Current challenges and therapeutic advances of CAR-T cell therapy for solid tumors.

The application of chimeric antigen receptor (CAR) T cells in the management of hematological malignancies has emerged as a noteworthy therapeutic breakthrough. Nevertheless, the utilization and effectiveness of CAR-T cell therapy in solid tumors are still limited primarily because of the absence of tumor-specific target antigen, the existence of immunosuppressive tumor microenvironment, restricted T cell invasion and proliferation, and the occurrence of severe toxicity. This review explored the history of CAR-T and its latest advancements in the management of solid tumors. According to recent studies, optimizing the design of CAR-T cells, implementing logic-gated CAR-T cells and refining the delivery methods of therapeutic agents can all enhance the efficacy of CAR-T cell therapy. Furthermore, combination therapy shows promise as a way to improve the effectiveness of CAR-T cell therapy. At present, numerous clinical trials involving CAR-T cells for solid tumors are actively in progress. In conclusion, CAR-T cell therapy has both potential and challenges when it comes to treating solid tumors. As CAR-T cell therapy continues to evolve, further innovations will be devised to surmount the challenges associated with this treatment modality, ultimately leading to enhanced therapeutic response for patients suffered solid tumors.

Correction: Lonicera japonica Thunb. as a promising antibacterial agent for Bacillus cereus ATCC14579 based on network pharmacology, metabolomics, and in vitro experiments.

[This corrects the article DOI: 10.1039/D3RA00802A.].

Understanding Hyperuricemia: Pathogenesis, Potential Therapeutic Role of Bioactive Peptides, and Assessing Bioactive Peptide Advantages and Challenges.

Hyperuricemia is a medical condition characterized by an elevated level of serum uric acid, closely associated with other metabolic disorders, and its global incidence rate is increasing. Increased synthesis or decreased excretion of uric acid can lead to hyperuricemia. Protein peptides from various food sources have demonstrated potential in treating hyperuricemia, including marine organisms, ovalbumin, milk, nuts, rice, legumes, mushrooms, and protein-rich processing by-products. Through in vitro experiments and the establishment of cell or animal models, it has been proven that these peptides exhibit anti-hyperuricemia biological activities by inhibiting xanthine oxidase activity, downregulating key enzymes in purine metabolism, regulating the expression level of uric acid transporters, and restoring the composition of the intestinal flora. Protein peptides derived from food offer advantages such as a wide range of sources, significant therapeutic benefits, and minimal adverse effects. However, they also face challenges in terms of commercialization. The findings of this review contribute to a better understanding of hyperuricemia and peptides with hyperuricemia-alleviating activity. Furthermore, they provide a theoretical reference for developing new functional foods suitable for individuals with hyperuricemia.

Lonicera japonica Thunb. as a promising antibacterial agent for Bacillus cereus ATCC14579 based on network pharmacology, metabolomics, and in vitro experiments.

Lonicera japonica Thunb. has attracted much attention for its treatment of bacterial and viral infectious diseases, while its active ingredients and potential mechanisms of action have not been fully elucidated. Here, we combined metabolomics, and network pharmacology to explore the molecular mechanism of Bacillus cereus ATCC14579 inhibition by Lonicera japonica Thunb. In vitro inhibition experiments showed that the Lonicera japonica Thunb.'s water extracts, ethanolic extract, luteolin, quercetin, and kaempferol strongly inhibited Bacillus cereus ATCC14579. In contrast, chlorogenic acid and macranthoidin B had no inhibitory effect on Bacillus cereus ATCC14579. Meanwhile, the minimum inhibitory concentrations of luteolin, quercetin, and kaempferol against Bacillus cereus ATCC14579 were 15.625 µg mL-1, 31.25 µg mL-1, and 15.625 µg mL-1. Based on the previous experimental basis, the metabolomic analysis showed the presence of 16 active ingredients in Lonicera japonica Thunb.'s water extracts and ethanol extracts, with differences in the luteolin, quercetin, and kaempferol contents between the water extracts and ethanol extracts. Network pharmacology studies indicated that fabZ, tig, glmU, secA, deoD, nagB, pgi, rpmB, recA, and upp were potential key targets. Active ingredients of Lonicera japonica Thunb. may exert their inhibitory effects by inhibiting ribosome assembly, the peptidoglycan biosynthesis process, and the phospholipid biosynthesis process of Bacillus cereus ATCC14579. An alkaline phosphatase activity assay, peptidoglycan concentration assay, and protein concentration assay showed that luteolin, quercetin, and kaempferol disrupted the Bacillus cereus ATCC14579 cell wall and cell membrane integrity. Transmission electron microscopy results showed significant changes in the morphology and ultrastructure of the cell wall and cell membrane of Bacillus cereus ATCC14579, further confirming the disruption of the cell wall and cell membrane integrity of Bacillus cereus ATCC14579 by luteolin, quercetin, and kaempferol. In conclusion, Lonicera japonica Thunb. can be used as a potential antibacterial agent for Bacillus cereus ATCC14579, which may exert its antibacterial activity by destroying the integrity of the cell wall and membrane.

Clinical efficacy of a combination treatment of traditional Chinese medicine for scalp seborrheic dermatitis.

OBJECTIVE: To evaluate the clinical efficacy of a combination treatment of traditional Chinese medicine (TCM) in scalp seborrheic dermatitis (SSD) of differing severity. METHODS: Our study included patients with typical SSD who visited the Medical Research Center for Hair and Skin at our hospital. Symptoms were evaluated using a "16-point scale" developed at the center. Patients who had mild SSD were treated with Pi Fu Kang Xi Ye (PFKXY), those with moderate SSD were treated with PFKXY combined with Run Zao Zhi Yang Jiao Nang (RZZYJN), and those with severe dermatitis were treated with PFKXY and RZZYJN along with garlicin enteric-coated tablets. Patients were asked to revisit 4 weeks later to evaluate the efficacy. RESULTS: Symptom scores of all patients decreased by (5.48 ± 2.51) after treatment as compared with before treatment, and the results of t-test and correlation test were significant (p < 0.01). The scores of patients with mild, moderate and severe SSD decreased by 3.14 ± 1.83, 4.90 ± 1.77, and 8.05 ± 2.21, respectively, after treatment as compared with before treatment. Among them, the changes in scores of patients with moderate dermatitis before and after treatment were significant in the t-test and correlation test (p < 0.01). CONCLUSION: In this study, the combination treatment of TCM showed significant efficacy in the treatment of mild, moderate, and severe SSD, and the efficacy was stable, especially for patients with moderate SSD.

Light plays a critical role in the accumulation of chlorogenic acid in Lonicera macranthoides Hand.-Mazz.

Light has important effects on plant metabolism. However, the relationship between the chlorogenic acid (CGA) content and light in plants remains unclear. Here, we investigated the effects of shading treatment on gene expression and CGA content in Lonicera macranthoides Hand.-Mazz. (LM), a widely used medicinal plant. A total of 1891 differentially expressed genes (DEGs) were obtained in flower buds and 819 in leaves in response to light in shading treatment compared to the control sample by RNA-Seq. After shading treatment, the content of CGA in LM leaves decreased significantly by 1.78-fold, the carotenoid content increased, and the soluble sugar and starch contents significantly decreased. WGCNA and the expression of related genes verified by qRT‒PCR revealed that CGA synthesis pathway enzyme genes form a co-expression network with genes for carbohydrate synthesis, photosynthesis, light signalling elements, and transcription factor genes (TFs) that affect the accumulation of CGA. Through a virus-induced gene silencing (VIGS) system and CGA assay in Nicotiana benthamiana (NB), we determined that downregulation of NbHY5 expression decreased the CGA content in NB leaves. In this study, we found that light provides energy and material for the accumulation of CGA in LM, and light affects the expression of CGA accumulation-related genes. Our results show that different light intensities have multiple effects on leaves and flower buds in LM and are able to coregulate LmHY5 expression and CGA synthesis.

One-stage freehand minimally invasive pedicle screw fixation combined with mini-access surgery through OLIF approach for the treatment of lumbar tuberculosis.

OBJECTIVE: To compare one-stage freehand minimally invasive pedicle screw fixation (freehand MIPS) combined with mini-access surgery through OLIF approach with posterior approach for treatment of lumbar tuberculosis (TB), and evaluate its feasibility, efficacy and safety in debridement, bone graft fusion and internal fixation. METHODS: 48 patients with single segment lumbar TB from June 2014 to June 2017 were included. Among them, 22 patients underwent one-stage freehand MIPS combined with mini-access surgery through OLIF approach (group 1), 26 patients were treated with posterior open surgery (group 2). Duration of operation, blood loss, and stay time in hospital were compared. Pre- and postoperative visual analog scale (VAS) pain scores, Oswestry disability index (ODI), erythrocyte sedimentation rate, complications and images were also recorded. RESULTS: Patients in group 1 showed significantly less blood loss (165 ± 73 ml vs 873 ± 318 ml, P < 0.001), shorter stay time in hospital (6/4-8 days vs 12/8-15 days, P < 0.001), while longer duration of operation (185 ± 14 min vs 171 ± 12 min, P < 0.001) than group 2 did. VAS scores significantly decreased after surgery in both groups, however, VAS scores of group 1 were significantly lower than that of group 2 immediately after surgery and during follow-ups (P < 0.001). ODI of group 1 was also significantly lower than that of group 2 at 12-month after surgery (P < 0.001). CONCLUSION: One-stage freehand MIPS combined with mini-access surgery through OLIF approach is a feasible, efficient and safe method in treating single segment lumbar TB. It shows advantages of less surgical trauma and faster postoperative recovery.

Efficacy and safety of anterior cervical discectomy and fusion (ACDF) through mini-incision and posterior laminoplasty (LAMP) for treatment of long-level cervical spondylosis: a retrospective cohort study.

BACKGROUND: The efficacy and safety of anterior cervical discectomy and fusion (ACDF) through mini-incision and posterior laminoplasty for long-level cervical spondylosis were investigated. METHOD: From January 2018 to September 2019, clinical patients data with 3-4 segments (C3-7) cervical spondylotic radiculopathy, cervical spondylotic myelopathy, or mixed cervical spondylosis who received ACDF (42 cases) throughwith mini-incision or LAMP (36 cases) treatment were retrospectively collected and analyzed. The operative time, bleeding volume, incisive length, and hospital stay were recorded. Moreover, the intervertebral height, functional segment height, cervical lordosis, cervical hyperextension and hyperflexion range-of-motion (ROM) and ROM in all directions of the cervical spine before and after the operation were measured. Additionally, all relevant postoperative complications were also recorded. Then, the therapeutic effects of both surgical methods were investigated. RESULTS: Patients in the ACDF group had less bleeding, shorter incision, and fewer hospitalization days than the LAMP group. There was no significant difference in JOA, VAS score of the upper limb, NDI score after surgery between two groups. Postoperative intervertebral height and functional segment height in the ACDF group were significantly higher than those before the operation, and postoperative functional segment height of the ACDF group was significantly higher than that of the LAMP group. Moreover, the postoperative cervical lordosis angle in the ACDF group was significantly larger than the LAMP group. There was no significant difference between preoperative and postoperative ROM in all directions of the cervical spine for the two groups. CONCLUSIONS: Both ACDF through mini-incision and LAMP are effective treatments for long-level cervical spondylosis. However, ACDF through mini-incision shows minor trauma, less bleeding, fast recovery, and it is beneficial for cervical lordosis reconstruction.

A Novel Antimicrobial Peptide Sp-LECin with Broad-Spectrum Antimicrobial Activity and Anti-Pseudomonas aeruginosa Infection in Zebrafish.

New antimicrobial agents are urgently needed to address the increasing emergence and dissemination of multidrug-resistant bacteria. In the study, a chemically synthesized truncated peptide containing 22-amino acids derived from a C-type lectin homolog SpCTL6 of Scylla paramamosain was screened and found to exhibit broad-spectrum antimicrobial activity, indicating that it is an antimicrobial peptide (AMP), named Sp-LECin. Sp-LECin possessed the basic characteristics of most cationic AMPs, such as positive charge (+4) and a relatively high hydrophobicity (45%). After treatment with Sp-LECin, the disruption of microbial membrane integrity and even leakage of cellular contents was observed by scanning electron microscopy (SEM). In addition, Sp-LECin could bind lipopolysaccharide (LPS), increase the outer and inner membrane permeability and induce reactive oxygen species (ROS) production, ultimately leading to the death of Pseudomonas aeruginosa. Furthermore, Sp-LECin exhibited potent anti-biofilm activity against P. aeruginosa during both biofilm formation and maturation. Notably, Sp-LECin had no obvious cytotoxicity and could greatly improve the survival of P. aeruginosa-infected zebrafish, by approximately 40% over the control group after 72 h of treatment. This study indicated that Sp-LECin is a promising antibacterial agent with the potential to be used against devastating global pathogen infections such as P. aeruginosa.

A Novel Antimicrobial Peptide Sparamosin26-54 From the Mud Crab Scylla paramamosain Showing Potent Antifungal Activity Against Cryptococcus neoformans.

Due to the increasing prevalence of drug-resistant fungi and the limitations of current treatment strategies to fungal infections, exploration and development of new antifungal drugs or substituents are necessary. In the study, a novel antimicrobial peptide, named Sparamosin, was identified in the mud crab Scylla paramamosain, which contains a signal peptide of 22 amino acids and a mature peptide of 54 amino acids. The antimicrobial activity of its synthetic mature peptide and two truncated peptides (Sparamosin1-25 and Sparamosin26-54) were determined. The results showed that Sparamosin26-54 had the strongest activity against a variety of Gram-negative bacteria, Gram-positive bacteria and fungi, in particular had rapid fungicidal kinetics (killed 99% Cryptococcus neoformans within 10 min) and had potent anti-biofilm activity against C. neoformans, but had no cytotoxic effect on mammalian cells. The RNA-seq results showed that after Sparamosin26-54 treatment, the expression of genes involved in cell wall component biosynthesis, cell wall integrity signaling pathway, anti-oxidative stress, apoptosis and DNA repair were significantly up-regulated, indicating that Sparamosin26-54 might disrupt the cell wall of C. neoformans, causing oxidative stress, DNA damage and cell apoptosis. The underlying mechanism was further confirmed. Sparamosin26-54 could bind to several phospholipids in the cell membrane and effectively killed C. neoformans through disrupting the integrity of the cell wall and cell membrane observed by electron microscope and staining assay. In addition, it was found that the accumulation of reactive oxygen species (ROS) increased, the mitochondrial membrane potential (MMP) was disrupted, and DNA fragmentation was induced after Sparamosin26-54 treatment, which are all hallmarks of apoptosis. Taken together, Sparamosin26-54 has a good application prospect as an effective antimicrobial agent, especially for C. neoformans infections.

The Long-Term Effect of a Nine Amino-Acid Antimicrobial Peptide AS-hepc3(48-56) Against Pseudomonas aeruginosa With No Detectable Resistance.

The emergence of multidrug-resistant (MDR) pathogens has become a global public health crisis. Among them, MDR Pseudomonas aeruginosa is the main cause of nosocomial infections and deaths. Antimicrobial peptides (AMPs) are considered as competitive drug candidates to address this threat. In the study, we characterized two AMPs (AS-hepc3(41-71) and AS-hepc3(48-56)) that had potent activity against 5 new clinical isolates of MDR P. aeruginosa. Both AMPs destroyed the integrity of the cell membrane, induced leakage of intracellular components, and ultimately led to cell death. A long-term comparative study on the bacterial resistance treated with AS-hepc3(41-71), AS-hepc3(48-56) and 12 commonly used antibiotics showed that P. aeruginosa quickly developed resistance to the nine antibiotics tested (including aztreonam, ceftazidime, cefepime, imipenem, meropenem, ciprofloxacin, levofloxacin, gentamicin, and piperacillin) as early as 12 days after 150 days of successive culture generations. The initial effective concentration of 9 antibiotics against P. aeruginosa was greatly increased to a different high level at 150 days, however, both AS-hepc3(41-71) and AS-hepc3(48-56) maintained their initial MIC unchangeable through 150 days, indicating that P. aeruginosa did not produce any significant resistance to both AMPs. Furthermore, AS-hepc3(48-56) did not show any toxic effect on mammalian cells in vitro and mice in vivo. AS-hepc3(48-56) had a therapeutic effect on MDR P. aeruginosa infection using a mouse lung infection model and could effectively increase the survival rate of mice by inhibiting bacterial proliferation and attenuating lung inflammation. Taken together, the short peptide AS-hepc3(48-56) would be a promising agent for clinical treatment of MDR P. aeruginosa infections.

Research on slipping-pattern recognition and positioning error compensation of wheeled robot.

The autonomous navigation and positioning system is one of the key equipment in industrial automation production. Due to slippage, the odometer (OD) data cannot reflect the real rotation of the wheeled robot, which may cause the unmanned robot to deviate from the preset route. To solve this problem, the integration of the strap-down inertial navigation system (SINS) and the OD is used, and a novel slipping recognition algorithm based on neural network learning and an error compensation method is proposed to improve the navigation accuracy when skidding. First, the output data of the SINS and OD are studied and features are extracted for neural network learning. After training and modeling, the state of the robot slipping can be identified quickly and effectively. Second, different models are designed to compensate the errors of the different slip patterns. Experimental results show that the comprehensive recognition rate of five modes within 1 s is better than 98.9%. After compensation, the positioning errors of the left and right slip modes have been reduced to 15 mm and the positioning errors of the both side and locked slip modes have been reduced to 40 mm. Compared with before compensation, the errors are reduced to less than 6%.

Identification of reliable reference genes for quantitative real-time PCR analysis of the Rhus chinensis Mill. leaf response to temperature changes.

Rhus chinensis Mill. (RCM) is the host plant of Galla chinensis, which is valued in traditional medicine. Environmental temperature directly determines the probability of gallnut formation and RCM growth. At present, there is no experiment to systematically analyse the stability of internal reference gene (RG) expression in RCM. In this experiment, leaves that did not form gallnuts were used as the control group, while leaves that formed gallnuts were used as the experimental group. First, we conducted transcriptome experiments on RCM leaves to obtain 45 103 differential genes and functional enrichment annotations between the two groups. On this basis, this experiment established a transcriptional gene change model of leaves in the process of gallnut formation after being bitten by aphids, and RCM reference candidate genes were screened from RNA sequencing (RNA-seq) data. This study is based on RCM transcriptome data and evaluates the stability of 11 potential reference genes under cold stress (4 °C) and heat stress (34 °C), using three statistical algorithms (geNorm, NormFinder, and BestKeeper). The results show that GAPDH1 + PP2A2/UBQ are stable reference genes under heat stress, while GAPDH1 + ACT are the most stable under cold stress. This study is the first to screen candidate reference genes in RCM and could help guide future molecular studies in this genus.

Characteristics of Metabolites by Seed-Specific Inhibition of FAD2 in Brassica napus L.

Fatty acid desaturase-2 (FAD2) is a key enzyme in the production of polyunsaturated fatty acids in plants. RNAi technology can reduce the expression of FAD2 genes in Brassica napus seeds and acquire transgenic B. napus plants with a high oleic acid content, but the effect of seed-specific inhibition of FAD2 expression on B. napus seed metabolites is not clear. Here we use widely targeted metabolomics to investigate the metabolites of normal-oleic-acid rapeseed (OA) and high-oleic-acid rapeseed (HOA) seeds, resulting in a total of 726 metabolites being detected. Among them, 24 differential metabolites were significantly downregulated and 88 differential metabolites were significantly upregulated in HOA rapeseed. In further lipid profile experiments, more lipids in B. napus seeds were accurately quantified. The contents of glycolipids and phospholipids that contain C18:1 increased significantly and C18:2 decreased because FAD2 expression was inhibited. The changes in the expression of key genes in related pathways were also consistent with the changes in metabolites. The insertion site of the ihpRNA plant expression vector was reconfirmed through genomewide resequencing, and the transgenic event did not change the sequence of FAD2 genes. There was no significant difference in the germination rate and germination potential between OA and HOA rapeseed seeds because the seed-specific ihpRNA plant expression vector did not affect other stages of plant growth. This work provides a theoretical and practical guidance for subsequent molecular breeding of high OA B. napus.

Analysis of the influencing factors of the clinical effect of respiratory humidifier in treating AIDS complicated with severe Pneumocystis jiroveci pneumonia.

OBJECTIVE: To analyze the factors influencing the clinical effect of using respiratory humidifier in patients with AIDS complicated with severe Pneumocystis jiroveci pneumonia (PCP). METHODS: According to the treatment results, AIDS patients with severe PCP were divided into two groups, successful group (n=68) and failure group (n=94), to compare the early ventilation changes between the two groups. RESULTS: The ICU ratio of the successful group was lower than that of the failure group (P<0.05). The respiratory frequency, heart rate, PaO2, C-reactive protein and SOFA score of the successful group were lower than those in the failure group (P<0.05), while SpO2, FiO2, PaO2/FiO2, SpO2/FiO2, Rox index and IL-10 levels were increased in the successful group (P<0.05). The successful group had higher IL-6 and IL-1ß level than that of the failure group. The levels of IL-8 were decreased (P<0.05). The success of respiratory humidifier was negatively correlated with the score of SOFA (P<0.05). CONCLUSION: The clinical effect of respiratory humidifier in the treatment of AIDS patients with severe PCP was related to PaO2/FiO2, PaO2, ROX index, SOFA score, and IL-6 and IL-8 levels.

The Tendency of Modified Electroconvulsive Therapy-Related Working Memory and Subjective Memory Deficits in Depression: A Prospective Follow-up Study.

OBJECTIVE: The aim of the study was to explore the tendency of modified electroconvulsive therapy (MECT)-related working memory and subjective memory deficits in depressed patients. METHODS: Sixty patients with unipolar/bipolar depression were prepared and enrolled for MECT and 56 subjects were enrolled as healthy controls (HCs). Their demographics (sex, age, body mass index, years of schooling, etc) and clinical characteristics (dosage and number of MECT, etc) were compared. Depression severity, working memory, and subjective memory were measured using the Hamilton Depression Rating Scale 17 (HAMD17), a Digit Span Backwards (DSB), and self-reported assessments, respectively. Measurements were taken at baseline, within 24 hours after each MECT session, and in every month for a 6-month follow-up period. RESULTS: (a) The patients had poorer performance than the HCs on DSB and HAMD17 at baseline, and the DSB score and HAMD17 total scores were negatively correlated. However, after the second MECT session, the patients' HAMD17 score was significantly improved compared with that at the baseline (P < 0.05), whereas the DSB score showed no significant difference compared with the HCs (P > 0.05). (b) After the first MECT session, 62% of the patients reported subjective memory deficits, which were exacerbated over the subsequent sessions and relieved with antidepressant treatment during the follow-up period. (c) The risk factors for prolonged subjective memory deficits were overweight and the maximum MECT dosage/age (dosage/age = the percentage of output part of total dosage × 100/age, unit: 1/year) ≥ 1.5/year (odds ratio [OR] = 15.36 and 7.98). CONCLUSIONS: Depressed patients showed poorer working memory than the HCs. Such memory deficit may be aggravated by MECT, although it may improve with the relief of depression. Although subjective memory deficits can occur after the first MECT session and gradually recover after the treatment, they may last for 6 months or longer. Persistent deficits may be related to being overweight and having a high MECT dosage.

CuCo2O4 supported on activated carbon as a novel heterogeneous catalyst with enhanced peroxymonosulfate activity for efficient removal of organic pollutants.

CuCo2O4 was synthesized via a relatively simple method, and innovatively supported onto the activated carbon (AC) by calcination to obtain a novel heterogeneous catalyst (AC-CuCo2O4). Brilliant red 3BF (3BF) was selected as the probe compound to investigate the catalytic activity of AC-CuCo2O4 in the presence of peroxymonosulfate (PMS). The results showed that 98% removal rate could be achieved and the reaction rate constant (0.476 min-1) was 5.2 times greater than that of CuCo2O4 alone (0.091min-1), suggesting that the introduction of AC could greatly enhance the catalytic activity of pure CuCo2O4. Typically, the 3BF removal was as high as 96% after five cycles, showing the good stability of catalyst reuse. Additionally, the effects of the initial pH, catalyst dosage, PMS concentration and reaction temperature on the 3BF removal were investigated, demonstrating that AC-CuCo2O4 effectively remove 3BF over a wide pH range (5.0-10.0) and possessed temperature-tolerant performance. To further explore the 3BF removal mechanism, electron paramagnetic resonance technology combining with trapping agents was employed to confirm the involvement of reactive oxygen species including SO4•-, •OH, O2•- and 1O2, which distinctly differed from the reported CuCo2O4 for PMS activation. These findings provided an addition promising strategy in environmental remediation.

Influence of distal radius fractures involving the intermediate column on forearm rotation.

BACKGROUND: The objective of the study was to compare the radiologic and clinical outcome of patients with distal radius fractures involving the intermediate column and distal radial metaphyseal fractures treated conservatively. METHODS: Two cohorts of 52 matched patients with distal radius fractures treated conservatively, one with a fracture involving the intermediate column and the other with no intermediate column fracture, were retrospectively analyzed by examining the data. Patients were matched for age, sex, fracture side, and AO fracture type. The two groups were analyzed for differences in wrist motion; grip strength; Gartland and Werley score; Disabilities of the Arm, Shoulder and Hand (DASH) score; and visual analogue scale (VAS) score at 12 months. The differences in continuous variables were compared using the paired t test. Linear regression analyses or Pearson correlation analyses were used to evaluate the associations of radiological parameters with clinical outcomes. RESULTS: The analysis showed significant differences in the range of motion (ROM) for pronation (p = 0.000) and supination (p = 0.008) in the paired groups. There was a significant difference in DASH scores (p = 0.024) in the paired groups. Using Pearson correlation analysis, negative correlations (r = - 0.360, p = 0.000) were observed between articular step-off and ROM for pronation. Linear regression analyses also indicated that ROM for pronation had negative relationships (ß = - 6.327, p = 0.001) with articular step-off. CONCLUSIONS: Distal radius fractures involving the intermediate column had an adverse effect on forearm rotation after distal radius fractures treated conservatively.

Targeted salinomycin delivery with EGFR and CD133 aptamers based dual-ligand lipid-polymer nanoparticles to both osteosarcoma cells and cancer stem cells.

We previously developed salinomycin (sali)-entrapped nanoparticles labeled with CD133 aptamers which could efficiently eliminate CD133+ osteosarcoma cancer stem cells (CSCs). However, sufficient evidences suggest that the simultaneous targeting both CSCs and cancer cells is pivotal in achieving preferable cancer therapeutic efficacy, due to the spontaneous conversion between cancer cells and CSCs. We hereby constructed sali-entrapped lipid-polymer nanoparticles labeled with CD133 and EGFR aptamers (CESP) to target both osteosarcoma cells and CSCs. The cytotoxicity of CESP in osteosarcoma cells and CSCs was superior to that of single targeting or nontargeted sali-loaded nanoparticles. Administration of CESP in vivo showed the best efficacy in inhibiting tumor growth than other controls in osteosarcoma-bearing mice. Thus, CESP was demonstrated to be capable of efficiently targeting both osteosarcoma CSCs and cancer cells, and it represents an effective potential approach to treat osteosarcoma.