Objective : To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis. Methods : An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression. Results : Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01). Conclusion Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.

Checkpoint blockade immunotherapy has emerged as a transformative approach in cancer treatment by activating tumor-infiltrating T cells. However, the efficacy of PD-L1 blockade is restricted in "cold" tumors, which are characterized by low immunogenicity, presenting a challenge to immunotherapy. This study introduces an innovative strategy, utilizing cathepsin-cleavable N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-assisted combined photodynamic therapy (PDT) and PD-L1 degradation for the first time, effectively treating T cell-deficient tumors. The degradable main-chain polymer, conjugated with photosensitizer porphyrin, facilitates the accumulation of reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and promoting cytotoxic T lymphocytes (CTLs) infiltration into tumors. Multivalent peptide antagonists of PD-L1 promote PD-L1 degradation in lysosomes through receptor crosslinking, overcoming the adaptive cycling of PD-L1 to the tumor cell surface. These findings demonstrate that polymer-assisted PDT and PD-L1 crosslinking degradation represent a potential novel strategy for anti-tumor immunotherapy, providing valuable tools for expanding immunotherapy applications in immunosuppressive cancers.

Objective:To investigate the application and teaching effect of a new residency training model for emergency medicine in the context of sub-specialty zoning.Methods:A total of 30 emergency medicine residents were randomly divided into experimental group and control group, with 15 residents in each group. The residents in the experimental group received teaching based on the sub-specialty zoning model, while those in the control group received traditional teaching. SPSS 26.0 software was used for the t-test and the chi-square test, and the two groups were compared in terms of demographic variables, training assessment scores, and teaching feedback. Results:There were no significant differences between the two groups in the demographic variables such as age, sex, education background, and years of clinical work, and there was also no significant difference between the two groups in the final assessment score of Chongqing ( P>0.05), but there was a significant difference between the two groups in the score of intra-department theoretical examination before the final assessment [(81.20±2.83) vs. (89.73±3.01), P<0.001]. The survey of teaching feedback showed that both groups had high confidence in independent duty and a high degree of satisfaction with teaching, with no significant differences between the two groups ( P>0.05); however, compared with the control group, the experimental group had a significantly higher recognition of the development of emergency sub-specialties and significantly better orientations of scientific research and self-development. Conclusions:The new residency training model for emergency medicine in the context of sub-specialty zoning may help with the long-term development of emergency medicine and should be further promoted and validated in emergency medicine residency training.

Objective To investigate the mediating effect of mindfulness on the relations between FCR and QOL.Methods A total of 240 lung cancer patients who were admitted to 3 hospitals in Shanxi Province,from January 2022 to January 2023,were enrolled in the study by convinient sampling.The fear of progression questionnaire-short form(FoP-Q-SF),mindfulness attention awareness scale(MAAS)in Chinese and the European Organisation for Research and Treatment for Cancer Quality of life questionnaire(EORTC QLQ)were employed in the cross-sectional survey.Multiple linear regression was used to analyse the association between FCR and QOL,and Bootstrap Model was adopted to analyse the mediating effect of mindfulness between FCR and QOL.Results A total of 240 questionnaires were distributed and 217 of them were retrieved,with an effective retrieval rate of 96.42%.FCR was found at a moderate level in all lung cancer patients,and it was negatively associated with the mindfulness and QOL(r=-0.348,P<0.01:r=-0.331,P<0.01).Bootstrap analysis revealed that the changes in mindfulness score acted as an intermediate variable between FCR and QOL,mediating 25.68%of the relationship.Conclusions FCR in lung cancer patients is negatively associated with QOL.This association may be explained by the reduction in mindfulness experienced by the patients.

BackgroundFunctional near-infrared spectroscopy （fNIRS） is a new generation of imaging tool that can be used to assist the diagnosis of psychiatric disorders. However， whether the patterns of prefrontal cortex activation observed by fNIRS are specific for different psychiatric disorders remains to be explored. ObjectiveTo investigate the characteristics of prefrontal cortex activation in patients with depression， anxiety disorder， bipolar disorder and schizophrenia in verbal fluency task （VFT） using fNIRS. MethodsFrom September to December 2021， 39 patients with schizophrenia， 205 patients with depressive disorder， 212 patients with anxiety disorder and 77 patients with bipolar disorder meeting the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited in the outpatient and inpatient department of West China Hospital， Sichuan University. fNIRS was used to monitor the prefrontal cortex hemodynamic changes of patients under VFT， and the clinical symptoms of patients were assessed by Symptom Checklist 90 （SCL-90） and Hypomania Checklist-32 items（HCL-32）. Differences in mean oxyhemoglobin （HbO₂） concentration and the initial slope from 2 to 7 second during VFT were compared among patients with different diseases， and the correlation between mean HbO₂ concentration/initial slope and clinical symptoms was analyzed by partial correlation analysis. ResultsThe concentration of HbO₂ in channel 4 （Z=2.828， P=0.028） and channel 6 （Z=2.912， P=0.022） in patients with depression were significantly higher than those in patients with schizophrenia. Patients with anxiety had significantly higher changes in mean HbO₂ concentration in channel 4 （Z=3.154， P=0.010）， channel 5 （Z=3.021， P=0.015）， channel 6 （Z=2.980， P=0.017） and of all channels （Z=2.881， P=0.024） than those of schizophrenia patients. There was a statistically significant difference in the initial slope of channel 3 between patients with depressive disorder and those with bipolar disorder （Z=2.691， P=0.039）. Among patients with bipolar disorder， the anger-hostility scores of SCL-90 were negatively correlated with the mean HbO₂ concentration changes in channel 4 （r=-0.505， P=0.004）， channel 6 （r=-0.390， P=0.004）， channel 15 （r=-0.546， P=0.002）， channel 16 （r=-0.550， P=0.002） and the mean HbO₂ concentration changes of all channels （r=-0.491， P=0.006）. ConclusionPatients with schizophrenia had lower activation in frontopolar and orbitofrontal region than patients with depression and anxiety disorder， and the initial slope of the right frontopolar， inferior frontal and orbitofrontal region in patients with depression is higher than patients with bipolar disorder. In addition， patients with bipolar disorder had less activation in the frontopolar and orbitofrontal lobe， the insular cover of Broca's area and the upper outer frontal cortex， and were more irritable and hostile. ［Funded by 1·3·5 Project for Disciplines of Excellence-Clinical Research Incubation Project， West China Hospital， Sichuan University （number， ZYJC21083）］

OBJECTIVES: The aim of this study was to evaluate the disease burden of prostate cancer (PC) and assess key influencing factors associated with the disease expenditures of PC in the United States. METHODS: The total deaths, incidence, prevalence, and disability-adjusted life-years of PC were obtained from the Global Burden of Disease Study 2019. The Medical Expenditure Panel Survey was used to estimate healthcare expenditures and productivity loss and to investigate patterns of payment and use of healthcare resources in the United States. A multivariable logistic regression model was conducted to identify key factors influencing expenditures. RESULTS: For patients aged 50 and older, the burden for all age groups showed a modest increase over the 6-year period. Annual medical expenditures were estimated to range from US$24.8 billion to US$39.2 billion from 2014 to 2019. The annual loss in productivity for patients was approximately US$1,200. The top 3 major components of medical costs were hospital inpatient stays, prescription medicines, and office-based visits. Medicare was the largest source of payments for survivors. In terms of drug consumption, genitourinary tract agents (57.0%) and antineoplastics (18.6%) were the main therapeutic drugs. High medical expenditures were positively associated with age (p=0.005), having private health insurance (p=0.016), more comorbidities, not currently smoking (p=0.001), and patient self-perception of fair/poor health status (p<0.001). CONCLUSIONS From 2014 to 2019, the national real-world data of PC revealed that the disease burden in the United States continued to increase, which was partly related to patient characteristics.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

BACKGROUND: Corneal disease is second only to cataract considered as the leading cause of blindness in the world, with high morbidity. Construction of corneal substitutes In Vitro by tissue engineering technology to achieve corneal regeneration has become a research hotspot in recent years. We conducted in-depth research on the biocompatibility, physicochemical and mechanical properties of rat bone marrow mesenchymal stem cells (rBM-MSCs)-seeded gelatin methacrylate (GelMA) as a bioengineered cornea. METHODS: Four kinds of GelMA with different concentrations (7, 10, 15 and 30%) were prepared, and their physicchemical, optical properties, and biocompatibility with rBM-MSCs were characterized. MTT, live/dead staining, cell morphology, immunofluorescence staining and gene expression of keratocyte markers were performed. RESULTS: 7%GelMA hydrogel had higher equilibrium water content and porosity, better optical properties and hydrophilicity. In addition, it is more beneficial to the growth and proliferation of rBM-MSCs. However, the 30%GelMA hydrogel had the best mechanical properties, and could be more conducive to promote the differentiation of rBM-MSCs into keratocyte-like cells. CONCLUSION As a natural biological scaffold, GelMA hydrogel has good biocompatibility. And it has the ability to promote the differentiation of rBM-MSCs into keratocyte-like cells, which laid a theoretical and experimental foundation for further tissue-engineered corneal stromal transplantation, and provided a new idea for the source of seeded cells in corneal tissue engineering.

Objective:To explore the mediating effect of self-compassion between family cohesion and loneliness among adolescents.Method:From November to December 2020, a total of 626 adolescents were investigated with the family adaptability and cohesion scale, children loneliness scale and the self-compassion scale short form.Data were analyzed by SPSS 23.0 and PROCESS v 2.16 softwares.The statistical methods included t-test, one-way ANOVA, Pearson correlation analysis and intermediary effect analysis. Results:Compared with girls, boys’ score of family cohesion((63.52±8.47), (65.48±9.07)) was significantly lower but the scores of self-compassion((37.68±5.26), (36.49±5.75)) and loneliness((37.74±10.44), (36.01±10.48)) were significantly higher( t=-2.79, 2.06, 2.70; all P<0.05). There was no significant difference in the scores of family cohesion((63.67±8.71), (64.74±8.85)), self-compassion((37.45±5.71), (36.98±5.49)) and loneliness((36.60±10.52), (36.96±10.49)) between left-behind and non-left-behind children( t=1.29, -0.87, 0.38, all P>0.05). The score of family cohesion of the adolescents from Grade 7 was significantly lower than those of Grade 8, Grade 10 and Grade 11( P<0.01), while the score of self-compassion of the adolescents from Grade 10 was significantly lower than those of Grade 7 and Grade 11(both P<0.01), but the score loneliness of the adolescents from Grade 11 was significantly lower than those of Grade 8 and Grade 10(both P<0.05). Family cohesion(64.50±8.82)was significantly positively associated with self-compassion(37.09±5.54)( r=0.22; P<0.01). Loneliness(36.88±10.49)were significantly negatively associated with self-compassion( r=-0.27, P<0.01) and family cohesion( r=-0.28, P<0.01). The relation between family cohesion and loneliness was partly mediated by self-compassion and the effect of mediation was 20.9%. Conclusion:Family cohesion will not only directly affect the loneliness of adolescents, but also affect loneliness through the mediating effect of self-care.

Carbon nanotube (CNT) composite materials are very attractive for use in neural tissue engineering and biosensor coatings. CNT scaffolds are excellent mimics of extracellular matrix due to their hydrophilicity, viscosity, and biocompatibility. CNTs can also impart conductivity to other insulating materials, improve mechanical stability, guide neuronal cell behavior, and trigger axon regeneration. The performance of chitosan (CS)/polyethylene glycol (PEG) composite scaffolds could be optimized by introducing multi-walled CNTs (MWCNTs). CS/PEG/CNT composite scaffolds with CNT content of 1%, 3%, and 5% (1%=0.01 g/mL) were prepared by freeze-drying. Their physical and chemical properties and biocompatibility were evaluated. Scanning electron microscopy (SEM) showed that the composite scaffolds had a highly connected porous structure. Transmission electron microscope (TEM) and Raman spectroscopy proved that the CNTs were well dispersed in the CS/PEG matrix and combined with the CS/PEG nanofiber bundles. MWCNTs enhanced the elastic modulus of the scaffold. The porosity of the scaffolds ranged from 83% to 96%. They reached a stable water swelling state within 24 h, and swelling decreased with increasing MWCNT concentration. The electrical conductivity and cell adhesion rate of the scaffolds increased with increasing MWCNT content. Immunofluorescence showed that rat pheochromocytoma (PC12) cells grown in the scaffolds had characteristics similar to nerve cells. We measured changes in the expression of nerve cell markers by quantitative real-time polymerase chain reaction (qRT-PCR), and found that PC12 cells cultured in the scaffolds expressed growth-associated protein 43 (GAP43), nerve growth factor receptor (NGFR), and class III β‍-tubulin (TUBB3) proteins. Preliminary research showed that the prepared CS/PEG/CNT scaffold has good biocompatibility and can be further applied to neural tissue engineering research.
Animals ; Axons ; Biocompatible Materials/chemistry* ; Chitosan/chemistry* ; Nanotubes, Carbon/chemistry* ; Nerve Regeneration ; Polyethylene Glycols ; Porosity ; Rats ; Tissue Engineering/methods* ; Tissue Scaffolds/chemistry*