Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
Adipogenesis/drug effects* ; Triazoles/chemical synthesis* ; Ginsenosides/chemical synthesis* ; Saponins/chemical synthesis* ; Animals ; Mice ; Structure-Activity Relationship ; PPAR gamma/genetics* ; 3T3-L1 Cells ; Adipocytes/metabolism* ; Panax notoginseng/chemistry* ; Drug Design ; Molecular Structure ; Humans ; Cell Differentiation/drug effects* ; Fatty Acid-Binding Proteins/genetics*

Objective To study the brain functional connectivity(FC)changes in patients with normal tension glau-coma(NTG)and healthy volunteers using FC technique of resting-state functional magnetic resonance imaging(rs-fMRI)based on V1 region seed point(ROI),so as to explore the pathogenesis and early diagnosis of NTG.Methods Fourteen NTG patients(NTG group)who met the inclusion criteria and 14 healthy controls(HCs group)were enrolled.The clinical data of all subjects were collected,and rs-fMRI was performed in both groups.The magnetic resonance data was pre-pro-cessed by software,and bilateral A1 regions were taken as the ROI to analyze their correction with the whole brain voxel time series and obtain the FC value between the ROI and the whole brain by comparison of FC values in resting state be-tween the groups.Pearson correlation analysis was used to explore the relationship between FC value in the brain regions with significant differences with the ROI and clinical variables in the NTG group.Results Compared with the subjects in the HCs group,there were no statistically significant differences in age,gender,body weight,cup-disc ratio and 24 h mean intraocular pressure of patients in the NTG group(all P＞0.05),and there were statistically significant differences in the best corrected visual acuity(BCVA)of both eyes and peripapillary retinal nerve fiber layer thickness(RNFLT)(all P＜0.05).The Pearson correlation analysis showed that FC value of the brain regions with abnormal FC to V1 region were cor-related with RNFLT in the NTG group(P＜0.05).ROI1-left superior frontal gyrus,ROI1-right superior frontal gyrus,ROI2-left cingulate gyrus and ROI2-right middle frontal gyrus were significantly positively correlated with RNFLT(all P＜0.05).Compared with the HCs group,the brain regions with reduced FC to the right ROI in the NTG group were the left superior frontal gyrus and right superior frontal gyrus;the brain regions with reduced FC to the left ROI were the left cingulate gyrus and right middle frontal gyrus.Conclusion Compared to healthy individuals,NTG patients have significant changes in the functional connections between certain specific brain regions and V1 region,including bilateral superior frontal gyrus,left cingulate gyrus,and middle frontal gyrus.The changes in brain functional activity may be caused by visual dysfunction caused by NTG,leading to functional impairment of the visual and cognitive emotion processing brain regions,which may be one of the potential neuropathological mechanisms in NTG patients.

Objective To explore the changes in macular microcirculation status and visual function in patients with normal tension glaucoma(NTG)using the optical coherence tomography angiography(OCTA)and microperimeter MP-3 and analyze the correlation between the two.Methods In this cross-sectional observational study,17 NTG patients(30 eyes)were collected as the NTG group and then divided into mild,moderate and severe NTG subgroups according to the severity of the disease.During the same period,13 healthy subjects(23 eyes)with the same age and gender distribution were selected as the control group.OCTA was used to obtain linear density(LD)and perfusion density(PD)of superficial retinal vessels in the macular area.The microperimeter MP-3 was used to measure retinal sensitivity(RS)within 10° and fixation rate at 2° and 4° of the macular area.The OCTA parameters and microperimeter MP-3 parameters were compared among all groups,and the correlation between OCTA parameters and microperimeter MP-3 parameters in NTG patients was analyzed.Results There were no significant differences in LD and PD between the control group and the mild NTG sub-group in the central and nasal sides of the macula;the LD and PD in the remaining regions and overall average LD and PD showed a gradual downward trend in the control group and the mild,moderate and severe NTG subgroups.Compared with the control group,the RS of the mild NTG subgroup was lower in the inferior and temporal regions of the macular area.The RS of each region and overall average RS in the macular area decreased with the aggravation of the NTG.In the NTG group,LD and PD were significantly positively correlated with RS in each region and overall average RS in the macular area(all P＜0.05).In the NTG group,LD and PD were positively correlated with P2 in some regions of the macular area.Con-clusion Compared with the control group,the macular microcirculation status and visual function of NTG patients signif-icantly decreased with the progression of the disease;there is a significant correlation between macular LD and RS in NTG patients.

Objective:To establish a high-performance liquid chromatography(HPLC)method for the simultaneous determination of 10 bacteriostatic agents in Kangfuxin solution.Methods:The HPLC method parameters were as follows,a Thermo AcclaimTM 120 column(4.6 mm × 250 mm,5 μm),a gradient mobile phase of 0.1％glacial acetic acid-0.02 mol·L-1 ammonium acetate solution and methanol at a flow rate of 1 mL·min-1,and the scan-ning wavelength of 200-700 nm.Results:In the corresponding concentration range,the linear relationship be-tween the mass concentration of the 10 bacteriostatic agents and the peak area was good(r≥0.999 8);the preci-sion was good with RSD of 0.33％-0.38％;The RSD values of the repeatability test and the stability test were＜0.5％,the recovery rate was 97.4％-101.1％,and the RSD was between 0.4％-1.8％.According to the pro-posed method,the content results of benzoic acid,sorbic acid,hydroxyphenyl ethyl ester and hydroxyphenyl propyl ester in the test sample were 0.15-0.34％,0-0.48％,0-0.02％,and 0-0.02％,respectively.Conclu-sion:This method is sensitive,rapid,specific and accurate,and can be used for the determination of the content of bacteriostatic agents in Kangfuxin solution.

Objective To investigate the role of miR-194-3p in regulating functional changes in osteoblasts in a simulated microgravity environment and to provide a theoretical foundation for understanding the mechanical response mechanisms of osteoblasts in extreme mechanical environments.Methods The effects of microgravity on osteoblasts were simulated by using a rotary cell culture system.MC3T3-E1 osteoblasts were transfected with an miR-194-3p inhibitor and changes in proliferation,differentiation,apoptosis,and mineralization were assessed using MTT assay,RT-PCR,Western blot,double fluorescence staining,and alizarin red staining.Results Elevated expression of miR-194-3p under simulated microgravity conditions led to the suppression of osteoblast proliferation,differentiation,and mineralization to a certain extent,while promoting osteoblast apoptosis.However,transfection with the miR-194-3p inhibitor significantly downregulated miR-194-3p expression and partially reversed the reduced osteoblast proliferation,decreased expression of osteogenic differentiation markers such as ALP,OCN,and COL-I genes and proteins,decreased bone mineralization nodules,and increased osteoblast apoptosis induced by microgravity exposure.These findings indicated that miR-194-3p effectively ameliorates abnormal osteoblast function under microgravity conditions.Conclusions MiR-194-3p acts as a negative regulatory factor in the mechanical responses of osteoblasts under simulated microgravity.

Objective To investigate the diagnostic value of serum lamin A(LMNA)and leukotriene(LT)B4 for adverse pregnancy outcomes in patients with hypertensive disorders of pregnancy(HDP).Methods A total of 83 HDP patients admitted to the hospital from January 2021 to May 2023 were selected as the HDP group and 83 healthy pregnant women in the same period were selected as the control group.According to the pregnancy outcome,the HDP patients were divided into a poor outcome group(38 cases)and a good outcome group(45 cases).Serum LMNA and LTB4 levels were measured by enzyme-linked immunosorbent assay.Multivariate Logistic regression was used to analyze the influencing factors of adverse pregnancy outcomes in patients with HDP.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of serum LMNA and LTB4 levels for adverse pregnancy outcomes in patients with HDP.Results Compared with the control group,the serum LMNA level was decreased and the LTB4 level was increased in the HDP group(P＜0.05).Compared with the good outcome group,the serum LMNA level was significantly de-creased,and the LTB4 level was increased in the poor outcome group(P＜0.05).Preeclampsia,severe pre-eclampsia and elevated LTB4 level were independent risk factors for adverse pregnancy outcomes in patients with HDP,and elevated LMNA level was an independent protective factor(P＜0.05).The area under the curve of serum LMNA and LTB4 levels in the diagnosis of adverse pregnancy outcomes of HDP patients was 0.873,which was larger than 0.787 and 0.786 of serum LMNA and LTB4 levels alone(P＜0.05).Conclusion De-creased serum LMNA and increased LTB4 levels are associated with adverse pregnancy outcomes in patients with HDP.Combined detection of serum LMNA and LTB4 levels have a high diagnostic value for adverse pregnancy outcomes in patients with HDP.

Objective:To investigate the clinical phenotype and gene mutation in a child with developmental disorders caused by CTNNB1 gene mutation. Methods:Clinical data of a child with CTNNB1 gene mutation who was admitted to Xiamen Hospital of Fudan University Affiliated Pediatric Hospital in May 2017 were collected, whole exome sequencing technology was applied to verify the family lineage of the child, and the pathogenicity of mutation site was analyzed. Results:The patient was a 6 years and 1 month old male, with a clinical phenotype including mental retardation, motor developmental disorders, speech disorders, visual disorders (internal strabismus), microcephaly, and behavioral problems (social withdrawal, overdependence, etc.), as well as panic syndrome (i.e., sudden shrieking in response to auditory and visual stimuli, extensional rigidity of the body, etc., followed by short periods of general extensional rigidity). The whole exome sequencing results showed the presence of a de novo mutation c.283(exon4)C>T in the CTNNB1 gene, and the c.283(exon4)C>T mutation was interpreted as pathogenic (PVS1+PS2+PS1+PM2+PM) according to the American College of Medical Genetics and Genomics variant classification criteria and guidelines. No relevant genetic variants were found in the parental family verification. Conclusion:CTNNB1 gene mutation c.283(exon4)C>T can cause neurodevelopmental disorders, including mental retardation, motor developmental disorders, speech disorders, visual disorders, microcephaly and behavioral abnormalities.

The geometric bone model of patients is an important basis for individualized biomechanical modeling and analysis, formulation of surgical planning, design of surgical guide plate, and customization of artificial joint. In this study, a rapid three-dimensional (3D) reconstruction method based on statistical shape model was proposed for femur. Combined with the patient plain X-ray film data, rapid 3D modeling of individualized patient femur geometry was realized. The average error of 3D reconstruction was 1.597-1.842 mm, and the root mean square error was 1.453-2.341 mm. The average errors of femoral head diameter, cervical shaft angle, offset distance and anteversion angle of the reconstructed model were 0.597 mm, 1.163°, 1.389 mm and 1.354°, respectively. Compared with traditional modeling methods, the new method could achieve rapid 3D reconstruction of femur more accurately in a shorter time. This paper provides a new technology for rapid 3D modeling of bone geometry, which is helpful to promote rapid biomechanical analysis for patients, and provides a new idea for the selection of orthopedic implants and the rapid research and development of customized implants.
Humans ; Imaging, Three-Dimensional/methods* ; Tomography, X-Ray Computed/methods* ; Femur/surgery* ; Femur Head ; Lower Extremity

Objective To evaluate biomechanical properties of the personalized titanium alloy short femoral prosthesis by finite element analysis. Methods Based on the validated femoral finite element model, the base of the femoral neck was simulated, and by inserting different short femoral prostheses, four total hip replacement (THR) models, namely, the SMF stem model (Model A), BE1 stem model (Model B), MINI stem model (Model C) and personalized stem model (Model D) were established, respectively. The same loads and constraints were applied to four groups of models, and the von Mises stress distribution and deformation were calculated and analyzed, so as to compare mechanical stability of each model. Results The deformation of all THR models was smaller than that of the femur model under physiological state. The deformation of Model B was close to that of Model C, and the deformation of Model A was close to that of Model D. The peak stress of Model C was higher than that of the other 3 models, reaching 9555 MPa. The overall stress trend was Model C > Model B > Model D> Model A > Model under physiological state. Conclusions The peak stress, stress distribution of personalized short femoral stem were similar to that of SMF stem, with reasonable stress distribution, small stress shielding of the proximal femur, minimum overall deformation and shear stress of the prosthesis, and its effectiveness and stability could meet the requirements of human biomechanics, which could provide references for joint surgeons and prosthesis researchers.

Objective To observe the changes and significance of the protein expression levels of nuclear factor-κB p65 (NF-κB p65), transforming long factor-β1 (TGF-β1) and apoptosis-related factors Bcl-2 and Bax in myocardial tissue of Bama miniature pig model of diabetic cardiomyopathy (DCM). Methods Ten healthy male Guangxi Bama miniature pigs, aged 4 to 5 months old, were selected and divided into control group and model group according to the random number table method, with 5 pigs in each group. After 12 hours of fasting in the two groups, the DCM model was replicated by intravenous injection of streptozotocin (STZ) 150 mg/kg; for the Bama miniature pigs in the control group, citric acid-sodium citrate buffer 150 mg/kg was injected intravenously. After 10 months of modeling, the basic conditions of the two groups of animals were observed and their fasting blood glucose (FPG) levels were detected. The protein expression levels of NF-κB p65, TGF-β1, Bcl-2 and Bax in myocardial tissue of two groups were detected by Western Blot and the pathological changes of myocardial tissue were observed under electron microscope. Results In the model group, 4 models were successfully established, and 1 died. The model pigs had symptoms such as polydipsia, polyphagia, polyuria and decreased body weight. The FPG level in the model group was significantly higher than that in the control group (mmol/L: 25.53±3.75 vs. 4.68±0.77, P < 0.01). Compared with the control group, the protein expression levels of NF-κB p65, Bax and TGF-β1 in the myocardial tissue of model group were significantly increased (NF-κB p65/GAPDH: 0.46±0.05 vs. 0.38±0.02, Bax/GAPDH: 0.46±0.01 vs. 0.35±0.01, TGF-β1/GAPDH: 0.39±0.01 vs. 0.33±0.01, all P < 0.05) and the expression level of Bcl-2 protein was significantly decreased (Bcl-2/GAPDH: 0.33±0.01 vs. 0.42±0.01, P < 0.01). Electron microscopy results showed that the myofibrils of myocardial tissue in the DCM model group were disordered, and the number of mitochondria in the gap was significantly reduced. A large number of mitochondria with vacuolar degeneration were observed. Conclusions The DCM model of Bama miniature pigs can be successfully replicated after 10 months of high-dose STZ disposable ear vein injection. The DCM model miniature pigs have obvious glucose metabolism disorder, and their myocardial tissue has inflammatory reaction, cardiomyocyte apoptosis and fibrosis.