Steroid-induced osteonecrosis of the femoral head （SONFH） is a severe musculoskeletal disorder often induced by the prolonged or excessive use of glucocorticoids. Characterized by ischemia of bone cells， necrosis， and trabecular fractures， SONFH is accompanied by pain， femoral head collapse， and joint dysfunction， which can lead to disability in severe cases. The pathogenesis of SONFH involves hormone-induced osteoblast apoptosis， bone microvascular endothelial cell （BMEC） apoptosis， oxidative stress， and inflammatory responses. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a pivotal role in the development of the disease. Modulating the PI3K/Akt signaling pathway can promote Akt phosphorylation， thereby stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts， promoting angiogenesis in BMECs， and inhibiting osteoclastogenesis. The research on the treatment of SONFH with traditional Chinese medicine （TCM） has gained increasing attention. Recent studies have shown that TCM monomers and compounds have potential therapeutic effect on SONFH by intervening in the PI3K/Akt signaling pathway. These studies not only provide a scientific basis for the application of TCM in the treatment of SONFH but also offer new ideas for the development of new therapeutic strategies. This review summarized the progress in Chinese and international research on the PI3K/Akt signaling pathway in SONFH over the past five years. It involved the composition and transmission mechanisms of the signaling pathway， as well as its regulatory effects on osteoblasts， mesenchymal stem cells， osteoclasts， BMECs， and other cells. Additionally， the review explored the TCM understanding of SONFH and the application of TCM monomers and compounds in the intervention of the PI3K/Akt pathway. By systematically analyzing and organizing these research findings， this article aimed to provide references and point out directions for the clinical prevention and treatment of SONFH and promote further development of TCM in this field. With in-depth research on the PI3K/Akt pathway and the modern application of TCM， it is expected to bring safer and more effective treatment options for patients with SONFH.

Objective To evaluate the test-retest reliability of the ballistic push-up(BPU)test and establish predictive models for upper-limb strength and explosive power in young males.Methods A total of 71 male college students performed assessments of upper-limb bench press 1 repetition maximum(1RM)strength,bench press explosive power,and two BPU tests with a 48-hour interval.BPU test data were recorded using a three-dimensional(3D)force platform and motion capture system to calculate concentric metrics such as peak force(PF)and mean velocity(MV).The intraclass correlation coefficient(ICC)was used to examine the retest reliability of the BPU test.The Pearson correlation coefficient was used to evaluate the correlation of the BPU metrics with upper-limb strength and explosive power.Predictive models for upper-limb strength and explosive power were created using stepwise regression analysis.Results BPU metrics showed a good test-retest reliability(ICC=0.764-0.935).PF and MV,along with body weight(BW),were effective predictors of bench press 1RM in young males:bench press 1RM=0.129PF-16.772[R2=0.790,standard error of the estimate(SEE)=8.17 kg];bench press 1RM=1.511BW+87.15 MV-110.136(R2=0.767,SEE=8.60 kg).PF and BW were also predictors of bench press explosive power:bench press explosive power=2.755BW+0.287PF-17.351(R2=0.620,SEE=46.1 W).Conclusions The BPU test demonstrates a good test-retest reliability,and PF and MV from the BPU test can be used to predict upper-limb strength and explosive power in young males.

Radiation-induced thrombocytopenia(RIT)faces a perplexing challenge in the clinical treatment of cancer patients,and current therapeutic approaches are inadequate in the clinical settings.In this research,oxy-matrine,a new molecule capable of healing RIT was screened out,and the underlying regulatory mecha-nism associated with magakaryocyte(MK)differentiation and thrombopoiesis was demonstrated.The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro.The ability to induce thrombopoiesis was subsequently demonstrated in Tg(cd41:enhanced green fluorescent protein(eGFP))zebrafish and RIT model mice.In addition,we carried out network pharmacological pre-diction,drug affinity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)analyses to explore the potential targets of oxymatrine.Moreover,the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,Western blot(WB),and immunofluorescence.Oxymatrine markedly promoted MK differentiation and maturation in vitro.Moreover,oxymatrine induced thrombopoiesis in Tg(cd41:eGFP)zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice.Mechanistically,oxymatrine directly binds to toll-like receptor 2(TLR2)and further regulates the downstream pathway stimulator of interferon genes(STING)/nuclear factor-kappaB(NF-κB),which can be blocked by C29 and C-176,which are specific inhibitors of TLR2 and STING,respectively.Taken together,we demonstrated that oxymatrine,a novel TLR2 agonist,plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis,suggesting that oxymatrine is a promising candidate for RIT therapy.

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with hereditary Spastic paraplegia type 52 (SPG52) due to variant of AP4S1 gene. METHODS: A child diagnosed with SPG52 at the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University in May 2010 was selected as the study subject. Whole-exome sequencing (WES) was carried out for the child and his parents. Candidate variants were confirmed by Sanger sequencing. Pathogenicity of the candidate variant was interpreted according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). The study protocol was approved by the Ethics Committee of the Hospital (Ethics No.: PJ2024-04-56). RESULTS: The child had presented with global developmental delay from infancy, and featured progressive lower limb spasticity, contractures, talipes equinovarus, and muscle weakness, but with no significant facial dysmorphism. His first febrile seizure occurred before one year of age, followed by several afebrile seizures. The seizures had remitted after 3 to 4 years of antiepileptic therapy, and electroencephalography was normal. However, he had severe intellectual disability, and MRI revealed reduced white matter. WES identified a homozygous AP4S1 c.289C>T (p.Arg97*) variant in the child, for which both of his parents were heterozygous carriers. The variant was rated as pathogenic based on the ACMG guidelines. Literature review has identified 8 publications on SPG52, involving 18 patients from 12 pedigrees. Combined with our case, 14 had carried homozygous variants of the AP4S1 gene, 3 had compound heterozygous variants, and 2 had heterozygous variants, involving 12 distinct variant sites. The cohort included 7 males and 12 females. All patients exhibited progressive lower limb spasticity and weakness as the primary feature, with certain loss of independent ambulation. Most patients had intellectual disability, some had distinctive facial features, though febrile seizures or epilepsy were common. Electroencephalography often showed increased slow-wave activity. Brain MRI frequently demonstrated ventriculomegaly, a thin corpus callosum, and reduced white matter. CONCLUSION The homozygous c.289C>T (p.Arg97*) variant of the AP4S1 gene probably underlay the pathogenesis of SPG52 in this child. Above discovery has expanded the mutational spectrum of AP4S1 and provided valuable insights for the genetic diagnosis, counseling, and clinical management of SPG52.
Humans ; Male ; Spastic Paraplegia, Hereditary/genetics* ; Child, Preschool ; Female ; Exome Sequencing ; Child ; Infant ; Adaptor Protein Complex 4/genetics* ; Phenotype ; Mutation

Objective:To explore the clinical phenotype and genetic characteristics of a child with hereditary Spastic paraplegia type 52 (SPG52) due to variant of AP4S1 gene. Methods:A child diagnosed with SPG52 at the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University in May 2010 was selected as the study subject. Whole-exome sequencing (WES) was carried out for the child and his parents. Candidate variants were confirmed by Sanger sequencing. Pathogenicity of the candidate variant was interpreted according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). The study protocol was approved by the Ethics Committee of the Hospital (Ethics No.: PJ2024-04-56).Results:The child had presented with global developmental delay from infancy, and featured progressive lower limb spasticity, contractures, talipes equinovarus, and muscle weakness, but with no significant facial dysmorphism. His first febrile seizure occurred before one year of age, followed by several afebrile seizures. The seizures had remitted after 3 to 4 years of antiepileptic therapy, and electroencephalography was normal. However, he had severe intellectual disability, and MRI revealed reduced white matter. WES identified a homozygous AP4S1 c. 289C>T (p.Arg97*) variant in the child, for which both of his parents were heterozygous carriers. The variant was rated as pathogenic based on the ACMG guidelines. Literature review has identified 8 publications on SPG52, involving 18 patients from 12 pedigrees. Combined with our case, 14 had carried homozygous variants of the AP4S1 gene, 3 had compound heterozygous variants, and 2 had heterozygous variants, involving 12 distinct variant sites. The cohort included 7 males and 12 females. All patients exhibited progressive lower limb spasticity and weakness as the primary feature, with certain loss of independent ambulation. Most patients had intellectual disability, some had distinctive facial features, though febrile seizures or epilepsy were common. Electroencephalography often showed increased slow-wave activity. Brain MRI frequently demonstrated ventriculomegaly, a thin corpus callosum, and reduced white matter. Conclusion:The homozygous c. 289C>T (p.Arg97*) variant of the AP4S1 gene probably underlay the pathogenesis of SPG52 in this child. Above discovery has expanded the mutational spectrum of AP4S1 and provided valuable insights for the genetic diagnosis, counseling, and clinical management of SPG52.

The theory of five spirits(mind,eternal soul,corporeal soul,consciousness and will)is an important part of traditional Chinese medicine(TCM)theory,which reveals the human mental and psychological activities.Five-spirit theory takes the shape of modern cognitive psychology.Language is an important part of cognitive activities.Under the guidance of the five-spirit theory of TCM,and by combining the research results of modern cognitive psychology,this paper initially constructs a language processing model,and proposes that heart-mind,spleen-consciousness,kidney-will,and liver-soul are all involved in the formation of language.Moreover,the pathogenesis of post-stroke aphasia(PSA)is explored from the perspective of the five spirits.It is proposed that PSA refers to the comorbidity of body and spirit,and its pathogenesis is related to the disorders of the five spirits.After analyzing the clinical manifestations of PSA,it is suggested that malnutrition of heart-mind and insufficient kidney-will contribute to the pathogenesis of auditory comprehension and reading obstacles in patients with PSA,and the deactivation of liver-soul is closely related to spontaneous speech and naming obstacles.The treatment of PSA should be focused on nourishing blood and tranquilizing mind,enhancing consciousness and strengthening will,and suppressing liver to tranquilize soul.And the prescriptions of Pingbu Zhenxin Pills,Zhiyi Decoction plus Dingzhi Pills,and Dinghun Decoction can be chosen for modified use.The acupuncture and moxibustion can also be used for PSA,by performance mainly on the acupoints of heart meridians,pericardial meridians,spleen meridians,kidney meridians and liver meridians.The syndrome differentiation and treatment system for PSA with the combination of Chinese medicine and acupuncture based on the five-spirit theory makes up for the shortcomings of stress on the physique while ignorance of the spirit in the conventional zang-fu organ syndrome differentiation,and expands the methods for early intervention of PSA with TCM and approaches to improve the prognosis of rehabilitation.

Objective: To predict and screen potential biomarkers of systemic lupus eythematosus(SLE) based on machine learning algorithms and structural biology, and to reveal their mechanisms of action and to provide new targets for disease diagnosis and treatment. Methods: Four machine learning algorithms, random forest(RF), eXtreme gradient boosting(XGBoost), support vector machine(SVM), least absolute shrinkage and selection operator(LASSO), were used to analyze the gene expression data of SLE patients in GEO(datasets: GSE121239 and GSE11907) to analyze the gene expression data of SLE patients and screen key markers. Peripheral blood single nucleated cells(PBMCs) from SLE patients were collected and RT-qPCR was used to detect differential gene expression levels. Subsequently, GSEA enrichment analysis was used to identify biomarker-related pathways. CIBERSORT immune infiltration analysis and protein interactions network were applied to calculate the sample immune cell infiltration abundance. Single-cell data were analyzed for gene expression specificity in immune cells. Interaction relationships in combination with AlphaFold3(AF3) were predicted. Results: Multiple algorithms were screened together to identify the unique marker gene HERC5 , and expression analysis of multiple datasets showed that HERC5 was highly expressed in SLE compared to the normal group (P < 0. 05) , and RT⁃qPCR verified the same trend (P = 0. 006 2) . Functional enrichment analysis identified the major pathway promoted by HERC5 in SLE as the interferon receptor signalling pathway (P < 0. 05) . Immune infiltration analysis showed that HERC5 was closely associated with immune cells (Neutrophils : r = 0. 39 , P < 0. 05 ; Memory B cells : r = 0. 33 , P < 0. 05 ; Activated dendritic cell : r = 0. 52 , P < 0. 05) . Most HERC5 ⁃related interacting proteins were associated with SLE ,and potential transcription factors of HERC5 and its related genes were also significantly associated with immune responses. Conclusion The HERC5 gene is an important biomarker for SLE , which upregulates the interferon pathway to promote SLE progression and provides a new target for SLE diagnosis and treatment.

ObjectiveTo identify key factors influencing cognitive function in the elderly, including traditional Chinese medicine (TCM) constitutional classification, and to rank their relative importance.MethodsWe used cross-sectional data from seven geographical regions across mainland China. The Changsha version of the Montreal Cognitive Assessment was used to assess cognitive function. A “least absolute shrinkage and selection operator” (LASSO) model, multivariate linear regression analysis, and random forest (RF) model were used. Subgroup analyses were performed to examine the correlation between key TCM constitution types and cognitive function in different population subgroups.ResultsA total of 24 803 individuals aged 60 and above were included in the study. We selected 18 influential factors using the LASSO model. Higher education, being married, and having insurance were positively correlated with cognitive function in the elderly (all P .05). In contrast, poor sleep, vision impairment, hearing impairment, basic activities of daily living disability, instrumental activities of daily living disability, depression, hypertension, coronary heart disease, diabetes, stroke, yang-deficiency constitution (YADC), yin-deficiency constitution (YIDC), qi deficiency constitution (QDC), and blood stasis constitution (BSC) were negatively correlated with cognitive function (all P .05). YIDC and BSC affected all dimensions of cognitive function (all P .05). YADC mainly affected attention, language, abstraction (verbal analogies), memory, and orientation to time and place dimensions (P .001). QDC mainly affected language and abstraction (verbal analogies) dimensions (P .05). The negative correlations between BSC, YADC, YIDC, and QDC scores and cognitive function revealed statistically significant differences across most subgroups. The RF model identified education, BSC, and poor sleep quality as the three most influential factors in our study.ConclusionBSC, YADC, YIDC, and QDC were associated with cognitive decline in the elderly. Our findings provide new perspectives and significant references for interventions for early-stage cognitive disorders.

Objective:To use machine learning to predict the efficacy of accelerated corneal collagen cross-linking (A-CXL) surgery, identify prognostic factors, and construct models to predict postoperative disease progression.Methods:A single-center retrospective study was conducted.A total of 82 keratoconus patients (112 eyes) who underwent A-CXL surgery at the West China Hospital of Sichuan University between March and December 2021 were enrolled.Preoperative and follow-up examinations included anterior segment evaluation by slit-lamp microscopy, corneal topography using Pentacam, and corneal biomechanical indices using Corvis ST.Disease progression was defined as an increase in maximum keratometry (Kmax) of ≥1 D from the preoperative level at the last follow-up.Various machine learning algorithms were employed to analyze corneal topography, biomechanical parameters and corneal densitometry values to identify prognostic factors and construct models for predicting postoperative disease progression.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of West China Hospital, Sichuan University (No.2023496).Written informed consent was obtained from each subject.Results:During follow-up, 15.1% (17/112) of the eyes showed progression after A-CXL.The preoperative astigmatism and stress-strain index (SSI) in the progression group were (-5.41±2.72)D and 1.41±0.78, respectively, which were significantly higher than (-3.30±2.54)D and 0.95±0.98 in the non-progression group ( t=2.80, 2.03; both P<0.05).Cox regression analysis identified preoperative astigmatism (hazard ratio [HR]=1.20), SSI (HR=1.10), and anterior corneal densitometry of 2-6 mm (CDA6) (HR=2.10) as significant risk factors for post-A-CXL progression.Among various machine learning models developed and validated, the area under the curve (AUC) values for logistic regression, multilayer perceptron (MLP) model, and random forest (RF) exceeded 0.700.For F1-score, the AUC values for logistic regression, MLP, and RF were 0.870, 0.880, and 0.880, respectively.The network structure of the visualized MLP was a single-layer, 24-neurons neural network with 80% accuracy in predicting whether progression occurred after A-CXL.The clinical nomogram developed in conjunction with astigmatism, SSI, and CDA6 predicted the cumulative probability of progression at 0.5, 1, and 2 years postoperatively based on the sum of the specified values for each variable, and based on the optimal cutoff value, keratoconus corneas could be classified into high-, intermediate-, and low-risk groups, respectively.The time-dependent subject operating characteristic curves of the nomogram showed AUCs of 0.734, 0.685, and 0.935 at 0.5, 1, and 2 years postoperatively, respectively, all of which performed well in predicting progression. Conclusions:Preoperative astigmatism, SSI, and CDA6 are significant risk factors for post-A-CXL progression in keratoconus.The MLP model can accurately predict postoperative disease progression, and the clinical nomogram combining preoperative astigmatism, SSI, and CDA6 can effectively differentiate between low-, medium-, and high-risk postoperative progression outcomes.

This study evaluates the safety and early clinical outcomes of a novel 3D-printed titanium alloy "sleeve" component for revising fractured femoral stem prostheses in distal femoral megaprostheses without removing the fractured stem. The six patients included 2 males and 4 females, with an age range of 8-57 years. They were treated at Peking University People's Hospital between August 2020 and December 2023 and underwent revision surgery using the customized sleeve. A self-designed 3D-printed titanium alloy "sleeve" component was used for revision without removing the fractured stem, in the form of an external sleeve around the stem. Postoperative imaging was performed every three months to assess implant stability and bone integration. Functional outcomes were evaluated using the Musculoskeletal Tumor Society (MSTS)-93 score. All six patients successfully completed the surgery and follow-up, with surgical durations ranging from 120 to 230 minutes and intraoperative blood loss ranging from 150 to 800 ml. The follow-up period ranged from 6 to 46 months. At three months postoperatively, X-ray and CT imaging showed cortical bridging between the host bone and the "sleeve" component. By six months, full integration of the host cortical bone with the metal trabecular interface of the "sleeve" was observed. At the final follow-up, MSTS-93 scores ranged from 26 to 29 points, with no complications such as wound healing issues, implant loosening, fracture, infection, or degenerative arthritis. These findings suggest that 3D-printed titanium "sleeve" provide an effective, bone-preserving solution for femoral stem revision in oncologic megaprostheses, leading to favorable early stability and functional recovery.