OBJECTIVE: To explore the displacement and pressure distribution of American Chiropractic in a model of third lumbar syndrome based on finite element analysis. METHODS: On March 2021, CT and MRI images of a 23-year-old male patient with right third lumbar syndrome were selected. A 3D stl model was established using Mimics and CATIA, and the data was imported into Hypermesh, Abaqus & ANSYS. The elastic modulus and Poisson's ratio of the affected side material were adjusted to establish its finite element model. Based on the comparison of the operating positions and routines of the American Chiropractic and the lumbar spine oblique pull method, but with differences in the focus and direction of force, the experimental group simulated the American Chiropractic with the healthy side (left side) lying position of the model. The upper endplate of L₃ and the lower part below L₃ twisted accordingly with the body position, we applied a vertical forward thrust of 246 N to the plane formed by the L₄, L₅ spinous processes and L₄ upper articular processes;The control group simulates the oblique pull method of the lumbar spine, requiring the model to lie on the healthy side (left side), fix the upper endplate of L₄, and perform a horizontal rotation along the longitudinal axis of L₃ vertebral body. At this time, the contact force in the upward direction is also set to 246 N. Compare the displacement and stress differences between the L₁-L₅ intervertebral bodies, intervertebral discs, articular processes, and transverse process muscles in two intervention models. RESULTS: ① Under safe load conditions, a test force of 246 N was applied to the model, and the maximum vertebral displacement occurred on the right side of the L₃ vertebral body (1.197 mm) after manual intervention in the control group. The vertebral displacement between L₁-L₅ induced by manual intervention in the experimental group was smaller than that of the control group's manual intervention (P<0.05). ② The maximum vertebral body stress occurred on the right side of the L₃ vertebral body after manual intervention in the control group (98.425 MPa). The stress on each vertebral body formed by the experimental group's manual intervention was lower than that of the control group's manual intervention (P<0.05). ③The maximum intervertebral disc stress occurred on the right side of the L_2,3 intervertebral disc (6.282 MPa) after manual intervention in the control group. ④ The maximum joint process stress occurred on the right side of the L₄ upper joint process after manual intervention in the experimental group (1.587 MPa). The joint process stress on the left side below L₁ and the left side above and below L₂ induced by manual intervention in the experimental group was lower than that of the control group (P<0.05). ⑤The maximum stress on the intertransverse process muscle was observed at the right lateral L₃ process end (31.960 MPa) of L_3,4 in the control group after manual intervention. The stress on the L_2,3 and L_4,5 segments of the intertransverse process muscle induced by manual intervention in the experimental group was lower than that of the control group's manual intervention (P<0.05). CONCLUSION The mechanical feedback of the L₁-L₅ vertebral body, the lower left side of the articular process L₁, the upper and lower left side of the articular process L₂, and the L_2,3 and L_4,5 segments of the transverse process muscle in the model indicates that performing American Chiropractic for the treatment of third lumbar transverse process syndrome can accurately hit the target pain point and allow the patient's tissue to form a low stress and low tension state after manual operation, thereby reducing the possibility of tissue damage caused by hypertonia after intervertebral joint movement, making it relatively safe. The application of American Chiropractic will be a new supplement to the traditional treatment plan for third lumbar transverse process syndrome.
Humans ; Finite Element Analysis ; Male ; Lumbar Vertebrae/physiopathology* ; Biomechanical Phenomena ; Young Adult ; Manipulation, Chiropractic ; Adult ; Tomography, X-Ray Computed ; Magnetic Resonance Imaging

OBJECTIVES: The core pathology of osteoporosis lies in bone resorption exceeding bone formation; thus, promoting osteogenesis is a key therapeutic strategy. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) forms the biological basis of bone formation. Astragaloside IV (A-IV), a major active component of Astragalus membranaceus, is known to enhance osteogenesis, but its precise molecular mechanisms remain unclear. This study aims to investigate the effects of A-IV on the proliferation and osteogenic differentiation of BMSCs from osteoporotic rats and to elucidate its molecular mechanism through the regulation of microRNA-21 (miR-21) and Notch2 expression. METHODS: After 1 week of adaptive feeding, mature female SD rats were randomly divided into a sham-operated (Sham) group (n=4) and an ovariectomized (OVX) group (n=8) to establish an osteoporosis model. Twelve weeks after surgery, BMSCs were isolated from femoral bone marrow and cultured. Cells were divided into a S-BMSCs group (from Sham), an O-BMSCs group (from OVX), and an A-BMSCs group (from OVX-derived BMSCs treated with A-IV). S-BMSCs and O-BMSCs were induced for osteogenic differentiation using osteogenic induction medium, whereas A-BMSCs were treated with A-IV before induction. Flow cytometry was used to identify mesenchymal stem cell surface markers (CD29) and hematopoietic stem cell marker (CD34) to confirm BMSC characteristics. Cell proliferation was assessed using the methyl thiazolyl tetrazolium (MTT) assay. Alizarin red staining was performed to quantify calcium nodule formation, and alkaline phosphatase (ALP) activity assays were used to evaluate osteogenic differentiation. Real-time reverse transcription PCR (real-time RT-PCR) was used to detect changes in osteogenic-related genes, runt-related transcription factor 2 (Runx2) and osteopontin (OPN), as well as miR-21 expression. Western blotting was performed to assess Runx2, OPN, and Notch2 protein expression. RESULTS: Flow cytometry confirmed that O-BMSCs retained the phenotypic characteristics of mesenchymal stem cells. A-IV significantly enhanced the proliferation of BMSCs from osteoporotic rats (P<0.05), increased ALP activity, and upregulated the mRNA and protein expression of Runx2 and OPN (P<0.05). Bioinformatic and experimental analyses demonstrated that miR-21 directly targeted Notch2. A-IV treatment increased miR-21 expression while suppressing Notch2 protein expression and inhibiting activation of the Notch signaling pathway (P<0.05). CONCLUSIONS Astragaloside IV promotes the osteogenic differentiation of BMSCs derived from osteoporotic rats by upregulating miR-21 expression and inhibiting the key Notch signaling protein Notch2, thereby relieving the Notch2-mediated suppression of osteogenesis.
Animals ; Triterpenes/pharmacology* ; Saponins/pharmacology* ; Osteogenesis/drug effects* ; MicroRNAs/metabolism* ; Rats, Sprague-Dawley ; Female ; Cell Differentiation/drug effects* ; Mesenchymal Stem Cells/drug effects* ; Signal Transduction/drug effects* ; Osteoporosis/pathology* ; Rats ; Cells, Cultured ; Receptor, Notch2/metabolism* ; Receptors, Notch/metabolism* ; Ovariectomy ; Cell Proliferation/drug effects*

Nigella sativa L. seeds have been traditionally utilized in Chinese folk medicine for centuries to treat vitiligo. This study revealed that the ethanolic extract of Nigella sativa L. (HZC) enhances melanogenesis and mitigates oxidative stress-induced cellular senescence and dysfunction in melanocytes. In accordance with established protocols, the ethanol fraction from Nigella sativa L. seeds was extracted, concentrated, and lyophilized to evaluate its herbal effects via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, tyrosinase activity evaluation, measurement of cellular melanin contents, scratch assays, senescence-associated β-galactosidase (SA-β-gal) staining, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis for expression profiling of experimentally relevant proteins. The results indicated that HZC significantly enhanced tyrosinase activity and melanin content while notably increasing the protein expression levels of Tyr, Mitf, and gp100 in B16F10 cells. Furthermore, HZC effectively mitigated oxidative stress-induced cellular senescence, improved melanocyte condition, and rectified various functional impairments associated with melanocyte dysfunction. These findings suggest that HZC increases melanin synthesis in melanocytes through the activation of the MAPK, PKA, and Wnt signaling pathways. In addition, HZC attenuates oxidative damage induced by H₂O₂ therapy by activating the nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway and enhancing the activity of downstream antioxidant enzymes, thus preventing premature senescence and dysfunction in melanocytes.
Oxidative Stress/drug effects* ; Melanocytes/cytology* ; Cellular Senescence/drug effects* ; Nigella sativa/chemistry* ; Plant Extracts/pharmacology* ; Seeds/chemistry* ; Mice ; Animals ; Melanins/metabolism* ; Monophenol Monooxygenase/metabolism* ; Humans

Objective To analyze the diversity and composition changes of gut fungal communities between mouse model of total parental nutrition(TPN)and normal control mice.Methods After mouse model of TPN was constructed,fresh feces were collected from TPN mice(n=5)and normal control mice(n=5).Internal transcribed spacer(ITS)DNA sequencing was applied to determine intestinal fungi,and then bioinformatics analysis was conducted to identify the differences in fungal diversity,structure,and functional properties between the 2 groups of mice.Results There were significant differences in Alpha diversity(P＜0.05)and Beta diversity(P＜0.01)of intestinal fungi between the 2 groups.In the TPN model group,the relative abundances of Candida,Penicillium,Aspergillus and Talaromyces were obviously reduced(all P＜0.01).LEfSe analysis indicated that the above 4 strains were notably enriched in the normal control mice.Conclusion TPN mice exhibit characteristic changes in the composition of gut fungal flora compared to normal control mice.Dysfunction of gut fungal community may promote the occurrence of TPN related complications,and regulating the balance of gut fungal community may become a new strategy for preventing TPN related complications.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Objective To investigate the current situation and influencing factors of latent tuberculosis infection(LTBI)among close contacts of positive etiology pulmonary tuberculosis(PTB)patients,provide basis for formula-ting intervention measures for LTBI.Methods A multi-stage stratified cluster random sampling method was used to select close contacts of positive etiology PTB patients from 39 districts and counties in Chongqing City as the study objects.Demographic information was collected by questionnaire survey and the infection of Mycobacterium tuberculosis was detected by interferon gamma release assay(IGRA).The influencing factors of LTBI were analyzed by x2 test and binary logistic regression model.Results A total of 2 591 close contacts were included,the male to female ratio was 0.69∶1,with the mean age of(35.72±16.64)years.1 058 cases of LTBI were detected,Myco-bacterium tuberculosis latent infection rate was 40.83％.Univariate analysis showed that the infection rate was dif-ferent among peoples of different age,body mass index(BMI),occupation,education level,marital status,wheth-er they had chronic disease or major surgery history,whether they lived together with the indicator case,and whether the cumulative contact time with the indicator case ≥250 hours,difference were all statistically significant(all P＜0.05);infection rate presented increased trend with the increase of age and BMI(both P＜0.001),and decreased trend with the increase of education(P＜0.05).Logistic regression analysis showed that age 45-54 years old(OR=1.951,95％CI:1.031-3.693),age 55-64 years old(OR=2.473,95％CI:1.279-4.781),other occupations(OR=0.530,95％CI:0.292-0.964),teachers(OR=0.439,95％CI:0.242-0.794),students(OR=0.445,95％CI:0.233-0.851),junior high school education or below(OR=1.412,95％CI:1.025-1.944),BMI＜18.5 kg/m2(OR=0.762,95％CI:0.586-0.991),co-living with indicator cases(OR=1.621,95％CI1.316-1.997)and cumu-lative contact time with indicator cases ≥250 hours(OR=1.292,95％CI:1.083-1.540)were the influential fac-tors for LTBI(all P＜0.05).Conclusion The close contacts with positive etiology PTB have a high latent infection rate of Mycobacterium tuberculosis,and it is necessary to pay attention to close contacts of high age,farmers,and frequent contact with patients,and take timely targeted interventions to reduce the risk of occurrence of disease.

Objective:To investigate the causal correlation between depression and stress urinary incontinence(SUI)using Mendelian randomization(MR)analysis.Methods:We searched the FinnGen Consortium database for genome-wide association studies(GWAS)on depression and obtained 23 424 case samples and 192 220 control samples,with the GWAS data on SUI provided by the UK Biobank,including 4 340 case samples and 458 670 control samples.We investigated the correlation between depression and SUI based on the depression data collected from the Psychiatric Genomics Consortium(PGC).We employed inverse-variance weighting as the main method for the MR study,and performed sensitivity analysis to verify the accuracy and stability of the findings.Results:Analysis of the data from the UK Biobank and FinnGen Consortium showed that depression was significantly correlated with an increased risk of SUI(P=0.005),but not SUI with the risk of depression(P=0.927).And analysis of the PGC data verified the correlation of depression with the increased risk of SUI(P=0.043).Conclusion:Depression is associated with an increased risk of SUI,while SUI does not increase the risk of depression.

As a key epigenetic regulator, histone deacetylases (HDACs) play a crucial role in cancer development. Small molecule HDAC inhibitors have been shown to inhibit tumor proliferation and induce apoptosis, attracting significant research attention. In this study, we designed and synthesized a series of novel saccharin derivatives as HDAC inhibitors. Biological experiments demonstrated that the target compound 9a exhibited superior HDACs inhibition activity to vorinostat and demonstrating promising in vitro and in vivo anti-tumor activity against triple-negative breast cancer (TNBC). All animal experiments in this study were performed in strict accordance with the protocols approved by the Ethical Committee of School of Pharmaceutical Sciences in Shandong University (Approval No. 230094). This work represents an initial exploration of developing saccharin-based HDAC inhibitors, and the active compound 9a could serve as a lead compound for further study.

OBJECTIVE: Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome). METHODS: We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period. RESULTS: Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome，featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated. CONCLUSION Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.
Rats ; Animals ; Arsenic/toxicity* ; Fluorides ; RNA, Ribosomal, 16S/genetics* ; Rats, Sprague-Dawley ; Metabolome ; Microbiota

Schisandra chinensis, a traditional Chinese medicinal herb, is rich in chemical constituents, including lignans, triterpenes, polysaccharides, and volatile oils. Clinically, it is commonly used to treat cardiovascular, cerebrovascular, liver, gastrointestinal, and respiratory diseases. Modern pharmacological studies have shown that S. chinensis extract and monomers have multiple pharmacological activities in lowering liver fat, alleviating insulin resistance, and resisting oxidative stress, and have good application prospects in alleviating nonalcoholic fatty liver disease(NAFLD). Therefore, this study reviewed the research progress on chemical constituents of S. chinensis and its effect on NAFLD in recent years to provide references for the research on S. chinensis in the treatment of NAFLD.
Non-alcoholic Fatty Liver Disease ; Schisandra ; Insulin Resistance ; Lignans