Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

Objective:To investigate the clinical characteristics of psoriasis and status quo of medical care for patients in county areas of China.Methods:This study was a cross-sectional investigation. Based on the “Qianxian Wuyin” Project (a national project for upgrating ability for psoriasis care at county level), an online questionnaire survey was conducted in the dermatology departments of 459 county hospitals in 404 pilot administrative counties across China from February to June 2023. The questionnaire included demographic information of patients (gender, ethnicity, age, place of residence, education, marital status), and clinical characteristics of psoriasis (disease course, type, comorbidities, body surface area (BSA) and previous treatment. The Dermatology Life Quality Index (DLQI) and Psoriasis Area and Severity Index (PASI) were applied for assessing the quality of life and disease severity, and completed by patients or guardian and doctors, respectively.Results:A total of 16 935 patients completed the questionnaire. The age of patients was 1-102(44.17±11.58)years, and 71.0% (12 036/16 935) were 30-59 years old. The ratio of male to female was 2.21∶1; 24.3%(4 117/16 935) of patients had high school education; there were 9 940 patients(58.7%) with previous or current smoking and/or alcohol use; 42.8%(7 218/16 855) of patients had a disease course of 1-5 years. There were 15 630 patients(92.3%) with DLQI≥10, 8 346 patients(49.7%) with PASI≥10, 15 017 patients(89.2%) with BSA≥10%. The plaque type was the most common disease type ( n=14 965, 88.7%), and spotting type ranked the second ( n=1 141, 6.8%). The most common initial site was the trunk ( n=12 309, 72.9%). Among the comorbidities, hypertension was the most common one ( n=1 681, 10.0%). There were 7 650 reports of treatment response to conventional topical drug therapy and 3 112 reports of treatment response to systemic drug therapy, with 6 269 (81.9%) and 2 493 (80.1%) reporting poor or no response, respectively. Conclusions:The survey shows that in the county areas of China, the majority of psoriasis patients are severe patients with short course of disease, plaque type is the most common type, and hypertension is the most common comorbidity; and the conventional treatment is less effective for most patients.

Objective To explore the effects of drug therapy combined with multi-dimensional psychological intervention on the insomnia of shift medical staff in"sunshine hospital"mode,and to provide a reference for improving the physical and mental health of shift medical staff.Methods A total of 140 cases of medical staff with insomnia in shifts in Wuhan were included and divided into study group and control group by random number table method,70 cases in each group.The control group was given drug treatment,and the study group was treated combined with multi-dimensional psychological intervention.based on"sunshine hospital"model.The scale and questionnaire of PSQI,ISI,ESS and FAS were used to evaluate sleep status and HAMD,HAMA,PHQ-9 and SAS were used to evaluate psychological status,at baseline,visit 1(baseline+intervention for 1 month)and visit 2(baseline+intervention for 3 months),respectively.Results(1)Sleep status:There were differences in 7 dimensions of PSQI score,ISI,ESS,and FAS score between the study group and the control group at different periods(P<0.05);Among them,the PSQI scores of the two groups showed significant difference between the two groups at interview 2(P<0.05);There were significant differences in sleep quality,sleep efficiency scores,ESS and FAS between the two groups at visit 1 and visit 2(P<0.05).(2)Psychological status:HAMD,HAMA,PHQ-9 and SAS scores of the study group and the control group were different in different periods(P<0.05).At interview 2,there were significant differences in HAMA and SAS scores between the two groups(P<0.05).Conclusion Based on the"sunshine hospital"model of drug therapy combined with multi-dimensional psychological intervention,it can significantly improve sleepiness,fatigue symptoms,sleep quality,sleep efficiency,and anxiety and depression of first-line shift medical staff in the short term,and significantly alleviate overall insomnia and anxiety in the long term.

Objective:To explore the characteristics of endothelial function in children with incomplete Kawasaki disease (IKD) of different ages and its relationship with coronary artery lesion (CAL).Methods:A total of 200 children with IKD admitted to the Affiliated Hospital of Jining Medical University from February 2020 to May 2022 were selected as the IKD group, and another 200 healthy children who underwent physical examinations during the same period were selected as the control group. According to the age of children with IKD, infants ( n=78) were classified as those under 1 year old, infants ( n=62) were classified as those between 1-3 years old, and preschool children ( n=60) were classified as those over 3-6 years old. The endothelial function characteristics of IKD children in different age groups and normal control group children were analyzed and compared. In addition, IKD patients were divided into CAL group ( n=110) and nCAL group ( n=90) based on whether CAL was merged. The age, carotid intima-media thickness (IMT), flow-mediated-dilation (FMD), carotid stiffness index (SI), nitroglycerin-mediated dilation (NMD), tumor necrosis factor α (TNF-α), C-reactive protein (CRP), brachial artery endothelial dependent dilation function (EDD) and other clinical data were compared between the two groups. Cox proportional hazards model was used for univariate and multivariate analysis to identify the risk factors for CAL in IKD patients. A column chart prediction model was constructed and evaluated. Results:There were statistically significant differences in FMD, NMD, SI, IMT, reactive congestion index (RHI), and EDD between IKD patients and normal control group children (all P<0.05). There were statistically significant differences in FMD, NMD, SI, IMT, RHI, and EDD among three groups of IKD children of different ages (all P<0.05). There were statistically significant differences in the proportion of children aged ≤3 years, TNF-α, CRP, SI, IMT, EDD, FMD, and NMD between the nCAL and CAL groups (all P<0.05). Age ≤3 years, elevated levels of TNF-α, CRP, SI, IMT, and EDD, as well as decreased levels of FMD and NMD, were independent risk factors for CAL in children with IKD (all P<0.05). The column chart prediction model had high discrimination, and the area under the curve for predicting CAL occurrence in children with IKD was 0.868 and 0.830, respectively. Conclusions:There are significant differences in endothelial function among children with IKD of different ages, and endothelial function is closely related to the occurrence of CAL. When endothelial function is abnormal, CAL is more likely to occur.

ObjectiveTo investigate the effects of Anmeidan （AMD） on cognitive function， cytochrome C （Cyt C） signaling pathway protein expression， and apoptosis in a geriatric sleep deprivation model. MethodSixty aged C57 mice were randomly divided into a blank group， a model group， AMD high， medium， and low dose （26.26， 13.13， 6.565 g·kg^-1·d^-1） groups， and a melatonin group （1.3 mg·kg^-1·d^-1）， with 10 mice in each group. Continuous sleep deprivation was performed for 4 weeks using a homemade sleep deprivation box. Cognitive function was assessed using the Morris water maze， and morphological changes in pyramidal cells in the CA1 area of the hippocampus were observed by hematoxylin-eosin （HE） staining and Nissl staining. Transmission electron microscopy was used to observe the mitochondrial morphology and structure of hippocampal neurons. Western blot was used to detect Cyt C， cysteine-aspartate protease-3 （Caspase-3）， cysteine-aspartate protease-9 （Caspase-9）， brain-derived neurotrophic factor （BDNF）， mitochondrial transcription factor A （TFAM）， and voltage-dependent anion channel 1 （VDAC1） protein expression. Immunohistochemistry was used to detect protein expression levels of Cyt C， Caspase-3， and Caspase-9， and immunofluorescence was used to detect the protein expression of B-cell lymphoma 2 （Bcl-2） and Bcl-2-associated X protein （Bax）. ResultCompared with the blank group， the model group showed prolonged platform latency （P<0.01）， reduced number of platform crossings， and reduced time and distance in the target quadrant （P<0.01）. The mitochondrial structure was damaged， with disappearance or breakage of cristae， and increased swelling and deformation. The protein expression levels of Cyt C， Caspase-3， Caspase-9， Bax， and VDAC1 were significantly increased （P<0.01）， while BDNF， TFAM， and Bcl-2 protein expression levels were decreased （P<0.01）. Compared with the model group， the AMD high， medium， and low dose groups improved spatial exploration and navigation abilities in geriatric sleep-deprived mice （P<0.05， P<0.01）， alleviated mitochondrial damage， and increased the number of Nissl bodies. Additionally， the expression levels of Cyt C， Caspase-3， Caspase-9， Bax， and VDAC1 proteins were significantly reduced （P<0.05， P<0.01）， while the expression levels of BDNF， TFAM， and Bcl-2 proteins were significantly increased （P<0.05， P<0.01）. ConclusionAMD improved the cognitive function of geriatric sleep-deprived mice， and its effect may be related to the reduction of apoptosis mediated by the Cyt C signaling pathway.

BACKGROUND:The distribution of the necrotic area plays an important role in hip preservation treatment.At present,there are few studies on whether the difference in the three-dimensional spatial distribution of osteonecrosis of the femoral head affects the clinical outcome of fibular support. OBJECTIVE:To explore the relationship between the spatial distribution and clinical outcome at the sites of osteonecrosis of the femoral head and fibular support using CT three-dimensional reconstruction so as to provide a basis for optimizing the applicable conditions of fibular support and improving the hip preservation effect of fibular support. METHODS:Eighty patients with osteonecrosis of the femoral head who were treated with fibular support for hip preservation from January 2010 to January 2021 were selected as the study subjects according to the inclusion criteria.They were followed up for at least 2 years.According to the clinical outcome,the patients were divided into the successful hip preservation group(n=55)and the failure hip preservation group(n=25).3D reconstruction was performed according to the preoperative and postoperative CT images of the patients.According to the three-column theory,the femoral head was divided into outer nine areas,middle nine areas and inner nine areas(L1-9,C1-9,and M1-9)to explore the spatial distribution of necrotic area of the femoral head and fibular support area and its relationship with clinical outcome. RESULTS AND CONCLUSION:(1)Before operation,the necrotic area of the femoral head was mainly distributed in L1,L2,L4,L5,C1,C2,C4,and C5(the upper and middle part of the anterior part of the outer ninth area and the middle part of the middle ninth area).After operation,the fibular support area was mainly distributed in L5,L6,C5,and C6(the middle and lower part of the outer ninth area and the middle and lower part of the middle ninth area).(2)There were significant differences in the distribution of osteonecrosis of the femoral head between the successful hip preservation group and the failure hip preservation group in L8(the posterior middle part of the outer ninth area),C3(the anterior lower part of the middle ninth area),C6(the lower middle part of the middle part of the inner ninth area)and M2(the anterior middle part of the inner ninth area)(P<0.05).There was a significant difference in the distribution of fibular support in L5 and L6(middle and lower part of outer nine)(P<0.05).Among them,the L8 region could be used as an independent predictor of hip preservation failure in fibular support surgery.The area under the curve of the L8 single factor prediction model was 0.698[95%CI(0.575,0.822)];the sensitivity was 76%,and the specificity was 63.6%.(3)It turns out,when the necrotic area involves L8,C3,C6,and M2,especially L8,the failure of fibular support may increase,and when the fibular support involves L5 and L6,the effect of hip preservation is often not ideal.

BACKGROUND:The appearance of the crescent sign in femoral head necrosis is a"turning point"in the progression of the disease,and repairing and stabilizing the bone-cartilage interface is particularly important in preventing further progression and collapse of the femoral head.Tissue engineering offers potential advantages in the simultaneous repair and integration of the bone-cartilage interface. OBJECTIVE:To review potentially suitable techniques addressing the subchondral separation in femoral head necrosis. METHODS:Relevant articles from January 1970 to April 2023 were searched in PubMed,Web of Science,and China National Knowledge Infrastructure(CNKI)using English search terms"femoral head necrosis,avascular necrosis of femoral head,osteonecrosis of femoral head"and Chinese search terms"femoral head necrosis,subchondral bone,cartilage,integration of cartilage and subchondral bone".A total of 114 articles were included for review and analysis. RESULTS AND CONCLUSION:(1)Structural defects,ischemic and hypoxic environment,inflammatory factors,and stress concentration may cause subchondral separation in osteonecrosis of the femoral head.Subchondral bone collapse and failure of hip-preserving surgery may be associated.Integration of tissue engineering scaffolds with the bone-cartilage interface is one potential approach for treating subchondral separation in osteonecrosis of the femoral head.(2)Current literature suggests that multiphase scaffolds,gradient scaffolds,and composite materials have shown improvements in promoting cell adhesion,proliferation,and deposition of bone and cartilage matrix.These advancements aid in the integration of scaffolds with the bone-cartilage interface and have implications for the treatment of subchondral separation in osteonecrosis of the femoral head.(3)Surface modifications of scaffolds can enhance interface integration efficiency,but they have their advantages and disadvantages.Scaffolds providing different environments can induce differentiation of mesenchymal stem cells and facilitate integration between different interfaces.(4)Future scaffolds for subchondral separation in osteonecrosis of the femoral head are expected to be composite materials with gradient and differentiated biomimetic structures.Surface modifications and stem cell loading can promote integration between the bone-cartilage interface and scaffolds for therapeutic purposes,but further experimental verification is still needed.Challenges include synchronizing scaffold degradation rate with repair progress and ensuring stability between different interfaces.

BACKGROUND:Bone has bioelectric effects.However,bone defects can lead to loss of endogenous bioelectricity in bone.The implantation of bone tissue engineering scaffolds with bioelectric effect into bone defects will replenish the missing electrical signals and accelerate the repair of bone defects. OBJECTIVE:To introduce the bioelectric effect of bone tissue and expound the repair effect of electrical stimulation on bone defects,summarize the research progress of bioelectric effect applied to bone tissue engineering,in order to provide new ideas for the research of bone tissue engineering. METHODS:Relevant articles were searched on CNKI,WanFang,PubMed,Web of Science and ScienceDirect databases,using"bioelectrical effect,bioelectrical materials,electrical stimulation,bone tissue engineering,bone scaffold,bone defect,bone repair,osteogenesis"as the English and Chinese search terms.Finally,87 articles were included for analysis. RESULTS AND CONCLUSION:(1)Bioelectrical effect combined with ex vivo electrical stimulation to design bone tissue engineering scaffolds is an ideal and feasible approach,and the main materials involved include metallic materials,graphene materials,natural bio-derived materials,and synthetic biomaterial.At present,the most widely used conductive material is graphene material,which benefits from its super conductivity,large specific surface area,good biocompatibility with cells and bones,and excellent mechanical properties.(2)Graphene materials are mainly introduced into the scaffold as modified materials to enhance the conductivity of the overall scaffold,while its large surface area and rich functional groups can promote the loading and release of bioactive substances.(3)However,there are still some major challenges to overcome for bioelectrically effective bone tissue engineering scaffolds:not only electrical conductivity but also the overall performance of the bracket needs to be considered;lack of uniform,standardized preparation of bioelectrically effective bone tissue engineering scaffolds;extracorporeal electrical stimulation intervention systems are not yet mature enough;lack of individualized guidance on stent selection to enable the selection and design of the most appropriate stent for patients with different pathologies.(4)When designing conductive scaffolds,researchers have to deeply consider the comprehensive effects of the scaffolds,such as biocompatibility,mechanical properties,and biodegradability.This combination of properties can be achieved by combining multiple materials.(5)Beyond that,clinical translation should be the ultimate consideration for conductive stent design.On the basis of evaluating the safe current threshold for electrical stimulation to act on the human body and facilitate the repair of bone defects,animal experiments as well as basic experiments are designed and then applied to the clinic to achieve the ultimate goal of applying bioelectrical effect bone tissue engineering scaffolds in the clinic.

Background Under the backdrop of the national innovation-driven development strategy, the increasing occupational stress and job burnout among employees are noteworthy for their impact on employees' subjective well-being. Objective To clarify the status, distribution characteristics, and the relationship between subjective well-being, occupational stress, and job burnout of employees in research and development (R&D) enterprises, in order to improve their subjective well-being. Methods A total of 3366 employees from R&D departments at 7 enterprises in Minhang District of Shanghai were selected. The well-being level of the research subjects was investigated by using the World Health Organization Well-Being Index (WHO-5) that yielded total scores from 0 to 25, and a higher total score indicated a higher well-being level; the levels of occupational stress and job burnout were investigated by using the Chinese version of the Job Content Questionnaire, and the Chinese version of the Maslach Burnout Inventory-General Survey (MBI-GS). The scores of WHO-5, JDC, and MBI-GS were incorporated into structural equation modeling (SEM) as numerical variables to analyze their relationship. Results The scores of subjective well-being, occupational stress, and job burnout of employees in the R&D enterprises were 13.30±6.09, 1.12±0.45, and 2.18±1.12, respectively. The positive rates of occupational stress and job burnout were 44.4% and 70.9% respectively, and the positive rate of severe job burnout was 11.7%. There were statistically significant differences in the score of subjective well-being among the participants by gender, age, educational level, marital status, registered residence, working seniority, and jobs (P<0.05); there were statistically significant differences in the positive rate of occupational stress by gender, educational level, marital status, working seniority, and jobs (P<0.05); there were statistically significant differences in the positive rate of job burnout by gender, age, educational level, marital status, registered residence, working seniority, and jobs (P<0.05). There was a negative correlation between subjective well-being and occupational stress (r=−0.1747, P < 0.01), a negative correlation between subjective well-being and job burnout (r=−0.2987, P < 0.01), and a positive correlation between occupational stress and job burnout (r=0.3342, P < 0.01). A structural equation containing partial mediating effect of job burnout on the relationship between occupational stress and subjective well-being was established, and the partial effect accounting for 52.5% of the total effect. Conclusion The job burnout among employees in R&D companies partially mediates the impact of occupational stress on subjective well-being. Reducing the level of job burnout will help alleviate occupational stress and thus improve employees' subjective well-being.