ObjectiveBased on the experience of traditional quality evaluation， the quality of Atractylodis Macrocephalae Rhizoma（AMR） with different production methods such as direct seeding， transplanting after seedling raising， topping and non-topping， and difference in growth years was compared. MethodVernier caliper was used to measure the trait data of AMR in different production methods. Paraffin sections of AMR with different production methods were made by saffron solid green staining， and the microstructure was observed. The contents of water-soluble and alcohol-soluble extracts in AMR with different production methods were determined according to the 2020 edition of Chinese Pharmacopoeia. The content of water-soluble total polysaccharides in AMR with different production methods was detected by sulfuric acid-anthrone method. Fiber analyzer was used to detect the content of fiber components in AMR with different production methods. The contents of monosaccharides， oligosaccharides and some secondary metabolites in AMR with different production methods were detected by ultra performance liquid chromatography（UPLC）， and the differences of chemical components were compared by multivariate statistical analysis methods such as principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA）. ResultIn terms of traits， the 3-year-old AMR with direct seeding and without topping was close to the high-quality AMR with "phoenix-head and crane-neck， strong sweetness and clear aroma" recorded in ancient materia medica， followed by the 3-year-old AMR with topping after transplanting， while the 2-year-old AMR with topping after transplanting with high market circulation rate was generally fat and strong with mild odor. In the microscopic aspect， the arrangement of xylem vessels and fiber bundles in the 3-year-old samples formed two obvious rings. Compared with the 2-year-old samples cultivated in Bozhou and Zhejiang， the 3-year-old samples without topping after transplanting had more wood fibers. In terms of chemical composition， the contents of 70% ethanol extract， fructose， glucose， sucrose， 1-kestose， atractylenolide Ⅰ， chlorogenic acid， neochlorogenic acid， cryptochlorogenic acid and other components in 3-year-old AMR with direct seeding and without topping were significantly higher than those in the other three samples（P<0.05）. The contents of cellulose， 70% ethanol extract， sucrose， atractylenolide Ⅰ， atractylone and other components in 3-year-old AMR with topping after transplanting were significantly higher than those in the 2-year-old AMR with high market circulation rate（P<0.05）， while the contents of water-soluble extract and water-soluble total polysaccharides in 2-year-old samples with topping after transplanting were significantly higher than those in the 3-year-old AMR with topping after transplanting， direct seeding and without topping（P<0.05）. ConclusionUnder the current mainstream production mode， too much manual intervention makes AMR heavily enriched in polysaccharides and increased the yield， but the accumulation of sweet substances， fragrant substances and fiber substances is insufficient， which affects its quality. The current quality standard of AMR has some shortcomings in guiding the high quality production of it， it is suggested to revise the quality standard of AMR， supplement the quantitative analysis of secondary metabolites， and strengthen the production of imitation wild AMR.

AIM: To evaluate the clinical efficacy and safety of He-wei-zhi-xie (HWZX) capsules in diarrhea patients. METHODS: The clinical study was conducted in 35 clinical trials centers from October 2015 to December 2017 by multicenter, prospective, open and uncontrolled design methods. The primary efficacy endpoint is the effective rate of diarrhea, the secondary endpoints include recovery rate of diarrhea, recovery time of diarrhea, number of irregular stools and Leeds dyspepsia questionnaire. The pharmacodynamics model of time course was established by nonlinear mixed effect model, and the effect of covariates on pharmacodynamic parameters was investigated. The safety measures were the incidence of adverse events, adverse reactions and the laboratory test indicators. RESULTS: A total of 2 285 cases were included in full analysis set. The effective rate of diarrhea was 90.8%, and the diarrhea recovery rate was 77.3%. The median time of recovery was 3 days, and the Leeds score was reduced by 3.6 points. It is found that baseline has a significant effect on model parameter E

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

Objective To investigate the expression of serum pentraxin3（PTX3） and microRNA-199a（miR-199a） in patients with acute stroke，and to further analyze the relationship between PTX3 and miR-199a and the neurological function of the patients and their value in the diagnosis of the disease.Methods 83 patients with acute stroke who were treated in our hospital from January 2018 to December 2019 were selected as the study group. According to National Institute of Health stroke scale（NIHSS） score，the patients were divided into mild group（26 cases），moderate group（30 cases） and severe group（27 cases）.Another 40 volunteers who had physical examination in our hospital at the same time were selected as the control group. Serum levels of PTX3，miR-199a，soluble protein 100β（S100-β），and neuron specific enolase（NSE） in all subjects were detected.Results The levels of PTX3，S100-β and NSE in the study group were higher than those in the control group，and the levels of miR-199a in the study group were lower than those in the control group（P<0.05）；The levels of PTX3，S100 -β，NSE，NIHSS and miR-199a in severe group were higher than those in moderate group and mild group（P<0.05），and the levels of PTX3，S100-β，NSE and NIHSS in the moderate group were higher than those in the mild group，and the level of miR-199a was lower than that in the mild group（P<0.05）；Pearson analysis showed that PTX3 was positively correlated with S100-β，NSE and NIHSS scores in patients with acute stroke（P<0.05），and miR-199a was negatively correlated with S100-β，NSE and NIHSS scores（P<0.05）；ROC analysis showed that serum PTX3 and miR-199a had certain diagnostic value for acute stroke.The area under the curve was 0.864（95%CI 0.799～0.928）and 0.807（95%CI：0.704～0.910），respectively. The combination of the two could further improve the diagnostic value for acute stroke.Conclusion Serum PTX3 is highly expressed and miR-199a is lowly expressed in patients with acute stroke，and the expression of both is closely related to the patient’s nerve function.Both of them have a certain value of diagnosis.

Accurate determination of biological activity is essential in quality control of recombinant human brain natriuretic peptide (rhBNP). In previous study, we successfully developed a genetically modified cell line 293GCAC3-based ELISA assay for rhBNP. But ELISA procedure is still tedious, so this study was aimed to develop a rapid and simple bioassay for rhBNP using GloSensor technology, which provides a platform of flexible luciferase-based biosensors for real-time detection of signaling events in live cells, including cGMP production. A reporter cell line 293GCAGlo-G1 was constructed by transfecting pGloSensor?40 F plasmid into 293GCAC3. The reporter assay based on 293GCAGlo-G1 showed high precision with intra-assay CV being 8.3% and inter-assay CV being 14.1%; high accuracy with 80%, 100% and 120% recovery rate being 99.2%, 102.4% and 99.0% respectively; and great linearity with R2of linear fitting equation being 0.99. Besides, no significant difference was found in test results of reporter assay and 293GCAC3-based ELISA assay (paired t test, p＝0.630). All these results suggested that the reporter assay was a viable assay for biological determination of rhBNP.

Objective To evaluate the clinical value of 6 androgens in the serum of Sj?gren's syndrome (SS) measured by liquid chromatography tandem mass spectrometry (LC-MS).Methods 32 SS patients (SS group) and 25 healthy people (healthy group) were included in this study.6 androgens in the serum were analyzed by LC-MS after prepared.PCA,PLS-DA models and t-test were used to class differentiation of androgens between two groups.Results The results of PLS-DA showed that SS group and healthy group could be well classed by 6 androgens.The levels of testerone (T),dihydrotestosterone (DHT),dehydroepiandrosterone (DHEA),androsterone and DHEAS in SS group were significantly lower than those in healthy group (t=8.536,2.438,3.172,4.158,4.489,all P<0.05).The samples before or after menopause could be distinguished between the two groups by PLS-DA.Conclusion The significant difference of androgens was discovered between SS patients and healthy people via the measurement of 6 androgens in serum.It may arise a new idea for diagnosis and treatment of SS.

Osteoporosis (OP) is one of the bone metabolic diseases which seriously harms the health and lives of people. The main cause of OP is that the balance between bone formation and bone absorption, i.e. the balance of the bone remodeling process,is no longer exist. When the bone absorption dominates the process, it will lead to osteopenia, destruction of bone microstructure and increased rate of fracture. Previous studies have shown that casein kinase 2-interacting protein-1 (CKIP-1) plays an important role in the process of bone tissue proliferation and differentiation. It mainly interacts with Smad ubiquitination regulatory factor 1 (Smurf 1) to affect bone metabolism. This review analyzes and summarizes the impact of CKIP-1 on bone tissue osteogenic differentiation direction and its mechanism, which may provide new idea and research orientation for future clinical treatment of osteoporosis.

Objective] To observe the clinical efficacy of Agkistrodon in treating Sjogren's syndrome. [Methods] 52 patients were randomly divided into two groups: Treatment of 26 patients taking Agkistrodon and the basic prescription medicine(YIQIYANGYINQUYU drugs); 26 patients in the control received the basic prescription medicine. The clinical symptoms,the disease activity score of SSDAI,the score of TCM symptom and life quality and the index of serology were recorded in this clinical observation. [Results] The treatment group had better results of immune function than the control group after treatment, in particular had a substantial decrease in IgG. In addition, the clinical symptoms, the disease activity score of SSDAI, the score of TCM symptom and life quality were improved. [Conclusion] Agkistrodon has significantly immunosuppressive effects on the patients with Sjogren's syndrome , thus improving the patients' condition,the standard of living and the quality of life.

Bone marrow mesenchymal stem cells (BMSCs) is a kind of multipotent adult stem cells,which is one of the most important seed sources of tissue engineering.Microgravity has inhibitory effects on osteogenic differentiation of BMSCs,which will cause bone mass reduction and changes of bone micro-structure that finally lead to osteoporosis.This process is regulated by multiple signaling pathways such as mitogen-activated protein kinase (MAPK) pathway,Notch pathway and Wnt/β-catenin pathway which co-regulated BMSCs osteogenic differentiation under microgravity.Studying the effects of microgravity on BMSCs into osteogenic differentiation can clarify the mechanism of bone loss,put forward new targets for the treatment of diseases and provide a useful reference for the development of China's space industry.

Objective To explore clinical feasibility of liver transplant from child of brain death to adult, to summarize the clinical experiences that a child of brain death transplants liver to an adult. Methods The recipient was a 39-year-old woman patient with primary hepatic carcinoma and posthepatitis cirrhosis (decompensation stage); while the donor was a 8-old-year child of brain death because of brain neoplasms. Donated liver was gained by the method of en bloc multivisceral procurement in a short time; the operative method was classic orthotopic liver transplantation. The postoperative managements included immunosuppression, prevention of infection, hepatic protection, and other relevant supports etc. Results The transplantation operative duration was 6 hours, after which not only did the recipient survive but also her body functioned well including the liver part, with no severe postoperative complications. Conclusions The technology of transplanting livers from children to adults is feasible. The key to ensure the success of transplant operation is systematic preoperative evaluation, excellent operative technique, and perfect postoperative treatment.