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.

This article reports 2 cases of urinary retention in Alzheimer's disease with agitation treated by acupuncture. Based on patients' clinical symptoms, the etiology and pathogenesis were determined, and acupuncture was applied to Baihui (GV20), Sishencong (EX-HN1), Shenting (GV24), and bilateral Ciliao (BL32), Zhongliao (BL33), Fengchi (GB20), Taiyang (EX-HN5), etc. to regulate the mind and promote water metabolism. The positive and negative electrodes of the SDZ-Ⅴ type electroacupuncture device were attached to ipsilateral Ciliao (BL32), Zhongliao (BL33) respectively, with continuous wave, at the frequency of 15 Hz, and the current of 3 to 10 mA, depending on patients' tolerance. The needles were retained for 20 min. The treatment was delivered once every other day, 3 interventions a week and 12 interventions as 1 course. Both patients reported the micturition desire after 1 intervention with acupuncture and the catheter was removed on the same day. The urination was ameliorated without dysuresia after 1-2 courses of treatment, and the agitated behavior was alleviated. It can be the reference for the clinical treatment of urinary retention in patients with Alzheimer's disease with agitation.
Humans ; Alzheimer Disease/psychology* ; Acupuncture Therapy ; Urinary Retention/etiology* ; Male ; Female ; Aged ; Acupuncture Points ; Psychomotor Agitation/complications*

Ganoderic acid is a class of lanostane-type triterpenoids found in Ganoderma species, and is one of the most important pharmacologically active components in G. lucidum, exhibiting antioxidant, anti-neuropsychiatric, anti-tumor, and immune-enhancing properties. The content of ganoderic acid in G. lucidum is very low, and the traditional extraction process is complex, yielding minimal amounts at high cost. The biosynthetic pathway of G. lucidum triterpenoids(GLTs), including the synthesis of different structural forms of ganoderic acid from lanosterol, as well as the molecular regulatory mechanisms involving key regulatory enzyme genes and their functions, are not yet fully understood. With the continuous development of synthetic biology technologies, there has been a deeper understanding of the biosynthesis and metabolic regulation pathways of ganoderic acid and its derivatives at the molecular level. Research has explored the key regulatory enzyme genes related to ganoderic acid biosynthesis and their functions. Moreover, through the optimization of synthetic biology and culture conditions, large-scale production and preparation of GLTs at the cellular level have been achieved. This paper reviews and analyzes the latest research progress on the biosynthesis pathways and metabolic regulation of GLTs, focusing on the configuration of ganoderic acid and its derivatives, the biosynthetic pathways, key enzyme genes, transcription factors related to ganoderic acid biosynthesis, signal transduction mechanisms, and factors affecting triterpenoid biotransformation. This review is expected to provide a theoretical basis and technical reference for improving the efficient production of triterpenoid pharmacological components and the exploitation and utilization of G. lucidum resources.
Triterpenes/chemistry* ; Reishi/chemistry* ; Biosynthetic Pathways ; Lanosterol

This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

OBJECTIVE: To study the effects and mechanisms of juglone on the proliferation and apoptosis of acute myeloid leukemia (AML) cells. METHODS: Juglone and AML targets were collected from public databases, and the intersecting target clusters were taken for functional enrichment analysis to explore the potential mechanism of juglone in the treatment of AML. Then wet experiments were performed to verify. AML cell lines including KG-1a, MV-411, THP-1 and MOLM-13 were treated with different concentrations of juglone for 24 h. MTT assay was used to detect cell viability and determine the IC₅₀, and the most sensitive cell line was screened for subsequent experiments. Flow cytometry was used to detect the apoptosis of cells treated with different concentrations of juglone. Western blot was performed to check the expression of relevant proteins. RESULTS: Eleven targets were obtained as potential targets for juglone in the treatment of AML, and the top ten significantly enriched pathways were intrinsic pathway of apoptosis, programmed cell death, cytochrome c-mediated apoptotic response, apoptosis, apoptotic factor-mediated response, regulated necrosis, cytokine signaling in immune system, signaling by interleukins, oncogene induced senescence, and signal transduction. The cell viability of KG-1a, MV-411, THP-1 and MOLM-13 was decreased with increasing juglone concentration after 24 h of juglone treatment (r =-0.992, -0.886, -0.956, -0.910). Among them, MOLM-13 was the most sensitive to juglone. The results of flow cytometry showed that the apoptosis rate of MOLM-13 tended to significantly increase with the increasing concentration of juglone (r =0.99). At the same time point, p-RIPK1/RIPK1, p-RIPK3/RIPK3, and p-MLKL/MLK were decreased in each juglone concentration group compared with control group. CONCLUSION Juglone inhibits the viability of KG-1a, MV-411, THP-1 and MOLM-13 cells, and induces apoptosis of MOLM-13 cells, the mechanism of which may be related to the inhibition of RIPK1/RIPK3/MLKL signaling pathway.
Humans ; Naphthoquinones/pharmacology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Leukemia, Myeloid, Acute/pathology* ; Cell Line, Tumor ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Protein Kinases/metabolism* ; Signal Transduction ; Cell Survival/drug effects*

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

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.

In developing rapid and living guidelines of traditional Chinese medicine （TCM） in response to public health emergencies， it is important that evidence continue to be reviewed， and clinical questions and recommendations updated if necessary， due to the rapid changes in disease progression and the continuous generation of relevant research evidence. This paper proposed that the updating scope in dynamic mode should first be identified； then evidence monitoring should be carried out in four aspects， including clinical research， related guidelines or laws and regulations， disease progression， as well as clinical use of recommendations and clinical needs； finally， based on the results of the evidence monitoring， different options should be made， including revising the clinical questions， updating the evidence and recommendations， and withdrawing the guideline.

Objective To investigate the impact of total parathyroidectomy with autotransplantation (tPTx+AT)on bone mineral density and serum soluble Klotho (sKlotho)level in patients with secondary hyperparathyroidism (SHPT).Methods A total of 86 patients undergoing tPTx+AT in the Second Affiliated Hospital of Anhui Medical University from June 2019 to May 2022 were recruited in this study.Their demographic characteristics were collected before surgery,along with serum levels of corrected calcium,phosphorus,intact parathyroid hormone (iPTH),alkaline phosphatase (ALP),fibroblast growth factor 23 (FGF23),and sKlotho before and at 5 d,and 1,3,6,12 and 24 months after surgery.Dual energy X-ray absorptiometry was used to determine the BMD values of the lumbar spine L1-L4 before surgery and at 3,6,12 and 24 months after surgery.The changes in BMD and serum FGF23 and sKlotho levels before and after tPTx+AT were observed.Results Surgical treatment was successfully completed in all 86 patients,with their clinical symptoms such as bone pain and skin itching significantly improved postoperatively,and markedly decreased serum calcium,phosphorus,iPTH,ALP and FGF23 levels.The sKlotho level was significantly lower at 5 d postoperatively than that preoperatively,with that at 1 month after surgery increased by approximately 24.5％ than the preoperative level,and then the level was in a stable trend.The BMD values at the lumbar spine L1-L4 were increased postoperatively,and reached the highest levels at 12 months postoperatively.Further analyses showed that dialysis vintage,duration of SHPT,and ALP,iPTH and FGF23 levels were negatively correlated with the Z-scores of the lumbar spine L1-L4,while sKlotho level was positively correlated with the Z-scores.Conclusion tPTx+Atcan significantly improve the clinical symptoms of SHPT patients,regulate the balance of calcium and phosphorus metabolism,increase sKlotho level and reduce FGF23 level.It is an effective method to improve BMD.