Objective: To compare the biological characteristics of human induced pluripotent stem cell-derived platelet exosomes (hiPSC-Plt-Exos) with those of conventional apheresis platelet exosomes (Plt-Exos), specifically focusing on their differential abilities to enhance the proliferation and migration of human umbilical cord mesenchymal stem cells (hUC-MSCs). Methods: Exosomes were isolated from hiPSC-derived Plt and apheresis Plt concentrate using size exclusion chromatography. These exosomes were then characterized through nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting. Co-culture experiments into hUC-MSCs were conducted with hiPSC-Plt-Exos and apheresis Plt-Exos, respectively. Their effects on the proliferation and migration of hUC-MSCs were assessed via cell proliferation assays and scratch tests. Results: hiPSC-Plt-Exos and apheresis Plt-Exos exhibited comparable particle sizes, morphological features (such as the characteristic cup-shaped structure), and surface markers (including CD9 and HSP70). Notably, hiPSC-Plt-Exos demonstrated a significantly greater ability to enhance the proliferation and migration of hUC-MSCs compared to apheresis Plt-Exos (P<0.05). These differences provide critical comparative data for their application in various clinical contexts. Conclusion: This study establishes a theoretical foundation for developing precise therapeutic strategies based on hiPSC-Plt-Exos. Furthermore, it underscores the necessity of selecting the appropriate type of exosomes according to the specific disease microenvironment to achieve optimal therapeutic outcomes.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

Objective To discuss the evaluation basis of the clinical rational use of Dahuang Zhechong Capsule and to establish its rationality evaluation criterion to promote the sensible use of Dahuang Zhechong Capsule.Methods The rationality evaluation criterion for Dahuang Zhechong Capsule was formulated by referring to the package insert,treatment guidelines,and other literature.According to the criterion,270 outpatient prescriptions using Dahuang Zhechong Capsule in Xiyuan Hospital,China Academy of Chinese Medical Sciences were reviewed from January to June 2020.The indication,usage and dosage,drug combination,and repeated administration were analyzed.The pharmaceutical intervention was performed to address the problems found in the prescription reviews,and 328 outpatient prescriptions using Dahuang Zhechong Capsule in October 2020 were reevaluated.Results The irrational use rate of Dahuang Zhechong Capsule from January to June 2020 was 42.22％(114 cases),including 108(40％)cases of inappropriate indications,five(1.85％)cases of improper usage and dosage,and one(0.37％)case of inappropriate administration route.However,the pharmaceutical intervention in October 2020 remarkably reduced the irrational use rate of Dahuang Zhechong Capsule(4.27％,14 cases),all of which were inappropriate indications.Conclusion Dahuang Zhechong Capsule is being used irrationally;therefore,establishing an evaluation criterion is required.The specific situation of irrational drug use can be identified by prescription review according to its rationality evaluation criterion to manage its clinical use better and promote its rational use.

ObjectiveTo explore the molecular mechanism of Sanhuang Xiexintang （SHXXT） in protecting stress gastric ulcer （SGU） in rats through network pharmacology， molecular docking， and animal experiments. MethodThe active ingredients and corresponding targets in SHXXT were collected and screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCMID）， Bioinformation Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and Swiss Target Prediction database. SGU-related targets were screened from the Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD）， GeneCards database， and PharmGKB database. Herbal-ingredient-target （H-C-T） network was constructed by using Cytoscape 3.9.1 software. Protein-protein interaction （PPI） of drug and disease intersection targets was analyzed by using the Protein Interaction Platform （STRING） database. Gene ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were conducted through the Database for Annotation Visualization and Integrated Discovery （DAVID）. The active ingredients and key targets were validated using AutodockVina 1.2.2 molecular docking software， and the experimental results were further validated through animal experiments. ResultThe 55 active ingredients were screened， and 255 potential target genes for SHXXT treatment of SGU were predicted. The PPI analysis showed that protein kinase B （Akt）， phosphatase and tensin homolog deleted on chromosome ten （PTEN）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and cyclooxygenase-2 （COX-2） are the core targets of SHXXT for protecting SGU. GO and KEGG analyses showed that SHXXT may affect the development of SGU by regulating various biological processes such as the phosphoinositide 3-kinase （PI3K）/Akt signaling pathway and inflammatory processes. The molecular docking results showed that both the active ingredients and key targets had good binding ability. Animal experiments showed that compared with the blank group， the ulcer index （UI） of the model group was significantly increased （P<0.01）， and the serum levels of TNF-α and IL-1β significantly increased （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly down-regulated （P<0.05）. The phosphorylation levels of PI3K， Akt， and nuclear factor kappa-B （NF-κB） were significantly up-regulated （P<0.05）. Compared with the model group， the UI of the treatment group was significantly reduced （P<0.01）， and the serum levels of TNF-α and IL-1β were significantly reduced （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly up-regulated （P<0.01）， and the phosphorylation levels of PI3K， Akt， and NF-κB were significantly downregulated （P<0.01）. ConclusionThe application of network pharmacology prediction， molecular docking simulation， and animal experimental validation confirms that SHXXT regulates the PI3K/Akt/NF-κB signaling pathway to regulate the inflammatory response of rats and thus protects the gastric mucosa of SGU rats.

Objective:To analyze the mobile of pediatric discharged patients in Beijing from 2013 to 2022 and provide data support for rational planning of pediatric medical resource allocation.Methods:The number,source and flow of pediatric discharges from secondary and higher-level medical institutions in Beijing were described and compared and analyzed visually.Two indicators,the cross-district consultation rate,and the load share ratio,were measured to reflect the outflow rate of patients from the outflow areas and the pressure on the supply of healthcare services in the inflow areas.Results:The proportion of pediatric discharged patients from secondary and upper medical institutions in Beijing was 53.34%.Hebei,Shandong,Henan,Inner Mongolia Autonomous Region,and Shanxi were the main source provinces,with a cumulative proportion of 68.02%.Pediatric patients from other provinces mainly flowed to Xicheng District,tertiary hospitals,and children's hospitals,which was consistent with the main flow of patients in Beijing.There was an interactive flow of pediatric patients between the 16 administrative districts.Between 2020 and 2022,the average annual cross-regional consultation rate of pediatric patients in Fangshan District,Daxing District,Huairou District,Pinggu District,Miyun District,and Yanqing District all had relatively large increases.After considering patients from outlying provinces,the load share of each administrative district increased to varying degrees,with Xicheng District showing a high multiplier increase.Conclusions:The mobility of pediatric patients from other provinces and cross-regional visits in Beijing was relatively high,and both had high targeting and concentration in their choice of visits.It is recommended that a targeted work plan for the relocation of medical functions be formulated,and paediatric patients should be reasonably triaged according to their population and needs,so as to guide a reasonable flow of paediatric patients to seek medical treatment.

Objective To investigate the protective effect of NDUFA13 protein against acute liver injury and liver fibrosis in mice and explore the possible mechanisms.Methods BALB/C mice(7 to 8 weeks old)were divided into normal group,CCl4 group,CCl4+AAV-NC group and CCl4+AAV-NDU13 group(n=18).Mouse models of liver fibrosis were established by intraperitoneal injection of CCl4 twice a week for 3,5 or 7 weeks,and the recombinant virus AAV8-TBG-NC or AAV8-TBG-NDUFA13 was injected via the tail vein 7-10 days prior to CCl4 injection.After the treatments,pathological changes in the liver of the mice were observed using HE and Masson staining.Hepatic expression levels of NDUFA13 and α-SMA were detected with Western blotting,and the coexpression of NDUFA13 and NLRP3,TNF-α and IL-1β,and α-SMA and collagen Ⅲ was analyzed with immunofluorescence assay.Results HE and Masson staining showed deranged liver architecture,necrotic hepatocytes and obvious inflammatory infiltration and collagen fiber deposition in mice with CCl4 injection(P<0.001).NDUFA13 expression markedly decreased in CCl4-treated mice(P<0.001),while a significant reduction in inflammatory aggregation and fibrosis was observed in mice with AAV-mediated NDUFA13 overexpression(P<0.001).In CCl4+AAV-NDU13 group,immunofluorescence assay revealed markedly weakened activation of NLRP3 inflammasomes(P<0.001),significantly decreased TNF-α and IL-1β secretion(P<0.001),and inhibited hepatic stellate cell activation(P<0.05)and collagen formation in the liver(P<0.001).Conclusion Mitochondrial NDUFA13 overexpression in hepatocytes protects against CCl4-induced liver fibrosis in mice by inhibiting activation of NLRP3 signaling.

Objective:To discuss the effect of sialic acid-binding immunoglobulin-like lectin-15(Siglec15)derived from M2 tumor-associated macrophages(M2-TAMs)on promoting the malignant biological behavior of the esophageal squamous cell carcinoma(ESCC)through bioinformatics analysis,and to validate the findings through cell experiment.Methods:The Tumor Immune Estimation Resource(TIMER)online Database was used to analyze the expression differences and immune infiltration of Siglec15 in pan-cancer and adjacent normal tissues.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Siglec15 mRNA in M2-TAMs and ESCC EC109 and KYSE150 cells.Based on the non-contact co-culture of M2-TAMs and ESCC cells,the following groups were set up,such as EC109/KYSE150 group,EC109/KYSE150+si-NC group(transfected with si-NC sequence),and EC109/KYSE150+si-Siglec15 group(transfected with si-Siglec15#1 and si-Siglec15#2 sequences).CCK-8 method was used to detect the proliferation activities of the cells in various groups;wound healing assay was used to detect the wound healing rates of the cells in various groups;Transwell chamber assay was used to detect the numbers of migration and invasion cells in various groups;flow cytometry was used to detect the apoptotic rates of the cells in various groups.Results:The bioinformatics analysis results showed that compared with adjacent normal tissue,the expression levels of Siglec15 mRNA in pan-cancer tissues such as esophageal cancer,colon cancer,and head and neck squamous cell carcinoma tissues were increased(P＜0.05 or P＜0.01),and the expression level of Siglec15 mRNA in esophageal cancer tissue was significantly positively correlated with the infiltration of the macrophages(P＜0.05).Compared with the EC109 cells and KYSE150 cells,the expression level of Siglec15 mRNA in M2-TAMs was significantly increased(P＜0.01).There was no significant difference in the proliferation rate of the cells among EC109/KYSE150 group,EC109/KYSE150+si-NC group,and EC109/KYSE150+si-Siglec15 group(P＞0.05).Compared with EC109/KYSE150 group,after treated for 24 and 48 h,the wound healing rate of the cells in EC109/KYSE150+si-NC group was increased(P＜0.01),the numbers of migration and invasion cells were increased(P＜0.05),and the apoptotic rate was decreased(P＜0.01).Compared with EC109/KYSE150+si-NC group,the wound healing rates of the cells in EC109/KYSE150+si-Siglec15#1 group and EC109/KYSE150+si-Siglec15#2 group were decreased(P＜0.05),the numbers of migration and invasion cells were decreased(P＜0.05),and the apoptotic rates of the cells had no significant difference(P＞0.05).Conclusion:Siglec15 derived from M2-TAMs may be a key factor in promoting the migration and invasion of the ESCC cells.

Objective To study the infection of multidrug-resistant organism(MDRO)in elderly pa-tients with catheter-associated urinary tract infection(CAUTI)and analyze the infection factors.Methods The medi-cal records of 175 elderly patients with CAUTI admitted to Jiangsu Province Hospital from January 2021 to July 2022 were selected,the distribution of MDRO infection in elderly patients with CAUTI was analyzed,and the influencing factors of MDRO infection were analyzed.The predictive value of independent risk factors for rele-vant nosocomial infections was analyzed by receiver operating characteristics(ROC)curves.Results Among the 175 elderly patients with CAUTI,87 cases(49.71％)developed MDRO infection and were included in the MDRO infection group),and 88 cases(50.29％)had no MDRO infection and were included in the non-MDRO infection group.A total of 432 MDRO pathogens were detected in the MDRO infection group,inclu-ding 415 strains of Gram-negative bacteria,accounting for 96.06％,186 strains of carbapenem-resistant Acine-tobacter baumannii(43.06％),147 strains of carbapenem-resistant Klebsiella pneumoniae(34.03％),79 strains of carbapenem-resistant Pseudomonas aeruginosa(18.29％)and 3 strains of carbapenem-resistant Escherichia coli(0.69％).There were 17 strains of Gram-positive bacteria(3.94％),all of which were methi-cillin-resistant Staphylococcus aureus.Multivariate analysis showed that the use of carbapenems,tigecycline,polymyxin,and days of central venous intubation were considered as independent risk factors.The area under the curve of MDRO infection was 0.883.Conclusion For elderly patients with CAUTI,it is necessary to take strict antimicrobial management measures,master the indications of antimicrobial application,shorten the hos-pitalization time of patients and reduce the incidence of MDRO infection.

Objective:To detect expression levels of complement regulatory proteins CD55 and CD59 in the peripheral blood of patients with Stevens-Johnson syndrome (SJS) /toxic epidermal necrolysis (TEN), and to preliminarily analyze their potential roles in the occurrence of SJS/TEN.Methods:Hospitalized patients with SJS/TEN (SJS/TEN group) were collected from the Department of Dermatology of the First Affiliated Hospital of Anhui Medical University and the Second Affiliated Hospital of Anhui Medical University from December 2017 to December 2022. Meanwhile, patients with maculopapular exanthema (MPE) and healthy physical examinees were also collected and served as the mild group and healthy control group, respectively. Flow cytometry was performed to determine the proportions of CD4 + T lymphocytes and CD8 + T lymphocytes in peripheral blood mononuclear cells (PBMCs). The expression levels of inflammatory cytokines tumor necrosis factor (TNF) -α, interleukin (IL) -6, IL-17, IL-10, interferon (IFN) -γ, IL-2, and IL-4 were detected using flow cytometric bead array technology. The mRNA expression levels of CD55 and CD59 in PBMCs were detected by real-time fluorescence-based quantitative PCR (qRT-PCR). Flow cytometry was also performed to determine the protein expression of CD55 and CD59 on the surface of CD8 + T lymphocytes. Statistical analyses were carried out using one-way analysis of variance and Tukey's test. Results:Totally, 13 patients with SJS/TEN, 27 patients with MPE, and 40 healthy controls were collected. Among the SJS/TEN patients, there were 8 males and 5 females, with their age being 18 to 84 (47.15 ± 19.99) years, and disease duration being 7.74 ± 2.63 days. No significant differences were observed in the gender distribution or age among the 3 groups (both P > 0.05). The proportions of CD4 + T lymphocytes did not differ among the 3 groups ( F = 3.84, P = 0.051). The proportions of CD8 + T lymphocytes in the peripheral blood were significantly higher in the SJS/TEN group (25.60% ± 4.57%) than in the healthy control group (16.20% ± 6.28%; q = 4.59, P = 0.018). The expression levels of inflammatory cytokines TNF-α, IL-6, IL-10, IL-17, and IFN-γ were significantly higher in the SJS/TEN group than in the healthy control group and mild group (all P < 0.001). In addition, the mRNA expression of CD55 ( F = 9.46, P < 0.001) and CD59 in PBMCs ( F = 15.14, P < 0.001) was significantly lower in the SJS/TEN group than in the mild group and healthy control group. The protein expression levels of CD55 ( F = 51.51, P < 0.001) and CD59 ( F = 31.59, P < 0.001) on the surface of CD8 + T lymphocytes were also significantly lower in the SJS/TEN group than in the other two groups and the healthy control group, respectively. Conclusion:Complement regulatory proteins CD55 and CD59 were downregulated in SJS/TEN patients, which may be associated with the activation of CD8 + T lymphocytes and excessive inflammatory responses.

Objective:To analyze the equality of health resource allocation in functional areas of Beijing from 2012 to 2022, so as to provide reference for optimizing the allocation of health resources during the 14th Five-Year Plan and long-term planning.Methods:According to the new urban master plan and the functional positioning of the capital, 16 districts in Beijing were divided into 4 functional regions(capital core area, urban functional expansion area, urban development new area, and ecological conservation area). Based on the analysis of permanent population, the levels of health resources in each region and each administrative district were compared, and the equity of health resources was measured by using the Dagum Gini coefficient.Results:In 2022, the Gini coefficients of medical and health resources in Beijing, including the number of beds, number of health technicians, and number of practicing(assistant) physicians, were 0.71, 0.65, and 0.63, respectively, with no significant change compared to 2012. While the Gini coefficient for equipment priced over 10 000 yuan was 0.75, slightly lower than 0.79 in 2012. The differences in resource allocation mainly came from different regions. The Gini coefficient of the above four indicators in the urban functional expansion area was the lowest, followed by the capital core area, and the Gini coefficient of the ecological conservation area was the highest. The Dagum Gini coefficient of the four indicators of urban development new area showed a decreasing trend year by year.Conclusions:In recent years, there has been no significant change in the overall equality of medical and health resource allocation in Beijing. Only the Gini coefficient of urban development new area has shown a downward trend. It is necessary to further promote the fair and reasonable allocation of medical and health resources among functional areas in Beijing.