Osteonecrosis of femoral head （ONFH） is a disease that causes osteocyte death due to interruption of blood supply of the femoral head， which may cause symptoms such as joint movement disorders， pain， and even femoral head collapse. Currently， the commonly used methods for treating ONFH in clinical practice are accompanied by problems such as long-term side effects， inaccurate efficacy， technical limitations， and complication risks. Traditional Chinese medicine （TCM） has shown unique advantages of holistic regulation， mild side effects， and symptom alleviation. A review of the related literature shows that Salviae Miltiorrhizae Radix et Rhizoma， as a representative Chinese herbal medicine for activating blood and resolving stasis， has the effects of activating blood， resolving stasis， dredging meridians， and relieving pain. Its active ingredients （such as salvianolic acid B， tanshinone Ⅱ_A， and tanshinone Ⅰ） interfere with bone metabolism balance， osteogenesis and differentiation， and improve bone microcirculation and bone microstructure. Salviae Miltiorrhizae Radix et Rhizoma is often combined with the herbal medicines with the effects of tonifying the liver and spleen or activing blood to form herb pairs （such as Salviae Miltiorrhizae Radix et Rhizoma-Angelicae Sinensis Radix， Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma， and Salviae Miltiorrhizae Radix et Rhizoma-Drynariae Rhizoma）， which enhances the efficacy through synergistic effects. In the application of TCM compound formulas， Bushen Huoxue prescription， Bushen Huoxue capsules， Gubi Tongxiao granules， and Shenggu Zaizao pills can regulate signaling pathways such as Wnt/β-catenin， Hedgehog， Notch， transforming growth factor（TGF）-β₁/Smads， and mitogen-activated protein kinase （MAPK） through multiple targets to significantly improve bone metabolism and hip joint function， playing an important role in preventing and treating ONFH. Through a review of available studies， this paper systematically explains the outstanding advantages of the active ingredients， herb pairs， and compound formulas of Salviae miltiorrhizae Radix et Rhizoma in the prevention and treatment of ONFH. The mechanisms may be related to factors such as promoting osteoblast generation and inhibiting osteoclast formation， increasing osteogenic differentiation， promoting angiogenesis， increasing bone density， inhibiting inflammatory response， and regulating signaling pathways. In the future， modern technology can be employed to optimize dosage forms， and high-quality clinical research should be conducted to further clarify its mechanism of action and promote the precise application of TCM. This review aims to provide more thinking directions for the application of Salviae miltiorrhizae Radix et Rhizoma in preventing and treating ONFH.

Objectives: . This study aimed to explore the role of the Pcdh15 gene in hearing maintenance and to examine the effects of its deficiency on cochlear structure, cochlear function, and hearing loss in mice. Methods: . CRISPR/Cas9 technology was used to generate Pcdh15 knockout (KO) mice. Auditory function was evaluated using hearing tests, while histological approaches were employed to assess morphological changes in cochlear hair cells and spiral ganglion neurons (SGNs). RNA sequencing (RNA-seq) was performed on cochlear tissue from postnatal day 18 (P18) wild-type (WT) and Pcdh15 KO mice to identify differentially expressed genes (DEGs). These DEGs were subjected to functional annotation and pathway analysis, with particular emphasis on oxidative phosphorylation (OXPHOS). Reactive oxygen species (ROS) levels were quantified using flow cytometry and DCFH-DA assays. Results: . Pcdh15 KO mice exhibited progressive sensorineural hearing loss, which worsened to profound deafness by P18. Notably, cochlear hair cells and SGNs showed substantial loss and pronounced morphological abnormalities, particularly within the basal high-frequency region. RNA-seq analysis identified 1,359 DEGs, including 1,024 downregulated and 335 upregulated genes. Pathway analysis indicated that Pcdh15 deficiency was associated with inhibition of the OXPHOS pathway, potentially disrupting mitochondrial respiratory chain complexes I, III, IV, and V and thereby impairing energy production and ATP metabolism. In addition, early-stage cochleae from KO mice demonstrated elevated ROS levels and increased oxidative stress, suggesting that redox imbalance may contribute to hearing damage. Conclusion . Pcdh15 plays a critical role in hearing maintenance. Its deficiency is associated with severe hearing loss and marked cochlear abnormalities, which are linked to inhibition of OXPHOS, disruption of energy metabolism, and exacerbation of oxidative stress. Together, these findings provide new insights into the mechanisms underlying hearing loss and suggest potential targets for therapeutic intervention.

Objective:To explore the cardioprotective effects of icariin (ICA) against radiation-induced cardiac disease (RICD) in C57BL/6 mice.Methods:A total of 48 female C57BL/6J mice aged 6-8 weeks were randomly divided into three groups: the control group (CON), the irradiation group (IR), and the irradiation combined with icariin group (IR+ ICA), with 16 mice in each group. The IR and IR+ ICA groups received a single cardiac irradiation at a dose of 30 Gy, while the CON group received no radiation treatment. The IR+ ICA group was treated with ICA (70 mg·kg -1·d -1) two weeks before irradiation until the end of the experiment through intragastric administration. In contrast, the CON and IR groups were treated with an equal volume of vehicle solution (0.5% sodium carboxymethyl cellulose, NaCMC) via intragastric administration. The mice′s mental status, food intake, body weight, and survival rates were monitored during the experiment. At two weeks post-irradiation, the venous blood of the mice was collected and serum was separated for the enzyme-linked immunosorbent assays (ELISA) of creatine kinase MB isoenzyme (CK-MB) and cardiac troponin T (cTnT/TNNT2). At 12 weeks post-irradiation, the cardiac function of the mice was assessed using echocardiography. After the mice were euthanized under anesthesia, the histopathological changes and fibrosis degree of their myocardial tissues were assessed using hematoxylin and eosin (HE) and Masson′s trichrome staining, followed by the calculation of collagen volume fraction (CVF). The differential gene expression of brain natriuretic peptide (BNP), transforming growth factor-β (TGF-β), and interleukin-6 (IL-6) in the cardiac tissues of the mice was detected using real-time reverse transcription-polymerase chain reaction (RT-PCR). Apoptosis-related proteins and proteins associated with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway were determined using Western blotting. The survival curves of the mice were plotted using Kaplan-Meier, and the survival differences of the mice among various groups were compared using the log-rank test. Results:After irradiation, the mice in the IR group showed lethargy, as well as decreased food intake and activity, while these symptoms in the IR+ ICA group were significantly alleviated. At two weeks post-irradiation, the CK-MB and cTnT levels of the IR group were significantly elevated compared with the CON group ( t = 5.28, 8.89, P < 0.01). At 12 weeks post-irradiation, the mice in the IR group exhibited significantly decreased body weight ( t = 2.47, P < 0.05) and decreased survival rates ( HR = 8.25, 95% CI: 1.157-58.770, P < 0.05) compared with the CON group. Echocardiography revealed that the IR group featured decreased left ventricular ejection fraction (EF), decreased fractional shortening (FS), and increased left ventricular end-diastolic diameter (LVDD) compared with the CON group ( t = 7.02, 4.45, P < 0.05). Histopathological examination revealed that the IR group suffered from cardiomyocyte edema, disordered arrangement, and increased fibrosis, with an elevated CVF. The IR group exhibited significantly upregulated gene expression of BNP, TGF-β, and IL-6 in cardiac tissues compared with the CON group ( t = 4.23, 6.39, 4.61, P < 0.05). After-irradiation, the IR group exhibited upregulated apoptosis-related proteins Cleaved Caspase-3 and Bax ( t = 6.29, 9.54, P < 0.05), decreased Bcl-2 expression ( t = 8.20, P < 0.001), and decreased phosphorylation levels of PI3K and Akt ( t = 6.47, 3.42, P < 0.001). The symptoms of the mice were partially ameliorated after treatment with ICA. Specifically, the mice in the IR+ ICA group exhibited higher body weight ( t = 5.13, P < 0.001) and significantly higher survival rates ( HR = 0.121, 95% CI: 0.017-0.864, P < 0.05) than the IR group. Compared to the IR group, the IR+ ICA group showed elevated cardiac function indicators EF and FS( t = 3.23, 3.05, P < 0.05), and reduced LVDD ( t = 3.02, P < 0.05). The histopathological analysis revealed mitigated edema and disordered arrangement of cardiomyocytes in the IR+ ICA group. Furthermore, the IR+ ICA group exhibited significantly lower BNP, TGF-β, and IL-6 expression levels than the IR group ( t = 2.83, 4.15, 2.96, P < 0.05). The expression of apoptosis-related proteins Cleaved Caspase-3 and Bax was lower ( t = 3.23, 3.24, P < 0.05), Bcl-2 expression was higher ( t = 5.92, P < 0.001), and restored phosphorylation levels of PI3K and Akt ( t = 2.89, 8.35, P < 0.001). Conclusions:Icariin has protective effects against the RICD. It alleviates cardiomyocyte apoptosis possibly by upregulating the phosphorylation levels of PI3K and Akt.

In 2024, notable progress was made in the clinical treatment of Parkinson′s disease (PD). These advancements encompass key areas such as novel drugs like glucagon-like peptide-1 receptor agonists, pralidoxime, and levodopa subcutaneous injection, novel neuroregulatory therapies like closed-loop adaptive deep brain stimulation, bilateral magnetic resonance imaging-guided focused ultrasound ablation, and fecal microbiota transplantation, all of which have propelled the precision treatment of PD. The significant advancements in the clinical treatment of PD published in major international academic journals in 2024 were systematically reviewed in this article.

This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.

Objective To explore the behavioral characteristics of using cognitive reappraisal(CR)and expressive suppression(ES)in high trait anxiety individuals under both explicit and implicit conditions.Methods A total of 57 non-psychology undergraduates and postgraduates were recruited in a military medical university from June to July in 2023.All the participants were surveyed with Trait Form of Spielberger's State-Trait Anxiety Inventory(STAI-T)and Emotion Regulation Questionnaire(ERQ)to investigate their level of anxiety and usage habits of CR and ES strategies.According to the STAI-T results,they were divided to a high trait anxiety(HTA)group(n=28)and a low trait anxiety(LTA)group(n=29).Then the implicit and explicit emotion regulation(ER)tasks were used to analyze and compare 2 strategies on improving negative emotional pleasure and arousal,and the differences in difficulty and success of using CR and ES under the explicit condition.Results ① Both the HTA and LTA individuals showed a higher use of CR and less use of ES[t(27)=3.94,P<0.001;t(28)=11.33,P<0.001],while the HTA individuals used more ES[t(55)=3.02,P<0.01]and less CR than the LTA individuals[t(55)=-2.20,P=0.02].②Compared with implicit neutral priming,both implicit CR(Pleasure:2.56±0.11 vs 2.73±0.12,P<0.01;Arousal:6.68±0.18 vs 6.51±0.20,P<0.05)and implicit ES priming(Pleasure:2.56±0.11 vs 2.86±0.11,P<0.001;Arousal:6.68±0.18 vs 6.30±0.20,P<0.001)improved the negative emotional experiences of both HTA and LTA groups,and ES showed better effect(Pleasure:P<0.001;Arousal:P<0.001).③ Explicit CR(Pleasure:2.92±0.12 vs 5.09±0.09,P<0.001;Arousal:6.43±0.20 vs 4.33±0.21,P<0.001)and explicit ES(Pleasure:2.92±0.12 vs 4.34±0.09,P<0.001;Arousal:6.43±0.20 vs 4.22±0.22,P<0.001)ameliorated the negative feelings in the HTA and LTA individuals,and the effect of explicit CR on improving pleasure was superior than that of explicit ES(P<0.001).For the HTA individuals,it is more difficult to implement CR and ES[CR:t(55)=2.16,P=0.02;ES:t(55)=2.92,P<0.01],and ES was less successful in emotion regulation when compared with the LTA individuals[t(55)=-1.88,P=0.03];the difficulty of using ES was significantly higher than that of CR[4.00±1.81 vs 5.00±1.80,t(27)=-2.78,P<0.01],and the success rate was also lower[7.04±1.00 vs 6.64±1.13,t(27)=2.09,P=0.02].④ Comparing the effects of emotion regulation under implicit and explicit conditions,it was presented that explicit CR and ES were better than implicit CR and ES for both HTA and LTA individuals(Pleasure:explicit CR vs implicit CR:5.09±0.09 vs 2.73±0.12,P<0.001;explicit ES vs implicit ES:4.34±0.09 vs 2.86±0.11,P<0.001;Arousal:explicit CR vs implicit CR:4.33±0.21 vs 6.51±0.20,P<0.001;explicit ES vs implicit ES:4.22±0.22 vs 6.30±0.20,P<0.001).Conclusion In terms of usage habits of ER strategies,HTA individuals tend to use ES more and CR less than LTA individuals.Under the implicit/explicit conditions,HTA individuals can both employ CR and ES to improve negative emotional experience,and the effect of explicit ER is significantly better than implicit condition.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of "palpitation" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.
Atrial Fibrillation/physiopathology* ; Humans ; Acupuncture Therapy ; Vagus Nerve/physiology* ; Animals

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective To comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*