Objective:To explore the feasibility and stability of using oleic acid to establish acute respiratory distress syndrome(ARDS) model in Beagle dogs.Methods:A total of 25 Beagle dogs were injected oleic acid with a speed of 0.25?0.03ml/Kg through jugular vein after being anesthetized.The gas ventilation index,oxygen metabolism,histopathological changes,chest-ray scan and stability of each index after establishing the ARDS situation were continuously monitored and evaluated.Results:All 25 dogs were reached the diagnosis criteria of ARDS in 4.16?0.92 hours after injection of oleic acid,The arterial PaCO2 of the animals was 27.98?8.25mmHg,PaO2 was 65.40?11.48mmHg,and PaO2/FiO2 was 182.3?29.6.After mechanical ventilation treatment,PaO2/FiO2≤200.Pulmonary mesenchyme,and alveolus edema,bleeding,shrinkage and transparent formation were seen under microscope.There was darkness or coarse shadow in the lung by the X-ray scan.Conclusions:Through injection of oleic acid via jugular vein,a Beagle dog ARDS model may be quickly established with stable changes of hemodynamics,pulmonary mechanics and histology.

Objective To understand the extensions of pharmaceutical care at medical institutions in China.Methods From June to October 2018, 196 cases were collected regarding " exploring new areas of pharmaceutical care" , which ranks one of the ten innovative medical services under China Healthcare Improvement Initiative(2018-2010). By means of statistics on the frequency of the subject words in the cases, the authors identified hotspots of these hospitals in this regard, and used descriptive analysis to study the data. Results The 196 cases covered 23 items of pharmaceutical care, including three traditional" guaranteed drug supply" services, i.e., drug supply, drug dispensing and drug storage management; one traditional Chinese medicine supply service, namely decoction and delivery of traditional Chinese medicine decoction; 19 pharmaceutical professional technical services, namely, prescription(doctor′s advice)review, patient education and guidance, and prescription ( doctor′s advice) comment among others. Conclusions The connotation of pharmaceutical care is extending rapidly. Therefore we should enhance the professional value of pharmacists, establish training programs for pharmaceutical talents, establish incentive mechanism for pharmaceutical care, and promote the rapid development of patient-centered pharmaceutical care.

Objective:To compare the surgical efficacy of pericardial soft ring tricuspid valvuloplasty with DeVega and artificial valvuloplasty.Methods:227 patients undergoing tricuspid valvuloplasty due to rheumatic heart disease complicated with functional tricuspid valve insufficiency were retrospectively analyzed and divided into 3 groups according to tricuspid valvuloplasty dynamic cohort(pericardial ring group, 89 cases; the artificial flap ring group, 61 cases, and the DeVega group, 77 cases) were matched 1∶1 for propensity score(match A: pericardial ring group and artificial flap ring group; match B: pericardial ring group and DeVega group), the successful matching was included in follow-up and data collection, and cases with incomplete case data during follow-up were removed from the study cohort in pairs according to matching conditions. The results of follow-up 1 month, 6 months and 24 months after surgery were compared.Results:1 month after operation: the tricuspid valve regurgitant in all groups was significantly reduced or even disappeared compared with that before operation, and the right atrium and right ventricle were also smaller than that before operation, with statistical significance( P<0.05). 6 months after surgery: There was no statistical significance in the area of tricuspid regurgitation and right atrial/indoor diameter between all groups compared with the results one month after surgery( P>0.05), and there was no statistical significance in the recurrence rate of tricuspid regurgitation between all groups( P>0.05). 24 months after surgery: There were no significant differences in the recurrence rate of tricuspid regurgitation, area of tricuspid regurgitation and right atrial/indoor diameter between the two groups in matching A( P>0.05). There was no statistical significance in the right atrial/indoor diameter between the matched pericardial ring group and the Devega group, but the tricuspid valve regurgentation area of the Devega group at 24 months after surgery was higher than that of the Devega group at 1 month after surgery, and the difference was statistically significant( P<0.05). The regurgitation area and recurrence rate of tricuspid valve were significantly higher than those of pericardium-TVP group( P<0.05). Conclusion:Pericardial soft ring tricuspid valvuloplasty can effectively correct functional tricuspid valvuloplasty and reverse right heart remodeling, which is an effective tricuspid valvuloplasty.

An ammonium-tolerant mutant of Actinobacillus succinogenes, YZ25, was obtained in the medium containing 61-242 mmol/L NH4+ after DES mutagenesis. Succinic acid produced by the mutant YZ25 reached 32.68 g/L when the medium contains 50 g/L glucose and 121 mmol/L ammonium, which was increased by 180.5% compared with that of the parent strain. The effects of different ammonium salts on the growth of the mutant and its metabolic response to high ammonium concentrations were investigated. The results showed that low ammonium concentration could improve the specific growth rates of the mutants, while high ammonium concentration inhibited cell growth. The ammonia-nitrogen half-inhibition constants (Ki) for different ammonium salts were as follows: 215 mmol/L for (NH4)2SO4, 265 mmol/L for NH4HCO3, 235 mmol/L for NH4Cl, and 210 mmol/L for NH4NO3. The process of ammonium inhibition on the mutant YZ25 was investigated in 3.0 L stirred fermenter. When NH4OH was used to buffer the pH, cell growth was not inhibited. However, production of succinic acid and consumption of glucose gradually decreased when cells entered the stationary phase, and the glucose could not be utilized completely at the end of fermentation. The possible ammonium inhibition mechanism was discussed based on the metabolic pathway of A. succinogenes.
Actinobacillus ; genetics ; growth & development ; metabolism ; Bioreactors ; Drug Tolerance ; Fermentation ; Industrial Microbiology ; Mutation ; Quaternary Ammonium Compounds ; metabolism ; pharmacology ; Succinic Acid ; metabolism

Metastasis is the leading cause of human cancer deaths. Unfortunately, no approved drugs are available for anti-metastatic treatment. In our study, high-throughput sequencing-based high-throughput screening (HTS) and a breast cancer lung metastasis (BCLM)-associated gene signature were combined to discover anti-metastatic drugs. After screening of thousands of compounds, we identified Ponatinib as a BCLM inhibitor. Ponatinib significantly inhibited the migration and mammosphere formation of breast cancer cells in vitro and blocked BCLM in multiple mouse models. Mechanistically, Ponatinib represses the expression of BCLM-associated genes mainly through the ERK/c-Jun signaling pathway by inhibiting the transcription of JUN and accelerating the degradation of c-Jun protein. Notably, JUN expression levels were positively correlated with BCLM-associated gene expression and lung metastases in breast cancer patients. Collectively, we established a novel approach for the discovery of anti-metastatic drugs, identified Ponatinib as a new drug to inhibit BCLM and revealed c-Jun as a crucial factor and potential drug target for BCLM. Our study may facilitate the therapeutic treatment of BCLM as well as other metastases.

Objective    To evaluate the effectiveness and safety of proximal aortic repair (PAR) versus total arch replacement (TAR) for treatment of acute type A aortic dissection (ATAAD). Methods     An electronic search was conducted for clinical controlled studies on PAR versus TAR for patients with ATAAD published in Medline via PubMed, EMbase, The Cochrane Library, Web of Science, Wanfang Database and CNKI since their inception up to April 30, 2022. The quality of each study included was assessed by 2 evaluators and the necessary data were extracted. STATA 16 software was used to perform statistical analysis of the available data. Results    A total of 28 cohort studies involving 7 923 patients with ATAAD were included in this meta-analysis, of whom 5 710 patients received PAR and 2 213 patients underwent TAR, and 96.43% of the studies (27/28) were rated as high quality. The meta-analysis results showed that: (1) patients who underwent PAR had lower incidences of 30 d mortality [RR=0.62, 95%CI (0.50, 0.77), P<0.001], in-hospital mortality [RR=0.64, 95%CI (0.54, 0.77), P<0.001], and neurologic deficiency after surgery [RR=0.84, 95%CI (0.72, 0.98), P=0.032] than those who received TAR; (2) the cardiopulmonary bypass time [WMD=–52.07, 95%CI (–74.19, –29.94), P<0.001], circulatory arrest time [WMD=–10.14, 95%CI (–15.02, –5.26), P<0.001], and operation time [WMD=–101.68, 95%CI (–178.63, –24.73), P<0.001] were significantly shorter in PAR than those in TAR; (3) there was no statistical difference in mortality after discharge, rate of over 5-year survival, renal failure after surgery and re-intervention, volume of red blood cells transfusion and fresh-frozen plasma transfusion, or hospital stay between two surgical procedures. Conclusion     Compared with TAR, PAR has a shorter operation time and lower early and in-hospital mortality, but there is no difference in long-term outcomes or complications between the two procedures for patients with ATAAD.