Effects of microplastics (MPs) and tributyltin (TBT) alone and in combination on bile acids and gut microbiota crosstalk in mice.

Microplastics (MPs) and tributyltin (TBT) are both potential environmental pollutants that enter organisms through the food chain and affect bodily functions. However, the effects and mechanisms of MPs and TBT exposure (especially the co-exposure of both pollutants) on mammals remain unclear. In this study, Ф5µm MPs (5MP) was administered alone or in combination with TBT to investigate the health risk of oral exposure in mice. All three treatments induced inflammation in the liver, altered gut microbiota composition and disturbed fecal bile acids profiles. In addition to decreasing triglyceride (TG) and increasing aspartate aminotransferase (AST) and macrophage-expressed gene 1 (Mpeg1), 5MP induced hepatic cholestasis by stimulating the expression of the cholesterol hydroxylase enzymes CYP8B1 and CYP27A1, and inhibiting multidrug resistance-associated protein 2 and 3 (MRP2, MRP3), and bile-salt export pump (BSEP) to prevent bile acids for entering the blood and bile. Correspondingly, 5MP treatment decreased 7-ketolithocholic acid (7-ketoLCA) and taurocholic acid (TCA), which were positively correlated with decreased Bacteroides and Marvinbryantia and negatively correlated with increased Bifidobacterium. In addition, TBT increased interferon γ (IFNγ) and Mpeg1 levels to induce inflammation, accompanied by decreased 7-ketoLCA, tauro-alpha-muricholic acid (T-alpha-MCA) and alpha-muricholic acid (alpha-MCA) levels, which were negatively related to Coriobacteriaceae_UCG-002 and Bifidobacterium. Co-exposure to 5MP and TBT also decreased TG and induced bile acids accumulation in the liver due to inhibited BSEP, which might be attributed to the co-regulation of decreased T-alpha-MCA and Harryflintia. In conclusion, the administration of 5MP and TBT alone and in combination could cause gut microbiome dysbiosis and subsequently alter bile acids profiles, while the combined exposure of 5MP and TBT weakened the toxic effects of 5MP and TBT alone.

Simultaneous determination of gallic acid, methyl gallate, and 1,3,6-tri-O-galloyl-ß-d-glucose from Turkish galls in rat plasma using liquid chromatography-tandem mass spectrometry and its application to pharmacokinetics study.

Turkish galls (TG) is a traditional Uygur medicine typically used in clinics for dental disease and chronic ulcerative colitis. In this study, a novel liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of gallic acid, methyl gallate, and 1,3,6-tri-O-galloyl-ß-d-glucose in rat plasma, which are the major bioactive compounds of TG. After a feasible protein precipitation using acetonitrile for sample preparation, chromatographic separation was performed with a BDS Hypersil C18 column (2.1 × 100 mm, 5 µm) at 30°C, and water containing 10 mmol of ammonium acetate and acetonitrile was used as the mobile phase with a flow rate of 0.3 mL/min. The MS detector was operated in the selective reaction monitoring with negative-ionization mode. The results of the method validation, including selectivity, linearity, accuracy, precision, extraction recovery, matrix effect, and stability of the compounds in the biosamples, were all within the current acceptance criteria. The established method was successfully applied to the pharmacokinetics study of three analytes in rats after an oral administration of TG extract and laid the foundation for studying the active components and mechanism of TG in vivo.

Transoral anterior release, odontoid partial resection, and reduction with posterior fusion for the treatment of irreducible atlantoaxial dislocation caused by odontoid fracture malunion.

PURPOSE: Several techniques have been introduced to manage irreducible atlantoaxial dislocation (IAAD). However, no study has reported the surgical method for the management of IAAD caused by odontoid fracture malunion. This study aimed to introduce a surgical method of transoral anterior release, odontoid partial resection, and reduction with sequential posterior fusion for the treatment of IAAD caused by odontoid fracture malunion. We also evaluated the clinical efficacy of this surgery. METHODS: This study included seven cases of IAAD caused by odontoid fracture malunion, collected from January 2008 to January 2011. Anterior atlantoaxial release was performed through anterior transoral approach, followed by partial resection of the odontoid process. C1-C2 were then fixed through pedicle screws and rods, and then fused posteriorly by single stage. Neurologic status was evaluated using the Japanese Orthopaedic Association (JOA) scoring system. RESULTS: All seven patients had complete release, and satisfactory reduction. Bony fusion was seen in all patients postoperatively. The patients were followed up for an average of 19.6 months (ranged from 9 to 36 months). The average of patients JOA scores at the final follow-up was significantly higher than that of their preoperative scores. Furthermore, the average improvement in neurological function was 87.4 %. No screw loosening, implant migration or implant failures, atlantoaxial redislocation, or signs of instability were observed in any of the patients during the follow-up period. CONCLUSIONS: Transoral anterior release, odontoid partial resection, and reduction combined with posterior fusion are effective, reliable, and safe procedures for the treatment of IAAD caused by odontoid fracture malunion.

[Advances in the research of transformation and stabilization of soil organic carbon from plant and microbe]. / æ¤ç‰©æºå’Œå¾®ç”Ÿç‰©æºåœŸå£¤æœ‰æœºç¢³è½¬åŒ–ä¸Žç¨³å®šç ”ç©¶è¿›å±•.

Soil organic carbon (SOC) is the core component of terrestrial carbon (C) sink. Exploring the transformation and stabilization mechanism of SOC is key to understand the function of terrestrial C sink which copes with climate change. The traditional perspective is that plant residues are the initial source of SOC. The new concept of "soil microbial C pump" emphasizes that the synthesized products of soil microbial assimilation are important contributors to the stable SOC. This provides a new insight to the sequestration mechanism of SOC. Due to the complex and variable decomposition process of plant residues and the high heterogeneity of microbial residues, the transformation and stabilization mechanism of plant residues and microbial residues into SOC is still unclear. We reviewed research progress in plant and microbial residues, and introduced the characterization methods of quantification and transformation of plant residues and microbial residues, and also summarized the new findings on the transformation of plant and microbial residues into SOC. We further discussed the contribution and driving factors of microbial and plant-derived C to SOC. Finally, we prospected the future development direction and research focus in this field. This review would provide the scientific reference for the research of soil C sequestration in terrestrial ecosystem.

X-linked Charcot-Marie-Tooth disease after SARS-CoV-2 vaccination mimicked stroke-like episodes: A case report.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations have been administered worldwide, with occasional reports of associated neurological complications. Specifically, the impact of vaccinations on individuals with X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is unclear. Patients with CMTX1 can have stroke-like episodes with posterior reversible encephalopathy syndrome on magnetic resonance imaging (MRI), although this is rare. CASE SUMMARY: A 39-year-old man was admitted with episodic aphasia and dysphagia for 2 d. He received SARS-CoV-2 vaccination 39 d before admission. Physical examination showed pes cavus and reduced tendon reflexes. Brain MRI showed bilateral, symmetrical, restricted diffusion with T2 hyperintensities in the cerebral hemispheres. Nerve conduction studies revealed peripheral nerve damage. He was diagnosed with Charcot-Marie-Tooth disease, and a hemizygous mutation in the GJB1 gene on the X chromosome, known to be pathogenic for CMTX1, was identified. Initially, we suspected transient ischemic attack or demyelinating leukoencephalopathy. We initiated treatment with antithrombotic therapy and immunotherapy. At 1.5 mo after discharge, brain MRI showed complete resolution of lesions, with no recurrence. CONCLUSION: SARS-CoV-2 vaccination could be a predisposing factor for CMTX1 and trigger a sudden presentation.

Sustained Release of Dicumarol via Novel Grafted Polymer in Electrospun Nanofiber Membrane for Treatment of Peritendinous Adhesion.

The prevention and treatment of post-traumatic peritendinous adhesion (PA) have always been a great difficulty for orthopedic surgeons. Current treatments include resecting surgery, non-steroidal anti-inflammatory drugs (NSAIDs) usage and implantable membranes, often target single disease pathogenic processes, resulting in unfavorable therapeutic outcomes. Here a polylactic acid (PLA)-dicumarol conjugates-electrospun nanofiber membrane (ENM) (PCD) is generated, which can achieve spatial accuracy and temporal sustainability in drug release. It is further demonstrated that PCD possesses a significantly higher and more sustainable drug release profile than traditional drug-loading ENM. By providing a physical barrier and continuous releasing of dicumarol, PCD implantation significantly reduces tissue adhesion by 25%, decreases fibroblasts activity and inhibits key fibrogenic cytokine transforming growth factor beta (TGFß) production by 30%, and improves the biomechanical tendon property by 14.69%. Mechanistically, PCD potently inhibits the connexin43 (Cx43) and thereby tunes down the fibroblastic TGFß/Smad3 signaling pathway. Thus, this approach leverages the anti-adhesion effect of dicumarol and drug release properties of grafted copolymer ENM by esters to provide a promising therapeutic strategy for patients who suffer from PA.

L-selectin and P-selectin are novel biomarkers of cervicovaginal inflammation for preclinical mucosal safety assessment of anti-HIV-1 microbicide.

A major obstacle thwarting preclinical development of microbicides is the lack of a validated biomarker of cervicovaginal inflammation. Therefore, the present study aims to identify novel noninvasive soluble markers in a murine model for assessment of microbicide mucosal safety. By performing cytokine antibody array analysis, we identified two adhesion molecules, L-selectin and P-selectin, which significantly increased when mucosal inflammation was triggered by nonoxynol-9 (N9), an anti-HIV-1 microbicide candidate that failed clinical trials, in a refined murine model of agent-induced cervicovaginal inflammation. We found that patterns of detection of L-selectin and P-selectin were obviously different from those of the two previously defined biomarkers of cervicovaginal inflammation, monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6). The levels of these two soluble selectins correlated better than those of MCP-1 and IL-6 with the duration and severity of mucosal inflammation triggered by N9 and two approved proinflammatory compounds, benzalkonium chloride (BZK) and sodium dodecyl sulfate (SDS), but not by two nonproinflammatory compounds, carboxymethyl celluose (CMC; microbicide excipients) and tenofovir (TFV; microbicide candidate). These data indicated that L-selectin and P-selectin can serve as additional novel cervicovaginal inflammation biomarkers for preclinical mucosal safety evaluation of candidate microbicides for the prevention of infection with HIV and other sexually transmitted pathogens.

Biogenetic Acellular Dermal Matrix Maintaining Rich Interconnected Microchannels for Accelerated Tissue Amendment.

Given that many people suffer from extensive skin damage, wound repair has drawn tremendous attention in research. Among the various assistant dressing materials that promote healing, a porcine acellular dermal matrix (PADM), as a skin substitute, can efficiently accelerate healing by promoting cell migration and proliferation. However, a simple, low-cost preparation process remains a challenge facing PADM development, particularly because of the inferior elasticity. To overcome these drawbacks, a CaCl2-ethanol-H2O solution (ternary solution) combined with an additional enzyme treatment was used to obtain a transparent, porous, and elastic PADM that retained the major extracellular matrix composition of the dermis. Our results indicated that alterations in the fiber organization and secondary structural changes in the collagen occurred after treatment. Furthermore, the in vivo wound healing and histological analyses clearly revealed an extremely expedited wound repair process following the application of the biocompatible PADM. In conclusion, this study provides new insights into the development of a transparent PADM with a porous structure and good elasticity that can be used as a skin substitute to accelerate the wound healing process. Moreover, this effective technique could potentially be used to extrapolate other decellularized materials in the future.

The Healing Rate of Type II Odontoid Fractures Treated With Posterior Atlantoaxial Screw-rod Fixation: A Retrospective Review of 77 Patients.

BACKGROUND: In theory, temporary posterior atlantoaxial screw-rod fixation for type II odontoid fractures is a way to preserve rotatory motion. However, the healing rate of type II odontoid fractures treated in this way is unknown; that is, the risk associated with conducting a temporary screw-rod fixation for type II odontoid fractures is unknown. This study investigates the healing rate of type II odontoid fractures treated with posterior atlantoaxial screw-rod fixation by CT imaging and evaluates the feasibility of conducting a temporary screw-rod fixation for type II odontoid fractures. METHODS: Patients with type II odontoid fracture who underwent posterior atlantoaxial screw-rod fixation in our spine center from January 2011 to December 2014 were identified. Patients older than 65 years or younger than 18 years were excluded. Those who were confirmed to have healing odontoid fractures on CT imaging were included. Those in whom fracture healing was not confirmed were asked to undergo a CT examination. Fracture healing was confirmed on the basis of the presence of bridging bone across the odontoid fracture site on CT imaging. RESULTS: Seventy-seven patients (56 men and 21 women) were included in the study. The average age of the patients was 40.7 ± 11.6 years (range, 18 to 64 years). The mean duration of follow-up was 26.4 ± 4.6 months (range, 24 to 40 months). Fracture healing was observed in 73 patients (94.8%). DISCUSSION: The healing rate of type II odontoid fractures (with an age range of 18 to 64 years) treated with modern posterior atlantoaxial fixation is relatively high. For patients at that age range, posterior atlantoaxial temporary screw-rod fixation for type II odontoid fractures can be conducted with a low risk of nonunion. LEVEL OF EVIDENCE: Level IV, therapeutic.

Second-generation Flagellin-rPAc Fusion Protein, KFD2-rPAc, Shows High Protective Efficacy against Dental Caries with Low Potential Side Effects.

Dental caries is one of the most common global chronic diseases affecting all ages of the population; thus a vaccine against caries is urgently needed. Our previous studies demonstrated that a fusion protein, KF-rPAc, in which rPAc of S. mutans is directly fused to the C-terminal of E. coli-derived flagellin (KF), could confer high prophylactic and therapeutic efficiency against caries. However, possible side effects, including the high antigenicity of flagellin and possible inflammatory injury induced by flagellin, may restrict its clinical usage. Here, we produced a second-generation flagellin-rPAc fusion protein, KFD2-rPAc, by replacing the main antigenicity region domains D2 and D3 of KF with rPAc. Compared with KF-rPAc, KFD2-rPAc has lower TLR5 agonist efficacy and induces fewer systemic inflammatory responses in mice. After intranasal immunization, KFD2-rPAc induces significantly lower flagellin-specific antibody responses but a comparable level of rPAc-specific antibody responses in mice. More importantly, in rat challenge models, KFD2-rPAc induces a robust rPAc-specific IgA response, and confers efficient prophylactic and therapeutic efficiency against caries as does KF-rPAc, while the flagellin-specific antibody responses are highly reduced. In conclusion, low side effects and high protective efficiency against caries makes the second-generation flagellin-rPAc fusion protein, KFD2-rPAc, a promising vaccine candidate against caries.

Posterior C1-C2 screw-rod fixation and autograft fusion for the treatment of os odontoideum with C1-C2 instability.

OBJECTIVE: To report our experience treating os odontoideum with C1-C2 instability via C1-C2 screw-rod fixation and autograft fusion and to explore the clinical efficacy of such a treatment strategy. PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients who were diagnosed with os odontoideum with C1-C2 instability and treated by posterior C1-C2 screw-rod fixation and fusion. Neurological deficits were measured with the Japanese Orthopedic Association (JOA) scoring system and neck pain was assessed using the Visual Analogue Scale (VAS) score. Fusion was determined based on the presence of bridging bone in computed tomography (CT) imaging, whereas stability was determined based on the lack of movement in dynamic radiographs. RESULTS: Thirty-two patients (18 males) were included in the study. The surgery was successfully accomplished in all patients. Thirty (93.8%) patients had confirmed C1-C2 bony fusion in CT images and all patients (100%) were stable in dynamic radiographs. The mean preoperative JOA score was 14.3±1.4 (range 11-16); at the final visit, it increased to 16.2±0.8 (range 14-17) (p<0.001). The mean preoperative VAS score was 3.8±0.7 (range 3-5) and decreased at the final visit to 1.0±0.6 (range 0-2) (p<0.001). CONCLUSION: Our treatment strategy (C1-C2 screw-rod fixation and autograft fusion) can achieve excellent clinical results with minor complications for patients with os odontoideum with C1-C2 instability.

[Clinical, pathological and genetic studies in a Chinese Charcot-Marie-Tooth disease type 2 family].

OBJECTIVE: To report a Chinese Charcot-Marie-Tooth disease type 2 (CMT2) family. METHODS: All the members in the family were studied clinically,and 6 patients were studied electrophysiologically. Sural nerve biopsy was performed in the proband. PMP22 gene duplications were detected by highly polymorphic short tandem repeat. Point mutation analysis of PMP22, MPZ and NEFL gene was screened by PCR-SSCP combined with DNA direct sequencing. A genome-wide screening was carried out to the family. RESULT: Except 2 who had weakness and atrophy in both proximal and distal muscles of the lower limbs, all patients presented muscle wasting and a predominating weakness of distal parts of the lower limbs, and mild to moderate sensory impairments. In 6 patients who were subjected to elctrophysiological examinations, median-nerve conduction velocity (NCV) of the median nerve was normal. Electromyograms (EMGs) revealed signs of denervation with large motor unit potentials, fibrillation potentials and positive sharp waves. Sural nerve biopsy of the proband confirmed the presence of axonal neuropathy with an important loss of large myelinating fibers and a large number of clusters with mostly thinly myelinated axons. PMP22, MPZ and NEFL gene mutations were not found. The results of genome-wide screening revealed a linkage of CMT2 to a locus at chromosome 12q24. CONCLUSION: The results are consistent with the diagnosis of CMT2. This family represents a rare genetic type of CMT2 which can be designated as CMT2L.

[Cloning of differentially displayed cDNAs involved in NaF-treated osteoblasts].

OBJECTIVE: To explore the effects of excessive fluoride on the gene expression of rat osteoblasts. METHODS: Rat osteoblasts were treated with 2.0 mmol/L of sodium fluoride (NaF) for two weeks in vitro, and difference in the gene expression between the NaF-treated and normal osteoblasts was compared with mRNA differential display (DD-PCR) technique. RESULTS: Among the six differentially expressed gene fragments which had been cloned, expression of the ribosomal protein L5 gene, ATPase Na(+)K(+) transporting beta polypeptide 3 gene, karyopherin alpha 2 gene and cis-Golgi body p28 gene was lower and expression of ubiquitous-conjugating enzyme E2D 3 gene and a newly-discovered gene fragment in this study showed up-regulated in the NaF-treated osteoblasts of the rats. CONCLUSIONS: Expression of genes changed in the osteoblasts after treatment with fluoride for two weeks and most of them associated with synthesis, transportation and processing of protein. It suggested that excessive fluoride could affect the protein synthesis in osteoblasts by changing the expression of the related genes. A novel gene related to excessive fluoride exposure was also found.

Compatibility of olfactory ensheathing cells with functionalized self-assembling peptide scaffold in vitro.

BACKGROUND: Olfactory ensheathing cell (OEC) transplantation is a promising or potential therapy for spinal cord injury (SCI). However, the effects of injecting OECs directly into SCI site have been limited and unsatisfied due to the complexity of SCI. To improve the outcome, proper biomaterials are thought to be helpful since these materials would allow the cells to grow three-dimensionally and guide cell migration. METHODS: In this study, we made a new peptide hydrogel scaffold named GRGDSPmx by mixing the pure RADA16 and designer peptide RADA16-GRGDSP solution, and we examined the molecular integration of the mixed nanofiber scaffolds using atomic force microscopy. In addition, we have studied the behavior of OECs in GRGDSPmx condition as well as on RADA16 scaffold by analyzing their phenotypes including cell proliferation, apoptosis, survival, and morphology. RESULTS: The experimental results showed that GRGDSPmx could be self-assembled to form a hydrogel. Inverted optical microscopic and scanning electron microscopic analyses showed that OECs are viable and they proliferate within the nanostructured environment of the scaffold. Thiazolyl blue (MTT) assay demonstrated that OEC proliferation rate was increased on GRGDSPmx scaffold compared with the pure RADA16 scaffold. In addition, OECs on GRGDSPmx scaffolds also showed less apoptosis and maintained the original spindle-shaped morphology. Calcein-AM/PI fluorescence staining revealed that OECs cultured on GRGDSPmx grew well and the viable cell count was 95%. CONCLUSION: These results suggested that this new hydrogel scaffold provided an ideal substrate for OEC three-dimensional culture and suggested its further application for SCI repair.

One-stage anterior release and reduction with posterior fusion for treatment of irreducible atlantoaxial dislocation.

OBJECTIVE: To analyze the approach and feasibility of one-stage anterior release and reduction with posterior fusion for irreducible atlantoaxial dislocation. METHODS: Ten male and 6 female patients, with an average age of 36 years, including 13 patients with old trauma, 2 with rheumatoid disease, and 1 with os odontoideum were studied. Anterior release and reduction was performed in the supine position. The atlas and vertebra dentate were fixed posteriorly and fused by one stage. RESULTS: All patients were followed up from 15 to 40 months (mean, 23 months), and all gained anatomic reduction and bone fusion. Six months postoperatively, the Japanese Orthopaedic Association (JOA) score of the 12 patients with cord symptoms had improved from 8.3 preoperatively to 13.9, with a mean improvement of 87.5%. CONCLUSION: Treatment of irreducible atlantoaxial dislocation with one-stage anterior release and reduction with posterior fusion is a reliable method.

[Free anterolateral thigh flap for repairing the defects of oral cavity and maxillofacial].

OBJECTIVE: To investigate the outcomes following the tumor resection of oral cavity and maxillofacial and reconstruction with free anterolateral thigh flaps (ALT). METHODS: Thirty one patients underwent ALT reconstruction following the tumor resection from Dec. 2004 to Dec. 2005. Among them, 17 cases were squamous cell carcinoma (SCC) of tongue, 6 cases of buccal SCC and 8 other malignant. The size of the ALT flaps ranged from 4 to 8 cm in width and 6 to 23 cm in length. Tracheotomy were performed for 4 cases intraoperatively. RESULTS: The overall successful rate was 96.8%. Thirty cases survival no cancer, 1 case died of recurrent and no-controlled of lymph-node in 8 months after operation. Postoperative vessel thrombosis occurred in 3 flaps between 12 hours to 4 days after operation. Two of them were saved. The necrosis area of the third flap was 25%. CONCLUSIONS: The ALT was benefit to repair the defects of oral cavity and maxillofacial, and the donor place was more easily hidden and didn't not influence the outlook and function; the important normal functional framing such as teeth and bone should be preserved; the pedicle of vessel could't be twisted during the procedure of reconstruction to avoid vein oppressed; the size of flap should be suitable to defects in order to avoid flaps being crowd and blood clot; tracheotomy was safe while repairing the defect of hard and soft palate. Reconstructive surgical procedures;