A novel mutation in COL1A1 causing osteogenesis imperfecta/hearing loss

Abstract Objectives: To screen the COL1A1 and COL1A2 gene mutation sites in a family with type I osteogenesis imperfecta (OI)/hearing loss and analyze the characteristics and recovery of hearing loss in patients with osteogenesis imperfecta. Methods: The basic clinical data of Ol proband and her parents were collected, and the COL1A1 and COL1A2 genes were detected in peripheral blood by PCR amplification and generation Sanger sequencing. Literature of stapedial surgery in patients with osteogenesis imperfecta was collected. Results: The heterozygous mutation of the 26 exon c.1922_1923 ins C in the Ol progenitor COL1A1 gene led to the amino acid frameshift mutation of p.Pro 601FS, which was not detected in the phenotypic parents. The homozygous of exon 28 c.1782>G in COL1A2 was detected in the proband and her parents, resulting in changes in the protein p.Pro 549Ala. Conclusion: The clinical symptoms of the Ol proband is caused by heterozygous mutation of the 26 exon c.1922_1923 ins C in COL1A1 gene. Stapedial surgery can provide short-term and long-term hearing benefits for Ol patients with hearing loss. Level of evidence: Level 4.

A novel mutation in COL1A1 causing osteogenesis imperfecta/hearing loss.

OBJECTIVES: To screen the COL1A1 and COL1A2 gene mutation sites in a family with type I osteogenesis imperfecta (OI)/hearing loss and analyze the characteristics and recovery of hearing loss in patients with osteogenesis imperfecta. METHODS: The basic clinical data of OI proband and her parents were collected, and the COL1A1 and COL1A2 genes were detected in peripheral blood by PCR amplification and generation Sanger sequencing. Literature of stapedial surgery in patients with osteogenesis imperfecta was collected. RESULTS: The heterozygous mutation of the 26 exon c.1922_1923 ins C in the OI progenitor COL1A1 gene led to the amino acid frameshift mutation of p.Pro 601FS, which was not detected in the phenotypic parents. The homozygous of exon 28 c.1782>G in COL1A2 was detected in the proband and her parents, resulting in changes in the protein p.Pro 549Ala. CONCLUSION: The clinical symptoms of the OI proband is caused by heterozygous mutation of the 26 exon c.1922_1923 ins C in COL1A1 gene. Stapedial surgery can provide short-term and long-term hearing benefits for OI patients with hearing loss. LEVEL OF EVIDENCE: Level 4.

Thrombopoietin is associated with a prognosis of gastric adenocarcinoma.

OBJECTIVE Thrombopoietin (THPO) is well-known as a megakaryocyte growth and development factor (MGDF) involved in megakaryocyte proliferation and maturation. To explore the biological effects of THPO in gastric adenocarcinoma, we conducted this study. Methods: By accessing the TCGA database, the expression level of THPO was determined in tumor tissues. The association between THPO expression and clinical features, or prognostic significance was described by Cox regression analysis and Kaplan-Meier. The SiRNA method was used to decline the THPO expression; then cell viability, invasion, and migration were detected to verify the effects of the knockdown of THPO. qPCR and western blotting were implemented to examine the expression level of THPO. Results: The expression of THPO was increased in tumor tissue and cells, its high-regulation was associated with a poor prognosis in patients with gastric adenocarcinoma. Cell viability, invasion, and migration were suppressed in AGS with the down-regulation of THPO. Furthermore, on the basis of si-THPO transfection, E-cadherin was promoted while N-cadherin and Vimentin were attenuated. CONCLUSION Our results revealed that THPO may be a potent marker of gastric adenocarcinoma, providing a novel potential screening method for gastric adenocarcinoma.

Recent advances in pristine tri-metallic metal-organic frameworks toward the oxygen evolution reaction.

Pristine metal-organic frameworks (MOFs) have received much attention in recent years due to their high specific surface areas, large porosity, excellent pore size distributions, flexible structure, and remarkable catalytic properties. The design of functional MOFs that can function as efficient HER and OER catalysts is significant in solving the energy crisis but remains a big challenge. Tri-metallic metal-organic frameworks show a good application prospect in water oxidation. In this review, we are going to focus on the latest progress and future trends in the development of pristine trimetallic MOFs with respect to the OER. The synergistic effect between multi-metal active sites is effective at improving the intrinsic activity of MOFs toward the OER. By summarizing the synthesis method of tri-metallic MOFs and observing their performance toward the oxygen evolution reaction, we hope that this review will trigger new developments in coordination chemistry, electrochemistry, nanomaterials and energy materials.

Thrombopoietin is associated with a prognosis of gastric adenocarcinoma

SUMMARY OBJECTIVE Thrombopoietin (THPO) is well-known as a megakaryocyte growth and development factor (MGDF) involved in megakaryocyte proliferation and maturation. To explore the biological effects of THPO in gastric adenocarcinoma, we conducted this study. Methods: By accessing the TCGA database, the expression level of THPO was determined in tumor tissues. The association between THPO expression and clinical features, or prognostic significance was described by Cox regression analysis and Kaplan-Meier. The SiRNA method was used to decline the THPO expression; then cell viability, invasion, and migration were detected to verify the effects of the knockdown of THPO. qPCR and western blotting were implemented to examine the expression level of THPO. Results: The expression of THPO was increased in tumor tissue and cells, its high-regulation was associated with a poor prognosis in patients with gastric adenocarcinoma. Cell viability, invasion, and migration were suppressed in AGS with the down-regulation of THPO. Furthermore, on the basis of si-THPO transfection, E-cadherin was promoted while N-cadherin and Vimentin were attenuated. CONCLUSION Our results revealed that THPO may be a potent marker of gastric adenocarcinoma, providing a novel potential screening method for gastric adenocarcinoma.

RESUMO OBJETIVO Trombopoetina (THPO) é um conhecido fator de desenvolvimento e crescimento megacariócito (MGDF) envolvido na proliferação e maturação de megacariócitos. Realizamos este estudo para explorar os efeitos biológicos do THPO no adenocarcinoma gástrico. Metodologia: O nível de expressão do THPO em tecidos tumorais foi determinado acessando a banco de dados TCGA. A associação entre a expressão de THPO e características clínicas ou relevância no prognóstico foi descrita através da análise de Kaplan-Meier e regressão de Cox. O método SiRNA foi utilizado para reduzir a expressão da THPO e, em seguida, a viabilidade, invasão, e migração celular foram detectadas para verificar os efeitos da redução do THPO. qPCR e western blotting foram utilizados para examinar o nível de expressão do THPO. Resultados: A expressão do THPO estava aumentada em tecido e células tumorais, esse aumento estava associado com um prognóstico negativo para pacientes com adenocarcinoma gástrico. A invasão e migração celular foram suprimidos em AGS com a redução do THPO. Além disso, com base na transfecção de si-THPO, a E-caderina foi promovida, enquanto a N-caderina e Vimentina foram atenuadas. Conclusão nossos resultados demonstram que o thpo pode ser um potente marcador de adenocarcinoma gástrico, com potencial para ser um novo tipo de triagem para adenocarcinoma gástrico.

Chemical diversity from the Tibetan Plateau fungi Penicillium kongii and P. brasilianum.

Two new secondary metabolites, kongiilines A and B (1, 7), and two asperphenamate derivatives, asperphenamates B and C (5-6), together with 16 known compounds (2-4, 8-20), were isolated from Tibetan Plateau fungi Penicillium kongii and Penicillium brasilianum. This is the first report on asperphenamates B and C as naturally occurring compounds, and that aspterric acid is isolated from P. brasilianum for the first time. Their structures were elucidated by different spectroscopic techniques including high-resolution electrospray ionisation mass spectrum, 1D nuclear magnetic resonance (NMR), and 2D NMR as well as electronic circular dichroism. Compounds 4, 5, and 10 exhibited cytotoxicity activities against human colon carcinoma HCT116 cell line with IC50 values of 88.16, 77.68, and 36.92 µM, respectively. Fungi from Tibetan Plateau represent important and rich resources for the investigation of new chemicals.

Rapamycin Combi with TAE on the Growth, Metastasis, and Prognosis of Hepatocellular Carcinoma in Rat Models.

INTRODUCTION AND AIM: To investigate the effect of mTOR inhibitor Rapamycin combined with transcatheter arterial embolization (TAE) on the growth, metastasis, and prognosis of hepatocellular carcinoma (HCC) in rat model. MATERIAL AND METHOD: McARH7777 cells were used to construct rat models of HCC, which were randomly divided into Model, Rapamycin, TAE, and Rapamycin + TAE groups. Quantitative reverse transcription-PCR (qRT-PCR) and Western Blot were used to detect the expression of Epithelial-Mesenchymal Transition (EMT)-related molecules, and immunohistochemical staining to determine the expression of EMTrelated proteins, angiogenic factors as well as microvessel density (MVD)-CD34. RESULTS: The hepatic tumor volume of rats in the other three groups were all significantly smaller than the Model group on the 7th, 14th, and 21st day after treatment and the combination treatment was apparently more effective than either treatment alone. Besides, both the number and the size of metastatic nodules of HCC rats after combination treatment were remarkably reduced. In addition, compared with rats in the Rapamycin + TAE group, N-cadherin, Vimentin, HIF-1α, VEGF, and MVD-CD34 were obviously enhanced, while E-cadherin was lowered in those TAE group, which were the complete opposite to the Rapamycin group. Besides, the median survival time of rats in the Rapamycin + TAE group was evidently longer than the resting groups. CONCLUSION: Rapamycin combined with TAE may effectively suppress the EMT formation and angiogenesis, thereby inhibiting the growth and lung metastasis of HCC rats, which provides a new idea for countering the recurrence and metastasis of HCC.

Repeatability of the "flash-replenishment" method in contrast-enhanced ultrasound for the quantitative assessment of hepatic microvascular perfusion.

This study aimed to evaluate the feasibility and repeatability of the flash-replenishment method in contrast-enhanced ultrasound (CEUS) perfusion imaging and assess quantitatively microvascular perfusion in the liver. Twenty healthy New Zealand rabbits were submitted to CEUS perfusion imaging with continuous intravenous infusion. Using flash-replenishment kinetics, the dynamic process of depletion and refilling of microbubble contrast agent was recorded. The hepatic microvascular perfusion parameters were calculated, including region of interest, peak intensity (PI), area under the curve (AUC), and hepatic artery to vein transit time (HA-HVTT). A consistency test was performed for multiple measurements by the same operator and blind measurements by two different operators. The hepatic perfusion imaging of 3×108 bubbles/min had minimal error and the best imaging effect and repeatability. The variability of the perfusion parameter measured at 3 cm depth under the liver capsule was at a minimum with coefficient of variation of 3.9%. The interclass correlation coefficient (ICC) of measurements taken by the same operator was 0.985, (95% confidence interval, CI=0.927-0.998). Measurements taken by two operators had good consistency and reliability, with the ICC of 0.948 (95%CI=0.853-0.982). The PI and AUC of liver parenchyma after reperfusion were lower than before blocking; and HA-HVTT was significantly longer than before blocking (P<0.05). The flash-replenishment method in CEUS perfusion imaging showed good stability and repeatability, which provide a valuable experimental basis for the quantitative assessment of hepatic microvascular perfusion in clinical practice.

Repeatability of the "flash-replenishment" method in contrast-enhanced ultrasound for the quantitative assessment of hepatic microvascular perfusion

This study aimed to evaluate the feasibility and repeatability of the flash-replenishment method in contrast-enhanced ultrasound (CEUS) perfusion imaging and assess quantitatively microvascular perfusion in the liver. Twenty healthy New Zealand rabbits were submitted to CEUS perfusion imaging with continuous intravenous infusion. Using flash-replenishment kinetics, the dynamic process of depletion and refilling of microbubble contrast agent was recorded. The hepatic microvascular perfusion parameters were calculated, including region of interest, peak intensity (PI), area under the curve (AUC), and hepatic artery to vein transit time (HA-HVTT). A consistency test was performed for multiple measurements by the same operator and blind measurements by two different operators. The hepatic perfusion imaging of 3×108 bubbles/min had minimal error and the best imaging effect and repeatability. The variability of the perfusion parameter measured at 3 cm depth under the liver capsule was at a minimum with coefficient of variation of 3.9%. The interclass correlation coefficient (ICC) of measurements taken by the same operator was 0.985, (95% confidence interval, CI=0.927-0.998). Measurements taken by two operators had good consistency and reliability, with the ICC of 0.948 (95%CI=0.853-0.982). The PI and AUC of liver parenchyma after reperfusion were lower than before blocking; and HA-HVTT was significantly longer than before blocking (P<0.05). The flash-replenishment method in CEUS perfusion imaging showed good stability and repeatability, which provide a valuable experimental basis for the quantitative assessment of hepatic microvascular perfusion in clinical practice.

Hydroclimate changes across the Amazon lowlands over the past 45,000 years.

Reconstructing the history of tropical hydroclimates has been difficult, particularly for the Amazon basin-one of Earth's major centres of deep atmospheric convection. For example, whether the Amazon basin was substantially drier or remained wet during glacial times has been controversial, largely because most study sites have been located on the periphery of the basin, and because interpretations can be complicated by sediment preservation, uncertainties in chronology, and topographical setting. Here we show that rainfall in the basin responds closely to changes in glacial boundary conditions in terms of temperature and atmospheric concentrations of carbon dioxide. Our results are based on a decadally resolved, uranium/thorium-dated, oxygen isotopic record for much of the past 45,000 years, obtained using speleothems from Paraíso Cave in eastern Amazonia; we interpret the record as being broadly related to precipitation. Relative to modern levels, precipitation in the region was about 58% during the Last Glacial Maximum (around 21,000 years ago) and 142% during the mid-Holocene epoch (about 6,000 years ago). We find that, as compared with cave records from the western edge of the lowlands, the Amazon was widely drier during the last glacial period, with much less recycling of water and probably reduced plant transpiration, although the rainforest persisted throughout this time.

Rhizobium acidisoli sp. nov., isolated from root nodules of Phaseolus vulgaris in acid soils.

Two Gram-negative, aerobic, non-motile, rod-shaped bacterial strains, FH13T and FH23, representing a novel group of Rhizobium isolated from root nodules of Phaseolus vulgaris in Mexico, were studied by a polyphasic analysis. Phylogeny of 16S rRNA gene sequences revealed them to be members of the genus Rhizobium related most closely to 'Rhizobium anhuiense' CCBAU 23252 (99.7 % similarity), Rhizobium leguminosarum USDA 2370T (98.6 %), and Rhizobium sophorae CCBAU 03386T and others ( ≤ 98.3 %). In sequence analyses of the housekeeping genes recA, glnII and atpD, both strains formed a subclade distinct from all defined species of the genus Rhizobium at sequence similarities of 82.3-94.0 %, demonstrating that they represented a novel genomic species in the genus Rhizobium. Mean levels of DNA-DNA relatedness between the reference strain FH13T and the type strains of related species varied between 13.0 ± 2.0 and 52.1 ± 1.2 %. The DNA G+C content of strain FH13T was 63.5 mol% (Tm). The major cellular fatty acids were 16 : 0, 17 : 0 anteiso, 18 : 0, summed feature 2 (12 : 0 aldehyde/unknown 10.928) and summed feature 8 (18 : 1ω7c). The fatty acid 17 : 1ω5c was unique for this strain. Some phenotypic features, such as failure to utilize adonitol, l-arabinose, d-fructose and d-fucose, and ability to utilize d-galacturonic acid and itaconic acid as carbon source, could also be used to distinguish strain FH13T from the type strains of related species. Based upon these results, a novel species, Rhizobium acidisoli sp. nov., is proposed, with FH13T ( = CCBAU 101094T = HAMBI 3626T = LMG 28672T) as the type strain.

Relationship between the maxillary transverse dimension and palatally displaced canines: A cone-beam computed tomographic study.

OBJECTIVES: To examine the relationship between palatally displaced maxillary canines (PDC) and the maxillary transverse dimension using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Thirty-three patients (11 males and 22 females, mean age 18.2 years) with PDC were matched to 66 patients (22 males and 44 females, mean age 18.1 years) without PDC (control) by gender, age, and posterior occlusion. A CBCT image was taken on all the patients prior to any orthodontic treatment. For each patient the maxillary basal bone widths and interdental widths at the maxillary first molars and first and second premolars were measured on axial and coronal sections of CBCT images. In addition, the presence of permanent tooth agenesis and the widths of maxillary incisors were recorded. RESULTS: Similar maxillary transverse dimensions, both skeletally and dentally, were found between the PDC and control groups. In the PDC group, the number of patients with permanent tooth agenesis was six times higher than in the control group. In addition, the maxillary lateral incisors on PDC-affected sides were smaller than those of control group (P < .05). CONCLUSIONS: The maxillary transverse dimension, both skeletally and dentally, had no effect on the occurrence of PDC. The higher prevalence of permanent tooth agenesis was found in the PDC group. Moreover, the mean mesiodistal width of maxillary lateral incisors in the PDC group was significantly smaller than in the control group (P < .05).

Treatment of unstable sacral fractures with percutaneous reconstruction plate internal fixation.

PURPOSE: To study the effects of percutaneous reconstruction plate internal fixation in the treatment of unstable sacral fractures. METHODS: Percutaneous reconstruction plate internal fixation was applied on 21 cases of unstable sacral fracture (15 males and six females, at age range of 16-65 years, mean 38.3 years) including four cases of Denis Zone I, 14 cases of Zone II and three cases of Zone III. In operation, an arc incision (about 3-5 cm long) was made along the iliac crest on the outside border of posterior superior iliac spine (PSIS) on both sides, and then the plate was transported from the wounded side to the opposite one through the subcutaneous tunnel. RESULTS: The mean incision length, operation time, intraoperative blood loss was 4.3 cm, 45.2 min, and 160.8 ml respectively. All these patients were followed up for 12-33 months (average 16.3 months), which showed no incision infection, intraoperative neurovascular injury, internal fixation loose or breakage, disunion, or obvious lower limb length inequality. The function result was rated as excellent in six cases, good in 12 and fair in 3, with excellence rate of 85.7%, according to the Majeed scoring system. CONCLUSION: Percutaneous reconstruction plate internal fixation is an ideal surgical approach to unstable sacral fractures, as it is easy, safe, causing less trauma and fewer complications, and conducive to quicker recovery.

Treatment of unstable sacral fractures with percutaneous reconstruction plate internal fixation / Tratamento de fraturas sacrais instáveis com reconstrução percutânea com fixação de placa interna

PURPOSE: To study the effects of percutaneous reconstruction plate internal fixation in the treatment of unstable sacral fractures. METHODS: Percutaneous reconstruction plate internal fixation was applied on 21 cases of unstable sacral fracture (15 males and six females, at age range of 16-65 years, mean 38.3 years) including four cases of Denis Zone I, 14 cases of Zone II and three cases of Zone III. In operation, an arc incision (about 3-5 cm long) was made along the iliac crest on the outside border of posterior superior iliac spine (PSIS) on both sides, and then the plate was transported from the wounded side to the opposite one through the subcutaneous tunnel. RESULTS: The mean incision length, operation time, intraoperative blood loss was 4.3cm, 45.2min, and 160.8ml respectively. All these patients were followed up for 12-33 months (average 16.3 months), which showed no incision infection, intraoperative neurovascular injury, internal fixation loose or breakage, disunion, or obvious lower limb length inequality. The function result was rated as excellent in six cases, good in 12 and fair in 3, with excellence rate of 85.7%, according to the Majeed scoring system. CONCLUSION: Percutaneous reconstruction plate internal fixation is an ideal surgical approach to unstable sacral fractures, as it is easy, safe, causing less trauma and fewer complications, and conducive to quicker recovery.

OBJETIVO: Estudar os efeitos da reconstrução percutânea com fixação de placa interna no tratamento de fraturas sacrais instáveis. MÉTODOS: A reconstrução percutânea com fixação de placa interna foi aplicada em 21 casos de fratura sacral instável (15 homens e seis mulheres, com idade variando entre 16 e 65 anos, média de 38,3 anos) incluindo quatro casos de Zona I de Denis, 14 casos de Zona II e três casos de Zona III. No ato operatório, uma incisão arqueada (cerca de 3 a 5cm de comprimento) foi feita ao longo da crista ilíaca na borda externa da espinha ilíaca supero-posterior (PSIS) em ambos os lados, e então a placa foi transportada do lado da ferida para o lado oposto através do túnel subcutâneo. RESULTADOS: O comprimento médio da incisão, tempo operatório e perda sanguínea intra-operatória foram, respectivamente, 4,3cm, 45,2min e 160,8ml. Todos estes pacientes foram acompanhados por 12 a 33 meses (média 16,3 meses), o que mostrou nenhuma infecção de ferida operatória, lesão neurovascular intraoperatória, perda da fixação interna ou quebra, desunião ou desigualdade nos comprimentos dos membros inferiores. O resultado funcional foi excelente em seis casos, bom em doze e falho em três, com taxa excelente de 85,7%, de acordo com o sistema de escore de Majeed. CONCLUSÃO: Reconstrução percutânea com fixação de placa interna é uma abordagem cirúrgica ideal para fraturas sacrais instáveis, sendo fácil e segura, causando menos trauma e poucas complicações, conduzindo a uma recuperação mais rápida.

Treatment of unstable sacral fractures with percutaneous reconstruction plate internal fixation / Tratamento de fraturas sacrais instáveis com reconstrução percutânea com fixação de placa interna

PURPOSE: To study the effects of percutaneous reconstruction plate internal fixation in the treatment of unstable sacral fractures. METHODS: Percutaneous reconstruction plate internal fixation was applied on 21 cases of unstable sacral fracture (15 males and six females, at age range of 16-65 years, mean 38.3 years) including four cases of Denis Zone I, 14 cases of Zone II and three cases of Zone III. In operation, an arc incision (about 3-5 cm long) was made along the iliac crest on the outside border of posterior superior iliac spine (PSIS) on both sides, and then the plate was transported from the wounded side to the opposite one through the subcutaneous tunnel. RESULTS: The mean incision length, operation time, intraoperative blood loss was 4.3cm, 45.2min, and 160.8ml respectively. All these patients were followed up for 12-33 months (average 16.3 months), which showed no incision infection, intraoperative neurovascular injury, internal fixation loose or breakage, disunion, or obvious lower limb length inequality. The function result was rated as excellent in six cases, good in 12 and fair in 3, with excellence rate of 85.7%, according to the Majeed scoring system. CONCLUSION: Percutaneous reconstruction plate internal fixation is an ideal surgical approach to unstable sacral fractures, as it is easy, safe, causing less trauma and fewer complications, and conducive to quicker recovery.(AU)

OBJETIVO: Estudar os efeitos da reconstrução percutânea com fixação de placa interna no tratamento de fraturas sacrais instáveis. MÉTODOS: A reconstrução percutânea com fixação de placa interna foi aplicada em 21 casos de fratura sacral instável (15 homens e seis mulheres, com idade variando entre 16 e 65 anos, média de 38,3 anos) incluindo quatro casos de Zona I de Denis, 14 casos de Zona II e três casos de Zona III. No ato operatório, uma incisão arqueada (cerca de 3 a 5cm de comprimento) foi feita ao longo da crista ilíaca na borda externa da espinha ilíaca supero-posterior (PSIS) em ambos os lados, e então a placa foi transportada do lado da ferida para o lado oposto através do túnel subcutâneo. RESULTADOS: O comprimento médio da incisão, tempo operatório e perda sanguínea intra-operatória foram, respectivamente, 4,3cm, 45,2min e 160,8ml. Todos estes pacientes foram acompanhados por 12 a 33 meses (média 16,3 meses), o que mostrou nenhuma infecção de ferida operatória, lesão neurovascular intraoperatória, perda da fixação interna ou quebra, desunião ou desigualdade nos comprimentos dos membros inferiores. O resultado funcional foi excelente em seis casos, bom em doze e falho em três, com taxa excelente de 85,7%, de acordo com o sistema de escore de Majeed. CONCLUSÃO: Reconstrução percutânea com fixação de placa interna é uma abordagem cirúrgica ideal para fraturas sacrais instáveis, sendo fácil e segura, causando menos trauma e poucas complicações, conduzindo a uma recuperação mais rápida.(AU)