This study aims to investigate the potential effect of the water extract of fresh Rehmanniae Radix on hypercholesterolemia in mice that was induced by a high-fat and high-cholesterol diet and explore its possible mechanism from bile acid reabsorption. Male C57BL/6 mice were randomly assigned into the following groups: control, model, low-and high-dose(4 and 8 g·kg~(-1), respectively) fresh Rehmanniae Radix, and positive drug(simvastatin, 0.05 g·kg~(-1)). Other groups except the control group were fed with a high-fat and high-cholesterol diet for 6 consecutive weeks to induce hypercholesterolemia. From the 6th week, mice were administrated with corresponding drugs daily via gavage for additional 6 weeks, while continuing to be fed with a high-fat and high-cholesterol diet. Serum levels of total cholesterol(TC), triglycerides(TG), low density lipoprotein-cholesterol(LDL-c), high density lipoprotein-cholesterol(HDL-c), and total bile acid(TBA), as well as liver TC and TG levels and fecal TBA level, were determined by commercial assay kits. Hematoxylin-eosin(HE) staining, oil red O staining, and transmission electron microscopy were performed to observe the pathological changes in the liver. Three livers samples were randomly selected from each of the control, model, and high-dose fresh Rehmanniae Radix groups for high-throughput transcriptome sequencing. Differentially expressed genes were mined and KEGG pathway enrichment analysis was performed to predict the key pathways and target genes of the water extract of fresh Rehmanniae Radix in the treatment of hypercholesterolemia. RT-qPCR was employed to measure the mRNA levels of cholesterol 7α-hydroxylase(CYP7A1) and cholesterol 27α-hydroxylase(CYP27A1) in the liver. Western blot was employed to determine the protein levels of CYP7A1 and CYP27A1 in the liver as well as farnesoid X receptor(FXR), apical sodium-dependent bile acid transporter(ASBT), and ileum bile acid-binding protein(I-BABP) in the ileum. The results showed that the water extract of fresh Rehmanniae Radix significantly lowered the levels of TC and TG in the serum and liver, as well as the level of LDL-c in the serum. Conversely, it elevated the level of HDL-c in the serum and TBA in feces. No significant difference was observed in the level of TBA in the serum among groups. HE staining, oil red O staining, and transmission electron microscopy showed that the water extract reduced the accumulation of lipid droplets in the liver. Further mechanism studies revealed that the water extract of fresh Rehmanniae Radix significantly down-regulated the protein levels of FXR and bile acid reabsorption-related proteins ASBT and I-BABP. Additionally, it enhanced CYP7A1 and CYP27A1, the key enzymes involved in bile acid synthesis. Therefore, it is hypothesized that the water extract of fresh Rehmanniae Radix may exert an anti-hypercholesterolemic effect by regulating FXR/ASBT/I-BABP signaling, inhibiting bile acid reabsorption, and increasing bile acid excretion, thus facilitating the conversion of cholesterol to bile acids.
Animals ; Male ; Bile Acids and Salts/metabolism* ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat/adverse effects* ; Cholesterol/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Hypercholesterolemia/genetics* ; Receptors, Cytoplasmic and Nuclear/genetics* ; Rehmannia/chemistry* ; Liver/drug effects* ; Humans ; Cholesterol 7-alpha-Hydroxylase/genetics* ; Plant Extracts

OBJECTIVE: To investigate the short-term clinical effect of closed reduction single arm external fixator combined with percutaneous needle fixation in the treatment of C1 distal radius fracture in elderly patients. METHODS: Between December 2022 and December 2023, a total of 60 elderly patients diagnosed with type C1 distal radius fractures were treated, comprising 9 males and 51 females. The age ranged from 65 to 84 years old, with an average of (72.69±8.14) years old. Among them, there were 18 cases on the left side and 42 cases on the right side. There were 55 cases of falling injury and 5 cases of traffic accident injury. According to the different surgical methods, the patients were divided into observation group and control group, with 30 cases in each group. The control group underwent manual reduction and unilateral external fixator fixation, consisting of 4 males and 26 females. The mean age was (72.54±8.67) years old. The body mass index (BMI) was (20.61±2.17) kg·m^-2. There were 10 cases on the left side and 20 cases on the right side. Among them, there were 27 cases of falling injury and 3 cases of traffic accident injury. The observation group was treated with manual reduction and unilateral external fixator combined with percutaneous Kirschner wire fixation, including 5 males and 25 females. The mean age was (72.76±7.23) years old. BMI (20.82±2.03) kg·m^-2. The left side was involved in 8 cases and the right side in 22 cases. There were 28 cases of falling injury and 2 cases of traffic accident injury. The changes in radial height, ulnar declination, palmar inclination angle parameters and patient-rated wrist evaluation (PRWE) were assessed on X-ray films before surgery, 2 days after surgery, and 12 weeks after surgery between the two groups. RESULTS: All surgical procedures were successfully completed in both groups without any significant complications. All patients were followed up for a duration from 12 to 20 weeks with an average of(14.50±2.78) weeks. The two groups exhibited significant differences in radial height, palmar inclination angle, and ulnar deviation angle at 2 days and 12 weeks post-operation (P<0.05). However, there was no statistically significant difference observed in radial height, palmar inclination, and ulnar deviation between the two groups at 2 days after the operation (P>0.05). There were significant differences in radial height, palmar inclination angle, and ulnar deviation between the two groups at 12 weeks after operation (P<0.05). At 2 days and 12 weeks after the operation, there were significant differences in PRWE scores of the two groups compared with preoperative scores(P<0.05). At 2 days after the operation, there was no significant difference in PRWE score between the two groups (P>0.05). The PRWE score showed a significant difference between the two groups at 12 weeks post-operation(P<0.05). CONCLUSION The combination of closed reduction and unilateral external fixator, along with percutaneous pin fixation provides move stable fixation for type C1 distal radius fractures. Gradual removal of external fixator further facilitatse the recovery of wrist joint function.
Humans ; Male ; Female ; Radius Fractures/surgery* ; External Fixators ; Aged ; Aged, 80 and over ; Bone Wires ; Fracture Fixation/instrumentation* ; Wrist Fractures

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.

BACKGROUND:Iron overload is an independent factor inducing osteoporosis,but the action mechanism is currently unclear.Therefore,exploring the effects of iron overload on osteoblast-related cells will help to deeply understand the pathogenesis of osteoporosis and provide potential strategies for osteoporosis treatment.OBJECTIVE:To explore the effects of iron overload environment on osteoblast precursor cell activity,ferroptosis,and osteogenic differentiation.METHODS:Osteoblast precursor cells(MC3T3-E1 cells)were divided into blank group,iron overload group,fer-1 group,and deferoxamine group.The iron overload group was treated with 300 μmol/L ammonium ferric citrate in the culture medium for 48 hours to simulate the iron overload microenvironment.The cells in fer-1 group and deferoxamine group were pretreated with 5 μmol/L antioxidant fer-1 and 5 μmol/L deferoxamine for 8 hours,respectively,and then added with 300 μmol/L ammonium ferric citrate for 48 hours.CCK-8 assay was used to determine the cell viability.Intracellular reactive oxygen species levels were detected employing a reactive oxygen species fluorescent probe.Changes in mitochondrial membrane potential were monitored with a mitochondrial membrane potential fluorescent probe.Mitochondrial morphology was observed employing transmission electron microscopy.Cellular glutathione levels were measured with a reduced glutathione colorimetric assay kit.Lipid peroxidation levels were assessed with a malondialdehyde colorimetric assay kit.Cellular ferrous ion levels were determined with a ferrous ion colorimetric assay kit.The osteogenic and mineralization capabilities of the cells were verified by alkaline phosphatase staining and alizarin red staining.Collagen secretion ability was detected using Sirius Red staining.The expression of osteogenic/ferroptosis-related genes and proteins was examined through reverse transcription quantitative polymerase chain reaction and western blot analysis.RESULTS AND CONCLUSION:(1)In an iron-overload environment,the mitochondrial membrane potential of cells decreased and their structure was compromised,with an elevation in intracellular lipid peroxidation levels and a downregulation of genes and proteins associated with ferroptosis resistance.However,pretreatment with fer-1 and deferoxamine led to an increase in mitochondrial membrane potential and partial restoration of morphology,a reduction in intracellular lipid peroxidation levels,and an upregulation of genes and proteins related to ferroptosis resistance.(2)In an iron-overload environment,the levels of cellular alkaline phosphatase,the formation of mineralized nodules,and the synthesis of collagen fibers were all found to be decreased.Pretreatment with fer-1 and deferoxamine was observed to upregulate the expression of osteogenic differentiation in cells.(3)In summary,iron overload could increase intracellular oxidative stress levels,mediate ferroptosis in MC3T3-E1 cells and inhibit osteogenic differentiation,thereby inducing osteoporosis.Therefore,maintaining iron homeostasis and inhibiting osteogenesis-related ferroptosis may be potential strategies to prevent or treat osteoporosis.

Objective To investigate the dosimetric differences in preoperative short-course volumetric modulated arc therapy(VMAT)for rectal cancer using different fluence smoothing(FS)levels in the Monaco Treatment Planning System(Monaco TPS).Methods Twenty rectal cancer patients who received preoperative neoadjuvant short-course VMAT at some hospital from September 2021 to December 2022 were retrospectively selected.Four groups of radiotherapy plans were formulated using the Monaco TPS for each case,which were classified into an off group,a low group,a medium group and a high group based on the FS levels.Then the four groups were compared in terms of the dosimetric parameters,monitor unit and number of the segments in the planning target volume(PTV)and organ at risk(OAR).Statistical analysis was performed using SPSS 27.0 software.Results All the four groups had the doses to the target volume meeting clinical requirements,which had no significant differences in the doses to 5％(D5％)and 95％(D95％)to the target volume and the maximum dose(Dmax),minimum dose(Dmin),mean dose(Dmean)and conformity index(all P＞0.05).Statistical differences were found between the homogeneity indexes of the four groups(P＜0.05),with the medium group behaving the best.The number of the segments rose while the mornitor units decreased siginificantly with the increase of FS levels,with the differences being statistically significant(P＜0.05).There were no significant differences between the V25,V20,V15 and V10 of the small intestine,the V25 and V20 of the bladder and the V15 and V10 of the left and right femur(all P＞0.05).Conclusion In preoperative short-course VMAT for rectal cancer,clinical requirements can be met with different FS levels in the Monaco TPS,and medium-level FS results in optimal overall dose distribution in terms of treatment planning.[Chinese Medical Equipment Journal,2025,46(5):48-53]

BACKGROUND:Titanium implants are widely used in clinical practice because of their high strength and good biocompatibility.However,during implantation,bacterial infection and tissue damage environment produce a large number of reactive oxygen species,which can easily lead to delayed tissue healing and surgical failure.Consequently,the development of titanium implants with antimicrobial and antioxidant properties becomes paramount. OBJECTIVE:Considering the potent antimicrobial attributes of copper ions and the remarkable antioxidant qualities of polyphenols,we proposed the fabrication of polyphenol-mediated copper ion coatings on titanium surfaces.These coatings were subsequently assessed for their in vitro antimicrobial and antioxidant properties. METHODS:Nanostructures were generated on the titanium surface using the alkali thermal method.The titanium was immersed in a solution containing tannic acid and copper ions to achieve polyphenol-mediated copper ion coatings.The surface morphology and water contact angle were detected.The loading and release of copper ions were examined using atomic absorption spectroscopy.Staphylococcus aureus was inoculated on the surface of pure titanium sheet(blank group),alkali heat treated titanium sheet(control group),and polyphenol mediated copper ion modified titanium sheet(experimental group)to observe the bacterial survival status.Osteoblast precursor cells MC3T3-E1 were co-cultivated on the surface of three groups of titanium sheets to assess their antioxidant properties and bioactivity. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the polyphenol-mediated copper ion modified titanium sheet had rod-like nanostructures and no cracks on the surface.The surface hydrophilicity of copper ion modified titanium sheet mediated by polyphenol was close to that of pure titanium sheet.Atomic absorption spectrometry results showed a 51%increase in the loading capacity of copper ions after polyphenol mediation,with a uniform release of copper ions.(2)The antibacterial rates of titanium sheets in the blank group,control group,and experimental group were 0%,21.65%,and 93.75%,respectively.The live/dead staining and CTC staining showed that the live bacteria on the surface of titanium plates in the blank group were the most,and the live bacteria on the surface of titanium plates in the experimental group were the least.(3)The results of live/dead staining and CCK-8 assay showed that the three groups of titanium sheets had good cytocompatibility,and the titanium sheets in the experimental group were more conducive to the proliferation of MC3T3-E1 cells.Active oxygen fluorescence probe detection exhibited that compared with the other two groups,the fluorescence intensity of active oxygen on the surface of the experimental group was significantly reduced.The results of alkaline phosphatase and alizarin red S staining showed that the osteogenic differentiation and extracellular matrix mineralization of MC3T3-E1 cells on the surface of titanium sheets in the experimental group were stronger than those in the other two groups.(4)These results show that the polyphenol-mediated copper ion coating has strong antibacterial and antioxidant properties and promotes osteogenic differentiation.

Background: This study aimed to estimate temporal trends in metabolically unhealthy obesity (MUO) among United States (US) adults by age, sex, race/ethnicity, and income from 1999 to 2018. Methods: We included 17,230 non-pregnant adults from a nationally representative cross-sectional study, the National Health and Nutrition Examination Survey (NHANES). MUO was defined as body mass index ≥30 kg/m2 with any metabolic disorders in blood pressure, blood glucose, and blood lipids. The age-adjusted percentage of MUO was calculated, and linear regression models estimated trends in MUO. Results: The weighted mean age of adults was 47.28 years; 51.02% were male, 74.64% were non-Hispanic White. The age-adjusted percentage of MUO continuously increased in adults across all subgroups during 1999–2018, although with different magnitudes (all P<0.05 for linear trend). Adults aged 45 to 64 years consistently had higher percentages of MUO from 1999–2000 (34.25%; 95% confidence interval [CI], 25.85% to 42.66%) to 2017–2018 (42.03%; 95% CI, 35.09% to 48.97%) than the other two age subgroups (P<0.05 for group differences). The age-adjusted percentage of MUO was the highest among non-Hispanic Blacks while the lowest among non-Hispanic Whites in most cycles. Adults with high-income levels generally had lower MUO percentages from 1999–2000 (22.63%; 95% CI, 17.00% to 28.26%) to 2017–2018 (32.36%; 95% CI, 23.87% to 40.85%) compared with the other two subgroups. Conclusion This study detected a continuous linear increasing trend in MUO among US adults from 1999 to 2018. The persistence of disparities by age, race/ethnicity, and income is a cause for concern. This calls for implementing evidence-based, structural, and effective MUO prevention programs.

BackgroundNon-suicidal self-injury （NSSI） behavior among adolescents has become a global public health concern. Anxiety and depression are considered key factors influencing NSSI behavior， while social support may play a protective role in alleviating emotional and behavioral issues. However， existing research has primarily focused on the direct impact of individual factors on NSSI behavior， with insufficient exploration of the combined effects of anxiety， depression and social support. ObjectiveTo investigate the direct effect of anxiety on NSSI， the mediating role of depression and the moderating role of social support in relationship between anxiety and NSSI behavior， thus to provide references for the prevention and intervention of NSSI behavior among adolescents. MethodsIn February 2022， a total of 40 820 students in grades 7 to 12 across 10 middle schools in a district of Chengdu were selected as participants， and they were assessed using Generalized Anxiety Disorder Scale-7 item （GAD-7）， Patient's Health Questionnaire Depression Scale-9 item （PHQ-9）， Social Support Scale for Urban Students （SSSUS） and Adolescent Self-Harm Scale （ASHS）. Pearson correlation analysis was conducted to examine the correlations between scale scores among adolescents with NSSI behaviors. Mediation and moderation analyses were performed using Process 3.5 in SPSS， and the significance was tested with bootstrapping. The interaction was visualized by using simple slope analysis. ResultsAmong 34 534 （84.60%） valid respondents， 542 adolescents （1.57%） reported engaging in NSSI behavior. Significant differences in gender， GAD-7 scores， PHQ-9 scores， and SSSUS scores were observed between NSSI behavior group and non-NSSI group （χ²/t=62.889， 71.120， 94.365， -41.464， P<0.01）.Adolesents with NSSI showed positive correlations between GAD-7 scores and both ASHS and PHQ-9 scores （r=0.158， 0.166， P<0.01）. PHQ-9 scores were positively correlated with ASHS scores （r=0.364， P<0.01）， but negatively correlated with SSSUS scores （r=-0.290， P<0.01）. SSSUS scores were negatively correlated with ASHS scores （r=-0.247， P<0.01）. Depression partially mediated the relationship between anxiety and NSSI behavior， with an effect size of 0.544 （95% CI： 0.162~0.944）， accounting for 35.79% of the total effect. Social support moderated the relationship between depression and NSSI bahavior， with an effect value of -0.082 （95% CI： -0.135~-0.029）. ConclusionAnxiety not only directly influences NSSI bahavior among adolescents， also indirectly exacerbates it through depression， while social support mitigates the impact of depression on NSSI behavior. ［Funded by Youth Project of National Natural Science Foundation of China （number， 82401812）； Project of Health Commission of Sichuan Province （number， 24LCYJPT18）］

Foodborne illnesses caused by Salmonella pose significant threats to worldwide public health safety.In this study,a rapid method for screening viable Salmonella in oyster sauce and milk was developed by utilizing an electronic microbial growth analyzer(EMGA).Target food samples were diluted 10-fold with RVS broth and loaded into test tubes.Test tubes were positioned in the EMGA to determine the bacterial growth curves and the time required to reach the maximum growth rate(Tmgr).Using Salmonella typhimurium(S.typhimurium)asan model species,there was linear relationship between the logarithmic value of viable bacterial concentration(lgC)and Tmgr over the range of 5×101-5×106 CFU/mL,with a detection limit of 10 CFU/mL.For oyster sauce,the regression equation was Tmgr(min)=-80.775lg[C/(CFU/mL)]+754.96(R2=0.9907),and the recovery rates of S.typhimurium ranged from 95.2%to 119.8%,with relative standard deviations(RSD)ranging from 3.5%to 16.3%.For milk,the regression equation was Tmgr(min)=-71.922 lg[C/(CFU/mL)]+618.65(R2=0.9985),with recovery rates ranging from 98.4%to 110.6%and RSD ranging from 6.4%to 12.8%.The EMGA method required only one portable instrument,and involving only three manual steps,i.e.,dilution,transfer,and insertion.When S.typhimurium contamination reached 106 CFU/mL,the total time consumption,from the unwrapping of samples to the readout of bacterial concentration,was no more than 7 h.When applied to detection of actual oyster sauce and milk samples,the new method demonstrated strong consistency with plate counting results in positive detection rates.This method was superior to the plate counting method,which was generally considered as a gold standard,in terms of accuracy,precision,simplicity and efficiency,representing a promising alternative for the on-site screening and quantification of viable Salmonella in oyster sauce and milk products.