Background: Gout is the most prevalent form of inflammatory arthritis in the world. Total hip arthroplasty (THA) has emerged as a widely sought-after and highly effective surgical procedure for advanced hip diseases. However, there is a lack of research on the impact of gout on primary THA outcomes in large cohorts. This study aimed to address this gap by primarily investigating complications following THA in patients with or without gout. Methods: Patients with records of gout in the 2 years leading up to their primary THA and who also have at least 2 years of follow-up were identified using a national insurance database and compared to a 5:1 matched control. A total of 32,466 patients with gout and 161,514 patients without gout undergoing THA were identified. Multivariable logistic regression analyses were done for medical complications up to 90 days and surgical complications up to 2 years. In addition, 90-day emergency department (ED) visits and inpatient readmission were also documented. Results: Patients with gout demonstrated higher rates of medical complications including deep vein thrombosis, transfusion, acute kidney injury, and urinary tract infection than non-gout patients (p < 0.001). Gout patients also showed higher rates of pulmonary embolism (p = 0.017). Increased incidences of surgical complications were identified in gout patients, specifically wound complications and periprosthetic joint infection (p < 0.001). There was an increased risk of revision for gout patients up to 90 days (p = 0.003), 1 year (p = 0.027), and 2 years (p = 0.039). There was also an increased risk of dislocation for gout patients up to 90 days (p = 0.022) and 1 year (p = 0.047), but not at 2 years. No significant difference was observed in aseptic loosening or periprosthetic fracture. Additionally, gout patients also demonstrated a higher likelihood of 90-day ED visits and readmission (p < 0.001). Conclusions Primary THA in gout patients is associated with increased risks of multiple medical and surgical complications. Our findings provide insights into the planning and expectation of THA for patients with gout. These insights have the potential to benefit the decision-making process for gout patients considering THA.

OBJECTIVE To investigate the improvement effects and mechanism of imperatorin on cachexia model mice. METHODS Fifteen male C57BL/6J mice were randomly divided into blank control group， model group and imperatorin group， with 5 mice in each group. Except for blank control group， the remaining mice were inoculated with LLC cell suspension subcutaneously on the dorsal surface， and the drug was administered by gavage daily from the 7th day of inoculation. The imperatorin group was gavaged with imperatorin suspension （0.5% sodium carboxymethylcellulose solution as solvent） at 60 mg/kg； blank control group and model group were given an equal volume of 0.5% sodium carboxymethylcellulose solution， for 13 d of continuous administration. During the administration period， food intake and body mass of mice were recorded daily and regularly， tumor long and short diameters were measured every two days， and tumor volume was calculated. The skeletal muscle mass and tumor mass of each group were weighed and the tumor-free body weight was calculated； the pathological changes of skeletal muscle were observed and the cross-sectional area of skeletal muscle fibers was calculated； the phosphorylation levels of signal transduction and activator of transcription 3 （STAT3） （measured as p-STAT3/STAT3 ratio）， muscle atrophy box F gene （MAFbx）， myostatin （Myog）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， Caspase3 protein and mRNA expression were all detected. RESULTS Compared with blank control group， body mass and skeletal muscle mass of model group were decreased significantly （P＜0.05）， and reduced food intake， loose arrangement of skeletal muscle， large cell space were observed； the cross-sectional area of skeletal muscle fiber was significantly reduced， while p-STAT3/STAT3 ratio， protein and mRNA expressions of MAFbx， Bax and Caspase3 were somo_amour@163.com increased significantly （P＜0.05）. The protein and mRNA expressions of Myog and Bcl-2 were significantly reduced （P＜ 0.05）. Compared with model group， body weight， tumor-free weight and skeletal muscle weight were increased significantly in imperatorin group （P＜0.05）； food intake increased， while the expressions of tumor weight and volume were decreased significantly （P＜0.05）； the expressions of above proteins and genes were improved significantly （P＜0.05）. CONCLUSIONS Imperatorin can improve the tumor cachexia state， the mechanism of which may be related to the regulation of ubiquitin-proteasome pathway and anti-apoptosis.

OBJECT IVE To analyze the situation of comprehensive drug evaluation research in China. METHODS Using the method of bibliometrics ，CiteSpace 5.8.R3 analysis tool was used to summarize the research situation and hotspots from 6 dimensions，such as safety ，effectiveness，economy，innovation，suitability and accessibility. RESULTS & CONCLUSIONS At present，there were many types of researches on safety and effectiveness. The economic evaluation was increasing. There were still not much researches on the comprehensive evaluation of drugs from 6 dimensions. Researchers were concentrated ，and there was less collaboration between researchers or research institutions. In terms of methods ，systematic review ，meta-analysis，clinical observational research and retrospective research were more common. The topic selection of antibacterial drugs ，anti-tumor drugs ， and cardiovascular drugs were more popular. It is recommended to establish a unified method and standard for clinical comprehensive evaluation of drugs ，clarify the coordination medianism of the comprehensive drug evaluation ，make full use of real-world data to enrich the contents of 6 dimensions，implement quality control for all segments of the evaluation ，and form a comprehensive evaluation report with sufficient evidence and definite results ，so as to promote the clinical application of the results.

PURPOSE: Lung adenocarcinoma (LA) is one of the major types of lung cancer. MicroRNAs (miRNAs) play an essential role in regulating responses of natural killer (NK) cells to cancer malignancy. However, the mechanism of miR-218-5p involved in the killing effect of NK cells to LA cells remains poorly understood. MATERIALS AND METHODS: The expression of miR-218-5p was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Serine hydroxymethyl transferase 1 (SHMT1) level was detected by qRT-PCR or western blots. Cytokines production of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were detected by ELISA. The killing effect of NK cells to LA cells was investigated using lactate dehydrogenase cytotoxicity assay kit. The interaction of miR-218-5p and SHMT1 was probed by luciferase activity assay. Xenograft model was established to investigate the killing effect of NK cells in vivo. RESULTS: miR-218-5p was enhanced and SHMT1 was inhibited in NK cells of LA patients, whereas stimulation of interleukin-2 (IL-2) reversed their abundances. Addition of miR-218-5p reduced IL-2-induced cytokines expression and cytotoxicity in NK-92 against LA cells. Moreover, SHMT1 was negatively regulated by miR-218-5p and attenuated miR-218-5p-mediated effect on cytotoxicity, IFN-γ and TNF-α secretion in IL-2-activated NK cells. In addition, miR-218-5p exhaustion inhibited tumor growth by promoting killing effect of NK cells. CONCLUSION: miR-218-5p suppresses the killing effect of NK cells to LA cells by targeting SHMT1, providing a potential target for LA treatment by ameliorating NK cells function.
Adenocarcinoma ; Blotting, Western ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Heterografts ; Homicide ; Humans ; Interleukin-2 ; Killer Cells, Natural ; L-Lactate Dehydrogenase ; Luciferases ; Lung Neoplasms ; Lung ; MicroRNAs ; Necrosis ; Real-Time Polymerase Chain Reaction ; Serine ; Transferases

Mitochondrial diseases are maternally inherited heterogeneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruction of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m.3243A>G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes (MELAS). We engineered mitochondrial-targeted transcription activator-like effector nucleases (mitoTALENs) and successfully eliminated the m.3243A>G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Furthermore, we successfully achieved reduction in the human m.3243A>G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.
Animals ; DNA, Mitochondrial ; genetics ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; MELAS Syndrome ; genetics ; Male ; Mice ; Microsatellite Repeats ; genetics ; Mitochondria ; genetics ; metabolism ; Mutation ; genetics

OBJECTIVE:To construct integrated medication decision-making system,and to provide reference for safe,effec-tive,economical and reasonable drug use in clinic. METHODS:The construction of integrated medication decision-making system was introduced in our hospital. RESULTS&CONCLUSIONS:The integrated medication decision-making system included three as-pects as real-time intervention in advance,interactive review in the matter,afterward comment and analysis,as 3 steps before and after the implementation of inpatient medical order and outpatient prescription. The real-time intervention in advance was mainly to control the rationality of medical orders or prescriptions from their source,thus requiring the timely treatment. The interactive re-view in the matter required that pharmacists judged the medical order or prescription and made a decision of refusing prescribing within the fixed time. To make a decision accurately,the clinical information should be highly structured and correlated with drug signs. Afterward comment and analysis required that pharmacists evaluated the medical order or prescription regularly after the im-plementation. The three were not only different,but also coordinated,and they were an organic unity,especially interactive review in the matter needed to be coordinated with the other two processes. After the implementation of integrated medication decision-mak-ing system,the proportion of irrational medical orders or prescriptions in our hospital decreased from 6.07％ in the first half of 2016 to 2.56％ at corresponding period of 2017. Drug dose errors and incompatibility were greatly reduced,and medication against contraindications was more likely to be found in the review and analysis. The system can improve the efficiency of prescription re-view,improve rational drug use,and effectively ensure the safety,effectiveness,economy and rationality of clinical drug use.

Orphan nuclear receptor NR4A1 from the NR4A subfamily is one of the transcriptional factors that have not identified specific ligands .Previous studies have found that NR4A1 could regulate cell proliferation ,apoptosis ,differentiation and stress responses by changing gene expression ,post-translational modification and interactions between coregulatory pro-teins .Recently ,it has shown that NR4A1 has an abnormal expression in human atherosclerotic lesions and has been identified as a key regulator gene in vascular cells dysfunction .Regulating NR4A1 expression can have an important impact on the prolif-eration of smooth muscle cell and endothelial cell activation ,meanwhile it could reduce inflammation ,foam cell formation and lipid deposition ,inhibit vascular remodeling ,and prevent the development of atherosclerosis .These studies suggest that NR4A1 might be a novel target for drug development in prevention and treatment of atherosclerosis .

OBJECTIVE:To provide reference and evidence for rational use of clinical nutrition. METHODS:The types of en-teral and parenteral nutrition and the cost of prescription were analyzed statistically in 17 third grade class A general hospitals,3 third grade class A special hospitals and 14 secondary general hospitals from Shanghai area during 2011 to 2013. RESULTS:Nutri-tion preparations were mainly used by hospitalized patients. Total cost of nutrition preparations in outpatient and emergency depart-ment respectively occupied 8.14%,8.77% and 8.89% of total cost of nutrition preparations in the hospital during 2011-2013. The parenteral nutrition was the main form of nutritional support. There were only three kinds of enteral nutrition in top ten nutrition preparations in the list of prescription cost. Although seven out of ten kinds of nutrition preparations were given enterally which was the main mode for outpatients and emergency patients,the cost of prescriptions of parenteral nutrition increased faster compared to enteral nutrition,especially alanyl-glutamine. CONCLUSIONS:Parenteral nutrition is the main mode of nutrition support,especial-ly for inpatients;great attention should be paid to the increase of the cost of prescriptions about parenteral nutrition in outpatients and emergency patients.

OBJECTIVE:To discuss the mode and feasibility of informatization and automation construction in the inpatient pharmacy. METHODS:The practice of informatization and automation construction of inpatient pharmacy in our hospital was intro-duced,as well as the change of drug dispensing model. The influence of them on drug dispensing process was analyzed. RESULTS&CONCLUSIONS:2 automatic single dose tablets dispense packing machines,2 rapid dispensing machines and 2 automatic injec-tion chests are introduced in automatic inpatient pharmacy of our hospital. The informatization construction contain the establish-ment of inpatient pharmacy database,drug dispensing and recheck,the application of code,etc. Due to the implementation of auto-matic drug dispensing information system,drug dispensing mode have changed,i.g. drug dispensing by area instead of wards;in-jection and large volume transfusion are dispensed by wards;oral preparation and discharge medication are dispensed by prescrip-tion;dispensed drugs are distributed to wards with professional logistics. The implementation of informatization and automation of inpatient pharmacy in our hospital improve pharmaceutical administration and pharmaceutical care,and add automatic expiry date management and code tracking to guarantee the accuracy,timeliness and high efficiency of drug dispensing.

OBJECTIVE:To improve the information system of Out-patient pharmacy intravenous admixture center (OUIVA) to improve the pharmaceutical service rendered to the transfusion patient and ensure the safety of drug use. METHODS:The defi-ciency in OUIVA information system of our hospital were analyzed,in which improvement was made with respect to ungrouped doctor’s orders,inconsistency between the total doses charged and the prescribed doses and the error of transfusion days that occurred fre-quently. The conformity rate of out-patient fluid transfusion prescriptions and the time of patients’waiting for transfusion before and after the improvement were compared and evaluated. RESULTS:Improvement was made to OUIVA information system through the optimization of transfusion process,the application of condition limit,the adding of logical operation and verification and the other measures. After improvement,the unconformity rate of out-patient prescriptions in our hospital descended from 11.24% in 2013 to 3.69% in 2014,with an obvious increase in the accuracy rate of dispensing for fluid transfusion;and the time of patients’waiting for transfusion was shortened from 30-40 min to 15-20 min,with an increase in the degree of satisfaction of transfusion patients. CONCLUSIONS:The OUIVA information system can reduce the errors of drug dispensing for fluid transfusion and improve pharmaceutical services.