BACKGROUND:The use of exosomes as drug carriers can not only precisely target the therapeutic site,but also increase the local concentration,opening up a new way for drugs to enter the central nervous system.OBJECTIVE:To explore the biogenesis and biological functions of exosomes and summarize the current state-of-the-art regarding extracellular vesicles as drug carriers in the treatment of central nervous system diseases.METHODS:The first author searched Web of Science,PubMed,and CNKI for relevant literature from January 1976 to January 2024.The English search terms were"exosomes,extracellular vesicles,central nervous system,drug delivery,ischemic stroke,Alzheimer's disease,Parkinson's disease,spinal cord injury,brain tumor."The Chinese search terms were"exosomes,extracellular vesicles,central nervous system diseases,drug delivery,stroke,Alzheimer's disease,Parkinson's disease,spinal cord injury,brain tumor."Finally,94 articles were included for analysis.RESULTS AND CONCLUSION:(1)Exosomes can easily cross the blood-brain barrier and deliver proteins,metabolites,and nucleic acids to recipient cells to regulate cellular metabolism.Since exosomes are small vesicles secreted by cells,they have a much lower circulating immunogenicity and can be less likely to be recognized and cleared by macrophages in the internal circulation.(2)Exosomes can be engineered to deliver different therapeutically ingredients,including RNA,proteins,chemotherapeutic drugs,and immunomodulators,and are capable of delivering them to the desired target areas.Engineered modified exosomes have better targeting properties.Furthermore,this exosome-mediated delivery is extremely low in immunogenicity and is expected to provide a safer and more effective method for precision therapy of central nervous system diseases in the future.

Objective:To analyze the distribution of allergen components of dust mite in children with airway allergic diseases.Methods:This was a cross-sectional study. The clinical data of children with dust mite-induced allergic asthma (AA) complicated with allergic rhinitis (AR) or allergic rhinitis who were treated in Department of Allergy,Beijing Children′s Hospital from January 2019 to October 2022 were retrospectively analyzed. The spedific IgE (sIgE) levels to Der p1,Der p2,Der p5,Der p7,Der p10,Der p21,Der p23 and Der f1,Der f2 were detected by protein chip method. The distribution of dust mite sensitized components and the sIgE levels in children with different airway allergic diseases and different ages were compared.Results:Among 138 children with airway allergic diseases,there were 97 boys and 41 girls,age (6.86±2.61) years old,and there were 106 cases of AA combined AR (AAAR group) and 32 cases of AR alone (AR group). The sensitization rates of Der p2 was the highest (75.4%,104/138),followed by Der f2 (74.6%,103/138),Der f1 (73.9%,102/138),Der p1 (71.7%,99/138),Der p21 (19.6%,27/138),Der p5 (16.7%,23/138),Der p23 (14.5%,20/138),Der p7 (11.6%,16/138) and Der p10 (2.9%,4/138). The co-sensitization rate of Der p1,Der p2,Der f1 and Der f2 was the highest (31.2%,43/138). There was no significant difference in sensitization rate of dust mites components between AAAR group and AR group(all P>0.05). AAAR group had higher levels of sIgE to Der p23 than AR group [0.1 (0,0.1) IU/ml vs. 0 (0,0.1) IU/ml,Z=-2.819, P=0.005]. There were no significant differences in the positive rate of dust mite components and sIgE levels between children aged≤6 and>6 years old with airway allergic diseases(all P>0.05). Conclusions:Der p1,Der p2,Der f1 and Der f2 are the major components of dust mites sensitizing airway allergic diseases in children. Der p1,Der p2,Der f1 and Der f2 are the main co-sensitizing components in children with dust mite-induced airway allergic diseases. Compared with AR,the sIgE level to Der p23 in children with AAAR is higher.

Objective:To introduce the research and innovations around the application of aquatic rehabilitation techniques in the treatment of lumbago, and to summarize specific methods and applications in aeromedicine. Literature resource and selection Literature on the prevention and treatment of lumbago using aquatic rehabilitation techniques as well as on the rehabilitation of lumbago in pilots was retrieved and selected. Literature quotation Sixty-one references were cited. Literature synthesis Aquatic rehabilitation techniques can be classified into shower therapy, immersion therapy, and aquatic exercise therapy according to treatment regimens. Among them, immersion therapy and aquatic exercise therapy are commonly used in the treatment of lumbago. Aquatic rehabilitation techniques can effectively alleviate patients′ lumbago, improve their functional disorders, and enhance their quality of life. Prior to aquatic therapy, patients with lumbago need to have their motor function assessed to tailor the treatment protocol based on diagnostic findings and specific therapeutic objectives. Aquatic rehabilitation techniques, when used to prevent and treat lumbago in pilots under convalescence, are not only more effective than land-based training, but also more accessible to pilots due to their comfort and compliance. Many of our military rehabilitation and convalescent centers in China have integrated modern aquatic rehabilitation techniques into rehabilitation treatment by drawing on their rich water resources so as to improve the physical and mental health, social adaptability and military adaptability of pilots. Conclusions:When used for the prevention and treatment of lumbago, aquatic rehabilitation techniques are highly effective, safe and enjoyable, so they should be made more accessible to pilots during convalescence.

OBJECTIVE: To observe the effects of electroacupuncture (EA) on improving motor function and regulating microglial activation based on Notch receptor 1 (Notch1)/Hes family bHLH transcription factor 1 (Hes1) pathway in mice with Parkinson's disease (PD). METHODS: Thirty-six male C57BL/6 mice were randomly divided into a control group, a model group and an EA group, 12 mice in each group. PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days in the model group and the EA group. From the 1st day of modeling, EA was applied at "Baihui" (GV20) and bilateral "Shenshu" (BL23) in the EA group, with continuous wave, in frequency of 2 Hz and current of 2 mA, 15 min a time, once a day for 14 days continuously. The behavioral performance was evaluated by gait test, pole climbing test and hanging test, the number of positive cells of tyrosine hydroxylase (TH) and the co-expression positive cells of Notch1/ionized calcium binding adaptor molecule 1 (Iba-1) in the substantia nigra of midbrain was assessed by immunofluorescence, the protein expression of TH, α-synuclein (α-syn), Notch1, Hes1, Iba-1, inducible nitric oxide synthase (iNOS), Arginase-1 (ARG1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 was detected by Western blot, the mRNA expression of Notch1 and Hes1 was detected by real-time PCR. RESULTS: Compared with the control group, in the model group, the stride frequency was accelerated (P<0.001) and the stride length was shortened (P<0.001) for the four limbs, the pole climbing test time was prolonged (P<0.01) and the grip level was reduced (P<0.01); in the substantia nigra of midbrain, the number of positive cells of TH was decreased (P<0.001), the number of co-expression positive cells of Notch1/Iba-1 was increased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-1βand IL-6 was increased (P<0.01, P<0.05, P<0.001), the protein expression of TH, ARG1 and IL-10 was decreased (P<0.01, P<0.001), the mRNA expression of Notch1 and Hes1 was increased (P<0.01). Compared with the model group, in the EA group, the stride frequency was decelerated (P<0.001) and the stride length was increased (P<0.05, P<0.01, P<0.001) for the four limbs, the pole climbing test time was shortened (P<0.05) and the grip level was increased (P<0.05); in the substantia nigra of midbrain, the number of positive cells of TH was increased (P<0.01), the number of co-expression positive cells of Notch1/Iba-1 was decreased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-6 and IL-1β was decreased (P<0.05, P<0.01), the protein expression of TH, ARG1 and IL-10 was increased (P<0.05, P<0.001, P<0.01), the mRNA expression of Notch1 and Hes1 was decreased (P<0.05). CONCLUSION EA can improve the behavioral performance and protect the dopaminergic neurons in PD mice, its mechanism may relate to the inhibition of Notch1/Hes1-mediated neuroinflammation, thus inhibiting the microglial activation.
Animals ; Electroacupuncture ; Microglia/metabolism* ; Male ; Receptor, Notch1/metabolism* ; Parkinson Disease/physiopathology* ; Transcription Factor HES-1/metabolism* ; Mice ; Mice, Inbred C57BL ; Humans ; Signal Transduction

BACKGROUND:The use of exosomes as drug carriers can not only precisely target the therapeutic site,but also increase the local concentration,opening up a new way for drugs to enter the central nervous system.OBJECTIVE:To explore the biogenesis and biological functions of exosomes and summarize the current state-of-the-art regarding extracellular vesicles as drug carriers in the treatment of central nervous system diseases.METHODS:The first author searched Web of Science,PubMed,and CNKI for relevant literature from January 1976 to January 2024.The English search terms were"exosomes,extracellular vesicles,central nervous system,drug delivery,ischemic stroke,Alzheimer's disease,Parkinson's disease,spinal cord injury,brain tumor."The Chinese search terms were"exosomes,extracellular vesicles,central nervous system diseases,drug delivery,stroke,Alzheimer's disease,Parkinson's disease,spinal cord injury,brain tumor."Finally,94 articles were included for analysis.RESULTS AND CONCLUSION:(1)Exosomes can easily cross the blood-brain barrier and deliver proteins,metabolites,and nucleic acids to recipient cells to regulate cellular metabolism.Since exosomes are small vesicles secreted by cells,they have a much lower circulating immunogenicity and can be less likely to be recognized and cleared by macrophages in the internal circulation.(2)Exosomes can be engineered to deliver different therapeutically ingredients,including RNA,proteins,chemotherapeutic drugs,and immunomodulators,and are capable of delivering them to the desired target areas.Engineered modified exosomes have better targeting properties.Furthermore,this exosome-mediated delivery is extremely low in immunogenicity and is expected to provide a safer and more effective method for precision therapy of central nervous system diseases in the future.

Objective:To analyze the distribution of allergen components of dust mite in children with airway allergic diseases.Methods:This was a cross-sectional study. The clinical data of children with dust mite-induced allergic asthma (AA) complicated with allergic rhinitis (AR) or allergic rhinitis who were treated in Department of Allergy,Beijing Children′s Hospital from January 2019 to October 2022 were retrospectively analyzed. The spedific IgE (sIgE) levels to Der p1,Der p2,Der p5,Der p7,Der p10,Der p21,Der p23 and Der f1,Der f2 were detected by protein chip method. The distribution of dust mite sensitized components and the sIgE levels in children with different airway allergic diseases and different ages were compared.Results:Among 138 children with airway allergic diseases,there were 97 boys and 41 girls,age (6.86±2.61) years old,and there were 106 cases of AA combined AR (AAAR group) and 32 cases of AR alone (AR group). The sensitization rates of Der p2 was the highest (75.4%,104/138),followed by Der f2 (74.6%,103/138),Der f1 (73.9%,102/138),Der p1 (71.7%,99/138),Der p21 (19.6%,27/138),Der p5 (16.7%,23/138),Der p23 (14.5%,20/138),Der p7 (11.6%,16/138) and Der p10 (2.9%,4/138). The co-sensitization rate of Der p1,Der p2,Der f1 and Der f2 was the highest (31.2%,43/138). There was no significant difference in sensitization rate of dust mites components between AAAR group and AR group(all P>0.05). AAAR group had higher levels of sIgE to Der p23 than AR group [0.1 (0,0.1) IU/ml vs. 0 (0,0.1) IU/ml,Z=-2.819, P=0.005]. There were no significant differences in the positive rate of dust mite components and sIgE levels between children aged≤6 and>6 years old with airway allergic diseases(all P>0.05). Conclusions:Der p1,Der p2,Der f1 and Der f2 are the major components of dust mites sensitizing airway allergic diseases in children. Der p1,Der p2,Der f1 and Der f2 are the main co-sensitizing components in children with dust mite-induced airway allergic diseases. Compared with AR,the sIgE level to Der p23 in children with AAAR is higher.

Objective:To introduce the research and innovations around the application of aquatic rehabilitation techniques in the treatment of lumbago, and to summarize specific methods and applications in aeromedicine. Literature resource and selection Literature on the prevention and treatment of lumbago using aquatic rehabilitation techniques as well as on the rehabilitation of lumbago in pilots was retrieved and selected. Literature quotation Sixty-one references were cited. Literature synthesis Aquatic rehabilitation techniques can be classified into shower therapy, immersion therapy, and aquatic exercise therapy according to treatment regimens. Among them, immersion therapy and aquatic exercise therapy are commonly used in the treatment of lumbago. Aquatic rehabilitation techniques can effectively alleviate patients′ lumbago, improve their functional disorders, and enhance their quality of life. Prior to aquatic therapy, patients with lumbago need to have their motor function assessed to tailor the treatment protocol based on diagnostic findings and specific therapeutic objectives. Aquatic rehabilitation techniques, when used to prevent and treat lumbago in pilots under convalescence, are not only more effective than land-based training, but also more accessible to pilots due to their comfort and compliance. Many of our military rehabilitation and convalescent centers in China have integrated modern aquatic rehabilitation techniques into rehabilitation treatment by drawing on their rich water resources so as to improve the physical and mental health, social adaptability and military adaptability of pilots. Conclusions:When used for the prevention and treatment of lumbago, aquatic rehabilitation techniques are highly effective, safe and enjoyable, so they should be made more accessible to pilots during convalescence.

Objective:To construct a multi-sequence MRI radiomics combined with KRAS mutation nomogram model to predict the efficacy of pathological complete response (pCR) in patients with rectal cancer after neoadjuvant chemoradiotherapy.Methods:This study was a case-control study. A total of 126 patients with rectal cancer who were treated with neoadjuvant chemoradiotherapy in the Second Affiliated Hospital of Harbin Medical University from June 2020 to December 2023 were retrospectively collected. The pathological response of the postoperative specimens was graded, with 64 cases of pCR and 62 cases of non-pCR. KRAS gene detection was performed on the pathological tissues before neoadjuvant chemoradiotherapy. Among the patients, 34 cases had KRAS mutants and 92 cases had KRAS wild-types. The 126 patients were randomly divided into a training set and a validation set at a ratio of 8∶2 by the random number method, with 101 and 25 cases, respectively. The difference in KRAS mutation status between the pCR group and the non-pCR group was compared by the χ2 test. The radiomic features were extracted from the baseline T 2WI, diffusion-weighted imaging, and apparent diffusion coefficient images of the patients. The optimal radiomic features were screened out to establish the radiomics model. The radiomics-KRAS joint model was constructed by logistic regression, and a nomogram was drawn. The application efficiency of the model was evaluated by the receiver operating characteristic curve and calibration curve. Results:There was a statistically significant difference in KRAS mutation between the pCR group and the non-pCR group in the training set ( χ2=4.69, P=0.032). Ten radiomics features were screened out in MRI images to establish the radiomics model. In the training set and validation set, the areas under the curve (AUC) of KRAS mutation, radiomics model and radiomics-KRAS nomogram model for evaluating pCR after neoadjuvant chemoradiotherapy were 0.665 (95% CI 0.592-0.757), 0.746 (95% CI 0.651-0.895) and 0.818 (95% CI 0.742-0.934), respectively, and the AUCs of the validation set were 0.613 (95% CI 0.582-0.755), 0.738 (95% CI 0.627-0.839) and 0.833 (95% CI 0.768-0.961), respectively. The results of DeLong test showed that the AUC of radiomics-KRAS nomogram model was higher than that of KRAS mutation and radiomics model, and the difference was statistically significant ( Z=0.58, 0.63, P=0.024, 0.022 in the training set; Z=0.54, 0.61, P=0.018, 0.035 in the validation set). The calibration curve showed that the predicted probability of the radiomics-KRAS nomogram model was consistent with the actual probability. Conclusions:The multi-sequence MRI radiomics combined with the KRAS mutation nomogram model has the best efficacy in predicting pCR in patients with rectal cancer after neoadjuvant chemoradiotherapy, and has good practical application value.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

OBJECTIVE To investigate the effects of aucubin （Auc） on the malignant biological behavior of breast cancer cells by regulating cyclin-dependent kinase 1（CDK1）/cyclin B1（CCNB1）/Polo-like kinase 1 （PLK1） signaling pathway. METHODS Human breast cancer cells MCF-7 were divided into control group， Auc low-， medium- and high-concentration groups （AUC-L， AUC-M， AUC-H groups， 20， 40 and 80 μmol/L Auc）， Auc-H+pcDNA-NC group （80 μmol/L Auc+transfected pcDNA- NC plasmid）， and Auc-H+pcDNA-CDK1 group （80 μmol/L Auc+transfected pcDNA-CDK1 plasmid）. Cell proliferation， clonal formation， invasion and migration abilities， apoptosis and cycle distribution， and the expressions of related proteins of apoptosis， epithelial-mesenchymal transformation （EMT） and CDK1/CCNB1/PLK1 signaling pathway were detected in each group. The transplanted tumor model of BALB/c nude mice was established by subcutaneous inoculation of MCF-7 cell suspension， and the mice were divided into control group and Auc group （12 mice in each group）. The tumor volume， mass and the expressions of related proteins of CDK1/CCNB1/PLK1 signaling pathway in tumor tissues were detected. RESULTS Compared with control group， the number of clonal formation， proliferation rate， cell invasion number， scar healing rate， G1/G0 phase and S phase cell proportions， and the expressions of B cell lymphoma-2 （Bcl-2）， N-cadherin， fibronectin， CDK1， CCNB1 and PLK1 were decreased significantly （P＜0.05）. The apoptotic rate， G2/M phase cell proportion and the expressions of Bcl-2 associated X protein and E-cadherin were significantly increased， in a dose-dependent manner （P＜0.05）. Compared with the Auc-H+pcDNA-NC group， there was no statistical significance in the above indexes in the Auc-H group （P＞0.05）， while the above indexes in the Auc-H+ pcDNA-CDK1 group were significantly reversed （P＜0.05）. Compared with the control group， the tumor volume and mass， and the expressions of CDK1， CCNB1 and PLK1 in tumor tissue of Auc group were significantly decreased （P＜0.05）. CONCLUSIONS Auc can inhibit the proliferation， invasion and migration of breast cancer cells， induce cell cycle arrest， and inhibit the progression of EMT， which may be related to inhibiting the activation of the CDK1/CCNB1/PLK1 signaling pathway.