This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals ; Isoproterenol/adverse effects* ; Male ; Mice ; Signal Transduction/drug effects* ; Vanillic Acid/administration & dosage* ; Dynamins/genetics* ; Mice, Inbred C57BL ; Fibrosis/genetics* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Myocardium/metabolism* ; Humans

OBJECTIVE: To explore clinical effect of bone cement-strengthened pedicle screw technique in the correction of stage Ⅲ asymptomatic Kümmell disease with kyphosis. METHODS: A retrospective analysis was conducted on clinical data of 40 asymptomatic stage Ⅲ Kümmell disease patients admitted between March 2019 and December 2021, including 15 males and 25 females, aged from 61 to 81 years old with an average of (67.4±5.2) years old;according to different surgical methods, they were divided into percutaneous kyphoplasty group (PKP) and reinforced screw group. There were 18 patients in PKP group, including 7 males and 11 females, aged from 61 to 78 years old with an average of (66.2±5.5) years old;the courses of disease ranged from 5 to 12 months with an average of (7.33±1.78) months;bone mineral density(BMD) T values ranged from -2.45 to -4.00 with an average of (-3.08±0.46);2 patients with T₈-T₉, 10 patients with T₁₀-T₁₂, and 6 patients with L₁-L₂;treated with PKP. There were 22 patients in reinforced screw group, including 8 males and 14 females, aged from 65 to 81 years old with an average of (68.5±3.8) years old;the courses of disease ranged from 4 to 15 months with an average of (7.86±2.73)months;bone mineral density(BMD) T values ranged from -2.40 to -4.50 with an average of (-3.18±0.54);3 patients with T₈-T₉, 12 patients with T₁₀-T₁₂, and 7 patients with L₁-L₂;treated with bone cement reinforced pedicle screw internal fixation combined with kyphoplasty. Cobb angle and anterior margin height of the injured vertebra were compared before operation, 3 d and 12 months after operation. Visual analogue scale (VAS) and Oswestry disability index (ODI) were compared between two groups before operation and 12 months after operation. The incidence of postoperative complications was compared between two groups. RESULTS: All patients were followed up, PKP group followed up for 11 to 14 months with an average of (11.97±0.96) months and 10 to 14 months with an average of (12.05±1.09) months in reinforced screw group;there was no significant difference between two groups (P>0.05). Postoperative Cobb angle at 3 days and 12 months in reinforced screw group were (7.34±2.26) ° and (18.86±1.96) °, while in PKP group were (18.88±1.89) ° and (23.28±1.90) °;there were statistical difference between two groups (P<0.05). The anterior margin height of the injured vertebra in reinforced screw group were (25.28±1.33) mm and (19.62±2.22) mm at 3 days and 12 months after operation, while in PKP group were (18.61±2.16) mm and(15.93±1.34) mm;there were statistical difference between two groups (P<0.05). Cobb angle and the anterior margin height of the injured vertebra were significantly improved at 3 days and 12 months after operation between two groups (P<0.05). Postoperative VAS and ODI at 12 months in PKP group were (2.00±0.69) score and (13.44±4.02)%, while in reinforced screw group were(1.91±0.61) score and (10.18±4.26)%;which were significantly lower than (6.89±0.76) score and (36.33±3.40)% in PKP group, (7.23±0.75) score and (37.09±3.73) % in reinforced screw group before operation. There were no difference in postoperative VAS between two groups at 12 months (P>0.05);postoperative ODI in reinforced screw group at 12 months was lower than that in PKP group(P<0.05). There was no significant difference in complications between two groups (χ²=0.071, P>0.05). CONCLUSION PKP and bone cement reinforced nail combined with PKP could improve kyphotic deformity and postoperative function, and relieve pain. The application of bone cement-reinforced nail fixation technology could provide a more stable support, more obvious functional recovery, lower the risk of re-collapse of the injured vertebra, and maintain the long-term stability of spine.
Humans ; Male ; Female ; Aged, 80 and over ; Kyphosis/surgery* ; Aged ; Bone Cements ; Middle Aged ; Retrospective Studies ; Pedicle Screws ; Spinal Fractures/surgery* ; Fracture Fixation, Internal/methods* ; Bone Screws ; Kyphoplasty

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

OBJECTIVE: To analyze the distribution characteristics of glucose-6-phosphate-dehydrogenase (G6PD) mutations and their enzyme activity in newborns patients with G6PD deficiency in Guilin region. METHODS: From July 2022 to July 2024, umbilical cord blood samples from 4 554 newborns in Guilin were analyzed for G6PD mutations using fluorescence PCR melting curve analysis. Enzyme activity was detected in 4 467 cases using the rate assay. RESULTS: Among 4 467 newborns who underwent G6PD activity testing, 162 newborns (3.63%) were identified as G6PD-deficient, including 142 males (6.04%) and 20 females (0.94%), the prevalence of G6PD deficiency was significantly higher in males than in females (P < 0.001). Genetic analysis of 4 554 newborns detected G6PD mutations in 410 cases (9%), including 171 males (7.13%) and 239 females (11.09%), with a significantly higher mutation detection rate in females than in males (P < 0.001). A total of nine single mutations and four compound heterozygous mutations were identified. The most common mutations were c.1388G>A (33.66%), c.1376G>T (23.66%) and c.95A>G (16.34%). Among newborns who underwent both enzyme activity and genetic mutation testing, males with G6PD mutations had significantly lower enzyme activity than that of females with G6PD mutations(P < 0.001). Specifically, among newborns carrying the mutations c.1388G>A, c.1376G>T, c.95A>G, c.1024C>T or c.871G>A, males consistently exhibited lower enzymatic activity than females with the same mutations (P < 0.001). Furthermore, in male G6PD-deficient newborns, the enzyme activity levels in those carrying c.1388G>A, c.1376G>T, c.95A>G, c.1024C>T, or c.871G>A were lower than those in both the control group and the c.519C>T group (P < 0.05). CONCLUSION This study provides a comprehensive profile of G6PD deficiency incidence and mutation spectrum in the Guilin region. By analyzing enzyme activity and genetic mutation results, this study provides insights into potential intervention strategies and personalized management approaches for the prevention and treatment of neonatal G6PD deficiency in the region.
Humans ; Infant, Newborn ; Glucosephosphate Dehydrogenase Deficiency/epidemiology* ; Glucosephosphate Dehydrogenase/genetics* ; Female ; Male ; Mutation ; China/epidemiology*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective To observe the value of shear wave elastography(SWE)for evaluating therapeutic effect of ultrasound-guided drug injection for muscle injury.Methods Eighty patients with unilateral muscle injury were retrospectively included,including 40 cases underwent ultrasound-guided drug injection(group A)and 40 cases underwent electromagnetic wave physiotherapy plus external application of Yunnan Baiyao Gao(group B).Pain intensity was assessed using visual analogue scale(VAS)before treatment and 3 weeks after the final treatment,while the Young modulus(E)value of the injured muscle was measured before treatment and 1,2 and 3 weeks after final treatment,and the improvements of VAS scores and E values were compared between groups.Results The total effective rate in group A(35/40,87.50%)was higher than that in group B(21/40,52.50%;P＜0.05).Before treatment,no significant difference of VAS score was found between group A(8.07±0.83)and group B(7.88±0.85)(P＞0.05).After treatment,VAS scores decreased in both groups(both P＜0.05),which in group A(2.30±1.07)was more obviously than that in group B(4.80±0.82)(P＜0.05).After treatment,E values of injury muscles increased significantly in both groups(P＜0.05),while group A had a greater increase in overall magnitude and overall rate than group B(P＜0.05).Conclusion Ultrasound-guided drug injection therapy had significant therapeutic effect for muscle injuries,which could be dynamically monitored with SWE.

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.

Objective:To apply bioinformatics methods to screen and analyze differentially expressed genes and biological processes specific to peripheral blood mononuclear cells in postmenopausal women with osteoporosis.Methods:From the Gene Expression Omnibus database, GSE56814, GSE56815, and GSE2208 datasets were screened as the research objects. The limma package in R language was used to screen differentially expressed genes, and the multigene Meta-analysis function in Metascape platform was utilized to perform enrichment analysis of gene ontology and pathway. Protein-protein interaction network construction, module analysis, core gene, and enrichment analysis will be carried out.Results:In the GSE56814 dataset, there were 84 significantly up-regulated genes and 73 significantly down-regulated genes. In the GSE56815 dataset, there were 8 significantly up-regulated genes and 33 significantly down-regulated genes. In the GSE2208 dataset, there were 21 significantly up-regulated genes and 10 significantly down-regulated genes. The multigene Meta-analysis identified 3 modules and 19 core genes in the Metascape platform. The core genes of MCODE1 included STXBP2, EIF2S2, EIF3J, PTPN6, FLNA, HLA- DQA1, CTSD, HSPA6, HLA- DPB1, EIF3E, PLEC. They mainly enriched formation of cytoplasmic translation initiation complex, antigen processing and presentation of exogenous peptide antigen via major histocompatibility complex Ⅱ, cytoplasmic translational initiation, nsp1 from SARS-CoV-2 inhibits translation initiation in the host cell, programmed cell death 1 signaling pathway, allograft rejection reaction. The core genes of MCODE2 included FOS, FOSB, EGR1, EGR2, JUNB. They mainly enriched RNA polymerase Ⅱ-specific, DNA-binding transcription activator activity, cellular response to salt, nerve growth factor-stimulated transcriptional pathways, nuclear kinase and transcription factor activation activation pathways, neurotrophic receptor tyrosine kinase 1 signaling pathway. The core genes of MCODE3 included CEBPA, H2AC6, SPI1. They mainly enriched transcriptional regulation of granulopoiesis. Conclusion:This study obtained a total of 3 modules, 19 core genes, and enriched them in the biological processes related to postmenopausal osteoporosis, providing new ideas and biological targets for exploring its occurrence pathogenesis and drug treatment.