Risk of internal fixation treatment in intertrochanteric fracture based on different lateral femoral wall thickness: finite element analysis.

OBJECTIVE: The thickness of the lateral femoral wall, which is an important indicator for evaluating the stability and integrity of intertrochanteric fractures, has been widely studied in recent years. However, as a typical representative of internal fixation treatment, there are few reports on the biomechanical comparison between PFNA and DHS + CS. This study focused primarily on the biomechanical effects of different lateral femoral wall thicknesses on two types of internal fixation through finite element analysis. METHODS: We randomly recruited a healthy adult and collected his femoral CT data to establish a model of femoral intertrochanteric fracture with different lateral femoral wall thicknesses. Following PFNA and DHS + CS fixation, femoral models were simulated, and variations in stress and displacement of the internal fixation and femoral head were recorded under the same physiological load. RESULTS: First, finite element mechanical analysis revealed that the stress and displacement of the internal fixation and femoral head were lower in the femoral model after PFNA fixation than in the DHS + CS model. Second, as the outer wall thickness decreased, the stress and deformation endured by both types of internal fixation gradually increased. CONCLUSIONS: Finite element analysis determined that PFNA exhibits significantly better biomechanical stability than DHS + CS when subjected to varying lateral femoral wall thicknesses. Moreover, lateral femoral wall thickness substantially affects the stability of the two internal fixation biomechanical environments. When the thickness of the lateral femoral wall is too small, we do not recommend using extramedullary fixation because there is a significant risk of internal fixation fracture.

Biomechanical study of a biplanar double support screw (BDSF) technique based on Pauwels angle in femoral neck fractures: finite element analysis.

Objective: The objective of the present study is to conduct a comparative analysis of the biomechanical advantages and disadvantages associated with a biplanar double support screw (BDSF) internal fixation device. Methods: Two distinct femoral neck fracture models, one with a 30° angle and the other with a 70° angle, were created using a verified and effective finite element model. Accordingly, a total of eight groups of finite element models were utilized, each implanted with different configurations of fixation devices, including distal screw 150° BDSF, distal screw 165° BDSF, 3 CLS arranged in an inverted triangle configuration, and 4 CLS arranged in a "α" configuration. Subsequently, the displacement and distribution of Von Mises stress (VMS) in the femur and internal fixation device were assessed in each fracture group under an axial load of 2100 N. Results: At Pauwels 30° Angle, the femur with a 150°-BDSF orientation exhibited a maximum displacement of 3.17 mm, while the femur with a 165°-BDSF orientation displayed a maximum displacement of 3.13 mm. When compared with the femoral neck fracture model characterized by a Pauwels Angle of 70°, the shear force observed in the 70° model was significantly higher than that in the 30° model. Conversely, the stability of the 30° model was significantly superior to that of the 70° model. Furthermore, in the 70° model, the BDSF group exhibited a maximum femur displacement that was lower than both the 3CCS (3.46 mm) and 4CCS (3.43 mm) thresholds. Conclusion: The biomechanical properties of the BDSF internal fixation device are superior to the other two hollow screw internal fixation devices. Correspondingly, superior biomechanical outcomes can be achieved through the implementation of distal screw insertion at an angle of 165°. Thus, the BDSF internal fixation technique can be considered as a viable closed reduction internal fixation technique for managing femoral neck fractures at varying Pauwels angles.

Fast Discrimination and Quantification Analysis of Atractylodis rhizoma Using NIR Spectroscopy Coupled with Chemometrics Tools.

In this study, near-infrared (NIR) spectroscopy and high-performance liquid chromatography (HPLC) combined with chemometrics tools were applied for quick discrimination and quantitative analysis of different varieties and origins of Atractylodis rhizoma samples. Based on NIR data, orthogonal partial least squares discriminant analysis (OPLS-DA) and K-nearest neighbor (KNN) models achieved greater than 90% discriminant accuracy of the three species and two origins of Atractylodis rhizoma. Moreover, the contents of three active ingredients (atractyloxin, atractylone, and ß-eudesmol) in Atractylodis rhizoma were simultaneously determined by HPLC. There are significant differences in the content of the three components in the samples of Atractylodis rhizoma from different varieties and origins. Then, partial least squares regression (PLSR) models for the prediction of atractyloxin, atractylone, and ß-eudesmol content were successfully established. The complete Atractylodis rhizoma spectra gave rise to good predictions of atractyloxin, atractylone, and ß-eudesmol content with R2 values of 0.9642, 0.9588, and 0.9812, respectively. Based on the results of this present research, it can be concluded that NIR is a great nondestructive alternative to be applied as a rapid classification system by the drug industry.

Two undescribed benzopyran derivatives from Ranunculus sceleratus L. with their in vitro anti-inflammatory activity in lipopolysaccharide-activated RAW 264.7 cells.

Previous studies on Ranunculus sceleratus L. have shown the existence of coumarins and their anti-inflammatory effect. Phytochemical work was conducted to investigate the bioactive compounds, leading to the isolation of two undescribed benzopyran derivatives, namely ranunsceleroside A (1) and B (3), together with two known coumarins (2, 4) from the whole plant of R. sceleratus L. All compounds were structurally identified by extensive spectroscopic analysis and then investigated for their inhibitory effect on nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) production induced by lipopolysaccharide (LPS) in RAW 264.7 murine macrophages, repectively. As a result, compound 1-4 presented inhibitory effects on the production of NO, TNF-α, IL-1ß, and IL-6 in a concentration-dependent manner, which provides a potential chemical basis for the traditional use of R. sceleratus L. as an anti-inflammatory plant.

Transcriptome analysis of three medicinal plants of the genus Polygonatum: identification of genes involved in polysaccharide and steroidal saponins biosynthesis.

Polysaccharides and saponins are the main active components of Polygonati Rhizoma. Studying the molecular mechanism of their synthesis pathway is helpful in improving the content of active components at the molecular level. At present, transcriptome analysis of three Polygonatum species (Polygonatum sibiricum Red., Polygonatum cyrtonema Hua, Polygonatum kingianum Coll. et Hemsl.) has been reported, but no comparative study has been found on the transcriptome data of the three species. Transcriptome sequencing was performed on the rhizomes of three Polygonatum species based on high-throughput sequencing technology, and all transcripts were assembled. A total of 168,108 unigenes were generated after the removal of redundancy, of which 121,642 were annotated in seven databases. Through differential analysis and expression analysis of key enzyme genes in the synthesis pathway of three Polygonatum polysaccharides and steroidal saponins, 135 differentially expressed genes encoding 18 enzymes and 128 differentially expressed genes encoding 28 enzymes were identified, respectively. Numerous transcription factors are involved in the carbohydrate synthesis pathway. Quantitative real-time PCR was used to further verify the gene expression level. In this paper, we present a public transcriptome dataset of three medicinal plants of the genus Polygonatum, and analyze the key enzyme genes of polysaccharide and steroidal saponins synthesis pathway, which lays a foundation for improving the active component content of Polygonati Rhizoma by molecular means.

Prediction of hip joint function and analysis of risk factors for internal fixation failure after Femoral Neck System (FNS).

OBJECTIVE: Analysis of the risk factors affecting hip function and complications after femoral neck system (FNS) surgery for femoral neck fractures is of great significance for improving the procedure's efficacy. METHODS: The data of patients with femoral neck fractures who underwent FNS surgery in our hospital between October 2019 and October 2020 were retrospectively analyzed. Age, gender, time from injury to operation, fracture classification, operation time, fracture reduction, and postoperative weight-bearing time information were set as potential factors that may affect the results. Hip Harris scores were performed at 12 months postoperatively, and postoperative complication data (e.g., femoral head necrosis, nonunion, and femoral neck shortness) were collected. The risk factors affecting hip function and complications after FNS surgery were predicted using linear and logistic regression analyses. RESULTS: A total of 69 cases of femoral neck fracture were included, with an average age of 56.09 ± 11.50 years. The linear analysis demonstrated that the age and fracture type of the patients were the risk factors affecting the Harris score of the hip joint after FNS surgery. Older patients with displaced femoral neck fractures had an inferior postoperative hip function. In addition, fracture type, reduction of the femoral neck, and postoperative weight-bearing significantly impacted postoperative complications. Displaced fractures, negative fixation, and premature weight-bearing (< 6 weeks) were risk factors for postoperative complications. The Harris score of patients with a shortened femoral neck in the included cases was not significantly different from that of patients without shortening (P = 0.25). CONCLUSIONS: Advanced age and fracture type are important evaluation indicators of the Harris score after FNS internal fixation of femoral neck fractures in young patients. Fracture type, fracture reduction, and postoperative weight-bearing time are risk factors for complications after FNS.

Correlation analysis of larger side bone cement volume/vertebral body volume ratio with adjacent vertebral compression fractures during vertebroplasty.

Objective: To investigate the correlation analysis of larger side bone cement volume/vertebral body volume ratio (LSBCV/VBV%) with adjacent vertebral compression fracture (AVCF) in percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fracture (OVCF). Methods: A retrospective analysis of 245 OVCF patients who underwent PVP treatment from February 2017 to February 2021, including 85 males and 160 females. The age ranged from 60 to 92 years, with a mean of (70.72 ± 7.03) years. According to whether AVCF occurred after surgery, they were divided into 38 cases in the AVCF group (fracture group) and 207 cases in the no AVCF group (non-fracture group). The correlation between gender, age, bone mineral density (BMD), body mass index (BMI), thoracolumbar segment fracture, bone cement disc leakage, LSBCV, bone cement volume (BCV), VBV, LSBCV/VBV ratio (LSBCV/VBV%), and BCV/VBV% and AVCF were analyzed in both groups. Risk factors for AVCF after PVP were analyzed by multifactorial logistic regression, and then the receiver operating characteristic curves (ROC curves) were plotted to identify the critical value of LSBCV/VBV%. Results: 38 patients (15.5%) developed AVCF postoperatively. Univariate analysis showed that BMD, bone cement disc leakage, LSBCV, and LSBCV/VBV% were risk factors for AVCF after PVP (P<0.05), while gender, age, BMI, thoracolumbar segment fracture, BCV, VBV, and BCV/VBV% were not significantly different in both groups (P>0.05). Multifactorial logistic regression analysis revealed that BMD, bone cement disc leakage, and LSBCV/VBV% were independent risk factors for AVCF after PVP (P<0.05). According to the ROC curve, the LSBCV/VBV% had an area under the curve of 71.6%, a sensitivity and specificity of 89.5% and 51.7%, respectively, and a critical value of 13.82%. Conclusion: BMD, bone cement disc leakage and LSBCV/VBV% are independent risk factors for AVCF after PVP. With LSBCV/VBV at 13.82%, the incidence of AVCF significantly increased.

Comparison of femoral neck system and three cannulated cancellous screws in the treatment of vertical femoral neck fractures: clinical observation and finite element analysis.

OBJECTIVE: The purpose of this study was to compare the biomechanical and clinical results of two surgical methods for the treatment of vertical femoral neck fractures: Femoral neck system (FNS) and traditional three cannulated cancellous screws (CCS). METHODS: First, we developed three different vertical femoral neck fracture models for the finite element analysis, with angles of 55°, 65°, and 75°, respectively. Two experimental groups were set up: the FNS group and the CCS group. Each fracture group was tested under axial loads of 2100 N to measure the femur's displacement, Von Mises stress (VMS), and its internal fixation components. Secondly, we retrospectively included the cases of vertical femoral neck fractures with FNS and CCS in our hospital from May 2019 to May 2021. In this study, we compared the duration of intraoperative fluoroscopy, operative time, hospital stay, fracture healing time, Hemoglobin loss, Harris score of hip joint function, and postoperative complications among patients undergoing hip joint replacement. RESULTS: In terms of finite element analysis, FNS has better anti-displacement stability than CCS at 55°and 65°, while FNS is greater than CCS in Von Mises stress. Clinically, we followed up on 87 patients for an average of 12 months. FNS was superior to traditional CCS in fracture healing time, operation time, fluoroscopy duration, fracture healing time, and Harris hip function score. CONCLUSION: FNS is superior to traditional CCS in biomechanical and clinical aspects of treating vertical femoral neck fractures. There is potential for FNS to become a new treatment option for vertical femoral neck fractures.

Isolation, characterisation, and expression profiling of DXS and DXR genes in Atractylodes lancea.

1-Deoxy-d-xylulose-5-phosphate synthase and 1-deoxy-d-xylulose-5-phosphate reductoismerase are considered two key enzymes in the 2-C-methyl-d-erythritol-4-phosphate pathway of terpenoid biosynthesis and are related to the synthesis and accumulation of sesquiterpenoids. We cloned two DXS and DXR genes from Atractylodes lancea and analysed their expression in different tissues and in response to methyl jasmonate (MeJA). Subcellular localisation analysis revealed that the AlDXS and AlDXR1 proteins are located in the chloroplasts and cytoplasm, whereas AlDXR2 is only located in the chloroplasts. pET-AlDXS-28a and pGEX-AlDXR-4T-1 were expressed in Escherichia coli BL21(DE3) and BL21, respectively. Based on the abiotic stress analysis, the growth rate of the recombinant pGEX-AlDXR-4T-1 was higher than that of the control in HCl and NaOH. AlDXS exhibited the highest expression level in rhizomes of A. lancea from Hubei but was highest in leaves from Henan. In contrast, AlDXR showed maximum expression in the leaves of A. lancea from Hubei and Henan. Moreover, DXS and DXR gene expression, enzyme activities, and antioxidant enzyme activities oscillated in response to MeJA, with expression peaks appearing at different time points. Our findings indicated that the characterisation and function of AlDXS and AlDXR could be useful for further elucidating the functions of DXR and DXR genes in A. lancea.

[Complete chloroplast genome sequencing and phylogeny of wild Atractylodes lancea from Yuexi, Anhui province].

This study investigated the choroplast genome sequence of wild Atractylodes lancea from Yuexi in Anhui province by high-throughput sequencing, followed by characterization of the genome structure, which laid a foundation for the species identification, analysis of genetic diversity, and resource conservation of A. lancea. To be specific, the total genomic DNA was extracted from the leaves of A. lancea with the improved CTAB method. The chloroplast genome of A. lancea was sequenced by the high-throughput sequencing technology, followed by assembling by metaSPAdes and annotation by CPGAVAS2. Bioiformatics methods were employed for the analysis of simple sequence repeats(SSRs), inverted repeat(IR) border, codon bias, and phylogeny. The results showed that the whole chloroplast genome of A. lancea was 153 178 bp, with an 84 226 bp large single copy(LSC) and a 18 658 bp small single copy(SSC) separated by a pair of IRs(25 147 bp). The genome had the GC content of 37.7% and 124 genes: 87 protein-coding genes, 8 rRNA genes, and 29 tRNA genes. It had 26 287 codons and encoded 20 amino acids. Phylogenetic analysis showed that Atractylodes species clustered into one clade and that A. lancea had close genetic relationship with A. koreana. This study established a method for sequencing the chloroplast genome of A. lancea and enriched the genetic resources of Compositae. The findings are expected to lay a foundation for species identification, analysis of genetic diversity, and resource conservation of A. lancea.

Chemical Constituent Analysis of Ranunculus sceleratus L. Using Ultra-High-Performance Liquid Chromatography Coupled with Quadrupole-Orbitrap High-Resolution Mass Spectrometry.

Ranunculus sceleratus L.(RS) has shown various pharmacological effects in traditional Chinese medicine. In our previous study, the positive therapeutic effect on α-naphthylisothiocyanate induced intrahepatic cholestasis in rats was obtained using TianJiu treatment with fresh RS. However, the chemical profile of RS has not been clearly clarified, which impedes the research progress on the therapeutic effect of RS. Herein, an ultra-high performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) method was developed to rapidly separate and identify multiple constituents in the 80% methanol extract of RS. A total of sixty-nine compounds (19 flavonoids, 22 organic acids, 6 coumarins, 4 lignans, 14 nitrogenous compounds, and 4 anthraquinones) were successfully characterized. A total of 12 of these compounds were unambiguously identified by standard samples. Their mass spectrometric fragmentation pathways were investigated. It is worth noting that flavonoids and lignans were identified for the first time in RS. In this study, we successfully provide the first comprehensive report on identifying major chemical constituents in RS by UHPLC-Q-Orbitrap HRMS. The obtained results enrich the RS chemical profile, paving the way for further phytochemical study, quality control, and pharmacological investigation of RS.

On-line screening of natural antioxidants and the antioxidant activity prediction for the extracts from flowers of Chrysanthemum morifolium ramat.

ETHNOPHARMACOLOGY RELEVANCE: Chrysanthemum morifolium Ramat. (Flos Chrysanthemi, FC) the most economically significant "food and drug dual-use" plants, with positive effects on relieving eye fatigue, and reduce internal heat, shows significant activities, such as anti-inflammatory, antioxidant, and neuroprotective, as well as alleviating diabetes effects. AIM OF THE STUDY: This study was undertaken to a screening of natural antioxidants in five kinds of medicinal FC and development of an integrated quality control method based on the antioxidant activity. MATERIALS AND METHODS: A novel quality control method for FC was established by combining the on-line HPLC-DPPH, ESI-MS, and NIR spectra analysis. Firstly, the on-line HPLC-DPPH-MS system was employed to identify the antioxidants in FC extracts. Then, the relationship between the NIR spectra and antioxidant activities of FC samples was calibrated to evaluate the total antioxidant capacity of FC rapidly. RESULTS: The established antioxidant activity-fingerprints contain both chemical information and antioxidant activity characteristics of FC. A total of 16 antioxidants were identified by on-line HPLC-ESI-MS analysis. The results of heat map analysis and cluster analysis showed that the classification method based on antioxidants in FC can be used to identify different cultivars of FC. The optimal pretreatment of the NIR spectra was determined to be row center (RC) 1st der + multiple-scatter correction (MSC) with an optimal LV value of 11. The developed spectral-antioxidant activity model had the excellent predictive ability and was successfully used to evaluate new batches of FC samples, where Rcal = 0.9445 and Rval = 0.8821. CONCLUSIONS: This comprehensive strategy may prove to be a powerful technique for the rapid screening, identification, and activity prediction of antioxidants, which could be used for the quality control of FC, and can serve as reference for design of quality control of other herbs and foods samples.

A novel model of traumatic femoral head necrosis in rats developed by microsurgical technique.

BACKGROUND: Clinical angiography and vascular microperfusion confirmed that the femoral head retains blood supply after a collum femur fracture. However, no animal model accurately mimics this clinical situation. This study was performed to establish a rat model with retained viability of the femoral head and partial vasculature deprivation-induced traumatic caput femoris necrosis by surgery. METHODS: Thirty rats were randomly divided into three groups (n = 10 per group): normal group, sham-operated group (Control), and ischemic osteonecrosis group. The femoral head of the normal group of rats underwent a gross anatomy study and microangiography to identify femoral head blood supply. Microsurgical techniques were used to cauterize the anterior-superior retinacular vessels to induce osteonecrosis. Hematoxylin and Eosin (H&E) staining were used for femoral head histologic assessment. Morphologic assessments of the deformity in and trabecular bone parameters of the femoral head epiphysis were performed using micro-CT. RESULTS: The blood supply of the femoral head in rats primarily came from the anterior-superior, inferior, and posterior retinacular arteries. However, anterior-superior retinacular vasculature deprivation alone was sufficient in inducing femoral head osteonecrosis. H&E showed bone cell loss in nuclear staining, disorganized marrow, and trabecular structure. The bone volume (BV) decreased by 13% and 22% in the ischemic group after 5 and 10 weeks, respectively. The mean trabecular thickness (Tb.Th) decreased from 0.09 to 0.06 mm after 10 weeks. The trabecular spacing (Tb.Sp) increased from 0.03 to 0.05 mm after 5 weeks, and the epiphyseal height-to-diameter (H/D) ratio decreased. CONCLUSIONS: We developed an original and highly selective rat model that embodied femoral head traumatic osteonecrosis induced by surgical anterior-superior retinacular vasculature deprivation.

A Comparative Analysis of Femoral Neck System and Three Cannulated Screws Fixation in the Treatment of Femoral Neck Fractures: A Six-Month Follow-Up.

OBJECTIVE: To investigate the efficacies of Femoral Neck System (FNS) and the three cannulated screws fixation (3CS) as therapeutic options for femoral neck fractures. METHOD: This was a retrospective study involving 69 patients (26 males and 43 females; mean age of 54.9 years (range, 28-66 years)) subjected to either FNS or 3CS for femoral neck fracture therapy. These patients were treated in our hospital from October 2019 to May 2020. Patient follow up was done at 1, 2, 3 and 6 months. During the short-term (6 months) follow-up period, surgical procedures for the two groups and incidences of complications were analyzed. Perioperative parameters were recorded and analyzed. Postoperative hip joint functions were measured and compared using the Harris score. The assessed perioperative parameters included surgical time, hemoglobin loss, fluoroscopy duration, hospitalization length and hospitalization cost. The main complications at last follow-up (6 months) included varus tilting, femoral neck shortness, and implant removal. RESULTS: Differences in the number of patients, age, Garden type of fracture and time from injury to surgery between the two groups were not significant (P > 0.05). With regards to perioperative parameters, compared to 3CS, FNS treatment performed better in surgical time (60.00 ± 12.44 vs 76.81 ± 13.10 min, P = 0.000), blood loss (13.67 ± 8.02 vs 16.58 ± 4.16 g/L, P = 0.059) and fluoroscopy time (39.73 ± 9.57 vs 58.14 ± 9.15 s, P = 0.000). Differences in hospitalization length and cost between the groups were not significant (P > 0.05). During the whole follow-up period, all patients did not exhibit dysfunction, pulmonary embolism or even death as a result of long-term immobilization of affected limbs. Surgical incisions for all patients healed well without infections. During the 6-month follow-up period, the FNS group exhibited a higher Harris score (84.61 ± 3.42 vs 78.67 ± 3.72, p = 0.000). In addition, treatment-associated complications (FNS vs 3CS) included femoral neck varus tilt (3.03% vs 11.11%), femoral neck shortness (6.06% vs 13.89%), and implant removal (0% vs. 13.89%). Implant removal rate for the FNS group was significantly less than that of the 3CS group (P = 0.026). Differences in incidences of femoral neck varus tilt (P = 0.196) and femoral neck shortness (P = 0.282) between the two groups were not significant. However, the difference in number was significant (FNS group was less). CONCLUSION: FNS treatment is associated with a smaller surgical trauma, stronger stability, and reductions in post-operative complication incidences, therefore, it is a potential therapeutic option for femoral neck fractures.

Broadband RCS Reduction by a Quaternionic Metasurface.

A quaternionic metasurface consisting of two pairs of units with destructive phase difference is proposed to extend the bandwidth of radar cross section (RCS) reduction. The two pairs of units are designed to have complementary phase-different bandwidth, which extends the bandwidth of RCS reduction. The overlaps of their bandwidth enhance the RCS reduction, resulting in a metasurface having broadband and strong RCS reduction. This design and the wideband RCS reduction of the quaternionic metasurface were verified by analytical calculation with superposition principle of electric field, numerical simulation with commercial software package CST Microwave Studio and experiment in microwave anechoic chamber. The scattering mechanism and the angular performance of the quaternionic metasurface were also investigated.

Regorafenib-loaded poly (lactide-co-glycolide) microspheres designed to improve transarterial chemoembolization therapy for hepatocellular carcinoma.

Transarterial chemoembolization (TACE) has been widely introduced to treat hepatocellular carcinoma (HCC) especially for unresectable patients for decades. However, TACE evokes an angiogenic response due to the secretion of vascular endothelial growth factor (VEGF), resulting in the formation of new blood vessels and eventually tumor recurrence. Thus, we aimed to develop regorafenib (REGO)-loaded poly (lactide-co-glycolide) (PLGA) microspheres that enabled localized and sustained drug delivery to limit proangiogenic responses following TACE in HCC treatment. REGO-loaded PLGA microspheres were prepared using the emulsion-solvent evaporation/extraction method, in which DMF was selected as an organic phase co-solvent. Accordingly, we optimized the proportion of DMF, which the optimal ratio to DCM was 1:9 (v/v). After preparation, the microspheres provided high drug loading capacity of 28.6%, high loading efficiency of 91.5%, and the average particle size of 149 µm for TACE. IR spectra and XRD were applied to confirming sufficient REGO entrapment. The in vitro release profiles demonstrated sustained drug release of microspheres for more than 30 d To confirm the role of REGO-loaded microspheres in TACE, the cell cytotoxic activity on HepG2 cells and anti-angiogenic effects in HUVECs Tube-formation assay were studied in combination with miriplatin. Moreover, the microspheres indicated the potential of antagonizing miriplatin resistance of HepG2 cells in vitro. Pharmacokinetics preliminary studies exhibited that REGO could be sustainably released from microspheres for more than 30 d after TACE in vivo. In vivo anti-tumor efficacy was further determined in HepG2 xenograft tumor mouse model, demonstrating that REGO microspheres could improve the antitumor efficacy of miriplatin remarkably compared with miriplatin monotherapy. In conclusion, the obtained REGO microspheres demonstrated promising therapeutic effects against HCC when combined with TACE.

Melatonin suppresses Ti-particle-induced inflammatory osteolysis via activation of the Nrf2/Catalase signaling pathway.

Aseptic loosening induced by osteolysis is recognized as a late complication of joint replacement. Osteoclasts stimulated by Titanium (Ti) nanoparticles play a critical role in periprosthetic osteolysis. Emerging evidence indicates that melatonin, a hormone primarily synthesized by the pineal gland, has been shown an inhibitory effect on osteoclast formation. However, it is unclear whether melatonin could suppress Ti-particle-induced osteoclastogenesis and what the underlying mechanisms were involved in. Herein, we aimed to investigate the effect of melatonin on osteoclast differentiation and osteolysis stimulated by Ti particles. Our results showed that the in vitro osteoclastogenesis of mouse bone marrow monocytes (BMMs) stimulated by Ti particles was suppressed by melatonin treatments in a dose-dependent manner. Further experiments revealed that melatonin up-regulated the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) and catalase (CAT) at both the mRNA and protein levels. The role of the Nrf2/CAT signaling pathway was confirmed by the fact that silencing the expression of NRF2 by small interfering RNA (siRNA) counteracted the anti-osteolysis effects of melatonin. Furthermore, in vivo intraperitoneal injection of melatonin successfully attenuated periprosthetic osteolysis induced by Ti particles in a murine calvarial model. Our findings demonstrate that melatonin is a promising therapeutic agent for treating periprosthetic osteolysis by inhibiting the Ti-particle-stimulated osteoclastogenesis via activation of the Nrf2/Catalase signaling pathway.

Melatonin Rescues the Ti Particle-Impaired Osteogenic Potential of Bone Marrow Mesenchymal Stem Cells via the SIRT1/SOD2 Signaling Pathway.

Wear particles released by joint implants are a major cause of osteolysis around the prosthesis by negatively affecting bone reconstruction. Bone marrow mesenchymal stem cells (BMMSCs) stimulated by wear particles showed an impaired osteogenic potential. Melatonin has been shown beneficial effects on intracellular antioxidant functions and bone formation; however, whether it could restore the osteogenic potential of BMMSCs inhibited by wear particles was unknown. This study aimed to evaluate the protective effect of melatonin on the osteogenic capacity of BMMSCs exposed to titanium (Ti) wear particles and to investigated the underlying mechanisms involving intracellular antioxidant properties. When BMMSCs were exposed to Ti particles in vitro, melatonin treatment successfully improved the matrix mineralization and expression of osteogenic markers in BMMSCs, while decreasing the levels of intracellular reactive oxygen species (ROS) and mitochondrial superoxide. The protective effect of melatonin on osteolysis was validated in a Ti particle-exposed murine calvarial model. Meanwhile, silent information regulator type 1 (SIRT1) and intracellular antioxidant enzymes were significantly up-regulated, particularly superoxide dismutase 2 (SOD2), in melatonin-treated BMMSCs. Furthermore, inhibition of SIRT1 by EX527 completely counteracted the protective effect of melatonin on Ti particle-treated BMMSCs, evidenced by the reduced expression of SOD2, increased ROS and superoxide, and decreased osteogenic differentiation. These results demonstrated that melatonin restored the osteogenic potential and improved the antioxidant properties of BMMSCs through the SIRT1 signaling pathway. Our findings suggest that melatonin is a promising candidate for treating osteolysis induced by wear particles.

A mid-pregnancy risk prediction model for gestational diabetes mellitus based on the maternal status in combination with ultrasound and serological findings.

Although previous studies have proposed predictive models of gestational diabetes mellitus (GDM) based on maternal status, they do not always provide reliable results. The present study aimed to create a novel model that included ultrasound data of maternal fat distribution and serum inflammatory factors. The clinical data of 1,158 pregnant women treated at Tangshan Gongren Hospital and eight other flagship hospitals in Tangshan, including the First Hospital of Tangshan Gongren Hospital group, Ninth Hospital of Tangshan Gongren Hospital group, Tangshan Gongren Hospital group rehabilitation hospital, Tangshan railway central hospital, Tangshan Gongren Hospital group Fengnan hospital, Tangshan Gongren Hospital group Qianan Yanshan hospital, Tangshan Gongren Hospital group Qianxi Kangli hospital and Tangshan Gongren Hospital group Jidong Sub-hospital, were analyzed following the division of subjects into GDM and non-GDM groups according to their diagnostic results at 24-28 weeks of pregnancy. Univariate analysis was performed to investigate the significance of the maternal clinical parameters for GDM diagnosis and a GDM prediction model was established using stepwise regression analysis. The predictive value of the model was evaluated using a Homer-Lemeshow goodness-of-fit test and a receiver operating characteristic curve (ROC). The model demonstrated that age, pre-pregnancy body mass index, a family history of diabetes mellitus, polycystic ovary syndrome, a history of GDM, high systolic pressures, glycosylated hemoglobin levels, triglyceride levels, total cholesterol levels, low-density lipoprotein cholesterol levels, serum hypersensitive C-reactive protein, increased subcutaneous fat thickness and visceral fat thickness were all correlated with an increased GDM risk (all P<0.01). The area under the curve value was 0.911 (95% CI, 0.893-0.930). Overall, the results indicated that the current model, which included ultrasound and serological data, may be a more effective predictor of GDM compared with other single predictor models. In conclusion, the present study developed a tool to determine the risk of GDM in pregnant women during the second trimester. This prediction model, based on various risk factors, demonstrated a high predictive value for the GDM occurrence in pregnant women in China and may prove useful in guiding future clinical practice.

Evaluation of the mechanism of Danggui-Shaoyao-San in regulating the metabolome of nephrotic syndrome based on urinary metabonomics and bioinformatics approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui-Shaoyao-San (DSS), a well-known classic Traditional Chinese medicine (TCM) formula for enhancing Qi (vital energy and spirit), invigorating blood circulation and promoting diuresis, has been widely used in the treatment of nephrotic syndrome (NS). Previously, we have reported some protective effects of DSS against NS, but the in-depth mechanisms remain unclear. AIM OF THE STUDY: In this study, an ultra performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q/TOF-MS)-based urinary metabonomics coupled with bioinformatics method was employed to evaluate the mechanisms of DSS in treating NS from the perspective of metabolism. MATERIALS AND METHODS: The rat models of NS were established using adriamycin injection. The regulative effects of DSS on NS in rats were first assessed by non-targeted metabonomics, which was based on UPLC-Q/TOF-MS. A series of target prediction models were used to predict the target of components identified in DSS and potential metabolites in NS, combined with the experimental results of metabonomics, to construct the biological network. RESULTS: A total of 16 potential metabolites were screened in NS, of which 13 were significantly regulated by DSS. Metabolic pathway analysis showed that the therapeutic effect of DSS on NS was mainly involved in regulating the amino acid metabolism and energy metabolism. The component-target-metabolites-pathway network revealed 29 targets associated with metabolites that were linked to 27 components of DSS. Bioinformatics analysis showed that the potential targets have various molecular functions (especially serine-type endopeptidase inhibitor activity) and biological process (such as positive regulation of peptidyl-tyrosine phosphorylation or autophosphorylation). CONCLUSIONS: The regulation of disrupted metabolic pathways and the relative targets may be the mechanism for DSS in the treatment of NS. Notably, metabonomics coupled with bioinformatics would be useful to explore the mechanism of DSS against NS and provide better insights on DSS for clinical use.