ObjectiveObesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer’s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved. MethodsA total of sixty 6-week-old male C57BL/6 mice, weighing between 20-30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totally 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axon length, dendritic complexity, number of spines, the expression of c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1β (IL-1β), and the number of major histocompatibility complex II (MHC-II) positive cells. ResultsMice with HFD-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the HFD-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the HFD-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the HFD-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity(P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the HFD-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of HFD-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a HFD. ConclusionTreadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in HFD-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against HFD-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.

ObjectiveExisting artificial vision devices can be divided into two types: implanted devices and extracorporeal devices, both of which have some disadvantages. The former requires surgical implantation, which may lead to irreversible trauma, while the latter has some defects such as relatively simple instructions, limited application scenarios and relying too much on the judgment of artificial intelligence (AI) to provide enough security. Here we propose a system that has voice interaction and can convert surrounding environment information into tactile commands on head and neck. Compared with existing extracorporeal devices, our device can provide a larger capacity of information and has advantages such as lower cost, lower risk, suitable for a variety of life and work scenarios. MethodsWith the latest remote wireless communication and chip technologies, microelectronic devices, cameras and sensors worn by the user, as well as the huge database and computing power in the cloud, the backend staff can get a full insight into the scenario, environmental parameters and status of the user remotely (for example, across the city) in real time. In the meanwhile, by comparing the cloud database and in-memory database and with the help of AI-assisted recognition and manual analysis, they can quickly develop the most reasonable action plan and send instructions to the user. In addition, the backend staff can provide humanistic care and emotional sustenance through voice dialogs. ResultsThis study originally proposes the concept of “remote virtual companion” and demonstrates the related hardware and software as well as test results. The system can not only achieve basic guide functions, for example, helping a person with visual impairment to shop in supermarkets, find seats at cafes, walk on the streets, construct complex puzzles, and play cards, but also can meet the demand for fast-paced daily tasks such as cycling. ConclusionExperimental results show that this “remote virtual companion” is applicable for various scenarios and demands. It can help blind people with their travels, shopping and entertainment, or accompany the elderlies with their trips, wilderness explorations, and travels.

【Objective】 To study and compare the effects of different storage temperature and time on coagulation factor after cryoprecipitated antihemophilic factor(CAF) melting, and to provide reference for the establishment of industry standards. 【Methods】 From June 2021 to May 2023, a total of 96 bags of CAF were sampled in 4 bags per month, and timely detected in the same month. After the CAF was melted in a 37℃ water bath, the mild to moderate lipemic blood was labeled. Each bag of CAF and two 50 mL transfer bags were divided into two bags and two groups of 20 mL each using a sterile adapter. One group was placed in a 4℃ refrigerator and the other in a 22℃ water bath for 0 h, 4 h, 8 h, 12 h, 24 h and 48 h. Then 2 mL of aseptic sample was taken separately and put into the test tube, and 1mL of sample and 3 mL of buffer were added into the other test tube with the sampling gun and mixed on the machine for testing. The experimental data of 60 bags without mild to moderate lipemic blood cryoprecipitation and coagulation factor were randomly selected and statistically analyzed by SPSS21.0. 【Results】 After melting, CAF was stored for 0 h, 4 h, 8 h, 12 h, 24 h and 48 h to detect the average content and growth rate of coagulation factor in the two groups: 1) Storage at 4℃, factor Ⅷ content was 118.62, 111.57(-5.95%), 105.51(-11.05%), 103.30(-12.92%), 94.35(-20.46%) and 83.25(-29.82%) IU/ bag, respectively; Storage at 22℃, the factor Ⅷ content was 118.62, 112.69(-5.00%), 111.41(-6.08%), 109.01(-8.10%), 101.55(-14.39%) and 92.75(-21.81%) IU/ bag, and the storage results of the two groups were compared. At 24 h at 4℃ and 48 h at 22℃, the content of factor Ⅷ had significant statistical significance(P<0.01), and when stored at 22℃, the decay rate of factor Ⅷ was slower; 2) When stored at 4℃, the content of factor V was 41.19, 41.31(0.29%), 40.52(-1.64%), 40.27(-2.23%), 39.05(-5.19%) and 36.99(-10.21%) IU/ bag, respectively; Stored at 22℃, the factor V content was 41.19, 41.71(1.25%), 42.54(3.28%), 41.94(1.80%), 39.21(-4.80%) and 35.64(-13.48%) IU/ bag, respectively. Comparison of storage results between the two groups showed that the content of factor V was statistically significant(P<0.05) and significantly significant(P<0.01) at 4℃48 h and 22℃48 h, respectively, and the decay rate of factor V was faster when stored at 22℃; 3) When stored at 4℃, the Fbg content was 268.86, 268.17(-0.26%), 262.46(-2.38%), 270.50(0.61%), 267.52(-0.50%) and 261.92(-2.58%) mg/ bag, respectively; Stored at 22℃, the Fbg content was 268.86, 265.86(-1.12%), 264.12(-1.77%), 265.89(-1.11%), 266.04(-1.05%) and 261.04(-2.91%) mg/ bag, respectively. There was no statistical significance between the 2 groups and the original 0 h content in each time period(P>0.05). 【Conclusion】 After CAF melting, coagulation factor decreased with the extension of storage time, especially the decrease of factor Ⅷ, followed by factor V, while Fbg basically unchanged. Comparison between the two groups showed that, factor Ⅷ decay rate is slower, factor V decay rate is faster of storage at 22℃. CAF should be transfused as soon as possible after melting. If the delay is unavoidable, for the delay time less than 12 h, storage at 4℃ is recommended, fot the delay time more than 12 h and less than 24 h, storage at 22℃ is recommended.

Objective:To carry out cytogenetic and molecular genetic analysis for two infertile patients carrying rare small supernumerary marker chromosomes (sSMC).Methods:Two infertile patients who received reproductive and genetic counseling at CITIC Xiangya Reproductive and Genetic Hospital on October 31, 2018 and May 10, 2021, respectively were selected as the study subjects. The origin of sSMCs was determined by conventional G banding, fluorescence in situ hybridization (FISH) and copy number variation sequencing (CNV-seq). Microdissection combined with high-throughput whole genome sequencing (MicroSeq) was carried out to determine the fragment size and genomic information of their sSMCs. Results:For patient 1, G-banded karyotyping and FISH revealed that he has a karyotype of mos47, XY, del(16)(p10p12), + mar[65]/46, XY, del(16)(p10p12)[6]/48, XY, del(16)(p10p12), + 2mar[3].ish mar(Tel 16p-, Tel 16q-, CEP 16-, WCP 16+ ). CNV analysis has yielded a result of arr[GRCh37]16p12.1p11.2(24999364_33597595)×1[0.25]. MicroSeq revealed that his sSMC has contained the region of chromosome 16 between 24979733 and 34023115 (GRCh37). For patient 2, karyotyping and reverse FISH revealed that she has a karyotype of mos 47, XX, + mar[37]/46, XX[23].rev ish CEN5, and CNV analysis has yielded a result of seq[GRCh37]dup(5)(p12q11.2)chr5: g(45120001_56000000)dup[0.8]. MicroSeq results revealed that her sSMC has contained the region of chromosome 5 between 45132364 and 55967870(GRCh37). After genetic counseling, both couples had opted in vitro fertilization (IVF) treatment and preimplantation genetic testing (PGT). Conclusion:For individuals harboring sSMCs, it is vital to delineate the origin and structural characteristics of the sSMCs for their genetic counseling and reproductive guidance. Preimplantation genetic testing after microdissection combined with high-throughput whole genome sequencing (MicroSeq-PGT) can provide an alternative treatment for carrier couples with a high genetic risk.

Background and purpose:Outcomes for cancer patients with steroid-resistant immune checkpoint inhibitor-associated myocarditis(srICIAM)are poor.Intensified immunosuppressive therapies,including tofacitinib,a novel Janus kinase(JAK)inhibitor,may have some therapeutic benefits.However,due to the lack of sufficient clinical data,the effectiveness of such treatments and their impact on cardiovascular outcomes remain unclear.This study aimed to investigate the therapeutic effect of tofacitinib on srICIAM.Methods:This retrospective case-control study included 36 malignant tumor patients who received immune checkpoint inhibitor treatment at Zhongshan Hospital affiliated to Fudan University from July 2019 to May 2022 and developed srICIAM.Patients receiving corticosteroids in combination with tofacitinib were assigned to the tofacitinib group(n=19),while those not treated with tofacitinib were allocated to the control group(n=17).The study compared clinical characteristics,laboratory findings,and imaging results between the two groups.Additionally,follow-up was conducted to monitor the incidence of cardiovascular endpoints in these patients.The research plan was approved by the Ethics Committee of Zhongshan Hospital Affiliated to Fudan University(Approval Number:B2021-275R).This study was conducted in accordance with the ethical guidelines of the Helsinki Declaration.Results:Compared to the control group,and with no significant difference in the cumulative dose and duration of corticosteroids(P＜0.05),the tofacitinib group showed a shorter myocarditis recovery time(median recovery time:86.5 days vs 126.5 days,P=0.021).The myocarditis-related mortality rate was significantly lower in the tofacitinib group than in the control group(5%vs 35%,P=0.025).Conclusion:Tofacitinib may reduce mortality and promote cardiac recovery in srICIAM patients without impeding the anti-tumor effect.It may become one of the potential treatment strategies in the future.

Objective To explore causal relationship between atopic diseases(asthma and atopic dermatitis)and os-teoarthritis(OA)by using mendelian randomization(MR).Methods Asthma and atopic dermatitis as instrumental variables were selected,searched them through IEU database,and selected the latest data with a large number of cases and single nu-cleotide polymorphism(SNP).Data were collected and processed using R language,inverse varianceweighted(IVW)method was adopted as main MR Evaluation method.Single linear regression was performed to estimate causality based on pooled knee and hip data from genome-wide association studies(GWAS).The forest map was drawn to visualize the results,and gene pleiotropy and sensitivity were analyzed by scatter plot and funnel plot.At the same time,asthma,atopic dermatitis,body mass index(BMI),osteoporosis and OA were selected for multivariate MR Analysis to exclude the effect of horizontal pleiotropy on the results in GWAS data.Results Analysis of MR-IVW results showed asthma was positively correlated with causal effect of OA[OR=1.41,95％CI(1.07,1.85),P=0.02],multivariate Mendelian randomization(MVMR)adjusted for BMI and osteo-porosis and a direct causal effect on OA was observed[OR=1.57,95％CI(1.03,2.39),P=0.03)].MR Results of two samples of atopic dermatitis and OA were[OR=1.01,95％CI(0.97,1.04),P=0.76],and MVMR results were[OR=1.02,95％CI(0.99,1.05),P=0.25],indicating no clear causal relationship between two samples.Conclusion Asthma could increase risk of OA,atopic dermatitis has no obvious relationship with OA,and the relationship between atopic diseases and OA still needs to be discussed.

Objective To evaluate the diagnostic efficacy of artificial vision,radiomics(RAD)and deep learning(DL)in distinguishing atypical usual interstitial pneumonia(UIP)from nonspecific interstitial pneumonia(NSIP).Methods A retrospective analysis was conducted on 300 patients diagnosed with interstitial pneumonia(IP).A total of 56 cases of atypical UIP and 57 cases of NSIP were included.All patients underwent CT examination before biopsy,and were randomly divided into training and test groups.DL and RAD artificial intelligence models were developed and trained.The consistency of artificial vision assessment was performed via Kappa test and receiver operating characteristic(ROC)curve analysis was performed via logistic regression.Then,the differences in the area under the curve(AUC)of different models were compared via DeLong analysis.The diagnostic efficiency of the model was evaluated via AUC and accuracy(ACC)as the main indicators and compared with the artificial vision evaluation.Results Two radiologists showed significant consistency in the CT diagnosis and interpretation of atypical UIP and NSIP(Kappa=0.852,P＜0.01).On high-resolution computed tomography(HRCT),the atypical UIP patients mainly showed basal bronchiectasis,honeycombing,and reticular opacities,while,the NSIP patients showed basal reticular opacities,ground glass opacity(GGO)and subpleural avoidance sign.The probability of GGO exceeding the reticular opacities of the NSIP patients was significantly higher than that of the atypical UIP patients(P＜0.05).The DL model showed significantly higher diagnostic efficiency than RAD and artificial vision in the differential diagnosis of atypical UIP and NSIP(AUC:0.94 vs 0.85 vs 0.65,P＜0.01).Conclusion CT and RAD have a certain significant diagnostic value for atypical UIP and NSIP.Atypical UIP and NSIP can be more accurately differentiated and diagnosed based on the DL model,thereby,the management of IP is further strengthened in clinical practice.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

Objective:To compare the clinical effect of "de-sharpening" intramedullary elastic reduction with Kirschner wire and traditional three-dimensional manipulation for the treatment of Gartland type III posterolaterally-displaced supracondylar humerus fracture in children.Methods:A retrospective cohort analysis was made on 106 children with Gartland type III posterolaterally-displaced supracondylar humerus fracture treated in Anhui Provincial Children′s Hospital from March 2020 to June 2022, including 58 males and 48 females; aged 1-12 years [(8.7±2.3)years]. The patients were assigned to "de-sharpening" intramedullary elastic reduction with Kirschner wire (study group, n=50) and traditional three-dimensional manipulation (control group, n=56). The operation time, frequency of intraoperative fluoroscopy, fracture healing time, difference of Baumann angle between the normal and injured side at postoperative 3 and 6 months, elbow function Flynn score at last follow-up and complications were compared between the two groups. Results:All children were followed up for 6-12 months [(8.5±1.2)months]. The operation time and frequency of intraoperative fluoroscopy were (32.9±3.7)minutes and (20.6±5.4)times in study group, significantly different from (45.6±10.1)minutes and (32.5±8.2)times in control group (all P<0.05). The fracture healing time was (33.0±5.1)days in study group, similar with (33.8±4.7)days in control group ( P>0.05). At 3 and 6 months after operation, the difference of Baumann angle between the normal and injured side was (3.2±0.8)°and (2.3±0.6)°in study group compared to (6.0±2.1)°and (5.8±1.3)°in control group (all P<0.01). According to the elbow function Flynn score at the last follow-up, the results were excellent in 44 children, good in 5 and fair in 1, with the excellent and good rate of 98.0% (49/50) in study group, and were excellent in 47 children, good in 5 and fair in 4, with the excellent and good rate of 92.9% (52/56) in control group ( P>0.05). There were no following complications in both groups, such as osteomyelitis, poor fracture healing, compartment syndrome, iatrogenic neurovascular injury or myositis ossificans. Conclusions:Both "de-sharpening" intramedullary elastic reduction with Kirschner wire and traditional three-dimensional manipulation for the treatment of Gartland type III posterolaterally-displaced supracondylar humerus fracture in children can achieve elbow joint function recovery, with low incidence of complications. However, the former avoids repeated manual reduction, with shorter operation time, less frequency of intraoperative fluoroscopy and better correction of the coronal plane deformity and rotation deformity.

OBJECTIVE: To explore the potential mechanism of resistance to axitinib in clear cell renal cell carcinoma (ccRCC), with a view to expanding the understanding of axitinib resistance, facilitating the design of more specific treatment options, and improving the treatment effectiveness and survival prognosis of patients. METHODS: By exploring the half maximum inhibitory concentration (IC₅₀) of axitinib on ccRCC cell lines 786-O and Caki-1, cell lines resistant to axitinib were constructed by repeatedly stimulated with axitinib at this concentration for 30 cycles in vitro. Cell lines that were not treated by axitinib were sensitive cell lines. The phenotypic differences of cell proliferation and apoptosis levels between drug resistant and sensitive lines were tested. Genes that might be involved in the drug resistance process were screened from the differentially expressed genes that were co-upregulated in the two drug resistant lines by transcriptome sequencing. The expression level of the target gene in the drug resistant lines was verified by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB). The expression differences of the target gene in ccRCC tumor tissues and adjacent tissues were analyzed in the Gene Expression Profiling Interactive Analysis (GEPIA) public database, and the impact of the target gene on the prognosis of ccRCC patients was analyzed in the Kaplan-Meier Plotter (K-M Plotter) database. After knocking down the target gene in the drug resistant lines using RNA interference by lentivirus vector, the phenotypic differences of the cell lines were tested again. WB was used to detect the levels of apoptosis-related proteins in the different treated cell lines to find molecular pathways that might lead to drug resistance. RESULTS: Cell lines 786-O-R and Caki-1-R resistant to axitinib were successfully constructed in vitro, and their IC₅₀ were significantly higher than those of the sensitive cell lines (10.99 μmol/L, P < 0.01; 11.96 μmol/L, P < 0.01, respectively). Cell counting kit-8 (CCK-8) assay, colony formation, and 5-ethynyl-2 '-deoxyuridine (EdU) assay showed that compared with the sensitive lines, the proliferative ability of the resistant lines decreased, but apoptosis staining showed a significant decrease in the level of cell apoptosis of the resistant lines (P < 0.01). Although resistant to axitinib, the resistant lines had no obvious new replicated cells in the environment of 20 μmol/L axitinib. Nuclear protein 1 (NUPR1) gene was screened by transcriptome sequencing, and its RNA (P < 0.0001) and protein expression levels significantly increased in the resistant lines. Database analysis showed that NUPR1 was significantly overexpressed in ccRCC tumor tissue (P < 0.05); the ccRCC patients with higher expression ofNUPR1had a worse survival prognosis (P < 0.001). Apoptosis staining results showed that knockdown ofNUPR1inhibited the anti-apoptotic ability of the resistant lines to axitinib (786-O, P < 0.01; Caki-1, P < 0.05). WB results showed that knocking downNUPR1decreased the protein level of B-cell lymphoma-2 (BCL2), increased the protein level of BCL2-associated X protein (BAX), decreased the protein level of pro-caspase3, and increased the level of cleaved-caspase3 in the resistant lines after being treated with axitinib. CONCLUSION ccRCC cell lines reduce apoptosis through theNUPR1 -BAX/ BCL2 -caspase3 pathway, which is involved in the process of resistance to axitinib.
Humans ; Carcinoma, Renal Cell/metabolism* ; Axitinib/pharmacology* ; Kidney Neoplasms/metabolism* ; bcl-2-Associated X Protein ; Nuclear Proteins ; Cell Line, Tumor ; Apoptosis ; Cell Proliferation