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OBJECTIVE To evaluate the rationality of clinical application of polymyxin B in the inpatients of a third grade class A hospital，so as to provide evidence for the optimization of clinical scheme of the drug. METHODS A retrospective method was conducted on the electronic medical records of inpatients treated with Polymyxin B sulfate for injection from January 2020 to March 2022 to collect the basic information of patients， inpatient departments and time， infection diagnosis， results of pathogenic bacteria test， laboratory test indicators， usage and dosage， and combined medication，etc. Based on the drug instructions， according to relevant guidelines and consensus， the rationality， efficacy and safety of polymyxin B in inpatient were evaluated. RESULTS & CONCLUSIONS A total of 101 inpatients were included， respiratory system infection was the main cause （62.4%）. All patients had received the etiological examination， and the pathogen with the highest detection rate was carbapenem‑resistant Acinetobacter baumannii （40.6%）. One hundred patients were treated by intravenous drip， and 4 patients were treated by combination of aerosol inhalation or intrathecal injection； 99 patients were given the dose of 500 thousand units by continuous intravenous infusion， q12 h. Totally 51.5% of patients were treated for 7-14 days； and 77 patients were treated with other anti-Gram-negative drugs. There were unreasonable phenomena including too short time of medication （29.7%）， no combination of medication （23.8%）， and no indication of medication （17.8%）. The clinical effective rate of 101 patients treated with polymyxin B was 49.5%， and 16 patients （15.8%） had acute kidney injury during the treatment. Clinical pharmacists should actively participate in the clinical treatment of polymyxin B， formulate individualized treatment plans according to the guidelines/consensus and in combination with the patient’s condition and infection status to improve the rationality of clinical medication.
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OBJECTIVE：To define the core competitiveness of drug manufacturing enterprises ，and build its evaluation system. METHODS ：With“core competitiveness ”and“pharmaceutical”as Chinese and English keywords ，the laws ，policies and interpretation documents published on relevant Chinese government websites （from the inception/establishment of the database to June 2020，the same below ）were retrieved. Related literatures were collected from PubMed ，Embase，CBM，Wanfang database ， CNKI，VIP databases. The evidence-based research method was adopted to define the core competitiveness and elements of drug manufacturing enterprises. Based on above elements and retrieval method ，guideline database （National Guideline Clearinghouse ， Guidelines International Network ，Trip database ，The National Institute for Health and Care Excellence ）and systematic review ， health technology assessment （HTA），health economics evaluation research databases （NHS Economic Evaluation Database ，the Cochrane Library ，HTA，etc.）were retrieved. The output indexes of the core competitiveness of drug manufacturing enterprises were extracted ；according to the principles of scientificity ，hierarchy，comparability and comprehensiveness ，the evaluation system of core competitiveness of drug manufacturing enterprises was constructed. RESULTS & CONCLUSIONS ：The definition of core competitiveness of drug manufacturers is proposed as the strategic needs of the enterprises ，actively undertaking major national science and technology projects ，introducing top scientific and technological talents at home and abroad ，having independent intellectual property rights ，enhancing the ability of scientific and technological support ，strengthening original innovation ， increasing R&D investment ， strengthening key technology breakthrough ， perfecting the innovation mechanism of enterprises-univerisities-researches integration with enterprises as the main body. The elements included original innovation ， 60362951。 R&D investment and scientific and technological talents. Atotal of 25 original innovation output indexes [including two aspects of innovation system （such as national science and technology innovation base ，national laboratory ），innovation achievements （such as National Natural Science Award ， National Technological Invention Award ）]，1 R&D input-output indicator （R&D amount ），7 scientific and technological talent output indicators of production enterprises （such as those selected in the “National Million Talent Project ”，“National Outstanding Scientific and Technological Talents ”award） were extracted. The evaluation system composed of original innovation ，R&D investment and scientific and technological talents is constructed ，which can provide objective evaluation for core competitiveness of pharmaceutical manufacturing enterprises.
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Aim To study the effect of artesunate on immuno-injured hepatic fibrosis induced by bovine ser-um albumin in rat model and the effect of artesunate on hepatic stellate cells ( HSCs ) proliferation, so as to provide experimental evidence for clinical application of artesunate and the treatment of hepatic fibrosis. Methods The model of immuno-injured hepatic fibro-sis induced by bovine serum albumin was established in Wistar rats. Rats were randomly divided into 5 groups:normal group, model group, low dose of arte-sunate, middle dose of artesunate and high dose of ar-tesunate. Drugs were given to the corresponding thera-peutic groups, and then were continued once a day for two months. Distilled water was given to the rats of normal and model groups according to the same meth-od. Liver tissues were used for measuring the content of collagen, the rat serum activities of albumin( Alb) , alanine aminotransferase ( ALT ) and aspartate amin-otransferase(AST). Liver tissue’ s pathological chan-ges were observed by HE and collagen staining. Isola-ted and cultured rat primary HSCs in the flask for 10 days to make cells activated, MTT assay was used to detect rate of cellular proliferation; concentration of hydroxyproline in supernatant was detected by digestive method; the expression of p53 was investigated by Western blot and RT-PCR. Results Serum levels of Alb in model group were significantly lower ( P <0. 05 ) , and levels of ALT and AST in model group were significantly higher ( P <0. 05 ) compared with normal group. Levels of AST in low, middle and high dose groups(3. 2, 9. 6, 28. 8 mg·kg-1 ) were signifi-cantly lower(P <0. 05) compared with model group, and levels of ALT in high dose groups were significant-ly lower(P<0. 01) compared with model group. The contents of collagen in model groups were significantly higher(P<0. 01) compared with normal group, while the contents of collagen in therapy groups significantly decreased ( P < 0. 05 ) compared with model group. Activated HSCs treated with various concentrations of artesunate (150, 175, 200 μmol·L-1 ) were inhibi-ted on dose and time-effect relationships. Production/secretion of hydroxyproline decreased after HSCs was treated by artesunate for 24 h; the expression of p53 was up-regulated showed by Western blot and RT-PCR in artesunate treated cells. Conclusion Artesunate brings about anti-fibrosis in vitro and in vivo by increas-ing the expression of p53 .
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BACKGROUND: Activation of hepatic stellate cells (HSCs) plays an important role in the development of cirrhosis through the increased production of collagen. p53, the "guardian of the genome", is a transcription factor that can bind to promoter regions of hundreds of genes where it either activates or suppresses gene expression. Thereby, p53 serves as a tumor suppressor by inducing cell cycle arrest, apoptosis, senescence and DNA repair. Artesunate is a derivative of Artemisinin, Scholars had found it had more extensive pharmacological effects past 10 years. However, little is known about the expression of p53 in the effects of Artesunate on induction of apoptosis and inhibition of proliferation in rat HSCs. METHODOLOGY/PRINCIPAL FINDINGS: Isolated and cultured rat primary HSCs in the flask for 10 days to make cells activated. HSCs were divided into two groups: experimental groups and control groups, experimental groups included with various concentrations of Artesunate (125, 150, 175, 200, 225 µmol/L) for 24, 48 and 72 hours. Analysis of MTT revealed that activated HSCs treated with various concentrations of Artesunate (150-225 µmol/L) were inhibited on dose and time-effect relationships; Concentration of hydroxyproline in supernatant was detected by digestive method; Analysis of flow cytometry demonstrated that Artesunate could arrest cell cycle in G1 and induce apoptosis; The nuclear morphological changes in apoptotic cells were evaluated with DNA staining by Hoechst 33258 dye; The expression of p53 were up-regulated showed by western blotting and RT-PCR. CONCLUSION: Artesunate could inhibit HSCs proliferation in dose-dependent and time-dependent manners in vitro through increase the expression of p53.
