Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objective To investigate the feasibility and accuracy of convolutional neural networks for automatically delineating the pancreatic cancer gross target volume(GTV)in pancreatic enhanced CT.Methods The localizable enhanced CT images of 114 patients with pancreatic cancer were retrospectively selected,in which the GTV was manually delineated using AccuContour.The imaging data were then import to AccuLearning and randomly divided as the training set,validation set and test set at a ratio of 8:1:1.Flex and Segresnet were used to train the automatic segmentation model,with each network structure trained continuously 3 times using fixed training parameters.The model was evaluated in terms of Dice similarity coefficient(DSC),95%Hausdorff distance(HD95),average symmetric surface distance(ASSD)and relative volume difference(RVD).Results In the model training phase,Flex-3 test results in Flex group were the worst,with a minimum DSC of 0.14%and an average DSC of 56.30%,while Flex-1 performed well,achieving a minimum DSC of 47.90%and an average DSC of 67.35%.Meanwhile,Segresnet-2 in Segresnet group had the worst test results,with a minimum DSC of 0.00%and an average DSC of 42.46%,while Segresnet-3 test results were better,with a minimum DSC of 42.65%and an average DSC of 63.28%.In the fixed testing phase,the best results among all were as follows:average DSC and RVD values of 63.88%and 29.41%in Segresnet-3 group,average ASSD value of 4.43 mm in Segresnet-2 group,and average HD95 value of 12.87 mm in Segresnet-1 group.Conclusion Both Flex and Segresnet architectures of convolutional neural network can be used for the automatic pancreatic tumor GTV segmentation training,with Segresnet performing better in comprehensive evaluation.

Objective To investigate the feasibility and accuracy of convolutional neural networks for automatically delineating the pancreatic cancer gross target volume(GTV)in pancreatic enhanced CT.Methods The localizable enhanced CT images of 114 patients with pancreatic cancer were retrospectively selected,in which the GTV was manually delineated using AccuContour.The imaging data were then import to AccuLearning and randomly divided as the training set,validation set and test set at a ratio of 8:1:1.Flex and Segresnet were used to train the automatic segmentation model,with each network structure trained continuously 3 times using fixed training parameters.The model was evaluated in terms of Dice similarity coefficient(DSC),95%Hausdorff distance(HD95),average symmetric surface distance(ASSD)and relative volume difference(RVD).Results In the model training phase,Flex-3 test results in Flex group were the worst,with a minimum DSC of 0.14%and an average DSC of 56.30%,while Flex-1 performed well,achieving a minimum DSC of 47.90%and an average DSC of 67.35%.Meanwhile,Segresnet-2 in Segresnet group had the worst test results,with a minimum DSC of 0.00%and an average DSC of 42.46%,while Segresnet-3 test results were better,with a minimum DSC of 42.65%and an average DSC of 63.28%.In the fixed testing phase,the best results among all were as follows:average DSC and RVD values of 63.88%and 29.41%in Segresnet-3 group,average ASSD value of 4.43 mm in Segresnet-2 group,and average HD95 value of 12.87 mm in Segresnet-1 group.Conclusion Both Flex and Segresnet architectures of convolutional neural network can be used for the automatic pancreatic tumor GTV segmentation training,with Segresnet performing better in comprehensive evaluation.

OBJECTIVE To evaluate the innovation and sustainable development ability of traditional Chinese medicine(TCM) preparation in medical institutions, and to provide reference for the decision-making of administrative departments and the sustainable development of TCM preparation in hospitals. METHODS Based on the information data of 133 medical institutions in Zhejiang Province, analytic hierarchy process was used to construct the evaluation system of innovation and sustainable development ability of TCM preparation of medical institutions, and the prediction model of evaluation system of TCM preparation room/center was built by back propagation neural network. RESULTS The evaluation index system for innovation and sustainable development of TCM preparations in medical institutions included 4 second-level indexes and 19 third-level indexes. Among them, the number of varieties developed, the number of over one million varieties, the number of registered varieties, the way of research and development, and the area of preparation room had higher weight values, which were 0.15758, 0.12928,0.09343, 0.07879 and 0.07458, respectively. The entropy weight method and analytic hierarchy process index weights were used to construct the back propagation neural network. The overall correlation coefficients of the training models of the Levenberg-Marquardt algorithm and the Scaled Conjugate Gradient algorithm were 0.98983 and 0.93480, respectively. CONCLUSION This study establishes a scientific and effective comprehensive evaluation system for the innovation and sustainable development ability of TCM preparations in medical institutions, which can realize the prediction and evaluation of the comprehensive ability of TCM preparations in medical institutions.

Objective To establish a high-precision and high-specificity quantitative nuclear magnetic resonance phosphorus spectrometry method(31P-qNMR)for detecting the phosphorus content in calcium hydrogen phosphate chewable tablets.Methods Hexamethyl phosphoramide was used as an internal standard,phosphorus spectrum data of calcium hydrogen phosphate chewable tablets solution was collected.The linear relationship of calcium hydrogen phosphate within the concentration range of 1.0 to 9.0 mg/ml was studied,and sample recovery rate and repeatability experiments were conducted.Results Calcium hydrogen phosphate and the internal standard demonstrated a good linear relationship within the concentration range of 1.0 to 9.0 mg/ml,with a regression equation A=0.004 3+0.183 6C.The recovery rates for low,medium,and high concentrations were 98.0%,98.1%,and 98.4%,respectively,with relative standard deviations(RSD)of 0.31%,0.68%,and 0.62%,respectively(n=9).The average content of calcium hydrogen phosphate in the chewable tablets was determined to be 98.1%.Conclusion This study successfully established a high-precision and highly specific method for quantifying the content of calcium hydrogen phosphate in chewable tablets,which did not require a self-reference substance,was simple in sample preparation,and had a fast detection speed.The method could provide a new technical support for the quality control of phosphorus-containing drugs.

Objective:To explore the clinical application value of pre-breathing mode in double-low imaging of 320-slices computed tomography(CT)for pulmonary artery.Methods:A total of 100 patients who underwent CT pulmonary angiography(CTPA)for suspected pulmonary embolism(PE)in Liuzhou People's Hospital from July 2021 to September 2022 were prospectively selected as the research subjects and they were randomly divided into observation group and control group,with 50 cases in each group.The patients of the control group adopted conventional breathing mode(the breathing password was activated after reaching the threshold,and the scan was triggered after 6 s),while the patients of the observation group adopted the pre-breathing mode(the breathing password was activated after 1 or 2 seconds,and the scan was triggered after reaching the threshold).Both two groups adopted double low-technique scan of 320 slices CT.The differences in delay time,radiation dose,the points of subjective and objective image quality,and other indicators were compared between the two groups.Results:The volume CT dose index(CTDIvol),dose length product(DLP),effective dose(ED)and delay time of the observation group were significantly lower than those of the control group(t=76.230,30.225,12.282,7.088,P<0.05),respectively.The comparison of the subjective points of image qualities between the two groups indicated that there were 25 cases with 5 points,23 cases with 4 points and 2 cases with 3 points in the observation group,and there were 21 cases with 5 points,26 cases with 4 points and 3 cases with 3 points in the control group.There was no significant difference in the averagely subjective points of image qualities between two groups(P>0.05).The signal-to-noise ratio(SNR)and signal to noise ratio(CNR)of the observation group were significantly lower than those of the control group,and the noise level(SD)of the observation group was significantly higher than that of the control group(t=25.441,23.886、11.426,P<0.05),respectively.The CT values of the artery trunk of right pulmonary,artery branch of right pulmonary,artery trunk of left pulmonary and artery branch of left pulmonary in the observation group were significantly higher than those in the control group(t=2.256,2.225,2.042,2.277,P<0.05),respectively.Conclusion:The pre-breathing mode can effectively improve CTPA image quality,and reduce radiation dose and the dosage of contrast agent,which clinical application effect is significant.It is worth learning.

Purpose: The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored. Materials and Methods: On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL). Results: A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse. Conclusion This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective:This study aimed to investigate the effect of tumor lysis syndrome (TLS) on the prognosis of children and adolescents with intermediate- or high-risk high-grade mature B-cell nonHodgkin lymphoma (HG B-NHL) .Methods:This study collected the clinical data and prognosis of 283 patients aged <18 years with newly diagnosed intermediate- or high-risk HG B-NHL treated at the Sun Yat-sen University Cancer Center from January 2010 to December 2022. The clinical characteristics, laboratory indicators during TLS, and prognosis of the patients were analyzed. The optimal cutoff values of laboratory indicators during TLS were identified using R studio according to event-free survival (EFS) .Results:Of the 283 patients enrolled, the median age was 7 (range: 1-18) years and the male-to-female ratio was 3.6∶1, 76 (26.9%) developed TLS, and 207 (73.1%) did not. Patients with TLS demonstrated higher proportions of the pathological subtype Burkitt lymphoma, high-risk stratification, age <12 years, and LDH of ≥1 000 IU/L compared with patients without TLS (all P<0.05). The 5-year EFS and overall survival (OS) rates of the entire group were (84.5±2.2) % and (88.2±2.0) %, respectively. The 5-year OS rate of patients with TLS was significantly lower than that of those without TLS [ (80.8±4.6) % vs (91.0±2.0) %, P=0.01]. Among patients with TLS, those with serum uric acid of ≤612.7 μmol/L ( n=36) exhibited lower 5-year EFS [ (67.8±8.1) % vs (87.5±5.2) %, P=0.04] and OS rates [ (69.9±8.1) % vs (90.0±4.7) %, P=0.04] compared with those with uric acid of >612.7 μmol/L ( n=40). Similarly, patients with serum phosphate of ≤1.89 mmol/L ( n=58) demonstrated lower 5-year EFS [ (71.6±6.0) % vs 100%, P=0.02] and OS rates [ (74.8±5.8) % vs 100%, P=0.03] compared with those with phosphate of >1.89 mmol/L ( n=18) . Conclusions:TLS is associated with poor prognosis in patients with HG B-NHL. Patients with lower serum uric acid and phosphate levels during TLS demonstrated worse prognoses, indicating their potential value in predicting prognosis and guiding stratified treatment.