Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

The gut microbiota regulates intestinal nutrient absorption, participates in modulating host glucolipid metabolism, and contributes to ameliorating glucolipid metabolism disorder. Dysbiosis of the gut microbiota can compromise the integrity of the intestinal mucosal barrier, induce inflammatory responses, and exacerbate insulin resistance and abnormal lipid metabolism in the host. Dangua Humai Oral Liquid, a hospital-developed formulation for regulating glucolipid metabolism, has been granted a national invention patent and demonstrates significant clinical efficacy. This study aimed to investigate the effects of Dangua Humai Oral Liquid on gut microbiota and the intestinal mucosal barrier in a mouse model with glucolipid metabolism disorder. A glucolipid metabolism disorder model was established by feeding mice a high-glucose and high-fat diet. The mice were divided into a normal group, a model group, and a treatment group, with eight mice in each group. The treatment group received a daily gavage of Dangua Humai Oral Liquid(20 g·kg~(-1)), while the normal group and model group were given an equivalent volume of sterile water. After 15 weeks of intervention, glucolipid metabolism, intestinal mucosal barrier function, and inflammatory responses were evaluated. Metagenomics and untargeted metabolomics were employed to analyze changes in gut microbiota and associated metabolic pathways. Significant differences were observed between the indicators of the normal group and the model group. Compared with the model group, the treatment group exhibited marked improvements in glucolipid metabolism disorder, alleviated pathological damage in the liver and small intestine tissue, elevated expression of recombinant claudin 1(CLDN1), occluding(OCLN), and zonula occludens 1(ZO-1) in the small intestine tissue, and reduced serum levels of inflammatory factors lipopolysaccharides(LPS), lipopolysaccharide-binding protein(LBP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). At the phylum level, the relative abundance of Bacteroidota decreased, while that of Firmicutes increased. Lipid-related metabolic pathways were significantly altered. In conclusion, based on the successful establishment of the mouse model of glucolipid metabolism disorder, this study confirmed that Dangua Humai Oral Liquid effectively modulates gut microbiota and mucosal barrier function, reduces serum inflammatory factor levels, and regulates lipid-related metabolic pathways, thereby ameliorating glucolipid metabolism disorder.
Animals ; Gastrointestinal Microbiome/drug effects* ; Mice ; Intestinal Mucosa/microbiology* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Glycolipids/metabolism* ; Lipid Metabolism/drug effects* ; Administration, Oral ; Disease Models, Animal

Colorectal cancer (CRC) poses a severe global health challenge with high incidence and mortality rates. USP37 has been identified as the bona fide deubiquitinase of SND1, playing a critical role in stabilizing SND1, thereby augmenting its oncogenic potential. The interaction between USP37 and SND1 was confirmed through extensive proteomics, ubiquitinomics, and interactomics, underscoring their synergistic effects on CRC proliferation and metastasis. Additionally, CDK1 has emerged as a pivotal regulator of USP37, phosphorylating it at threonine 631 rather than serine 628, enhancing its deubiquitinase activity, and consequently stabilizing SND1 to drive CRC malignancy further. Histological analyses of human CRC samples linked the upregulation of CDK1 and USP37 with increased SND1 levels and poor patient prognosis. High-throughput virtual screening and subsequent experimental validation identified Dacarbazine as a pharmacological inhibitor of USP37, and its inhibition disrupted SND1 stability, hindering CRC cell proliferation and metastasis. This study reveals a novel and promising molecular mechanism driving CRC progression through the CDK1-USP37-SND1 axis, highlighting the clinical importance of targeting this pathway to improve patient outcomes.

Background: In the field of neuroscience research, executive functions (EFs) are of great significance. Patients with Parkinson’s disease (PD) often encounter the problem of EFs impairment, which severely affects their lives and health.However, currently, the methods for evaluating EFs in experimental mice are limited, and there is a lack of effective evaluation indicators for touchscreen behavioral tests in different disease model mice. This study aims to establish a paradigm process and an evaluation baseline for touchscreen behavioral analysis in PD model mice, deeply explore the mechanisms of EFs impairment in PD, and provide a crucial foundation for subsequent research and treatment. Methods: Thirty clean - grade SNCA*A53T transgenic mice and forty clean - grade C57BL/6J wild - type mice were selected. For A53T mice, genetic identification was carried out. Molecular biology techniques such as PCR were used to determine their genetic characteristics. Protein detection was conducted through methods like Western blot to clarify the expression of relevant proteins. In terms of behavioral tests, the five - choice serial reaction time task (5 - CSRT) was adopted, and various behavioral data of mice in this task were recorded. Four groups were set up: the control group, the MPTP group. Different groups of mice were given specific treatments. For example, the MPTP group of mice was injected with MPTP to construct a drug - induced PD model. Principal component analysis (PCA) and receiver operating characteristic (ROC) curves were used to analyze the obtained touchscreen behavioral baseline indicators of mice, and key indicators were screened and evaluated. Results: In the 5 - CSRT, the optimal stage for wild - type C57 mice to achieve an accuracy rate of ≥ 80% was from the 11th to the 13th cycle, while for A53T mice, it was the 11th cycle. The EFs of A53T mice were impaired, with abnormalities in the accuracy rate, trace number, and number of punished times in the 5 - CSRT. When identifying drug - induced PD models, the 13th cycle of the 5 - CSRT was more effective; when identifying transgenic PD models, the 11th cycle was more suitable. Interventions could be carried out after the baseline accuracy rate reached 80%. Through the “genetic - environmental” dual - axis drive, the “chronic - acute” time - dimension complementarity, and the “mechanism - transformation” multi - level verification, the A53T and MPTP dual models were used to comprehensively cover the pathological cycle of PD EFs impairment. Conclusions This study has successfully established a paradigm process and an evaluation baseline for touchscreen behavioral analysis in PD model mice. This provides an important basis for a deep understanding of the mechanisms of EFs impairment in PD patients, has potential guiding significance for the development of intervention strategies and treatment methods for EFs impairment in PD patients, and is expected to promote new progress in PD research in the field of neuroscience.

Objective:To investigate the relationship and clinical significance of circulating tu-mor DNA(ctDNA)methylation with postoperative recurrence of thyroid cancer.Method:5 pa-tients with recurrent thyroid cancer in our hospital from March 2021 to April 2022 were selected as the observation group,and 2 healthy volunteers were selected as the control group.The level of ctDNA methylation in peripheral blood of the two groups was detected by Illumina high-throughput sequencing system.Gene ontology(GO)function analysis and Kyoto gene and genome encyclope-dia(KEGG)signal pathway analysis were carried out on the methylation region genes with signifi-cant differences through the DAVID gene function analysis platform.Result:There were 7787 dif-ferential ctDNA methylation sites between the two groups.2914(37.4％)were hypermethylation sites and 4873(62.6％)were low methylation sites.GO functional analysis showed that differentially methylated genes were enriched in molecular functions such as DNA-binding transcriptional acti-vation,cell-substrate adhesion,glycoprotein complex and other cellular components.KEGG path-way analysis showed that differentially methylated genes were enriched in thyroid carcinoma signal pathway,cell adhesion molecules,RAP1 signal pathway,RAS signal pathway,MAPK signal path-way and so on.Conclusion:ctDNA methylation may be involved in cancer recurrence in postop-erative patients with thyroid cancer.Monitoring the level of ctDNA methylation in peripheral blood may be an effective method to indicate the recurrence or metastasis of thyroid cancer and guide clinical diagnosis and treatment.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective To investigate the induction factors of hypotension during cesarean section for perilous placenta previa under combined spinal-epidural anesthesia (CSEA) and to construct a nomogram prediction model. Methods A total of 130 parturients who underwent cesarean section for perilous placenta previa under CSEA from January 2020 to December 2023 in Yulin Maternity and Child Healthcare Hospital were selected as study subjects. A self-designed general information questionnaire was used to investigate the basic information and the occurrence of hypotension of the subjects. According to the occurrence of intraoperative hypotension, the patients were divided into hypotension group (47 cases) and non-hypotension group (83 cases). Univariate analysis was performed on the general information of the two groups, and multivariate Logistic regression analysis was used to explore the induction factors of intraoperative hypotension. Results Univariate analysis showed that there were statistically significant differences in body mass index, anesthesia level, presence of multiple pregnancy, preoperative systolic blood pressure, operative time, and the occurrence of Bezold-Jarisch reflex between the two groups (P < 0.05). Multivariate Logistic regression analysis revealed that body mass index≥ 24 kg/m², anesthesia level was in the eighth thoracic vertebra(T8) or above, multiple pregnancy, preoperative systolic blood pressure < 90 mmHg, operative time >1.5 h, and the occurrence of Bezold-Jarisch reflex were independent risk factors for hypotension during cesarean section for perilous placenta previa under CSEA (P < 0.05). A regression equation for the induction factors of hypotension during cesarean section for perilous placenta previa under CSEA was constructed: Logit(P)=-23.211+1.079×(body mass index ≥ 24 kg/m²)+1.101×anesthesia level (≥T8)+3.193×multiple pregnancy+2.214×preoperative systolic blood pressure (< 90 mmHg)+4.606×operative time (>1.5 h)+2.011×occurrence of Bezold-Jarisch reflex. The nomogram showed high discrimination and accuracy for patients with preoperative systolic blood pressure < 90 mmHg. After 1, 000 times of Bootstrap resampling for the nomogram model, a calibration curve was obtained, and the consistency index was calculated as 0.850, indicating good calibration of the nomogram model. The receiver operating characteristic (ROC) curve was plotted, with an area under the curve of 0.896 and 95% confidence interval of 0.802 to 0.956, suggesting good predictive performance. Conclusion Body mass index ≥24 kg/m², anesthesia level ≥ T8, multiple pregnancy, preoperative systolic blood pressure < 90 mmHg, operative time >1.5 h, and the occurrence of Bezold-Jarisch reflex are induction factors for hypotension during cesarean section for perilous placenta previa under CSEA.