Megafossils of Betulaceae from the Oligocene of Qaidam Basin and their paleoenvironmental and phytogeographic implications.

Understanding the paleoenvironment and phytogeographical history of the Tibetan Plateau, China relies on discovering new plant fossils. The Qaidam Basin has long been regarded as an ideal 'field laboratory' to investigate the paleoclimate and paleobiological evolution of the northern Tibetan Plateau. However, fossil angiosperms from the Qaidam Basin are rare, and our knowledge of its paleovegetation is poor. Here, we report fossil leaves and fruits of Betulaceae found from the Oligocene Shangganchaigou Formation of northwestern Qaidam Basin (Huatugou area). Comparative morphological analysis led us to assign the fruits to the Betula subgenus Betula and the leaves to Carpinus grandis. These findings, together with other reported fossil plants from the same locality, reveal a close floristic linkage between the Qaidam Basin and Europe during the Oligocene. The northern pathway of this floristic exchange may have crossed through the Qaidam Basin during the late Paleogene. This floristic linkage may have been facilitated by the continuous narrowing of the Turgai Strait and stronger westerlies, which transported moisture and provided favorable climatic conditions. Indeed, fossil plants collected from the Qaidam Basin suggest that during the Oligocene this region had warm and humid deciduous broad-leaf forest, which differs from the region's modern vegetation and indicates that the Qaidam Basin may have been a suitable region for these plants to flourish and spread during the Oligocene.

Role of Perforating Artery Pedicled Neurotrophic Flap in the Treatment of Compound Tissue Defect of Tibia Using the Ilizarov Technique.

OBJECTIVE: To describe our experience with the combined use of pedicled neurotrophic flap and distraction osteogenesis in the management of complex lower extremity injuries with composite bone and soft tissue defects and assess the functional and cosmetic results of this method. METHODS: A pedicled flap with a marked perforator artery was applied for soft tissue coverage after radical debridement and temporary external fixation. In the second stage, the Ilizarov external fixator was used in place of the temporary external fixator for reconstruction of the segmental bone defect by distraction osteogenesis. Twenty-five patients (16 men and nine women; mean age, 39.2 years) were treated by using this combined technique between 2008 and 2016. All cases were graded initially as Gustilo-Anderson grade IIIB open fractures. The soft tissue defect after radical debridement ranged from 9 cm × 5 cm to 14 cm × 11 cm, and the average size of segmental defect was 5.2 (Range, 2.5-8.5) cm. Seventeen of these patients had a history of local infection. The bone structure and function were evaluated by two independent evaluators using Paley's criteria. RESULTS: Twenty-five patients were followed up for an average of 28.96 (Range, 15-48) months. The distally based sural neurovascular flap was applied in 13 patients, and the greater saphenous neurocutaneous perforator flap in 12 patients. The flap area ranged from 10 cm × 5 cm to 14 cm × 12 cm. Sufficient coverage of soft tissue defect was achieved in all cases. All flaps survived completely without complications. The bone defects were corrected by a mean lengthening of 6.94 (Range, 4.5-9.5) cm. The residual discrepancy was <1 cm in all cases, which was not clinically significant. The function was evaluated as excellent in 12 patients and good in 13 patients. Bone results were graded as excellent in 18 patients and good in seven patients. Complications during treatment included pain, pin tract infections, ankle midfoot joint stiffness, and docking site nonunion. No recurrence of infection was observed in infected patients. All cases achieved successful limb salvage and satisfactory function recovery without recurrence of infection. CONCLUSIONS: The combined technique of a perforator artery pedicled neurotrophic flap and distraction osteogenesis is an effective alternative approach in the salvage treatment of massively traumatized and chronically infected lower extremities.

Synthesis and fungicidal activity of phenazine-1-carboxylic triazole derivatives.

A total of 15 novel-substituted 3-(benzylsulfanyl)-1H-1,2,4-triazol-5-ylamine and 10 novel-substituted 3-benzylmercapto-1,2,4-triazol derivatives were synthesized based on the natural product phenazine-1-carboxylic acid (PCA). Their structures were confirmed by 1H-NMR, 13C-NMR, HRMS, and X-ray. Most substituted 3-benzylmercapto-1,2,4-triazol derivatives displayed very strong fungicidal activity against one or multiple plant pathogens in vitro and in vivo. Compounds 8b, 8h, and 8i showed a broad spectrum of fungicidal activity. Further field experiments indicated that compounds 8b, 8c, and 8h displayed better efficacy against rice blast (Pyricularia oryzae) than PCA. These data demonstrate that compounds 8b, 8c, and 8h are promising fungicidal candidates, deserving further studies.[Formula: see text].

Articular Cartilage Stem Cells Influence the Postoperative Repair of Hip Replacement by Regulating Endoplasmic Reticulum Stress in Chondrocytes via PERK Pathway.

OBJECTIVE: Endoplasmic reticulum stress (ERS) is present in chondrocytes of osteoarthritis, and the intensity of ERS is related to the degree of cartilage degeneration. In vitro intervention strategies can change the status of ERS and induce the inhibition of ERS-related pathway. Therefore, this study is designed to explore the role and molecular mechanism of cartilage stem cells (ACSCs) of ERS in chondrocytes after hip replacement. METHODS: Human cartilage cell lines C28/I2 were cultured as the control group. The ERS inducer was added into C28/I2 as ERS group. The third ERS + stem cells group was formed by adding cartilage stem cells into ERS group, and further transfection of si-PERK was defined as si-PERK + ERS + stem cells group. Cell cycle and apoptosis in the four groups were determined by flow cytometry. The protein expression of GRP78, PERK, ATF4, TMEM119, CDK4, Cyclin D, and BMP6 in chondrocytes in the four groups were investigated by western blot, and the distribution of PERK, TMEM119, and BMP6 in chondrocytes were observed by immunofluorescence assay. In addition, the transcriptional levels of Bcl2, Bax, and Caspase 3 were also determined by RT-PCR. RESULTS: In cell cycle assay, ERS increased the accumulation of cells in G0 /G1 and G2 /M, while cartilage stem cells weakened the effects. The apoptosis rates in control group, ERS, ERS + stem cells, si-PERK + ERS + stem cells were 0%, 21.3%, 18.9%, and 15.9%, respectively, and the difference of apoptosis rate between the latter three groups and control group was statistically significant (P < 0.01). Stem cells could weaken the ERS-induced cell apoptosis, especially reducing the number of cells in the late stage of apoptosis from 5.4% to 1.1%. The protein level of GRP78, PERK, ATF4, TMEM119, and BMP6 in the group of ERS, ERS + stem cells, and si-PERK + ERS + stem cells were all significantly higher than those in control group, and the group of ERS + stem cells was the highest, all of the differences were significant (P < 0.01). However, the protein level of CDK4 and Cyclin D presented an absolutely opposite trend and the difference was still significant (P < 0.05). The group of si-PERK + ERS + stem cell was lower than those in the group of ERS + stem cell but higher than those in the group of ERS (P < 0.05). The level of Caspase 3 in the latter three groups was significantly higher than those in the control group, and the group of ERS was the highest (P < 0.01). Besides, the relative level of Bcl-2/Bax in control group was 1, but the group of ERS was about 0.5, and there was significant difference (P < 0.01). The ratio of Bcl-2/Bax in the group of ERS + stem cells was more than 2 and significantly higher than those of other groups. CONCLUSION: ACSCs could reduce ERS-induced chondrocyte apoptosis by PERK and Bax/Bcl-2 signaling pathway.

A Novel lncRNA HOXC-AS3 Acts as a miR-3922-5p Sponge to Promote Breast Cancer Metastasis.

Purpose: The function of long noncoding RNAs (lncRNA) in breast cancer metastasis remains largely unknown. In this work, the role of HOXC-AS3 in breast cancer progression was investigated.Methods: By using Cancer Genome Atlas (TCGA) Database, we investigated the expression of HOXC-AS3 in breast cancer and explored the association between HOXC-AS3 expression and prognosis. Then, we studied the biological function of HOXC-AS3 in cell migration and invasion both in vitro and in vivo. Furthermore, the target miRNA of HOXC-AS3, and the target mRNA of miR-3922-5p were proved.Results: HOXC-AS3 is aberrantly overexpressed in breast cancers especially the HER2+ type. Moreover, high expression of HOXC-AS3 has a relationship with poor clinical outcomes of breast cancer. In addition, HOXC-AS3 regulates cell Invasion and migration both in vitro and in vivo. Our results demonstrated that miR-3922-5p was a direct target of HOXC-AS3, and PPP1R1A was a target of miR-3922-5p in breast cancer.Conclusions: The novel lncRNA HOXC-AS3 acts as a miR-3922-5p sponge to upregulate PPP1R1A protein expression, and thus results in promoting breast cancer metastasis. HOXC-AS3 could be a novel therapeutic target for breast cancer therapeutics.

Long non-coding RNA BRAF-regulated lncRNA 1 promotes lymph node invasion, metastasis and proliferation, and predicts poor prognosis in breast cancer.

Long non-coding RNAs (lncRNAs) are primary regulators of cancer development via their involvement in almost every aspect of cell biology. Recent studies have indicated that lncRNAs serve pivotal roles in breast cancer (BC) progression; however, to the best of our knowledge, the role of the lncRNA BRAF-regulated lncRNA 1 (BANCR) in BC has not yet been elucidated. The present study revealed that BANCR was overexpressed in BC cell lines and tissues, and could promote the clinical progression of disease, including increases in tumor size, lymph node metastasis and Tumor-Node-Metastasis stage. Furthermore, high BANCR expression was demonstrated to be associated with poor overall survival rates and early recurrence of BC in patients. Additionally, univariate and multivariate COX regression analyses identified high BANCR expression as an independent risk factor of poor prognosis of patients with BC. In addition, to verify the function of BANCR in BC cell lines, BANCR expression was silenced using short hairpin RNAs in MDA-MB-231 cells and overexpressed in MDA-MB-468 cells. An MTT assay and colony formation assay indicated that BANCR knockdown could suppress the proliferation of BC cells, whereas BANCR upregulation induced the proliferation of BC cells. Furthermore, BANCR silencing also reduced the migration and invasion of BC cells, as demonstrated via transwell migration and invasion assays. Consistently, the migration and invasion of BC cells increased upon BANCR ectopic overexpression in MDA-MB-468 cells. Mechanistically, matrix metallopeptidase 2/9 and epithelial-mesenchymal transition markers may be the potential targets of BANCR in regulating BC metastasis. In conclusion, BANCR overexpression could promote the clinical progression, metastasis and proliferation of BC and indicate poor prognosis of patients with BC. BANCR may therefore be a potential prognostic marker and therapeutic target of patients with BC.

Arthrolysis and delayed internal fixation combined with hinged external fixation for elbow stiffness associated with malunion or nonunion of capitellum fracture.

BACKGROUND: This study assessed outcomes after treatment of patients with capitellum fracture diagnosed >4 weeks after the trauma (delayed) who presented with stiff elbow. METHODS: We reviewed 7 patients with stiff elbows after delayed diagnosis of capitellum fractures between February 2007 and February 2012. They were treated with arthrolysis by twin incisions, late open reduction and internal fixation, and a hinged external fixator. According to the Bryan-Morrey-McKee classification, 3 patients had type I capitellum fractures and 4 patients had type IV. RESULTS: Mean follow-up was 28 months (range, 24-38 months). The mean delay from the initial trauma was 3.7 months. The flexion arc improved from a preoperative mean of 24° to a postoperative mean of 122°. The Mayo Elbow Performance Score increased from a mean of 56 points to 93 points. Anatomic fracture union occurred in all cases, and there was no secondary displacement. CONCLUSIONS: Arthrolysis, late internal fixation, and use of a hinged external fixator can solve problems associated with stiff elbow after delayed diagnosis of capitellum fracture. Combined use of these techniques may be a safe and effective treatment option.

Arthrolysis combined with reconstruction for treatment of terrible triad injury with a poor outcome after surgical as well as conservative intervention.

INTRODUCTION: The treatment of terrible triad injury with a poor outcome after intervention has not been successful thus far. The purpose of this study was to evaluate the efficacy of arthrolysis and reconstruction in the treatment of terrible triad injury with a poor outcome after surgical as well as conservative intervention. MATERIALS AND METHODS: Twelve patients (12 elbows) with the diagnosis of terrible triad injury were respectively reviewed. All the 12 patients had elbow dysfunction after conservative and surgical treatment of the terrible triad injury. Preoperatively, the flexion arc and forearm rotation were 36.7° ± 28.5° and 51.3° ± 43.4°, respectively, and the Mayo Elbow Performance Score was 56.3 points. The mean interval between the primary injury and our surgical treatment was 6.6 months. Our surgical intervention included elbow arthrolysis, ulnar nerve transposition, radial head replacement, coronoid process and ligament repair, and hinged external fixation. Patients were encouraged to participate in rehabilitation training 24 h after surgery. RESULTS: The mean follow-up duration was 20.1 months; the flexion arc and forearm rotation were 122° ± 18° and 140° ± 20°, respectively, and the mean Mayo Elbow Performance Score was 94.6 points (9 excellent, 3 good). Concentric stability was restored in all elbows. Complications included superficial pin tract infection (1), heterotopic ossification (3), and ulnar nerve palsy (1); the ulnar nerve symptoms had improved at the last follow-up. CONCLUSIONS: The combination of open arthrolysis and reconstruction performed at a mean interval of 6-month posttrauma can restore functional mobility in cases of terrible triad injury with a poor outcome after surgical as well as conservative intervention. Thus, it may be an effective alternative for the treatment of the poor outcome terrible triad injury. We recommend early functional rehabilitation with adherence to the guidelines for hinged external fixation.

Open arthrolysis and prosthetic replacement of the radial head for elbow stiffness associated with rotation limitation.

BACKGROUND: Limited forearm rotation is a frequent combined disorder in elbow stiffness. If the radial head cannot be saved during open arthrolysis, prosthetic replacement might be considered because it enhances stability and allows early motion. METHODS: In this study we retrospectively analyzed the outcome of 8 patients (7 men, 1 woman) who underwent open arthrolysis and simultaneous prosthetic replacement after resection of the radial head to restore elbow range of motion and forearm rotation. Patients were a mean age of 31.7 years (range, 22-40 years). RESULTS: Postoperatively, the mean (range) active range of motion improved from 29.4° (0°-70°) to 113.1° (80°-135°), mean (range) supination increased from 38.8° (0°-80°) to 77.5° (50°-90°), and mean (range) pronation improved from 18.8° (0°-80°) to 68.8° (50°-80°). The Mayo Elbow Performance Score improved from a mean (range) of 57.5 (50-70) to 92.5 (85-100) points. No elbow valgus instability was detected over a mean duration of 26 months of follow-up. The implant was considered stable in all patients. CONCLUSIONS: Open arthrolysis and prosthetic replacement of the radial head are effective in treating elbow stiffness with associated rotation limitation after resection of the radial head.

Prevention of peritendinous adhesions with electrospun ibuprofen-loaded poly(L-lactic acid)-polyethylene glycol fibrous membranes.

Physical barriers are commonly used to reduce peritendinous adhesion after injury. However, the inflammatory response to surgery cannot be prevented. This study was designed to evaluate the ability of ibuprofen-loaded poly(l-lactic acid)-polyethylene glycol (PELA) diblock copolymer fibrous membranes in preventing adhesion formation and reduce inflammation. Electrospun PELA fibrous membranes underwent mechanical testing and were characterized by morphology, surface wettability, drug release, and degradation. Results of an in vitro drug release study showed that a burst release was followed by sustained release from fibrous membranes with high initial ibuprofen content. Fewer L929 mouse fibroblasts adhered to and proliferated on the ibuprofen-loaded PELA fibrous membrane compared with tissue culture plates or PELA fibrous membrane without ibuprofen. In a chicken model of flexor digitorum profundus tendon surgery, the ibuprofen-loaded PELA fibrous membranes prevented tissue adhesion and significantly reduced inflammation. Taken together, these results demonstrate that ibuprofen-loaded PELA fibrous membranes prevent peritendinous adhesion formation better than membranes that do not contain ibuprofen, through anti-adhesion and anti-inflammatory actions.

Detection of H. pylori antibody profile in serum by protein array.

AIM: To detect multiple H. pylori antibodies in serum samples of individuals who carry H. pylori by protein array. METHODS: Recombinant H. pylori antigens, urease B subunit (UreB), vacuolating toxin A (VacA) and cytotoxin associated gene A protein (CagA), were prepared and immobilized in matrixes on nitrocellulose membrane by robotics to bind the specific immunoglobulin G (IgG) antibodies in serum. Staphylococcus protein A (SPA) labeled by colloid gold was used to integrate the immuno-complex and gave red color signal. The scanner based on charge-coupled device (CCD) could collect the image signal and convert it into digital signal. RESULTS: When human IgG was printed on the membrane in increasing concentrations and incubated with immunogold, a linear dose response curve was obtained and the detection limit for IgG was about 0.025 ng. The cutoff values, which were defined as the mean grey level plus 3 times of standard deviation, were 27.183, 28.546 and 27.402, for anti-UreB IgG, anti-CagA IgG and anti-VacA IgG, respectively, as 400 human serum samples with negative H. pylori antibodies were detected by the protein array. When 180 serum samples from patients in hospital were employed for detection of IgG against UreB, CagA and VacA, the sensitivity of the protein array was 93.4%, 95.4%, 96.0%, and the specificity was 94.8%, 94.4% and 97.5%, respectively, as compared with the results obtained by ELISA. The assay also showed high reproducibility, uniformity and stability, and the results were available within 30 min. CONCLUSION: The protein array is a very practical method for rapid detection of multiple antibodies in serum samples. It is especially useful for large scale epidemiological investigation of the infection of H. pylori.