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 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 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.

ObjectiveTo assess the clinical values of the longitudinal strain delay index(LSDI) and the delay of time in peak anterospetal wall to posterior wall strain(TAS-POST),which are analyzed by speckle tracking imaging,was discussed in the article.Methods The study included 39 patients with acute myocardial infarction,37 patients with coronary heart disease but not acute myocardial infarction which was confirmed by selective coronary angiography and 30 age-gender-related volunteers.Two-dimensional echocardiography was performed to collect dynamic images of left ventricular apical long axis view,two-chamber view,four-chamber view and parasternal short axis mitral view,papillary view and apical view.The time to minimal systolic longitudinal,radial,circumferential strain (Tssl,Tssr and Tssc) were measured from the start point of QRS wave of electrocardiogram.The left ventricular segmental standard deviation (Tssl-SD,Tssr-SD,Tssc-SD) and maximal difference (Tssl-Dif,Tssr-Dif,Tssc-Dif) were calculated.The left ventricular dyssynchrony was defined as TAS-POST≥130 ms and LSDI≥25％.ResultsThe dyssynchrony parameters in the acute myocardial infarction group were significantly increased compared to the control group ( P ＜0.001 or P ＜0.05 ).The parameters in the myocardial ischemia group were also higher than those in the control group ( P ＜0.05).Linear regression showed that LSDI was positive correlated with TAS-POST( r =0.676,P ＜0.05).In acute myocardial infarction group,LSDI was more sensitive in the detection of left ventricular dyssynchrony than TAS-POST ( P ＜ 0.05 ).Conclusions Left ventricular dyssynchrony can be evaluate accurately by speckle tracking imaging.LSDI and TAS-POST are quantitative parameters for the evaluation of left ventricular dyssynchrony in coronary heart disease.

A 41-year-old man presented with recurrent pustules and scales on both hands and feet for 1year and with neoplasm on the left toe for 4 months.On physical examination,there were multiple irregular rufous patches with lamellar white scales on bilateral thumbs,forefingers,thenar eminence,toes,and the onethird anterior part of bilateral soles.Deep-seated pustules and vesicles arising on some erythematous patches were disrupted with the formation of punctiform or patches of erosions covered by yellow brown crusts.Some toenails and fingernails were thickened and deformed.An obviously tender neoplasm measuring 4 cm × 3.5 cm× 3.5 cm was observed in the anterior part of the left fourth toe,which was a little indurated and obviously tender with superficial erosion,large amount of purulent exudates and fresh granulation tissue mixing to form black and thick blood crusts on the surface.Biopsy of the nail bed of the right index finger and neoplasm on the left toe revealed a diffuse,dense,and mixed infiltrate of small- to medium-sized atypical lymphocytes and a few inflammatory cells.Meanwhile,epidermotropism and Pautrier's microabscess were visible.Immunohistochemistry showed that the abnormal lymphocytes were positive for leukocyte common antigen (LCA),Vimentin,CD3,CD45RO,CD4,Bcl-2,partly positive for CD8,CD5,CD10,Ki-67 (＞ 80％ ),but negative for CD79a,CD20,CD30,cytokeratin,S-100,Bc1-6,anaplastic lymphoma kinase (ALK),HMBMS,CD1a or P63.Based on the above findings,a diagnosis of mycosis fungoides palmaris et plantaris was made.

Objective To evaluate left atrial function in patients with ischemic cardiomyopathy(ICM)and dilated cardiomyopathy(DCM)by two dimensional-speckle tracking imaging(2D-STI).Methods Twenty-two patients with ICM,twenty-six with DCM and thirty-two healthy subjects were studied.The maximum volume(LAVmax),minimum volume(LAVmin)and volume before the systole(LAVp)of left atria were acquired using biplane area-length method,and calculated the total emptying volume(LATV),expansion index(AEI),active emptying volume(LAEV)and fraction(LAEF)of left atria.The strain and strain rate during systole and late of diastole(Ss,SRs,Sa and SRa)were measured at each left atrial wall (septal,lateral,anterior and inferior).The average of them were worked out.The correlation of left atrial function and strain rate were analysed.Results ①No significant differences were found at the age,sex,heart rate and the E wave between the mitral leaflet tips during all the groups.Compared with the control group,the peak of A wave,the deceleration time of E wave and LVEF decreased in ICM and DCM groups,while the LAD,LVEDD and E/A increased significantly in the two groups(P＜0.05).There were no significant differences between ICM and DCM.②Compared with the controls,the LAVmax increased,AEI and LAEF decreased significantly in patients with ICM and DCM,even lower in DCM(p＜0.05).③Compared with the controls,the Ss,SRs,Sa and SRa reduced significantly in patients with ICM and DCM(P＜0.05),and the DCM showed much significant differences than ICM(P＜0.05).④The AEI had a positive correlation with SRs(r =0.765,P＜0.01).The LAEF had a significant correlation with SRa(r =0.830,P＜0.01).Conclusions The accumulation during systole and active emptying function during late of diastole are both lower in ICM and DCM,even worse in the latter.The 2D-STI may paly an important role in the evaluation of left atrial function.