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.

Purpose/Significance To summarize the application progress of artificial intelligence (AI) in the field of digestive endoscopy, to analyze the key challenges and look forward to future trends, so as to provide guidance for clinical practice and research. Method/Process Domestic and international literature databases such as PubMed, Web of Science, and CNKI are retrieved. The application research of AI in the auxiliary diagnosis, process optimization and treatment precision of digestive endoscopy is sorted out. Result/Conclusion Although AI has significant clinical value in the field of digestive endoscopy, its application still faces major challenges, and its prospects and limitations need to be further discussed.

Objective To investigate the effects of sufentanil on myocardial cells and renal function in rat models of non-stopping coronary artery bypass grafting.Methods SD rats were randomly divided into sham group(only thoracectomy without coronary artery ligation),model group(ischemia perfusion model was constructed),experimental-L group(ischemia perfusion model+0.5 μg·kg-1 sufentanil)and experimental-H group(ischemia perfusion model+1μg·kg-1 sufentanil).The mice were sacrificed 6 h after operation.The expressions of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β)and interleukin-6(IL-6)in cardiomyocytes and renal cells were detected by enzyme-linked immunosorbent assay(ELISA).The expressions of apoptosis-related proteins in cardiomyocytes and renal cells were detected by Western blot.Serum renal function was detected with serum renal function kit.Results The expression levels of TNF-α in myocardial cells were(50.41±6.03),(136.61±21.73),(102.36±12.84)and(74.21±16.32)pg·mg-1 in sham group,model group,experimental-L group and experimental-H group,respectively;the expression levels of cysteinyl aspartate specific proteinase-3(Caspase-3)were 0.31±0.02,1.26±0.18,0.83±0.12 and 0.67±0.08,respectively;blood urea nitrogen(BUN)levels were(5.94±1.12),(20.04±5.36),(16.84±4.19)and(10.96±3.64)μmol·L-1,respectively;the expression levels of TNF-α in renal cells were(146.49±16.13),(1 023.82±34.69),(841.65±49.66)and(324.84±48.93)pg·mg-1,respectively;the expression levels of Caspase-3 in renal cells were 0.48±0.06,1.15±0.17,0.96±0.06 and 0.74±0.07,respectively.The difference between experimental-H group and sham group,model group and experimental-L group were statistically significant(all P＜0.05).Conclusion Sufentanil can significantly reduce the production of inflammatory factors and the expression of apoptotic proteins in rat cardiomyocytes,significantly improve the renal function of rats,and significantly reduce the production of inflammatory factors and the expression of apoptotic proteins in rat renal cells.

Interleukin-35(IL-35)is an important immunosuppressive cytokine that has been shown to play a role in the immune response of various diseases.In this study,we cloned the coding sequence of human IL-35 gene,constructed single subunit expression vectors pXC17.4-p35 and pcDNA3.1(+)-EBI3,and co-transfected CHO-K1 cells to express IL-35 in vitro.No binding was found between subunits of p35 and EBI3.Knobs-into-Holes(KIH)can solve the problem of heavy chain mismatch of heterolo-gous antibodies.Therefore,expression vectors pXC17.4-p35-Fch and pcDNA3.1(+)-EBI3-Fck were constructed by fusing KIH structures on the basis of the original sequences to express the recombinant fu-sion protein of KIH-IL-35.The expression vectors of two subunits were exchanged at the same time to verify the influence of different vectors on the expression level of KIH-IL-35.The analysis of various pro-tein detection methods showed that the correct expression rate of KIH-IL-35 structure was significantly im-proved.Affinity purification of KIH-IL-35 was performed after large amount of expression,and the bind-ing activity of KIH-IL-35 to glycoprotein 130(gp130)was detected by ELISA.The results showed that the binding of KIH-IL-35 to gp130 was concentration dependent.The indirect activity of KIH-IL-35 and M1 cells was detected by cell activity assay.Further results showed that the inhibition rate of M1 cells in-creased in a dose-dependent manner with the concentration of KIH-IL-35.In addition,a method for de-termining IL-35 activity by activated human peripheral blood mononuclear cells was successfully estab-lished.Activated PBMCs increased in a dose-dependent manner with KIH-IL-35 concentration.In sum-mary,this study utilized the KIH-IL-35 model to enhance the expression of recombinant human IL-35 and validated its high activity in vitro,providing new ideas for the study of IL-35 and the recombinant expres-sion of similar heterodimeric cytokines.

The dried rattan stem of the Fibraurea Recisa Pierre plant contains the active ingredient known as fibrauretine (FN). Although it greatly affects Alzheimer's disease (AD), the mechanism of their effects still remains unclear. Proteomics and transcriptomics analysis methods were used in this study to determine the mechanism of FN in the treatment of AD. AD model is used through bilateral hippocampal injection of Aβ1-40. After successful modeling, FN was given for 30 days. The results showed that FN could improve the cognitive dysfunction of AD model rats, reduce the expression of Aβ and P-Tau, increase the content of acetylcholine and reduce the activity of acetylcholinesterase. The Kyoto Encyclopedia of Genes and Genomes enriched differentially expressed genes and proteins are involved in signaling pathways including metabolic pathway, AD, pathway in cancer, PI3K-AKT signaling pathway, and cAMP signaling pathway. Transcriptomics and proteomics sequencing resulted in 19 differentially expressed genes and proteins. Finally, in contrast to the model group, after FN treatment, the protein expressions and genes associated with the PI3K-AKT pathway were significantly improved in RT-qPCR and Western blot and assays. This is consistent with the findings of transcriptomic and proteomic analyses. Our study found that, FN may improve some symptoms of AD model rats through PI3K-AKT signaling pathway.

Objective:To investigate the clinical features, characteristics under white-light endoscopy and endoscopic ultrasonography, and treatment strategies of gastritis cystica profunda (GCP) accompanied with or without neoplastic lesions.Methods:Clinical data of 35 patients, who were pathologically diagnosed as having GCP after endoscopic or surgical resection in Beijing Friendship Hospital, Capital Medical University from January 2015 to February 2021, were retrospectively collected, including 27 patients with neoplastic lesions. The demographic information, clinical manifestations, endoscopic features, treatment methods, and pathological results of GCP were summarized.Results:Thirty-five patients with GCP were 68.26±8.08 years old, and mostly male (80.00%, 28/35). The most common symptom was upper abdominal pain, accounting for 31.43% (11/35), and 25.71% (9/35) had no symptoms. Other symptoms included acid reflux, heartburn, abdominal distension, anemia, and choking sensation after eating. The most common site of GCP was cardia (51.43%, 18/35), and the main endoscopic manifestations of GCP were flat mucosal lesions (68.57%, 24/35), mainly 0-Ⅱa and 0-Ⅱa+Ⅱc type lesions, accounting for 66.67% (16/24). The second common endoscopic manifestation was polypoid eminence (20.00%, 7/35). Endoscopic ultrasonography was performed in 15 patients, with main manifestations of uniform hypoechoic with or without cystic echo (73.33%, 11/15). Among the GCP cases, 33 patients received endoscopic resection, and 2 received surgical treatment. The treatment processes were all successfully completed, and en-bloc resection was accomplished for all lesions receiving endoscopy, with the mean endoscopic operation time of 86.13 min. One patient suffered postoperative delayed bleeding after ESD which was stopped by endoscopic hemostasis. Final pathological results showed that the proportion of GCP complicated with neoplastic lesions was 77.14% (27/35), 68.57% (24/35) with early gastric cancer or precursor. Twenty-three cases achieved R0 resection. One case showed positive basal resection margin and vascular invasion, and recurrence happened in situ at the 5th month of follow-up, surgical resection was then performed. The endoscopic complete resection rate was 95.83% (23/24).Conclusion:GCP usually occurs in middle-aged and elderly male, often located in cardia, manifested mainly as flat mucosal lesions and polypoid changes. Endoscopic ultrasonography shows a high diagnostic value for GCP, and endoscopic treatment is safe and effective minimally invasive treatment for GCP.

Humans ; Temperature ; Cities/epidemiology* ; Hot Temperature ; Cardiovascular Diseases/epidemiology* ; China/epidemiology* ; Mortality

BACKGROUND: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction. OBJECTIVE: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale. METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment. DISCUSSION This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).
Humans ; ST Elevation Myocardial Infarction/therapy* ; Stroke Volume ; Ventricular Remodeling ; Prospective Studies ; Microcirculation ; Ventricular Function, Left ; Myocardial Infarction/etiology* ; Treatment Outcome ; Percutaneous Coronary Intervention/adverse effects* ; Heart Failure/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic

BACKGROUND: Osteoporosis (OP) has become a major public health issue, threatening the bone health of middle-aged and elderly people from all around the world. Changes in the gut microbiota (GM) are correlated with the maintenance of bone mass and bone quality. However, research results in this field remain highly controversial, and no systematic review or meta-analysis of the relationship between GM and OP has been conducted. This paper addresses this shortcoming, focusing on the difference in the GM abundance between OP patients and healthy controls based on previous 16S ribosomal RNA (rRNA) gene sequencing results, in order to provide new clinical reference information for future customized prevention and treatment options of OP. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we comprehensively searched the databases of PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI). In addition, we applied the R programming language version 4.0.3 and Stata 15.1 software for data analysis. We also implemented the Newcastle-Ottawa Scale (NOS), funnel plot analysis, sensitivity analysis, Egger's test, and Begg's test to assess the risk of bias. RESULTS: This research ultimately considered 12 studies, which included the fecal GM data of 2033 people (604 with OP and 1429 healthy controls). In the included research papers, it was observed that the relative abundance of Lactobacillus and Ruminococcus increased in the OP group, while the relative abundance for Bacteroides of Bacteroidetes increased (except for Ireland). Meanwhile, Firmicutes, Blautia, Alistipes, Megamonas, and Anaerostipes showed reduced relative abundance in Chinese studies. In the linear discriminant analysis Effect Size (LEfSe) analysis, certain bacteria showed statistically significant results consistently across different studies. CONCLUSIONS: This observational meta-analysis revealed that changes in the GM were correlated with OP, and variations in some advantageous GM might involve regional differences.
Middle Aged ; Aged ; Humans ; Gastrointestinal Microbiome/genetics* ; RNA, Ribosomal, 16S/genetics* ; Genes, rRNA ; Osteoporosis ; Feces