This study aims to investigate the pharmacological effects and mechanisms of Yougui Yin in treating glucocorticoid-induced osteonecrosis. A rat model of glucocorticoid-associated osteonecrosis of the femoral head(GA-ONFH) was established by intramuscular injection of dexamethasone at 20 mg·kg~(-1) every other day for 8 weeks. Rats were randomly allocated into control, model, and low-and high-dose(1.5 and 3.0 g·kg~(-1), respectively) Yougui Yin groups. After modeling, rats in Yougui Yin groups were administrated with Yougui Yin via gavage, which was followed by femoral specimen collection. Hematoxylin-eosin staining was employed to observe femoral head repair, and immunofluorescence was employed to assess adipogenic differentiation of bone marrow mesenchymal stem cells(BMSCs) within the femoral head. Cell experiments were carried out with dexamethasone(1 μmol·L~(-1))-treated BMSCs to evaluate the effects of Yougui Yin-medicated serum on adipogenic differentiation. Animal experiments demonstrated that compared with the model group, Yougui Yin at both high and low doses significantly improved bone mineral density(BMD), bone volume/total volume(BV/TV) ratio, and trabecular thickness(Tb.Th) in the femoral head. Additionally, Yougui Yin alleviated necrosis-like changes and adipocyte infiltration and significantly reduced the expression level of peroxisome proliferator-activated receptor γ(PPARγ) in the femoral head, thereby suppressing the adipogenic differentiation of BMSCs in GA-ONFH rats. The cell experiments revealed that Yougui Yin-medicated serum markedly inhibited dexamethasone-induced adipogenic differentiation of BMSCs and down-regulated the level of PPARγ. The overexpression of PPARγ attenuated the inhibitory effect of Yougui Yin-medicated serum on the adipogenic differentiation of BMSCs, indicating the critical role of PPARγ in Yougui Yin-mediated suppression of adipogenic differentiation of BMSCs. In conclusion, Yougui Yin exerts therapeutic effects on glucocorticoid-induced osteonecrosis by down-regulating PPARγ expression and inhibiting adipogenic differentiation of BMSCs.
Animals ; Mesenchymal Stem Cells/metabolism* ; PPAR gamma/genetics* ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Glucocorticoids/adverse effects* ; Rats, Sprague-Dawley ; Adipogenesis/drug effects* ; Osteonecrosis/genetics* ; Cell Differentiation/drug effects* ; Bone Marrow Cells/metabolism* ; Femur Head Necrosis/chemically induced* ; Humans

The zebrafish model has attracted much attention due to its strong reproductive ability, short research cycle, and ease of maintenance. It has always been an important vertebrate model system, often used to carry out human disease research. Its motor behavior features have the advantages of being simpler, more intuitive, and quantifiable. In recent years, it has received widespread attention in the study of traditional Chinese medicine(TCM)for the treatment of sleep disorders, neurodegenerative diseases, fatigue, epilepsy, and other diseases. This paper reviews the characteristics of zebrafish motor behavior and its applications in the pharmacodynamic verification and mechanism research of TCM extracts, active ingredients, and TCM compounds, as well as in active ingredient screening and safety evaluation. The paper also analyzes its advantages and disadvantages, with the aim of improving the breadth and depth of zebrafish and its motor behavior applications in the field of TCM research.
Zebrafish/physiology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Disease Models, Animal ; Drug Evaluation, Preclinical/methods* ; Animals ; Sleep Wake Disorders/physiopathology* ; Epilepsy/physiopathology* ; Neurodegenerative Diseases/physiopathology* ; Fatigue/physiopathology* ; Behavior, Animal/physiology* ; Motor Activity/physiology*

PURPOSE: To judge the injury mode and injury severity of the real human body through the measured values of anthropomorphic test devices (ATD) injury indices, the mapping relationship of lumbar injury between ATD and human body model (HBM) was explored. METHODS: Through the ATD model and HBM simulation, the mapping relationship of lumbar injury between the 2 subjects was explored. The sled environment consisted of a semi-rigid seat with an adjustable seatback angle and a 3-point seat belt system with a seatback-mounted D-ring. Three seatback recline states of 25°, 45°, and 65° were designed, and the seat pan angle was maintained at 15°. A 23 g, 47 km/h pulse was used. The validity of the finite element model of the sled was verified by the comparison of ATD simulation and test results. ATD model was the test device for human occupant restraint for autonomous vehicles (THOR-AV) dummy model and HBM was the total human model for safety (THUMS) v6.1. The posture of the 2 models was adjusted to adapt to the 3 seat states. The lumbar response of THOR-AV and the mechanical and biomechanical data on L1 - L5 vertebrae of THUMS were output, and the response relationship between THOR-AV and THUMS was descriptive statistically analyzed. RESULTS: Both THOR-AV and THUMS were submarined in the 65° seatback angle case. With the change of seatback angle, the lumbar spine axial compression force (F_z) of THOR-AV and THUMS changed in the similar trend. The maximum F_z ratio of THOR-AV to THUMS at 25° and 45° seatback angle cases were 1.6 and 1.7. The flexion moment (M_y) and the time when the maximum M_y occurred in the 2 subjects were very different. In particular, the form of moment experienced by the L1 - L5 vertebrae of THUMS also changed. The changing trend of M_y measured by THOR-AV over time can reflect the changing trend of maximum stress of L1 and L2 of THUMS. CONCLUSION The F_z of ATD and HBM presents a certain proportional relationship, and there is a mapping relationship between the 2 subjects on F_z. The mapping function can be further clarified by applying more pulses and adopting more seatback angles. It is difficult to map M_y directly because they are very different in ATD and HBM. The M_y of ATD and stress of HBM lumbar showed a similar change trend over time, and there may be a hidden mapping relationship.
Humans ; Lumbar Vertebrae/injuries* ; Finite Element Analysis ; Biomechanical Phenomena ; Manikins ; Spinal Injuries/physiopathology*

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective To compare the efficacy of trastuzumab plus pertuzumab(HP)combined with either nab-paclitaxel plus carboplatin or docetaxel plus carboplatin as neoadjuvant therapy for HER2-positive breast cancer in real-world clinical practice.Methods Clinical data of HER2-positive breast cancer patients who received neoadjuvant therapy with either HP combined with nab-paclitaxel plus carboplatin or HP combined with docetaxel plus carboplatin and subsequently underwent surgery were retrospectively collected from 11 tertiary grade-A hospitals in Hebei Province from June 2019 to December 2021.The total pathological complete response(tpCR)rates of the two groups were compared.Results A total of 76 patients were included in the study,with 47 in the nab-paclitaxel group and 29 in the docetaxel group.The tpCR rate was significantly higher in the nab-paclitaxel group than that in the docetaxel group(72.3%vs.48.3%,χ2=4.463,P=0.035).Subgroup analysis indicated that patients older than 40 years,with cN2-3,cTNM stage Ⅲ,hormone receptor-positive status,and Ki67>30%had significantly higher tpCR rates in the nab-paclitaxel group than those in the docetaxel group(P<0.05).Conclusion In real-world clinical practice,the efficacy of HP combined with nab-paclitaxel plus carboplatin as neoadjuvant therapy for HER2-positive breast cancer is superior to that of HP combined with docetaxel plus carboplatin.

GNPS-based mass spectrum-molecular networks is an effective strategy for rapidly identifying known natural products and discovering novel structures. The chemical diversity of azaphilones from the fermentation extracts of Talaromyces sp. HK1-18 was studied by molecular network technique. Three linear tricyclic azaphilones, sequoiamonacins A-C (2a, 2b, 1), were isolated by silica gel column chromatography and high performance liquid chromatography from the extracts of the fungal strain of HK1-18, and their structures were identified by nuclear magnetic resonance and high-resolution mass spectrometry. Guided by the mass spectra of sequoiamonacins A-C (2a, 2b, 1), the cluster of sequoiamonacinoid analogues was discovered from the full molecular networking of HK1-18. By analyzing the MS/MS fragments of each parent ion in this cluster, 7 azaphilones (3-9) included 6 new ones (4-9) were predicted successfully. Then the MS/MS cracking regularity of this type of azaphilones was revealed. Compound 1 showed anti-inflammatory activity, which can inhibit the production of interleukin-1α (IL-1α) in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7, with an inhibitory rate of 29% at the concentration of 12.5 μg·mL^-1.

The gene GeDRP1E encoding dynamin-related protein 1E in Gastrodia elata was cloned by specific primers which were designed based on the transcriptome data of G. elata. Bioinformatics analysis on GeDRP1E gene was carried out by using ExPASy, ClustalW, MEGA, etc. Positive transgenic Arabidopsis plant and potato minituber were obtained with the genetic transformation system of Arabidopsis and potato. The plant height and seed setting rate of transgenic Arabidopsis, and agronomic characters, such as size, weight and starch content of potato minituber of transgenic potato were tested and analyzed. And GeDRP1E gene function was preliminarily investigated. The results showed that the open reading frame of GeDRP1E gene was 1 899 bp in length and 632 amino acids residues were encoded, with a relative molecular weight of 69.90 kDa and a molecular formula of C₃₀₇₉H₄₉₇₃N₈₈₃O₉₃₃S₁₉. It was predicted that the theoretical isoelectric point was 7.27, the instability coefficient was 43.34, and the average hydrophilicity index was -0.259, which was indicative of an unstable hydrophilic protein. GeDRP1E has no transmembrane structure and signal peptide, and was localized in the cytoplasm. The phylogenetic tree showed that GeDRP1E was highly homologous with DRP1E proteins of other plant species, among which GeDRP1E had the highest homology with DcDRP1E (XP_020689662.1) in Dendrobium candidum, reaching 90.05%. GeDRP1E plant expression vector pCambia1300-35Spro-GeDRP1E was constructed by double digests, and Arabidopsis complementary mutant and potato overexpression strain of GeDRP1E gene were obtained by Agrobacterium-mediated gene transformation. Compared with the Arabidopsis AtDRP1E mutant, the height and seed setting rate of the GeDRP1E complementation mutant were rescued. The minituber of GeDRP1E overexpression potato had larger size, heavier weight and higher starch content, comparing to wild-type potato. It was preliminarily induced that GeDRP1E was involved in mitochondrial morphology regulation, which related to the growth and development of Arabidopsis plants and potato miniature. The research results laid a foundation for further elucidating the molecular mechanisms underlying the growth and development of G. elata tuber development.

Objective To build a dataset encompassing a large number of stained tongue coating images and process it using deep learning to automatically recognize stained tongue coating images. Methods A total of 1 001 images of stained tongue coating from healthy students at Hunan University of Chinese Medicine and 1 007 images of pathological(non-stained)tongue coat-ing from hospitalized patients at The First Hospital of Hunan University of Chinese Medicine with lung cancer,diabetes,and hypertension were collected.The tongue images were randomi-zed into the training,validation,and testing datasets in a 7:2:1 ratio.A deep learning model was constructed using the ResNet50 for recognizing stained tongue coating in the training and validation datasets.The training period was 90 epochs.The model's performance was evaluated by its accuracy,loss curve,recall,F1 score,confusion matrix,receiver operating characteristic(ROC)curve,and precision-recall(PR)curve in the tasks of predicting stained tongue coating images in the testing dataset.The accuracy of the deep learning model was compared with that of attending physicians of traditional Chinese medicine(TCM). Results The training results showed that after 90 epochs,the model presented an excellent classification performance.The loss curve and accuracy were stable,showing no signs of overfitting.The model achieved an accuracy,recall,and F1 score of 92%,91%,and 92%,re-spectively.The confusion matrix revealed an accuracy of 92%for the model and 69%for TCM practitioners.The areas under the ROC and PR curves were 0.97 and 0.95,respectively. Conclusion The deep learning model constructed using ResNet50 can effectively recognize stained coating images with greater accuracy than visual inspection of TCM practitioners.This model has the potential to assist doctors in identifying false tongue coating and prevent-ing misdiagnosis.

Objective To observe the improvement of motor dysfunction and serum levels of C-reactive protein(CRP),blood glucose and blood lipid in post-stroke patients treated with scalp acupuncture at different needle retention time.Methods A total of 120 patients with motor dysfunction after stroke were randomly divided into control group,observation group 1 and observation group 2,with 40 cases in each group.The patients in the 3 groups were treated with scalp acupuncture,body acupuncture and routine rehabilitation exercise,once a day and 6 times a week,lasting for 2 weeks.The control group was given scalp acupuncture with retaining of needles for 30 minutes,the observation group 1 was given scalp acupuncture with retaining of needles for one hour,and the observation group 2 was given scalp acupuncture with retaining of needles for 2 hours.Before and after treatment,the 3 groups were observed in the changes of the scale scores of National Institutes of Health Stroke Scale(NIHSS),Fugl-Meyer Assessment(FM A),Berg Balance Scale(BBS)and modified Barthel Index(MBI),and the levels of laboratory indicators of peripheral blood CRP,fasting plasma glucose(FPG),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C).After treatment,the clinical safety of the three groups was evaluated.Results(1)After treatment,the scale scores of NIHSS in the three groups were lower(P＜0.01)and the scale scores FMA,BBS and MBI were higher than those before treatment(P＜0.05 or P＜0.01).The comparison of post-treatment scale scores showed that the differences among the three groups were statistically significant(P＜0.01).The intergroup comparison showed that the decrease of NIHSS score and the increase of FMA,BBS and MBI scores in the observation group 2 were significantly superior to those in the control group and the observation group 1(P＜0.01);the improvement of FMA score in the observation group 1 was significantly superior to that in the control group(P＜0.01),while the improvement of NIHSS,BBS and MBI scores tended to be superior to that in the control group without statistically significant differences(P＞0.05).The results indicated that the curative effect of scalp acupuncture plus exercise regimen was positively correlated with the duration of needle retention for scalp acupuncture.(2)After treatment,the laboratory indicator levels of CRP and FPG in the peripheral blood of the three groups,the levels of TG and LDL-C in the two observation groups and the level of HDL-C in the observation group 2 were improved compared with those before treatment(P＜0.05 or P＜0.01).Statistically significant differences were presented in the post-treatment levels of CRP and TG in peripheral blood among the three groups(P＜0.05 or P＜0.01).The intergroup comparison showed that the improvement of CRP and TG levels in the observation group 2 was significantly superior to that in the control group,and the improvement of CRP level in the observation group 2 was significantly superior to that in the observation group 1,the differences being statistically significant(P＜0.05 or P＜0.01).The TC level in the three groups after treatment did not differ from that before treatment,and there was no significant difference in TC level after treatment among the three groups either(P＞0.05).(3)During the treatment,no adverse reactions such as fainting,needle breaking and hematoma occurred in the three groups,the vital signs of the patients were stable,and there were no obvious abnormal changes in pulse,blood pressure and respiratory rate.Conclusion Scalp acupuncture can effectively improve the motor function of post-stroke patients in a pasitive time-effect relationship with the needle retention,and better the curative effect can be achieved by retaining of the needle for 2 h.

Osteonecrosis of the femoral head(ONFH)is a common orthopedic disease,and hip preservation surgery has high clinical value in the early stages of ONFH,especially for young and middle-aged patients.However,the repair of ONFH is heterogeneous,leading to inter-individual variations in the efficacy of hip preservation.Currently,the existing tissue-engineered scaffolds in the field of hip preservation are uncontrollable after implantation,making it difficult to achieve precise repair.Smart responsive materials have good biocompatibility and self-feedback capability.By combining them with therapeutic drugs to construct stimulus-responsive drug delivery systems,new possibilities are provided for the precise repair of ONFH.This paper reviews the research progress of smart responsive materials at home and abroad.Based on the response principles of various materials and the repair characteristics of ONFH,the application prospects of various smart responsive materials such as reactive oxygen species-responsive,fluid shear stress-responsive,and light/magnetic-responsive materials are discussed and prospected in the field of precise repair for ONFH,providing new ideas for the precise treatment of ONFH.