Unraveling Key m6A Modification Regulators Signatures in Postmenopausal Osteoporosis through Bioinformatics and Experimental Verification.

OBJECTIVE: Bone marrow mesenchymal stem cells (BMSCs) show significant potential for osteogenic differentiation. However, the underlying mechanisms of osteogenic capability in osteoporosis-derived BMSCs (OP-BMSCs) remain unclear. This study aims to explore the impact of YTHDF3 (YTH N6-methyladenosine RNA binding protein 3) on the osteogenic traits of OP-BMSCs and identify potential therapeutic targets to boost their bone formation ability. METHODS: We examined microarray datasets (GSE35956 and GSE35958) from the Gene Expression Omnibus (GEO) to identify potential m6A regulators in osteoporosis (OP). Employing differential, protein interaction, and machine learning analyses, we pinpointed critical hub genes linked to OP. We further probed the relationship between these genes and OP using single-cell analysis, immune infiltration assessment, and Mendelian randomization. Our in vivo and in vitro experiments validated the expression and functionality of the key hub gene. RESULTS: Differential analysis revealed seven key hub genes related to OP, with YTHDF3 as a central player, supported by protein interaction analysis and machine learning methodologies. Subsequent single-cell, immune infiltration, and Mendelian randomization studies consistently validated YTHDF3's significant link to osteoporosis. YTHDF3 levels are significantly reduced in femoral head tissue from postmenopausal osteoporosis (PMOP) patients and femoral bone tissue from PMOP mice. Additionally, silencing YTHDF3 in OP-BMSCs substantially impedes their proliferation and differentiation. CONCLUSION: YTHDF3 may be implicated in the pathogenesis of OP by regulating the proliferation and osteogenic differentiation of OP-BMSCs.

Three new tyrosol derivatives from Huangjing wine.

Phytochemical investigation on the concentrate of Huangjing wine, resulted in the isolation of three new tyrosol derivatives 4'''-hydroxyphenethyl 2-(R)-hydroxy-3-phenylpropionate (1), 4'''-hydroxyphenethyl(4'-hydroxy-3'-methoxyphenyl)propionate (2) and 4''-hydroxyphenethyl ethyl succinate (3), together with 5 known compounds, ferulic acid (4), L-phenyllactic acid (5), hydroxytyrosol (6), dihydroferulic acid (7), cyclo(L-Pro-D-Tyr) (8). Their structures were elucidated using spectroscopic analysis and by comparison with the literature data. All compounds displayed antioxidant effect in the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical. Among them, the new compound 2 exhibited obvious antioxidant effect, and new compounds 1 and 3 exhibited medium antioxidant effect.

Nitric Oxide-Driven Nanomotor for Deep Tissue Penetration and Multidrug Resistance Reversal in Cancer Therapy.

Poor permeation of therapeutic agents and multidrug resistance (MDR) in solid tumors are the two major challenges that lead to the failure of the current chemotherapy methods. Herein, a zero-waste doxorubicin-loaded heparin/folic acid/l-arginine (HFLA-DOX) nanomotor with motion ability and sustained release of nitric oxide (NO) to achieve deep drug penetration and effective reversal of MDR in cancer chemotherapy is designed. The targeted recognition, penetration of blood vessels, intercellular penetration, special intracellular distribution (escaping from lysosomes and accumulating in Golgi and nucleus), 3D multicellular tumor spheroids (3D MTSs) penetration, degradation of tumor extracellular matrix (ECM), and reversal of MDR based on the synergistic effects of the motion ability and sustained NO release performance of the NO-driven nanomotors are investigated in detail. Correspondingly, a new chemotherapy mode called recognition-penetration-reversal-elimination is proposed, whose effectiveness is verified by in vitro cellular experiments and in vivo animal tumor model, which can not only provide effective solutions to these challenges encountered in cancer chemotherapy, but also apply to other therapy methods for the special deep-tissue penetration ability of a therapeutic agent.

Combination of D-dimer and simplified pulmonary embolism severity index to improve prediction of hospital death in patients with acute pulmonary embolism.

OBJECTIVE: To investigate whether the combination of D-dimer and simplified pulmonary embolism severity index (sPESI) could improve prediction of in-hospital death from pulmonary embolism (PE). METHODS: Patients with PE (n = 272) were divided into a surviving group (n = 249) and an in-hospital death group (n = 23). RESULTS: Compared with surviving patients, patients who died in hospital had significantly higher rates of hypotension and tachycardia, reduced SaO2 levels, elevated D-dimer and troponin T levels, higher sPESI scores, and were more likely to be classified as high risk. Elevated D-dimer levels and high sPESI scores were significantly associated with in-hospital death. Using thresholds for D-dimer and sPESI of 3.175 ng/mL and 1.5, respectively, the specificity for prediction of in-hospital death was 0.357 and 0.414, respectively, and the area under the receiver operating characteristic curve (AUC) was 0.665 and 0.668, respectively. When D-dimer and sPESI were considered together, the specificity for prediction of in-hospital death increased to 0.838 and the AUC increased to 0.74. CONCLUSIONS: D-dimer and sPESI were associated with in-hospital death from PE. Considering D-dimer levels together with sPESI can significantly improve the specificity of predicting in-hospital death for patients with PE.

A case of fourth atlanto-axial facet joint: anatomical description.

PURPOSE: To report a rare fourth atlanto-axial joint. METHODS: A cadaveric specimen of a young male adult from occiput to C4 was dissected for anatomical study of craniocervical region. A true fourth atlanto-axial joint was confirmed. Its morphological characteristics were described. RESULTS: The fourth atlantoaxial joint is rarely seen. The possible embryogenesis is discussed. This case raises an anatomical possibility of a new variant in this region. CONCLUSIONS: A unique case with an anatomically proven fourth atlantoaxial joint is reported. This anomaly can lead to misdiagnosis. CT scan coupled with MRI can facilitate accurate diagnosis.

Expression of RRM1 and RRM2 as a novel prognostic marker in advanced non-small cell lung cancer receiving chemotherapy.

The aim of this study was to examine the prognostic value of BRCA1, RRM1, and RRM2 in patients with non-small cell lung cancer (NSCLC) who received adjuvant chemotherapy. A total of 418 patients who underwent curative pulmonary resection were obtained between January 2007 and November 2009. The relative cDNA quantification for BRCA1, RRM1, and RRM2 was conducted using a fluorescence-based, real-time detection method, and ß-actin was used as a reference gene. The low expression of RRM1 and RRM2 significantly increased the platinum-based chemotherapy response (For RRM1: odds ratio (OR) = 2.09, 95% confidence interval (CI) = 1.38-3.18; For RRM2: OR = 1.64, 95% CI = 1.09-2.48). The univariate analysis indicated that low expression of RRM1 attained a longer time to progression and overall survival time, with HR (95% CI) of 0.50 (0.33-0.77) and 0.60 (0.39-0.92), respectively. Similarly, low expression of RRM2 had a longer time to progression and overall survival, with HR (95% CI) of 0.57 (0.38-0.86) and 0.47 (0.31-0.71), respectively. In conclusion, low expression of RRM1 and RRM2 could be used to predict the treatment response to platinum-based chemotherapy and survival in NSCLC. The RRM1 and RRM2 could substantially contribute to the future design of individualized cancer treatment in NSCLC patients.

[An analysis of surgical outcome and influencing factors in patients of congenital basilar invagination with atlantal-axial dislocation: report of 120 cases].

OBJECTIVE: To investigate the surgical outcome and its influencing factors in patients of congenital basilar invagination (BI) with atlanto-axial dislocation (AAD). METHODS: From May 2004 to August 2010, 120 patients who had BI with AAD were surgically treated with direct posterior intraoperative distraction-reduction and fixation technique, 93 patients were successfully followed up by means of questionnaire survey, telephone and clinical evaluation. Pre- and postoperative dynamic cervical X-rays, computed tomographic scans, 3-dimentional reconstruction views and magnetic resonance imaging were performed. Pre- and postoperative Japanese Orthopaedic Association (JOA) score, distance between odontoid tip and Chamberlain's line and atlantodental interval were measured to evaluate the surgical result. Statistical analysis was performed by means of paired t test and Pearson Correlation analysis. RESULTS: There were 93 cases were followed up for 24-99 months with an average of 46.5 months. Until the final follow-up, clinical symptoms were improved in 79 patients (84.9%), and were stable in 7 patients (7.5%) and deteriorated in 4 patients (4.3%). Three patients died postoperatively (3.2%). Patients without intramedullary signal intensity change (ISIC) had better surgical outcome. Patients with compression from anterior odontoid tip and posterior bone margin of occipital foramen had the worst surgical outcome (F = 3.987, P < 0.01). Overall, good decompression and bone fusion were shown on postoperative image in 87 patients (93.5%). There were 3 deaths in this series because of basilar artery thrombosis, posterior fossa hematoma and unknown reasons each. CONCLUSIONS: The direct posterior intraoperative distraction-reduction and fixation technique is an effective simple and safe method for the treatment of BI with AAD. Anterior compression from odontoid tip and posterior compression from bone margin of occipital foramen-atlantal posterior arch play important roles in its developing mechanism. ISIC on MRI is a predictive factor for the worse surgical outcome.

Feasibility and limitations of C1 lateral mass screw placement in patients of atlas assimilation.

BACKGROUND: C1 lateral mass is a common place for screw fixation in normal anatomy; whereas there is no research about whether screw placement is suitable in patients of C1 assimilation (C1A). OBJECTIVE: To study the feasibility and limitations of C1 lateral mass screw placement in patients with C1A. PATIENTS AND METHODS: From April 2008 to March 2009, C1 lateral mass of 17 C1A patients with atlantoaxial instability (AAI) or dislocation (AAD) was observed and measured using CT reconstruction; and factors determining C1 lateral mass screw placement were studied before and during the operation. RESULTS: A screw of 3.5mm in diameter could be virtually inserted in 31 C1 lateral masses of total 17 C1A patients with maximal length of the screw 18.1±2.7mm; but the entry point of screw had to be modified in the posterior part of inferior facet of C1 instead of posterior middle wall of C1 lateral mass. Clinically, abnormal course of vertebral artery in 6 of 30 (20%) and abundance of venous plexi prevented the proper exposure of C1 lateral mass and screw placement. Hypoglossal canal also had potential risk of injury during screw placement. CONCLUSION: In patients of C1A, when C1 lateral mass screw placement is programmed, factors limit its use should be well studied, and CT angiography is essential.

[A coal mine and coal preparation plant coal dust workplace present situation investigation and analysis].

OBJECTIVE: Through a detection of dust in the coal mines workplace, to understand the status of occupational hazards, and the evaluation of occupational hazards, provide subject to control occupational hazards. METHOD: According to production process and "hazardous substances in workplace air monitoring, sampling norms" and other standards to determine the sampling points and sampling of coal dust. RESULT: Underground mining operations in 21 subjects with time-weighted average concentration of dust types pass rate of 28.6%, of which five types of dust hazard grade II, six types of dust hazard rating of 0, and the remaining types of grade I dust hazard levels. Coal dust test six types of time-weighted average concentration of 83.3% pass rate, only one types of dust hazard grade I, all the rest is 0. Calculated by the detection of dust overrun 18 times operating sites, the pass rate of 72.2% results. CONCLUSION: Purified water spray and air flow curtain of dust control has played a certain role, but the work of underground working conditions and environmental constraints, most of the dust concentration in workplace occupational exposure limits do not meet the requirements, recommended the strengthening of dust or Dust the daily management and maintenance of equipment, strengthen the ventilation, personal protection officers to strengthen operations.

2-[(2-Hy-droxy-4-meth-oxy-benzyl-idene)aza-nium-yl]benzoate monohydrate.

In the title compound, C(15)H(13)NO(4)·H(2)O, the Schiff base exists in a zwitterionic form and a bifurcated intra-molecular N-H⋯(O,O) hydrogen bond generates two S(6) rings. The dihedral angle between the two benzene rings is 25.8 (2)°. The crystal structure is stabilized by inter-molecular O-H⋯O hydrogen bonds.

[Effect of actovegin on intestinal mucosa and expression of bcl-2/bax genes in rats with acute radiation enteritis].

OBJECTIVE: To evaluate the effect of actovegin (Nycomed, deproteinized hemoderivative of calf blood injection) on intestinal mucosa in rats with acute radiation enteritis, and observe the changes of expression of apoptosis-related bcl-2/bax genes. METHODS: An abdominal irradiation in a dose of 9.0 Gy X-ray of linear accelerator was performed once on a group of Wistar rats to establish a model of acute intestinal radiation enteritis. The experimental rats were randomly divided into five groups. Group 1 was normal control group; group 2 was model control group; groups 3, 4 and 5 were treated with low, middle and high dose of actovegin, respectively. After the model was established, actovegin injection was given intraperitoneally for successive 4 days. Corresponding intestinal tissues were taken for morphological examination with an image analysis system. The expression of apoptosis related bax and bcl-2 protein in the intestinal mucosal epithelial cells was determined by immunohistochemistry. RESULTS: The groups 4 and 5 had significantly higher height of intestinal villi, the depth of crypt, the thickness of the mucosa and entire wall (254.66/261.71 microm, 166.47/165.41 microm, 510.44/511.71 microm, 610.38/608.98 microm), compared with those of the model control group (239.12 microm, 151.45 microm, 420.27 microm and 579.32 microm), respectively (P < 0.05). Treatment with middle and high doses of actovegin also significantly down-regulated the expression of activating apoptosis protein bax (24.54/23.24) compared with that of model control group (59.32) (P < 0.05) and up-regulated the expression of inhibiting apoptosis protein bcl-2 (55.54/52.21) compared with that of model control group (20.32) (P < 0.05). The ratio of bcl-2/bax was significantly higher in the groups 4 and 5 (2.2632, 2.1275) compared with that in the model control group (0.3425) (P < 0.01). CONCLUSION: Actovegin accelerates the recovery of the acute radiation-injured intestinal mucosal epithelium by decreasing apoptosis via down-regulation of the expression of activating apoptosis protein bax and up-regulation of inhibiting apoptosis protein bcl-2.

[Prodrug structural modifications of cyclovirobuxine D and their biological activity].

AIM: To search for compounds for the treatment of cardiovascular diseases through prodrug structural modifications of cyclovirobuxine D, a single efficient composition distilled from Box plant in China, which was used to treat angina and myocardial infarction. METHODS: According to prodrug design principle, a series of cyclovirobuxine D analogues were prepared, suc as succinate, phosphate and amino acid ester, and their biological activities were tested. RESULTS: Seven new compounds were obtained and confirmed with 1H NMR, MS, and element analysis. CONCLUSION: In pharmacology experiment, for treating arrhythmia induced by aconitine, succinate and amino acid ester of cyclovirobuxine D (I and VII) showed better activities than that of cyclovirobuxine D. The normal rhythm of the heart duration of I and VII were ( 11.53 +/- 7.62) min and (12.68 +/- 9.25) min, compared with 0.9% NaCl solution and cyclovirobuxine D, (2.36 +/- 1.68) min and (10.25 +/- 6.59) min (P < 0.01), respectively. Another pharmacology experiment, for treating arrhythmia induced by chloroform, the negative ratio of I and VII were 80% and 82%, compared with 0.9% NaCl solution and cyclovirobuxine D, 43% and 52% (P < 0.05), respectively. The difference between new compounds and cyclovirobuxine D was distinct.

[Minimally invasive surgery of the spinal cord hemangioblastoma].

OBJECTIVE: To clarify and discuss the diagnosis and minimally invasive surgery of spinal cord hemangioblastoma. METHODS: The clinical data of 16 patients with spinal cord hemangioblastoma who were operated on between 1992 and 2001 were analyzed retrospectively with a review of the literature. RESULTS: Twelve patients were subjected to MRI examination, nine to spinal cord angiography, and six to preoperative embolization. Thirteen patients underwent complete excision, and three underwent partial excision due to massive bleeding and anterior location of the tumor in spinal cord. Eleven patients showed improvement of their symptoms, four no change at all, and tumor recurrence was seen in one patient with aggravation. CONCLUSION: MRI and spinal angiography are essential for preoperative diagnosis and surgical planning. Early diagnosis and microsurgical resection greatly preserve the neurological function of the patients. Preoperative embolization sometimes is helpful in surgery.

[Structural modification and bioactivity of cyclovirobuxine D].

AIM: To search for new compounds for the treatment of cardiovascular diseases by structural modification of cyclovirobuxine D. METHODS: According to rational drug design principle, a series of cyclovirobuxine D analogues were prepared, and their bioactivities were tested. RESULTS: Ten new compounds were syntheized and confirmed by spectra. CONCLUSION: Endurance lacking oxygen activity and antiarrhythmia effects of some analogues of cyclovirobuxine D were tested. Some compounds showed better activity than cyclovirobuxine D.