In order to investigate the mechanical response of lumbar vertebrae during gait cycle in adolescents with idiopathic scoliosis (AIS), the present study was based on computed tomography (CT) data of AIS patients to construct model of the left support phase (ML) and model of the right support phase (MR), respectively. Firstly, material properties, boundary conditions and load loading were set to simulate the lumbar vertebra-pelvis model. Then, the difference of stress and displacement in the lumbar spine between ML and MR was compared based on the stress and displacement cloud map. The results showed that in ML, the lumbar stress was mostly distributed on the convex side, while in MR, it was mostly distributed on the concave side. The stress of the two types of stress mainly gathered near the vertebral arch plate, and the stress of the vertebral arch plate was transmitted to the vertebral body through the pedicle with the progress of gait. The average stress of the intervertebral tissue in MR was greater than that in ML, and the difference of stress on the convex and convex side was greater. The displacement of lumbar vertebrae in ML decreased gradually from L1 to L5. The opposite is true in MR. In conclusion, this study can accurately quantify the stress on the lumbar spine during gait, and may provide guidance for brace design and clinical decision making.
Humans ; Lumbar Vertebrae/diagnostic imaging* ; Scoliosis/diagnostic imaging* ; Adolescent ; Gait/physiology* ; Biomechanical Phenomena ; Tomography, X-Ray Computed ; Stress, Mechanical ; Female ; Male

Objective:To investigate the effect of repetitive transcranial magnetic stimulation(rTMS)on sleep structure and quality in children with autism spectrum disorder(ASD).Methods:Sixty children with ASD who met the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)criteria were randomly assigned to rTMS treatment group and pseudo-treatment group.The rTMS group received bilateral low-frequency(0.5 Hz)stimulation,and the pseudo-treatment group received pseudo-stimulation at the same time and place.Sleep quality and autism symptoms were assessed at baseline,midpoint(15 sessions),and endpoint(30 sessions),using the Childhood Sleep Disorders Scale(SDSC)and the Behavior Rating Scale for Children with Autism Spectrum Disorders(ABC)before treatment,15 times and 30 times of intervention,and statistical analysis was performed.Results:There was no significant difference in SDSC factor and total score between the two groups before treatment(P＞0.05).After 15 and 30 treatments,the total scores of SDSC and all factors were lower in the rTMS group than in the pseudo-treatment group(P＜0.05).Repeated measurement ANOVA found that there was an interaction be-tween the groups and the number of interventions,that is,the scores of the two groups had different downward trends,and the decline of the treatment group was more obvious than that of the pseudo-treatment group.There was no significant difference in the interaction between ABC scale scores and intervention times(P＞0.05).Conclu-sion:Repetitive transcranial magnetic stimulation significantly improves the sleep structure and quality in children with autism spectrum disorder.

Objective:To investigate the effect of PIK3CA mutations on the tumor immune microenvironment in Luminal breast cancer and evaluate the potential of Alpelisib-loaded pH-responsive polymer micelles in modulating the tumor immune microenvironment.Methods:PIK3CA mutations in breast cancer were analyzed using bioinformatics tools.A mouse xenograft model of Luminal breast cancer harboring a PIK3CA mutation was established,and alterations in the tumor immune microenvironment were examined using mass cytometry(CyTOF).During the period from August 2004 to December 2008 in Tianjin Medical University Cancer Hospital,tissue biopsies of 62 Luminal breast cancer patients in the BRCA cohort were collected Study the relationship between PIK3CA mutations and tumor immune microenvironment at the organizational level.Alpelisib-loaded polymer micelles(Alpelisib@MSPM)were synthesized,characterized,and evaluated for thera-peutic efficacy in Luminal breast cancer with PIK3CA mutations.Results:PIK3CA is one of the most frequently mutated genes in breast can-cer,with the highest prevalence in Luminal subtypes.CyTOF analysis demonstrated that PIK3CA mutations contribute to a tumor immun-osuppressive microenvironment in xenografts.Multiplex fluorescence immunohistochemistry revealed that PIK3CA-mutated tumors exhib-ited more infiltration of myeloid-derived suppressor cells(MDSCs)and less infiltration of CD8? T cells.The synthesized Alpelisib-loaded pH-re-sponsive polymer micelles had an average size of approximately 127 nm.Treatment with Alpelisib and Alpelisib@MSPM reduced tumor growth in mice with PIK3CA-mutated Luminal breast cancer.Notably,the proportion of MDSCs decreased,whereas CD8? T cell infiltration in-creased significantly,with the more pronounced effect observed in the Alpelisib@MSPM treatment group.Conclusions:PIK3CA mutations drive the formation of a tumor immunosuppressive microenvironment in Luminal breast cancer.Targeted Alpelisib delivery via pH-respons-ive polymer micelles significantly enhances therapeutic efficacy in PIK3CA-mutated breast cancer.

Mammalian fertilization is a highly complex and finely regulated process that involves sperm-oocyte fusion and subsequent cell fate decisions. This article reviews the molecular mechanisms underlying pronucleus formation and disappearance during mammalian fertilization, with particular focus on the key molecules and regulatory mechanisms involved in these processes. It further discusses how failures in pronucleus formation and disappearance may lead to abnormal embryonic development and various infertility issues, along with potential solutions to address these abnormalities. The aim is to provide a theoretical foundation for understanding the molecular mechanisms that contribute to abnormal pronucleus formation and disappearance in the context of reproductive biology and assisted reproductive technology, while also highlighting potential directions for future research.

Mammalian fertilization is a highly complex and finely regulated process that involves sperm-oocyte fusion and subsequent cell fate decisions. This article reviews the molecular mechanisms underlying pronucleus formation and disappearance during mammalian fertilization, with particular focus on the key molecules and regulatory mechanisms involved in these processes. It further discusses how failures in pronucleus formation and disappearance may lead to abnormal embryonic development and various infertility issues, along with potential solutions to address these abnormalities. The aim is to provide a theoretical foundation for understanding the molecular mechanisms that contribute to abnormal pronucleus formation and disappearance in the context of reproductive biology and assisted reproductive technology, while also highlighting potential directions for future research.

Objective:To investigate the effect of repetitive transcranial magnetic stimulation(rTMS)on sleep structure and quality in children with autism spectrum disorder(ASD).Methods:Sixty children with ASD who met the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)criteria were randomly assigned to rTMS treatment group and pseudo-treatment group.The rTMS group received bilateral low-frequency(0.5 Hz)stimulation,and the pseudo-treatment group received pseudo-stimulation at the same time and place.Sleep quality and autism symptoms were assessed at baseline,midpoint(15 sessions),and endpoint(30 sessions),using the Childhood Sleep Disorders Scale(SDSC)and the Behavior Rating Scale for Children with Autism Spectrum Disorders(ABC)before treatment,15 times and 30 times of intervention,and statistical analysis was performed.Results:There was no significant difference in SDSC factor and total score between the two groups before treatment(P＞0.05).After 15 and 30 treatments,the total scores of SDSC and all factors were lower in the rTMS group than in the pseudo-treatment group(P＜0.05).Repeated measurement ANOVA found that there was an interaction be-tween the groups and the number of interventions,that is,the scores of the two groups had different downward trends,and the decline of the treatment group was more obvious than that of the pseudo-treatment group.There was no significant difference in the interaction between ABC scale scores and intervention times(P＞0.05).Conclu-sion:Repetitive transcranial magnetic stimulation significantly improves the sleep structure and quality in children with autism spectrum disorder.

Objective:To investigate the effect of PIK3CA mutations on the tumor immune microenvironment in Luminal breast cancer and evaluate the potential of Alpelisib-loaded pH-responsive polymer micelles in modulating the tumor immune microenvironment.Methods:PIK3CA mutations in breast cancer were analyzed using bioinformatics tools.A mouse xenograft model of Luminal breast cancer harboring a PIK3CA mutation was established,and alterations in the tumor immune microenvironment were examined using mass cytometry(CyTOF).During the period from August 2004 to December 2008 in Tianjin Medical University Cancer Hospital,tissue biopsies of 62 Luminal breast cancer patients in the BRCA cohort were collected Study the relationship between PIK3CA mutations and tumor immune microenvironment at the organizational level.Alpelisib-loaded polymer micelles(Alpelisib@MSPM)were synthesized,characterized,and evaluated for thera-peutic efficacy in Luminal breast cancer with PIK3CA mutations.Results:PIK3CA is one of the most frequently mutated genes in breast can-cer,with the highest prevalence in Luminal subtypes.CyTOF analysis demonstrated that PIK3CA mutations contribute to a tumor immun-osuppressive microenvironment in xenografts.Multiplex fluorescence immunohistochemistry revealed that PIK3CA-mutated tumors exhib-ited more infiltration of myeloid-derived suppressor cells(MDSCs)and less infiltration of CD8? T cells.The synthesized Alpelisib-loaded pH-re-sponsive polymer micelles had an average size of approximately 127 nm.Treatment with Alpelisib and Alpelisib@MSPM reduced tumor growth in mice with PIK3CA-mutated Luminal breast cancer.Notably,the proportion of MDSCs decreased,whereas CD8? T cell infiltration in-creased significantly,with the more pronounced effect observed in the Alpelisib@MSPM treatment group.Conclusions:PIK3CA mutations drive the formation of a tumor immunosuppressive microenvironment in Luminal breast cancer.Targeted Alpelisib delivery via pH-respons-ive polymer micelles significantly enhances therapeutic efficacy in PIK3CA-mutated breast cancer.

Liver fibrosis is a wound healing response that occurs in the setting of chronic liver injury and is caused by imbalance in the synthesis and degradation of extracellular matrix （ECM）. If left untreated， it can progress to liver cirrhosis and hepatocellular carcinoma. The activation of hepatic stellate cell （HSC） is now well established as a central driver of liver fibrosis. The activated HSC will transform into myofibroblasts that produce ECM protein. Transforming growth factor-β₁ （TGF-β₁） can induce the activation of hepatic stellate cell （HSC）， and TGF-β₁/Smads signaling pathway is one of the important pathways to promote liver fibrosis. Non-coding RNA （ncRNA） does not encode proteins during the transcription but plays an important regulatory role in the post-transcriptional process of genes. Accumulating evidence shows that the occurrence of liver fibrosis is closely related to the abnormal expression of ncRNA which participates in the activation of HSC by regulating TGF-β₁ signal transduction and then affects the process of liver fibrosis. MiRNA-mediated TGF-β₁/Smads signaling pathway can not only promote liver fibrosis but also play a role in anti-fibrosis. Long non-coding RNA （lncRNA） not only promotes the development of liver fibrosis by binding to target genes but also enhances TGF-β₁ signal transduction by acting as competitive endogenous RNA. circular RNA （circRNA） acts as a ''sponge'' to regulate TGF-β₁/Smads pathway， thereby inhibiting HSC activation and exerting the anti-liver fibrosis effect. Chinese medicinal plays an essential part in the prevention and treatment of liver fibrosis， and the active components can inhibit TGF-β₁/Smads pathway by regulating the expression of miRNA， thus alleviating liver fibrosis. This article reviews the role and mechanism of miRNA-， lncRNA- and circRNA-mediated TGF-β₁/Smads signaling pathway in liver fibrosis and summarizes the anti-liver fibrosis effect of active components of Chinese medicinals by regulating miRNA-mediated TGF-β₁/Smads signaling pathway， which can serve as a reference for clinical treatment of liver fibrosis and the development of new drugs.

BACKGROUND: The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer. The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world setting. METHODS: The HELIOS registry is a prospective, multicenter, cohort study conducted at 38 centers across China between November 2018 and December 2019. A total of 3060 consecutive patients were enrolled after application of minimal inclusion and exclusion criteria. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, non-fatal target vessel myocardial infarction (MI), and clinically indicated target lesion revascularization (TLR) at 1-year follow-up. Kaplan-Meier methods were used to estimate the cumulative incidence of clinical events and construct survival curves. RESULTS: A total of 2998 (98.0%) patients completed the 1-year follow-up. The 1-year incidence of TLF was 3.10% (94/2998, 95% closed interval: 2.54-3.78%). The rates of cardiac death, non-fatal target vessel MI and clinically indicated TLR were 2.33% (70/2998), 0.20% (6/2998), and 0.70% (21/2998), respectively. The rate of stent thrombosis was 0.33% (10/2998). Age ≥60 years, diabetes mellitus, family history of coronary artery disease, acute myocardial infarction at admission, and device success were independent predictors of TLF at 1 year. CONCLUSION: The 1-year incidence rates of TLF and stent thrombosis were 3.10% and 0.33%, respectively, in patients treated with HELIOS stents. Our results provide clinical evidence for interventional cardiologists and policymakers to evaluate HELIOS stent. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT03916432.
Humans ; Middle Aged ; Sirolimus/therapeutic use* ; Drug-Eluting Stents/adverse effects* ; Prospective Studies ; Cohort Studies ; Treatment Outcome ; Risk Factors ; Time Factors ; Percutaneous Coronary Intervention/adverse effects* ; Cardiovascular Agents/therapeutic use* ; Coronary Artery Disease/therapy* ; Myocardial Infarction/etiology* ; Thrombosis/complications* ; Polymers ; Registries

Abstract OBJECTIVE To investigate the effect of isodon ternifolia-containing serum(ITS) on the activation of rat primary hepatic Kupffer cell(KC) induced by lipopolysaccharide(LPS) through TLR4/NF-κB/NLRP3 signal pathway. METHODS The primary KC of rats were isolated and cultured, and the primary KC induced by LPS were divided into blank control group, model control group, blank serum group, positive control group(colchicine containing serum group), ITS group, TLR4 blocker group and TLR4 blocker+ITS group. MTT assay was used to detect the effect of different concentrations of ITS on the proliferation activity of KC. The content of interleukin-1β(IL-1β), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in KC supernatant were detected by ELISA. Fluorescence quantitative polymerase chain reaction(PCR), Western blotting and immunofluorescence were used to detect the expression of TLR4, nuclear factor κB inhibitor protein α(IκBα), cysteine protease-1(Caspase-1), NLRP3 mRNA and TLR4, IκBα, phosphorylated IκBα(p-IκBα), Caspase-1, NLRP3 and NF-κBp65 in KC. RESULTS Compared with the model control group, the contents of IL-1β, IL-18, TNF-α and IL-6 in the supernatant of KC and the expression of TLR4, IκB α, Caspase-1, NLRP3 mRNA and TLR4, IκBα, p-IκBα, Caspase-1, NLRP3, NF-κBp65 protein in the supernatant of KC in all drug groups were down-regulated or decreased(P<0.05 or P<0.01). Compared with TLR4 blocker group, the improvement of most of the above indexes in TLR4 blocker+ITS group was more obvious. CONCLUSION Isodon ternifolia may inhibit the activation of KC and reduce the expression and release of inflammatory factors by down-regulating TLR4/NF-κB/NLRP3 signal pathway, thus alleviating the inflammatory injury of liver.