clinically tested drugs, we identified 27 candidate atypical inhibitors. Subsequently, ADMETlab was employed to predict the pharmacokinetic and toxicological properties of these candidates, while induced-fit docking (IFD) was performed to estimate their binding affinities. Six compounds were selected for in vitro assessments of neurotransmitter reuptake inhibitory activities. Among these, three exhibited significant inhibitory potency, with half maximal inhibitory concentration (IC₅₀) values of 0.753 μM, 0.542 μM, and 1.210 μM, respectively. Finally, molecular dynamics (MD) simulations and end-point binding free energy analyses were conducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation. In conclusion, our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

Computational approaches,encompassing both physics-based and machine learning(ML)methodolo-gies,have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities.The human dopamine(DA)transporter(hDAT)is the primary therapeutic target of numerous psychi-atric medications.However,traditional hDAT-targeting drugs,which interact with the primary binding site,encounter significant limitations,including addictive potential and stimulant effects.In this study,we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape(WHALES)descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs.Initially,WHALES descriptors facilitated a similarity search,employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates.Consequently,from a compound library of 4,921 marketed and clinically tested drugs,we identified 27 candidate atypical inhibitors.Subsequently,ADMETlab was employed to predict the pharmacokinetic and toxi-cological properties of these candidates,while induced-fit docking(IFD)was performed to estimate their binding affinities.Six compounds were selected for in vitro assessments of neurotransmitter re-uptake inhibitory activities.Among these,three exhibited significant inhibitory potency,with half maximal inhibitory concentration(IC50)values of 0.753 μM,0.542 μM,and 1.210 μM,respectively.Finally,molecular dynamics(MD)simulations and end-point binding free energy analyses were con-ducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation.In conclusion,our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

To reduce the dependency on high-carbon-load chromatographic columns,a new method has been established for the determination of the content of docusate sodium using ion-pair high-performance liquid chromatography(IP-HPLC).Tetrapropylammonium chloride was used as the ion-pair reagent with a mobile phase,composition of acetonitrile:10 mmol/L tetrapropylammonium chloride solution=66∶34,adjusting pH to 6.5 with 0.1%phosphoric acid solution,flow rate of 1.5 mL/min,detection wavelength of 214 nm,column temperature of 35℃,and an injection volume of 25 μL,and quantified by an external standard method.The main peak of docusate sodium exhibited a tailing factor of 1.34.The method showed good linearity within the range of 0.02 mg/mL to 0.40 mg/mL,with a correlation coefficient(r)of 0.999 9.It also demonstrated good repeatability,with recovery ranging from 97.0%to 98.2%(n=6).The quantification limit was 3.31 μg/mL,and the detection limit was 2.76 μg/mL.In summary,the new method shows good durability,a wide linear range,and high sensitivity,it is suitable for the determination of docusate sodium.

To reduce the dependency on high-carbon-load chromatographic columns,a new method has been established for the determination of the content of docusate sodium using ion-pair high-performance liquid chromatography (IP-HPLC). Tetrapropylammonium chloride was used as the ion-pair reagent with a mobile phase, composition of acetonitrile:10 mmol/L tetrapropylammonium chloride solution = 66∶34, adjusting pH to 6.5 with 0.1% phosphoric acid solution,flow rate of 1.5 mL/min, detection wavelength of 214 nm,column temperature of 35 °C, and an injection volume of 25 μL,and quantified by an external standard method. The main peak of docusate sodium exhibited a tailing factor of 1.34. The method showed good linearity within the range of 0.02 mg/mL to 0.40 mg/mL, with a correlation coefficient (r) of 0.999 9. It also demonstrated good repeatability, with recovery ranging from 97.0% to 98.2% (n=6). The quantification limit was 3.31 μg/mL, and the detection limit was 2.76 μg/mL.In summary,the new method shows good durability, a wide linear range, and high sensitivity, it is suitable for the determination of docusate sodium.

BACKGROUND:The asymmetrical biomechanical environment of adolescent idiopathic scoliosis can lead to further wedge deformation of the vertebral body,which may affect cardiopulmonary function and compress nerves in severe cases.Adolescent idiopathic scoliosis with different degrees of scoliosis should be treated with exercise,bracing,and surgery.However,the mechanical mechanism of selecting an orthopedic approach remains unclear due to the individual variability of patients.OBJECTIVE:To investigate the biomechanical mechanism of different orthopedic modalities for the treatment of adolescent idiopathic scoliosis to provide a basis for clinical selection of treatment modalities based on the spine model of adolescent idiopathic scoliosis patients.METHODS:Based on the CT images of an adolescent idiopathic scoliosis patient,a scoliosis model(C7-L5)was reconstructed in Mimics software in three dimensions,and lateral thrust force was applied at the T8/T9 thorax and vertical distraction force was applied over the C7 vertebra with the magnitude of 20,40,60,80,100,and 120 N.The intervertebral disc stress and vertebral displacement in concave and convex sides,and Cobb angle of the spine were analyzed under two orthopedic modalities.RESULTS AND CONCLUSION:(1)With lateral thrust,there was no significant change in the C7T1-T7T8 intervertebral disc.The concave and convex stress of T7T8-L4L5 segment decreased first and then increased with the increase of lateral thrust force.The correction effect of lateral thrust on the segment near T8T9 was obvious and weakened with the extension of the segment to the cephalic and caudal ends.At 120 N of lateral thrust,the thoracic Cobb angle changed from 53.2° to 32.5° and the lumbar Cobb angle changed from 50.2° to 43.9°.(2)With the vertical distraction,the thoracic intervertebral disc stresses first decreased and then increased,and all the lumbar disc stresses decreased.The C7 displacement was the most obvious,and the correction effect gradually diminished with the segment extended to the caudal end.At a vertical distraction force of 120 N,the thoracic Cobb angle changed from 53.2° to 39.4° and the lumbar Cobb angle changed from 50.2° to 47.6°.(3)It is concluded that both orthopedic modalities provide improvement in the degree of scoliosis,with the thoracic correction being greater than the lumbar correction.Also,the asymmetric stress distribution on the concave and convex sides is improved,which contributes to normal bone growth.A vertical distraction approach is appropriate for larger Cobb angles,and a lateral thrust approach is appropriate for smaller Cobb angles.The results of this study help to understand the mechanism of spinal orthosis and provide a theoretical basis for the choice of orthopedic approach.