Hepatocellular carcinoma(HCC)is a cancer with extremely high mortality and incidence rates.In recent years,with the development of multidisciplinary approaches,key characteristics of cancer have gradually been revealed.Studies have shown that dysregulated energy metabolism and metabolic reprogramming in tumor cells form the basis for tumor cell growth and are critical factors in shaping the tumor microenvironment,immune evasion,and drug resistance.Non-coding RNAs(ncRNAs),as important regulatory factors,play a crucial role in the metabolic reprogramming of HCC.This article focuses on summarizing the mech-anisms by which ncRNAs regulate metabolic repro-gramming in HCC and explores their applications in clinical diagnosis,treatment,and prognostic assess-ment,aiming to provide new perspectives for effec-tive HCC treatment and the development of novel drug targets.

Hepatocellular carcinoma(HCC)is a cancer with extremely high mortality and incidence rates.In recent years,with the development of multidisciplinary approaches,key characteristics of cancer have gradually been revealed.Studies have shown that dysregulated energy metabolism and metabolic reprogramming in tumor cells form the basis for tumor cell growth and are critical factors in shaping the tumor microenvironment,immune evasion,and drug resistance.Non-coding RNAs(ncRNAs),as important regulatory factors,play a crucial role in the metabolic reprogramming of HCC.This article focuses on summarizing the mech-anisms by which ncRNAs regulate metabolic repro-gramming in HCC and explores their applications in clinical diagnosis,treatment,and prognostic assess-ment,aiming to provide new perspectives for effec-tive HCC treatment and the development of novel drug targets.

Immunosuppressants(including cyclosporine,tacrolimus,mycophenolate esters,glucocorticoids,etc.)are the first choice of drugs to prevent organ rejection after liver transplantation,which can effectively reduce the host immune response to the graft,improve the success rate of transplantation,and prolong the survival of patients.Liver transplantation is associated with intestinal flora,while immunosuppressive agents interact with intestinal flora.Immunosuppressive agents change the abundance,composition and metabolites of intestinal flora,while a series of enzymes and metabolites produced by intestinal flora may chemically alter the absorption and metabolism of immunosuppressants.In addition,the incidence of postoperative infection in liver transplantion patients is relatively high,while gut flora affects inflammatory factors,and immunosuppressants interact with inflammatory factors.To some extent,immunosuppressants can be thought of as acting through intestinal flora in patients after liver transplantation.

OBJECTIVE To evaluate the influence of gene polymorphism on plasma minimum concentration(cmin)of voriconazole(VRZ)in patients with invasive fungal infection.METHODS The Cochrane Library,Embase,PubMed,Web of Science,China Biomedical Literature Database,CNKI,VIP and Wanfang Data were searched for literature on the correlation between gene polymorphisms andcmin of VRZ from inception to April 2024.After screening the literature,extracting data,and evaluating the quality of the literature,meta-analysis was performed using R 4.3.2 software.RESULTS A total of 21 studies with 2 454 patients were included.The results of meta-analysis showed that the VRZ cmin of CYP2C19 IM and PM types was significantly higher than EM type,and the VRZ cmin of IM type was significantly lower than PM type(P＜0.01).The VRZ cmin of CYP2C9 rs1057910 AA type was significantly higher than AC/CC type,and that of CYP3A5 rs776746 CC type was significantly higher than TT type(P＜0.01).The VRZ cmin of POR rs10954732 GG type was significantly higher than GA and AA types,and that of POR rs1057868 CT type was significantly lower than TT type(P＜0.01).The VRZ cminof ABCB1 rs1045642 CC type was significantly higher than TT type(P＜0.05).The VRZ cmin of NR1I2 rs2472677 CT type was significantly higher than TT type,and rs7643645 AA type was significantly higher than AG type(P＜0.05).The VRZ cmin of ABCC2 rs717620 CC type was significantly lower than CT type and TT type,and the CT type was significantly lower than TT type(P＜0.01).CONCLUSIONS Mutant alleles in CYP2C19,CYP2C9 rs1057910,CYP3A5 rs776746,POR rs10954732,ABCB1 rs1045642 and NR1I2 rs7643645 can lead to a decrease in VRZ plasma concentration,and mutant allele in ABCC2 rs717620 can lead to an increase in VRZ plasma concentration.

OBJECTIVE To compare the efficacy and safety of Cefazolin sodium for injection， Cefuroxime sodium for injection， and Ceftazidime for injection from nationally organized centralized drug procurement （hereinafter referred to as “centralized procurement”） and non-centralized procurement in patients with bacterial infection. METHODS The case data of hospitalized patients who had used 3 kinds of Cephalosporins for injection from centralized procurement or non-centralized procurement in the treatment of bacterial infections were retrospectively collected from 19 medical institutions in Kunming from January 2020 to September 2022. After balancing the baseline differences between the groups with the propensity score matching method， the effectiveness and safety differences of 3 kinds of Cephalosporins for injection from centralized procurement or non- centralized procurement were compared respectively. RESULTS After balancing the baseline differences among the groups， 394 cases in each group of Cefazolin sodium for injection from centralized procurement or non-centralized procurement， 472 cases in each group of Cefuroxime sodium for injection from centralized procurement or non-centralized procurement， 504 cases in group of Ceftazidime for injection from centralized procurement and 590 cases in group of non-centralized procurement were included in the analysis. In terms of effectiveness， there were no significant differences in clinical response rate， 72 h response rate， bacterial clearance rate， and the recovery rate of body temperature， white blood cell count， neutrophil count， neutrophil percentage， C-reactive protein， procalcitonin recovery between the centralized procurement group and non-centralized procurement group of Cefazolin sodium for injection and Cefuroxime sodium for injection （P＞0.05）. The proportion of patients in centralized procurement group of Ceftazidime for injection with C-reactive protein restored to normal reference range was significantly higher than that in non-centralized procurement group （46.9% vs. 27.9%， P＜0.05）， but there were no statistically significant differences in other effectiveness indicators among groups （P＞0.05）. In terms of safety， there was no statistical difference in the incidence of adverse drug reactions between centralized procurement group and non-centralized procurement group of 3 kinds of Cephalosporins for injection （P＞0.05）； the incidence of platelet count reduction in centralized procurement group of Cefazolin sodium for injection was significantly higher than non-centralized procurement group （20.7% vs. 7.1%， P＜0.05）， the incidence of eosinophilia elevation in centralized procurement group of Ceftazidime for injection was significantly higher than non-centralized procurement group （5.3% vs. 1.9%， P＜0.05）. In addition， there was no statistically significant difference in the abnormal rates of other laboratory indicators among the three types of injection Cephalosporins （P＞ 0.05）. CONCLUSIONS The efficacy of 3 kinds of Cephalosporin for injection from centralized procurement is not inferior to non- centralized procurement varieties， and the safety is equivalent to that of non-centralized procurement varieties.

Objective To investigate the expression of miR-6768-5p in lung cancer tissue and its effect on the proliferation and invasion of lung cancer cells through targeted regulation of carboxypeptidase A4(CPA4).Methods The expression of miR-6768-5p in lung cancer tissues and adjacent tissues was analyzed u-sing the TCGA database.Quantitative real-time PCR(qPCR)was used to detect the expression of miR-6768-5p in human lung cancer cell lines(HCC1588,H1650,H1299,A549,HCC827)and normal alveolar epithelial cells(HPAEpiC cells).Lung cancer cells were transfected with NC mimics and miR-6768-5p mimics,respec-tively,and divided into NC group and miR-6768-5p group.The MTS assay and Matrigel invasion assay were used to detect the cell proliferation and invasion ability of each group,respectively.The putative binding sites of miR-6768-5p and CPA4 were verified using RNAhybrid software and dual-luciferase reporter gene experi-ment.The expression of CPA4 mRNA in each group of cells was detected by qPCR.The expression of AKT/c-MYC signaling pathway proteins in the cells of each group was analyzed by Western blot.Results Com-pared with the adjacent tissues,the relative expression level of miR-6768-5p in lung cancer tissues was signifi-cantly decreased,and the difference was statistically significant(P＜0.05).Compared with HPAEpiC cells,the relative expression level of miR-6768-5p was significantly decreased in lung cancer cell lines,and the differ-ence was statistically significant(P＜0.05).Compared with the NC group,the cell proliferation rate of miR-6768-5p group was significantly decreased(P＜0.05).The number of invasive cells in NC group and miR-6768-5p group was(131.30±12.55)and(37.45±7.77),respectively,and the number of invasive cells in miR-6768-5p group was significantly lower than that in NC group(P＜0.05).The relative expression level of CPA4 mRNA in H1299 cells of miR-6768-5p group was significantly lower than that in NC group(t=4.93,P＜0.05).Compared with the NC group,the expressions of AKT/c-myC signaling pathway proteins p-AKT,p-mTORC1,XIAP,MDM2 and C-myC proteins in miR-6768-5p group were significantly decreased.Conclusion The expression of miR-6768-5p is decreased in lung cancer tissues,and miR-6768-5p may inhibit the activation of AKT/c-MYC signaling pathway by targeting CPA4,and reduce the proliferation and invasion ability of lung cancer H1299 cells.

OBJECTIVE To evaluate the accuracy of three individualized drug delivery tools,i.e.JPKD,SmartDose and NextDose,in predicting tacrolimus dose and blood concentration after kidney transplantation,and analyze the influential factors of prediction accuracy.METHODS The clinical data of adult hospitalized patients treated with tacrolimus after kidney transplantation from January 2021 to June 2023 were retrospectively collected.Three individualized dosing tools,i.e.JPKD,SmartDose and NextDose,were used to predict the dose and plasma concentration of tacrolimus.The absolute prediction error(APE)and prediction error(PE)between the measured value and the predicted value,and prediction success rate were calculated(APE＜30％indicating a good forecast).Pearson assay or Spearman assay was used to analyze the correlation between the predicted dosage and actual dosage,as well as the predicted and measured blood concentration values using three software;univariate analysis was used to investigate the influential factors for prediction accuracy of JPKD,SmartDose and NextDose.RESULTS A total of 110 hospitalized patients were included in this study,and 193 tacrolimus doses and plasma concentrations were monitored.The predicted doses of JPKD,SmartDose and NextDose were(2.0±0.7),(2.7±1.9),(1.8±0.8)mg,their measured value was(1.9±0.6)mg,and the correlation coefficients between the predicted values and the measured value were 0.841,0.450,0.247(P＜0.001);the median APEs were 6.00％,52.07％and 30.40％,and the median PEs were 5.00％,18.50％and-3.50％;the prediction success rates were 98.45％,30.05％and 49.22％.The predicted values of tacrolimus concentrations using JPKD,SmartDose,NextDose were(6.74±3.36),(6.93±5.02),9.00(5.80±12.60)ng/mL,the measured value was 8.64(7.11,9.77)ng/mL,and the correlation coefficients between the predicted values and the measured value were 0.997(P＜0.001),-0.066(P=0.360),0.920(P＜0.001).The median APEs were 5.54％,45.91％and 35.56％,and PEs were-4.94％(median),-17.050％(median)and 36.93％(average value);the prediction success rates were 97.93％,32.64％and 37.31％.Univariate analysis showed that the dosage,blood concentration,body weight,transplantation time and others were related to the prediction accuracy(P＜0.05).CONCLUSIONS The good prediction rates of tacrolimus dose and blood concentration in kidney transplant patients using three personalized drug delivery tools,from high to low,are JPKD,NextDose,and SmartDose,suggesting that JPKD can be prioritized in clinical use.

OBJECTIVE To explore the correlation between SLCO1B3 gene polymorphisms and early postoperative tacrolimus concentrations in renal transplant recipients. METHODS A total of 68 patients who underwent kidney transplantation in the First Hospital of Kunming were selected, tacrolimus plasma concentrations were monitored by chemoluminescence, CYP3A5*3, SLCO1B3 T334G and G699A gene polymorphisms were detected by polymerase chain reaction, and genotyping was performed to analyze the correlation between each genotype and tacrolimus plasma concentrations. RESULTS Different genotypes of CYP3A5*3 had significant effects on postoperative tacrolimus plasma concentration and standardized plasma concentration(P＜0.05), and different genotypes of SLCO1B3 T334G and G699A gene loci had no significant effect on postoperative tacrolimus plasma concentration and standardized plasma concentration. CONCLUSION Compared with CYP3A5*3/*3 genotype, CYP3A5*1 allele carriers need to reach the same tacrolimus concentration to increase tacrolimus dose. SLCO1B3 T334G and G699A gene polymorphisms has no effect on tacrolimus plasma concentration in the early stage after renal transplantation.

Objective:To investigate the effect of lncRNA AC132217.4 on the proliferation and invasion of liver cancer MHCC97-H cells and its molecular mechanism.Methods:The TCGA database was used to analyze the differential expression of AC132217.4 in liver cancer tissue and adjacent tissue, and to analyze the relationship between the expression level of AC132217.4 and the overall survival of liver cancer patients. Transfection of pcDNA-AC132217.4 plasmid into MHCC97-H cells was defined as AC132217.4 group, transfection of pcDNA plasmid into MHCC97-H cells was defined as negative control (NC) group, respectively. The proliferation and invasion ability of MHCC97-H cells were detected by MTT method and Matrigel invasion assay. The binding site between AC132217.4 and miR-18a-5p was analyzed by starBase v2.0 software and dual luciferase reporter gene assay. Real-time quantitative PCR (RT-qPCR) detected the differential expression of miR-18a-5p in the two groups of MHCC97-H cells. The expression of epithelial-mesenchymal transition protein was detected by Western-blotting. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s), and t-test was used for comparison between the two groups. Results:Compared with adjacent tissues, the expression of AC132217.4 was down-regulated in liver cancer tissues ( P<0.01). Compared with liver cancer patients with low expression of AC132217.4, the overall survival of liver cancer patients with high AC132217.4 expression was longer ( P<0.05). The pcDNA-AC132217.4 plasmid significantly inhibited the proliferation of MHCC97-H cells ( P<0.05). The number of invasive cells in the NC group and AC132217.4 group were (131.30±12.55) and (37.45±7.77), respectively. The pcDNA-AC132217.4 plasmid significantly inhibited the invasive ability of MHCC97-H cells ( t=6.36, P<0.01). AC132217.4 directly complemented miR-18a-5p ( P<0.01). The expression of miR-18a-5p in MHCC97-H cells in AC132217.4 group (1.04±0.30) was significantly lower than that in NC group (6.13±0.75) ( t=6.27, P<0.01). Compared with the NC group, the expressions of epithelial phenotype proteins Cytokeratin and Claudin-1 in MHCC97-H cells in AC132217.4 group were up-regulated, while the expressions of mesenchymal phenotype proteins Vimentin, Slug and Snail were down-regulated. Conclusions:The expression of AC132217.4 is low in liver cancer tissue, and it is related to the overall survival of liver cancer patients. AC132217.4 might inhibit the proliferation and invasion of liver cancer MHCC97-H cells by sponge miR-18a-5p.

Objective: To evaluate the accuracy and feasibility of coronary artery calcium score ( CACS) on virtual non-contrast scan ( VNC) images obtained from coronary artery CT angiography ( CCTA) scan with dual －layer spectral detector CT (SDCT) ． Methods : The data of 197 patients who underwent CCTA scan in hospital were analyzed retrospectively，and 88 patients with CACS ＞0 were further analyzed． Linear regression analysis of CACS and coronary artery calcium volume ( CACV) of true non-contrast (TNC) images and VNC images ( CACS-TNC， CACS-VNC，CACV-TNC，CACV-VNC) was performed to obtain linear regression equation and correction coefficients λ 1AVG and λ2AVG ．CACS-VNC and CACV-VNC were corrected by the corresponding regression equation and recorded as CCACS-VNC and CCACV-VNC，respectively．Spearman correlation coefficient was used for correlation analysis and Bland-Altman plot was used for consistency test．Mann-Whitney U test was used to compare the difference between the two groups. Results : For the total coronary artery，there was a strong correlation between CACS- TNC and CACS-VNC (rs = 0. 952，P ＜0. 001 ，λ 1AVG = 2. 19 ) ，CACV-TNC and CACV-VNC ( rs = 0. 954，P < 0. 001，λ2AVG = 1. 93) ．The results of Mann-Whitney U test showed that there was no significant difference between CACS-TNC and CCACS-VNC or between CACV-TNC and CCACV-VNC，and the Bland-Altman plot showed good consistency between CACS-TNC and CCACS-VNC ，CACV-TNC and CCACV-VNC． Conclusion VNC images based on SDCT can accurately measure CACS and be used for cardiovascular risk classification，which is expected to replace TNC scan and reduce the radiation dose of patients.