Aim To observe the effect of epimedium on the proliferation and stem cell-like character expression of breast cancer cells, and investigate the relationship between the inhibition of stem cell-like character and miR-148a by epimedium, and its molecular mechanism. Methods After treatment with different concentrations of epimedium, cell viability and population dependence were detected by MTT assay and colony formation assay; the breast cancer stem cell-derived mammosphere formation was examined by Mammosphere assay; the expression levels of CD44,ALDH-1, Oct4,BMIl and EpCAM were detected by qPCR; the protein expression levels of EpCAM, SOX4, ZO-1, E-cadherin and vimentin were detected by Western blot; the protein localization of EpCAM was observed by im-munofluorescence assay; the effect of epimedium on migration was detected by wound healing assay. The miR-148a mimic was transfected into MDA-MB-231 cells, and the effects of epimedium on stem-like character expression of transfected MDA-MB-231 cells were observed. Results Epimedium significantly inhibited the proliferation and population dependence of MDA-MB-231 cells (P < 0.05 ), and reduced the breast cancer stem cell-derived mammosphere formation; compared with control group, epimedium significantly decreased mRNA levels of CD44, ALDH-1, Oct4, BMI1 and EpCAM (P <0.05) ,decreased protein contents of EpCAM, SOX4 and Vimentin (P < 0.05 ), up-regulated the protein expression of ZO-1 and e-cadherin ( P <0.05) ,and decreased the migration ability of MDA-MB-231 cells (P < 0.05). Epimedium up-regulated the expression of miR-148a in MDA-MB-231 cells (P <0.01). YYH + miR-148a mimic group significantly inhibited stem-like character expression and EMT process of breast cancer MDA-MB-231 cells compared with control group (P <0.05). Conclusions Epimedium can inhibit the proliferation of MDA-MB-231 cells, which may be related to the up-regulation of miR-148a, decrease of stem-like character expression of breast cancer cells,and inhibition of EMT.

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.
China ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Prescriptions ; Public Health

OBJECTIVE: To investigate whether Lingbao Huxin Pill (LBHX) protects against acute myocardial infarction (AMI) at the infarct border zone (IBZ) of myocardial tissue by regulating apoptosis and inflammation through the sirtuin 1 (SIRT1)-mediated forkhead box protein O1 (FOXO1) and nuclear factor-κ B (NF-κ B) signaling pathways. METHODS: Six-week-old Wistar rats with normal diet were randomized into the sham, the model, Betaloc (0.9 mg/kg daily), LBHX-L (0.45 mg/kg daily), LBHX-M (0.9 mg/kg daily), LBHX-H (1.8 mg/kg daily), and LBHX+EX527 (0.9 mg/kg daily) groups according to the method of random number table, 13 in each group. In this study, left anterior descending coronary artery (LADCA) ligation was performed to induce an AMI model in rats. The myocardial infarction area was examined using a 2,3,5-triphenyltetrazolium chloride solution staining assay. A TdT-mediated dUTP nick-end labeling (TUNEL) assay was conducted to assess cardiomyocyte apoptosis in the IBZ. The histopathology of myocardial tissue at the IBZ was assessed with Heidenhain, Masson and hematoxylineosin (HE) staining assays. The expression levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1 β, and intercellular adhesion molecule-1 were measured using enzyme-linked immunosorbent assays (ELISAs). The mRNA expressions of SIRT1 and FOXO1 were detected by real-time qPCR (RT-qPCR). The protein expressions of SIRT1, FOXO1, SOD2, BAX and NF- κ B p65 were detected by Western blot analysis. RESULTS: The ligation of the LADCA successfully induced an AMI model. The LBHX pretreatment reduced the infarct size in the AMI rats (P<0.01). The TUNEL assay revealed that LBHX inhibited cardiomyocyte apoptosis at the IBZ. Further, the histological examination showed that the LBHX pretreatment decreased the ischemic area of myocardial tissue (P<0.05), myocardial interstitial collagen deposition (P<0.05) and inflammation at the IBZ. The ELISA results indicated that LBHX decreased the serum levels of inflammatory cytokines in the AMI rats (P<0.05 or P<0.01). Furthermore, Western blot analysis revealed that the LBHX pretreatment upregulated the protein levels of SIRT1, FOXO1 and SOD2 (P<0.05) and downregulated NF- κ B p65 and BAX expressions (P<0.05). The RT-qPCR results showed that LBHX increased the SIRT1 mRNA and FOXO1 mRNA levels (P<0.05). These protective effects, including inhibiting apoptosis and alleviating inflammation in the IBZ, were partially abolished by EX527, an inhibitor of SIRT1. CONCLUSION LBHX could protect against AMI by suppressing apoptosis and inflammation in AMI rats and the SIRT1-mediated FOXO1 and NF- κ B signaling pathways were involved in the cardioprotection effect of LBHX.
Animals ; Apoptosis ; Drugs, Chinese Herbal ; Inflammation/metabolism* ; Myocardial Infarction/pathology* ; NF-kappa B/metabolism* ; Nerve Tissue Proteins ; Rats ; Rats, Wistar ; Sirtuin 1/genetics*

OBJECTIVE: To explore the influence of controlling nutritional status (CONUT) score on the prognosis of newly diagnosed patients with multiple myeloma (MM). METHODS: The clinical data 119 patients with MM who were diagnosed according to the international myeloma diagnostic criteria in Lanzhou University Second Hospital from April 2010 to October 2018 were collected and retrospectively analyzed. The relationship between clinical indexes, including age, sex, MM type, absolute lymphocyte count (ALC), absolute neutrophil count (ANC), absolute monocyte count (AMC), hemoglobin (Hb), platelet (PLT), β RESULTS: Compared with high-scoring group, low-scoring group had a better OS ［median OS was 43.3 months and 127.67 months, respectively, 95% confidence interval (CI): 57.065-78.345, P=0.038］. At the same time, the low-scoring group also had higher level of ALC, ANC, AMC, Hb, PLT, ALB, and CHO but lower of GLO. Multivariate survival analysis showed that age (HR=1.027, 95%CI: 1.000-1.054, P=0.048), AMC (HR=11.284, 95%CI: 22.968-42.897, P<0.001), CONUT score (HR=1.198, 95%CI: 1.036-1.385, P=0.015), M protein (non-IgG/IgG type) type (HR=0.503, 95%CI: 0.259-0.977, P=0.043) were independent factors affecting the prognosis of MM patients. CONCLUSION The CONUT score as an immune-nutrition score is a convenient and easy-to-obtain index to effectively predict the prognosis of MM patients.
Humans ; Lymphocyte Count ; Multiple Myeloma/diagnosis* ; Nutritional Status ; Prognosis ; Retrospective Studies

To investigate the potential molecular markers and drug-compound-target mechanism of Mahuang Shengma Decoction(MHSM) in the intervention of acute lung injury(ALI) by network pharmacology and experimental verification. Databases such as TCMSP, TCMIO, and STITCH were used to predict the possible targets of MHSM components and OMIM and Gene Cards were employed to obtain ALI targets. The common differentially expressed genes(DEGs) were therefore obtained. The network diagram of DEGs of MHSM intervention in ALI was constructed by Cytoscape 3. 8. 0, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of target genes. The ALI model was induced by abdominal injection of lipopolysaccharide(LPS) in mice. Bronchoalveolar lavage fluid(BALF) was collected for the detection of inflammatory factors. Pathological sectioning and RT-PCR experiments were performed to verify the therapeutic efficacy of MHSM on ALI. A total of 494 common targets of MHSM and ALI were obtained. Among the top 20 key active compounds of MHSM, 14 from Ephedrae Herba were found to be reacted with pivotal genes of ALI [such as tumor necrosis factor(TNF), tumor protein 53(TP53), interleukin 6(IL6), Toll-like receptor 4(TLR4), and nuclear factor-κB(NF-κB)/p65(RELA)], causing an uncontrolled inflammatory response with activated cascade amplification. Pathway analysis revealed that the mechanism of MHSM in the treatment of ALI mainly involved AGE-RAGE, cancer pathways, PI3 K-AKT signaling pathway, and NF-κB signaling pathway. The findings demonstrated that MHSM could dwindle the content of s RAGE, IL-6, and TNF-α in the BALF of ALI mice, relieve the infiltration of inflammatory cells in the lungs, inhibit alveolar wall thickening, reduce the acute inflammation-induced pulmonary congestion and hemorrhage, and counteract transcriptional activities of Ager-RAGE and NF-κB p65. MHSM could also synergically act on the target DEGs of ALI and alleviate pulmonary pathological injury and inflammatory response, which might be achieved by inhibiting the expression of the key gene Ager-RAGE in RAGE/NF-κB signaling pathway and downstream signal NF-κB p65.
Acute Lung Injury/genetics* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Lipopolysaccharides ; Lung/metabolism* ; Mice ; NF-kappa B/metabolism* ; Network Pharmacology ; Receptor for Advanced Glycation End Products/metabolism* ; Signal Transduction

Objective:To explore the efficacy of rituximab combined with ABVD (epirubicin+ bleomycin+ vindesine +dacarbazine) regimen in treatment of Hodgkin lymphoma (HL) complicated with autoimmune hemolytic anemia (AIHA).Methods:The clinical data of 1 HL patient complicated with AIHA in November 2019 in Henan Cancer Hospital were retrospectively analyzed, and literatures were reviewed.Results:The patient received left cervical lymph node biopsy and bone marrow biopsy, and then lymphoma-related gene mutations and whole genetic genome detection were performed. The patient was diagnosed as HL (tuberous sclerosis in stage Ⅳ) complicated with AIHA. After 6 cycles of rituximab combined with ABVD regimen, the efficacy was evaluated. This patient's anemia was recovered, and HL also achieved complete remission.Conclusions:Rituximab combined with ABVD regimen is effective in treatment of HL patients complicated with AIHA.

Abscess ; Anti-Bacterial Agents/therapeutic use* ; Cerebral Ventriculitis/drug therapy* ; Encephalitis/drug therapy* ; Humans ; Pneumonia/etiology*

Objective:Cardiopulmonary resuscitation quality index (CQI) is based on pulse oximetry plethysmographic waveform (POP), which have been proved able to reflect the peripheral circulation state as good as the quality of chest compression during cardiopulmonary resuscitation (CPR). It has been confirmed that CQI is as good as the partial pressure of end-tidal carbon dioxide (P ETCO 2) in prognostic evaluation of CPR patients. The purpose of this study was to explore whether advanced airway establishment affects the prognostic value of CQI during CPR. Methods:This was a prospective descriptive study. 376 patients receiving CPR were divided into advanced airway group and non-advanced airway group according to whether advanced airway was established, each of which was divided into ROSC (return of spontaneous circulation) group and non-ROSC group according to whether they got ROSC. The changes of CQI and P ETCO 2 during CPR were collected, and the relation of these parameters and the prognosis of patients was analyzed. Results:In advanced airway group, both CQI [(63.3±20.7) vs (49.7±23.8)] and P ETCO 2 [(19.8 (11.4, 31.6) vs 8.8 (3.3, 15.8)] mmHg were statistically different between ROSC group and non-ROSC group ( P <0.05). The cut-off value for these two parameters were 60.4 and 16.3 mmHg respectively. There was no significant difference between the two curves ( P>0.05). In the non-advanced airway group, CQI [(63.0±21.8) vs (42.2±29.0)] were also statistically different between the ROSC group and the non-ROSC group ( P <0.05). The cut-off value of CQI in advanced airway group and non-advanced airway group were 60.4 and 61.1, respectively. And there was no statistical difference between the two curves ( P>0.05). Conclusions:During CPR, CQI can be used to evaluate the prognosis of patients, which is as good as that of P ETCO 2. Establishment of advanced airway does not affect the prognostic evaluation of CQI during CPR.

Objectives: To explore the modulating effects and related mechanisms of p53-miR-34a-SIRT1 feedback loop in the process of replication senescence of vascular endothelial progenitor cells (EPC). Methods: EPC derived from umbilical cord blood were cultured and identified. Differences on senescence, cell apoptosis, cell cycle and blood tube formation were observed in EPC of 3rdand 6thgeneration. Protein expression of p53, Acetyl-p53, and SIRT1 was also detected by Western blotting in EPC of 3rdand 6thgeneration. The miR-34a inhibitor lentiviral vector was constructed and used to identify whether miR-34a inhibitor can protect 6thgeneration EPC from apoptosis. Results: EPC derived from umbilical cord blood were successfully cultured. The cells senescence rate and apoptosis rate of the 6thgeneration EPC were significantly higher than those of the 3rdgeneration EPC. The cell cycle of 6thgeneration EPC was mainly arrested at G0/G1 phase. The protein expression level of p53 was significantly higher, while the protein expression of acetyl-p53 and SIRT1 was significantly lower in the 6thgeneration EPC than in the 3rdgeneration EPC, all P<0.05. The senescence was significantly attenuated, and late apoptotic cells were significantly reduced, while angiogenesis ability was significantly enhanced in the 6thgeneration EPC transfected with lentiviral vector carrying miR-34a inhibitor. Conclusions: p53-miR-34a-SIRT1 is an important feedback mechanism in the process of EPC replication senescence. The miR-34a inhibitor may be the potential target of delaying EPC senescence.