Brasilicardin A, a diterpene glycoside isolated from pathogenic actinomycete Nocardia brasiliensis IFM 0406, has become a novel immunosuppressant candidate due to its significant immunosuppressive activity, low toxicity and unique mechanism of action. However, brasilicardin A and its analogues have become a research hotspot to the development of this promising immunosuppressant because of the low-yield production in the natural pathogenic producer and the synthetically challenging skeleton. According to the reported biosynthetic pathway of brasilicardin A, the function of involved diterpene synthase was analyzed by bioinformatics. Then the genes bra1-5 that synthesize the brasilicardin A skeleton were directionally amplified from the pathogenic strain N. brasiliensis IFM 0406, and heterologous expression was achieved successfully in Streptomyces albus R1. The compounds were isolated and purified by using various column chromatographies including silica gel column chromatography and semi-preparative HPLC. Six new brasilicardins were established and named brasilicardin H-M. The activity of brasilicardins was screened using lipopolysaccharide (LPS)-activated mouse primary macrophage inflammation model. Brasilicardin H-M exhibited good inhibitory activity on nitric oxide (NO) release with IC₅₀ values of 28.24 ± 3.70, 37.44 ± 2.00, 39.85 ± 4.02, 26.77 ± 4.40, 65.25 ± 1.48 and 15.24 ± 2.72 μmol·L^-1, respectively (indomethacin as the positive control with IC₅₀ value of 34.28 ± 4.10 μmol·L^-1). The results indicated that six compounds had potential anti-inflammatory activity. This study laid a foundation for the elucidation of the brasilicardin A biosynthetic pathway and evaluation of the structure-activity relationship as well as new drug developments.

In recent years, the clinical treatment of colorectal cancer(CRC) has made great progress, but chemoresistance is still one of the main reasons for reducing the survival rate of patients with colorectal cancer. Therefore, ameliorating chemotherapy resis-tance is an urgent problem to be solved. The purpose of this study was to investigate the regulatory role and related molecular mechanisms of hydroxysafflor yellow A(HSYA) in colorectal cancer cell proliferation, migration, and 5-fluorouracil(5-FU) chemoresistance. In this study, HCT116 and HT-29 cells were used as research subjects. Firstly, methyl thiazolyl tetrazolium(MTT) assay and colony formation assay were used to detect and analyze the effect of HSYA on the proliferation of CRC cells. Secondly, the effect of HSYA on the cell cycle in CRC cells was analyzed by cell cycle assay. Furthermore, the effect of HSYA on the migration of CRC cells was analyzed by wound-healing assay and Transwell assay. Based on the above, the influences of HSYA on 5-FU chemoresistance of CRC cells and related molecular mechanisms were explored and analyzed. The results showed that HSYA significantly inhibited the proliferation and migration of CRC cells, and arrested the cell cycle in G_0/G_1 phase. In addition, HSYA significantly ameliorated the chemoresistance of CRC cells to 5-FU. The results of acridine orange staining and Western blot showed that the autophagy activity of CRC cells in the HSYA and 5-FU combined treatment group was significantly higher than that in the 5-FU single drug treatment group. As compared with the 5-FU single drug treatment group, the phosphorylation levels of protein kinase B(Akt) and mammalian target of rapamycin(mTOR) in the HSYA and 5-FU combined treatment group were significantly reduced, indicating that the Akt/mTOR signaling pathway in the combined treatment group was down-regulated in CRC cells. In conclusion, HSYA may upregulate autophagy activity through the Akt/mTOR signaling pathway, thereby inhibiting the proliferation and migration of CRC cells and ameliorating the chemoresistance to 5-FU.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; TOR Serine-Threonine Kinases/metabolism* ; Fluorouracil/pharmacology* ; Cell Proliferation ; Autophagy ; Colorectal Neoplasms/drug therapy*

This study aims to evaluate the methodological and reporting quality of diagnosis and treatment guidelines for hyperuricemia as well as the expert consensuses and promote the understanding and application of the diagnosis and treatment guidelines for hyperuricemia. With "hyperuricemia" "guidelines" "consensus" "recommendations" as the key words in titles, the authors searched for the published clinical guidelines on hyperuricemia in Chinese against CNKI, Wanfang, VIP, Medlive and the official website of the industry association. The retrieval time limit was until May 31, 2021. The appraisal of guidelines for research and evaluation Ⅱ(AGREEⅡ) and the reporting items for practice guidelines in health care(RIGHT) were employed to evaluate the methodological quality and reporting quality of 14 guidelines/consensuses included. The average scores of the guidelines/consensuses were 80.85%(48.61%-98.61%) for the domain of scope and purpose, 34.52%(0-69.44%) for the domain of stakeholder involvement, 35.53%(6.25%-92.19%) for the domain of rigor of development, 55.85%(23.61%-86.11%) for the domain of clarity of presentation, 26.19%(0-76.04%) for the domain of applicability, and 21.42%(0-50.00%) for the domain of editorial independence. Nine guidelines/consensuses were of medium overall quality with grade B recommendation, and five guidelines/consensuses were of poor quality with grade C recommendation. The RIGHT classified the fourteen guidelines/consensuses into one of high reporting quality, three of medium reporting quality, and ten of low reporting quality. The results of this study indicate that the standardization and rigor of the methodological quality and the reporting quality of the clinical guidelines/consensuses for hyperuricemia in China remain to be strengthened.
China ; Consensus ; Humans ; Hyperuricemia/drug therapy* ; Publications ; Reference Standards

Lower extremity deep vein thrombosis (DVT) is one of the main complications in patients with traumatic fractures, and for severe patients, the DVT can even affect arterial blood supply, resulting in insufficient limb blood supply. If the thrombus breaks off, pulmonary embolism may occur, with a high mortality. The treatment and rehabilitation strategies of thrombosis in patients with lower extremity fractures have its particularity. DVT in traumatic fractures patients has attracted extensive attention and been largely studied, and the measures for prevention and treatment of DVT are constantly developing. In recent years, a series of thrombosis prevention and treatment guidelines have been updated at home and abroad, but there are still many doubts about the prevention and treatment of DVT in patients with different traumatic fractures. Accordingly, on the basis of summarizing the latest evidence-based medical evidence at home and abroad and the clinical experience of the majority of experts, the authors summarize the clinical treatment and prevention protocols for DVT in patients with traumatic fractures, and make this consensus on the examination and assessment, treatment, prevention and preventive measures for DVT in patients with different fractures so as to provide a practicable approach suitable for China ′s national conditions and improve the prognosis and the life quality of patients.

OBJECTIVE: To investigate the incidence rate of infectious diseases during hospitalization in late preterm infants in Beijing, China, as well as the risk factors for infectious diseases and the effect of breastfeeding on the development of infectious diseases. METHODS: Related data were collected from the late preterm infants who were hospitalized in the neonatal wards of 25 hospitals in Beijing, China, from October 23, 2015 to October 30, 2017. According to the feeding pattern, they were divided into a breastfeeding group and a formula feeding group. The two groups were compared in terms of general status and incidence rate of infectious diseases. A multivariate logistic regression analysis was used to investigate the risk factors for infectious diseases. RESULTS: A total of 1 576 late preterm infants were enrolled, with 153 infants in the breastfeeding group and 1 423 in the formula feeding group. Of all infants, 484 (30.71%) experienced infectious diseases. The breastfeeding group had a significantly lower incidence rate of infectious diseases than the formula feeding group (22.88% vs 31.55%, CONCLUSIONS Breastfeeding can significantly reduce the incidence of infectious diseases and is a protective factor against infectious diseases in late preterm infants. Breastfeeding should therefore be actively promoted for late preterm infants during hospitalization.
Beijing/epidemiology* ; Breast Feeding ; China/epidemiology* ; Communicable Diseases/epidemiology* ; Female ; Hospitalization ; Hospitals ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Male ; Pregnancy

Since December 2019, novel coronavirus pneumonia (NCP) has been reported in Wuhan, Hubei Province, and spreads rapidly to all through Hubei Province and even to the whole country. The virus is 2019 novel coronavirus (2019-nCoV), never been seen previously in human, but all the population is generally susceptible. The virus spreads through many ways and is highly infectious, which brings great difficulties to the prevention and control of NCP. Based on the needs of orthopedic trauma patients for emergency surgery and review of the latest NCP diagnosis and treatment strategy and the latest principles and principles of evidence-based medicine in traumatic orthopedics, the authors put forward this expert consensus to systematically standardize the clinical pathway and protective measures of emergency surgery for orthopedic trauma patients during prevention and control of NCP and provide reference for the emergency surgical treatment of orthopedic trauma patients in hospitals at all levels.

Combined radiation-wound injury (CRWI) is characterized by blood vessel damage and pro-inflammatory cytokine deficiency. Studies have identified that the direct application of leptin plays a significant role in angiogenesis and inflammation. We established a sustained and stable leptin expression system to study the mechanism. A lentivirus method was employed to explore the angiogenic potential and peripheral inflammation of irradiated human umbilical vein endothelial cells (HUVECs). Leptin was transfected into human placenta-derived mesenchymal stem cells (HPMSCs) with lentiviral vectors. HUVECs were irradiated by X-ray at a single dose of 20 Gy. Transwell migration assay was performed to assess the migration of irradiated HUVECs. Based on the Transwell systems, co-culture systems of HPMSCs and irradiated HUVECs were established. Cell proliferation was measured by cell counting kit-8 (CCK-8) assay. The secretion of pro-inflammatory cytokines (human granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-1α, IL-6, and IL-8) was detected by enzyme-linked immunosorbent assay (ELISA). The expression of pro-angiogenic factors (vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)) mRNA was detected by real-time quantitative polymerase chain reaction (RT-qPCR) assay. Relevant molecules of the nuclear factor-κB (NF-κB) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways were detected by western blot assay. Results showed that leptin-modified HPMSCs (HPMSCs/ leptin) exhibited better cell proliferation, migration, and angiogenic potential (expressed more VEGF and bFGF). In both the single HPMSCs/leptin and the co-culture systems of HPMSCs/leptin and irradiated HUVECs, the increased secretion of pro-inflammatory cytokines (human GM-CSF, IL-1α, and IL-6) was associated with the interaction of the NF-κB and JAK/STAT signaling pathways. We conclude that HPMSCs/leptin could promote angiogenic potential and peripheral inflammation of HUVECs after X-ray radiation.
Cell Proliferation ; Cells, Cultured ; Cytokines/biosynthesis* ; Female ; Human Umbilical Vein Endothelial Cells/radiation effects* ; Humans ; Inflammation/etiology* ; Leptin/pharmacology* ; Mesenchymal Stem Cells/physiology* ; Neovascularization, Physiologic/physiology* ; Placenta/cytology* ; Pregnancy ; STAT3 Transcription Factor/genetics* ; Transcription Factor RelA/genetics* ; X-Rays

Objective To investigate the difference between mammary gland tissues and breast cancer tissues.Methods Monoclonal antibodies against Mam-A immunized epitopes were screened for immunohistochemical staining of normal breast tissues and breast cancer tissues.The average optical density was used as an index to identify the quantitative data by computer-aided technology to screen epitope-specific antibodies with significant difference in staining characteristics between two types of tissues.Furthermore the feasibility and effectiveness of breast cancer diagnosis were evaluated.Results Four anti-Mam-A epitope-specific monoclonal antibodies,mAb1152,mAb11617,mAb995 and mAb656,were obtained.Immunohistochemical staining showed that the average density of mAb1152,mAb11617 and mAb995 was significantly different between the two types of tissues.The difference was significant between normal breast tissues and breast cancer tissues under the same conditions.The results showed that mAb11617 was better than mAb1152 and mAb995.At the best working point,mAb11617 was the best,the specificity was 90％ and the sensitivity was 59.62％.Further analysis showed that the sensitivity of mAb11617 combined with mAb995 in the diagnosis of in situ breast cancer was 81.48％ and the specificity was 90％,which was of great diagnostic significance.Conclusion There is significant difference between breast tissues and breast cancer tissues in Mam-A protein immunological activity or expression.This difference,which can be recognized by the specific antibody staining and computer aided technology,is of important diagnostic value.

OBJECTIVES: To observe the expression changes of hypoxia inducible factor-1α（HIF-1α） and vascular endothelial growth factor-A （VEGF-A） in rats with arrhythmias, and to explore the differences of the expression pattern in the two indicators of acute myocardial ischemia caused by arrhythmias and coronary insufficiency. METHODS: The arrhythmia was induced by CaCl₂, and the expression changes of HIF-1α and VEGF-A were detected by immunohistochemistry, Western blotting and real-time PCR within 6 h after the arrhythmia in rats. RESULTS: The expression of HIF-1α and VEGF-A showed diffuse in the myocardial tissue of rats died from arrhythmias. Both of them increased in the early arrhythmia, then decreased. Extensive myocardial ischemia happened at the beginning of arrhythmia occurrence and its range didn't expand with time. CONCLUSIONS The expressions of HIF-1α and VEGF-A in myocardium of the rats with arrhythmia can provide evidence for the differential diagnosis of acute myocardial ischemia caused by fatal arrhythmia and coronary insufficiency.
Animals ; Arrhythmias, Cardiac/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Myocardial Ischemia/metabolism* ; Myocardium/metabolism* ; Rats ; Vascular Endothelial Growth Factor A/metabolism*

This article aims to compare the qualities of Armeniacae Semen Amarum before and after rancidness, in order to study the rancidness of Armeniacae Semen Amarum. In the experiment, content of fatty oil, acid value and peroxide value were determined before and after rancidness,respectively. Meanwhile, HPLC, GC-MS were utilized to analyze laetrile and fatty acid components. Besides, colorimeter and e-nose were introduced to quantify and compare "color and odor". A correlation analysis was conducted on the above results. The results showed that color of post-rancidness Armeniacae Semen Amarum changed from yellow to brown, with sour and lower content of laetrile. On the contrary, acid and peroxide values increased significantly, with changes in fatty acid component. There was a considerable correlation between appearance characteristics and changes in internal quality. The "sensory analysis-quality identification system" can provide a certain scientific basis for prediction of the content of chemical components in traditional Chinese medicine, preliminary judgment of quality of traditional Chinese medicine and real-time quality monitoring, which offers us novel ideas and reference for storage principles of traditional Chinese medicines of "pre-event prediction, during-event intervention and post-event identification".