AIM: To analyze the Pharmaceutical Care Network Europe (PCNE) classification system used for evaluating the drug related problems (DRPs) of tacrolimus concentration fluctuations in kidney transplant recipients. METHODS: Kidney transplant recipients were selected as the study subjects, who experienced fluctuations in tacrolimus blood concentrations and clinical pharmacist intervention during outpatient follow-up. PCNE (9.0) classification system was used to evaluate the DRPs of tacrolimus. And the DRP problems, causes, intervention plans, acceptance and status were analyzed. RESULTS: A total of 700 kidney transplant recipients were enrolled from July 2019 to December 2021, and 1014 DRPs were found. The problems of DRPs included the occurrence of adverse drug events (P2.1, 60.16%) and poor treatment outcomes (P1.2, 39.84%); The main reasons included dosage selection (C3, 43%), others (C9, 38.4%), and drug selection (C1, 9.41%); Clinical pharmacists actively intervened at the recipient level (I2, 98.92%) and drug level (I3, 1.08%); The acceptance rate of the intervention plan (A1.1+A1.3) reached 98.62%, and the complete implementation rate (A1.1) reached 72.09%; 79.29% of DPRs were fully or partially resolved (O1.1 and O2.1). CONCLUSION: Clinical pharmacists can use PCNE to evaluate tacrolimus therapeutic drug monitoring (TDM) related DRPs, help standardize TDM pharmaceutical service models, standardize TDM abnormal result interpretation and intervention workflows, and promote safe and rational drug utilization.

Severe infection is a significant threat to patient safety and survival. As the main treatment for hospital acquired infections, meropenem is limited in its effectiveness due to the emergence of drug resistance, especially after long-term use of antibiotics. Therefore, optimizing the efficacy of antibiotics such as meropenem and avoiding microbial resistance has become an urgent issue to be addressed. Therapeutic drug monitoring (TDM), as an important tool for achieving personalized drug administration, is increasingly recognized as an important strategy for optimizing antibiotic concentration, avoiding treatment failure and toxicity in critically ill patients and patients with renal insufficiency. By reviewing the current application status, pharmacokinetics, and TDM guidance of meropenem, clinical references are provided for the treatment of critically ill patients and patients with renal insufficiency, and guidance and support are provided for optimizing antibiotic treatment.

AIM: To research the effects of cytidine deaminase (CDA) C435T polymorphism on the long-term effectiveness of gemcitabine in non-small cell lung cancer (NSCLC). METHODS: Enrolled 145 NSCLC patients received gemcitabine-platinum regiments at the Affiliated Hospital of Xuzhou Medical University from August 2016 to February 2019, characteristics recorded such as: age, gender, pathological type, clinical stage (I-IIIA/IIIB-IV) and so on. Followed-up and evaluated according to RECIST1.1, the disease-free survival (DFS), progression-free survival (PFS) and overall survival (OS) was study endpoint. Cases were categorized into wild-type CC and mutant CT/TT group. Kaplan-Meier method and log-rank test were utilized to analyze the relationship between CDA C435T and DFS/PFS/OS. A cox model was implemented to analyze the prognostic factors. RESULTS: In stage I-IIIA, median DFS of CT/TT compared with CC was not obvious (16.8 vs. 35.7 months, P=0.294), same in median OS (54.3 vs. 81.9 months, P=0.256). In stage IIIB-IV, the median PFS in CT/TT was longer than CC (10.4 vs. 5.0 months, P=0.009), the median OS was undifferentiated (16.2 vs. 24.3 months, P=0.087). No difference of overall median OS in CC and CT/TT genotypes was seen (21.5 months vs. 25.3 months, P=0.077). Cox regression model showed CDA C435T polymorphism was an independent factor of PFS in stage IIIB-IV (P=0.019). CONCLUSION: CDA C435T polymorphism shows a function as a prediction influencing PFS of gemcitabine in IIIB-IV NSCLC, CT/TT genotype is significantly prolonged.

AIM: The purpose of this paper is to study whether the precise administration of vancomycin under the guidance of the model can achieve better clinical treatment effect by implementing the precise medication model in Sichuan Provincial People's Hospital, so as to promote its wide application in practice. METHODS: A prospective cohort study was conducted. The experimental group was patients who used the Model-informed Precision Dosing to determine the vancomycin dosing regimen, and the control group was patients who only decided the vancomycin dosing regimen based on the existing diagnosis and treatment process. Two sets of data were matched to compare whether there were significant differences between the two groups of patients in the TDM steady-state trough concentration or the steady-state AUC compliance ratio, and to evaluate the application value of the model software. RESULTS: According to the inclusion and exclusion criteria, the steady-state blood concentration data of vancomycin in a total of 280 patients were used for analysis. The final result of the experiment was that the number of people in the experimental group was 10, and the compliance rate was 62.50%. There were 64 cases in the control group, and the compliance rate was 24.24% (P=0.002). CONCLUSION: The study found that the model-guided precise dosing regimen can more accurately control the blood concentration of vancomycin in patients, and significantly improve the patient's steady-state trough concentration compliance rate. Therefore, it is recommended to increase the research on the program and promote its wide application in clinical practice. 

AIM: To examine the predictive performance of the PPK software JPKD for the steady-state concentrations of amikacin and recommend the applicable conditions under fixed daily dosage of 400 mg and 600 mg. METHODS: Inpatients using amikacin in the First Affiliated Hospital of Bengbu Medical University from July 2022 to February 2024 were enrolled, and the measured concentrations of amikacin were detected by LC-MS/MS; Verified the predictive performance of JPKD software for peak and trough concentrations of amikacin; JPKD software was applied to predict the steady-state concentrations of amikacin in the patients at the infusion time of 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 h, and then compared the variability of steady-state concentrations with different levels of renal function at optimal infusion time, then the Cmax/MIC values were measured. RESULTS: A total of 69 patients were enrolled, including 18 patients with steady state trough concentrations and 17 patients with steady state peak concentrations. It was found that JPKD had a poor predictive ability for steady state trough concentrations but a good predictive ability for peak concentrations, the WRES<10% between predictive and measured concentrations, and a strong correlation existed between them (r = 0.806). With the shortening infusion time, the higher peak concentrations. The predicted peak concentrations at 0.5 h and 1.0 h infusion time groups were (34.81±6.87) μg/mL and (32.51±6.07) μg/mL, respectively. With the decline of the renal function, the peak concentrations showed a increasing trend. On the same level of renal function, the peak concentrations in the 600 mg group was higher than that of the 400 mg group. When MIC ≤ 2 μg/mL, 400 mg daily dose was chosen; when MIC=4 μg/mL, 400 mg daily dose could be used for CKD3b stage patients, and 600 mg daily dose could be used for CKD1, CKD2, and CKD3a stage patients; when MIC=8 μg/mL, it was predicted that a higher dose was needed to achieve the expected target. CONCLUSION: Amikacin is preferably administered intravenously for 0.5 to 1.0 h, fixed daily doses of 400 mg and 600 mg are indicated for some patients according to the target bacterial MIC and renal function.

AIM: In this study, bioinformatics technology was used to explore the differentially expressed genes in antibody-mediated rejection after renal transplantation, and to screen out the possible mechanisms and potential therapeutic targets of AMR-related miRNAs after renal transplantation, in order to provide new idea for the targeted therapy of AMR after transplantation. METHODS: The dataset GSE115816 was downloaded from the GEO database, and the differential expression of miRNAs in stable renal transplantation (SGF) group and the antibody-mediated rejection (AMR) group after renal transplantation was analyzed online by using DESeq 2R software. TargetScan software predicted the related targets of miRNAs, and the differentially expressed genes (DEGs) were analyzed through through gene ontology (GO) enrichment analysis and Kyoto gene and genome encyclopedia (KEGG) enrichment analysis, then key genes were screened by String database and Cytoscape, and finally verified by TargetScan online analysis. RESULTS: A total of 10 differentially expressed miRNAs were identified in the AMR group by comparison with the SGF group, with the most significant difference in expression of miR-144-5p. A total of 143 miR-144-5p related targets were predicted by Targetscan software. GO analysis showed that DEGs were mainly involved in angiogenesis, synaptic signaling, and transcriptional co-activator regulation. KEGG analysis showed that DEGs were mainly enriched in the thyroid hormone signaling pathway, human papillomavirus infection, and PI3K-AKT signaling pathway. The 10 Hug genes were screened by PPI network. Based on the 6 algorithms in cytoHubba, 5 key genes were obtained by taking the intersection of the top 10 Hug genes of each algorithm, which were NCOA2, NCOA1, FOXO1, PAX3, and PPARGC1A. After the literature review, we found that FoxO1 plays an essential role in immune system diseases and kidney diseases. In our study, we chose FoxO1 as a potential target protein for miR-144-5p. Finally, TargetScan online analysis showed that miR-144-5p has a targeted binding site with the 3' UTR region of FoxO1. CONCLUSION: MiR-144-5p plays an important role in AMR after Kidney transplantation. MiR-144-5p targeting FoxO1 may be a potential therapeutic target and prognostic biomarker for AMR.

Voriconazole (VRC) is a broad-spectrum triazole antifungal drug used for the systemic prophylaxis and treatment of invasive fungal infections (IFI) in adults and children. However, VRC has a typical nonlinear pharmacokinetic profile and highly variable inter- and intra-individual variability, limiting its rational clinical use. Special populations have even greater variation due to physiologic reasons, especially younger pediatric patients, with less evidence and greater limitations in the use of VRC. In recent years more and more VRC population pharmacokinetic (PPK) research results have been published, identifying many covariates, which provides ideas and methods for the rational use of VRC. Based on the latest national and international research results, this article introduced the latest progress of PPK of VRC applied to special populations and demonstrated how PPK could be used to adjust the dose and optimize the treatment. 

Hypertriglyceridemia (HTG) during pregnancy may cause serious complications such as acute pancreatitis, gestational diabetes mellitus, and preeclampsia, especially the high mortality rate of maternal acute pancreatitis is of concern.The physiologic increase in triglyceride (TG) levels during pregnancy poses a challenge for the diagnosis of HTG, there are no diagnostic criteria for pregnant women. The management of HTG in pregnancy remains focused on early screening and a scientifically based fat-restricted diet. Omega-3 fatty acid therapy may be considered for those who cannot be controlled after strict dietary restriction and lifestyle changes, and fibrates may be  used in late pregnancy when the benefits outweigh the risks, as appropriate, and plasma exchange may be a safe and effective option for extremely severe patients. TG levels in early pregnancy are associated with maternal postpartum and neonatal prognosis. Further studies on pharmacologic treatments and management for HTG in pregnancy are expected.

Rheumatic autoimmune diseases are chronic conditions affecting multiple systems, predominantly occurring in young women of childbearing age. Given the nature of diseases and unique physiological changes during pregnancy, they may adversely impact pregnancy outcomes and endanger maternal and fetal health. In recent years, with the deepening of immunological research, biologically targeted therapy has gradually become a focus of attention in the treatment of rheumatic autoimmune diseases in pregnancy. Biologics effectively alleviate disease symptoms, mitigate pregnancy complications, and improve adverse pregnancy outcomes by targeting pivotal inflammatory factors. The review systematically discusses the structure and pharmacokinetic characteristics of biologics, and comprehensively reviews the current application and future prospects in managing rheumatic autoimmune diseases in pregnancy based on their specific targets. It aims to provide scientific references and guidance on the safe administration of medications and therapeutic strategies for these patients, ultimately enhancing health outcomes for mothers and infants.

AIM: To understand the efficacy and safety of amikacin (AMK) for the treatment of carbapenem-resistant Klebsiella pneumoniae pneumoniae (CRKP) in preterm infants and to establish a management process for the use of amikacin in preterm infants. METHODS: CRKP-infected preterm infants treated with amikacin between January 2019 and December 2021 were retrospectively analyzed, and parametric data paired t-tests were used to assess the efficacy and safety of amikacin for the included infectious and safety indicators, and to establish a management process for amikacin use in preterm infants. RESULTS: Eight cases of CRKP infection were included, with the main diagnosis of pneumonia and sepsis. eight preterm infants were screened for the AMK ototoxicity gene mitochondrial gene MT-RNR1 (MT-RNR1 1494C>T and MT-RNR11555A>G) before amikacin treatment, and none of them were found to have the gene variant. after receiving amikacin sulphate injection treatment for 7 days, the indicators of infectivity were improved, and was statistically significant (P<0.01). No clinical ototoxicity or nephrotoxicity was observed in the children before or after treatment. CONCLUSION: Aminoglycosides are still the main antibiotics used for the empirical treatment of suspected infections in preterm infants, especially drug-resistant bacterial infections. Despite the risk of ototoxicity and nephrotoxicity, we provide management procedures and recommendations for neonatal treatment with amikacin to reduce the risk of ototoxicity and nephrotoxicity in AMK.

AIM: To study the in vivo material basis that is involved in the rapid antidepressant effects of saffron glycoside-I, so as to provide evidences to facilitate the interpreting  the inconsistency of PK-PD, and the exploring the underlying mechanism. METHODS: The antidepressant efficacy of saffron glycoside-I and saffron aglycone was evaluated by investigating depressive-like behaviors such as Sucrose Preference Test (SPT), Social Interaction Test (SIT), Tail Suspension test (TST), and the Forced Swim Test (FST) in mice induced by Chronic Unpredictable Stress (CUMS) and Chronic Social Defeat Stress (CSDS). The LPS-induced model of inflammation was used to investigate the regulatory effect of saffron glycoside-I on primary inflammatory factors. The regulation of saffron glycoside-I and saffron aglycone on small molecules and neurotransmitters in blood and intestine were further studied by non-targeting metabolomics and targeting metabolites of neural transmitters based on HPLC-qTOF/MS and LC/MS-MS techniques. RESULTS: Saffron glycoside-I and its aglycone showed rapid and efficient antidepressant effects, and they significantly improved the performance of CSDS mice on SIT, TST, and FST. Saffron glycoside-I did not show obvious effect on reducing LPS-induced inflammatory factors of IL-6 and TNF-α. On the contrary, typical anti-inflammatory drug components of paeoniflorin, silybin and magnesium isoglycyrrhizinate significantly reversed the elevation of IL-6 and TNF-α induced by LPS, but they could not rescue the depressant behaviors of CSDS mice. Metabolomic study revealed perturbation of metabolic phenotype, small molecules and neural transmitters in plasma and gut contents of both CUMS and CSDS mice. To a large content, and Saffron glycoside-I and saffron aglycone modulated metabolic phenotype, similar to the normal controls. Saffron aglycone successfully regulated a variety of metabolites, metabolites associated in purine pathway, and transmitters, such as 5-HT, γ-GABA, glutamic acid and norepinephrine that were perturbed in plasma and gut contents in CSDS mice. CONCLUSION: Saffron aglycone shows a rapid antidepressant effect similar to saffron  glycoside-I, the antidepressant effect of saffron glycoside-I is closely associated with its primary metabolite saffron aglycone in vivo. The antidepressant effect of saffron aglycone is involved in its regulation effects on endogenous small molecules and neurotransmitters in the circulatory system and intestinal tract of depression model mice, instead of that on inhibition on inflammatory factors.

AIM: To investigate the effects and possible mechanisms of liraglutide on postoperative cognitive function in aged mice. METHODS: C57BL/6J male-aged mice were randomly divided into 4 groups: control group (N group), liraglutide group (L group), model group (M group), and model+liraglutide group (ML group). There were 12 mice in each group. The model was constructed by using sevoflurane anesthesia combined with dissecting the abdominal cavity in M and ML groups. In L and M groups, liraglutide was injected into the peritoneal cavity at 300 μg/kg, once per day, for 14 days. Postoperatively, the cognitive function of mice was detected by using the open field test, the Y maze experiment, and the conditioned fear experiment. Western blotting and ELISA were used to detect the expression of hippocampal glucagon-like peptide-1 receptor (GLP1R), β-arrestin2 (β-arrestin2), stimulator of interferon genes (STING), TANK-binding kinase 1 (TBK1), IL-1β, and IL-6; immunofluorescence was used to observe the Iba1-positive microglial cell quantity. RESULTS: Compared with N group, M group showed a decrease in the postoperative spontaneous alternation rate, percentage of freezing time, and GLP1R expression in hippocampal tissue (P<0.05) and an increase in the expression of β-arrestin2, STING, P-TBK1, IL-6, IL-1β, and the number of Iba1-positive cells (P<0.05). Compared with M group, postoperative spontaneous alternation rate, percentage of freezing time, and GLP1R expression were increased in ML group (P<0.05), and the number of β-arrestin2, P-TBK1, IL-6, IL-1β, and Iba1-positive cells was significantly decreased in ML group (P<0.05). CONCLUSION: Liraglutide may ameliorate postoperative cognitive impairment in aged mice by inhibiting the β-arrestin2/STING/TBK1 pathway.

AIM: To investigate the correlation between vitamin D levels and urinary incontinence in women with type 2 diabetes mellitus (T2DM). METHODS: A total 366 female T2DM patients who were hospitalized in Department of Endocrinology, First Hospital of Lanzhou University from May 2022 to July 2023 were selected and were classified as vitamin D deficiency (<20 ng/mL), insufficiency (20-30 ng/mL), and sufficiency (>30 ng/mL) according to serum 25-hydroxyvitamin D ［25(OH)D］ concentration. The prevalence of urinary incontinence and severity was compared among three groups. Adjusted logistic regression was used to analyze the correlation between vitamin D levels and urinary incontinence and its subtypes. RESULTS: Of the 366 patients, 174 (47.5%) T2DM with urinary incontinence. 25(OH)D level was significantly lower in group with urinary incontinence than without (11.9 ng/mL vs. 17.8 ng/mL, P<0.01). The prevalence of urinary incontinence and moderate and severe urinary incontinence was significantly higher in group with vitamin D deficiency than groups with insufficiency and sufficiency (P<0.05). Adjusted logistic regression analysis showed that vitamin D deficiency was associated with an increased risk of any incontinence and urgency incontinence compared to vitamin D sufficiency (P<0.05), vitamin D insufficiency was not associated with urinary incontinence. Age, BMI, parity and low 25(OH)D levels were independent risk factors for combined urinary incontinence in women with T2DM. CONCLUSION: Vitamin D deficiency is significantly associated with the risk of urinary incontinence in women with T2DM, and appropriate vitamin D supplementation may have some benefits for urinary incontinence.

AIM: To explore the therapeutic efficacy and influencing factors of differentiated thyroid cancer (DTC) after the first postoperative 131I treatment. METHODS: We retrospectively analyzed the clinical data of 116 DTC patients treated with 131I　for the first time after thyroid cancer surgery in the Department of Nuclear Medicine of the First Affiliated Hospital of Wannan Medical College, analysed their therapeutic efficacy, and Univariate and multivariate Logistic analyses were performed for the factors that may affect the efficacy of the treatment, respectively, and established ROC curves to analyse the diagnostic and ER efficacy of those with psTg and TTR that had a significant effect on the multifactorial Logistic analyses. RESULTS: In DTC patients who were followed up 3-9 months after the first postoperative 131I treatment, 69.0% (80/116) achieved ER. Univariate analysis revealed no statistical significance between ER and NER groups in terms of age, gender, TSH, TgVR, maximum tumour diameter, presence of lymph node metastasis, bilaterality of tumour, multifocality and clinical stage (P>0.05). While 131I dose, nsTg, psTg, TgV and TTR（Tg/TSH ratio） were statistically significant (P<0.05). The results of multifactorial Logistic analysis showed that psTg and TTR were independent risk factors for the first 131I treatment after DTC, with a psTg OR of 5.950 (95% CI 1.437-24.639, P<0.05) and a TTR OR of 4.137 (95%CI 1.073-15.947, P<0.05). The best threshold value of psTg for ROC curve analysis to predict the efficacy of the first postoperative 131I treatment for DTC was 8.935 μg/L, with a sensitivity of 80.6%, a specificity of 83.6%, and a Yuden's index of 0.64. And the best threshold value of TTR for predicting the efficacy of the first postoperative 131I treatment for DTC was 125.72 ng/mIU, with a sensitivity, specificity of 80.6% and 91.2%, and the Yuden index was 0.618. psTg and TTR areas under the curve were 0.839 and 0.833, respectively. psTg<8.935 μg/L patients achieved ER after 3-9 months of follow-up in DTC patients (67/74, 90.5%). psTg>8.935 μg/L patients achieved ER (13/42, 30.95%). Correspondingly TTR<125.72 ng/mIU achieved ER (65/72, 90.2%). psTg>125.72 ng/mIU achieved ER (15/44, 34.1%). CONCLUSION: The efficacy of the first 131I treatment after surgery for differentiated thyroid cancer is significant. psTg and TTR are independent risk factors for the first 131I treatment after DTC and have an important predictive value of efficacy.