AIM: To explore the diagnostic value of 18 MHz color Doppler ultrasonography for epiretinal membrane.METHODS: A total of 44 cases(80 eyes)of patients with proposed diagnosis of cataract and vitreous opacity by fundus examination in our hospital between January 2020 and January 2022 were collected, and the affected eyes were examined by optical coherence tomography(OCT)and 18 MHz color Doppler ultrasonography, and the differences in the diagnostic sensitivity, specificity, and accuracy were compared between 18 MHz color Doppler ultrasonography and OCT for the diagnosis of epiretinal membrane.RESULTS: In the 80 eyes detected by 18 MHz color Doppler ultrasonography, 62 had epiretinal membrane and 18 had non epiretinal membrane. Totally 54 eyes were confirmed to have epiretinal membrane by OCT, 13 eyes were not diagnosed with epiretinal membrane, 5 eyes were missed diagnosis, and 8 eyes were misdiagnosed. The diagnostic consistency between 18 MHz color Doppler ultrasonography and OCT was high(Kappa=0.892, P<0.05); the 18 MHz color Doppler ultrasonography detection sensitivity of epiretinal membrane was 92%, specificity was 62%, missed diagnosis rate was 8%, misdiagnosis rate was 38%, and accuracy was 84%; compared with OCT detection, 18 MHz color Doppler ultrasonography detected a lower specificity, correct rate, positive prediction accuracy, negative prediction accuracy, and higher misdiagnosis rate(all P<0.05), and the difference in diagnostic sensitivity compared with leakage rate was not statistically significant(all P>0.05).CONCLUSION: 18 MHz color Doppler ultrasonography has some value in identifying epiretinal membrane lesions and is consistent with OCT testing.

O-acetyl-L-homoserine (OAH) is a promising platform compound for the production of L-methionine and other valuable compounds, while its low yield and low conversion rate limit the industrial application. To solve these problems, we constructed a strain for high OAH production with the previously constructed L-homoserine producer Escherichia coli HS33 as the chassis by systematic metabolic engineering. Firstly, PEP accumulation, pyruvate utilization, and OAH synthesis pathway (overexpressing aspB, aspA, and thrA^C1034T) were enhanced to obtain an initial strain accumulating 13.37 g/L OAH. Subsequently, the co-factor synthesis genes were integrated to supply reducing power and energy, which increased the yield to 15.79 g/L. The OAH yield of the engineered strain OAH28 was further increased to 17.49 g/L by strengthening the acetic acid reuse pathway, improving the supply of acetyl-CoA, and regulating the expression of MetX from different sources. Finally, in a 5 L fermenter, OAH28 achieved an OAH titer of 47.12 g/L, with a glucose conversion rate of 32% and productivity of 0.59 g/(L·h). The results lay a foundation for increasing the OAH production by metabolic engineering and give insights into the industrial production of OAH.
Metabolic Engineering/methods* ; Escherichia coli/genetics* ; Homoserine/biosynthesis* ; Fermentation

Synthetic biology is a crucial tool for the development of the bio-industry and bio-economy, representing a significant aspect of new quality productive forces. As a core course for graduate students in bioengineering, Synthetic Biology plays a vital role in ensuring the supply of essential talents for the development of the bio-industry in the new era. To better serve regional economic development and provide high-level talents for China's progress in the bio-industry, we analyzed typical issues encountered in the past teaching activities, set up a multi-disciplinary teaching team, optimized the course contents, adjusted the teaching mode, and mobilized students' learning interest. With the application of scientific research project as the starting point, we guided students to think and discuss deeply through the simulation of application writing and project defense, which improved students' critical thinking and innovative thinking. With industrialization as a focus, we explored a new training model combining production, education, and research through the joint practice base of the university and enterprises introduced typical cases of biomanufacturing to encourage students to engage in scientific research. The teaching reform significantly enhances the comprehensive abilities and national sentiments of graduate students. This paper hopes to serve as a reference for colleagues engaged in teaching in this field.
Synthetic Biology/education* ; Teaching ; China ; Humans

Objective:To evaluate the efficacy of remimazolam-based anesthesia in daytime laparoscopic cholecystectomy.Methods:In this multicenter, non-inferiority, randomized controlled trial, 300 American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients of either sex, aged 18-60 yr, with body mass index of 18-28 kg/m 2, who underwent daytime laparoscopic cholecystectomy under general anesthesia with tracheal intubation at Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, the Fourth Affiliated Hospital of Zhejiang University School of Medicine, Jinhua Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou First People′s Hospital Affiliated to Westlake University School of Medicine, Ningbo No. 2 Hospital, and the Second Affiliated Hospital of Nanchang University from August 2021 to August 2023, were selected and divided into 2 groups ( n=150 each) using a random number table method: remimazolam group (R group) and propofol group (P group). Anesthesia was induced as follows: Sufentanil was intravenously injected at a rate of 0.5 μg/kg, remimazolam was intravenously injected at a rate of 0.3 mg/kg in group R, propofol was intravenously injected at a rate of 2.0-2.5 mg/kg in group P, and cisatracurium besilate was intravenously injected at a rate of 0.2 mg/kg after loss of consciousness in two groups. The patients were mechanically ventilated after tracheal intubation. Anesthesia was maintained as follows: Remimazolam was intravenously injected at a rate of 0.5-1.0 mg·kg -1·h -1 in group R, propofol was intravenously injected at a rate of 4-10 mg·kg -1·h -1 in group P, and remifentanil was intravenously infused at a rate of 0.25-2.00 μg·kg -1·min -1, maintaining intraoperative bispectral index value of 40-60. The success rate of sedation was recorded, and non-inferiority tests were conducted. The time to loss of consciousness, emergence time, extubation time, recovery time of orientation, time of stay in post-anesthesia care unit and occurrence of delayed emergence were recorded. Liver function and renal function were measured before operation and within 24 h after operation. The occurrence of abnormal alanine transaminase, abnormal aspartate transaminase, abnormal creatinine and abnormal urea was recorded. The occurrence of adverse reactions during and after operation was recorded. Results:The success rates of sedation were 98.6% and 99.3% in group R and group P, respectively, there was no statistically significant difference in the success rate of sedation between the two groups ( P>0.05), and the difference in the success rates of sedation between the two groups was -0.007 (95% confidence interval-0.0301-0.0161), which met the pre-set non-inferiority criteria(95% confidence interval >-0.055). Compared with group P, the time to loss of consciousness and recovery time of orientation were significantly prolonged, and the incidence of delayed emergence was increased ( P<0.05), and no statistically significant changes were found in the emergence time, extubation time, time of stay in post-anesthesia care unit and severity of postoperative nausea and vomiting in group R ( P>0.05). There was no statistically significant difference in the abnormal rates of alanine transaminase, aspartate transaminase, creatinine and urea before and after operation between the two groups ( P>0.05). Conclusions:The efficacy of remimazolam-based anesthesia in daytime laparoscopic cholecystectomy is not inferior to that of propofol-based anesthesia.

Objective:To investigate the clinicopathological characteristics and differential diagnosis of DICER1-mutant primary intracranial sarcoma.Methods:Five cases of DICER1-mutant primary intracranial sarcoma at Sanbo Brain Hospital, Capital Medical University, Beijing, China during May 2013 to November 2024 were collected. The clinical and imaging data were retrieved. Histological evaluation, immunohistochemical staining and next generation sequencing were performed. Additionally, a literature review was conducted.Results:All five DICER1-mutant primary intracranial sarcomas were located in the supratentorial region, with one case involving the basal ganglia. There were two males and three females. The median age at diagnosis was 25 (14.0, 30.5) years. Morphologically, they were characterized by high-grade spindle cell sarcoma, with brisk mitotic activity and cytoplasmic eosinophilic globules. Myxoid degeneration, necrosis, and invasion into surrounding brain tissue were observed in some cases. The tumor cells showed diffuse staining of vimentin and variable expression of myogenic marker (desmin), with or without focal MyoD1 and/or Myogenin expression. Four tumors exhibited diffuse, strong expression of TLE1 and p53, while only three tumors showed loss of ATRX (nuclear) expression. Two cases showed mosaic loss of H3K27me3 expression in neoplastic cells. The Ki-67 proliferation index was high (40%-80%). Various neuronal markers, such as synaptophysin, NF, SOX2 and MAP2, were expressed in all tumor samples. Genetically, all tumors samples harbored biallelic abnormalities of DICER1. One was a hotspot missense mutation in the RNase Ⅲb domain within exon 25 on one allele (p.E1813 or p.D1810), while the other allele had mutations including a germline mutation in one case, a somatic mutation in two cases, and a copy number deletion in two cases. In addition, these sarcomas showed alterations in TP53 (4/5), ATRX (3/5), and the genes of the mitogen-activated protein kinase pathway (3/5). Finally, all five cases were diagnosed as DICER1-mutant primary intracranial sarcoma. All patients underwent craniotomy that led to complete tumor resection. Three patients received adjuvant radiotherapy and chemotherapy, with progression-free survival time of 28, 48, and 50 months, respectively. Patient 2 succumbed to the tumor after 3 months post-surgery due to rapid progression and tumor dissemination. Patient 5 was lost to follow-up 3 months after the surgery.Conclusions:DICER1-mutant primary intracranial sarcoma is a newly defined tumor entity in the fifth edition of the World Health Organization Classification of Central Nervous System Tumors, and commonly occurs in children and young adults. High-grade malignant spindle cells are their typical morphological feature. Eosinophilic cytoplasmic globules and myogenic differentiation can help establish the diagnosis. This study suggests that DICER1-mutant primary intracranial sarcomas exhibit immunophenotypic neuronal differentiation. Rendering the diagnosis of DICER1-mutant primary intracranial sarcoma largely relies on detecting DICER1 pathogenic alterations or DNA methylation profiling.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Sophora Flavescens is the dried root of the leguminous plant Sophora Flavescens Ait. It was first published in Shen Nong's Herbal Classic. Sophora Flavescens contains a variety of active ingredients, mainly including matrine and oxymatrine, with anti-inflammatory, anti-tumor, anti-arrhythmia, disease-resistant pathogenic microorganisms and other pharmacological effects. Clinically, the compound preparations of Sophora Flavescens include Compound KuShen injection and KuShen gel and so on, which can be used to treat many types of cancers and improve skin, mucous pruritus, pain and other symptoms. Due to the poor bioavailability, the structure of matrine needs to be reformed. MASM, matrine derivative, only needs a low concentration to have a good therapeutic effect on sepsis and liver fibrosis. In this article, the chemical composition, pharmacological effects, compound preparations and structural modification of matrine were mainly discussed, aiming to provide a theoretical basis for the clinical application of Sophora Flavescens and the development of new drugs.

Thermal ablation, an established minimally invasive technique, is increasingly utilized in treating thyroid nodules and microthyroid papillary carcinoma.Compared to conventional surgery, it offers advantages including minimal trauma, rapid recovery, and fewer complications.Recent technological advances have revealed its potential for managing primary hyperthyroidism. This review examines current evidence on thermal ablation applications in hyperthyroidism, analyzes its efficacy and safety, and discusses future challenges to inform clinical practice and research.

Animal models combining disease and syndrome are important research tools to explore the nature of traditional Chinese medicine (TCM) syndromes. At present, the construction and evaluation methods of animal models have preliminarily established the foundation for standardized development. Qi-yin deficiency syndrome is a common type of TCM syndrome in cardiovascular diseases. It is an important pathogenic factor causing the onset, pathological damage, and chronic nature of cardiovascular diseases, as well as triggering other illnesses. The establishment of an animal model of cardiovascular disease with the characteristics of Qi-yin deficiency, along with an objective and standardized evaluation system, has become an important part of modern cardiovascular disease research. In recent years, research on the construction and evaluation of animal models of heart Qi-yin deficiency syndrome has increased, but the construction methods and evaluation criteria vary. Compared with other animal models, the literature is limited, lacking statistics and overall analysis. Therefore, based on the scientific connotation of heart Qi-yin deficiency syndrome, this article systematically reviews the evaluation system of its animal model, covering multidimensional methods such as macroscopic characterization assessment, physicochemical indicators and objective evaluation, and syndrome differentiation based on prescriptions. The specific model construction strategies are described, including single-factor induction methods (sleep deprivation, chronic intermittent hypoxia, arterial occlusion, high-salt feeding) and the compound-factor induction methods (sleep deprivation combined with drug method, chronic intermittent hypoxia combined with drug method, exhaustive swimming combined with drug method). Meanwhile, application examples of each model in the research are listed, the existing problems in the current model construction and evaluation are analyzed, and optimization directions are proposed, such as promoting the compound factor induction strategy and improving the objectivity of the evaluation criteria. This article aims to provide theoretical references for constructing an animal model of heart Qi-yin deficiency syndrome that conforms to TCM characteristics, and thereby laying a scientific foundation for the prevention and treatment of cardiovascular diseases with TCM.

Objective:To analyze the epidemiological and clinical characteristics of respiratory pathogens in China.Methods:This study was a cross-sectional study, which encompassed 19 core units of the clinical pathogen network and established a three-tiered clinical pathogen surveillance system. Thirty respiratory samples were collected every two weeks from various units from January to December 2024, and the clinical and pathogen diagnostic information were gathered. A total of 11 864 samples were tested using this system. The tier-1 clinical pathogen surveillance system covered influenza A virus (Flu-A), influenza B virus (Flu-B), respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The tier-2 clinical pathogen surveillance system focused on 18 key respiratory pathogens. The tier-3 clinical pathogen surveillance system further clarified whether any emerging infectious diseases had occurred.Results:The tier-1 clinical pathogen surveillance system showed Flu-A predominated in December, Flu-B predominated in January, SARS-CoV-2 peaked in March and August, whereas RSV circulated sporadically throughout the year. Geographic trends were broadly consistent across the seven major regions, although Flu-A detection in December was notably higher in Northeast China (48.1%(111/231)) and East China (36.2%(148/409)), and RSV detection was concentrated in the Northwest and South China from January to March. Data from the tier-2 clinical pathogen surveillance system indicated that Streptococcus pneumoniae, Mycoplasma pneumoniae, rhinovirus, and adenovirus were detected year-round, of these, Streptococcus pneumoniae and rhinovirus showed elevated positive detection rates from August to September, while adenovirus peaked in January. Legionella pneumophila was not detected throughout the year, and other pathogens fluctuated throughout the year without a consistent pattern. The predominant etiologic agents of pediatric pneumonia were Mycoplasma pneumoniae (35.0%(105/300)), rhinovirus (25.7%(77/300)), and adenovirus (17.3%(52/300)), whereas adult pneumonia was mainly caused by Streptococcus pneumoniae (10.5%(29/277)), Staphylococcus aureus (6.9%(19/277)), Mycoplasma pneumoniae (6.9%(19/277)), and Flu-A (6.1%(17/277)). The tier-3 clinical pathogen surveillance system did not identify any emerging respiratory pathogens. Conclusion:Respiratory pathogens in China in 2024 exhibit distinct temporal and spatial distribution patterns and vary among different populations.