BACKGROUND:Some studies have found that ferroptosis of osteoblasts can be an important mechanism to induce the occurrence and development of hormone-induced femoral head necrosis.With the development of Chinese medicine,some scholars have found that some Chinese medicine monomer,Chinese medicine compound and Chinese patent medicine can regulate the ferroptosis of osteoblasts through various pathway mechanisms,and finally play a role in the treatment of steroid-induced avascular necrosis of femoral head. OBJECTIVE:To investigate the relationship between ferroptosis and steroid-induced avascular necrosis of femoral head and the mechanism of Chinese medicine regulating ferroptosis of osteoblasts in the treatment of steroid-induced avascular necrosis of femoral head,so as to provide new ideas for the diagnosis and treatment of steroid-induced avascular necrosis of femoral head. METHODS:With"ferroptosis,steroid-induced avascular necrosis of femoral head,osteoblast,Chinese herbal medicine,glucocorticoid,iron metabolism,reactive oxygen species,glutathione peroxidase"as Chinese search terms,and"ferroptosis,hormonal necrosis of the femoral head,osteoblast,Chinese herbal medicine,glucocorticoid,iron metabolism,ROS,GPX4"as English search terms,the search was conducted on CNKI,PubMed,WanFang,VIP and other databases.The relevant articles on osteoblast ferroptosis and steroid-induced avascular necrosis of femoral head and the regulation of Chinese herbal medicine intervention from the establishment of each database to 2023 were screened.Finally,76 articles were systematically analyzed. RESULTS AND CONCLUSION:(1)Ferroptosis of osteoblasts plays an important role in the pathogenesis of steroid-induced avascular necrosis of femoral head.(2)The occurrence of ferroptosis in osteoblasts is regulated by a variety of mechanisms,such as intracellular iron overload causing ferroptosis.Lipid peroxidation damages cell membrane and causes ferroptosis.Cystine/glutamate reverse transporter induced ferroptosis by influencing glutathione level and glutathione peroxidase 4 activity.Fenton reaction in the cell produces a large number of reactive oxygen species and causes ferroptosis.(3)Chinese medicine monomer icariin,Chinese medicine compound Qinge pills and Chinese patent medicine Bushen Huoxue granules can regulate the occurrence of osteoblast ferroptosis,and help to prevent and treat steroid-induced avascular necrosis of femoral head.(4)The mechanism of ferroptosis in osteoblasts is still unclear.Further investigation on the mechanism of action of both is expected to provide a new choice for clinical treatment of steroid-induced avascular necrosis of femoral head.

BACKGROUND:With the variation of disease treatment modes and the in-depth research on senile osteoporosis in recent years,increasing studies have confirmed that traditional Chinese medicine has a significant effect on the prevention and treatment of senile osteoporosis. OBJECTIVE:To investigate the effect of Yishen Gushu Formula on bone metabolic markers in patients with osteoporosis of kidney deficiency and blood stasis type. METHODS:102 patients with senile osteoporosis of kidney deficiency and blood stasis type who were treated at Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine from July 2020 to March 2022 were enrolled,including 32 males and 70 females,aged 71-93 years.All patients were randomly divided into two groups,with 51 patients in each group.The control group was treated with calcium carbonate D3 granules and sodium alendronate tablets,while the treatment group was treated with Yishen Gushu Formula beyond the control group.Treatments in each group lasted 3 months.Bone mineral density of the L1-4 lumbar vertebrae and left femoral neck,visual analog scale score,and serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were measured before and 3 months after treatment.Traditional Chinese medicine syndrome score and therapeutic efficiency were also assessed. RESULTS AND CONCLUSION:After 3 months of treatment,the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly increased in both two groups(P<0.05),and the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly higher in the treatment group than the control group(P<0.05).The visual analog scale scores of both groups after 3 months of treatment were lower than those before treatment(P<0.05),and the visual analog scores of the treatment group after 3 months of treatment were lower than those of the control group(P<0.05).After 3 months of treatment,the serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly improved in both two groups,while compared with the control group,the serum levels of osteocalcin and osteopontin were significantly higher(P<0.05)and the serum levels of type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly lower in the treatment group(P<0.05).After 3 months of treatment,the Traditional Chinese medicine syndrome scores were decreased in both two groups,while the Traditional Chinese medicine syndrome scores in the treatment group were lower than those in the control group.After 3 months of treatment,no significant adverse reactions occurred in both groups.The total effective rate was 88.2%and 70.6%in the treatment and control groups respectively,and there was a significant difference between the two groups(P<0.05).To conclude,Yishen Gushu Formula combined with anti-osteoporosis drugs can significantly improve the clinical symptoms of patients with senile osteoporosis of kidney deficiency and blood stasis type and prevent disease progression by regulating bone metabolism,increasing bone mineral density,and relieving pain.

Objective:To explore the effect of chronic intermittent hypoxia(CIH)on learning and memory dysfunc-tion in rats,as well as the expression of high mobility group box-1(HMGB1)and nuclear transcription factor-KB(NF-κB)in the hippocampus region.Methods:The CIH rat model was established,and forty SD rats were randomly divid-ed into four groups:normoxia group,hypoxia for 4 weeks group(CIH4 group),hypoxia for 8 weeks group(CIH8 group),and hypoxia for 12 weeks group(CIH12 group).Morris water maze was used to assess the learning memory ability of rats,and immunohistochemistry and ELISA were used to detect the expression of HMGB1 and NF-κB in the hippocampus of rats.Results:Compared with the normoxia group,the CIH12 and CIH8 groups had longer escape la-tency,the number of crossing the platform and the residence time in the quadrant of the platform were significantly shortened,but there was no significant difference in the CIH4 group.Additionally,there was no significant expression of HMGB1 and NF-κB in the hippocampal region of the normoxia group,but little expression was observed in CIH4 group,and significantly expressed in CIH8 group and CIH12 group,and the expression of CIH12 group was significantly higher than that of CIH8 group.Conclusion:CIH can lead to a decline in learning and memory function in rats,and the longer time of intermittent hypoxia led to the more significant effect on their learning and memory function.In addi-tion,CIH also leads to increased expression levels of HMGB1 and NF-κB in the hippocampus region,and the expres-sion increased more significantly after hypoxia for 12 weeks,comparing to hypoxia for 8 weeks.

Mitral regurgitation is the most common heart valvular disease at present. In the past, mitral regurgitation was mainly treated by surgical mitral valve repair or replacement. However, with the progress of transcatheter interventional techniques and instruments in recent years, transcatheter mitral valve interventional therapy has gradually shown its advantages and benefited patients. The purpose of this article is to review the progress of transcatheter mitral valve intervention in this year, and to provide prospects for the future of transcatheter mitral valve treatment.

Objective To investigate the material basis and antitumor mechanism of Marsdenia tenacissima (MT) on hepatocellular carcinoma (HCC) by bioinformatics, network pharmacology and molecular docking technology. Methods Active ingredients of MT were collected by literature search and screened by Swiss ADME website, which targets were predicted by Swiss Target Prediction. The chip data of HCC (GSE147888) were downloaded from the NCBI Gene Expression Omnibus (GEO) database. Differentially expressed genes were screened by R software. HCC-related targets were collected from the Genecards and OMIM databases. The Venny online tool was used to obtain the intersection of the herbal medicine targets and the disease targets. Subsequently, drug-target network and protein–protein interaction (PPI) network were constructed by Cytoscape software and String platform. GO enrichment analysis and KEGG pathway analysis were performed to analysis the functions and pathways enriched by key genes. The expression of key genes in HCC and its effect on survival were analyzed by the GEPIA database. The Human Protein Atlas (HPA) was used to analyze the immunohistochemical expression of key genes in HCC. Finally, molecular docking was carried out to investigate interactions between the top five targets and their related active compounds. Results A total of 50 active components were screened and 12 common targets were identified related to MT and HCC. Scutellarein-4-Methylether, Tenasogenin, Sinapic Acid, Dresgenin and Kaempferol were considered as the critical components. JUN, MMP9 and PTGS2 were recognized as key therapeutic targets. The GO analyses demonstrated that key targets mainly involved in the process of gene silencing and inflammatory response. KEGG analysis suggested that key targets were enriched in TNF signaling pathway and IL-17 signaling pathway. Survival analysis by the GEPIA showed significant differences in the expression of ESR1, MMP1, MMP9, JUN, and PPARG between high and low risk groups. Immunohistochemical results showed that ESR1 and MMP9 were differentially expressed in normal and hepatocellular carcinoma tissues. The molecular docking results verified that the drug active ingredient could be stably bound to the target protein. Conclusion This study reflected the multi-component, multi-target and multi-pathway characteristics of the MT in the treatment of HCC, which could provide a scientific basis for the clinical application of MT in HCC.

Humans ; Aortic Valve/surgery* ; Retrospective Studies ; Transcatheter Aortic Valve Replacement ; Sex Factors ; Heart Valve Prosthesis Implantation ; Treatment Outcome ; China ; Aortic Valve Stenosis/surgery* ; Risk Factors ; Risk Assessment

Objective:To investigate the clinical features of ocular involvement and the application of Rose criteria in patients with relapsing polychondritis (RP).Methods:The data from RP patients with ocular involvement were collected and analyzed. Patients included must have at least one major criteria of Michet criteria and the application Rose criteria was also investigated. Demographic data of these patients was presented as percentages. The difference between types of disease onset was tested by Mann-Whitney U and comparison among groups was tested by False Discovery Rate. Results:A total of 192 patients were enrolled 98 males and 94 females. The mean age of disease onset was (42±14) (0.5-79) years old, the median disease duration (DD) was 13(0.5, 600) months. The median RP disease activity index (RPDAI) was 39(9-74) and the median RP organ damage index (RPODI) was 2.5(0.1, 108). The median RP damage index (RPDAM) was 3(1-6). The statistical significant difference was identified in median DD between groups of nose and pinna ( Z=10.775, P<0.01), nose and OEH ( Z=9.277, P<0.01), in RPODI between groups of nose and pinna ( Z=7.999, P=0.031), nose and and extra-cranial organs ( Z=8.115, P=0.030) and eye and airway involvement of RPDAM could be seen between groups ( Z=7.683, P=0.037) respectively. Ocular involvement(50.0%), auricular chondritis(21.4%) and airway chondritis(13.5%) were the top three most common symptoms at disease onset. The ocular involvement(100%), airway chondritis (75.0%) and inner ear involvement(69.3%) were the top three most frequent affected organs. All parts of eye could be involved in RP ocular damage. Single-organ involvement was 59.9%; and multi-organ involvement could be seen in 40.1% patients. Diagnostic strength was enhanced by application of Rose criteria in 171 cases fulfilled Michet criteria and 21(10.9%) cases partially fulfilled Michet criteria fulfilled Rose criteria. Active screening for organ (especially inner ear and airway) involvement would improve the rate of early diagnosis. The pinna and airway involvement suggested nose and middle-ear might be involved. Conclusion:Ocular involvement in RP can involve all parts of the eye ball. Examining the inner ear and airway may help to confirm the diagnosis. It is worthy to apply this to clinical practice.

Objective:To identify the population who can obtain clinical benefit from concurrent chemoradiotherapy through the survival analysis during concurrent chemoradiotherapy in different subgroups.Methods:All data from a phase Ⅲ randomized controlled clinical trial were collected to compare the efficacy between preoperative concurrent chemoradiotherapy and preoperative radiotherapy from 2002 to 2012 in Cancer Hospital of the Chinese Academy of Medical Sciences. A total of 222 patients received radiation therapy with a median dose of 69.96 Gy (27.56-76.00 Gy). The cisplatin chemotherapy regimen was adopted and the median dose was 250 mg (100-570 mg). In total, 98 patients received intensity-modulated radiotherapy (IMRT). The survival analysis was conducted with Kaplan- Meier method and univariate analysis was performed with log-rank test. The multivariate prognostic analysis was conducted with Cox’s regression model. Results:The median follow-up time was 59 months (7-139 months). Among them, 104 patients were assigned in the chemoradiotherapy group and 118 patients in the radiotherapy alone group. The local and regional recurrence rates did not significantly differ between two groups (both P>0.05), while chemoradiotherapy tended to decrease the distant metastasis rate compared with the radiotherapy alone (14.4% vs. 24.6, P=0.058). Univariate analysis showed that concurrent chemoradiotherapy significantly increased the local recurrence-free survival in the early N stage subgroup ( P=0.009), and there was an increasing trend in patients aged≤55 years and female patients ( P=0.052, 0.066). The distant metastasis-free survival was significantly improved in T 4( P=0.048), N 3( P=0.005), non-IMRT treatment ( P=0.001) and hypopharyngeal carcinoma ( P=0.004) subgroups, there was an increasing trend in male ( P=0.064), high-and moderate-grade squamous cell carcinoma ( P=0.076) and non-surgical treatment subgroups ( P=0.063). Multivariate analyses showed that concurrent chemoradiotherapy significantly prolonged the progression-free survival and overall survival in patients aged≤55 years ( P=0.017 and 0.039), women ( P=0.041 and 0.039), high-and moderate-grade squamous cell carcinoma ( P=0.006 and 0.022), N 3 stage ( P=0.001 and 0.017), non-surgical treatment ( P=0.007 and 0.033) and non-IMRT treatment subgroups ( P=0.030 and 0.024), and it significantly increased the progression-free survival in patients with hypopharyngeal carcinoma ( P=0.022). Conclusion:Concurrent chemoradiotherapy can be actively delivered for young age, female, high-and moderate-grade squamous cell carcinoma, N 3 stage, non-surgical treatment and non-IMRT treatment patients.

Medium spiny neurons (MSNs) in the striatum, which can be divided into D1 and D2 MSNs, originate from the lateral ganglionic eminence (LGE). Previously, we reported that Six3 is a downstream target of Sp8/Sp9 in the transcriptional regulatory cascade of D2 MSN development and that conditionally knocking out Six3 leads to a severe loss of D2 MSNs. Here, we showed that Six3 mainly functions in D2 MSN precursor cells and gradually loses its function as D2 MSNs mature. Conditional deletion of Six3 had little effect on cell proliferation but blocked the differentiation of D2 MSN precursor cells. In addition, conditional overexpression of Six3 promoted the differentiation of precursor cells in the LGE. We measured an increase of apoptosis in the postnatal striatum of conditional Six3-knockout mice. This suggests that, in the absence of Six3, abnormally differentiated D2 MSNs are eliminated by programmed cell death. These results further identify Six3 as an important regulatory element during D2 MSN differentiation.

Mouse cortical radial glial cells (RGCs) are primary neural stem cells that give rise to cortical oligodendrocytes, astrocytes, and olfactory bulb (OB) GABAergic interneurons in late embryogenesis. There are fundamental gaps in understanding how these diverse cell subtypes are generated. Here, by combining single-cell RNA-Seq with intersectional lineage analyses, we show that beginning at around E16.5, neocortical RGCs start to generate ASCL1