Objective To investigate the biological functions of the ERG3 gene in Candida albicans and its potential value in antifungal therapy. Methods The ERG3 null mutant was constructed by the CRISPR/Cas9 technology. Gas chromatography-mass spectrometry, microbroth dilution method, hyphal induction and mouse systemic infection models were carried out to evaluate sterol metabolism, drug susceptibility, hyphal formation ability and pathogenicity in C. albicans. Results The disruption of the ERG3 gene led to disordered sterol metabolism in C. albicans with a significant increased level of episterol, 14α-methylfecosterol and ergosta-7,22-dienol. The ERG3 null mutant exhibited significantly reduced susceptibility to antifungal azole and polyene drugs, which suggested that ERG3 involve in regulating drug resistance. Although the disruption of ERG3 inhibited hyphal growth and biofilm formation, it did not significantly alter the pathogenicity of the strain in a mouse model of systemic fungal infection. Conclusion The ERG3 gene was a key regulator in the ergosterol synthesis pathway in C. albicans. Its deletion induced multi-drug resistance by reshaping sterol metabolism, while pathogenicity maintenance depended on compensatory mechanisms. This study provided critical insights for developing antifungal drugs targeting sterol metabolism and overcoming drug resistance.

To address issues such as loss of detailed information, blurred target boundaries, and unclear structural hierarchy in medical image fusion, this paper proposes an adaptive feature medical image fusion network based on a full-scale diffusion model. First, a region-level feature map is generated using a kernel-based saliency map to enhance local features and boundary details. Then, a full-scale diffusion feature extraction network is employed for global feature extraction, alongside a multi-scale denoising U-shaped network designed to fully capture cross-layer information. A multi-scale feature integration module is introduced to reinforce texture details and structural information extracted by the encoder. Finally, an adaptive fusion scheme is applied to progressively fuse region-level features, global features, and source images layer by layer, enhancing the preservation of detail information. To validate the effectiveness of the proposed method, this paper validates the proposed model on the publicly available Harvard dataset and an abdominal dataset. By comparing with nine other representative image fusion methods, the proposed approach achieved improvements across seven evaluation metrics. The results demonstrate that the proposed method effectively extracts both global and local features of medical images, enhances texture details and target boundary clarity, and generates fusion image with high contrast and rich information, providing more reliable support for subsequent clinical diagnosis.
Humans ; Image Processing, Computer-Assisted/methods* ; Algorithms ; Neural Networks, Computer ; Diagnostic Imaging/methods* ; Image Interpretation, Computer-Assisted/methods*

Pinelliae Rhizoma (PR), known as Banxia in Chinese, Hange in Japanese, and Banha in Korean, is a renowned herbal medicine in East Asia derived from the dry tuber of Pinellia ternata (Thunb.) Breit. (PT). It is extensively utilized in dispensing granules, classical prescriptions, and herbal formulas to treat various conditions, including cough, infection, phlegm, nausea, asthma, and inflammation. Despite numerous studies on PR and its classical prescriptions over recent decades, a comprehensive synthesis of available evidence regarding its multifunctional roles and therapeutic potential is lacking. This review aims to address this gap by examining emerging evidence from metabonomics, preclinical studies, and clinical trials, while exploring potential trends and prospects for future research. A systematic literature search was conducted across six electronic databases, including PubMed, Web of Science, Scopus, ScienceDirect, Wanfang, and China National Knowledge Infrastructure, to identify relevant articles on PR published until March 2023. PR contains 107 compounds with diverse pharmacological activities, including anti-inflammatory, immune regulatory, anti-viral, anti-cancer, anti-asthma, antitussive and expectorant, antioxidant, anti-obesity, anti-atherosclerosis, anti-microbial, emetic and anti-emetic, anti-convulsant and anti-epileptic, sedative and hypnotic, learning and memory enhancement, and anti-depressant effects. Metabonomic studies suggest that raw PR may exhibit cardiotoxicity and pregnancy toxicity while showing no apparent hepatorenal toxicity. However, limited pharmacokinetic investigations on PR constrain its clinical translation. Furthermore, clinical safety data on PR is scarce, with only four clinical trials assessing its positive effects in pediatric epilepsy, nausea and vomiting, soft tissue injury, and chronic sinus tract. This review aims to enhance understanding of PR and provide valuable information and recommendations for further research and development of herbal medicine.
Humans ; Pinellia/chemistry* ; Animals ; Ethnopharmacology ; Drugs, Chinese Herbal/chemistry* ; Phytochemicals/chemistry* ; Rhizome/chemistry*

Objective To clarify the metabolic phenotypic changes in the serum and placenta of pre-eclampsia(PE)patients and their potential impact on fetal serum,and to identify and explore potential predic-tive biomarkers related to PE by using non-targeted metabolomics technology,thereby providing a reference for clinical diagnosis and disease monitoring.Methods Based on non-targeted metabolomics using liquid chro-matography-mass spectrometry(LC-MS),metabolomic analyses were performed on serum,placenta and um-bilical cord blood samples from 6 PE patients(PE group)and 6 healthy pregnant women in the late trimester(control group).Differential endogenous metabolites in each sample were screened using multivariate and uni-variate statistical methods.Metabolic pathways involved in the differential metabolites were enriched using MetaboAnalyst software.Additionally,potential biomarkers for predicting PE were identified based on binary logistic regression models.Results Compared with the control group,significant differences in the metabolic profiles of serum,placenta,and fetal serum were observed in the PE group.In the serum of PE patients,major metabolic abnormalities included α-linolenic acid metabolism,taurine metabolism,glycine,serine and threonine metabolism.In the placenta,abnormalities in linoleic acid metabolism,taurine metabolism,α-linolenic acid me-tabolism,and unsaturated fatty acid biosynthesis were detected.In the fetus of PE patients,metabolic abnor-malities were found in glutamine and glutamate metabolism,α-linolenic acid metabolism,and alanine,aspar-tate,and glutamate metabolism,involving polyunsaturated fatty acids and amino acids.The receiver operating characteristic(ROC)curves of differential metabolites were plotted using binary logistic regression models,and 4 serum metabolites with an area under the curve(AUC)＞0.9 were identified,mainly polyunsaturated fatty acid metabolites.The AUC of α-linolenic acid,a common differential metabolite in all three samples,was 0.806,with a sensitivity of 66.67％and specificity of 100.00％,indicating high diagnostic value.Conclusion The serum,placenta,and fetal serum metabolic profiles of PE patients and healthy pregnant women in the late trimester are significantly different and affect the metabolic phenotypes of offspring,providing insights into the pathogenesis of PE.

Objective To investigate the relationship between Klotho,insulin-like growth factor-1(IGF-1),and Irisin in the placentas of pregnant rats and the intrauterine development of fetuses.Methods Thirty SD rats were divided into the intrauterine growth restriction(IUGR)experimental animal model group(IUGR group),the macrosomia experimental animal model group(macrosomia fetal group),and the control group ac-cording to different feeding diets(low-protein diet,high-protein diet,and normal diet).All pregnant mice were subjected to laparotomy for tissue sampling on the 21st day of pregnancy.The birth weight,body length,and placental mass of fetal rats were recorded.The relative mRNA expression levels of Klotho,IGF-1,and Irisin in the placentas were detected by quantitative real-time fluorescent reverse transcription-PCR(qRT-PCR),and the correlations between various factors above were analyzed.Results Compared with the control group,the birth weight,body length and placental mass of fetal rats in the IUGR group were lower,while those in the macrosomia fetal group were higher,with statistically significant differences(P<0.05).Compared with the control group,the relative mRNA expression levels of Klotho,IGF-1,and Irisin in the IUGR group were de-creased,while those in the macrosomia fetal group were increased,with statistically significant differences(P<0.05).Correlation analysis showed that Klotho mRNA was positively correlated with the relative expres-sion levels of placental IGF-1 mRNA and Irisin mRNA,and IGF-1 mRNA were also positively correlated with the relative expression level of placental Irisin mRNA(P<0.05).Conclusion Klotho,IGF-1,and Irisin in the placenta are associated with fetal growth and possibly regulated through the Klotho/IGF-1/Irisin axis.

[This corrects the article DOI: 10.11909/j.issn.1671-5411.2017.08.005.].

Objective:To compare the preoperative presentation, intraoperative findings, and postoperative outcomes between middle ear cholesteatoma with tympanosclerosis （MECwTS） and middle ear cholesteatoma without tympanosclerosis （MECw/oTS）, thereby investigating the clinical characteristics of MECwTS. Methods:A retrospective analysis was conducted on the clinical data of 120 patients with middle ear cholesteatoma. Patients were divided into two groups based on the presence or absence of concomitant tympanosclerosis: the MECwTS group （n=49） and the MECw/oTS group （n=71）. All patients underwent preoperative evaluations including temporal bone CT, otoscopic examination, pure-tone audiometry, tympanometry, and assessment using the Zurich Chronic Middle Ear Inventory （ZCMEI-21） quality of life scale. All patients underwent canal wall down mastoidectomy with tympanoplasty. Concurrent ossicular chain reconstruction was performed: partial ossicular replacement prosthesis （PORP） in 83 cases and total ossicular replacement prosthesis （TORP） in 37 cases. Intraoperative disease severity was assessed using the Cholesteatoma Comprehensive Score Scale （CCSS）. Postoperative follow-up lasted at least one year and included pure-tone audiometry, otoscopic examination, and the ZCMEI-21 scale administered at ≥1 year post-surgery. Preoperative and postoperative air-bone gap （ABG） and ZCMEI-21 scores were compared between the MECwTS and MECw/oTS groups. Additionally, surgical efficacy was defined as a postoperative ABG ≤20 dB; the hearing improvement efficacy of PORP versus TORP was compared based on this criterion. Results: ①Preoperative ABG showed no significant difference between the MECw/oTS and MECwTS groups（P>0.05）. Postoperative ABG was （18.65±10.21） dB in the MECw/oTS group versus （22.55±9.53） dB in the MECwTS group, demonstrating a statistically significant intergroup difference （P<0.05）. ②Intraoperative CCSS scores were significantly higher in the MECwTS group （8.04±2.18） compared to the MECw/oTS group （5.93±1.44） （P<0.05）. ③Preoperative ZCMEI-21 scores showed no significant difference between groups （P>0.05）. Postoperative ZCMEI-21 scores were （22.24±8.11） in the MECw/oTS group versus （27.02±7.21） in the MECwTS group, indicating a statistically significant difference （P<0.05）. ④Postoperative ABG ≤20 dB was achieved in 54 patients （65.06%, 54/83） in the PORP group and 16 patients （43.24%, 16/37） in the TORP group. This difference in efficacy rates was statistically significant （P<0.05）. The overall efficacy rate for ossiculoplasty was 58.33% （70/120）. Conclusion: Patients with MECwTS exhibit more severe middle ear and mastoid pathology compared to those with MECw/oTS, resulting in poorer postoperative hearing levels and quality of life outcomes. Both PORP and TORP implantation can improve postoperative hearing to some extent; however, PORP appears to offer superior hearing improvement efficacy compared to TORP.
Humans ; Cholesteatoma, Middle Ear/complications* ; Retrospective Studies ; Tympanoplasty ; Myringosclerosis/surgery* ; Female ; Male ; Adult ; Middle Aged ; Ossicular Replacement ; Ossicular Prosthesis ; Young Adult ; Ear, Middle ; Treatment Outcome ; Mastoidectomy ; Audiometry, Pure-Tone ; Adolescent ; Quality of Life

The influenza A virus (IAV), renowned for its high contagiousness and potential to catalyze global pandemics, poses significant challenges due to the emergence of drug-resistant strains. Given the critical role of RNA polymerase in IAV replication, it stands out as a promising target for anti-IAV therapies. In this study, we identified a novel C-3-substituted oleanolic acid benzyl amide derivative, A5, as a potent inhibitor of the PA_C-PB1_N polymerase subunit interaction, with an IC₅₀ value of 0.96 ± 0.21 μmol/L. A5 specifically targets the highly conserved PA_C domain and demonstrates remarkable efficacy against both laboratory-adapted and clinically isolated IAV strains, including multidrug-resistant strains, with EC₅₀ values ranging from 0.60 to 1.83 μmol/L. Notably, when combined with oseltamivir, A5 exhibits synergistic effects both in vitro and in vivo. In a murine model, dose-dependent administration of A5 leads to a significant reduction in IAV titers, resulting in a high survival rate among treated mice. Additionally, A5 treatment inhibits virus-induced Toll-like receptor 4 activation, attenuates cytokine responses, and protects against IAV-induced inflammatory responses in macrophages. In summary, A5 emerges as a novel inhibitor with high efficiency and broad-spectrum anti-influenza activity.

OBJECTIVES: We propose a multi-scale jaw cyst segmentation model, AConvLSTM U-Net, which is based on bidirectional dense connections and attention mechanisms to achieve accurate automatic segmentation of mandibular cyst images. METHODS: A dataset consisting of 2592 jaw cyst images was used. AConvLSTM U-Net designs a MBC on the encoding path to enhance feature extraction capabilities. A DPD was used to connect the encoder and decoder, and a bidirectional ConvLSTM was introduced in the jump connection to obtain rich semantic information. A decoding block based on scSE was then used on the decoding path to enhance the focus on important information. Finally, a DS was designed, and the model was optimized by integrating a joint loss function to further improve the segmentation accuracy. RESULTS: The experiment with AConvLSTM U-Net for jaw cyst lesion segmentation showed a MCC of 93.8443%, a DSC of 93.9067%, and a JSC of 88.5133%, outperforming all the other comparison segmentation models. CONCLUSIONS The proposed algorithm shows a high accuracy and robustness on the jaw cyst dataset, demonstrating its superior performance over many existing methods for automatic segmentation of jaw cyst images and its potential to assist clinical diagnosis.
Humans ; Jaw Cysts/diagnostic imaging* ; Algorithms ; Image Processing, Computer-Assisted/methods* ; Neural Networks, Computer