ObjectiveTo elucidate the chemical composition of Danshenyin and its blood components in rats after oral administration. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） coupled with PeakView 1.2 software was used to systematically characterize and identify the components of Danshenyin aqueous extract and its migratory components in rat blood after oral administration based on the retention time， quasi-molecular ion peaks， secondary fragmentation ions， and literature reports， and a preliminary compounds identification of Salviae Miltiorrhizae Radix et Rhizoma aqueous extract， the co-decoction of Santali Albi Lignum and Amomi Fructus was carried out to attribute the chemical constituents of the aqueous extract of Danshenyin. ResultsA total of 73 compounds， including 21 phenolic acids， 23 diterpenes， 6 flavonoids， 7 organic acids， 3 volatile oils and 13 others， were identified from the aqueous extract of Danshenyin. And 36 prototypes and 15 metabolites were identified in rat plasma， the major metabolic pathways included reduction， hydration， hydroxylation， demethylation， methylation， sulfation and others， these metabolites were mainly derived from tanshinones and salvianolic acids. ConclusionThe main blood components of the aqueous extract of Danshenyin are salvianolic acids and tanshinones， which may be the material basis of the efficacy. This study can provide reference for pharmacological research， quality control， and clinical application of Danshenyin.

【Objective】 To establish an information management platform for provincial rare blood group bank to achieve the interconnection and sharing of data such as rare blood group types, donor information and blood inventory, so as to enhance the supply security of rare blood group blood. 【Methods】 The information barriers of rare blood group management in each business link and among blood stations in Zhejiang province were analyzed using fishbone diagram. Data modeling technology was introduced based on the unified blood collection and supply business system and blood cloud platform of Zhejiang, the database view of rare blood group donors and rare blood group was constructed through demand analysis and model design, and a unified query platform was developed to achieve the sharing of rare blood group information. 【Results】 The system integrated, retrievaled and displayed rare blood type information, achieving the interconnection of information among various business links and blood stations within blood banks. Up to now, in addition to RhD negative blood group, there were 8 types of rare red blood cells in the bank, covering 7 blood group systems, 289 rare blood group donors and 216 units of frozen red blood cells of rare blood group. 【Conclusion】 The information system based on data modeling can improve the overall efficiency and collaboration of the system, and reduce the workload of system development and operation. It can provide reference for standardized data management and application, and also provide a model for establishing and improving of a national rare blood group information network.

As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-β-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-β receptor type-1 (TGFβR1) and abrogated the kinase activity of TGFβR1, thereby blocking the TGF-β-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFβR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFβR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFβR1 were found to be crucial for the interaction of ITSN with TGFβR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-β-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFβR1 in TNBC metastasis, but also provide a leading compound targeting TGFβR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFβR1 inhibitor.

Objective:To explore the clinical and pathological characteristics and prognostic factors of gastric neuroendocrine carcinoma(G-NEC)and gastric mixed adenoendocrine carcinoma(G-MANEC).Methods:Retrospective analysis was conducted on the clinical data of 67 patients with G-NEC and G-MANEC who underwent surgical treatment at Heping Hospital Affiliated to Changzhi Medical College from May 2015 to May 2023.The study included an analysis of the pathological characteristics distinguishing G-NEC from G-MANEC.Results:Com-pared to gastric adenocarcinoma,patients with G-NEC and G-MANEC in the stomach showed a higher incidence of gastric cancer in the male gastric cardia and were diagnosed at a later age.Tumors with larger diameters increase susceptibility to anemia,low albumin levels,and in-vasion of nerves and vasculature.Deeper tumor infiltration is associated with increased local lymph node metastases,later TNM staging,and a higher likelihood of distant metastasis post-surgery.The prognosis of G-NEC and G-MANEC is worse than that of gastric adenocarcinoma(P=0.001).However,there is no statistically significant difference in the pathological characteristics(P>0.05)and prognosis analysis(P=0.212)between G-NEC and G-MANEC.Univariate survival analysis identified age,preoperative albumin,preoperative CEA,number of lymph node metastases,TNM staging,and postoperative distant metastasis as risk factors affecting patient's overall survival(OS).In the multivariate ana-lysis,age,preoperative albumin,TNM staging,and postoperative distant metastasiswere identified as independent risk factors for OS.Con-clusions:There is a significant difference in clinical characteristics between G-NEC,G-MANEC,and gastric adenocarcinoma,often diagnosed at an advanced stage,which is prone to distant metastasis post-surgery.Poor prognosis is observed in patients aged over 60 years,with pre-operative albumin<40g/L,TNM stage Ⅱ/Ⅲ,and postoperative distant metastasis.

Objective To delve into the causal relationship between 211 gut microbiota and sepsis employing bidirectional Mendelian randomization(MR).Methods The gut microbiota genome-wide association study(GWAS)data from the Microbiome Genetics Consortium(MiBioGen,n = 18 340)and sepsis GWAS data from the FinnGen(n = 286 146)were harnessed for this study.Initially,single nucleotide polymorphisms(SNP)significantly associated with the relative abundance of 211 gut microbiota taxa were identified as instrumental variables using predefined selection criteria.The primary analytical approach was characterized by the application of inverse variance weighting(IVW),with the effect measure represented by the odds ratio(OR)to assess the results of MR.To ensure precision and reliability,analyses were conducted,including leave-one-out analysis,heterogeneity testing,and tests for pleiotropy at both coherent and incoherent levels.Results The increased risk of sepsis was associated with the elevated abundance of Collinsella[OR = 1.28,95%confidence interval(95%CI)was 1.06-1.56,P = 0.01]and Ruminococcus(OR = 1.19,95%CI was 1.05-1.35,P = 0.005).Furthermore,a protective effect against the development of sepsis was observed in association with the increased abundance of Prevotella(OR = 0.88,95%CI was 0.79-0.97,P = 0.01)and Firmicutes(OR = 0.86,95%CI was 0.75-0.996,P = 0.04).No obvious heterogeneity and irrelevant level pleiotropy were detected.Conclusion Collinsella and Ruminococcus increase the risk of sepsis,while Prevotella and Firmicutes have protective effects against sepsis.

Humans ; Aripiprazole/therapeutic use* ; Schizophrenia/drug therapy* ; Antipsychotic Agents/therapeutic use* ; Risperidone ; China ; Treatment Outcome

Objective:To summarize the clinical characteristics of children with dystonia 28 (DYT28) caused by KMT2B gene variations so as to improve clinicians′ understanding of the disease. Methods:The clinical manifestations, treatment and gene variation data of 11 children with DYT28 caused by KMT2B gene variations were retrospectively collected and analyzed.The subjects were recruited from the Department of Neurology, Beijing Children′s Hospital, Capital Medical University from March 2018 to January 2021.The patients were followed up. Results:There were 8 males and 3 females.The age at onset was ranging from 1 month to 6 years without inducement.Eight cases were gene-ralized dystonia and 3 cases were multifocal dystonia.The initial symptoms of 7 cases were unilateral or bilateral lower limbs tiptoeing.Four cases presented dysarthria, retching or swallowing difficulties at onset.As the disease progressed, all the cases had laryngeal dystonia, 10 cases had lower limbs dystonia, and 8 cases had upper limbs dystonia.Six cases were complicated with other dyskinesia symptoms.Ten cases had varying degrees of short stature, microcephalus, micrognathia, musculoskeletal abnormalities, intellectual disability, endocrinopathies and sleep difficulties.The brain magnetic resonance imaging showed abnormal in only 1 case.Eleven KMT2B gene pathogenic variants were found, including 8 frameshift variants, 1 in-frame variant and 2 missense variants.Four variants were novel.Eleven cases were followed up at the age of 1 year and 7 months to 17 years and 9 months.One case wasn′t given therapy.The dystonia in 3 cases was mildly improved after medication.Dysfunction of urination and defecation was disappeared in 1 case after medication.The symptom of 6 cases had no improvement after drug therapy.Among the above 6 cases, 5 drug refractory cases had deep brain stimulation, and their dystonia symptoms are all obviously improved; 2 cases had normal control of urination and defecation after deep brain stimulation.The motor scores in the Burke-Fahn-Marsden dystonia rating scale were improved by 55.8%-90.7%, and the disability scores were improved by 14.8%-69.6%. Conclusions:DYT28 caused by KMT2B gene variations is one of the most common and early-onset genetic dystonia in children.The dystonia symptom progresses from local parts to the whole body, prominently involving laryngeal muscles and lower limbs.Control of urination and defecation requires attention.Patients with mild dystonia symptoms can be effectively treated by drugs.However, patients with severe dystonia symptoms were drug refractory, and their dystonia symptoms can be effectively improved by deep brain stimulation.

Objective:To investigate the prognostic value and related factors of heart-type fatty acid binding protein (H-FABP) in patients with heart failure.Methods:A total of 877 consecutive patients who were admitted to heart failure care unit of Fuwai hospital and diagnosed as heart failure from July 2015 to July 2017 were enrolled in this study. Baseline serum H-FABP concentration was measured by fluorescence lateral flow immunoassay. According to serum H-FABP levels, patients were divided into three groups: low H-FABP group (H-FABP≤4.04 ng/ml, n=292), middle H-FABP group (H-FABP 4.04-7.02 ng/ml, n=292) and high H-FABP group (H-FABP≥7.02 ng/ml, n=293). The general clinical characteristics were collected and compared among the three groups. According to whether heart failure was caused by coronary artery disease or not, patients with heart failure were divided into ischemic heart failure and non-ischemic heart failure. Multivariate linear regression analysis was performed to explore the independent risk factors of H-FABP. The primary endpoint events were the composite of all-cause death or heart transplantation. Multivariate Cox regression analyses, receiver operating characteristic (ROC) curves, risk prediction tests with multivariate Cox regression model and Kaplan-Meier analyses were conducted to investigate the relationship between H-FABP and the prognosis of heart failure. Results:Multivariate linear regression analysis showed that age, coronary artery disease, alanine aminotransferase, uric acid and N-terminal pro-B type natriuretic peptide (NT-proBNP) were positively associated with H-FABP (β=0.012, 0.238, 0.001, 0.345 and 0.063 respectively,all P<0.05), while female, hemoglobin, albumin, sodium, and estimated glomerular filtration rate (eGFR) were negatively associated with H-FABP (β=-0.184, -0.006, -0.016, -0.034 and -0.006 respectively, all P<0.05). One hundred and nineteen patients (13.6%) lost to follow-up, and 246 patients (32.5%) suffered from all-cause death or heart transplantation during the median follow-up duration of 931 (412-1 185) days. Multivariate Cox regression analysis showed that baseline H-FABP (log 2H-FABP) level was the independent predictor of all-cause death or heart transplantation in patients with heart failure ( HR=1.39, P<0.001). ROC curves showed that baseline H-FABP was a predictor of all-cause death or heart transplantation in patients with heart failure within 3 months, 1 year and 2 years (areas under the curves were 0.69, 0.69 and 0.71 respectively), and the best cut-off values were 5.85 ng/ml, 6.54 ng/ml and 6.54 ng/ml respectively. Risk prediction test with multivariate Cox regression model showed that baseline H-FABP could provide additional prognostic value in predicting all-cause death or heart transplantation for patients with heart failure on top of basic model and baseline NT-proBNP ( P<0.001). Taking 6.54 ng/ml and trisected levels of H-FABP as cut-off values respectively, Kaplan-Meier analyses showed that the survival rates were significantly different among the two or three groups ( P<0.001). Subgroup analyses showed that baseline H-FABP (log 2H-FABP) level was an independent predictor of all-cause death or heart transplantation in patients with ischemic heart failure ( HR=1.74, P<0.001), as well as in patients with non-ischemic heart failure ( HR=1.28, P=0.027). Conclusions:Age, sex, coronary artery disease, hemoglobin, albumin, alanine aminotransferase, sodium, eGFR, uric acid and NT-proBNP are associated with H-FABP level. Baseline H-FABP level is an independent predictor of all-cause death or heart transplantation in patients with heart failure. On top of basic model and baseline NT-proBNP, baseline H-FABP could provide additional prognostic value in predicting adverse events for patients with heart failure.

In recent years, the science and technology of organ transplantation have developed rapidly, which has been widely applied worldwide. However, multiple challenges remain to be resolved by clinicians, such as functional damage and immune rejection of transplant organs, immune deficiency caused by extensive use of immunosuppressants, chronic allograft dysfunction and adverse reactions. This article introduced relevant key research results published in 2021, taking the function and mechanism of immune cell subsets in the process of organ transplantation rejection or immune tolerance, and the research and application of new materials and drugs in organ transplantation as the main clues. The latest research progresses on regional immune response, especially the application of tissue-resident memory T cell in organ transplantation, were briefly summarized, and the future development of transplantation immunology was prospected.

Objective:To investigate the application and effect of personalized teaching mode based on Xuexitong learning platform in physiology.Methods:Four parallel classes from the nursing specialty were randomized into two groups, of which the class 1 and class 2 were taken as the experimental group, and the class 3 and class 4 were taken as the control group, with 102 students in both groups. The students number of these two groups is both 102. The experimental group adopted the personalized teaching mode based on Xuexitong learning platform, with the features of preparation before the class, the teaching in class and testing after class; while the control group adopted the traditional teaching mode. The final results of students from the two groups were compared, and questionnaires were send out. The data were processed by SPSS 22.0 software and analyzed by rank-sum test.Results:The final scores of the students from the experimental group were better than those of the control group ( P<0.001). The experimental group was significantly better than the control group in improvement of self-learning, teamwork, personality development and medical literacy ( P<0.05). And there was no significant difference in the recognition of language expression ability between the two groups ( P>0.05). Conclusion:The personalized teaching based on Xuexitong learning platform can play an important role in developing the personalities of students and improving the educational effect of teaching students in accordance with their aptitude, which has a popularization significance in the teaching of physiology.