S1PR1 serves as a viable drug target against pulmonary fibrosis by increasing the integrity of the endothelial barrier of the lung

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

URA3 affects artemisinic acid production by an engineered Saccharomyces cerevisiae in pilot-scale fermentation / 生物工程学报

CRISPR/Cas9 has been widely used in engineering Saccharomyces cerevisiae for gene insertion, replacement and deletion due to its simplicity and high efficiency. The selectable markers of CRISPR/Cas9 systems are particularly useful for genome editing and Cas9-plasmids removing in yeast. In our previous research, GAL80 gene has been deleted by the plasmid pML104-mediated CRISPR/Cas9 system in an engineered yeast, in order to eliminate the requirement of galactose supplementation for induction. The maximum artemisinic acid production by engineered S. cerevisiae 1211-2 (740 mg/L) was comparable to that of the parental strain 1211 without galactose induction. Unfortunately, S. cerevisiae 1211-2 was inefficient in the utilization of the carbon source ethanol in the subsequent 50 L pilot fermentation experiment. The artemisinic acid yield in the engineered S. cerevisiae 1211-2 was only 20%-25% compared with that of S. cerevisiae 1211. The mutation of the selection marker URA3 was supposed to affect the growth and artemisinic acid production. A ura3 mutant was successfully restored by a recombinant plasmid pML104-KanMx4-u along with a 90 bp donor DNA, resulting in S. cerevisiae 1211-3. This mutant could grow normally in a fed-batch fermentor with mixed glucose and ethanol feeding, and the final artemisinic acid yield (> 20 g/L) was comparable to that of the parental strain S. cerevisiae 1211. In this study, an engineered yeast strain producing artemisinic acid without galactose induction was obtained. More importantly, it was the first report showing that the auxotrophic marker URA3 significantly affected artemisinic acid production in a pilot-scale fermentation with ethanol feeding, which provides a reference for the production of other natural products in yeast chassis.

Immunomodulatory activity of polysaccharides from Brassica rapa by activating Akt/NF-κB signaling / 中草药·英文版

Objective: To investigate the immunomodulatory activity of polysaccharides from the roots of Brassica rapa. Methods: The crude polysaccharide from roots of B. rapa (BRP) was extracted and purified to further investigate the active fraction of BRT for inducing macrophage phagocytosis. Results: Effects on RAW264.7 cells demonstrated that BRP behaved better phagocytic capacity and had potent immunomodulatory activity, including increasing production of nitric oxide (NO), tumor necrosis factor α (TNFα) and upregulating mRNA levels of inducible NO synthase (iNOS) and TNFα. Furthermore, modulation of macrophage by BRP was indicated to be mediated via the activation of Akt and nuclear factor-kappa B (NF-κB). Conclusion: The beneficial effects of BRP could be used as an immunotherapeutic adjuvant in treatment of inflammatory diseases.

Influence of bionic texture coronary stent on hemodynamics after implantation / 生物医学工程学杂志

To explore the influence of bionic texture coronary stents on hemodynamics, a type of bioabsorbable polylactic acid coronary stents was designed, for which a finite element analysis method was used to carry out simulation analysis on blood flow field after the implantation of bionic texture stents with three different shapes (rectangle, triangle and trapezoid), thus revealing the influence of groove shape and size on hemodynamics, and identifying the optimal solution of bionic texture groove. The results showed that the influence of bionic texture grooves of different shapes and sizes on the lower wall shear stress region had a certain regularity. Specifically, the improvement effect of grooves above 0.06 mm on blood flow characteristics was poor, and the effect of grooves below 0.06 mm was good. Furthermore, the smaller the size is, the better the improvement effect is, and the 0.02 mm triangular groove had the best improvement effect. Based on the results of this study, it is expected that bionic texture stents have provided a new method for reducing in-stent restenosis.

Advances of structure, function, and catalytic mechanism of methyl-coenzyme M reductase / 生物工程学报

Methanogens are unique microorganisms for methane production and the main contributor of the biogenic methane in atmosphere. Methyl-coenzyme M reductase (Mcr) catalyzes the last step of methane production in methanogenesis and the first step of methane activation in anaerobic oxidation of methane. The genes encoding this enzyme are highly conserved and are widely used as a marker in the identification and phylogenetic study of archaea. There has been a longstanding interest in its unique cofactor F430 and the underpinning mechanisms of enzymatic cleavage of alkane C-H bond. The recent breakthroughs of high-resolution protein and catalytic-transition-state structures further advanced the structure-function study of Mcr. In particular, the recent discovery of methyl-coenzyme M reductase-like (Mcr-like) enzymes that activates the anaerobic degradation of non-methane alkanes has attracted much interest in the molecular mechanisms of C-H activation without oxygen. This review summarized the advances on function-structure-mechanism study of Mcr/Mcr-like enzymes. Additionally, future directions in anaerobic oxidation of alkanes and greenhouse-gas control using Mcr/Mcr-like enzymes were proposed.

A novel S1P1 modulator IMMH002 ameliorates psoriasis in multiple animal models

Psoriasis is characterized by abnormal proliferation of keratinocytes, as well as infiltration of immune cells into the dermis and epidermis, causing itchy, scaly and erythematous plaques of skin. The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently. Here, we showed that IMMH002, a novel orally active S1P modulator, desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus. Using different psoriasis animal models, we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PASI score and pathological injure evaluation. Mechanistically, IMMH002 regulated CD3 T lymphocytes re-distribution by inducing lymphocytes' homing, thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus. Our results suggest that the novel S1P agonist, IMMH002, exert extraordinary capacity to rapidly modulate T lymphocytes distribution, representing a promising drug candidate for psoriasis treatment.

20()-Protopanaxatriol promotes the binding of P53 and DNA to regulate the antitumor network multiomic analysis

Although the tumor suppressor P53 is known to regulate a broad network of signaling pathways, it is still unclear how certain drugs influence these P53 signaling networks. Here, we used a comprehensive single-cell multiomics view of the effects of ginsenosides on cancer cells. Transcriptome and proteome profiling revealed that the antitumor activity of ginsenosides is closely associated with P53 protein. A miRNA-proteome interaction network revealed that P53 controlled the transcription of at least 38 proteins, and proteome-metabolome profiling analysis revealed that P53 regulated proteins involved in nucleotide metabolism, amino acid metabolism and "Warburg effect". The results of integrative multiomics analysis revealed P53 protein as a potential key target that influences the anti-tumor activity of ginsenosides. Furthermore, by applying affinity mass spectrometry (MS) screening and surface plasmon resonance fragment library screening, we confirmed that 20()-protopanaxatriol directly targeted adjacent regions of the P53 DNA-binding pocket and promoted the stability of P53-DNA interactions, which further induced a series of omics changes.

Practice of improving the management quality of critical care medicine based on informatization / 中华医院管理杂志

Informatization plays an important role in the management of clinical diagnosis and treatment. However, due to the specialty of the discipline, the informatization construction of critical care medicine(CCM)is faced with such problems as the inefficient application of data, the low compliance of diagnosis and treatment operation, and the lack of intelligent quality control tools. The authors discussed the new mode of CCM information management based on data driven. By upgrading clinical information system, establishing single disease control system, introducing comprehensive intelligent analysis platform and building open remote platform, the bottleneck of CCM informatization was broken. The information collection and interaction in ICU was realized, the automatic monitoring and early warning of diagnosis and treatment process was realized, the operation of medical staff according to the guidelines was effectively improved, and the ability of diagnosis and treatment and management efficiency was improved.Furthermore, the homogenization of regional critical medical information could be promoted.

Application of liquid biopsies in diagnosis and treatment of epithelial ovarian cancer / 国际肿瘤学杂志

Liquid biopsies have made a great progress in malignant tumors research.Circulating tumor cells,circulating tumor DNA and exosomes can be regarded as biomarkers to be applied in diagnosis of epithelial ovarian cancer,monitoring progress dynamically,estimating prognosis and drug resistance in chemotherapy,which can help doctors provide patients with individual treatment to realize precision medicine in epithelial ovarian cancer.

Establishment of the real-time monitoring information system of ICU nursing quality indicators and applications / 中国实用护理杂志

Objective To establish a set of ICU care quality indicators real-time monitoring information system. Methods Based on the evaluation index system of ICU nursing safety quality, the real-time monitoring information system of ICU nursing quality indicators is established which quality evaluation index of structure quality、process quality and outcome quality is planted. To investigate the satisfaction of ICU medical staff in the use of informatization system and compare the quality of care quality before and after the use of the system. Results The satisfaction of ICU nurses in reducing working load, recording time, operation convenience, parameter acquisition and quality index monitoring were all greater than 90％. System before and after six months of intensive medicine nursing quality indicators, the overall quality had improved.The rate of ventilator recumbent incorrect position, the nonconformity rate of oral cavity clean, incidence of catheter-associated urinary tract infections, incidence of central line-associated bloodstream infection, incidence of ventilator associated pneumonia before information system were 2.03％ (118/5806), 0.53％ (10/1883), 0.51‰(4/7818), 0, 1.55‰(9/5614), which were lower than 4.90％(275/5614), 3.92％(69/1734), 3.12‰(24/7685), 1.06‰(8/7547), 4.81‰(27/5614) after six months (χ2=8.16-70.56, P<0.01).The accidental release rate of artificial airway was not statistically significant (P> 0.05). Conclusion The ICU nursing quality indicator real- time monitoring information system makes nursing management digital, improves the satisfaction of medical staff, and significantly improves the quality of care.

Clinical Study on Acupuncture plus Medication and Kinesiotherapy for Cerebral Stroke / 上海针灸杂志

Objective To observe the clinical efficacy of acupuncture plus medication and kinesiotherapy in treating cerebral stroke.Method A total of 126 patients with cerebral stroke were randomized into a treatment group of 42 cases, control group 1 of 40 cases and control group 2 of 44 cases. The treatment group was intervened by acupuncture, Chinese medication plus kinesiotherapy, control group 1 by acupuncture alone and control group 2 by kinesiotherapy alone. Before the intervention and respectively after 2-week and 4-week treatment, the three groups were observed by adopting the modified Barthel Index (MBI) and Fugl-Meyer Assessment (FMA), as well as the Activities of Daily Living (ADL).Result After the treatment, the MBI score, FMA score and ADL grading were significantly changed in the three groups (P<0.01). After 4-week treatment, the MBI score in the treatment group was significantly different from that in control group 2 (P<0.05). After 4-week treatment, the FMA score and ADL grading in the treatment group were significantly different from those in both control group 1 and 2 (P<0.05).Conclusion Acupuncture plus medication and kinesiotherapy is an effective approach in treating cerebral stroke and it can improve the ADL.

Therapeutic Observation of Electroacupuncture plus Moxibustion for Infantile Cerebral Palsy / 上海针灸杂志

Objective To observe the clinical efficacy of electroacupuncture plus moxibustion in treating infantile cerebral palsy. Method Eighty eligible patients with infantile cerebral palsy were randomized into a treatment group of 42 cases and a control group of 38 cases. The control group was intervened by physiotherapy (PT), while the treatment group was given electroacupuncture at scalp acupoints, body acupuncture, and moxibustion along the Governor Vessel in addition to the treatment given to the control group. The two groups were treated once a day, 6 months in total. The comprehensive ability and the Gross Motor Function Measure (GMFM) were evaluated before and after the interventions in the two groups, and the clinical efficacies were compared.Result After 6-month treatment, the total effective rate was 92.9% in the treatment group versus 78.9% in the control group, and the total effective rate of the treatment group was superior to that of the control group (P<0.05). The motor function and activities of daily living were significantly improved in both groups after the interventions (P<0.05,P<0.01); after the treatment, there were significant differences in comparing the motor function and activities of daily living between the two groups (P<0.05). The GMFM scores of each domain were significantly changed after the treatment in both groups (P<0.05); after the treatment, there were significant differences in comparing the GMFM scores of each domain between the two groups (P<0.05).Conclusion Compared with being used alone, conventional PT can more significantly benefit the improvement of motor function of cerebral palsy patients when electroacupuncture and moxibustion were added.

Multidisciplinary team confirmed the simultaneous diagnosis of CLL and AML-M5 / 中国肿瘤临床

A 54-year-old man diagnosed with chronic lymphocytic leukemia (CLL) was admitted in our department in June 2014. After one cycle of FC chemotherapy, a bone marrow examination revealed normalized lymphocyte count and another acute myeloid leuke-mia (AML)-M5 clone. The patient refused sequential treatment and only received follow-up examination. He had continuous hemato-logically stable disease and died of pulmonary infection on July 2015. After a multidisciplinary team discussion, we confirmed the si-multaneous diagnosis of CLL and AML-M5. Through this discussion,tumor second hit model,tumor evolution model,andtumor heterogeneitywere further defined.

Effect of central venous pressure waveforms on location of power PICC tip localization / 现代临床护理

Objective To explore the effect of central venous pressure waveforms on the location of power PICC tip. Methods From January 2015 to December 2015, we placed power PICC for 47 patients in our intensive care unit. The CVP waveforms were applied to detect any displacement into small thoracic veins after a four-step localization method. The position of the catheter tip was finally confirmed by X-ray inspection. Results Among the 47 cases undergoing PICC implantation, 45(95.75%) displayed a typical CVP waveform, with the catheter tip positions were located in the superior vena cava inferior segment, 1 (2.13%) displayed a typical CVP waveform, with the catheter tip was misplaced into axillary vein and retraced and 1(2.13%) did not display typical CVP waveforms and CVP value was negative, with the catheter tip was in left internal jugular vein. To locate the catheter tip position with CVP waveform and chest X-rang were 100.00%the same. Conclusions The central venous pressure waveform can be used to determine whether the catheter tip is located in the inferior segment of the superior vena cava or not immediately after the placement of a power PICC. However, chest X-ray inspection conformation is still needed.

Effect of central venous pressure waveforms on location of power PICC tip localization / 现代临床护理

Objective To explore the effect of central venous pressure waveforms on the location of power PICC tip. Methods From January 2015 to December 2015, we placed power PICC for 47 patients in our intensive care unit. The CVP waveforms were applied to detect any displacement into small thoracic veins after a four-step localization method. The position of the catheter tip was finally confirmed by X-ray inspection. Results Among the 47 cases undergoing PICC implantation, 45(95.75%) displayed a typical CVP waveform, with the catheter tip positions were located in the superior vena cava inferior segment, 1 (2.13%) displayed a typical CVP waveform, with the catheter tip was misplaced into axillary vein and retraced and 1(2.13%) did not display typical CVP waveforms and CVP value was negative, with the catheter tip was in left internal jugular vein. To locate the catheter tip position with CVP waveform and chest X-rang were 100.00%the same. Conclusions The central venous pressure waveform can be used to determine whether the catheter tip is located in the inferior segment of the superior vena cava or not immediately after the placement of a power PICC. However, chest X-ray inspection conformation is still needed.

Biological characteristics of endothelial progenitor cells derived from granulocyte colony-stimulating factor mobilized peripheral blood / 中国组织工程研究

BACKGROUND:Endothelial progenitor cells have good prospects for clinical application;especial y as seed cells, they are involved in construction of tissue engineered blood vessels and disease treatment. OBJECTIVE:To investigate the biological characteristics of endothelial progenitor cells derived from granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood. METHODS:Mononuclear cells from G-CSF mobilized peripheral blood (n=9) and normal adult peripheral blood (n=8) were obtained and cultured in expanded medium. The immunophenotype of endothelial progenitor cells was investigated by FACS and immunohistochemistry. Real-time PCR was used to detect the expression of different cytokines. Proliferation and adhesion ability of endothelial progenitor cells were detected by MTT assay and adhesion assay. Moreover, the abilities of vasculogenesis in vitro and Dil-labeled acetylated low density lipoprotein uptake were detected. The acquired cells were seeded onto the basilar membrane gel containing vascular endothelial growth factor and basic fibroblast growth factor to induce angiogenesis. RESULTS AND CONCLUSION:Endothelial progenitor cells derived from G-CSF mobilized peripheral blood were similar to those from normal adult peripheral blood in phenotype and morphology. FACSs and immunohistochemistry showed that endothelial progenitor cells were positive for endothelial cellmarkers, such as CD31, vWF, CD34, FLK-1, VE-Cadherin and CD133. In addition, the expression of vascular endothelial growth factor and stromal cel-derived factor 1 were significantly increased in G-CSF mobilized endothelial progenitor cells. Moreover, endothelial progenitor cells derived from two sources possessed the abilities of angiogenesis in vitro and Dil-labeled acetylated low density lipoprotein uptake. But, the number and the proliferation ability of endothelial progenitor cells derived from G-CSF mobilized peripheral blood were better than that of endothelial progenitor cells derived from normal adult peripheral blood. These findings indicate that there is a population of cells with characteristics of endothelial progenitor cells in G-CSF mobilized peripheral blood. They possess the abilities of vasculogenesis in vitro. Moreover, compared to endothelial progenitor cells derived from normal adult peripheral blood, we could obtain more endothelial progenitor cells in G-CSF mobilized peripheral blood and those cells show better proliferation ability.

Immunogenicity, immune mechanisms and immune modulatory effects of mesenchymal stem cells derived from bone marrow of patients with multiple myeloma / 中华器官移植杂志

Objective To study the immunogenicity,immune modulatory effects and mechanisms of mesenthymal stem ceils (MSCs) derived from the bone marrow of patients with multiple myeloma (MM).Methods The mononuclear cells from the bone marrow of MM patients were obtained and cultured.Immunophenotypes were investigated by using FACS.The levels of cytokines were determined by using enzyme linked immunosorbant assay (ELISA).The endocytosis of monocyte-derived dendritic cells (DCs) was investigated by using FACS.Moreover,the immunoregulatory ability of DCs on proliferation of T lymphocytes was detected by using mixed lymphocyte culture assay.Results MM-derived MSCs had no expression of HLA-DR and costirnulatory molecules (CD40,CD80,CD83 and CD86).MM-derived MSCs could significantly suppress proliferation of T lymphocytes in a dose-dependent manner,which could be reversed by antiTGF-β1 and anti-HGF antibodies.MM-derived MSCs inhibit the endocytosis of DCs.MM-derived MSCs could inhibit the secretion of IL-12 and significantly inhibit the function of DCs on proliferation of T lymphocytes.Conclusion MM-derived MSCs harbored low immunogenicity and immunoregulatory effect in vitro,and this effect was achieved through cytokines.

Clinical Effect of Cetuximab Combined with Chemotheraphy on Metastastic Colorectal Cancer / 中国肿瘤临床

Objective: To evaluate the efficacy and the adverse reactoions of cetuximab combined with cheomotherapy (oxapliplatin or iriticon) for metastastic colorectal cancer. Methods: A total of 22 patients with metastastic colorectal cancer were treated with cetuximab combined with FOLFIRI or mFOLFOX6. The patients received cetuximab at an initial dose of 400 mg/m~2 intravenously on day 1 in the first cycle, followed by weekly infusion of 250 mg/m~2; FOLFIRI: irinotecan 180 mg/ m~2 on day 1, CF 400 mg/m~2, 5-FU bolus 400 mg/m~2, 5-FU infusion 2400 mg/m~2 over 46 hours, once every 2 weeks; mFOLF-OX6: oxaliplatin 85mg/m~2 on day 1, CF 400 mg/m~2, 5-FU bolus 400 mg/m~2, 5-FU infusion 2400 mg/m~2 over 46 hours, once every 2 weeks. The immediate response, complete response and partial response and changes in tumor marker levels were observed. Results: There were 12 PR cases, 6 SD cases, and no CR cases. The rate of (CR+PR) was 57.1% and the rate of (CR+PR+SD) was 85.7%. The adverse reactions during the theraphy were skin toxicity and neutropenia. Conclu-sion: Safe and effective for metastastic colorectal cancer, cituximab combined with oxaliplatin or irinotecan can increase the resectabiliy rate and prolong patient survival.

Ethics Value Foundation of the Hygiene Economic Policy / 中国医学伦理学

Abstract: Hygiene economic policy results from value choosing, so the research on hygiene economic policy must pay more attention to the value problems. Nowadays, our hygiene economic policy should base on these ethical principles, such as"Health Fairness","Hygiene Justice", which decide that the formulation and implementation of hygiene economic policy must reflect the value orientation.