The Connotation and Clinical Significance of “Spleen Governs Time” based on the Zangxiang （藏象） Time-space View / 中医杂志

There are different views on the theory of “spleen governs time”， which is still a hot spot in the study of Zangxiang （藏象） theory. Based on Zangxiang time-space view， it is found that the thinking mode of the spleen governing time theory follows space-time logic. It is believed that the different time views of the spleen governing time are all formed based on the space view that the spleen belongs to earth and resides in the center， and the zang time theory is developed with the unified time and space logic. Guided by Zangxiang time-space view， the origin of the spleen belonging to earth and residing in the center is traced， and the theoretical connotation and its clinical application of spleen governing time under different time-space logic are explored with reference to the four season and five zang theory， five season and five zang theory， six season and six zang theory， and eight season and eight zang theory.

Plasma metabolic profiling of patients with tetralogy of fallot.

BACKGROUND: Tetralogy of Fallot (TOF) is a common congenital heart disease with high mortality. However, the medical imageology and liquidbiopsy techniques present certain limitations. Thus, this study investigated the plasma metabolic profiles to distinguish key metabolites for early diagnosis of TOF. METHODS: In total, 69 patients with TOF and 43 normal controls were enrolled for targeted metabolomics based on liquid chromatography-tandem mass spectroscopy (LC-MS/MS). Absolute quantification of metabolites was performed using our standard database. The differentially expressed metabolites (DEMs) were screened by fold change (FC), VIP value and pearson correlation coefficient of OPLS-DA model. Receiver operating characteristic curve (ROC) was used to evaluate predictive ability of DEMs. RESULTS: Different metabolic profiles were presented between TOF and Normal.The pathway analysis showed that significantly changed metabolites were enriched in nicotinamide and purine metabolism. Many intermediatesproductof purine and amido acid were higher in TOF than in Normal group, while energy substrates and electron carriers were lower in TOF than in Normal group. ROC analysis revealed a high diagnostic value of plasma FAD for differentiating TOF from Normal (AUC = 1). CONCLUSION: Our study quantitatively characterized plasma metabolites in patients with TOF and may help to develop reliable biomarkers that contribute to the early TOF screening.

Mechanism of tonifying Qi by traditional Chinese medicine from mitochondrial dynamics / 中国中药杂志

According to the traditional Chinese medicine(TCM) theory, Qi is the essential component maintaining life. Mitochondria are the cellular organelles that generate energy. Qi exhibits abundant common characteristics in bioenergetics compared with mitochondria which control the cellular energy through fusion and fission. Studies have proven that the qi-tonifying function of Chinese medicinal plants and their components facilitates mitochondrial fusion, therefore enhancing ATP synthesis. These studies provide a framework for deciphering the pharmacological mechanisms of Qi-tonifying herbs. This article introduces the common source and function shared by Qi and mitochondria and the regulatory effects of herbal remedies on energy from mitochondria dynamics. This review aims to interpret the connotation of tonifying qi in TCM theory based on the modern biomedical theory.

Analysis of the relationship between MRI imaging characteristics and clinical symptoms and therapeutic efficacy in adenomyosis patients / 中华妇产科杂志

Objective: To investigate the relationship between magnetic resonance imaging (MRI) imaging characteristics and clinical symptoms and therapeutic efficacy in adenomyosis patients. Methods: The clinical characteristics of the adenomyosis questionnaire was self-designed. This was a retrospective study. From September 2015 to September 2020, totally 459 patients were diagnosed with adenomyosis and underwent pelvic MRI examination at Peking University Third Hospital. Clinical characteristics and treatment were collected, MRI was used to determine the lesion location, and to measure the maximum lesion thickness, the maximum myometrium thickness, uterine cavity length, uterine volume, the minimum distance between the lesion and serosa or endometrium, and whether combined with ovarian endometrioma. The difference of MRI imaging characteristics in patients with adenomyosis and its relationship with clinical symptoms and therapeutic efficacy were analyzed. Results: (1) Among the 459 patients, the age was (39.1±6.4) years. There were 376 patients (81.9%, 376/459) with dysmenorrhea. Whether patients had dysmenorrhea were related to uterine cavity length, uterine volume, ratio of the maximum lesion thickness to the maximum myometrium thickness, and whether patients had ovarian endometrioma (all P<0.001). Multivariate analysis suggested that ovarian endometrioma was the risk factor for dysmenorrhea (OR=0.438, 95%CI: 0.226-0.850, P=0.015). There were 195 patients (42.5%, 195/459) with menorrhagia. Whether patients had menorrhagia were related to age, whether patients had ovarian endometrioma, uterine cavity length, the minimum distance between lesion and endometrium or serosa, uterine volume, ratio of the maximum lesion thickness to the maximum myometrium thickness (all P<0.001). Multivariate analysis suggested that ratio of the maximum lesion thickness to the maximum myometrium thickness was the risk factor for menorrhagia (OR=774.791, 95%CI: 3.500-1.715×105, P=0.016). There were 145 patients (31.6%, 145/459) with infertility. Whether the patients had infertility were related to age, the minimum distance between lesion and endometrium or serosa, and whether patients had ovarian endometrioma (all P<0.01). Multivariate analysis suggested that young and large uterine volume were risk factors for infertility (OR=0.845, 95%CI: 0.809-0.882, P<0.001; OR=1.001, 95%CI: 1.000-1.002, P=0.009). (2) The success rate of in vitro fertilization-embryo transfer (IVF-ET) was 39.2% (20/51). Dysmenorrhea, high maximum visual analogue scale score and large uterine volume affected the success rate of IVF-ET (all P<0.05). The smaller the maximum lesion thickness, the smaller the distance between the lesion and serosa, the larger the distance between the lesion and endometrium, the smaller the uterine volume, and the smaller the ratio of the maximum lesion thickness to the maximum myometrium thickness, the better the therapeutic efficacy of progesterones (all P<0.05). Conclusions: Concomitant ovarian endometrioma increases the risk of dysmenorrhea in patients with adenomyosis. The ratio of the maximum lesion thickness to the maximum myometrium thickness is an independent risk factor for menorrhagia. Young and large uterine volume may increase the risk of infertility. Severe dysmenorrhea and large uterine volume affect the success rate of IVF-ET. The therapeutic efficacy of progesterones is relatively better when the lesion is small and far away from the endometrium.

Genome-wide identification of bZIP family genes and screening of candidate AarbZIPs involved in terpenoid biosynthesis in Artemisia argyi / 中国中药杂志

Artemisia argyi is an important medicinal and economic plant in China, with the effects of warming channels, dispersing cold, and relieving pain, inflammation, and allergy. The essential oil of this plant is rich in volatile terpenoids and widely used in moxi-bustion and healthcare products, with huge market potential. The bZIP transcription factors compose a large family in plants and are involved in the regulation of plant growth and development, stress response, and biosynthesis of secondary metabolites such as terpenoids. However, little is known about the bZIPs and their roles in A. argyi. In this study, the bZIP transcription factors in the genome of A. argyi were systematically identified, and their physicochemical properties, phylogenetic relationship, conserved motifs, and promoter-binding elements were analyzed. Candidate AarbZIP genes involved in terpenoid biosynthesis were screened out. The results showed that a total of 156 AarbZIP transcription factors were identified at the genomic level, with the lengths of 99-618 aa, the molecular weights of 11.7-67.8 kDa, and the theoretical isoelectric points of 4.56-10.16. According to the classification of bZIPs in Arabidopsis thaliana, the 156 AarbZIPs were classified into 12 subfamilies, and the members in the same subfamily had similar conserved motifs. The cis-acting elements of promoters showed that AarbZIP genes were possibly involved in light and hormonal pathways. Five AarbZIP genes that may be involved in the regulation of terpenoid biosynthesis were screened out by homologous alignment and phylogenetic analysis. The qRT-PCR results showed that the expression levels of the five AarbZIP genes varied significantly in different tissues of A. argyi. Specifically, AarbZIP29 and AarbZIP55 were highly expressed in the leaves and AarbZIP81, AarbZIP130, and AarbZIP150 in the flower buds. This study lays a foundation for the functional study of bZIP genes and their regulatory roles in the terpenoid biosynthesis in A. argyi.

An improved synthesis of azedarachol.

An improved synthesis of azedarachol is reported in 10 steps with an overall yield of 12% from pregnanetriol. A proper use of p-anisaldehyde dimethyl acetal provided a chance of regioselective reduction of 2-enepregnane-16R,20R-p-anisaldehyde acetal(6) and in turn allowed a selective protection at C16-hydroxy and enabled a stereoselective reduction of C20-ketone to establish the configuration at C20.

Molecular Mechanism of Nardostachyos Radix et Rhizoma-Agrimoniae Herba in Treatment of Arrhythmia Based on Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo explore the material basis and mechanism of Nardostachyos Radix et Rhizoma （NRER）-Agrimoniae Herba （AH）， the herbal pair effective in regulating the liver， invigorating Qi， and calming palpitations， in the treatment of premature ventricular contractions （PVCs） by network pharmacology and molecular docking. MethodThe chemical components and targets of NRER and AH were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） combined with relevant literature. GeneCards，Online Mendelian Inheritance in Man（OMIM），and DrugBank were used to predict the potential targets against PVCs. STRING platform was used for protein-protein interaction （PPI） analysis. Metascape platform was used for Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis. Cytoscape 3.8.0 was used to construct the NRER-AH component-potential target-signaling pathway network. The main target proteins underwent molecular docking to the active components of NRER-AH by AutoDock 4.2.6. ResultThe targets of nine active components in NRER-AH （such as quercetin，kaempferol，and acacetin） against PVCs mainly involved tumor necrosis factor （TNF），mitogen-activated protein kinase 1（MAPK1），and protein kinase B1（Akt1）. The potential targets were mainly enriched in 26 signaling pathways，such as pathways in cancer and the advanced glycosylation end product （AGE）-receptor of advanced glycosylation end product（RAGE） signaling pathway. The results of molecular docking showed that the majority of the active components （92.59%） of NRER-AH had good binding activities with the main target proteins TNF，MAPK1，and Akt1. ConclusionThe active components of NRER-AH can regulate cardiac ion channels，resist inflammation， and combat oxidative stress to treat PVCs through multi-target and multi-pathway interventions. They can also improve symptoms related to depression and anxiety by inhibiting monoamine oxidase activity and protecting nerves from damage. This study is expected to provide research ideas and the theoretical basis for further exploring the material basis and mechanism of NRER-AH in the treatment of PVCs.

Utility of GPR68 and TIL in TPF-induced chemotherapy and prognosis evaluation in middle-advanced hypopharyngeal squamous cell carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To evaluate the roles of G Protein-Coupled Receptor 68 (GPR68) and tumor infiltrating lymphocytes (TIL) in TPF-(paclitaxel, cisplatin and 5-fluorouracil) induced chemotherapy for middle-advanced hypopharyngeal squamous cell carcinomas. Methods: A total of 31 patients with middle-advanced hypopharyngeal squamous cell carcinoma before TPF-inducted chemotherapy were enrolled from September 2012 to November 2017 in Beijing Tongren Hospital, Capital Medical University, including 28 males and 3 females, aged 43 to 71 years old. The expression of GPR68 and tumor infiltrating CD4+and CD8+T cells before chemotherapy was detected by immunohistochemical staining, and the relationships between GPR68 expression and clinical features, chemotherapy efficacy and overall survival (OS) were analyzed using t-test. Results: After 3 cycles of chemotherapy, there were 4, 14, 10 and 3 patients respectively with complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). The positive rates of GPR68 and CD8 were 25% and 40% respectively in the effective group (CR+PR), while 50% and 15% in the ineffective group (SD+PD), with statistically significant differences between two groups (t=5.17 and 12.86,P<0.001). Linear regression analysis showed that GPR68 was negatively correlated with CD8+T cells (r=-0.64,P<0.001). There was no significant correlation between the CD4 expression and TPF efficacy (P>0.05). The mean OS was 12.5 months in patients with high-expressed GPR68 and 25.0 months in patients with low-expressed GPR68, with a statistically significant difference (P=0.005). And mean OS was 25.0 months in patients with high-expressed CD8 and 14.5 months in low-expressed CD8, with a statistically significant difference (HR=2.58, P=0.019). Cox regression analysis showed that GPR68 and CD8+T cells were significant prognostic factors (OR(95%CI)=3.27(2.46-5.97) and 1.53(0.78-1.82), all P<0.05), while CD4 had no significant effect on prognosis (P>0.05). Conclusion: GPR68 and CD8+T cells are expected to be biomarkers for evaluating the efficacy and prognosis of TPF-induced chemotherapy in patients with middle-advanced hypopharyngeal squamous cell carcinoma.

Coma in spontaneous intracranial hypotension complicated with subdural hematoma: a case report / 中华神经科杂志

Spontaneous intracranial hypotension can frequently result in several complications including subdural hygroma, subdural hematoma and cerebral venous thrombosis, but coma rarely. A case of spontaneous intracranial hypotension presented with orthostatic headaches was described. He experienced somnolence, disorientation, incontinence, and then coma, though received conservative treatment. Brain imaging demonstrated acute-on-chronic subdural hematoma, magnetic resonance myelography using heavily T 2-weighted fast spin-echo pulse sequences showed spinal longitudinal extradural collection, and magnetic resonance myelography with intrathecal gadolinium revealed cerebrospinal fluid leak at the level of T 6, T 7. The patient recovered consciousness after surgical evacuation of the hematoma, and the headache disappeared after a targeted epidural blood patch. The hematoma resolved 2 months later and the patient kept free from headache during follow-up.

Evaluation of blood flow as a route for propagation in experimental synucleinopathy.

In Parkinson's disease, synucleinopathy is hypothesized to spread from the enteric nervous system, via the vagus nerve, to the central nervous system. Recent evidences collected in non-human primates challenge however the hypothesis of a transmission of α-synuclein (α-syn) pathology through the vagus nerve. Would the hypothesis whereby the bloodstream acts as a route for long-distance transmission of pathological α-syn hold true, an inter-individual transmission of synucleinopathy could occur via blood contact. Here, we used a parabiosis approach to join the circulatory systems of wild type and GFP transgenic C57BL/6 J mice, for which one of the partners parabiont received a stereotaxic intranigral injection of patient-derived α-syn aggregates. While the Lewy Body-receiving mice exhibited a loss of dopamine neurons and an increase in nigral S129 phosphorylated α-syn immunoreactivity, their parabiotic bloodstream-sharing partners did not show any trend for a lesion or change in S129 phosphorylated-α-syn levels. Altogether, our study suggests that, in the patient-derived α-synuclein aggregates-injected mouse model and within the selected time frame, the disease is not "transmitted" through the bloodstream.

Comparative study of metagenomics next generation sequencing of cerebrospinal fluid in the diagnosis test of the pathogen of neurobrucellosis / 中华神经科杂志

Objective:To explore the value of metagenomics next generation sequencing of cerebrospinal fluid in the diagnosis test of the pathogen of neurobrucellosis.Methods:Medical records of neurobrucellosis patients who were admitted to Xuanwu Hospital, Capital Medical University from May 2017 to February 2021 were reviewed. Seven patients who underwent cerebrospinal fluid metagenomics next generation sequencing were enrolled. Their clinical characteristics, cerebrospinal fluid results, serological and pathogenic results were analyzed.Results:Among the seven neurobrucellosis patients, including five males and two females, the age was from 21 to 49 [38 (24, 47)] years. Three patients had a history of exposure to cattle and sheep. The duration from onset to diagnosis was 2 to 30 [12 (5, 18)] months. The main neurological manifestations were headache for seven patients, loss of hearing for three patients, paralysis for four patients and urinary and fecal dysfunction for four patients. The blood tests showed that the rose bengal test was positive in three of seven patients, Brucella serum agglutination test was positive in four of six patients, and the blood culture was negative in four patients. The cerebrospinal fluid tests showed that rose bengal test was positive in one of five patients, Brucella serum agglutination test was positive in two of four patients, and the cerebrospinal fluid culture was positive in two of five patients. Cerebrospinal fluid metagenomics next generation sequencing was positive for Brucella in five patients.Conclusions:Comparing with the cerebrospinal fluid Brucella serum agglutination test and cerebrospinal fluid culture, cerebrospinal fluid metagenomics next generation sequencing is sensitive to the diagnosis of neurobrucellosis. It is recommended to perform cerebrospinal fluid metagenomics next generation sequencing in patients with clinically suspected neurobrucellosis or central nervous system infections of which the pathogen cannot be confirmed.

Progress in diagnosis and treatment of primary lymphoma of bone / 白血病·淋巴瘤

Primary lymphoma of bone (PLB) is a rare extra nodal lymphoma, which accounts for 3%-7% of malignant bone tumors, about 5% of extra nodal lymphomas, and 2% of lymphomas in adults. PLB can occur in any age group, but it is more commonly found in middle-aged and elderly people with the average age of onset of 45-60 years old, and it is slightly more common in males than in females. The patients with PLB usually present with pain or swelling of local soft tissue, and the radiological feature is atypical. It must be diagnosed by pathological biopsy. At present, PLB is mainly treated by systemic chemotherapy combined with radiotherapy of the affected bone. This article will review the current progress in the diagnosis and treatment of PLB.

Small molecules inhibit SARS-COV-2 induced aberrant inflammation and viral replication in mice by targeting S100A8/A9-TLR4 axis

The SARS-CoV-2 pandemic poses an unprecedented public health crisis. Accumulating evidences suggest that SARS-CoV-2 infection causes dysregulation of immune system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced by SARS-CoV-2 in animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could reduce inflammatory response and rescue the pneumonia with substantial reduction of viral titers in SASR-CoV-2 infected animals. Remarkably, Paquinimod treatment resulted in 100% survival of mice in a lethal model of mouse coronavirus (MHV) infection. A novel group of neutrophils that contributed to the uncontrolled inflammation and onset of COVID-19 were dramatically induced by coronavirus infections. Paquinimod treatment could reduce these neutrophils and regain antiviral responses, unveiling key roles of S100A8/A9 and noncanonical neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention.

Recapitulation of SARS-CoV-2 Infection and Cholangiocyte Damage with Human Liver Organoids

The newly emerged pandemic coronavirus, SARS-CoV-2, has posed a significant public health threat worldwide. However, the mode of virus transmission and tissue tropism is not well established yet. Recent findings of substantial liver damage in patients and ACE2+ cholangiocytes in healthy liver tissues prompted us to hypothesize that human liver ductal organoids could serve as a model to determine the susceptibility and mechanisms underlining the liver damage upon SARS-CoV-2 infection. By single-cell RNA sequencing, we found that long-term liver ductal organoid culture preserved the human specific ACE2+ population of cholangiocytes. Moreover, human liver ductal organoids were permissive to SARS-CoV-2 infection and support robust replication. Notably, virus infection impaired the barrier and bile acid transporting functions of cholangiocytes through dysregulation of genes involved in tight junction formation and bile acid transportation, which could explain the bile acid accumulation and consequent liver damage in patients. These results indicate that control of liver damage caused directly by viral infection should be valued in treating COVID-19 patients. Our findings also provide an application of human organoids in investigating the tropism and pathogenesis of SARS-CoV-2, which would facilitate novel drug discovery.

Genome-wide identification and analysis of AP2/ERF transcription factors related to camptothecin biosynthesis in Camptotheca acuminata / 中国天然药物

Camptotheca acuminata produces camptothecin (CPT), a monoterpene indole alkaloid (MIA) that is widely used in the treatment of lung, colorectal, cervical, and ovarian cancers. Its biosynthesis pathway has attracted significant attention, but the regulation of CPT biosynthesis by the APETALA2/ethylene-responsive factor (AP2/ERF) transcription factors (TFs) remains unclear. In this study, a systematic analysis of the AP2/ERF TFs family in C. acuminata was performed, including phylogeny, gene structure, conserved motifs, and gene expression profiles in different tissues and organs (immature bark, cotyledons, young flower, immature fruit, mature fruit, mature leaf, roots, upper stem, and lower stem) of C. acuminata. A total of 198 AP2/ERF genes were identified and divided into five relatively conserved subfamilies, including AP2 (26 genes), DREB (61 genes), ERF (92 genes), RAV (18 genes), and Soloist (one gene). The combination of gene expression patterns in different C. acuminata tissues and organs, the phylogenetic tree, the co-expression analysis with biosynthetic genes, and the analysis of promoter sequences of key enzymes genes involved in CPT biosynthesis pathways revealed that eight AP2/ERF TFs in C. acuminata might be involved in CPT synthesis regulation, which exhibit relatively high expression levels in the upper stem or immature bark. Among these, four genes (CacAP2/ERF123, CacAP2/ERF125, CacAP2/ERF126, and CacAP2/ERF127) belong to the ERF-B2 subgroup; two genes (CacAP2/ERF149 and CacAP2/ERF152) belong to the ERF-B3 subgroup; and two more genes (CacAP2/ERF095 and CacAP2/ERF096) belong to the DREB-A6 subgroup. These results provide a foundation for future functional characterization of the AP2/ERF genes to enhance the biosynthesis of CPT compounds of C. acuminata.

Mechanisms of miR-103a-3p/CHI3L1 in proliferation and vascular mimicry of ovarian cancer cells / 国际肿瘤学杂志

Objective:To investigate the mechanisms of microRNA (miR)-103a-3p/chitinase-3-like protein 1 (CHI3L1) in the proliferation and vascular mimicry of ovarian cancer cells and its effect on transforming growth factor-β (TGF-β) pathway.Methods:The relationship between the expression level of miR-103a-3p and the overall survival rate of ovarian cancer patients was analyzed by bioinformatics. The human ovarian adenocarcinoma SKOV3 cells were divided into 4 groups: control group, miR-103a-3p mimic group, miR-103a-3p mimic+ CHI3L1 group and CHI3L1 group. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to detect the expression levels of miR-103a-3p, CHI3L1 mRNA and CHI3L1 protein respectively. The expression level of YKL-40 in cell culture fluid was detected by enzyme-linked immunosorbent assay. The cell viability, proliferation ability and angiogenesis ability of the 4 groups were detected by CCK-8 method, clone formation experiment and angiogenesis experiment. The dual luciferase report verified that miR-130a-3p targeted CHI3L1.Results:The overall survival rate of ovarian cancer patients with high expression of miR-103a-3p was higher than that of patients with low expression of miR-103a-3p ( χ2=6.187, P=0.048). The differences in miR-103a-3p and CHI3L1 mRNA levels among the control group, miR-103a-3p mimic group, miR-103a-3p mimic+ CHI3L1 group and CHI3L1 group were statistically significant ( F=198.254, P<0.001; F=60.214, P<0.001), miR-103a-3p mimic group and miR-103a-3p mimic+ CHI3L1 group had higher miR-103a-3p levels than the control group (all P<0.001), CHI3L1 group had higher CHI3L1 mRNA level than the control group ( P<0.001). The expression levels of CHI3L1 protein in the 4 groups were 2.25±0.23, 1.19±0.12, 2.29±0.28 and 4.31±0.37, and the difference was statistically significant ( F=18.675, P<0.001). The expression levels of YKL-40 in the cell culture fluids of the 4 groups were (1.84±0.20) ng/ml, (0.95±0.08) ng/ml, (2.64±0.25) ng/ml, (6.27±0.79) ng/ml, and the difference was statistically significant ( F=35.297, P<0.001). The YKL-40 level of the CHI3L1 group was significantly higher than that of the control group ( P<0.001), the miR-103a-3p mimic group was lower than the control group ( P<0.001), and the miR-103a-3p mimic+ CHI3L1 group was higher than the miR-103a-3p mimic group ( P<0.001). The cell viabilities of the 4 groups were 100%±2.54%, 76.23%±2.13%, 104.89%±3.56% and 137.42%±2.80%, and the difference was statistically significant ( F=23.584, P<0.001). The cell viability of the miR-103a-3p mimic group was significantly lower than that of the control group ( P<0.001), the CHI3L1 group was higher than the control group ( P<0.001), and the miR-103a-3p mimic+ CHI3L1 group was higher than the miR-103a-3p mimic group ( P<0.001). The number of clones formed in the 4 groups were 76.85±4.67, 21.56±2.85, 72.06±5.07 and 169.63±9.21, and the difference was statistically significant ( F=31.541, P<0.001). The proliferation capacity of the miR-103a-3p mimic group was significantly lower than that of the control group ( P<0.001), the CHI3L1 group was higher than the control group ( P<0.001), and the miR-103a-3p mimic+ CHI3L1 group was significantly higher than the miR-103a-3p mimic group ( P<0.001). The differences in the relative tube lengths and the tube bramches of the 4 groups were both statistically significant ( F=24.254, P<0.001; F=27.564, P<0.001). The differences in TGF-β and Smad levels of the 4 groups were both statistically significant ( F=30.254, P<0.001; F=34.187, P<0.001). The results of dual luciferase experiments showed that compared with the NC group, the luciferase activity in cells co-transfected of miR-103a-3p and CHI3L1-wt was significantly reduced. The difference of luciferase activity between the cells transfected with NC and co-transfected with miR-103a-3p and CHI3L1-mut was not significant. Conclusion:MiR-103a-3p can directly inhibit the expression of CHI3L1 and inhibit the proliferation and angiogenesis of ovarian cancer SKOV3 cells to inhibit ovarian lymphatic metastasis and distant metastasis, which may be related to the TGF-β pathway.

Simultaneous Determination of Pyrrolidine Alkaloids and Their Nitrogen Oxides in Farfarae Flos by UPLC-MS/MS / 中国实验方剂学杂志

<b>Objective::To establish an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the simultaneous determination of 15 pyrrolidine alkaloids (PAs) and their nitrogen oxides, and determine the content of the 15 PAs in the 15 batches of Farfarae Flos samples obtained from different sources, in order to understand the distribution status of these 15 PAs in Farfarae Flos from different sources, and provide relevant references for the safe and rational use of this medicinal materials. <b>Method::The method was achieved by Agilent Eclipse Plus C₁₈ column (3.0 mm×150 mm, 1.8 μm) using a mobile phase made up of 0.05%formic acid and 2.5 mmol·L^-1 ammonium formate in water (A)-0.05%formic acid and 2.5 mmol·L^-1 ammonium formate in methanol(B). The flow rate and the injection volume were 0.4 mL·min^-1 and 2 μL, respectively. The column temperature was 40 ℃. The instrument was Agilent 1290-6470 QQQ ultra high performance liquid chromatography-triple quaternary bar mass spectrometer. The components were detected in multiple reaction monitoring mode by mass spectrometry with ionizationmode of ESI⁺. The content of the components measured in the samples was calculated by using the external standard method, and the difference between samples was analyzed based on RSD of different components. <b>Result::The established method had a high sensitivity and good separation degree. The results of methodological investigation met the requirements. The results showed that all of the 15 batches of Farfarae Flos contained PAs and their nitrogen oxides. These PAs had almost the same types of structure. There were significant differences in the content and distribution of PAs in Farfarae Flos obtained from different sources. <b>Conclusion::In general, Farfarae Flos contains pyrrolidine alkaloids and their nitrogen oxides. Senkirkine with a significant hepatotoxicity is the main compound. The content determination of PAs will provide scientific fundaments for the safe and effective use of Farfarae Flos.

Atypical Gerstmann-Str(a)ussler-Scheinker syndrome caused by PRNP P102L mutation: a case report and literature review / 中华神经科杂志

Objective To improve the clinician's recognition of Gerstmann-Str(a)ussler-Scheinker syndrome (GSS).Methods The detailed clinical information,neuropsychological examination,cerebrospinal fluid examination,imaging characteristics,electroencephalogram examination and gene detection were analyzed in a case of GSS similar to Creutzfeldt-Jakob disease (CJD) in symptomatology.The differences between the two different prion diseases were compared in combination with the literature review.Results The patient is a 62-year-old woman,with cerebellar ataxia as the first symptom,followed by rapid dementia,accompanied by pyramidal and extrapyramidal signs.Magnetic resonance imaging showed hyper-intense signal in diffusion weighted imaging in caudatum and cortical ribboning,and protein 14-3-3was negative.PRNP gene analysis showed P102L gene mutation.Conclusions The typical clinical manifestation of GSS is hereditary ataxia followed by cognitive decline of varying severity.Detection of PRNP plays an important role in the diagnosis of GSS.

Atypical Gerstmann-Sträussler-Scheinker syndrome caused by PRNP P102L mutation: a case report and literature review / 中华神经科杂志

Objective@#To improve the clinician′s recognition of Gerstmann-Sträussler-Scheinker syndrome (GSS).@*Methods@#The detailed clinical information, neuropsychological examination, cerebrospinal fluid examination, imaging characteristics, electroencephalogram examination and gene detection were analyzed in a case of GSS similar to Creutzfeldt-Jakob disease (CJD) in symptomatology. The differences between the two different prion diseases were compared in combination with the literature review.@*Results@#The patient is a 62-year-old woman, with cerebellar ataxia as the first symptom, followed by rapid dementia, accompanied by pyramidal and extrapyramidal signs. Magnetic resonance imaging showed hyper-intense signal in diffusion weighted imaging in caudatum and cortical ribboning, and protein 14-3-3 was negative. PRNP gene analysis showed P102L gene mutation.@*Conclusions@#The typical clinical manifestation of GSS is hereditary ataxia followed by cognitive decline of varying severity. Detection of PRNP plays an important role in the diagnosis of GSS.

Numerical study on the mechanical coupling of external vascular stent and vein graft in coronary artery bypass surgery / 生物医学工程学杂志

External support stent is a potential means for restricting the deformation and reducing wall stress of the vein graft, thereby improving the long-term patency of the graft in coronary artery bypass surgery. However, there still lacks a theoretical reference for choosing the size of stent based on the diameter of graft. Taking the VEST (venous external support) stent currently used in the clinical practice as the object of study, we constructed three models of VEST stents with different diameters and coupled them respectively to a model of the great saphenous vein graft, and numerically simulated the expansion-contraction process of the vein graft under the constraint of the stents to quantitatively evaluate the influence of stent size on the radial deformation and wall stress of the vein graft. The results showed that while the stent with a small diameter had a high restrictive effect in comparison with larger stents, it led to more severe concentration of wall stress and sharper changes in radial deformation along the axis of the graft, which may have adverse influence on the graft. In order to solve the aforementioned problems, we ameliorated the design of the stent by means of changing the cross-sectional shape of the thick and thin alloy wires from circle into rectangle and square, respectively, while keeping the cross-sectional areas of alloy wires and stent topology unchanged. Further numerical simulations demonstrated that the ameliorated stent evidently reduced the degrees of wall stress concentration and abrupt changes in radial deformation, which may help improve the biomechanical environment of the graft while maintaining the restrictive role of the stent.