Objective To investigate the effect of midazolam on neuronal damage in ischemic stroke （IS） rats and its regulatory effect on PTEN-induced putative kinase 1 （PINK1）/E3 ubiquitin ligase （PARKIN） signaling pathway. Methods An IS rat model was established using arterial occlusion method. The rats with successful model were randomly divided into IS group, drug-low, medium, high-dose （drug-L, M, H, 30, 60, 90 mg/kg midazolam） groups, drug-H+autophagy inhibitor 3-MA group （90 mg/kg midazolam+30 mg/kg 3-MA）, and rats with only isolated blood vessels were used as sham surgery groups. Each group received corresponding doses of drugs or physiological saline intervention, and the neurological function scoring, brain histopathology, neuronal apoptosis, ultrastructure, and expression of PINK1, PARKIN, microtubule-associated protein 1 light chain 3 （LC3）, and P62 protein in mitochondria were detected. Results Compared with the IS group, the pathological damage of the drug-L group, drug-M group, and drug-H group was improved, and autophagosomes showed an increasing trend, the expression of PINK1, PARKIN, and LC3 proteins increased, the neurological function score, neuronal apoptosis rate, and P62 protein obviously decreased in a dose-dependent manner （P<0.01 or P<0.001）; compared with the drug-H group, the pathological damage in the drug-H+3-MA group increased and autophagosomes decreased, the expression of PINK1, PARKIN, and LC3 proteins decreased, the neurological function score, neuronal apoptosis rate, and P62 protein obviously increased （P<0.001）. Conclusion Midazolam induced mitochondrial autophagy in IS rats by activating the PINK1/PARKIN signaling pathway, neuronal apoptosis was reduced and neuronal damage were improved in IS rats.

BackgroundAs a high prevalence disorder， schizophrenia has caused significant burden to family and society due to the impairment of occupational and social function. Currently， the dominant vocational training model in China follows a paternalistic， clinician-led decision-making approach. Although it improves patients' social function to some extent， it undermines their autonomy and treatment adherence. Therefore， it is urgently necessary to explore a new intervention method to enhance treatment compliance and social function in patients. ObjectiveTo explore the impact of shared decision-making oriented vocational training on social function in hospitalized schizophrenia patients， so as to provide references for rehabilitation interventions. MethodsA total of 68 patients diagnosed with schizophrenia according to the International Classification of Diseases， tenth edition （ICD-10） criteria were consecutively enrolled from January to June 2024 at The Third People's Hospital of Wenjiang Distric， Chengdu. Participants were randomly allocated into the research group （n=34） and the control group （n=34） using a random number table method. Both groups received routine rehabilitation training， while the research group received shared decision-making oriented vocational training for 12 weeks， 2 times a week for 2 hours each time. Before and at the 4^th and 12^th week of intervention， two groups were evaluated by General Self-Efficacy Scale （GSES）， Stigma Scale for Mental Illness （SSMI）， Scale of Social function of Psychosis Inpatients （SSFPI） and Inpatient Psychiatric Rehabilitation Outcome Scale （IPROS）. ResultsA total of 63 participants completed the study， with 30 cases in the research group and 33 cases in the control group. Repeated measures ANOVA revealed statistically significant time effects and interaction effects in both groups for GSES， SSMI， SSFPI and IPROS scores （F=20.451， 16.022； 26.193， 12.944； 23.957， 5.023； 11.776， 3.985， P<0.05 or 0.01）， while no significant group effects were observed （F=0.188， 0.742， 1.878， 0.474， P>0.05）. At the 12^th week of intervention， there were statistically significant differences in GSES， SSMI， SSFPI and IPROS scores between the two groups. ConclusionShared decision-making oriented vocational training may help to improve social function in patients with schizophrenia. ［Funded by 2023 Chengdu Medical Research Project （number， 2023468）］

BACKGROUND:Bioactive glass bone repair material has bone-bonding ability,bone induction ability and bone conduction characteristics.However,the performance of bioactive glass does not meet the requirements of clinical application,and the addition of boron is expected to improve the performance of bioactive glass. OBJECTIVE:To study the effect of different contents of B2O3 replacing SiO2 on the mechanical properties and bioactivity of bioactive glass. METHODS:Based on bioactive glass containing phosphorus nitrogen and oxygen(composition:SiO2-CaO-ZnO-Na2O-Si3N4-P2O5),B2O3 was used to partially replace the SiO2.The basic glass containing B2O3 with a mass fraction of 0%(group A),5%(group B),10%(group C),and 15%(group D)was fired using the high-temperature melting method(the total mass fraction of SiO2 and B2O3 in the basic broken glass was 41%).Porous bioactive glass scaffolds were fabricated by the organic foam impregnation method.Uniaxial compression and three-point bending method of universal mechanical testing machine were used to test mechanical properties.Four groups of scaffolds were immersed in simulated body fluids to detect the degradation performance of scaffolds.Scanning electron microscopy was used to observe the morphological changes of scaffolds before and after soaking.X-ray diffraction was used to analyze the phase composition of scaffolds before and after soaking. RESULTS AND CONCLUSION:(1)With the increase of the mass fraction of B2O3,the compressive strength and bending strength of the porous bioactive glass scaffold increased,and there was a significant difference between the compressive strength and bending strength of the four groups(P≤0.05).(2)After soaking in simulated body fluids,the porous bioactive glass scaffolds degraded gradually with the extension of time.At the same soaking time point,the degradation rate of the scaffolds was accelerated with the increase of the mass fraction of B2O3,and the compressive strength and bending strength of the scaffolds in the four groups were significantly different(P≤0.05).(3)Scanning electron microscopy after soaking in simulated body fluids showed that a large number of granular materials were deposited on the surface of group A and group B after soaking for 1 day.After 3 days,the granular materials on the surface fused with each other to form film-like deposits.After 7 days,the films on the surface fused with each other to form pieces,basically covering the entire surface of the specimen.After soaking for 1 day,film-like material deposition was formed on the surface of group C,and after 3 days,the films on the surface were fused into pieces,basically covering the whole surface of the specimen.After soaking for 1 day in group D,flake material covering the whole surface of the specimen could be seen.(4)X-ray diffraction analysis after 1 day of immersion in simulated body fluids showed that the deposits on the surface of the four groups of scaffolds were crystallized hydroxyapatite.(5)B2O3 replacement of SiO2 can enhance the mechanical properties,degradation properties and in vitro mineralization activity of porous bioactive glass scaffolds.

BACKGROUND:The traditional view is that proximal fibular fractures do not require fixation.Others and our research suggest that the proximal fibular structure plays an important role in the stability of the posterolateral structure of the knee joint,and its mechanism of action is worth studying. OBJECTIVE:To investigate the biomechanical effects of proximal fibular fractures on various structures of the knee joint in an extended state. METHODS:Finite element method was used to conduct simulated biomechanical experiments.A healthy young male volunteer was selected to establish a finite element model of the knee joint in an extended state using MRI and CT image data,and four proximal fibular shapes were simulated(Model A:intact,Model B:1 cm fracture below the fibular head,Model C:1 cm tip defect fracture from the proximal end of the fibula to the distal end,and Model D:2 cm bone defect from the proximal end of the fibula).A longitudinal concentrated load of 1 500 N was applied to the femoral shaft to compare and analyze the distribution and changing trend of the maximum equivalent stress and maximum first principal stress of each structure of the knee joint in an extended state under four working conditions. RESULTS AND CONCLUSION:(1)In Model A,the maximum equivalent stress in the tibial cartilage and lateral compartment of the meniscus was greater than that in the medial compartment,while the maximum first principal stress in the tibial plateau and medial compartment of the meniscus was greater than that in the lateral compartment.The maximum equivalent stress of the medial condyle of the femoral cartilage was greater than that of the lateral condyle,and the maximum first principal stress of the medial condyle of the femoral cartilage was greater than that of the medial condyle.(2)Compared to Model A,there was no significant difference in the magnitude and distribution of the maximum equivalent stress and maximum first principal stress in the cartilage and meniscus of Model C.(3)Compared to Model A,the maximum equivalent stress increase amplitude of Model B was in the order of medial tibial cartilage(14.9％),medial condyle of femoral cartilage(13.6％),and medial meniscus(6.6％).The maximum first principal stress increase amplitude was the medial meniscus(11.06％),the medial tibial cartilage(8.65％),and the medial condyle of the femoral cartilage(7.46％).The maximum equivalent stress increase amplitude of the ligament was as follows:popliteal arch ligament(33.2％)>anterior cruciate ligament(21.3％)>fibular collateral ligament(17％)>posterior cruciate ligament(14.3％)>anterior lateral collateral ligament(13.2％)>medial collateral ligament(10.1％).(4)Compared to Model A,the maximum equivalent stress increasing trend of Model D followed the medial tibial cartilage(19.5％),femoral cartilage medial condyle(17.9％),and medial meniscus(9.9％).The maximum first principal stress in sequence was the medial meniscus(14.04％),the medial tibial cartilage(13.03％),and the medial condyle of the femoral cartilage(11.37％).The increasing trend of maximum equivalent stress in ligaments was as follows:anterior cruciate ligament(25.2％)>posterior cruciate ligament(18.9％)>medial collateral ligament(18.5％)>anterior lateral collateral ligament(12.7％).(5)It is suggested that when the knee joint is extended,a 1 cm fracture below the fibular head and a 2 cm fibular tip bone defect have a significant impact on the structure of the medial ventricular cartilage,anterior cruciate ligament,and posterior lateral ligament complex.

Objective:To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China.Methods:Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (＜60, 60-＜70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values.Results:A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening.Conclusion:To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.

Objective:To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China.Methods:Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (＜60, 60-＜70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values.Results:A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening.Conclusion:To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.

Objective To explore the value of serum soluble transferrin receptor(sTFR)and urinary tryp-sin inhibitor(Bikunin)in assessing the short-term prognosis of patients with hepatitis B virus related acute on chronic live failure(HBV-ACLF).Methods A total of 103 patients with HBV-ACLF admitted to Weifang People's Hospital from January 2019 to December 2022 were collected as HBV-ACLF group,who were classi-fied into early stage group(n=46),middle stage group(n=34)and late stage group(n=23)according to the disease progression,and classified into good prognosis group(n=67)and poor prognosis group(n=36)according to clinical outcomes at 30 d after hospital admission.At the same time,65 patients with chronic hep-atitis B virus infection were selected as chronic hepatitis B group and 65 healthy volunteers were selected as control group were enrolled in the study.The clinical medical records of research objects were collected at the time of admission.Serum sTFR and Bikunin levels were detected by enzyme-linked immunosorbent assay.Spearman rank correlation analysis was performed to analyze the association between serum sTFR,Bikunin and disease progression.Multivariate Logistic regression analysis was performed to analyze factors affecting short-term poor prognosis of patients with HBV-ACLF.Receiver operating characteristic(ROC)curve was used to assess the predictive value of serum sTFR and Bikunin on prognosis.Results Serum sTFR and Bikun-in levels were lower in HBV-ACLF group and chronic hepatitis B group than those in control group,and those in HBV-ACLF group were lower than those in chronic hepatitis B group,and the differences were statistically significant(P＜0.05).Model for End-Stage Liver Disease(MELD)score was higher in HBV-ACLF group and chronic hepatitis B group than that in control group,and that in HBV-ACLF group was higher than that in chronic hepatitis B group,and the differences were statistically significant(P＜0.05).Compared with early stage group,serum sTFR and Bikunin levels decreased in middle stage group and late stage group,and those in late stage group were lower than those in middle stage group,and the differences were statistically significant(P＜0.05).MELD score increased in middle stage group and late stage group,and that in late stage group was higher than that in middle stage group,and the differences were statistically significant(P＜0.05).Serum sTFR and Bikunin in HBV-ACLF patients were associated with MELD score(r=-0.638,-0.592,P＜0.05),which were also associated with severity of disease(rs=-0.722,-0.671,P＜0.05).Elevated HB-sAg,elevated quantitative HBV DNA,middle and late stages of HBV-ACLF and elevated MELD score were independent risk factors for poor short-term prognosis in patients with HBV-ACLF(OR＞1,P＜0.05),while elevated serum sTFR and Bikunin were protective factors for poor short-term prognosis in patients with HBV-ACLF(OR＜1,P＜0.05).Serum sTFR and Bikunin both had some predictive value for poor short-term prog-nosis,and the predictive value of the combination was greater than that of single indicator(Z=2.139,2.165,P＜0.05).Conclusion Serum sTFR and Bikunin levels are decreased in patients with HBV-ACLF,which are associated with disease progression and short-term prognosis.Early combined detection of two indicators could predict the risk of poor prognosis in patients with HBV-ACLF at 30 d after hospital admission.

Objective To investigate the effects of three-dimensional(3D)screws and circular plates on the biomechanical stability of Sanders ABⅢ calcaneal fractures.Methods Calcaneal computed tomography(CT)and magnetic resonance imaging(MRI)data from a 26-year-old volunteer were collected to establish a 3D finite element model of Sanders ⅢAB calcaneal fracture fixed with 3D screws and circular plates.A longitudinal load of 700 N was applied to compare the variations in the stress,displacement of the bone block,and internal fixation in the different models.Results Under 700 N longitudinal loads,the maximum displacement of the bone block and the maximum stress of the bone block and internal fixation were concentrated at the intersection of the posterior talar articular plane internal fixation and fracture line.The overall displacements of the bone blocks in the 3D screw and circular plate models were similar.Compared with the circular plate model,the maximum and average stresses of the bone block and internal fixation in the 3D screw model were lower,and the displacement and stress changes of the 3D screw model were closer to those of the complete calcaneal bone model.Conclusions In the fixation of Sanders ⅢAB calcaneal fractures,both 3D screw and circular plate fixation method can provide good stability.The biomechanical properties of the 3D screws were better than those of the circular plates,which is consistent with the biomechanical characteristics.

BACKGROUND: This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings. METHODS: We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022. RESULTS: Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001). CONCLUSION The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.
Humans ; Antiretroviral Therapy, Highly Active/adverse effects* ; Anti-HIV Agents/adverse effects* ; HIV Infections/drug therapy* ; Tenofovir/therapeutic use* ; Retrospective Studies ; Emtricitabine/pharmacology* ; Adenine/therapeutic use* ; Lipids

Objective:To prepare liquid-gas phase modified nanoparticles (TMZ/PFP/PLGA NPs) of perfluoropentane (PFP) and temozolomide (TMZ) encapsulated by polylactic-glycolic acid copolymer (PLGA), combined with low intensity focused ultrasound (LIFU) irradiation, and to investigate its ultrasound imaging ability and intervention effect on human glioma cells in vitro.Methods:TMZ/PFP/PLGA NPs were prepared by compound emulsion method. The basic physical and chemical properties and drug loading ability of TMZ/PFP/PLGA NPs were detected. CCK-8 assay was used to detect the cytotoxicity of nanoparticles in vitro and the effect of synergistic intervention with LIFU on the survival rate of glioma cells. The expression levels of apoptosis related proteins Bcl-2, Bax and caspase-3 were detected by Western blot.Results:Under transmission electron microscope, TMZ/PFP/PLGA NPs showed a circular core-shell structure with regular morphology, particle size was (137.9±63.31)nm, encapsulation efficiency of TMZ was (83.01±5.57)%, drug loading was (3.19±0.22)%. The survival rate of U251 cells was still above 70% after 24 hours of co-incubation with nanoparticles. Under the synergistic effect of LIFU irradiation, the apoptosis of U251 cells was accelerated and the survival rate of U251 cells was significantly decreased. The results of Western blot showed that the synergic intervention could significantly down-regulate the expression of apoptosis related protein Bcl-2, and significantly up-regulate the expression of Bax protein and caspase-3 protein (all P<0.05). Conclusions:TMZ/PFP/PLGA NPs have good basic physical and chemical properties. TMZ/PFP/PLGA NPs have low cytotoxicity in vitro while efficiently loading chemotherapeutic drug timozolomide. Synergistic intervention under LIFU irradiation can significantly accelerate the apoptosis of U251 glioma cells, which has a good application prospect.