OBJECTIVE To investigate the independent risk factors for carbapenem-resistant Klebsiella pneumoniae （CRKP） infection， develop a nomogram prediction model and validate it. METHODS Clinical data of hospitalized patients infected with CRKP between April 2020 and May 2023 at Kunming First People’s Hospital were retrospectively collected and matched 1∶1 with patients infected with carbapenem-susceptible Klebsiella pneumoniae （CSKP） during the same period as the modeling group. Using the same criteria， data from patients hospitalized and infected with CRKP and matched CSKP between June 2023 and June 2024 were collected as the validation group. Univariate analysis， LASSO regression and multivariate Logistic regression were conducted to identify independent risk factors for CRKP infection and to develop a nomogram prediction model. Internal validation of the model was performed using Bootstrap resampling， and external validation was carried out using the data of validation group. The predictive performance of the model was evaluated using receiver operating characteristic （ROC） curves and calibration plots. RESULTS A total of 530 patients were enrolled， with 372 in the modeling group and 158 in the validation group. Cerebrovascular disease， indwelling gastric tube， mechanical ventilation， exposure to carbapenem antibiotics， and exposure to β-lactamase inhibitor compound agents were identified as independent risk factors for CRKP infection （P＜0.05）. The nomogram predicting CRKP infection risk achieved an area under ROC of 0.729 and 0.803 in internal and external validations， respectively. Calibration curves indicated a high degree of consistency between predicted and observed probabilities. CONCLUSIONS Cerebrovascular disease， indwelling gastric tube， mechanical ventilation， exposure to carbapenem antibiotics， and exposure to β-lactamase inhibitor compound agent are independent risk factors for CRKP infection. The developed nomogram model for predicting CRKP infection risk demonstrates good predictive performance and can aid in the early identification of patients at high risk for CRKP infection.

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 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.

Rejection has constantly been an unresolved challenge in the field of organ transplantation. The research on the mechanism of rejection plays a significant role in improving the efficacy of organ transplantation and enhancing the survival rate of graft. The innate and specific immune responses of the human body jointly participate in the graft rejection, leading to graft injury. In recent years, multiple researchers have conducted in-depth studies on the mechanism underlying the role of microRNA (miR) in regulating rejection. Among them, miR-155 has been widely considered as a key factor involved in immune regulation. The expression level and functional status of miR-155 may be intimately associated with the occurrence of rejection, which may become a new target for overcoming rejection. In this article, relevant studies on the role of miR-155 in regulating key immune cells in innate and specific immune responses were reviewed, aiming to provide novel ideas for the development of new immunosuppressants and rejection therapy.

Tacrolimus (Tac) is a commonly used immunosuppressant after organ transplantation, which has high immunosuppressive efficacy. However, the pharmacokinetics of Tac significantly differ among individuals, and gene polymorphism is the main influencing factor. In recent years, the gene polymorphism of drug transporter has become a novel research hotspot. Nevertheless, the effect of the gene polymorphism of transporter on Tac pharmacokinetics remains controversial. Consequently, the correlation between the gene polymorphism of transporter and Tac blood concentration plays a significant role in guiding Tac-based individualized immunosuppressive therapy. In this article, the research progresses on the gene polymorphism of adenosine triphosphate-binding cassette (ABC) transporter and solute carrier (SLC) transporter in organ transplantation was reviewed. The correlation between the gene polymorphism of transporter and Tac blood concentration was summarized, aiming to provide reference for Tac-based individualized therapy.