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

This article reports the clinical features and gene mutation types of a large family with Nascimento form of syndromic X-linked intellectual developmental disorder (MRXSN), involving 9 individuals across 3 generations, and a literature review was conducted. In this family, 9 individuals had similar manifestations including mental retardation and unusual facies, and 4 of them had passed away. Genetic testing showed that the proband had the deletion of exons 2-3 of the UBE2A gene, which was inherited from the mother. Fluorescent quantitative polymerase chain reaction showed that the proband and his uncle had the deletion of exons 2-3 of the UBE2A gene; the proband's mother, grandmother, and great-aunt had a heterozygous deletion of exons 2-3 of the UBE2A gene; the proband's father, sister, and aunt had a normal copy number of exons 2-3 of the UBE2A gene. The 34 patients reported in the literature had diverse clinical phenotypes, and UBE2A gene mutations (22/34, 65%) and large fragment deletions (12/34, 35%) were the main mutation types. Moderate to severe mental retardation (34/34, 100%), speech and language impairment (33/34, 97%), and unusual facies (32/34, 94%) were the main clinical manifestations of MRXSN patients. The disease has obvious phenotypic heterogeneity, and early diagnosis facilitates optimal prenatal and postnatal management to improve reproductive outcomes.
Humans ; Male ; Ubiquitin-Conjugating Enzymes/genetics* ; Female ; X-Linked Intellectual Disability/genetics* ; Gene Deletion ; Child ; Pedigree ; Child, Preschool ; Adult

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

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The methanol extract of Huperzia serrata was separated and purified by ODS, AB-8 macroporous adsorption resin, dextran gel Sephadex LH-20 and silica gel column chromatography combined with the semi-pre HPLC. The chemical structures of the isolated compounds were identified by MS, IR, NMR, etc. Four compounds were isolated from Huperzia serrata and identified, named as serratinine C (1), lycobeline C (2), diphaladin A (3) and crenatine (4). Compound 1 is a new alkaloid, compounds 2-4 were isolated for the first time. In vitro biological activity experiments showed that compound 1 could significantly reduce the levels of nitric oxide and reactive oxygen species in glial cells induced by lipopolysaccharide and had significant antioxidant biological activity.

Cardiac contractility modulation(CCM),as a new implantable electronic therapy device for treating chronic heart failure with reduced ejection fraction(HFrEF),has rapidly become a hot topic in the cardiovascular field due to its ability to enhance ventricular myocardial contractility,improve patients'symptoms and signs,cardiac function indexes and even long-term prognosis.This article reviews the mechanism and clinical studies of CCM in treating HFrEF,and based on its mechanism and signal transduction algorithm,further analyzes and prospects its efficacy in patients with heart failure with preserved ejection fraction,cardiac resynchronization therapy non-response,and HFrEF with concomitant atrial fibrillation,aiming to promote CCM to meet the needs of more diverse clinical situations in heart failure patients.

Major depressive disorder(MDD)is a prevalent con-dition associated with substantial impairment and low remission rates.Traditional antidepressants demonstrate delayed effects,low cure rate,and inadequate therapeutic effectiveness for man-aging treatment-resistant depression(TRD).Several studies have shown that ketamine,a non-selective N-methyl-D-aspartate receptor(NMDAR)antagonist,can produce rapid and sustained antidepressant effects.Ketamine has demonstrated efficacy for reducing suicidality in TRD patients.However,the pharmaco-logical mechanism for ketamine's antidepressant effects remains incompletely understood.Previous research suggests that the an-tidepressant effects of ketamine may involve the monoaminergic,glutamatergic and dopaminergic systems.This paper provides an overview of the pharmacological mechanism for ketamine's anti-depressant effects and discuss the potential directions for future research.

Objective:To compare the efficacy of double Z-shaped suture and modified Kessler suture in the repair of acute closed Achilles tendon rupture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 27 patients with acute closed Achilles tendon rupture admitted to the Second Affiliated Hospital of Xi′an Jiaotong University from July 2018 to July 2022, including 24 males and 3 females, aged 14-53 years [(35.7±8.2)years]. All the patients underwent primary open surgical repair of the Achilles tendon, among whom 16 patients were treated with the double Z-shaped suture technique (double Z-shaped suture group) and 11 with the modified Kessler suture technique (modified Kessler suture group). Visual analogue scale (VAS) scores preoperatively and at 2, 4, and 6 weeks postoperatively as well as at the last follow-up were compared between the two groups. American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores, Achilles tendon total rupture scores (ATRS), ankle range of motion (dorsiflexion and plantarflexion angles), and shear wave elastography (SWE) [with its results recorded as shear wave velocity (SWV)] were applied to evaluate the recovery of tendon function and quality. High-frequency ultrasonography was also used to evaluate the recovery of morphological structure of the Achilles tendon and soft tissue adhesion. Tolerance to early rehabilitation at 2 weeks postoperatively and the incidence of postoperative complications were compared between the two groups.Results:All the patients were followed up for 6-12 months [(9.6±1.3)months]. There was no statistically significant difference in preoperative VAS scores between the two groups ( P>0.05). At 2, 4, and 6 weeks postoperatively, the VAS scores in the double Z-shaped suture group were 4.6(4.0, 5.0)points, 1.6(1.0, 2.0)points, and 0.5(0.0, 1.0)points respectively, significantly lower than those in the modified Kessler suture group [6.9(6.0, 8.0)points, 2.5(2.0, 3.0)points, and 1.4(1.0, 2.0)points] ( P<0.05 or 0.01). At the last follow-up, the VAS decreased to 0.0(0.0, 0.0)points in both groups. VAS score in the double Z-shaped suture group significantly decreased at 2 weeks postoperatively compared to that preoperatively, with a consistent downward trend observed at all the postoperative time points ( P<0.05). In the modified Kessler suture group, there was no significant difference in VAS scores preoperatively and at 2 weeks postoperatively ( P>0.05), but a downward trend was noted at 4 and 6 weeks postoperatively and at the last follow-up ( P<0.05). There were no significant differences in AOFAS ankle-hindfoot scores, ATRS or SWV at 2, 4, and 6 weeks postoperatively and at the last follow-up ( P>0.05). At 2, 4, and 6 weeks postoperatively, dorsiflexion angles in the double Z-shaped suture group were (-18.2±3.9)°, (-13.7±2.8)°, and (-6.6±2.4)° respectively, significantly better than those in the modified Kessler suture group [(-24.1±2.7)°, (-18.3±3.0)°, and (-12.0±2.8)°] ( P<0.01). No significant difference in dorsiflexion angles was observed between the groups at the last follow-up ( P>0.05). No significant differences in plantarflexion angles were noted at 2 weeks postoperatively and at the last follow-up ( P>0.05). At 4 and 6 weeks postoperatively, plantarflexion angles in the double Z-shaped suture group were (37.5±3.8)° and (42.1±3.3)°respectively, significantly better than those in the modified Kessler suture group [(34.6±2.0)° and (38.0±1.4)°] ( P<0.05 or 0.01). Both groups showed increasing trends in AOFAS ankle-hindfoot scores, dorsiflexion and plantarflexion angles, and SWV at 4 and 6 weeks postoperatively, as well as at the last follow-up ( P<0.05 or 0.01). No significant differences were noted in ATRS at 2 and 4 weeks postoperatively in the double Z-shaped suture group ( P>0.05), but significant improvements were observed at 6 weeks postoperatively and at the last follow-up ( P<0.05 or 0.01). In the modified Kessler suture group, no significant changes in ATRS scores were observed at 2, 4 and 6 weeks postoperatively ( P>0.05), except a significant increase at the last follow-up ( P<0.05). High-frequency ultrasonography at 2, 4, and 6 weeks postoperatively as well as at the last follow-up indicated good morphological recovery of the Achilles tendon in both groups, while soft tissue adhesion was significantly less in the double Z-shaped suture group compared with that of the modified Kessler suture group. Thirteen patients (81.3%) in the double Z-shaped suture group and 3 patients (27.3%) in the modified Kessler suture group were observed to tolerate the early rehabilitation at 2 weeks postoperatively as scheduled in the rehabilitation plan ( P<0.05). There was no statistically significant difference in the incidence of postoperative complications between the groups ( P>0.05). Conclusion:Compared with the modified Kessler suture technique, the double Z-shaped suture technique can reduce postoperative pain at an early stage, enhance the restoration of ankle joint mobility, lower the risk of postoperative soft tissue adhesion, and improve tolerance to rehabilitation in the repair of acute closed Achilles tendon rupture.

Objective To estimate adolescents and children age using stepwise regression and machine learning methods based on the pulp and tooth volumes of the left maxillary central incisor and cuspid on cone beam computed tomography(CBCT)images,and to compare and analyze the estimation re-sults.Methods A total of 498 Shanghai Han adolescents and children CBCT images of the oral and maxillofacial regions were collected.The pulp and tooth volumes of the left maxillary central incisor and cuspid were measured and calculated.Three machine learning algorithms(K-nearest neighbor,ridge regression,and decision tree)and stepwise regression were used to establish four age estimation models.The coefficient of determination,mean error,root mean square error,mean square error and mean ab-solute error were computed and compared.A correlation heatmap was drawn to visualize and the monotonic relationship between parameters was visually analyzed.Results The K-nearest neighbor model(R2=0.779)and the ridge regression model(R2=0.729)outperformed stepwise regression(R2=0.617),while the decision tree model(R2=0.494)showed poor fitting.The correlation heatmap demon-strated a monotonically negative correlation between age and the parameters including pulp volume,the ratio of pulp volume to hard tissue volume,and the ratio of pulp volume to tooth volume.Con-clusion Pulp volume and pulp volume proportion are closely related to age.The application of CBCT-based machine learning methods can provide more accurate age estimation results,which lays a founda-tion for further CBCT-based deep learning dental age estimation research.