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.

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.

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

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.

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.

With the continuous development of imaging techniques such as magnetic resonance imaging,the detection rate of brain metastases is increasing.Although the incidence rate of cystic brain metastasis is far lower than that of solid brain metastasis,patients with cystic brain metastasis are in urgent condition and have obvious space occupying effect,which is an urgent clinical problem.Previous literature has reported that cystic brain metastasis is more common in breast cancer and lung adenocarcinoma,especially in lung cancer patients with positive driver gene.This article reports a case of small cell lung cancer with cystic brain metastasis,which started with neurological symptoms,and was clinically cured under a multidisciplinary diagnosis and treatment model.Through dynamic imaging evaluation and molecular residual lesion detection,the patient can avoid overtreatment and achieved a relatively higher quality of life on the basis of prolonging survival.

BACKGROUND:Early diagnosis of pulmonary fibrosis is the foundation for timely antifibrotic drug therapy.Therefore,exploring and discovering ideal biomarkers that can be effectively used for the early diagnosis of pulmonary fibrosis is crucial for the treatment of the disease.OBJECTIVE:To conduct an in-depth analysis of key autophagy-related genes involved in the process of pulmonary fibrosis by means of bioinformatics and machine learning techniques,in order to investigate whether autophagy-related core genes of pulmonary fibrosis can be used as reliable biomarkers in the assessment of the progression of pulmonary fibrosis.METHODS:Two datasets of pulmonary fibrosis,GSE24206 and GSE110147,were downloaded from the Gene Expression Omnibus(GEO)database(a public database developed and maintained by the U.S.National Center for Biotechnology Information to store and share bioinformatics data),and the gene expression matrices of these two datasets were normalized by using the"limma"package in R software.The autophagy-related genes were extracted from GeneCards database(a database created by the U.S.National Center for Biotechnology Information,which automatically integrates gene-centric data from about 200 Web sources,including genomic,transcriptomic,proteomic,genetic,clinical,and functional information).Differential gene analysis was performed on the pulmonary fibrosis dataset,and the common genes were extracted by cross-comparing the differential genes with the autophagy genes,so as to identify autophagy genes that may play a role in the process of pulmonary fibrosis.The intersecting genes were analyzed for functional enrichment and cellular immune infiltration by gene ontology and Kyoto Encyclopedia of Genes and Genomes.Core genes of pulmonary fibrosis associated with autophagy were screened by protein-protein interactions and machine learning,and core genes were subjected to the enrichment analysis.Diagnostic models were constructed from the identified core genes.Calibration curves were used to assess the predictive ability of the line graph model.An external dataset,GSE21369,was used to perform a receiver operating characteristic curve analysis to validate the expression profiles of pulmonary fibrosis genes associated with autophagy,as well as to predict Chinese herbs associated with the genes IL6 and COL1A2 via the Coremine database.Finally,human embryonic lung fibroblasts were cultured and modelled by transforming growth factor-β1 treatment,and the relative expression of genes in the model cells was verified using qRT-PCR.RESULTS AND CONCLUSION:(1)A total of 51 pulmonary fibrosis differential genes and 25 genes intersecting with autophagy genes were obtained.Gene ontology analysis showed that the 25 intersecting genes were related to extracellular matrix tissue,collagen metabolism,collagen pro-fibroblasts,and growth factor binding,etc.The results of Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that they were mainly related to the Phosphatidylinositol 3-kinase/protein kinase B signaling pathway and the signaling pathway of the extracellular matrix-receptor interactions.(2)Immunoinfiltration analysis revealed that the expression of activated memory CD4+T cells,M0 macrophages,and resting dendritic cells was significantly elevated in the pulmonary fibrosis group(P＜0.05),showing a strong correlation.(3)Two autophagy signature genes involved in the progression of pulmonary fibrosis were identified:COL1A2 and IL6.The column-line diagram model showed that the two core genes predicted the onset of pulmonary fibrosis more accurately,and the receiver operating characteristic curve analysis showed that the two characteristic genes had diagnostic significance.COL1A2 and IL6 were related to the cell-cycle pathway,mitogen-activated protein kinase signaling pathway,Janus kinase-signal transduction and activator of transcription signaling pathway and cytokine-cytokine receptor interactions.A total of 20 Chinese herbs were predicted to be related to COL1A2 and IL6 genes,and their efficacies were mainly to clear away heat and detoxify toxins and to invigorate blood and move qi.COL1A2 and IL6 were verified to be highly expressed in pulmonary fibrosis.To conclude,COL1A2 and IL6 may be potential diagnostic biomarkers for pulmonary fibrosis,but its specificity to pulmonary fibrosis needs to be further investigated.

As the global population ages and cancer diagnostic and treatment technologies improve, the number of elderly cancer survivors continues to increase, and their complex care needs challenge the traditional mono-disciplinary care model. This paper explores the dilemmas of implementing a long-term care system and suggestions for future research through a comprehensive overview of the care needs of elderly cancer survivors and the progress of interdisciplinary research, with the aim of providing a theoretical basis and practical reference for improving the long-term care system and enhancing patients' quality of life.

Combined small cell lung cancer(C-SCLC)accounts for approximately 20%of all SCLC cases,while the propotion of C-SCLC mixed with squamous cell carcinoma component comprises less than 3%.At the pathological level,accurate diagnosis requires to distinguish it from other lung tumor types,and even rely on molecular testing.This article presents a case of a 67-year-old patient initially diagnosed with a peripheral lung tumor.The patient underwent comprehensive multidisciplinary management,including surgical resection,postoperative pathological differential diagnosis,chemotherapy,thoracic radiotherapy,brain metastasis,cranial radiotherapy,dynamic follow-up of imaging changes after cranial radiotherapy,and cranial surgery.Molecular residual disease(MRD)monitoring was integrated at critical time points during dynamic monitoring to inform personalized treatment decisions.The early MDT has brought the patient′s condition under control,and the overall survival of the patient exceeded 30 months.Through the introduction of the diagnosis and treatment process of this patient,we aim to offer novel perspectives on clinical decision-making for C-SCLC.