Guided by the theory of "the kidney storing essence, governing the bones, and producing marrow", this study explored the mechanism of icariin(ICA) in regulating the osteogenic differentiation of rat bone mesenchymal stem cells(BMSCs) through caveolin-1(Cav1) via in vitro and in vivo experiments, aiming to provide a theoretical basis for the prevention and treatment of postmenopausal osteoporosis with traditional Chinese medicine(TCM). Primary cells were obtained from 4-week-old female SD rats using the whole bone marrow adherent method. Flow cytometry was used to detect the expression of surface markers CD29, CD90, CD11b, and CD45. The potential for osteogenic and adipogenic differentiation was assessed. The effect of ICA on cell viability was determined using the CCK-8 assay, and the impact of ICA on the formation of mineralized nodules was verified by alizarin red staining. A stable Cav1-silenced cell line was constructed using lentivirus. The effect of Cav1 silencing on osteogenic differentiation was observed via alizarin red staining. Western blot analysis was conducted to detect the expression of Cav1, Hippo/TAZ, and osteogenic markers such as Runt-related transcription factor 2(RUNX2) and alkaline phosphatase(ALP). The results showed that primary cells were successfully obtained using the whole bone marrow adherent method, positively expressing surface markers of rat BMSCs and possessing the potential for both osteogenic and adipogenic differentiation. The CCK-8 assay and alizarin red staining results indicated that 1×10~(-7) mol·L~(-1) was the optimal concentration of ICA for intervention in this experiment(P<0.05). During osteogenic induction, ICA inhibited Cav1 expression(P<0.05) while promoting TAZ expression(P<0.05). Alizarin red staining demonstrated that Cav1 silencing significantly promoted the osteogenic differentiation of BMSCs. After ICA intervention, TAZ expression was activated, and the expression of osteogenic markers ALP and RUNX2 was increased. In conclusion, Cav1 silencing significantly promotes the osteogenic differentiation of BMSCs, and ICA promotes this differentiation by inhibiting Cav1 and regulating the Hippo/TAZ signaling pathway.
Animals ; Mesenchymal Stem Cells/metabolism* ; Caveolin 1/genetics* ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; Cell Differentiation/drug effects* ; Female ; Signal Transduction/drug effects* ; Flavonoids/administration & dosage* ; Protein Serine-Threonine Kinases/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Cells, Cultured ; Humans

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

The pathogenesis of depression is complex, and some existing monoamine antidepressants have problems such as drug resistance or off-target failure. Traditional Chinese medicine has the characteristics of "multi-component and multi-target", and has been used in the treatment of depression in clinical practice. Yueju pill is effective in the treatment of depression. Geniposide and ligustrazine, the active ingredients of Gardeniae fructus and Ligusticum sinense 'Chuanxiong', play a key role in the treatment of depression. In this study, based on the neuroprotective activity of genipin and the rapid antidepressant activity of tetramethylpyrazine, a series of novel genipin derivatives were designed and synthesized through pharmacophore assembly principle, and their neuroprotective activity and antidepressant effect were investigated. The results showed that the novel genipin derivatives had well neuroprotective activity on the glutamate-induced HT-22 cell model, with compounds W-1 and W-3 showing better protective activity. In behavioral despair depression (BDD) model mice, compound W-3 was found to have better antidepressant activity than W-1 in tail suspension test and forced swimming test. Further study on the behavior of chronic unpredictable mild stress (CUMS) model mice showed that W-3 could significantly improve the depression-like behavior of model mice. All animal experiments were approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-mouse-2022027). The effects of the preferred compound W-3 on protein kinase A (PKA), cAMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine 1A (5-HT_1A) receptor, N-methyl-D-aspartate ionic glutamate receptor 2A (GluN2A) and N-methyl-D-aspartate ionic glutamate receptor 2B (GluN2B) were analyzed by Western blot. W-3 treatment significantly up-regulated the protein expression of PKA, CREB, BDNF and 5-HT_1A, and down-regulated the protein expression of GluN2A and GluN2B. The results of qRT-PCR were consistent with those of Western blot. According to the above results, compound W-3 has a potential antidepressant effect, and its mechanism may be related to the activation of PKA-CREB-BDNF signaling pathway by regulating the expression of GluN2A, GluN2B and 5-HT_1A receptor proteins.

Objective To provide reference for the optimization and improvement of interoperability between the standard system of the Chinese Pharmacopoeia and other standards.Methods The interoperability of various pharmacopoeia standard systems was compared by searching for citations from the Chinese Pharmacopoeia,the United States Pharmacopoeia-National Formulary,the European Pharmacopoeia,the Japanese Pharmacopoeia,and other standards,including references to domestic regulations and guidelines,standards of the International Organization for Standardization,guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use,documents of the World Health Organization,and standards from other countries and international organizations.Results In recent years,pharmacopoeias in the world had continuously increased the citation of non pharmacopoeial standards.The types,quantities,and fields of the United States Pharmacopoeia-National Formulary referencing other standards far exceed those of other pharmacopoeias.The Chinese Pharmacopoeia cites the least number of other standards.Conclusion It is suggested that the Chinese Pharmacopoeia should enhance the interoperability with other standard systems in the standards of various professional fields,enhance the openness,harmonization and advantages,and form a more complete standard system.

Objective:To investigate the clinical effect of magnetic stimulation combined with moxibustion on mild to moderate overactive bladder(OAB)and sexual function in women.Methods:We enrolled 80 female patients with mild to moderate OAB in this study and equally randomized them into a control and an experimental group,the former treated by magnetic stimulation and the latter by magnetic stimulation combined with moxibustion,both for 8 weeks.We obtained from the patients their OAB syndrome scores(OABSS),72-hour urination diary(72-h UD)scores,International Consultation on Incontinence Questionnaire-Overactive Bladder(ICIQ-OAB)scores and female sexual function indexes(FSFI),and compared them between the two groups before and after interven-tion.Results:A total of 77 patients completed the study,37 in the control and 40 in the experimental group.There were no statisti-cally significant differences in the baseline data between the two groups(P＞0.05).Compared with the baseline,the experimental group showed significant improvement after treatment in the OABSS(7.54±1.12 vs 4.46±0.96),72-h urine volume([126.40±46.04]vs[216.63±38.26]ml),urination frequency(15.55±3.21 vs 8.03±1.40),ICIQ-OAB score(10.25±1.15 vs 6.32±1.07)and FSFI(20.00±12.40 vs 33.30±21.00)(all P＜0.05),even more significantly than in the control group(OABSS:4.46±0.96 vs 5.59±0.90;72-h urine volume:[216.63±38.26]vs[173.41±15.55]ml;urination frequency:8.03±1.40 vs 9.90±1.49;ICIQ-OAB score:6.32±1.07 vs 7.89±0.77;FSFI:33.30±21.00 vs 30.40±10.40)(all P＜0.01).Conclu-sion:Magnetic stimulation combined with moxibustion can improve the symptoms of mild to moderate overactive bladder and improve sexual function in females.

Objective To explore characteristics of clinical and imaging findings in patients with fat embolism syndrome.Methods From January 2021 to October 2022,clinical manifestations of 13 patients with fat embolism due to fracture or or-thopaedic surgery were retrospectively analyzed,including 11 males and 2 females,aged from 17 to 60 years old.Mental and respiratory abnormalities and changes in vital signs occurred after admission or after surgery,and patient's chest and brain imaging results were abnormal.The patient's mental and respiratory abnormalities,vital signs,chest and brain imaging results were continuously monitored.Results The main clinical manifestations of fat embolism syndrome were abnormal pulmonary respiration in 13 patients,abnormal central nervous function in 7 patients,and spotted rash in 2 patients.Chest CT showed dif-fuse distribution of ground glass shadows in 13 patients,and severe symptoms were"snowstorm".Nine patients with ground glass fusion consolidation,5 patients with multiple nodules and 4 patients accompanied by bilateral pleural effusion.Head CT findings of 5 patients were negative,and head MRI findings of 1 patient showed multiple T1WI low signal,T2WI high signal shadow,DWI high signal shadow,and"starry sky sign"in basal ganglia,radiative crown,hemioval center,thalamus,frontal parietal cortex and subcortex.Conclusion Fat embolism syndrome has a high mortality rate.Clinical manifestations of respira-tory system and nervous system are not specific,and the skin spot rash has a characteristic manifestation.The"blizzard"sign is the specific manifestation of chest X-ray and CT examination of fat embolism,and the"starry sky"sign is the typical manifesta-tion of diffusion-weighted sequence of brain MRI examination of fat embolism.

OBJECTIVE: To establish the dynamic treatment strategy of Chinese medicine (CM) for metastatic colorectal cancer (mCRC) by machine learning algorithm, in order to provide a reference for the selection of CM treatment strategies for mCRC. METHODS: From the outpatient cases of mCRC in the Department of Oncology at Xiyuan Hospital, China Academy of Chinese Medical Sciences, 197 cases that met the inclusion criteria were screened. According to different CM intervention strategies, the patients were divided into 3 groups: CM treatment alone, equal emphasis on Chinese and Western medicine treatment (CM combined with local treatment of tumors, oral chemotherapy, or targeted drugs), and CM assisted Western medicine treatment (CM combined with intravenous regimen of Western medicine). The survival time of patients undergoing CM intervention was taken as the final evaluation index. Factors affecting the choice of CM intervention scheme were screened as decision variables. The dynamic CM intervention and treatment strategy for mCRC was explored based on the cost-sensitive classification learning algorithm for survival (CSCLSurv). Patients' survival was estimated using the Kaplan-Meier method, and the survival time of patients who received the model-recommended treatment plan were compared with those who received actual treatment plan. RESULTS: Using the survival time of patients undergoing CM intervention as the evaluation index, a dynamic CM intervention therapy strategy for mCRC was established based on CSCLSurv. Different CM intervention strategies for mCRC can be selected according to dynamic decision variables, such as gender, age, Eastern Cooperative Oncology Group score, tumor site, metastatic site, genotyping, and the stage of Western medicine treatment at the patient's first visit. The median survival time of patients who received the model-recommended treatment plan was 35 months, while those who receive the actual treatment plan was 26.0 months (P=0.06). CONCLUSIONS The dynamic treatment strategy of CM, based on CSCLSurv for mCRC, plays a certain role in providing clinical hints in CM. It can be further improved in future prospective studies with larger sample sizes.
Humans ; Colorectal Neoplasms/therapy* ; Machine Learning ; Female ; Male ; Middle Aged ; Neoplasm Metastasis ; Algorithms ; Medicine, Chinese Traditional/methods* ; Aged ; Adult ; Kaplan-Meier Estimate

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective:To investigate the ego-depletion level of adolescents with type 1 diabetes mellitus (T1DM) and to explore its association with glycemic control and quality of life.Methods:This was a cross-sectional survey study. A total of 195 adolescents with T1DM were recruited from the First Affiliated Hospital of Nanjing Medical University from March to September 2022 by convenient sampling method. The Self-Regulatory Fatigue Scale (SRF-S) and Short Form of the Chinese version Diabetes Quality of Life for Youth Scale (C-DQOLY-SF) and the general information questionnaire were collected and the glycated hemoglobin (HbA 1c) value was detected. Results:The total score of self-regulatory fatigue for 195 adolescents with T1DM was (42.23 ± 9.94) points, with a scoring rate of 52.79%, which was at a medium level. Pearson correlation analysis showed that the total score of self-regulatory fatigue was positively correlated with HbA1c ( r = 0.25, P<0.01), and negatively correlated with quality of life ( r = -0.61, P<0.01). The hierarchical linear regression results showed that after controlling for demographic sociolagy and disease variables, ego-depletion had a positive predictive effect on HbA1c ( t = 3.69, P<0.01), while ego-depletion had a negative predictive effect on Quality of life ( t = -8.48, P<0.01). Conclusions:Ego-depletion of adolescents with T1DM may affect their blood glucose control and quality of life, which should be noticed by medical workers.