PCOS is a highly prevalent disease in modern women of gestational age, characterized by infertility. Prevention before onset has been a key focus of national efforts in recent years. This article explored the prevention and treatment plan for polycystic ovary syndrome based on the three-level prevention theory of Academician Wang Qi. Primary prevention: control pathogenic risk factors; secondary prevention: precise screening and life intervention to prevent the formation of dangerous constitution; third level prevention: differentiation of body-differentiation of disease-differentiation of syndrome to achieve the goal of three-level prevention. In the prevention and treatment of PCOS, pre-disease prevention, post disease prevention and cure are tried to achieve, which could provide a truly effective, easy to operate, and applicable three-level prevention and treatment plan for a large population in clinical response to PCOS.

Objective To investigate the injury mechanisms of three-year-old child occupants by reconstructing a real traffic accident.Methods A traffic accident case from the CIREN database was reconstructed using a vehicle finite element model and a three-year-old child occupant injury bionic model(TUST IBMs 3YO-O).The Δv,mass of the vehicle,and deformation energy were comprehensively analyzed to calculate the collision velocity of the vehicle.This accident was simulated to present injuries to a child occupant,and the injury mechanisms were analyzed in depth.Results The TUST IBMs 3YO-O fully reconstructed the injuries of the child occupant in this case.The kinematic and biomechanical responses of the children's heads differed.The biomechanical response of the internal tissues and organs in the chest cavity showed no injury,however,the result ant chest acceleration at 3 ms reached 54 g,which exceeded the threshold.Conclusions In the future,it will be necessary to adopt biomechanical parameters for occupant safety evaluations.The application of human biomechanical models with high biofidelity to reconstruct occupant injuries in traffic accidents can not only be used to observe the kinematic responses of the occupant in the accident and analyze the injury mechanisms in depth,but also to provide references for virtual testing,as well as for the research and development of child occupant protection devices and the formulation of safety regulations.

The study presents a method for the personalized biomechanical modeling of the human head and validates the generated model.Based on the TUST 50th percentile head biomechanical model,the method utilizes head CT data of the target model,and employs three-dimensional point cloud registration and free-form deformation techniques to rapidly develop a personalized head finite element model with detailed brain tissue structures.By reconstructing classic cadaver tests,it is found that the personalized head biomechanical model created by the proposed method shows a good consistency with the results of cadaver tests in kinematic and biomechanical responses.Furthermore,no significant differences are observed when compared with the head biomechanical model developed using reverse engineering method,thus verifying the effectiveness of the developed model.Consequently,the proposed method can be used to quickly construct personalized head biomechanical models with detailed anatomical structures,providing a fundamental computational analysis tool for researches in injury biomechanics,clinical medicine,and forensic identification.

Pulmonary fibrosis (PF) is a pathological change caused by repeated injuries and repair dysfunction of the alveolar epithelium. Our previous study revealed that the residues Asn3 and Asn4 of peptide DR8 (DHNNPQIR-NH₂) could be modified to improve stability and antifibrotic activity, and the unnatural hydrophobic amino acids α-(4-pentenyl)-Ala and d-Ala were considered in this study. DR3penA (DHα-(4-pentenyl)-ANPQIR-NH₂) was verified to have a longer half-life in serum and to significantly inhibit oxidative damage, epithelial-mesenchymal transition (EMT) and fibrogenesis in vitro and in vivo. Moreover, DR3penA has a dosage advantage over pirfenidone through the conversion of drug bioavailability under different routes of administration. A mechanistic study revealed that DR3penA increased the expression of aquaporin 5 (AQP5) by inhibiting the upregulation of miR-23b-5p and the mitogen-activated protein kinase (MAPK) pathway, indicating that DR3penA may alleviate PF by regulating MAPK/miR-23b-5p/AQP5. Safety evaluation showed that DR3penA is a peptide drug without obvious toxicity or acute side effects and has significantly improved safety compared to DR8. Thus, our findings suggest that DR3penA, as a novel and low-toxic peptide, has the potential to be a leading compound for PF therapy, which provides a foundation for the development of peptide drugs for fibrosis-related diseases.

OBJECTIVE: Early bolting of Saposhnikovia divaricata has seriously hindered its medicinal value and sustainable development of resources. The molecular mechanism of bolting and flowering of S. divaricata is still unclear and worth of research. In our study, we explored the transcriptome of the genes related to the bolting and flowering of S. divaricata. METHODS: The transcriptome library was constructed, sequenced, assembled and annotated from the bolting and unbolting leaves of S. divaricata by high-throughput sequencing at the bud and flowering stage. Focus on the pathways related to bolting and flowering in plants, and exploring genes. The expression of seven candidate genes was verified by real-time fluorescence quantitative PCR (qRT-PCR). RESULTS: Transcriptome results showed that 249 889 422 high-quality clean reads were obtained. A total of 67 866 unigenes were assembled with an average length of 948.1 bp. Trinity de Novo assembly produced 67 866 unigenes with an average length of 948.1 bp. Among 993 differentially expressed genes, 484 genes were significantly up-regulated and 509 genes were down-regulated in the SdM group. A total of 79 GO terms were significantly enriched for differentially expressed genes. KEGG results showed that 11 154 unigenes were enriched in 89 pathways. And 21 candidate genes related to bolting and flowering of S. divaricata were excavated. The qRT-PCR results showed that expression trends of HDA9, PHYB, AP2, TIR1, Hsp90, CaM, and IAA7 were consistent with transcriptomic sequencing results. In addition, RNA-seq had identified 10 740 transcription factors and classified them into 58 families by their conserved domains. Further studies showed that the transcription factors regulating the flowering of S. divaricata were mainly distributed in the NAC, MYB_related, HB-other, ARF, and AP2 families. CONCLUSION Based on the results of this study, it was found that the plant hormone signal transduction pathway was one of the decisive factors to control bolting and flowering. Among them, auxin related genes IAA and TIR1 are the key genes in the bolting and flowering process of S. divaricata.

Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.
Humans ; Antineoplastic Agents/therapeutic use* ; Apoptosis ; beta Catenin/metabolism* ; Biomarkers, Tumor/metabolism* ; Cell Line, Tumor ; Coenzyme A Ligases/metabolism* ; Leukemia, Myeloid, Acute/metabolism* ; Lipoylation ; Prognosis ; Wnt Signaling Pathway

Senile dementia is a disease that gradually develops with age. At present, the etiology, pathogenesis and treatment of senile dementia cannot be completely determined clinically. Therefore, it is extremely necessary to prevent and treat senile dementia from prevention and disease management. For the non-ill people, this article analyzed the susceptible groups of senile dementia from the perspective of TCM constitution, combined with the current prevention plan of Alzheimer's disease, from the aspects of examination, nutritional supplementation, adjustment of work and rest, exercise, etc., early physical fitness prevention targeting populations at different stages was conducted; the early onset of senile dementia is not obvious, and the early prevention of senile dementia can be carried out from various aspects in combination with constitution identification and inspection of senile dementia; for the exact sick population, disease management guidance can be added on the basis of the above aspects to provide definite and feasible recommendations for disease prevention and management of the elderly.

Objective To predict and assess biomechanical responses and injury mechanisms of the thorax and abdomen for small-sized females in vehicle collisions. Methods The accurate geometric model of the thorax and abdomen was constructed based on CT images of Chinese 5th percentile female volunteers. A thoracic-abdominal finite element model of Chinese 5th percentile female with detailed anatomical structure was developed by using the corresponding software. The model was validated by reconstructing three groups of cadaver experiments (namely, test of blunt anteroposterior impact on the thorax, test of bar anteroposterior impact on the abdomen, test of blunt lateral impact on the chest and abdomen). Results The force-deformation curves and injury biomechanical responses of the organs from the simulations were consistent with the cadaver experiment results, which validated effectiveness of the model. Conclusions The model can be used for studying injury mechanisms of the thorax and abdomen for small-sized female, as well as developing small-sized occupant restraint systems and analyzing the forensic cases, which lays foundation for developing the whole body finite element model of Chinese 5th percentile female.

Abivertinib, a third-generation tyrosine kinase inhibitor, is originally designed to target epidermal growth factor receptor (EGFR)-activating mutations. Previous studies have shown that abivertinib has promising antitumor activity and a well-tolerated safety profile in patients with non-small-cell lung cancer. However, abivertinib also exhibited high inhibitory activity against Bruton's tyrosine kinase and Janus kinase 3. Given that these kinases play some roles in the progression of megakaryopoiesis, we speculate that abivertinib can affect megakaryocyte (MK) differentiation and platelet biogenesis. We treated cord blood CD34⁺ hematopoietic stem cells, Meg-01 cells, and C57BL/6 mice with abivertinib and observed megakaryopoiesis to determine the biological effect of abivertinib on MK differentiation and platelet biogenesis. Our in vitro results showed that abivertinib impaired the CFU-MK formation, proliferation of CD34⁺ HSC-derived MK progenitor cells, and differentiation and functions of MKs and inhibited Meg-01-derived MK differentiation. These results suggested that megakaryopoiesis was inhibited by abivertinib. We also demonstrated in vivo that abivertinib decreased the number of MKs in bone marrow and platelet counts in mice, which suggested that thrombopoiesis was also inhibited. Thus, these preclinical data collectively suggested that abivertinib could inhibit MK differentiation and platelet biogenesis and might be an agent for thrombocythemia.
Acrylamides/pharmacology* ; Animals ; Blood Platelets/drug effects* ; Cell Differentiation ; Megakaryocytes/drug effects* ; Mice ; Mice, Inbred C57BL ; Piperazines/pharmacology* ; Pyrimidines/pharmacology*

Objective To study influencing factors of renal blunt impact injury by using finite element (FE) method. Methods Based on CT images of the kidney, the kidney FE models for different age groups were constructed. The renal blunt impact test was reconstructed, and the influence of kidney material constitutive parameters, kidney tissue structure, kidney size, impact position and impact velocity on injury severity were analyzed. Results Under the same impact condition, the stress of renal cortex decreased with the kidney mass increasing, and increased with the impact velocity of the hammer increasing. The renal capsule had a certain energy absorption effect, so as to reduce the kidney stress. When the kidney was impacted, the stress of renal cortex under side impact was significantly higher than that under frontal impact. Conclusions Compared with viscoelastic constitutive model, Mooney Rivlin material constitutive model is more suitable for FE evaluation on renal injury severity. The renal injury decreases with the kidney mass increasing. The increase of impact velocity will intensify the renal injury severity. Renal capsule will reduce renal injury to a certain extent, so the existence of renal capsule structure must be considered in FE modeling of the kidney. Compared with frontal and rear impact, the renal injury severity is greater when the kidney is impacted from the lateral side.