Objective:To investigate the risk factors and their predictive efficacy for postoperative premature epiphyseal closure in pediatric patients with distal tibial epiphyseal fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 216 pediatric patients with distal tibial epiphyseal fractures admitted to Zhengzhou Orthopedics Hospital from January 2018 to December 2023, including 136 males and 80 females, aged 2-16 years [11.8(9.8, 13.3)years]. Among them, 112 patients were affected on the left side and 104 on the right. According to the Salter-Harris fracture classification, the fracture was classified as type I in 14 patients, type II in 97, type III in 38, type IV in 64 and type VI in 3. According to the presence of premature epiphyseal closure after surgery, the patients were divided into premature epiphyseal closure group ( n=38) and normal epiphyseal group ( n=178). Age, gender, body mass index (BMI), injury mechanism, side of injury, Salter-Harris classification of fracture, initial displacement distance of the fracture end, medial malleolar involvement by the fracture line surgical fixation method, operation duration, reduction method, and reduction quality were recorded in the two groups. Univariate analysis and binary Logistic regression analysis were used to evaluate and determine the independent risk factors for postoperative premature physeal closure in pediatric patients with distal tibial epiphyseal fracture. The receiver operating characteristic (ROC) curve was plotted and area under the curve (AUC) was calculated to evaluate the predictive efficacy of each risk factor for the occurrence of premature physeal closure in pediatric patients with distal tibial epiphyseal fractures. Results:Univariate analysis showed the occurrence of postoperative premature epiphyseal closure of the distal tibia was associated with age, Salter-Harris fracture classification, medial malleolar involvement by the fracture line, surgical fixation method, reduction method, and reduction quality ( P<0.05), while it was not correlated with gender, BMI, injury mechanism, side of injury, initial displacement distance of the fracture end, and operation duration ( P>0.05). Multivariate binary Logistic regression analysis showed that medial malleolar involvement by the fracture line ( OR=0.18, 95% CI 0.04, 0.76, P<0.05) and reduction quality ( OR=43.18,95% CI 10.71, 174.05, P<0.01) were significantly correlated with the occurrence of postoperative premature epiphyseal closure of the distal tibia. The results of ROC curve analysis showed that medial malleolar involvement by the fracture line had limited predictive efficiency (AUC=0.53, 95% CI 0.43, 0.63), reduction quality had moderate predictive efficacy (AUC=0.81, 95% CI 0.72, 0.91), while their combination demonstrated even higher predictive efficacy (AUC=0.83, 95% CI 0.74, 0.91). Conclusions:Medial malleolar involvement by the fracture line and reduction quality are independent risk factors for postoperative premature epiphyseal closure in pediatric patients with distal tibial epiphyseal fractures. Reduction quality demonstrates good predictive efficacy, while medial malleolar involvement by the fracture line shows limited predictive value. The combination of both factors achieves even better predictive performance.

Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

AIM:To investigate the mechanism by which exosomes(EXOs)derived from neural stem cells(NSCs)pretreated with astragaloside IV(ASIV)alleviate brain damage in rats after ischemic stroke.METHODS:Rat NSCs were isolated from fetal rats within 24 h of birth,cultured for 3 d,and subsequently treated with ASIV for additional 5 d.The EXOs from untreated NSCs and ASIV-pretreated NSCs(ASIV-EXOs)were isolated via ultracentrifugation of the cell supernatant.These EXOs were characterized using Western blot to detect specific markers such as CD63,tumor sus-ceptibility gene 101(TSG101)and calnexin.Nanoparticle analysis was employed to determine the size,and the morpholo-gy of the EXOs was observed under electron microscope.Six to eight-week-old SD male rats were randomly assigned to 6 groups:sham group,middle cerebral artery occlusion/reperfusion(MCAO/R)model group,edaravone(EDA)treatment(MCAO/R+EDA)group,EXOs treatement(MCAO/R+EXOs)group and ASIV-EXOs treatment(MCAO/R+ASIV-EXOs)group.Tail vein injections were administered within 2 h following the successful establishment of the MCAO/R model.The Zea Longa method was utilized to evaluate neurological deficits,while the TTC method was employed to assess brain infarc-tion.Pathological changes were examined through HE staining,and TUNEL and caspase-1 immunofluorescence double staining were conducted to detect cellular pyroptosis.Serum levels of interleukin-1β(IL-1β)and IL-18 were measured us-ing ELISA,and Western blot was performed to evaluate the expression of caspase-1,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),gasdermin D(GSDMD),and IL-18 proteins in the ischemic area of the rat cerebral cortex across all groups.RE-SULTS:The MCAO/R group exhibited significantly higher neurological deficit scores compared to the sham group(P＜0.01)and lower scores in the administered groups relative to the MCAO/R group(P＜0.05).Cerebral infarction was mark-edly increased in the MCAO/R group compared to the sham group(P＜0.01),whereas the infarction area was reduced in the administered groups compared to the MCAO/R group(P＜0.05).Serum levels of IL-1β and IL-18 were significantly el-evated in the MCAO/R group versus the sham group(P＜0.01)and were lower in the administered groups compared to the MCAO/R group(P＜0.01).Moreover,IL-1β and IL-18 levels in the MCAO/R+ASIV-EXOs group were lower than those in the MCAO/R+EXOs group(P＜0.05).HE staining revealed pronounced sieve-like infarction foci in the ischemic area of the rat cerebral cortex in MCAO/R group,characterized by disorganized neuronal arrangements,reduced or absent Nys-trom's vesicles,shrunken or fragmented nuclei,and numerous red neurons.In contrast,drug-treated groups exhibited milder pathological changes with clearer neuronal structures and a significant reduction in red neuron counts.Immunofluo-rescence double staining indicated a significant increase in double-positive cells in the MCAO/R group compared to the sham group(P＜0.01),with a decrease in double-positive cells in the administered groups relative to the MCAO/R group(P＜0.05)and a further reduction in the MCAO/R+ASIV-EXOs group compared to the MCAO/R+EXOs group(P＜0.05).The expression levels of caspase-1,NLRP3,ASC,IL-18 and GSDMD proteins in the ischemic region of the rat cerebral cortex were significantly reduced in the administered groups compared to the MCAO/R group(P＜0.01),with further re-duction observed in the MCAO/R+ASIV-EXOs group compared to the MCAO/R+EXOs group(P＜0.05).CONCLU-SION:Exosomes derived from ASIV-pretreated NSCs attenuate brain damage in ischemic stroke rats,potentially through a mechanism involving the inhibition of pyroptosis mediated by the NLRP3/caspase-1 pathway.

Objective:To analyze the epidemiological and clinical features of infectious diseases of the central nervous system (CNS).Methods:A cross-sectional study and analysis were conducted to summarize the epidemiological and clinical characteristics of 9 918 patients with CNS infectious diseases, who were diagnosed and treated at 29 hospitals across China from January 1, 2001 to December 31, 2020. Data collected included demographic data, clinical manifestations, health economic indicators, and prognostic outcomes.Results:Among the 9 918 collected cases of CNS infectious diseases, 5 559 were male (56.0%) and 4 359 were female (44.0%), with an onset age of 38 (25, 53) years. Education level: slightly more junior high school education (2 651 cases, 26.7%), and less elementary school education and below (2 181 cases, 22.0%) were found. Occupational distribution: farmers were found predominant (3 215 cases, 32.4%), followed by workers (1 826 cases, 18.4%) and students (1 633 cases, 16.5%). Clinical manifestations: headache (6 074 cases, 61.2%), fever (5 869 cases, 59.2%) and positive meningeal irritation signs (2 273 cases, 22.9%) were the 3 most common clinical manifestations, followed by nausea and (or) vomiting (2 095 cases, 21.1%), impaired consciousness (2 077 cases, 20.9%), psychiatric symptom (1 866 cases, 18.8%) and epilepsy (1 627 cases, 16.4%), etc., and cranial nerve involvement was found in 669 cases (6.7%). Major pathogens included viruses in 6 814 cases (68.7%), Mycobacterium tuberculosis in 1 677 cases (16.9%), common bacteria in 864 cases (8.7%), fungi in 254 cases (2.6%), spirochetes of syphilis in 183 cases (1.8%), parasites in 121 cases (1.2%), and rickettsiae in 5 cases (0.1%). Urban-rural distribution: slightly more cases were found in the countryside (5 418 cases, 54.6%) than in the towns (4 500 cases, 45.4%). Distribution of onset by season: 2 412 cases (24.3%) fell ill in spring, 2 835 cases (28.6%) in summer, 2 187 cases (22.1%) in fall, and 2 484 cases (25.0%) in winter. Health economics: the duration of hospitalization was 15 (8, 27) days, and the cost of hospitalization was 1.53 (0.91, 3.02)×10 000 yuan. Prognosis: 9 531 cases (96.1%) were cured or improved, and 92 cases (0.9%) died. Conclusions:The pathogens responsible for CNS infectious diseases are predominantly viruses. Although the incidence is slightly higher during the summer months, the overall seasonal pattern is not particularly pronounced. These infections are more commonly observed in young and middle-aged males and present with a diverse range of clinical manifestations, contributing to a significant disease burden.

Objective:In order to effectively educate students on tooth defect diseases and restoration techniques, the teaching and research team at the School of Stomatology of Qingdao University developed an integrated course operative dentistry. This course is specifically designed to align with the undergraduate curriculum reform requirements of "Three Early, Two Multiple and One Integration".Methods:The teaching practice of operative dentistry was conducted with the stomatology undergraduates of grade 2020 and 2021. The course group redesigned the curriculum by reorganizing teaching content, rebuilding teaching resources, reconstructing teaching mode, and reshaping the evaluation system. Evaluation of the curriculum design included test scores, satisfaction questionnaires, and teacher self-evaluation. Statistical analysis was performed using SPSS 27.0 software, including independent sample t-tests for numerical variables and Fisher's exact test or Wilcoxon rank sum test for categorical variables. Results:Through the integrated course learning, 92.68% (38/41) of the students of grade 2020 and 97.44% (38/39) of the students of grade 2021 can basically or completely master various dental defect repair schemes and understand the importance of preserving natural tooth. 82.93% (34/41) of the students of grade 2020 and 100.00% (39/39) of the students of grade 2021 could basically or completely master the key points of various dental defect restorations.Conclusions:Through the practice of teaching, it has been confirmed that the integrated course of operative dentistry is beneficial to students' mastering the knowledge and skills of dental defect diseases and their restoration in a more comprehensive way, and is conducive to the cultivation of clinical thinking, hands-on ability and the patient-centered, comprehensive problem-solving thinking, which is in line with the guidance on the innovation and development of medical education.

Objective:To investigate the clinical effectiveness of tumor lesion curettage and allogeneic bone grafting via the fovea of femoral head through the surgical hip dislocation approach in children and adolescents with femoral head chondroblastoma (FHCB).Methods:Case series study.The clinical data of 7 FHCB patients [3 males and 4 females with a mean age of 13.7 years (11-19 years)] treated at the Department of Pediatric Orthopedics, Zhengzhou Orthopedic Hospital from January 2016 to March 2023 were retrospectively analyzed.All patients underwent lesion curettage and allogeneic bone grafting via the fovea of femoral head through the surgical hip dislocation approach.The healing, local recurrence and complications were assessed via clinical and radiological tests.Functional outcomes were evaluated using the Musculoskeletal Tumour Society (MSTS) scoring system.A paired t-test was used to compare the MSTS scores before the operation and at the final follow-up. Results:All patients were followed up for 30 months on average (18-48 months).The average healing time for bone grafting was 4.9 (3-8) months.Local recurrence and serious postoperative complications such as avascular necrosis of femoral head, secondary osteoarthritis, ectopic ossification and nonunion of greater trochanter osteotomy end were not observed in all patients up to the last follow-up.The average MSTS score at the last follow-up was (29.14±0.45) points.Conclusions:Curettage and bone grafting via the fovea of femoral head through the surgical hip dislocation approach is effective and safe in the treatment of FHCB in children and adolescents.This method can maintain the integrity of the articular surface and growth plate, and also preserve the blood supply of the femoral head and the normal function of the hip joint, with satisfactory short-term effects.

OBJECTIVE To explore the significance of pharmaceutical care through the diagnosis and treatment of a patient with exogenous insulin autoimmune syndrome(EIAS),combined with the analysis of literature reports.METHODS Clinical pharmacist participated in the diagnosis and treatment process of one case of EIAS.Based on the characteristics of the patient's condition,the pharmacist provided medication suggestions and formulated pharmaceutical monitoring measures.At the same time,the pharmacist searched for relevant literature on insulin autoimmune syndrome(IAS)and EIAS,extracted data(gender,age,occurrence time,laboratory tests,clinical symptoms,intervention and outcome),and conducted analysis.RESULTS Based on the patient's medication information in the past 3 years,clinical pharmacist determined that the EIAS was likely caused by insulin aspartate 30.The clinician adopted the clinical pharmacist's suggestion to discontinue insulin and switch to oral hypoglycemic drugs.The patient improved after treatment.The literature analysis showed that among the 257 patients with IAS reported,212 cases were caused by drugs;among them,23 cases were caused by lipoic acid,and 56 cases were caused by exogenous insulin.There were no significant differences in age,glycosylated hemoglobin,and body mass index between the two groups.The lowest blood glucose level in the lipoic acid group was significantly lower than that in the exogenous insulin group(P＜0.05).The proportion of females and the proportion of fasting insulin≥1 000 μU/mL were significantly higher in the lipoic acid group than in the exogenous insulin group(P＜0.05).CONCLUSIONS Compared with EIAS,lipoic acid-induced IAS usually causes more severe hypoglycemia,and the fasting insulin level is usually higher than 1 000 μU/mL,which is more common in female patients.The participation of clinical pharmacists in the diagnosis and treatment of EIAS can help improve the diagnosis and treatment level of similar rare diseases and ensure the safety of patients'medication.