BACKGROUND:The plantarflexor weakness is a common muscle defect in patients with spastic cerebral palsy and Charcot-Marie-Tooth,which clinically manifests abnormal gaits,and the relationship between plantarflexor weakness and abnormal gaits is unclear. OBJECTIVE:To explore the biomechanical behavior of the lower limb under the action of a single factor of plantarflexor weakness to reveal the mechanism of abnormal gait induced by plantarflexor weakness and to provide guidance for the rehabilitation training of patients with plantarflexor weakness. METHODS:A predictive framework of musculoskeletal multibody dynamics in the sagittal plane was established based on OpenSim Moco to predict lower limb joint angles and muscle activation changes during walking in normal subjects.The validity of the framework was verified by combining the inverse kinematics and electromyogram activation time of the experimental data.Reduced isometric muscle forces were used to model plantarflexor weakness and to compare predicted lower extremity joint angles,joint moments,and muscle energy expenditure with normal subjects to analyze the effects of plantarflexor weakness on lower extremity biomechanics. RESULTS AND CONCLUSION:(1)The Moco-based prediction framework realistically predicted the biomechanical changes of the lower limbs during walking in normal subjects(joint angles:normalized correlation coefficient≥0.73,root mean square error≤7.10°).(2)The musculoskeletal model used a small stride support phase to increase the"heel-walking"gait during plantarflexor weakness.When the plantarflexor weakness reached 80%,the muscle energy expenditure was 5.691 4 J/kg/m,and the maximum activation levels of the gastrocnemius and soleus muscles were 0.72 and 0.53,which might cause the plantarflexor weakness patients to be more prone to fatigue when walking.(3)Muscle energy expenditure was significantly higher when the weakness of plantarflexors exceeded 40%,and the joint angles and moments of the lower limbs deteriorated significantly when the weakness of plantarflexors exceeded 60%,suggesting that there may be a"threshold"for the effect of plantarflexor weakness on gait,which may correspond to the point at which health care professionals should intervene in the clinical setting.

Objective: To analyze the trajectories of body mass index for age z-score (BAZ) and its influencing factors among children with congenital hypothyroidism (CH) based on latent class growth modeling (LCGM), so as to provide the evidence for improving treatment measures and optimizing growth management among children with CH. Methods Children with CH aged 0 to 3 years from the Newborn Disease Screening Center of Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital) between 2017 and 2022 were selected as the research subjects. Basic information, height and weight data from 3 to 36 months of age, age at treatment initiation, thyroid-stimulating hormone (TSH) levels at diagnosis, and family information were retrospectively collected. BAZ for children with CH at each month of age was calculated based on the WHO Child Growth Standards. The trajectories of BAZ were analyzed using LCGM, and factors affecting the trajectories of BAZ among children with CH were analyzed using a multinomial logistic regression model. Methods: Children with CH aged 0 to 3 years from the Newborn Disease Screening Center of Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital) between 2017 and 2022 were selected as the research subjects. Basic information, height and weight data from 3 to 36 months of age, age at treatment initiation, thyroid-stimulating hormone (TSH) levels at diagnosis, and family information were retrospectively collected. BAZ for children with CH at each month of age was calculated based on the WHO Child Growth Standards. The trajectories of BAZ were analyzed using LCGM, and factors affecting the trajectories of BAZ among children with CH were analyzed using a multinomial logistic regression model. Results: A total of 299 children with CH were included. There were 140 boys (46.82%) and 159 girls (53.18%). The median of BAZ was 0.50 (interquartile range, 1.68). The LCGM analysis categorized the subjects into three groups: the persistent high-growth pattern group with 24 cases (8.03%), the slow-growth pattern group with 39 cases (13.04%), and the appropriate-growth pattern group with 236 cases (78.93%). Multinomial logistic regression analysis showed that compared to the children with CH in the appropriate-growth pattern group, those who started treatment at the age of 30 to 60 days (OR=0.109, 95%CI: 0.016-0.732; OR=0.166, 95%CI: 0.032-0.852) had a lower risk of persistent high-growth and slow-growth patterns; CH children with TSH levels of 50 to 150 mIU/L at diagnosis (OR=3.554, 95%CI: 1.201-10.514) and those whose paternal had a senior high school/technical secondary school education (OR=2.975, 95%CI: 1.003-8.823) exhibited a higher risk of the persistent high-growth pattern. Conversely, CH children whose paternal reproductive age was 30 to 35 years (OR=0.166, 95%CI: 0.034-0.806) had a lower risk of the persistent high-growth pattern. Conclusions The BAZ trajectory of children with CH aged 0 to 3 years exhibited three patterns: persistent high-growth, slow-growth, and appropriate-growth. The persistent high-growth and slow-growth patterns were associated with treatment timing, TSH levels at diagnosis, paternal reproductive age, and paternal education level. It is recommended to strengthen early treatment interventions and provide family follow-up guidance.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

In recent years, hybrid brain-computer interfaces (BCIs) have gained significant attention due to their demonstrated advantages in increasing the number of targets and enhancing robustness of the systems. However, Existing studies usually construct BCI systems using intense auditory stimulation and strong central visual stimulation, which lead to poor user experience and indicate a need for improving system comfort. Studies have proved that the use of peripheral visual stimulation and lower intensity of auditory stimulation can effectively boost the user's comfort. Therefore, this study used high-frequency peripheral visual stimulation and 40-dB weak auditory stimulation to elicit steady-state visual evoked potential (SSVEP) and auditory steady-state response (ASSR) signals, building a high-comfort hybrid BCI based on weak audio-visual evoked responses. This system coded 40 targets via 20 high-frequency visual stimulation frequencies and two auditory stimulation frequencies, improving the coding efficiency of BCI systems. Results showed that the hybrid system's averaged classification accuracy was (78.00 ± 12.18) %, and the information transfer rate (ITR) could reached 27.47 bits/min. This study offers new ideas for the design of hybrid BCI paradigm based on imperceptible stimulation.
Brain-Computer Interfaces ; Humans ; Evoked Potentials, Visual/physiology* ; Acoustic Stimulation ; Photic Stimulation ; Electroencephalography ; Evoked Potentials, Auditory/physiology* ; Adult

BACKGROUND: To date, results on relationship between CYP3A4 gene polymorphism were limited and inconclusive, and no study focused on the influence of CYP3A4 gene-obesity interaction on breast cancer risk, especially in Chinese women. The purpose of this study was to evaluate the impact of four single nucleotide polymorphisms (SNPs) of CYP3A4 gene, the SNP-SNP and gene-environment interactions on the susceptibility to breast cancer in Chinese women. METHODS: Logistic regression was used to explore the relationship between four SNPs of CYP3A4 gene and the risk of breast cancer. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best SNP-SNP and gene-abdominal obesity interaction combinations among four SNPs and abdominal obesity. Haplotype examination among 4 SNPs was conducted using the SHEsis web-based platform. RESULTS: Logistic regression analysis showed that carriers of rs2242480- T allele have significantly higher breast cancer risk, than those with rs2242480- CC genotype, adjusted OR (95%CI) was 1.68 (1.23-2.16) and 2.03 (1.53-2.58) for participants with CT genotype and TT genotype under additive model. We did not find any notable interactions between the four SNPs within the CYP3A4 gene. GMDR model found a significant association in a two-locus model involving rs2242480 and obesity, with a p-value of 0.018. Stratified analysis found that breast cancer risk was the highest in obese participants with rs2242480- CT or TT genotype, compared to those non-obese participants with rs2242480- CC genotype, OR (95%CI) was 3.02 (1.83-4.25). We found that all haplotype combinations were not correlated with breast cancer risk. CONCLUSIONS We found that the T allele of rs2242480 within the CYP3A4 gene and interaction between rs2242480 and obesity were associated with an increased risk of breast cancer. However, the results of this study were only applicable to the Han ethnic group and cannot be generalized to other ethnic groups in China, and more SNPs of CYP3A4 gene should been enrolled in the analysis in the future, to verify the results obtained in this study.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/etiology* ; China/epidemiology* ; Cytochrome P-450 CYP3A/metabolism* ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Haplotypes ; Obesity/epidemiology* ; Polymorphism, Single Nucleotide ; Risk Factors ; East Asian People

Objective To investigate the mechanism and protective effect of Humanin(HN)on rotenone(Rot)-induced toxic damage for dopamine neurons.Methods The Rot-poisened PC12 cell model was constructed,and the control group,the Rot poisening group,the HN pretreated Rot poisening group,and the HN treatment group were set up.ELISA was used to detect the content of HN inside and outside of Rot-infected cells,CCK-8 assay was used to detect cell viability,and ATP detection kit was used to detect the intracellular ATP content.Dichloro-dihydro-fluorescein diacetate(DCFH-DA)assay was used to detect the level of reactive oxygen species(ROS)in cells.Western blotting was performed to detect the expression level of mitochondrial autophagy regulatory proteins Pink1,Parkin,p62,LC3,mitochondrial biogenesis regulatory protein PGC1α,division/fusion regulatory proteins OPA1,MFN2,DRP1,p-DRP1 and antioxidant stress regulatory proteins Keap1 and Nrf2.HBAD-mcherry-EGFP-LC3 adenovirus transfected cells was used to observed the number of autophagosomes and autophagolysosomes.Results The results showed that the intracellular concentration of HN in PC12 in the Rot poisening group was significantly higher than that in the control group(P＜0.05);Compared with the control group,the Rot poisening group had significantly decreased activity of PC12 cells,decreased ATP content and increased production of ROS.After the poisen of Rot in PC12 cells,the expression of Pink1 and p-Parkin,the ratio of LC3Ⅱ/LC3Ⅰ and the expression of p-DRP1 in mitochondrial fusion protein was increased,while the expression of p62,the expression of mitochondrial biogenesis protein PGC1 α,mitochondrial fusion proteins MFN2 and OPA1,and antioxidant stress proteins Keap1 and Nrf2 were decreased(all P＜0.05).The number of autophagosomes and autophagolysosomes in PC12 cells in the Rot poisening group was higher than that in the control group(P＜0.05),and HN pretreatment(20 μmol/L)could significantly improve the changes mentioned above caused by Rot poisening(P＜0.05).Conclusion HN ameliorates Rot-induced toxic damage for dopamine neurons by inhibiting mitophagy and mitochondrial division and promoting mitochondrial biogenesis and fusion,and anti-oxidative stress.

Secondary caries is one of the main reasons that affect the service life of the restoration. Compared with primary caries, secondary caries have some particularities in etiology, disease progression, clinical manifestation, clinical diagnosis, treatment and prevention. Starting from the above aspects, combined with the latest basic and clinical research on secondary caries, this paper summarizes and analyzes its pathogenesis and prevention strategies, which will lay a certain foundation for in-depth understanding of secondary caries and promoting its clinical prevention and treatment.

Dysbiosis can cause microenvironmental dysregulation, which can further lead to local or systemic diseases, such as caries, inflammatory bowel disease, obesity, and diabetes. Dysbiosis is primarily manifested as the disturbance of metabolic processes and products. Arginine plays an important role in various metabolic processes and homeostasis of the microbial flora and the host. This study aims to explore the potential therapeutic value of arginine and its metabolism and homeostasis regulation in diseases associated with oral-intestinal dysbiosis. Host and microbial homeostasis can be restored by regulating the composition or function of host microbiota, and arginine has been found to exhibit significant clinical potential in restoring host microbiota composition and function. For example, arginine can reduce the risk of caries by regulating the relative abundance of Streptococcus mutans and Streptococcus sanguineus. Additionally, arginine metabolism may play a therapeutic role in inflammatory bowel disease and obesity by regulating the relative abundance of Firmicutes and Bacteroidetes. In addition, supplementation of arginine and its metabolite polyamine has clinical prospects in the treatment of diabetic patients with ketoacidosis. Although studies have demonstrated the therapeutic role of arginine in oral, intestinal, and metabolism-related diseases, the specific mechanism is yet to be explored. In addition, further research is required to determine the optimal clinical dosage of arginine that can maintain microbiota homeostasis without causing any side effects.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the inhibitory effect and molecular mechanism of Huaier granule on the growth of sorafenib resistant hepatocellular carcinoma (HCC) cells. Methods The gradient concentration of Huaier granule was used to treat HCC cells, and the effect of Huaier granule on the proliferation, migration and invasion of sorafenib resistant HCC cells was analyzed. Bioinformatics methods were used to analyze the possible interaction between microRNA-31-5p (miR-31-5p) and sprouty-related proteins with an EVH1 domain 1 (SPRED1). The expression levels of miR-31-5p and SPRED1 in HCC cells were detected by real time fluorescence quantitative polymerase chain reaction (qRT-PCR); cell viability, proliferation, migration, invasion and apoptosis were detected by CCK-8, colony formation, scratch healing, Transwell and flow cytometry; RNA immunoprecipitation (RIP) assay and dual luciferase assay were used to verify the binding relationship between miR-31-5p and SPRED1. Results Huaier granule could significantly inhibit the proliferation, migration and invasion of sorafenib resistant HCC cells, and induce apoptosis. Bioinformatics analysis showed that miR-31-5p was highly expressed in HCC, and Huaier granule was able to down-regulate the expression of miR-31-5p, inhibit the proliferation and metastasis of sorafenib resistant HCC cells, and induce apoptosis; miR-31-5p showed a targeted inhibition effect on the expression of SPRED1. SPRED1 was down-regulated in HCC, and overexpression of SPRED1 was able to reverse the promoting effect of overexpression of miR-31-5p on proliferation and metastasis of sorafenib resistant HCC. Conclusion Huaier granule can inhibit sorafenib resistant HCC metastasis through the miR-31-5p/SPRED1 axis, indicating that Huaier granule has the potential to be used as a novel drug for HCC treatment.