Significance of phosphate adsorbed on the cellular surface as a storage pool and its regulation in marine microalgae.

The increasing prevalence of phosphorus limitation in coastal waters has drawn attention to the bioavailability of cellular surface-adsorbed phosphorus (SP) as a reservoir of phosphorus in phytoplankton. This study examined the storage, utilization, and regulation of SP in the coastal waters of the East China Sea, as well as three cultivated algal bloom species (Skeletonema marinoi, Prorocentrum shikokuense, and Karenia mikimotoi) prevalent in the area. SP accounted for 14.3%-45.5% of particulate phosphorus in the field and laboratory species. After the depletion of external phosphate, the studied species can rapidly transport SP within 3-24 h. The storage of SP is regulated by both external phosphate conditions and the internal growth stage of cells, but it is not influenced by the various cellular surface structures of the studied species. This study highlights the significance of SP as a crucial phosphorus reservoir and the potential use of the SP level as an indicator of phosphorus deficiency in phytoplankton.

Formation mechanism and environmental drivers of Alexandrium catenella bloom events in the coastal waters of Qinhuangdao, China.

In the last 5 years, paralytic shellfish toxins (PSTs) have been recurrently detected in mollusks farmed in the mussel culture area of Qinhuangdao city, along with the occurrence of toxic outbreaks linked to dinoflagellate species of the Alexandrium genus. To understand the formation mechanism and variation of these events, continuous and comprehensive PSTs monitoring was carried out between 2017 and 2020. Through the analysis of both phytoplankton and cysts via light microscopy and quantitative polymerase chain reaction, it was shown that Alexandrium catenella was responsible for the production of PSTs, which consisted mainly of gonyautoxins 1,4 (GTX1/4, 87%) and GTX2/3 (13%). During bloom events in 2019, mussels accumulated the highest PSTs value (929 µg STX di-HCl eq·kg-1) in conjunction with the peak of cell abundances, and toxin profiles were consistent with high distributions of GTX1/4, GTX2/3, and Neosaxitoxin. Toxin metabolites vary in different substances and mainly transferred to a stable proportion of α-epimer: ß-epimers 3:1. The environmental drivers of Alexandrium blooms included the continuous rise of water temperature (>4 °C) and calm weather with low wind speed and no significant precipitation. By comparing toxin profiles and method sensitivity, it was found that dissolved toxins in seawater are more useful for early warning. These results have important implications for the effective monitoring and management of paralytic shellfish poisoning outbreaks.

Proposal for modified inguinofemoral lymphadenectomy derived from investigation of anatomic distribution of sentinel and metastatic nodes in vulvar cancer.

OBJECTIVE: We aimed to develop a less invasive inguinofemoral lymphadenectomy (IFL) approach for vulvar cancer based on the investigation of the anatomic distribution of sentinel and metastatic nodes. METHODS: Patients with vulvar cancer treated by surgery between 1995 and 2019 were retrospectively reviewed. A seven-field method was adopted to assign the anatomic locations for lymph nodes removed via IFL or sentinel node biopsy. Only patients with nodal metastasis or sentinel nodes were included. RESULTS: A total of 102 patients with eligible data were analyzed. Nodal metastasis was confirmed in 118 groins undergoing IFL; sentinel node detection succeeded in 46 groins. The medial-inguinal field had the highest rate of nodal metastasis involvement (59.3%, 70/118) and sentinel nodes present (73.9%, 34/46). The inferior-femoral field was involved only in one groin with quadruple-field metastases. The lateral-inguinal field was not involved in any groin. Neither the lateral-inguinal nor the inferior-femoral field presented sentinel nodes. CONCLUSION: The lateral-inguinal and inferior-femoral fields of the groins have a low risk of developing nodal metastasis. Therefore, a modified IFL preserving these fields can be established to reduce surgical morbidity without sacrificing its therapeutic effect.

Sectioning protocol determines accuracy of intraoperative pathological examination of sentinel lymph node in cervical cancer: A systematic review and meta-analysis.

OBJECTIVES: To determine the diagnostic performance and optimal protocol of frozen section examination (FSE) in SLNB for cervical cancer. METHODS: PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure were searched from inception to July 30, 2019, for studies concerning SLNB with FSE in cervical cancer. Sensitivity of FSE in detecting SLN metastasis was the primary diagnostic indicator for evaluation. RESULTS: The pooled sensitivity of FSE among 31 eligible studies (1887 patients) was 0.77 (95% CI 0.66-0.85) with high heterogeneity (I2 = 69.73%). Two representative sectioning protocols for FSE were identified from 26 studies, described as equatorial (E-protocol, SLN was bisected) and latitudinal (L-protocol, SLN was cut at intervals). Meta-regression showed that FSE protocol was the only source of heterogeneity (p < 0.001). The pooled sensitivity was 0.86 (95% CI 0.79-0.91, I2 = 0%) and 0.59 (0.46-0.72, I2 = 58.47%) for FSE using L- (13 studies, 650 patients) and E- (13 studies, 1047 patients) protocol, respectively. Among the available data, marcometastases (>2 mm) were missed in 4 and 20 patients; small-volume metastases (≤2 mm) were detected in 13 and 2 patients, respectively, under L- and E-protocol. The pooled sensitivity of FSE using L-protocol would reach 0.97 (95% CI 0.89-0.99) if only marcometastases were considered. These findings were robust to sensitivity analyses. CONCLUSION: The sectioning protocol determines the accuracy of FSE in SLNB. With L-protocol, FSE can provide precise intraoperative pathology for SLNB, which enables immediate decision-making for individualized managements.

Computed tomography-guided radiofrequency ablation combined with transarterial embolization assisted by a three-dimensional visualization ablation planning system for hepatocellular carcinoma in challenging locations: a preliminary study.

OBJECTIVE: To assess the clinical efficacy and safety of computed tomography-guided radiofrequency ablation(CT-RFA) combined with transarterial embolization(TAE) assisted by a three-dimensional visualization ablation planning system(3DVAPS) for hepatocellular carcinoma(HCC) in challenging locations. METHODS: Data from 62 treatment-naive patients with hepatocellular carcinoma(HCC), with 83 lesions in challenging locations, and who met the Milan criteria and underwent CT-RFA between June 2013 and June 2016 were reviewed. Patients were divided into one of two groups according to different treatment modalities: study group (TAE combined with RFA assisted by 3DVAPS [n = 32]); and control (RFA only [n = 30]). Oncological outcomes included ablation-related complications, local tumor progression (LTP), and overall survival (OS). Univariate and multivariate Cox proportional hazards regression analyses were performed to assess risk factors associated with LTP and OS. RESULTS: HCC lesions (mean size, 1.9 ± 1.0 mm in diameter) abutting the gastrointestinal tract (n = 25), heart and diaphragm (n = 21), major vessels (n = 13), and gallbladder (n = 3) were treated. A significant difference was detected in LTP between the two groups (P = 0.034), with no significant difference in OS between the two groups (P = 0.193). There were no severe complications related to ablation. Univariate analysis revealed that sex (P = 0.046) and child-turcotte-pugh (CTP) grade (P<0.001) were risk factors for OS, whereas CTP grade and treatment method (P<0.001) were risk factors for LTP. Multivariate analysis revealed that CTP grade B (P = 0.005) was independently associated with poor OS, and RFA alone (P<0.001) was independently associated with poor LTP. CONCLUSION: CT-RFA combined with TAE assisted by a 3DVAPS provided ideal clinical efficiency for HCC in challenging locations and was a highly safe treatment modality.

Combined score of pretreatment platelet count and CA125 level (PLT-CA125) stratified prognosis in patients with FIGO stage IV epithelial ovarian cancer.

BACKGROUND: The majority of death-related ovarian cancer is epithelial ovarian cancer (EOC). Regarding the Federation of Gynecology and Obstetrics (FIGO) stage IV EOC, the 5-year overall survival (OS) has not changed in last decades. Platelet (PLT) count and CA125 level are both prognostic markers that related to inflammation and immune evasion in EOC. This study intended to assess the prognostic value of pretreatment PLT count and CA125 level in FIGO stage IV EOC. METHODS: The study included 108 patients diagnosed with FIGO stage IV EOC and treated with surgery and/or chemotherapy between January 1995 and December 2016. The PLT counts and CA125 levels of the patients before any treatment were analysed with clinical and pathological parameters, OS and progression-free survival (PFS). The survival of different groups was analyzed using the Kaplan-Meier method. The PLT-CA125 scores (0, 1, and 2) were defined basing on the presence of thrombocytosis (PLT count > 400,000/µL), an elevated CA125 level (CA125 > 1200 U/mL), or both. The prognostic value of PLT-CA125 was assessed with a Cox regression model. RESULTS: Median OS, but not median PFS, was significantly decreased in patients with thrombocytosis or elevated CA125 levels when compared with the others (p = 0.011 & p = 0.004). The median OS was significantly decreased in patients with a PLT-CA125 score of 2 [37.8 months; 95% confidence interval (CI) 20.6-54.9] compared with patients with a PLT-CA125 score of 0 (70.0 moths, 95% CI 38.0-101.9, p < 0.001). The median PFS was also significantly decreased in patients with a PLT-CA125 score of 2 (19.6 months; 95% CI 13.0-26.3) compared with patients with a PLT-CA125 score of 0 (32.0 months; 95% CI 23.3-40.7, p = 0.011). Furthermore, multivariate analysis identified both PLT-CA125 scores of 2 and 1 as independent poor prognostic factors for OS (p = 0.004 & p < 0.001) and PFS (p = 0.033 & p = 0.017) compared with a PLT-CA125 score of 0. CONCLUSIONS: The pretreatment PLT-CA125 score can be a reliable marker with high accessibility for stratifying prognosis in patients with FIGO stage IV EOC.

Phycotoxins in scallops (Patinopecten yessoensis) in relation to source, composition and temporal variation of phytoplankton and cysts in North Yellow Sea, China.

The North Yellow Sea is a major aquaculture production area for the scallop Patinopecten yessoensis. In this study, the temporal and spatial variation of phycotoxins in scallops, phytoplankton, and their cysts were analyzed during a survey conducted from June 2011 to April 2012 around Zhangzi Island. The study area is a semi-enclosed epicontinental sea surrounded by the Shandong Peninsula, the Liaodong Peninsula and the Korean Peninsula. The three main results of the study were as follows: (1) The saxitoxin-group toxins, okadaic acid and analogues, and pectenotoxins were the major phycotoxin residues found in scallops; (2) Six kinds of toxic microalgae were identified, Protoperidinium spp., Gonyaulax spp., and Alexandrium spp. were the dominant taxa; Seven types of potential marine toxin-producing dinoflagellates, A. tamarense, A. catenella, Dinophysis fortii, G. catenatum, Gambierdiscus toxicus, Azadinium poporum, and Pseudo-nitzschia pungen were identified as the primary source of phycotoxins and were present at relatively high density from June to October; and (3) azaspiracids and domoic acid might be new potential sources of toxin pollution. This study represents the first assessment to phycotoxins around Zhangzi Island in the North Yellow Sea.

Comparison of the effect of radiation exposure from dual-energy CT versus single-energy CT on double-strand breaks at CT pulmonary angiography.

PURPOSE: To compare the effect of dual-source dual-energy CT versus single-energy CT on DNA double-strand breaks (DSBs) in blood lymphocytes at CT pulmonary angiography (CTPA). METHODS AND MATERIALS: Sixty-two patients underwent either dual-energy CTPA (Group 1: n = 21, 80/Sn140 kVp, 89/38 mAs; Group 2: n = 20, 100/Sn140 kVp, 89/76 mAs) or single-energy CTPA (Group 3: n = 21, 120 kVp, 110 mAs). Blood samples were obtained before and 5 min after CTPA. DSBs were assessed with fluorescence microscopy and Kruskal-Walls tests were used to compare DSBs levels among groups. Volume CT dose index (CTDIvol), dose length product (DLP) and organ radiation dose were compared using ANOVA. RESULTS: There were increased excess DSB foci per lymphocyte 5 min after CTPA examinations in three groups (Group 1: P = .001; Group 2: P = .001; Group 3: P = .006). There were no differences among groups regarding excess DSB foci/cell and percentage of excess DSBs (Group 1, 23%; Group 2, 24%; Group 3, 20%; P = .932). CTDIvol, DLP and organ radiation dose in Group 1 were the lowest among the groups (all P < .001). CONCLUSION: DSB is increased following dual-source and single-source CTPA, while dual-source dual-energy CT protocols do not increase the estimated radiation dose and also do not result in a higher incidence of DNA DSBs in patients undergoing CTPA.

The Bidirectional Regulation between MYL5 and HIF-1α Promotes Cervical Carcinoma Metastasis.

Myosin light chains (MLC) serve important regulatory functions in a wide range of cellular and physiological processes. Recent research found that MLC are also chromatin-associated nuclear proteins which regulate gene transcription. In this study, the MLC member myosin regulatory light chain 5 (MYL5) expression was upregulated in late stage cervical cancer patients, positively correlated with pelvic lymph node metastasis, and identified as a poor survival indicator. MYL5 overexpression promoted metastasis in cervical cancer in vitro and in vivo models, whereas MYL5 silencing had the converse effect. We demonstrated a bidirectional regulation between MYL5 and hypoxia inducible factor-1α (HIF-1α). HIF-1α activates MYL5 via binding to the hypoxia response element (HRE) in the promoter of MYL5, and MYL5 could sustain HIF-1α expression by tethering to recognition sequence AGCTCC in the HIF-1α promoter region. Clinical data confirmed a positive correlation between MYL5 and HIF-1α. In summary, our data show that MYL5 may act as a prognosis predictive factor in cervical carcinoma, and strategies that inhibit the interaction of MYL5 and HIF-1α may benefit the cervical carcinoma patients with metastasis.

Exosomes containing differential expression of microRNA and mRNA in osteosarcoma that can predict response to chemotherapy.

A major challenge in osteosarcoma (OS) is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent. We developed a profiling strategy for serum exosomal microRNAs and mRNAs in OS patients with differential chemotherapeutic responses. Twelve miRNAs were up regulated and 18 miRNAs were under regulated significantly in OS patient with poor chemotherapeutic response when compared with those in good chemotherapeutic response (p<0.05). In addition, miR-124, miR133a, miR-199a-3p, and miR-385 were validated and significantly reduced in poorly responded patients with an independent OS cohort. While miR-135b, miR-148a, miR-27a, and miR-9 were significantly over expressed in serum exosomes. Bioinformatic analysis by DIANA-mirPath demonstrated that Proteoglycans in cancer, Hippo signaling pathway, Pathways in cancer, Transcriptional misregulation in cancer, PI3K-Akt signaling pathway, Ras signaling pathway, Ubiquitin mediated proteolysis, Choline metabolism in cancer were the most prominent pathways enriched in quantiles with the miRNA patterns related to poor chemotherapeutic response. Messenger RNAs(mRNAs) includingAnnexin2, Smad2, Methylthioadenosine phosphorylase (MTAP), Cdc42-interacting protein 4 (CIP4), Pigment Epithelium-Derived Factor (PEDF), WW domain-containing oxidoreductase (WWOX), Cell division cycle 5-like (Cdc5L), P27 were differentially expressed in exosomes in OS patients with different chemotherapeutic response. These data demonstrated that exosomal RNA molecules are reliable biomarkers in classifying osteosarcoma with different chemotherapy sensitivity.

Radiation Optimized Dual-source Dual-energy Computed Tomography Pulmonary Angiography: Intra-individual and Inter-individual Comparison.

OBJECTIVES: This study aimed to intra-individually and inter-individually compare image quality, radiation dose, and diagnostic accuracy of dual-source dual-energy computed tomography pulmonary angiography (CTPA) protocols in patients with suspected pulmonary embolism (PE). METHODS: Thirty-three patients with suspected PE underwent initial and follow-up dual-energy CTPA at 80/Sn140 kVp (group A) or 100/Sn140 kVp (group B), which were assigned based on tube voltages. Subjective and objective CTPA image quality and lung perfusion map image quality were evaluated. Diagnostic accuracies of CTPA and perfusion maps were assessed by two radiologists independently. Effective dose (ED) was calculated and compared. RESULTS: Mean computed tomography (CT) values of pulmonary arteries were higher in group A than group B (P = .006). There was no difference in signal-to-noise ratio and contrast-to-noise ratio between the two groups (both P > .05). Interobserver agreement for evaluating subjective image quality of CTPA and color-coded perfusion images was either good (κ = 0.784) or excellent (κ = 0.887). Perfusion defect scores and diagnostic accuracy of CTPA showed no difference between both groups (both P > .05). Effective dose of group A was reduced by 45.8% compared to group B (P < .001). CONCLUSIONS: Second-generation dual-source dual-energy CTPA with 80/Sn140 kVp allows for sufficient image quality and diagnostic accuracy for detecting PE while substantially reducing radiation dose.

Clinical Outcomes of Coronary Artery Bypass Grafting vs Percutaneous Coronary Intervention in Octogenarians With Coronary Artery Disease.

BACKGROUND: The number of elderly people receiving treatment for coronary artery disease (CAD) is increasing, and there are few studies that compared the outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in the elderly. The objective of this study was to compare outcomes of CABG and PCI in octogenarians with CAD. METHODS: We conducted a search to identify articles that reported the results of 2-arm studies that compared CABG with PCI in octogenarians. The primary outcomes were short-term mortality and overall survival, and secondary outcomes included length of hospital stay and cerebrovascular accident (CVA) and myocardial infarction (MI) rates. RESULTS: Seven studies that enrolled 1879 patients who received CABG and 1432 treated with PCI were included. Short-term mortality was significantly less for patients in the PCI arms (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.05-2.06; P = 0.02), as was duration of hospital stay (difference in means, 6.07; 95% CI, 2.81-9.34; P < 0.001). Patients in the CABG arms had longer overall survival (hazard ratio, 0.81; 95% CI, 0.73-0.89; P < 0.001). CVA and MI rates were similar (CVA: OR, 1.06; 95% CI, 0.57-1.95; P = 0.86; MI: OR, 0.70; 95% CI, 0.42-1.17; P = 0.17). CONCLUSIONS: The results suggest that physicians should consider not only the clinical features of CAD, but also the elderly patients future health outlook when choosing a revascularization procedure.

Efficacy and Safety of Denosumab in Postmenopausal Women With Osteoporosis: A Meta-Analysis.

The purpose of this study was to perform a meta-analysis to examine the efficacy and safety of denosumab in postmenopausal women with osteoporosis.Medline, Cochrane Library, EMBASE, and Google Scholar databases were searched until October 30, 2014 using combinations of the following search terms: osteoporosis, postmenopause, postmenopausal, women, denosumab. The primary outcome was bone mineral density (BMD) change, and secondary outcomes were change in the bone turnover markers ß-isomerized carboxy-terminal cross-linking telopeptide of type I collagen (CTX) and serum procollagen type I amino-terminal propeptide (P1NP), and adverse events.Patients treated with denosumab had significantly increased BMD of the lumbar spine (7.58%), total hip (4.86%), and distal third of the radius (2.92%) than those treated with placebo (all, P < 0.001). Patients treated with denosumab had a significant decrease of CTX (-66.16%) and P1NP (-64.65%) as compared with those treated with placebo (both, P < 0.001). Adverse events were similar between the 2 groups (pooled odds ratio = 1.04, P = 0.625).Denosumab increases BMD and decreases markers of bone turnover in postmenopausal women with osteoporosis, and is not associated with significant side-effects.

Altered microRNA expression profile in synovial fluid from patients with knee osteoarthritis with treatment of hyaluronic acid.

OBJECTIVE: The aim of this study was to investigate the microRNA (miRNA) expression pattern in synovial fluid from patients with knee osteoarthritis (OA) after treatment with intra-articular injection of hyaluronan (HA). METHODS: Twelve OA patients were enrolled in accordance with the Kellgren-Lawrence classification of knee OA. All patients received intra-articular injection of HA once a week for 5 weeks and were evaluated with the Western Ontario and McMaster Universities (WOMAC) index at baseline. TaqMan miRNA assay profiling was performed on synovial fluid RNAs extracted from OA patients pre-injection and after 5 weeks of treatment with HA. Validation was performed using independent samples, including ten healthy controls and ten matched OA patients. RESULTS: Forty-three miRNAs (21 overexpressed miRNAs and 22 underexpressed miRNAs) were differentially expressed in OA patients before and after treatment with HA (P < 0.05, false discovery rate corrected). Further bioinformatics prediction by mirPath indicated that the differential miRNA signatures in synovial fluid extracted from the OA patients demonstrated primarily upregulation of the PI3K-Akt signaling pathway, mitogen-activated protein kinase signaling pathway, regulation of autophagy, mRNA surveillance pathway, and B cell receptor signaling pathway. In addition, TaqMan real-time reverse transcription polymerase chain reaction was performed for validation on miR-146a, miR-155, let-7a, miR-181a, miR-454, and let-7b, which were significantly changed in abundance, using an independent cohort of ten healthy controls and ten OA patients as compared with those with intra-articular injection of HA. CONCLUSION: Our results demonstrated that dysregulation in miRNAs in synovial fluid from OA patients and their affected biologic cellular processes might play important role in OA pathogenesis and HA-mediated therapeutics.

[Case-control study on superior labrum from anterior to posterior repair and biceps tenodesis for the treatment of type II SLAP injury].

OBJECTIVE: To compare clinical outcomes of superior labrum from anterior to posterior (SLAP) repair and biceps tenodesis in treating type I SLAP injury. METHODS: From March 2009 to March 2012, 38 patients with type II SLAP injury were treated with SLAP repair and biceps tenodesis, and all patients were unilateral SLAP injury. Sixteen patients treated with biceps tenodesis included 8 males and 7 females with an average age of (49.3±3.7) years old (ranged, 45 to 54); 10 cases were on the left side and 6 cases on the right side; 10 cases were caused by falling down, 2 cases were caused by throwing damage and 4 cases were caused by daily life damage; the time from injury to operation were from 3 to 8 weeks. Twenty-two patients treated with SLAP repair included 14 males and 8 females with an average age of (49.0±2.8) years old (ranged, 44 to 56); 13 cases were on the left side and 9 cases were on the right side; 14 cases were caused by falling down, 5 cases were caused by throwing damage and 3 cases were caused by daily life damage; the time from injury to operation were from 3 to 7 weeks. Preoperative, postoperative at 6 months, 1 year and 2 years' UCLA and SST score were compared between two groups. RESULTS: There was no significant differences in UCLA and SST score between two groups before operation. At 6 months after operation, UCLA and SST score in biceps tenodesis group was higher than SLAP group, and action,range of anteflexion, strength of anteflexion, degree of satisfaction in biceps tenodesis group was higher than SLAP group. There was no significant meaning in SST and UCLA score between two groups at 1 and 2 years after operation. CONCLUSION: Short-term efficacy of biceps tenodesis for SLAP injury is better than SLAP repair, but long-term efficacy is fairly.

CD47 blockade inhibits tumor progression human osteosarcoma in xenograft models.

Osteosarcoma is the most common bone tumors in children and adolescents. Despite intensive chemotherapy, patients with advanced disease still have a poor prognosis, illustrating the need for alternative therapies. In this study, we explored the use of antibodies that block CD47 with a tumor growth suppressive effect on osteosarcoma. We first found that up-regulation of CD47 mRNA levels in the tumorous tissues from eight patients with osteosarcoma when compared with that in adjacent non-tumorous tissues. Further western-blot (WB) and immunohistochemistry (IHC) demonstrated that CD47 protein level was highly expressed in osteosarcoma compared to normal osteoblastic cells and adjacent non-tumorous tissues. Osteosarcoma cancer stem cell markers staining shown that the majority of CD44+ cells expressed CD47 albeit with different percentages (ranging from 80% to 99%). Furthermore, high CD47 mRNA expression levels were associated with a decreased probability of progression-free and overall survival. In addition, blockade of CD47 by specific Abs suppresses the invasive ability of osteosarcoma tumor cells and further inhibits spontaneous pulmonary metastasis of KRIB osteosarcoma cells in vivo. Finally, CD47 blockade increases macrophage phagocytosis of osteosarcoma tumor cells.In conclusion, our findings demonstrate that CD47 is a critical regulator in the metastasis of osteosarcoma and suggest that targeted inhibition of this antigen by anti-CD47 may be a novel immunotherapeutic approach in the management of this tumor.

Association of GPR126 gene polymorphism with adolescent idiopathic scoliosis in Chinese populations.

Idiopathic scoliosis is the most common pediatric spinal deformity affecting 1% to 3% of the population, and adolescent idiopathic scoliosis (AIS) accounts for approximately 80% of these cases; however, the etiology and pathogenesis of AIS are still uncertain. The current study aims to identify the relationship between G protein-coupled receptor 126 (GPR126) gene and AIS predisposition, to identify the relationship between the genotypes of the GPR126 SNPs and the clinical phenotypes of AIS. We conducted a case-control study and genotyped twenty SNPs of GPR126 gene including ten exonic SNPs and ten intronic polymorphisms in 352 Chinese sporadic AIS patients and 149 healthy controls. We provided evidence for strong association of three intronic SNPs of the GPR126 gene with AIS susceptibility: rs6570507 A > G (p =0 .0035, OR = 1.729), rs7774095 A > C (p = 0.0078, OR = 1.687), and rs7755109 A > G (p = 0.0078, OR = 1.687). However, we did not identify any significant association between ten exonic SNPs of GPR126 and AIS. Linkage disequilibrium analysis indicated that rs7774095 A > C and rs7755109 A > G could be parsed into one block. The association between the intronic haplotype and AIS was further confirmed in an independent population with 110 AIS individuals and 130 healthy controls (p = 0.046, OR = 1.680). Furthermore, molecular mechanisms underlying intronic SNP regulation of GPR126 gene were studied. Although intronic SNPs associated with AIS didn't influence GPR126 mRNA alternative splicing, there was a strong association of rs7755109 A > G with decreased GPR126 mRNA level and protein levels. Our findings indicate that genetic variants of GPR126 gene are associated with AIS susceptibility in Chinese populations. The genetic association of GPR126 gene and AIS might provide valuable insights into the pathogenesis of adolescent idiopathic scoliosis.

Altered microRNA expression profile in exosomes during osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.

The physiological role of microRNAs (miRNAs) in osteoblast differentiation remains elusive. Exosomal miRNAs isolated from human bone marrow-derived mesenchymal stem cells (BMSCs) culture were profiled using miRNA arrays containing probes for 894 human matured miRNAs. Seventy-nine miRNAs (∼8.84%) could be detected in exosomes isolated from BMSC culture supernatants when normalized to endogenous control genes RNU44. Among them, nine exosomal miRNAs were up regulated and 4 miRNAs were under regulated significantly (Relative fold>2, p<0.05) when compared with the values at 0 day with maximum changes at 1 to 7 days. Five miRNAs (miR-199b, miR-218, miR-148a, miR-135b, and miR-221) were further validated and differentially expressed in the individual exosomal samples from hBMSCs cultured at different time points. Bioinformatic analysis by DIANA-mirPath demonstrated that RNA degradation, mRNA surveillance pathway, Wnt signaling pathway, RNA transport were the most prominent pathways enriched in quantiles with differential exosomal miRNA patterns related to osteogenic differentiation. These data demonstrated exosomal miRNA is a regulator of osteoblast differentiation.

Molecular phylogeny and PSP toxin profile of the Alexandrium tamarense species complex along the coast of China.

To explore the genetic diversity and paralytic shellfish poisoning (PSP) toxin profile of the Alexandrium tamarense species complex along the coast of China, 67 strains of A. tamarense from the China Sea were collected and genetic diversity were analyzed based on the rDNA sequences. In addition, PSP toxin compositions and contents were detected by HPLC. According to the 5.8S rDNA and ITS, and LSU rDNA D1-D2 sequence, A. tamarense in the China Sea comprises at least Group IV and Group I ribotypes. In these Chinese strains, the toxins with the highest concentration in the profile were C1/2, gonyautoxins 1/4 (GTX1/4) and neosaxitoxin (NEO). However, the toxin profiles were atypical and C1/2 toxins were not detected in some strains. No strict correlation was observed between the PSP toxins profile and the geographical distribution.