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.

A single-center, randomized, double-blind, dose-controlled trial of modified Sini Powder in treating mild to moderate generalized anxiety disorder(GAD) in the patients with syndrome of liver depression transforming into fire was conducted at Xiyuan Hospital, China Academy of Chinese Medical Sciences. A total of 80 patients with mild to moderate GAD and the syndrome of liver depression transforming into fire were included. Patients were assigned by the central randomization system at a ratio of 3∶1 into an observation group(n=60, receiving a conventional-dose of granules of modified Sini Powder) and a control group(n=20, receiving low-dose granules with the active ingredients being 50% of that in observation group). Assessments were conducted before treatment(baseline), after 2 weeks of introduction, after 2/4/8 weeks of treatment, and after 4 weeks of follow-up. The results were summarized as follows. In terms of primary outcome indicators, the observation group(62.2%) showed higher total response rate than the control group(26.6%)(P<0.05), and greater Hamilton anxiety scale(HAMA) score reduction after 8 weeks of treatment(P<0.05). In terms of secondary outcome indicators, the HAMA score(somatic anxiety score), traditional Chinese medicine(TCM) syndrome scores, Pittsburgh sleep quality index(PSQI) scale, and clinical global impression(CGI) scale score in the observation group showed a significant compared to the control group at each visit points(P<0.05). Adverse events occurred in 10 cases, including 9(16.9%) cases in the observation group and 1(6.6%) case in the control group. No adverse reaction was observed. In conclusion, conventional-dose modified Sini Powder demonstrated superior efficacy and favorable safety for mild and moderate GAD in the patients with the syndrome of liver depression transforming into fire over low-dose treatment.
Humans ; Male ; Female ; Adult ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/administration & dosage* ; Anxiety Disorders/drug therapy* ; Treatment Outcome ; Young Adult ; Powders ; Aged ; Liver/drug effects* ; Generalized Anxiety Disorder

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Objective:To investigate the effects of bunched cognitive behavior intervention on disease fear and psychological security in patients with glioma.Methods:A total of 92 patients with glioma who underwent surgical treatment from January 2022 to June 2023 were selected.According to the order of enrollment, all subjects were divided into research group( n=44)and control group( n=48). The patients in control group received routine medical and nursing intervention, and patients the research group adopted glioma bunched cognitive behavior intervention on the basis of routine medical and nursing intervention, including 4 intervention cycles.At enrollment, 2 weeks after intervention, and 4 weeks after intervention, all subjects were evaluated by the fear of progression questionnaire-short form (FoP-Q-SF), safety questionnaire (SQ), self-rating anxiety scale (SAS) and self-rating depression scale (SDS). All the data in this study were processed by SPSS 26.0 statistical software.The scores of FoP-Q-SF, SQ, SAS and SDS before and after intervention were compared by repeated measures ANOVA between the two groups. Results:(1)The total FoP-Q-SF score, physiological health dimension scores, and social family dimension scores of the two groups showed significant interaction effects before and after intervention ( F=254.839, 52.738, 12.237, all P<0.05). Further simple effect analysis showed that after 2 and 4 weeks of intervention, the FoP-Q-SF scores of the research group (2 weeks after intervention: 33.80±4.94, 36.48±4.04; 4 weeks after intervention: 31.25±4.55, 35.94±4.47) and social family dimensions (2 weeks after intervention: 15.32±2.56 points, 17.06±2.14; 4 weeks after intervention: 14.05±2.59, 16.96±1.99) were lower than those of the control group (all P<0.05). The physiological health dimension score of the research group was lower than that of the control group after 4 weeks of intervention (4 weeks after intervention: 17.30±2.92, 19.06±2.38) ( P<0.05). After 4 weeks of intervention, the FoP-Q-SF score, physiological health dimension score, and social family dimension score of the research group were all lower than those at 2 weeks after intervention and before intervention (all P<0.05). (2)The total SQ score, interpersonal security dimension score and the determined control score of the two groups showed significant interaction effects before and after intervention( F=193.129, 54.706, 44.015, all P<0.05). Further simple effect testing showed that after 2 and 4 weeks of intervention, the total SQ score and interpersonal security score of the research group were higher than those of the control group (all P<0.05). The determined control score of the research group was higher than that of the control group after 4 weeks of intervention ( P<0.05). After 2 and 4 weeks of intervention, the total SQ score, interpersonal security score, and determination control score of the research group were higher than before intervention (all P<0.05), and the total SQ score and interpersonal security score of the research group were higher than 2 weeks after intervention (both P<0.05). (3)The SAS score and SDS score of the two groups showed significant interaction effects before and after intervention( F=237.867, 282.882, both P<0.05). Further simple effect analysis showed that after 2 and 4 weeks intervention, the SAS and SDS scores of the research group were lower than those of the control group (all P<0.05). The SAS and SDS scores of the research group were lower after 2 weeks and 4 weeks intervention than before intervention (all P<0.05). The SAS and SDS scores of the research group at 4 weeks after intervention were lower than those at 2 weeks after intervention (both P<0.05). Conclusion:Bundled cognitive behavioral intervention can improve disease fear and negative emotions in patients with glioma, and enhance psychological security.

Objective:To investigate the effects of the serine/threonine kinase family member 1(PIM1)gene on the proliferation and apoptosis of acute myeloid leukemia(AML)U937 cells,and the regulation effect on Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods:Bone marrow mononuclear cells from newly diagnosed adult AML patients and patients with iron deficiency anemia were collected and PIM1 mRNA expression was detected by RT-qPCR.AML cell line U937 cells were divided into U937 group(U937 cells were cultured normally),Si-PIM1 group(U937 cells were transfected with low expression adenovirus vector containing PIM1 mRNA),Si-NC group(U937 cells were transfected with low expression adenovirus vector without PIM1 mRNA),coumermycin A1(CoA1)group(JAK2 activator CoA1 was added to U937 cells at a concentration of 20 μ mol/L),and Si-PIM1+CoA1 group(U937 cells were transfected with adenoviral vector containing low expression of PIM1 mRNA and added with CoA1 at a concentration of 20 μ mol/L).After culture for 24 h,the expressions of PIM1 mRNA and protein,JAK2/STAT3 pathway,cell cycle and apoptosis-related proteins in U937 cells were detected by RT-qPCR and Western blot,the cell proliferation activity was detected by MTT assay,and flow cytometry was used to detect cell cycle changes and apoptosis rate.Results:The PIM1 mRNA expression level in bone marrow mononuclear cells in AML patients was higher than that in patients with iron deficiency anemia(P＜0.05).Compared with U937 group,PIM1 mRNA and protein,phosphorylated JAK2(p-JAK2)/JAK2,phosphorylated STAT3(p-STAT3)/STAT3,Cyclin D1,cyclin-dependent kinase 2(CDK2)protein,cell proliferation activity,S phase and G2/M phase proportions were decreased in Si-PIM1 group(all P＜0.05),while p27,Caspase-3 protein,G0/G,phase proportion and apoptosis rate were increased(all P＜0.05).However,the changes of above indicators in CoA1 group were just opposite to those in Si-PIM1 group,indicating that CoA1 could reverse the effect of Si-PIM1 on U937 cells.There were no significant differences in above indexes of U937 cells between U937 group,Si-PIM1+CoA1 group and Si-NC group(P＞0.05).Conclusion:Knockdown of PIM1 gene expression can inhibit U937 cell proliferation and promote apoptosis,in order to alleviate ALM process,which may be related to the inhibition of JAK2/STAT3 pathway activation.

Objective To observe the effects of moxibustion on myocardial pathological morphology,α-smooth muscle actin(α-SMA)and chromosome 10 deletion phosphatase and tensin homologous protein(PTEN)/mammalian target of rapamycin(mTOR)signalling pathway in rats with chronic heart failure(CHF),and to explore the possible mechanism of moxibustion in attenuating myocardial fibrosis in rats with CHF.Methods According to the random number table method,60 male SD rats were divided into the normal group(n=10)and the surgery group(n=50),and the rats in the surgery group were ligated the left coronary artery to replicate the CHF model.According to the random number table method,40 successfully modelled rats were divided into the model group,the moxibustion group,the bpV(phen)group,and the moxibustion+bpV(phen)group,with 10 rats in each group.The normal and model groups were not given any intervention;in the moxibustion group,customized moxa sticks were used to moxibrate the bilateral"Feishu"(BL13)and"Xinshu"(BL15)on the back of the rats for 30 min at each point once a day;the bpV(phen)group was injected intraperitoneally with the bpV(phen)solution(0.15 mg/kg)twice a week;the moxibustion+bpV(phen)group was based on the bpV(phen)group,and moxibustion was applied according to the moxibustion group.The intervention was carried out for 4 weeks.The general conditions of rats,such as feeding and activity were observed;HE staining was used to detect morphological changes of the cardiomyocytes;Masson staining was used to detect myocardial fibrosis;the cardiac echocardiography was used to detect ejection fraction(EF)and fractional shortening(FS);real-time PCR was used to detect the mRNA expressions of PTEN and mTOR in the cardiac muscle tissues;protein expressions of PTEN,mTOR,α-SMA in rat myocardial tissue were detected by Western blotting.Results Compared with the normal group,rats in the model group had altered cardiomyocyte morphology,severe damage to myocardial fiber structure,significantly lower EF,FS,and mTOR mRNA and protein expressions,and significantly higher PTEN,α-SMA protein expressions and PTEN mRNA expression(P<0.05).Compared with the model group,myocardial ultrastructural damage was attenuated in the moxibustion group,bpV(phen)group,and moxibustion+ bpV(phen)group,and EF,FS,and mRNA and protein expressions of mTOR were significantly higher,α-SMA protein expression was significantly lower,and mRNA and protein expressions of PTEN were significantly lower(P<0.05).Compared with the moxibustion+bpV(phen)group,myocardial ultrastructural damage was worsen in the moxibustion and bpV(phen)groups,with significantly lower EF,FS,and mRNA and protein expressions of mTOR,significantly higher α-SMA protein expression,and significantly higher mRNA and protein expressions of PTEN(P<0.05).Conclusion Moxibustion can improve the pathological morphology and function of cardiomyocytes and attenuate myocardial fibrosis in rats with CHF,and its mechanism may be related to the down-regulation of PTEN expression,and then the up-regulation of mTOR expression.

Objective To assess the feasibility of sound touch elastography(STE)and sound touch quantify(STQ)in convex transducer and linear transducer for female levator ani muscles stiffness assessment.Methods A total of 69 healthy volunteers underwent STE and STQ examinations of the right levator ani muscles at three different locations(anterior,middle,and posterior)during rest,contraction,and stretch states.The study analyzed the success rate,variability,and measurements(Young's modulus)of the detection techniques,as well as assessed the inter-operator and intra-operator consistency.Results Both convex transducer STE and linear transducer STQ techniques exhibited higher overall success rates and lower variability in detecting the middle segment of the levator ani muscles compared to convex transducer STQ and linear transducer STE techniques,with statistically significant differences(all P<0.05).There was statistically significant difference in the measurements of levator ani muscles detected by convex transducer STQ technique and linear transducer STE technique(P<0.05).There was no statistically significant difference in the measurements of levator ani muscles detected by convex transducer STE technique and linear transducer STQ technique(P>0.05).The inter-operator and intra-operator consistency of convex transducer STE and linear transducer STQ technology were determined to be 0.869,0.919,0.772,0.850,respectively.Conclusion Both convex transducer STE and linear transducer STQ techniques demonstrate high success rates and low variability in assessing levator ani muscles stiffness,and there was no significant difference in the measurements of them,they were suitable for clinical promotion widely.

Objective To establish the pharmacokinetic model of linezolid in neonates,and to optimize the administration regimen. Methods A prospective study was conducted among 64 neonates with sepsis who received linezolid as anti-infective therapy,and liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of the drug. Clinical data were collected,and nonlinear mixed effects modeling was used to establish a population pharmacokinetic (PPK) model. Monte Carlo simulation and evaluation was performed for the optimal administration regimen of children with different features. Results The pharmacokinetic properties of linezolid in neonates could be described by a single-compartment model with primary elimination,and the population typical values for apparent volume of distribution and clearance rate were 0.79 L and 0.34 L/h,respectively. The results of goodness of fit,visualization verification,and the Bootstrap method showed that the model was robust with reliable results of parameter estimation and prediction. Monte Carlo simulation results showed that the optimal administration regimen for linezolid in neonates was as follows:6 mg/kg,q8h,at 28 weeks of gestational age (GA);8 mg/kg,q8h,at 32 weeks of GA;9 mg/kg,q8h,at 34-37 weeks of GA;11 mg/kg,q8h,at 40 weeks of GA. Conclusions The PPK model established in this study can provide a reference for individual administration of linezolid in neonates. GA and body weight at the time of administration are significant influencing factors for the clearance rate of linezolid in neonates.

Objective To explore the acupoint selection rules of acupuncture treatment for cerebellar ataxia using data mining techniques.Methods Taking the related literature of acupuncture treatment of cerebellar ataxia as the retrieval content,the computer retrieval of China National Knowledge Internet(CNKI),China Biomedical Literature Database(SinoMed),Wanfang Data Knowledge Service Platform(Wanfang),China Science and Technology Journal Database(VIP),American Biomedical Information Retrieval System(PubMed)and other major databases.The eligible acupoints in the literature were entered into the Microsoft Excel 2021 software table to establish a database of acupoints frequency,meridian tropism,specific acupoints,distribution sites and other information for acupuncture treatment of cerebellar ataxia.SPSS Modeler 18.0 Apriori algorithm,SPSS Statistics 25.0 and SPSS Modeler 18.0 Web complex network were used to analyze the association rules of the included prescription acupoints,Ward cluster analysis and draw the tree diagram and the Web network diagram of high-frequency acupoints and core prescriptions.Results(1)A total of 93 articles were included,including 117 acupuncture prescriptions and 172 acupoints,with a total frequency of 1 199 times of acupoints.(2)The top 10 acupoints were Fengchi(GB20),Zusanli(ST36),Hegu(LI4),Baihui(DU20),Sanyinjiao(SP6),Taichong(LR3),Quchi(LI11),Yanglingquan(GB34),Wangu(GB12),and Tianzhu(BL10).(3)The top five meridians used frequently were gallbladder meridian of foot shaoyang,governor vessel(GV),stomach meridian of foot yangming,large intestine meridian of hand yangming and bladder meridian of foot taiyang.(4)The selection of acupoints is mainly based on the head,face,neck and lower limbs.(5)The highest frequency of the use of specific points is the intersection point.(6)The high-frequency acupoints for acupuncture treatment of cerebellar ataxia are Fengchi-Wangu,Fengchi-Tianzhu and Fengchi-Tianzhu-Wangu.The top 31 high-frequency acupoints(frequency＞10 times)can be divided into nine effective clusters.Conclusion Acupuncture treatment for cerebellar ataxia has formed a compatibility rule with the main principle of"regulating the mind and constraining the bones,extinguishing wind and stopping the movement",with the far and near acupoints as the main body,and attaches importance to the application of yang meridians with multiple qi and blood,presenting the basic acupoint prescription with Fengchi-Wanggu-Tianzhu as the core.