[Chronic myeloid leukemia with e6a2 fusion gene: a case report and literature review].

Chronic myeloid leukemia (CML) with e6a2 transcript type is very rare in clinic,which is usually related to disease aggressiveness. Its clinical characteristics and relationship with tyrosine kinase inhibitor efficacy are still unclear. In this paper, the clinical characteristics and related laboratory tests of a patient with e6a2 fusion gene positive CML characterized by multiple osteolytic bone destruction throughout the body and eosinophil infiltration in gastrointestinal tract, lymph nodes and other organs were retrospectively analyzed, and the relevant literature was reviewed. The patient was Ph chromosome positive with chromosome +8, and the common BCR::ABL1 transcript of CML was negative, but e6a2 transcript was positive detected by RT-PCR. The patient was treated with dasatinib 100 mg/d. Three months later, the patients achieved CHR, CCyR and MR4.0. However, the e6a2 transcript is very rare in clinical practice, and more cases of e6a2 transcript need to be studied to clarify its clinical characteristics and improve the treatment effect of these rare cases.

Intelligently Quantifying the Entire Irregular Dental Structure.

Quantitative analysis of irregular anatomical structures is crucial in oral medicine, but clinicians often typically measure only several representative indicators within the structure as references. Deep learning semantic segmentation offers the potential for entire quantitative analysis. However, challenges persist, including segmentation difficulties due to unclear boundaries and acquiring measurement landmarks for clinical needs in entire quantitative analysis. Taking the palatal alveolar bone as an example, we proposed an artificial intelligence measurement tool for the entire quantitative analysis of irregular dental structures. To expand the applicability, we have included lightweight networks with fewer parameters and lower computational demands. Our approach finally used the lightweight model LU-Net, addressing segmentation challenges caused by unclear boundaries through a compensation module. Additional enamel segmentation was conducted to establish a measurement coordinate system. Ultimately, we presented the entire quantitative information within the structure in a manner that meets clinical needs. The tool achieved excellent segmentation results, manifested by high Dice coefficients (0.934 and 0.949), intersection over union (0.888 and 0.907), and area under the curve (0.943 and 0.949) for palatal alveolar bone and enamel in the test set. In subsequent measurements, the tool visualizes the quantitative information within the target structure by scatter plots. When comparing the measurements against representative indicators, the tool's measurement results show no statistically significant difference from the ground truth, with small mean absolute error, root mean squared error, and errors interval. Bland-Altman plots and intraclass correlation coefficients indicate the satisfactory agreement compared with manual measurements. We proposed a novel intelligent approach to address the entire quantitative analysis of irregular image structures in the clinical setting. This contributes to enabling clinicians to swiftly and comprehensively grasp structural features, facilitating the design of more personalized treatment plans for different patients, enhancing clinical efficiency and treatment success rates in turn.

[RBMX overexpression inhibits proliferation, migration, invasion and glycolysis of human bladder cancer cells by downregulating PKM2].

OBJECTIVE: To investigate the role of RNA-binding motif protein X-linked (RBMX) in regulating the proliferation, migration, invasion and glycolysis in human bladder cancer cells. METHODS: A lentivirus vectors system and RNA interference technique were used to construct bladder cancer 1376 and UC-3 cell models with RBMX overexpression and knockdown, respectively, and successful cell modeling was verified using RT-qPCR and Western blotting. Proliferation and colony forming ability of the cells were evaluated using EdU assay and colony-forming assay, and cell migration and invasion abilities were determined using Transwell experiment. The expressions of glycolysis-related proteins M1 pyruvate kinase (PKM1) and M2 pyruvate kinase (PKM2) were detected using Western blotting. The effects of RBMX overexpression and knockdown on glycolysis in the bladder cancer cells were assessed using glucose and lactic acid detection kits. RESULTS: RT-qPCR and Western blotting confirmed successful construction of 1376 and UC-3 cell models with RBMX overexpression and knockdown. RBMX overexpression significantly inhibited the proliferation, clone formation, migration and invasion of bladder cancer cells, while RBMX knockdown produced the opposite effects. Western blotting results showed that RBMX overexpression increased the expression of PKM1 and decreased the expression of PKM2, while RBMX knockdown produced the opposite effects. Glucose consumption and lactate production levels were significantly lowered in the cells with RBMX overexpression (P < 0.05) but increased significantly following RBMX knockdown (P < 0.05). CONCLUSION: RBMX overexpression inhibits bladder cancer progression and lowers glycolysis level in bladder cancer cells by downregulating PKM2 expression, suggesting the potential of RBMX as a molecular target for diagnosis and treatment of bladder cancer.

[Clinical research of multisystem inflammatory syndrome in children].

Objective: To analyze the clinical characteristics of children with multisystem inflammatory syndrome (MIS-C) associated with SARS-CoV-2 in China, and to improve the understanding of MIS-C among pediatricians. Methods: Case series study.Collect the clinical characteristics, auxiliary examinations, treatment decisions, and prognosis of 64 patients with MIS-C from 9 hospitals in China from December 2022 to June 2023. Results: Among the 64 MIS-C patients, 36 were boys and 28 were girls, with an onset age being 2.8 (0.3, 14.0) years. All patients suffered from fever, elevated inflammatory indicators, and multiple system involvement. Forty-three patients (67%) were involved in more than 3 systems simultaneously, including skin mucosa 60 cases (94%), blood system 52 cases (89%), circulatory system 54 cases (84%), digestive system 48 cases (75%), and nervous system 24 cases (37%). Common mucocutaneous lesions included rash 54 cases (84%) and conjunctival congestion and (or) lip flushing 45 cases (70%). Hematological abnormalities consisted of coagulation dysfunction 48 cases (75%), thrombocytopenia 9 cases (14%), and lymphopenia 8 cases (13%). Cardiovascular lesions mainly affected cardiac function, of which 11 patients (17%) were accompanied by hypotension or shock, and 7 patients (12%) had coronary artery dilatation.Thirty-six patients (56%) had gastrointestinal symptoms, 23 patients (36%) had neurological symptoms. Forty-five patients (70%) received the initial treatment of intravenous immunoglobulin in combination with glucocorticoids, 5 patients (8%) received the methylprednisolone pulse therapy and 2 patients (3%) treated with biological agents, 7 patients with coronary artery dilation all returned to normal within 6 months. Conclusions: MIS-C patients are mainly characterized by fever, high inflammatory response, and multiple organ damage. The preferred initial treatment is intravenous immunoglobulin combined with glucocorticoids. All patients have a good prognosis.

[Liposome nanoparticles for targeted delivery of parthenolide induce colorectal cancer necroptosis to ameliorate tumor-infiltrating T cell exhaustion in mice].

OBJECTIVE: To investigate the mechanism of parthenolide for inducing necroptosis and ameliorating CD8+ T cell exhaustion in colorectal cancer (CRC) and construct liposome nanoparticles for targeted delivery of parthenolide. METHODS: The inhibitory effect of parthenolide on proliferation of different CRC cell lines was examined using CCK8 assay, and ROS LDH detection and Western blotting were used to analyze the cell death pathways. In a mouse model bearing subcutaneous MC38 cell xenografts, the effects of 5 and 15 mg/kg parthenolide on tumor growth and CD8+ T cell depletion were observed. In a mouse model bearing orthotopic CRC cell xenograft in the ileocecal region, free parthenolide (100 µg/mL) or low (100 µg/mL) and high doses (200 µg/mL) of liposome nanoparticles loaded with parthenolide were injected via the tail vein, and the changes in CD8 expression in the xenografts were analyzed using immunohistochemistry. RESULTS: Treatment with parthenolide dose-dependently lowered the viability of the CRC cell lines SW480, DLD1, HCT116 and MC38 cells, and its effect was obviously antagonized by Nec-1. Immunoblotting analysis showed that parthenolide treatment resulted in increased RIP3 and MLKL phosphorylation in the CRC cells. In the mouse model bearing subcutaneous xenografts, parthenolide treatment at the high dose, but not at the low dose, significantly increased the number of infiltrating CD3+ CD8+ T cells and PD1hiTIM3+ T cell percentage (P<0.01) and lowered the percentage of PD1loTIM3- T cells in the tumor tissue (P<0.01). In the mouse models bearing orthotopic CRC xenograft, intravenous injection of the liposomes loaded with parthenolide, especially at the high dose, significantly increased CD8 expression in the tumor tissue (P<0.01). CONCLUSION: Parthenolide induces necroptosis in CRC and increases infiltrating CD8+ T cells to ameliorate CD8+ T cell exhaustion in the tumor. Liposome nanoparticles for targeted delivery of parthenolide produce stronger, anti-tumor effect.

[Bronchoscopic manifestations and interventional treatment of pulmonary mucormycosis].

Objective: To analyze the bronchoscopic manifestations and interventional treatment of pulmonary mucormycosis. Methods: Clinical data of patients with pulmonary mucormycosis undergoing bronchoscopy and interventional therapy in 4 tertiary general hospitals in China from May 2006 to May 2022 were retrospectively analyzed and the literature on the subject were reviewed. Results: The data of 10 patients with pathologically diagnosed pulmonary mucormycosis undergoing bronchoscopy and interventional therapy were collected, including 8 males and 2 females. The patients' age ranged from 21 to 72 (44±15) years. The underlying diseases included 6 cases of diabetes ketoacidosis, 3 cases of leukemia, 1 case after operation of lung cancer. Bronchoscopy showed that white viscous necrotic matters grew along the airway and blocked the airway in 9 cases, accompanied by airway bleeding in 3 cases, bloody secretion blocked the airway in 1 case, and bronchopulmonary cavity fistula in 2 cases. The biopsy histopathology of white necrotic matters showed that many mucor filaments were tangled together which were named mucormycelium. Among the 10 patients, 9 were treated with systemic drugs, including intravenous application of amphotericin B deoxycholate in 5 cases, intravenous application of amphotericin B liposome in 4 cases, oral posaconazole in 6 cases and intravenous injection in 1 case. Local drug therapy included aerosol inhalation of amphotericin B deoxycholate in 8 cases and local perfusion under bronchoscope in 5 cases. Bronchoscopic interventional therapy was used to remove mucormycelium in the bronchus, including cryotherapy in 8 cases, biopsy forceps in 7 cases, snare treatment in 2 cases and foreign body forceps in 2 cases. All 10 patients were clinical cured and with no death. Conclusions: Pulmonary mucormycosis is more common in immunocompromised hosts. Bronchoscopy often showed mucormycelium blocking the airway. Systemic and local drug therapy combined with bronchoscopic interventional therapy can achieve good clinical efficacy.

The influence of stigma and disability acceptance on psychosocial adaptation in patients with stoma: A multicenter cross-sectional study.

Background: The stoma can cause serious physical and psychological distress to the patient, leading to an inability to live a normal life; although it effectively improves the 5-year survival rate of patients. Objective: The purpose of this study is to explore the status of stigma and disability acceptance of patients with stoma and their influences on psychosocial adaptation. Design: A multicenter cross-sectional study. Methods: A total of 259 patients with stoma in 6 hospitals from southeast China were enrolled. And this research adhered to the STROBE guideline and approved by the Ethics Committee of Fu Jian Provincial Hospital. The ostomy adjustment inventory-20、acceptance of disability scale and social impact scale were used to collect data. The hypothetical path model was tested using the SPSS version 22.0 software and AMOS version 26.0 software. Results: Stigma, disability acceptance and psychosocial adaptation was associated. The sense of stigma was severe (72.76 ± 12.73), the acceptance of disability was medium (179.24 ± 32.29) and the psychosocial adaptation was poor (38.06 ± 8.76). Also, the hypothesis model of this study fitted the data well (AGFI = 0.967>0.08; χ 2/df = 1.723, p = 0.08 > 0.05), and the results showed that disability acceptance positively affected psychosocial adaptation; while stigma negatively affected psychosocial adaptation, and disability acceptance mediated between stigma and psychosocial adaptation (p < 0.01). Conclusion: The stigma and disability acceptance of patients with stoma are serious problems that are closely related to their psychosocial adaptation. Medical staff should take some interventions based on different paths to reduce stoma patients' stigma and guide them to improve disability acceptance, thus to improve the level of psychosocial adaptation of patients with stoma.

[Identification of potential regulatory genes for embryonic stem cell self-renewal and pluripotency by random forest].

OBJECTIVE: To identify novel genes associated with self-renewal and pluripotency of mouse embryonic stem cells(mESCs)by integrating multiomics data based on machine learning methods. METHODS: We integrated multiomics information of mESCs involving transcriptome, histone modifications, chromatin accessibility, transcription factor binding and architectural protein binding, and compared the signal differences between known stem cell self-renewal and pluripotency genes and other genes.By integrating these multiomics data, we established prediction models based on several machine learning classifiers including random forests and performed 5-fold cross validations.The model was trained using the training dataset containing two thirds of the input samples, and the remaining one third of the input samples were used as the test dataset to assess the performance of the model in independent tests.Finally, the results predicted by the model were validated through gene function annotation and cell function experiments including cell viability assay, colony formation assay and cell cycle analysis. RESULTS: Compared with the random genes, the genes known to be associated with self-renewal and pluripotency of mESCs in the multiomics data showed significantly different features.Random forest outperformed the other machine learning algorithms tested on these multiomics data, with an area under the curve (AUC) of 0.883±0.018 for cross validation and an AUC of 0.880±0.028 for independent test.Based on this model, we identified 893 potential regulatory genes associated wwith self-renewal and pluripotency of mESCs, which were similar to the known genes in functional annotation.Known-down of the predicted novel regulator gene Cct6a resulted in significant decreases in the cell viability of mESCs (P < 0.0001) and the number of cell clones (P < 0.01), significantly increased the number of cells in G1 phase (P < 0.01) and decreasedthe number of S phase cells (P < 0.05).Knockdown of Cct6a also led to failure of positive alkaline phosphatase staining of the mESCs. CONCLUSION: Machine learning model based on multiomics data can be used to predict potential self-renewal and pluripotency regulators with high performance.By using this model, we predicted potential self-renewal and pluripotency regulatory genes including Cct6a and applied experimental validation.This model provides new insights into the regulatory mechanism of mESCs and contribute to stem cell research.

[The application of indocyanine green fluorescent navigation in laparotomy of cholecystectomy].

Objective: To explore the application of indocyanine green fluorescence navigation in open cholecystectomy. Methods: Forty-eight patients with extrahepatic cholangiography who underwent open cholecystectomy in our hospital from March 2016 to February 2018 were enrolled. They were divided into the control group (24 cases) and the experimental group (24 cases) by using the random number table method. The control group was treated with conventional X-ray cholangiopancreatography, and the experimental group was treated with indocyanine green near-infrared fluorescence imaging for extrahepatic cholangiography. The cholangiography success rate, cholangiography time, cholangiography economic costs, imaging accuracy and security were compared between two groups. The operation time, intraoperative blood loss, blood transfusion amount, length of hospital stays, and hospital expenses were also compared between two groups. Results: The success rate of cholangiography (98.62% vs 97.22%) and the incidence of adverse reactions (25.00 vs 29.17) were not significantly different between the two groups (P>0.05). The cholangiography time (25.69±3.47 min vs 31.42±4.66 min), operation time (90.18±10.27 min vs 81.44±9.35 min), intraoperative blood loss (82.35±8.24 ml vs 78.14±7.82 ml), blood transfusion volume (35.19±4.77 ml vs 29.58±4.03 ml), hospitalization time (7.59±1.52 d vs 6.24±1.25 d), and hospitalization cost (12.7±3.1 thousands vs 10.4±2.5 thousands) of the experimental group were significant lower than those of the control group. The accuracy rate (92.22% vs 87.50%), sensitivity (85.71% vs 50.00%) and specificity (88.24% vs 68.75%) of cholangiography in the experimental group were significantly higher than those in the control group, with statistically significant differences (P<0.05). Conclusion: Indocyanine green fluorescent navigation is more timely and accurate than traditional X-ray cholangiography during temporary angiography in open cholecystectomy, which can effectively shorten the operation time, intraoperative blood loss, blood transfusion, hospitalization time and hospitalization expenses. It does not increase the incidence of adverse reactions, has high safety, and is worthy of clinical promotion.

MicroRNA-24 attenuates vascular remodeling in diabetic rats through PI3K/Akt signaling pathway.

BACKGROUND AND AIMS: The vascular remodeling plays a crucial role in pathogenesis of diabetic cardiovascular complications. In this study, we intended to explore the effects and potential mechanisms of microRNA-24 (miR-24) on vascular remodeling under diabetic conditions. METHODS AND RESULTS: MiR-24 recombinant adenovirus (Ad-miR-24-GFP) was used to induce miR-24 overexpression either in carotid arteries or high glucose (HG)-induced vascular smooth muscle cells (VSMCs). Cell proliferation was analyzed using CCK-8 method. Cell migration was examined using wound-healing and transwell assay. mRNA and protein expressions of critical factors were, respectively, measured by real-time PCR and western blot as follows: qRT-PCR for the levels of miR-24, PIK3R1; western blot for the protein levels of PI3K (p85α), Akt, p-Akt, mTOR, p-mTOR, 4E-BP1, p-4E-BP1, p70s6k, p-p70s6k, MMP 2, MMP 9, collagen Ⅰ, as well as collagen Ⅲ. Carotid arteries in diabetic rats suffered balloon injury were harvested and examined by HE, immunohistochemical and Masson trichrome staining. The expression of miR-24 was decreased in HG-stimulated VSMCs and balloon-injured carotid arteries of diabetic rats, accompanied by increased mRNA expression of PIK3R1. The up-regulation of miR-24 suppressed VSMCs proliferation, migration, collagen deposition not only induced by HG in vitro, but also in balloon-injured diabetic rats, which were related to inactivation of PI3K/Akt signaling pathway. CONCLUSION: The up-regulation of miR-24 significantly attenuated vascular remodeling both in balloon-injured diabetic rats and HG-stimulated VSMCs via suppression of proliferation, migration and collagen deposition by acting on PIK3R1 gene that modulated the PI3K/Akt/mTOR axes.

Causes of ozone pollution in summer in Wuhan, Central China.

In August 2016, continuous measurements of volatile organic compounds (VOCs) and trace gases were conducted at an urban site in Wuhan. Four high-ozone (O3) days and twenty-seven non-high-O3 days were identified according to the China's National Standard Level II (∼100 ppbv). The occurrence of high-O3 days was accompanied by tropical cyclones. Much higher concentrations of VOCs and carbon monoxide (CO) were observed on the high-O3 days (p < 0.01). Model simulations revealed that vehicle exhausts were the dominant sources of VOCs, contributing 45.4 ±â€¯5.2% and 37.3 ±â€¯2.9% during high-O3 and non-high-O3 days, respectively. Both vehicle exhausts and stationary combustion made significantly larger contributions to O3 production on high-O3 days (p < 0.01). Analysis using a chemical transport model found that local photochemical formation accounted for 74.7 ±â€¯5.8% of the daytime O3, around twice the regional transport (32.2 ±â€¯5.4%), while the nighttime O3 was mainly attributable to regional transport (59.1 ±â€¯9.9%). The local O3 formation was generally limited by VOCs in urban Wuhan. To effectively control O3 pollution, the reduction ratio of VOCs to NOx concentrations should not be lower than 0.73, and the most efficient O3 abatement could be achieved by reducing VOCs from vehicle exhausts. This study contributes to the worldwide database of O3-VOC-NOx sensitivity research. Its findings will be helpful in formulating and implementing emission control strategies for dealing with O3 pollution in Wuhan.

[Research progress on early diagnosis, reasonable prevention and treatment of symptomatic spinal epidural hematoma following spinal surgery].

Symptomatic spinal epidural hematoma (SSEH) following spinal surgery is rare but one of the serious complications. SSEH can leave devastating neurological consequences if missing the optimal timing for treatment. The early diagnosis of SSEH is critical to the neurologic recovery, and MRI examination can help to check the location and the scope of the hematoma and provide imaging information for surgical operation. The risk factors of SSEH can be divided into preoperative factors, intraoperative factors and postoperative factors. The occurrence of SSEH can be minimized by controlling the risk factors, exact hemostasis and reasonable perioperative management. Patients with mild paralysis can choose conservative treatment, while patients with severe or progressive nerve injury (manual muscle testing <3) and unendurable nerve root pain should choose to clean the hematoma and decompress the nerve as soon as possible.

Efficacy of minimally invasive tonsil surgery for treatment of obstructive sleep apnea-hypopnea syndrome in children.

This study aimed to investigate the efficacy of minimally invasive tonsil surgery for the treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS) in children. Tonsil ablation or turbinate reduction was performed on 49 pediatric patients with OSAHS by minimally invasive tonsil surgery. In order to evaluate the efficacy of surgery, a comparison was conducted between pre-operation and post-operation data in terms of the symptoms, signs and polysomnography test. Total effectiveness rate of the surgery was 83.7%. Subgroup analysis was also performed based on the severity of their conditions: mild, moderate, and severe groups had an effectiveness rate of 90.0, 88.9, and 66.7%, respectively (Hc=6.665, P<0.05). Postoperatively, the apnea-hypopnea index, the minimum oxygen saturation (SaO2), and corresponding symptoms improved compared to pre-operation conditions (P<0.05). Minimally invasive tonsil surgery was a safe and effective method for treating OSAHS in children.

Identification of genes involved in rice seed priming in the early imbibition stage.

Phase II of seed imbibition is a critical process during seed priming. To identify genes involved in rice seed priming, the altered proteins between the dry and imbibed (24 h) seeds were compared using a two-dimensional gel electrophoresis system in this study. Ten significantly changed proteins (fold change ≥ twofold; P < 0.01) were successfully identified, which could be categorised as carbohydrate and protein biosynthesis and metabolism-related, signalling-related, storage and stress-related proteins. A meta-analysis indicated that the highest expression of the identified genes was at the milk and dough stages and in the endosperm tissue. Quantitative real-time PCR analysis showed that there was significant variation in gene expression (except FAD-dependent oxidoreductase) in embryos during seed priming (0-48 h). The expression of genes associated with stress appeared at the early imbibition stage, while those associated with carbohydrate metabolism, protein synthesis and signalling increased at the late imbibition stage. Three identified proteins (glucose-1-phosphate adenylyltransferase large subunit, aminotransferase and prolamin precursor) had similar transcript and protein expression patterns in embryos. Based on phenotype and gene expression, the optimal stop time for seed priming is 24 h, when these three genes have relatively low expression, followed by significant induction during imbibition in embryos. These three genes are ideal candidate biomarkers for rice seed priming.