Uridine is one of the essential nutrients in organisms. To maintain normal cell growth and intracellular metabolism, the uridine must be maintained at certain concentration. Recent studies have shown that uridine can reduce inflammatory response in organisms, participate in glycolysis, and regulate intracellular protein modification, such as glycosylation and acetylation. Furthermore, it can protect cells from hypoxic injury by reducing intracellular oxidative stress, promoting high-energy compounds synthesis. Previous studies have shown that the protective effects of uridine are closely related to its effect on mitochondria. This review summarizes the effect of uridine on mitochondrial function.
Uridine/metabolism* ; Mitochondria/metabolism*

The Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021 (2021 guideline) was recently released. The guidelines summarized the evidences from literatures through to July 2019, and composed by 6 parts as "screening and early treatment", "infection", "hemodynamic management", "ventilation", "additional therapies" and "long-term outcomes and goals of care" with a total of 93 items and 99 recommendations. Compared with the 2016 guideline (96 recommendations), although the total number of recommendations in the 2021 guideline is similar, the number of "strong recommendations (recommend)" in 2021 guideline has dropped significantly, while as the number of "weak recommendations (suggest)" has increased significantly, and the level of the quality of evidence on which the recommendations are based has been significantly lowered. Furthermore, 2021 guideline has also markedly deleted or simplified the recommendations regarding infection prevention, acute respiratory distress syndrome (ARDS) treatment, nutritional support and so on. While, the most obvious improvement appears in the segment of "long-term outcomes and goals of care", in which the patients and their families could get help in term of determining their physical rehabilitation and discharge follow-up plans and formulating exact goals of care. 2021 guideline did not adopt new and emerging therapies or treatments, such as metagenomic next-generation sequencing (mNGS), diaphragm protective ventilation, timing of initiating renal replacement therapy for acute kidney injury, early mobility, endotoxin adsorption, tranexamic acid, E-medicine and telemedicine, big data & artificial intelligence and other new therapies. Collectively, it may suggest the 2021 guideline tend to be conservative and simplified rather than fairly optimized and logicalized, which may arouse controversy in the future and affect clinician compliance.

Previously, we reported that Y, a new epigallocatechin gallate derivative, is efficacious in reversing doxorubicin (DOX)--mediated resistance in hepatocellular carcinoma BEL-7404/DOX cells. In this study, we evaluated the efficacy of Y in reversing drug resistance both and by determining its effect on the adenosine triphosphate-binding cassette protein B1 transporter (ABCB1 or P-glycoprotein, P-gp). Our results showed that Y significantly sensitized cells overexpressing the ABCB1 transporter to anticancer drugs that are ABCB1 substrates. Y significantly stimulated the adenosine triphosphatase activity of ABCB1. Furthermore, Y exhibited a higher docking score as compared with epigallocatechin gallate inside the transmembrane domain of ABCB1. In addition, in the nude mouse tumor xenograft model, Y (110 mg/kg, intragastric administration), in combination with doxorubicin (2 mg/kg, intraperitoneal injection), significantly inhibited the growth of BEL-7404/DOX cell xenograft tumors, compared to equivalent epigallocatechin gallate. In conclusion, Y significantly reversed ABCB1-mediated multidrug resistance and its mechanisms of action may result from its competitive inhibition of the ABCB1 drug efflux function.

Objective:To investigate the correlation between plexinC1 (PLXNC1) rs2272335 polymorphism and the family clus-tering genetic susceptibility to primary liver cancer (PLC) in Guangxi and the expression of PLXNC1. Methods:Genotype and alleles of rs2272335 were determined in 20 liver cancer family groups (79 cases) and 10 healthy normal control groups (40 cases) in Fusui County through Time of Flight Mass Spectrometer. Immunohistochemistry detected the PLEXNC1 protein expression. Results:For the alleles of PLXNC1 (rs2272335) site, the risk of hepatocellular carcinoma (HCC) for individuals with [C] allele was 4.16-fold (95%CI=0.37-47.3, P=0.032) compared with that for individuals with [T] allele among the members of the healthy normal control group. The fre-quencies of the [C] and [T] alleles were similar in the HCC patients and the core individuals of liver cancer families (P>0.05). For the genotype of the PLXNC1 (rs2272335) site, the differences in frequencies of TT, TC, and CC genotypes were not statistically significant among the PLC patients and the core individuals of the liver cancer families and normal controls. The PLXNC1 protein expression in HCC (3.12±1.12) was higher than in hepatocellular paracancerous tissues (1.54±0.67) and in benign hepatocellular lesions (1.23±0.87) (P<0.05). Conclusion:The [C] allele of PLXNC1 (rs2272335) site might be the risk gene for the occurrence of PLC family clustering in Guangxi. PLXNC1 protein overexpression was closely correlated with PLC oncogenesis.

Objective To assess left ventricular (LV) untwisting in patients with acute myocardial infarction(AMI) in different location by two-dimensional speckle tracking imaging(2D-STI),searching for sensitive parameter to evaluate the untwisting motion,to explore the impact of myocardial infarction(MI)location and number of MI segments on left ventricular untwisting movement.Methods Forty-one patient with AMI (AMI Group) were divided into two groups (anterior wall-anteroseptum group and inferior wall-posterior wall group) according to the MI location,and 31 age matched subjects were involved as the control group.Acquire the bull's eyes map of systolic strain (LPSS) values by automated function imaging(AFI)and locate the position and number of segments of MI by it.Access twist at aortic valve closure (AVCtw),twist at mitral valve open (MVOtw),peak twist velocity(PTV),untwisting rate in IVRT (Untw-R),peak untwisting velocity(PUV),time to peak untwisting velocity(TPUV) and half time of untwisting (UHT)with STI.Results Compared with control group,left ventricular ejection fraction (LVEF),global LPSS,PUV and Untw-R of AMI group decreased significantly (P ＜0.001),T-PUV (P ＜0.001) and UHT (P =0.028) increased significantly.The number of MI segments correlated with Untw-R (r =-0.420,P =0.006) significantly.There was no significant correlation between number of MI segments and UHT,PUV,TPUV.Untw-R in anterior wall-anteroseptum group were lower than inferior wall-posterior wall group(P =0.022).For PTV,PTW,T-Ptw,PUV,UHT and T-PUV,there was no significant difference between anterior wall-anteroseptum group and inferior wall-posterior wall group.Conclusions LV untwisting motion of AMI patients can be observed by 2D-STI.Untw-R is a sensitive parameter to evaluate the untwisting motion of AMI patients.The untwisting motion of AMI patients decrease significantly,even worse in anterior wall-anteroseptum AMI patients.

Objective To assess the left ventricular dyssynchrony in coronary artery disease(CAD) without visual segmental wall motion abnormalities using strain delay index (SDI).Methods A total of 135 patients under suspicion of CAD were recruited in this study.Two-dimensional cchocardiography was performed to collect dynamic images of left ventricular apical long axis views,tow-chamber views,four chamber views and parasternal short axis mitral views,papillary views and apical views.The time to minimal systolic longitudinal,radial,circumferential strain (Tssl,Tssr and Tssc) were measured from the start point of QRS wave in electrocardiogram.The left ventricular segmental standard deviation (Tssl-SD,Tssr-SD,Tssc-SD),maximal difference (Tssl-Dif,Tssr-Dif,Tssc-Dif) and longitudinal,radial,circumferential SDI (LSDI,RSDI,CSDI) of 18 left ventricular segments were calculated.Results According to coronary angiography results,patients were divided into three groups:severe stenosis group,mild stenosis group and control group.Compared with the other two groups,SDI and Tssl-SD,Tssl-Dif were decreased in severe stenosis group (P ＜0.001 or P ＜0.05).However,there were not significant differences between the mild stenosis group and the control group except Tssr-SD.The receiver operating characteristic (ROC) curves analysis demonstrated that LSDI had the highest accuracy and Tssl-SD had the lowest accuracy for detecting severe CAD (areas under the curve were 0.891,0.797,0.666,0.580 and 0.556 respectively).High sensitivity and specificity (80.6％ and 86.7％,respectively) were shown when using-12.67％ as a cutoff point of LSDI to diagnose severe CAD.Conclusions SDI can be helpful for assessing the left ventricular dyssynchrony in patients without visual segmental wall motion abnormalities,and LSDI is the most effective parameter to detecting severe CAD.

Objective To evaluate the function and synchronization in patients with paroxysmal atrial fibrillation(PAF) by two dimensional speckle tracking imaging(2D-STI) measuring the strain of left atrial.Methods Thirty healthy controls and thirty-five patients with PAF were studied.The PAFs were divided into group PAF1 during the diapause and group PAF2 during the stage of attack.From the strain-time curve of 2D-STI workstation,the peak velocity(Vs,Ve and Va),the peak amplitude of longitudinal strain (Ss,Se and Sa) and strain rate (SRs,SRe and SRa) were acquired in the course of systole,the early and the late diastole respectively.The synchronization of left atrial (Ts-SD,Te-SD and Ta-SD) could be gotten from the time to the peak strain.The correlation were analysed between the synchronization indices and the strain rate parameters.Results ①No significant differences were found at the age,heart rate,E/A,IVS,LVEDD and LVEF.Compared with the control group,the LAD increased and DT decreased in PAF1 and PAF2 groups (P ＜0.05).②The peak velocity were slower,the peak strain were shorter and the peak strain rate were lessened in the PAFs than the controls(P ＜0.05),except the SRa(P ＞0.05).③The Ts-SD and Te-SD were much more different during the three groups(P ＜0.05),the PAF2 showed fewer synchronization; the Ta-SD was higher in the PAF1 than the controls(P ＜0.05).④The Ta-SD had a positive correlation with SRa(r =0.61,P ＜0.01).Conclusions The reservoir and conduit function of left atrial are impaired in PAFs during the diapause,the booster pump could recover partially,however,there are dyssynchronization.The booster pump function disappear during the stage of attack and there are worse synchronization.2D-STI may paly important roles in the assessment of function and synchronization of left atrial.

Objective To evaluate the usefulness of speckle tracking imaging(STI) for assessment of left ventricular(LV) and right ventricular (RV) functions in patients with isolated disease of right coronary artery.Methods 45 cases were diagnosed as single right coronary lesions given echocardiography,30 cases had chest pain but coronary angiography had not seen the obvious narrow as a comparison.The twodimensional loop-cinec were obtained in apical 4-chamber view,apical 2-chamber view and long axis of LV view.Eighteen segments of LV longitudinal peak systolic strain,global peak systolic strain of each view and three segments of RV free wall were measured by two-dimensional strain software.Results In the patients who had right coronary lesions but did not happen myocardial infarction,the strain(S) values in the base,mid and apex segmental of LV post wall,the base and mid segmental of LV inferior wall and the base and mid segmental of LV septum were significantly lower( P ＜0.05).The S values in the mid segment of RV free wall was lower( P ＜0.05).In the patients who had right coronary lesions and myocardial infarction,the S values in the base,mid segmental of LV antsept,the apex segmental of LV anterior wall,the base,mid and apex segmental of LV post wall,the base and mid segmental of LV inferior wall and the base and mid segmental of LV septum were significantly lower( P ＜0.05).The S values in the mid and apex segments of RV free wall were lower ( P ＜0.05).And the LV global longitudinal strains were lower in the two groups (P ＜0.05).Conclusions STI is a new and useful technology for assessment ventricular functions in patients with isolated disease of right coronary artery,and there are multiple segments impaired.

Objective To assess left ventricular function early and late improvement of patients with acute myocardial infarction (AMI) treated by percutaneous coronary intervention (PCI) by speckle tracking imaging (STI).The clinical values of the assessment of STI for the prognosis and heart function improvement of AMI patients treated by PCI were discussed.Methods 73 AMI patients who had AMI for the first time and had been treated by primary PCI from September 2010 to July 2011 and were examined in the follow-ups from December 2010 to February 2012 in our hospital were enrolled.Dynamic images were acquired before PCI,at 3 months and 6 months after PCI and analyzed by STI.Dynamic images were analyzed for longitudinal peak systolic strain (LPSS),radial peak systolic strain (RPSS) and circumferential peak systolic strain (CPSS) values by STI.According to the comparison of left ventricular ejection fraction (LVEF) before PCI and 6 months after PCI,patients were divided into left ventricular function improved group (ΔLVEF6＞5％) and not-improved group.According to the comparison of LVEF before PCI and 3 months after PCI,improved group were divided into left ventricular function early-improved group (ΔLVEF3 ＞5％) and late-improved group.Results The values of all STI parameters before PCI,3 months and 6 months after PCI in improved group were higher than those in not-improved group (P ＜0.001,all).LPSS before PCI and at the follow-ups and RPSS at 3 months after PCI in early-improved group were higher than those in late-improved group (LPSS at 3 months after PCI:P＜0.001;Other parameters:P ＜0.05).There were significant correlations between all STI parameters and both ΔLVEF3 and ΔLVEF6.LPSS before PCI was more closely related to ΔLVEF3 (r =-0.781,P ＜0.001).CPSS at 6 months after PCI was more closely related to ΔLVEF6 (r =-0.834,P ＜ 0.001).Conclusions Early and late function improvement of left ventricle in AMI patients who is treated by PCI are accurately assessed by STI.The precise analyses of longitudinal and circumferential movements in STI are important for clinical diagnosis.

Objective To assess the left ventricular function of patients with acute myocardial infarction (AMI) treated by percutaneous coronary intervention (PCI) by speckle tracking imaging (STI).Methods 75 AMI patients who had AMI for the first time and have been treated by primary PCI were enrolled.Dynamic images were acquired before PCI,at 6 months after PCI and analyzed by STI.Dynamic images were analyzed for longitudinal peak systolic strain (LPSS),radial peak systolic strain (RPSS) and circumferential peak systolic strain (CPSS) values by STI.According to the comparison of left ventricular ejection fraction (LVEF) before PCI and 6 months after PCI,patients were divided into left ventricular function improved group (△LVEF≥5％) and not-improved group.Results Compared to non-improved group,LPSS (P ＜0.001),RPSS (P ＜0.05,P ＜0.001) and CPSS (P ＜0.001) of improved group were all higher before and 6 months after PCI.LPSS (r =-0.578,P ＜0.001) and CPSS (r =-0.817,P ＜0.001) before PCI were both closely related to △LVEF.In single parameter mode of ROC curve analysis,the area under the ROC curve (AUC) (0.867),sensitivity (94.7％) and specificity (74.4％) of CPSS are relatively higher than other STI parameters.In multiple parameters united mode of ROC curve analysis,AUC (0.897),sensitivity (94.7％) and specificity (74.4％) of LPSS,RPSS and CPSS united were the highest among all the combinations of all STI parameters.Conclusions Left ventricular function improvement of patients with AMI 6 months after PCI is accurately assessed and predicted by STI.CPSS is a strong predictor for left ventricular function improvement 6 months after PCI of AMI patients among all the STI parameters and is an effective indicator for the assessment of left ventricular function improvement of AMI patients.