ObjectiveThe most prevalent mRNA modification, N6-methyladenosine (m⁶A) plays an important role in various RNA metabolism, including gene expression and translation. By recruiting different “reader” proteins and their cofactors, m⁶A modification can affect messenger RNA (mRNA) degradation, splicing, nuclear export and translation. However, the selective mechanism by which m⁶A sites regulate mRNA translation through m⁶A reader YTHDF1 binding remains poorly understood, due to a lack of computational methods for identifying context-specific m⁶A sites that regulate translation. To address this, we developed a novel computational framework named m⁶ATEpre, the first tool designed to predict cell-specific m⁶A sites that regulate translation efficiency. Methodsm⁶ATEpre integrates multi-omics data, introduces a novel feature representation strategy for m⁶A site sequences, and employs an autoencoder to effectively capture embedded feature representations. Specifically, m⁶ATEpre first integrated MeRIP-seq data and PAR-CLIP data through overlapping m⁶A sites with YTHDF1 binding sites and identified YTHDF1-mediated m⁶A sites. Then, m⁶ATEpre detected the translation gene by analyzing the Ribo-seq data under YTHDF1 knockdown vs control condition. Genes whose translation is mediated by YTHDF1 in an m⁶A-dependent manner were identified by a significant decrease in translation efficiency upon YTHDF1 knockdown. Next, we proposed a binary vector indicating the presence or absence of YTHDF1 binding motifs to characterize each m⁶A site sequence. This represents a novel feature representation strategy for m⁶A sites. m⁶ATEpre utilized the autoencoder to extract the potentially important feature representations and constructed a multilayer perceptron neural networks model to predict potential m⁶A sites that regulating translation efficiency. ResultsA comprehensive evaluation of m⁶ATEpre was conducted through a series of experiments. We compared its performance against that of a similar prediction task model, as well as other classifiers. The results indicate that m⁶ATEpre achieved the best prediction performance. In addition, we analyzed different feature representation strategies and performed ablation experiments to validate the rationality of the model design. The results demonstrate that our proposed feature representation strategy has a greater advantage in improving prediction performance. In the HeLa cell line, bioinformatic analysis of the metagene distribution and sequence minimum free energy of m⁶A sites regulating translation efficiency (m⁶A-reg-TE sites) revealed their specific properties in translation regulation. Functional enrichment analysis indicated that m⁶A-reg-TE genes are associated with specific biological processes and KEGG pathways. By integrating the binding sites of YTHDF1 co-factors with m⁶A-reg-TE sites, we revealed that YTHDF1-mediated and m⁶A-dependent translation efficiency regulation requires the cooperation of multiple translation-regulatory RNA-binding proteins among its co-factors in the HeLa cell line. Furthermore, we extended our predictions to the dataset of the HEK293T cell line. Similarly, bioinformatic analysis of the metagene distribution and functional enrichment revealed the cell-specific characteristic of these predicted m⁶A-reg-TE sites in HEK293T cells. Likewise, integrated analysis of multiple YTHDF1 co-factors and m⁶A-reg-TE sites predicted in the HEK293T cell line reveals their m⁶A-dependent cooperation in regulating translation efficiency. Conclusionm⁶ATEpre is a timely tool that will advance our understanding of the mechanisms of m⁶A regulation in translation efficiency. The source code and datasets used in this work can be downloaded from https://www.scidb.cn/s/bAZZFr.

Objective To develop a three-dimensional(3D)deep neural network based preoperative classification model for coronary computed tomography angiography(CTA)in atrial fibrillation patients,and to explore the effects of transfer learning on the performance of medical image classification models,thereby providing preoperative decision support for catheter ablation to advance atrial fibrillation treatment toward precision and personalization.Methods Utilizing 3D ConvNet and 3D ResNet as backbone network,the three-dimensional classification features were extracted from coronary CTA sequences.The publicly available pre-trained weights were used for transfer learning.The model performance was evaluated through metrics such as confusion matrix,classification accuracy,and area under the curve(AUC).A comparative analysis was also conducted to evaluate the performance differences between the transfer learning model and the initialized training model.Results Transfer learning yielded significant performance improvements over the initialized training models,attaining AUC improvement of 9.1%-16.7%and accuracy enhancement of 6.2%-23.5%.Among all models,3D-ResNet18 model with MedicalNet pre-training weights performed the best,achieving an AUC of 0.77 and an accuracy of 0.71.Conclusion The proposed three-dimensional deep network enhanced by transfer learning can effectively identify atrial fibrillation patients requiring additional ablation besides pulmonary vein isolation through preoperative coronary CTA,which will assist clinicians in optimizing surgical strategies and improving treatment outcomes,thereby reducing long-term postoperative recurrence rates.

As an innovative dosage form, traditional Chinese medicine(TCM) dry powder inhalers have emerged as a focal point in the research and development of new preparations due to its high efficiency, safety, and bioavailability. This paper systematically reviewed the relevant literature and patents associated with TCM dry powder inhalers to analyze the origins and the current research and development status. Furthermore, this paper probed into the research and development ideas of TCM dry powder inhalers regarding clinical positioning, prescription screening, and druggability. Additionally, the paper thoroughly analyzed the technical barriers in druggability studies and elaborated on corresponding research techniques and coping measures. Furthermore, it emphasized the need for improved regulations and policies governing TCM dry powder inhalers, advocated for strengthened oversight, and called for the establishment of a scientific quality evaluation system. Measures such as promoting production-education-research collaboration, enhancing personnel training, and fostering international exchanges were proposed to provide a scientific and systematic reference for the future research, development, and application of TCM dry powder inhalers, thereby facilitating the rapid modernization of TCM.
Humans ; Dry Powder Inhalers/trends* ; Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/instrumentation* ; Administration, Inhalation

Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 10 6 cells, 5 × 10 6 cells, and 1 × 10 7 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1 st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
Male ; Animals ; Erectile Dysfunction/metabolism* ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods* ; Rats ; Penis/pathology* ; Humans ; Disease Models, Animal ; Umbilical Cord/cytology* ; Peripheral Nerve Injuries/complications* ; Mesenchymal Stem Cells ; Nitric Oxide Synthase Type III/metabolism* ; Actins/metabolism* ; Nitric Oxide Synthase Type I/metabolism*

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

Objective:To investigate the expression of protein kinase D2(PRKD2)in bladder cancer(BLCA)tissue using bioinformatics analysis method and its effect on the prognosis of BLCA patients,and to clarify the role of PRKD2 in the occurrence and development of BLCA.Methods:The data from 9 normal bladder samples,19 BLCA paracancerous samples,and 407 BLCA tumor samples were downloaded from the UCSC Cancer Genome Database.The Mann-Whitney U test was applied to analyze the difference in expression of PRKD2 mRNA in BLCA tumor and normal bladder tissues,and the Human Protein Atlas(HPA)database was used for proteomic validation.DESeq2 package in R software was applied to screen the differentially expressed genes(DEGs)in BLCA tissue in PRKD2 low-and high-expression groups.The co-expression heatmaps of PRKD2 were plotted using the ggplot2 package,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used for functional annotation analysis and pathway enrichment analysis of DEGs,and Gene Set Enrichment Analysis(GSEA)was used to obtain the gene sets that were significantly enriched for DEGs.The BLCA samples were divided into low-and high-expression groups according to the expression level of PRKD2,and the correlations between PRKD2 expression and immune cell infiltration in the BLCA patients were analyzed with GSVA package.The relationship between PRKD2 and prognosis of BLCA patients was further analyzed using the survival package and the survminer package.The PRKD2 gene mutations in BLCA tissue were analyzed using the cBioPortal database.The cystitis,bladder polyp and BLCA tissues were collected,and the expression levels of interleukin-17F(IL-17F)protein in BLCA and control tissues were detected using immunohistochemical staining technique.Results:PRKD2 was highly expressed in a variety of malignant tumors,and the expression levels of PRKD2 mRNA and protein in BLCA tissue were significantly increased compared with those in normal bladder tissue(P＜0.05).Single gene differential analysis of PRKD2 yielded a total of 1 058 DEGs,of which a total of 29 genes were up-regulated and 1 029 were down-regulated.The results of GO functional enrichment analysis showed that DEGs were mainly enriched in the biological process(BP),such as chemical stimuli involved in sensory perception,Cajal body,and endopeptidase inhibitor activity.The results of KEGG pathway analysis showed that DEGs were mainly enriched in the pathway of Staphylococcus aureus infection and the pathway of maturity onset diabetes of the young.GSEA analysis showed that DEGs were mainly enriched in the Notch signaling pathway,the retinoic acid-inducible gene-Ⅰ(RIG-Ⅰ)-like receptor signaling pathway,the cytoplasmic DNA screening pathway,the base excision repair signaling pathway,natural killer(NK)cell-mediated cytotoxicity signaling pathway and T cell receptor signaling pathway.The results of immune infiltration analysis indicated that the expression of PRKD2 was positively correlated with five types of cells,such as activated dendritic cells(aDC),NK CD56dim cells and central memory T cells(Tcm)(P＜0.05),and negatively correlated with three types of immune cells,including macrophages,effector memory T cells(Tem)and plasmacytoid dendritic cells(pDC)(P＜0.05).The clinical characteristic subgroup analysis results showed that the expression levels of PRKD2 mRNA in BLCA patients who were over 70 years old and developed lymphovascular invasion were decreased(P＜0.05);the overall survival(OS),disease-specific survival(DSS)and progression-free interval(PFI)in the BLCA patients with PRKD2 high expression were significantly longer than those with PRKD2 low expression(P＜0.05).The univariate and multivariate Cox analyses indicated that distant metastasis,primary therapy outcome and clinicopathologic stage were the important factors affecting BLCA prognosis.About 9％patients had PRKD2 gene mutations,including missense mutation,gene amplification,mRNA low or high expression,and multi-motif mutation.The immunohistochemistry results showed that the expression level of IL-17F protein in BLCA tissue was significantly higher than that in cystitis tissue(P＜0.05).Conclusion:The expression level of PRKD2 in BLCA tissue is obviously increased,which could up-regulate the expression of IL-17F protein,and the decrease of PRKD2 protein expression may be a potential factor for the poor prognosis of BLCA patients.

Infectious chronic refractory wounds are common in the department of dermatology,and have a great influence on the quality of life of patients.Their incidence is increasing year by year.The pathogensis of infectious chronic refractory wounds is due to the exuberance of pathogenic heat and toxin,disharmony between nutritive qi and defensive qi,and imbalance of zang-fu organs,which is related with the theory of qi-fluid and sweat pores.Therefore,it is proposed that stagnation and obstruction of sweat pores contribute to the pathological basis for the onset of infectious chronic refractory wounds,and therapeutic principle of opening sweat pores was presented.In the medication view of treating the skin diseases with the skin-related Chinese medicinals,skin-related Chinese medicinals are good at treating skin diseases,and consequently the application of skin-related Chinese medicinals to open sweat in treating infectious chronic refractory wounds was discussed.It is suggested that for the treatment of infectious chronic refractory wounds due to pathogenic fire-toxin accumulation in sweat pores,therapy of clearing heat and expelling fire to open sweat pores should be exployed,and skin-related Chinese medicinals such as Phellodendri Chinensis Cortex,Dictamni Cortex and Fraxini Cortex can be selected;for the treatment of infectious chronic refractory wounds due to blood-stasis stagnation in sweat pores,therapy of cooling and activating blood to open sweat pores should be exployed,and skin-related Chinese medicinals such as Moutan Cortex and Lycii Cortex can be selected;for the treatment of infectious chronic refractory wounds due to wind and dampness obstructing sweat pores,therapy of expelling wind and eliminating dampness to unblock sweat pores should be exployed,and skin-related Chinese medicinals such as Acanthopanacis Cortex,Citri Reticulatae Pericarpium,and Poriae Cutis can be selected;for the treatment of infectious chronic refractory wounds due to healthy qi deficiency resulting in the obstruction of sweat pores,therapy of invigorating spleen and tonifying kidney to nourish sweat pores should be exployed,and skin-related Chinese medicinals such as Cinnamomi Cortex,Eucommiae Cortex,and black soybean testa(Testa Glycinea Macids)can be chosen.Guided by the theory of qi-fluid and sweat pores,this paper explored the application of skin-related Chinese medicinals in the treating infectious chronic refractory wounds,which provides theoretical basis for such an approach,enriches the theory of traditional Chinese medicine for the treatment of infectious chronic refractory wounds,and expands the clinical application of the theory of sweat pores.

Objective To explore the effect of the method of cooling blood and removing stasis on promoting the relief of swelling and pain symptoms and the recovery of joint mobility in the early stage of acute ankle sprains.Methods From January 2023 to January 2024,a total of 88 patients with early-stage acute ankle sprains admitted to the Eighth Clinical Medical School of Guangzhou University of Chinese Medicine(Foshan Hospital of Traditional Chinese Medicine)were selected.The patients were randomly divided into an observation group and a control group using a random allocation method(random number table),with 44 patients in each group.The control group was treated following the PRICE principle for acute sports injury,with the measures such as ice compress,immobilization,and compression.The observation group,in addition to receiving the same treatment as the control group,was given the decoction of Liangxue Quyu Prescription orally(a formula with the actions of cooling blood and removing stasis,and composed of Ilicis Pubescentis Radix,Paeoniae Radix Rubra,Moutan Cortex,Rehmanniae Radix,Achyranthis Bidentatae Radix,Jujubae Fructus,and Glycyrrhizae Radix et Rhizoma),and external washing with Shujin Xi External Washing Granules(mainly composed of Clematidis Radix et Rhizoma,Sappan Lignum,Artemisiae Anomalae Herba,Uncariae Ramulus cum Uncis,and Glechomae Herba,and others.The treatment period for both groups lasted for one week.Before and after treatment,the changes in Visual Analogue Scale(VAS)scores of pain,ankle swelling scores,ankle range of motion(including plantar flexion and dorsiflexion),and the American Orthopedic Foot&Ankle Society(AOFAS)ankle-hindfoot scale scores in the two groups were observed.After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After one week of treatment,the total effective rate in the observation group was 95.45%(42/44),and that in the control group was 86.36%(38/44).The intergroup comparison by chi-square test showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the VAS scores for pain in both groups were significantly reduced(P＜0.05)and the AOFAS scores for ankle function were significantly increased(P＜0.05)compared to those before treatment.The observation group showed significant reduction in VAS scores and obvious improvement in AOFAS scores compared to the control group(P＜0.05 or P＜0.01).(3)After treatment,the ankle swelling scores in both groups were significantly reduced(P＜0.05)and the ankle range of motion was significantly improved(P＜0.05)compared to those before treatment.The observation group showed significant reduction in ankle swelling scores and obvious improvement in the range of motion compared to the control group(P＜0.05 or P＜0.01).(4)After treatment,the scores for TCM symptoms of pain,ecchymosis and swelling,and scores of functional disorders in both groups were significantly reduced(P＜0.05)compared to those before treatment.The observation group showed significant reduction in pain,ecchymosis,and swelling scores compared to the control group(P＜0.01),while there was no significant difference in dysfunction scores between the two groups after treatment(P＞0.05).Conclusion The method of cooling blood and removing stasis has significant effects on improving swelling and pain symptoms during the early treatment of acute ankle sprains.It is effective on relieving swelling and pain,and is helpful for promoting the recovery of ankle joint function.

Objective To investigate the probability and dosimetric risk factors of lung injury after sequential immune checkpoint inhibitors (ICIs) and thoracic radiotherapy. Methods A retrospective analysis was conducted on 139 patients who received sequential ICIs and thoracic radiotherapy in Xuzhou Cancer Hospital and Affiliated Hospital of Xuzhou Medical University between February 2020 and February 2024. The relationships of clinical factors and lung and heart volume dose parameters with grade ≥ 2 acute lung injury (ALI) in patients with thoracic tumors were studied using univariable (χ² test, t test, nonparametric test) and multivariable (binary logistic regression analysis) methods. The thresholds of dosimetric risk factors were determined using the receiver operating characteristic curves. Clinical factors included age, gender, smoking history, type of ICIs, cycle of ICI application, and the interval between ICI application and thoracic radiotherapy. Dose parameters included total radiotherapy dose, single dose, planning target volume, maximum dose of planning target volume, average dose of planning target volume, total lung volume, heart volume, and the V₅, V₁₀, V₁₅, V₂₀, V₂₅, V₃₀, V₃₅, and V₄₀ of lung and heart. Results The incidence of grade ≥ 2 ALI in the included cases was 36% (50/139). The χ² test did not find any statistically significant clinical factors. In the univariable and binary Logistic regression analysis, lung V₁₅ and V₂₀, heart V₁₅ and V₂₀, and lung volume were independent risk factors for the occurrence of grade ≥ 2 ALI in sequential ICIs and thoracic radiotherapy. The thresholds were 18.51% for lung V₁₅, 14.43% for lung V₂₀, 32.41% for heart V₁₅, and 17.74% for heart V₂₀. Conclusion For patients who are going to receive thoracic radiotherapy after ICIs, the thresholds of lung V₁₅ and V₂₀ and heart V₁₅ and V₂₀ in the radiotherapy plan are recommended to be less than 18.51%, 14.43%, 32.41%, and 17.74%, respectively, which can effectively reduce the occurrence of grade ≥ 2 ALI.

BackgroundAtypical antipsychotics have been widely used in patients with chronic schizophrenia， and aripiprazole and risperidone are the most commonly used drugs. The mechanism of action of the two is different， while previous studies have provided insufficient credible evidence from multiple perspectives to support the comparative efficacy of the two drugs in improving symptoms in patients with chronic schizophrenia. ObjectiveTo compare the efficacy of aripiprazole and risperidone on the improvement of symptoms， prepulse inhibition （PPI）， cognitive functioning and neurotrophic factors in patients with chronic schizophrenia， so as to provide effective treatment regimens for these patients. MethodsA total of 86 patients with chronic schizophrenia attending the psychiatry department of the Third People's Hospital of Fuyang from March 2021 to March 2023 and fulfilling the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） were enrolled and grouped using random number table method， each with 43 cases. Aripiprazole group was given oral aripiprazole once daily at an initial dose of 5 mg for one week and then gradually increased to a maximum dose of 25 mg. Risperidone group received oral risperidone twice daily at an initial dose of 0.5 mg for one week and then gradually increased to a maximum dose of 3 mg. Treatment in both groups lasted 3 months. Before treatment and 3 months after treatment， Patients were required to complete Positive and Negative Symptom Scale （PANSS）， detection of both strong and weak PPIs in a startle modification passive attention paradigm， Wisconsin Card Sorting Test （WCST） and the measurement of neurotrophic factors at baseline and after treatment. The adverse reactions were recorded. Analysis of covariance was used to test the difference between the PANSS score， PPI， WCST and neurotrophic factor levels of the groups， with the pretest used as the covariate. Results3 months after treatment， no statistical difference was found in the scores of PANSS general psychopathology subscale， positive symptom subscale， negative symptom subscale and total score between two groups after treatment （F=0.621， 0.815， 0.743， 0.752， P>0.05）. There were no statistically significant differences between the two groups in PPI inhibition rate， single intense stimulus amplitude， single intense stimulus latency， prepulse inhibition amplitude， or prepulse inhibition latency （F=0.174， 0.001， 0.183， 0.171， 0.001， P>0.05）. There was no statistically significant difference in the total number of WCST tests between two groups （F=0.512， P>0.05）， whereas aripiprazole group reported significantly larger total numbers of categories completed and correct responses as well as smaller total numbers of random errors and perseverative errors compared to risperidone group （F=3.737， 4.621， 4.892， 5.130， P<0.05）. A significant increase in brain-derived neurotrophic factor （BDNF） and nerve growth factor （NGF） along with a reduction in glial fibrillary acidic protein （GFAP） were documented in risperidone group when compared to risperidone group （F=4.414， 3.781， 6.319， P<0.05）. No significant difference was demonstrated in the incidence of adverse reactions between the two groups （χ²=0.261， P>0.05）. ConclusionAripiprazole may be more beneficial than risperidone in improving cognitive functioning and neurotrophic factor levels in patients with chronic schizophrenia. ［Funded by Scientific Research Project of Fuyang Municipal Health Commission in 2021 （number， FY2021-147）］