Artificial intelligence （AI） and population pharmacokinetics （PPK） technologies have demonstrated significant potential in the personalized medication of immunosuppressants after organ transplantation, enabling precise prediction of drug dosages. This article provides a comprehensive review of the application status of AI and PPK in the individualized administration of immunosuppressants after organ transplantation， focuses on monitoring blood drug concentration， predicting efficacy/adverse reactions， and establishing individualized dosing models for organ transplant recipients after immunosuppressant administration， and analyzes and compares the application characteristics of different methods in different organ transplant patients as well as the integration and future development of AI and PPK technologies. AI and PPK technologies can not only significantly reduce the dependence on human resources， but also greatly improve the level of individualized treatment of immunosuppressants after organ transplantation， and reduce the discomfort and burden caused by frequent blood concentration monitoring to patients.

Glucagon-like peptide-1 （GLP-1） receptor agonists are a novel class of antidiabetic drugs that also possess lipid- lowering and cardiovascular protective effects， with liraglutide and semaglutide being their representative medications. Based on a systematic literature search， this review summarizes the lipid-lowering mechanisms by which liraglutide and semaglutide exert direct effects on the liver and kidney （regulating autophagy， key lipid metabolism pathways， reverse cholesterol transport， etc.）， direct actions on adipose tissue （affecting adipocyte proliferation and differentiation， expression of lipid metabolism proteins， and gene transcription）， activation of sympathetic pathways through the central nervous system， and modulation of the gut microbiota. Additionally， it summarizes the clinical evidence of their lipid-lowering effects in populations with type 2 diabetes mellitus， overweight individuals， and others. These findings indicate that GLP-1 receptor agonists exert lipid-lowering effects by acting on multiple tissues or systems， providing crucial evidence for further elucidating the molecular mechanisms of these drugs in lipid regulation and exploring potential new ideas for their clinical applications.

Venetoclax is a selective bcl-2 inhibitor that has shown promising efficacy in acute myeloid leukemia (AML) in combination with hypomethylating agents or low-dose cytarabine. However, the drug resistance remains major concern. This review provides a comprehensive summary of the known mechanisms of venetoclax resistance, so as to provide a reference for designing rational drug combination regimens.

Objective:To compare the efficacy and safety of insulin degludec and insulin glargine U100 in patients with type 2 diabetes mellitus.Methods:This study was a retrospective cohort study. The subjects were patients with type 2 diabetes mellitus who were hospitalized in 13 3A-level general hospitals in Shandong Province from September 2018 to December 2021. According to the type of basal insulin used, the patients were divided into insulin degludec group and insulin glargine U100 group. The basic information and laboratory test results in patients in the 2 groups were collected, the differences of fasting blood glucose level and incidence of hypoglycemia between the 2 groups were compared. The patients with complete blood glucose monitoring data in the 2 groups were selected and their blood glucose fluctuations were compared.Results:A total of 1 152 patients were entered in the study, including 552 patients in the insulin degludec group and 600 patients in the insulin glargine U100 group. The difference in the basic conditions in patients in the 2 groups was not statistically significant (all P>0.05). After treatment, the fasting blood glucose levels in patients in the 2 groups were lower than those before treatment, with statistically significant differences [10.2 (8.8, 12.5) mmol/L vs. 7.5 (6.6, 8.7) mmol/L, Z=-19.443, P<0.001; 10.0 (8.6, 11.7) mmol/L vs. 7.8 (6.6, 9.0) mmol/L, Z=-15.449, P<0.001], but the difference in fasting blood glucose levels between the 2 groups after treatment was not statistically significant ( Z=-1.427, P>0.05). The incidence of hypoglycemia in the insulin degludec group was lower than that in the insulin glargine U100 group [1.09% (6/552) vs. 2.83% (17/600), Z=4.481, P=0.032]. The intraday blood glucose standard deviation, maximum blood glucose fluctuation range, postprandial blood glucose fluctuation range, and average blood glucose fluctuation range in patients with complete blood glucose monitoring data in the insulin degludec group were significantly lower than those in the insulin glargine U100 group [(1.7±0.6) mmol/L vs. (2.4±1.0) mmol/L, (4.5±1.6) mmol/L vs. (6.7±2.9) mmol/L, (1.8±1.0) mmol/L vs. (3.3±1.2) mmol/L, (2.9±1.3) mmol/L vs. (4.6±2.1) mmol/L; all P<0.001]. Conclusion:The efficacy of insulin degludec in the treatment of type 2 diabetes mellitus is equivalent to that of insulin glargine U100, but the risk of hypoglycemia and blood glucose fluctuation is lower.

Objective:To compare the efficacy and safety of insulin degludec and insulin glargine U100 in patients with type 2 diabetes mellitus.Methods:This study was a retrospective cohort study. The subjects were patients with type 2 diabetes mellitus who were hospitalized in 13 3A-level general hospitals in Shandong Province from September 2018 to December 2021. According to the type of basal insulin used, the patients were divided into insulin degludec group and insulin glargine U100 group. The basic information and laboratory test results in patients in the 2 groups were collected, the differences of fasting blood glucose level and incidence of hypoglycemia between the 2 groups were compared. The patients with complete blood glucose monitoring data in the 2 groups were selected and their blood glucose fluctuations were compared.Results:A total of 1 152 patients were entered in the study, including 552 patients in the insulin degludec group and 600 patients in the insulin glargine U100 group. The difference in the basic conditions in patients in the 2 groups was not statistically significant (all P>0.05). After treatment, the fasting blood glucose levels in patients in the 2 groups were lower than those before treatment, with statistically significant differences [10.2 (8.8, 12.5) mmol/L vs. 7.5 (6.6, 8.7) mmol/L, Z=-19.443, P<0.001; 10.0 (8.6, 11.7) mmol/L vs. 7.8 (6.6, 9.0) mmol/L, Z=-15.449, P<0.001], but the difference in fasting blood glucose levels between the 2 groups after treatment was not statistically significant ( Z=-1.427, P>0.05). The incidence of hypoglycemia in the insulin degludec group was lower than that in the insulin glargine U100 group [1.09% (6/552) vs. 2.83% (17/600), Z=4.481, P=0.032]. The intraday blood glucose standard deviation, maximum blood glucose fluctuation range, postprandial blood glucose fluctuation range, and average blood glucose fluctuation range in patients with complete blood glucose monitoring data in the insulin degludec group were significantly lower than those in the insulin glargine U100 group [(1.7±0.6) mmol/L vs. (2.4±1.0) mmol/L, (4.5±1.6) mmol/L vs. (6.7±2.9) mmol/L, (1.8±1.0) mmol/L vs. (3.3±1.2) mmol/L, (2.9±1.3) mmol/L vs. (4.6±2.1) mmol/L; all P<0.001]. Conclusion:The efficacy of insulin degludec in the treatment of type 2 diabetes mellitus is equivalent to that of insulin glargine U100, but the risk of hypoglycemia and blood glucose fluctuation is lower.

OBJECTIVE: To study the value of ADRB2, GLCCI1, FCER2 gene detection in individualized medication of children with refractory asthma.METHODS: Clinical pharmacists participated in therapy for 2 cases of refractory asthma, and comprehensively analyzed risk factors as its pathogenic factors (allergens and pathogens of respiratory infections), lung function indexes and family history. It was suggested to conduct anti-asthmatic drugs gene [p2-adrenergic receptor (ADRB2), glucocorticoid induced transcriptional 1 gene (GLCCI1), low affinity IgE receptor (FCER2)] testing. According to detection results, the suggestions were put forward such as increasing the dose of Glucocorticoid for inhalation, stopping β2 receptor agonist, additionally using anticholinergic drug. RESULTS: The clinical physicians adopted the suggestions of clinical pharmacists. After optimizing refractory asthma therapy plan according to the results of gene testing and clinical factors, 2 patients were stable and the number of seizures decreased significanthy. CONCLUSIONS: Gene test can provide evidence for the formulation of individualized therapy in asthma children.

Wuxistatin, a novel and potent statin, is converted from lovastatin by Amycolatopsis sp. CGMCC1149. In the bioconversion, lovastatin is firstly hydroxylated by a hydroxylase. To obtain the critical hydroxylase, a novel hydroxylase gene was isolated from Amycolatopsis sp. CGMCC1149 by Degenerate PCR and Self-Formed Adaptor PCR and expressed in Escherichia coli. BLAST sequence analysis revealed that the gene belonged to cytochrome P450 gene superfamily and could encode a 403-amino-acid protein with a molecular weight of 44.8 kDa. The secondary structure prediction result showed that this protein contained many typical functional regions of P450, such as oxygen binding site, ion-pair region and heme binding region. Meanwhile, a catalytic function verification system was constructed by NADH, ferredoxin and ferredoxin reductase which could catalyze lovastatin hydroxylation into the target product. These would be helpful for further studies in large-scale production of wuxistatin.
Actinomycetales ; enzymology ; genetics ; Amino Acid Sequence ; Butyrates ; metabolism ; Cloning, Molecular ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Hydroxylation ; Industrial Microbiology ; Lovastatin ; metabolism ; Molecular Sequence Data

2,3-butanediol (2,3-BD) is a major byproduct of 1,3-propandediol (1,3-PDO) fermentation by Klebsiella pneumoniae. To decrease the formation of 2,3-BD, the budC and budA gene, coding two key enzymes of 2,3-BD synthetic pathway in K. pneumoniae, were knocked out using Red recombination technology. The growth of the two mutants were suppressed in different level. The budC deficient strain fermentation results showed that 1,3-PDO concentration increased to 110% and 2,3-butanediol concentration dropped to 70% of the parent strain. However, the budA deficient strain did not produce 1,3-PDO and 2,3-BD, and the final titer of lactic acid, succinic acid, ethanol and acetic acid increased remarkably compared with the parent strain. Further analysis of budC deficient strain fermentation inferred that K. pneumoniae possessed the 2,3-BD cycle as a replenishment pathway. The consequence provided a new evidence for reforming low-byproduct K. pneumoniae.
Acetolactate Synthase ; genetics ; metabolism ; Bacterial Proteins ; genetics ; Butylene Glycols ; metabolism ; Carboxy-Lyases ; genetics ; Gene Knockout Techniques ; Glycerol ; metabolism ; Klebsiella pneumoniae ; genetics ; metabolism ; Mutation ; Propylene Glycols ; metabolism