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1.
Bioengineered ; 13(5): 11402-11416, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35510414

RESUMO

Patellar instability (PI) is a common knee injury in adolescents, but the crucial biomarkers and molecular mechanisms associated with it remain unclear. We established a PI mouse model and investigated PI-related changes in gene expression by RNA sequencing (RNA-seq). Differentially expressed gene (DEG) analysis and enrichment analysis were performed to identify crucial genes and pathways associated with PI. Subsequently, a protein-protein interaction, DEG-miRNA, DEG-transcription factors, and DEG-drug interaction networks were constructed to reveal hub genes, molecular mechanism, and potential drugs for PI. Finally, the reliability of the sequencing results was confirmed by real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. Upon comparison with the control group, 69 genes were differently expressed in PI, including 17 upregulated and 52 downregulated ones. The DEGs were significantly enriched in Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway and immune responses. The protein-protein interaction network identified ten PI-related hub genes, all of which are involved in the JAK/STAT signaling pathway or inflammation-related pathways. DEG-miRNA and DEG-transcription factor networks offered new insights for regulating DEGs post-transcriptionally. We also determined potential therapeutic drugs or molecular compounds that could restore dysregulated expression of DEGs via the DGIdb database. RT-qPCR results were consistent with the RNA-seq, confirming the reliability of the sequencing data. Immunohistochemistry results suggested that JAK1 and STAT3 expression was increased in PI. Our study explored the potential molecular mechanisms in PI, provided promising biomarkers and suggested a molecular basis for therapeutic targets for this condition.


Assuntos
Instabilidade Articular , MicroRNAs , Articulação Patelofemoral , Animais , Biomarcadores , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Articulação Patelofemoral/metabolismo , RNA-Seq , Reprodutibilidade dos Testes
2.
Artigo em Inglês | MEDLINE | ID: mdl-35486522

RESUMO

BACKGROUND: It has been reported that trochlear dysplasia occurs very early in development, and environmental factors like swaddling may cause developmental dysplasia of the hip, which is associated with a shallower trochlear groove. However, to our knowledge, there are no definitive studies about the relationship between trochlear dysplasia and traditional straight-leg swaddling. QUESTIONS/PURPOSES: Using a rat model of femoral trochlear dysplasia, we asked: Does straight-leg swaddling for 1 and 2 weeks in newborn Wistar rats alter the femoral trochlea with respect to (1) gross morphology, (2) histologic appearance, as well as (3) trochlear sulcus angle, width, and depth? METHODS: Eighty-four newborn Wistar rats (44 females and 40 males) were divided into two equal groups: 42 in the unswaddled group and 42 in the swaddled group; each group was comprised of 22 females and 20 males. In the swaddled group, the rats were wrapped in surgical tape to maintain hip and knee extension to simulate traditional human straight-leg swaddling. To determine whether longer periods of swaddling were associated with more severe trochlear dysplasia, 21 rats in each group were euthanized at 1 and 2 weeks, respectively, and the gross morphology of the femoral trochlea was observed by one observer blinded to condition. Then hematoxylin and eosin staining of the femoral trochlea was performed and the distribution and number of the chondrocytes of the trochlear groove were viewed through a microscope. The trochlear sulcus angles, depth, and width were measured by an experienced technician blinded to condition. RESULTS: By observing the gross morphology, we found that the trochlear groove in the swaddled group became qualitatively flatter compared with the unswaddled group at 1 week, and at 2 weeks, the trochlear groove became much shallower. At 1 and 2 weeks, histologic examinations showed obvious qualitative changes in the distribution and number of chondrocytes of the trochlear groove in the swaddled than in the unswaddled groups. In the swaddled group, trochlear dysplasia was more common at 2 weeks, occurring in 62% (26 of 42 [16 of 22 females and 10 of 22 males]) versus 33% (14 of 42 [8 of 22 females and 6 of 20 males]) at 1 week. At 1 week, the swaddled group showed more trochlear dysplasia compared with the unswaddled group as measured by angle of the trochlear groove (137° ± 6° versus 132°± 3.6°, mean difference 5° [95% confidence interval 2.9° to 7.2°]; p < 0.001), depth of the trochlear grove (0.28 ± 0.04 mm versus 0.31 ± 0.02 mm, mean difference 0.03 mm [95% CI 0.01 to 0.04]; p < 0.001). At 2 weeks, the swaddled group showed more severe trochlear dysplasia than at 1 week compared with the unswaddled group as measured by the angle of the trochlear groove (135° ± 6.0° versus 128° ± 4.8°, mean difference 7° [95% CI 5.7° to 10.4°]; p < 0.001), depth of the trochlear grove (0.32 ± 0.04 mm versus 0.36 ± 0.02 mm, mean difference 0.04 mm [95% CI 0.03 to 0.06]; p < 0.001). There was no difference in the width of the trochlear sulcus between the swaddled and the unswaddled groups at 1 week (1.29 ± 0.14 mm versus 1.30 ± 0.12 mm, mean difference 0.01 mm [95% CI -0.05 to 0.07]; p = 0.73) and 2 weeks (1.55 ± 0.12 mm versus 1.56 ± 0.12 mm, mean difference 0.01 mm [95% CI -0.05 to 0.07]; p = 0.70). CONCLUSION: Our results indicate that traditional straight-leg swaddling could induce trochlear dysplasia in this model of newborn rats. With an increased swaddling time of 2 weeks, more severe trochlear dysplasia appeared in the swaddled group. CLINICAL RELEVANCE: Our findings suggest that traditional straight-leg swaddling may impair trochlear development in the human neonate and lead to trochlear dysplasia in infants. We believe our animal model will be useful in future work to observe and study the change of cartilage and subchondral bone in each stage of the development of trochlear dysplasia and the change of mechanotransduction-associated proteins (such as, TRPV4/ Piezo1 and CollagenⅡ) in cartilage and subchondral osteocytes. It will also be helpful to further investigate the mechanism of developmental femoral trochlea dysplasia caused by biomechanical changes.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35482508

RESUMO

A Gram-negative, rod-shaped aerobic bacterium designated as strain 2R12T was isolated from the rhizosphere soil of Hosta plantaginea. Phylogenetic analyses based on the 16S rRNA gene revealed that strain 2R12T should be assigned to the genus Chitinophaga with the highest sequence similarity to Chitinophaga arvensicola DSM 3695T (99.1 %) and Chitinophaga ginsengisegetis DSM 18108T (98.6 %). The major fatty acids of strain 2R12T (>10 %) were iso-C15 : 0, C16 :1 ω5c and iso-C17 : 0 3-OH. The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids and five unidentified lipids. The predominant respiratory quinone was MK-7. The genomic DNA G+C content was 46.1 mol%. The average nucleotide identity values of strain 2R12T with C. arvensicola DSM 3695T and C. ginsengisegetis DSM 18108T were 77.9 and 78.8 %, respectively, while in silico DNA-DNA hybridization values for strain 2R12T with these strains were 22.8 and 23.3 %, respectively. Based on comparative analysis of phylogenetic, phylogenomic, phenotypic and chemotaxonomic characteristics, strain 2R12T represents a novel species in the genus Chitinophaga, for which the name Chitinophaga hostae sp. nov. is proposed. The type strain is 2R12T (=ACCC 61757T=JCM 34719T).


Assuntos
Gammaproteobacteria , Hosta , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Gammaproteobacteria/genética , Hosta/genética , Filogenia , RNA Ribossômico 16S/genética , Rizosfera , Análise de Sequência de DNA , Solo , Microbiologia do Solo , Vitamina K 2
4.
Opt Express ; 30(7): 11684-11692, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35473107

RESUMO

Quantum interference plays an essential role in understanding the concepts of quantum physics. Moreover, the interference of photons is indispensable for large-scale quantum information processing. With the development of quantum networks, interference of photons transmitted through long-distance fiber channels has been widely implemented. However, quantum interference of photons using free-space channels is still scarce, mainly due to atmospheric turbulence. Here, we report an experimental demonstration of Hong-Ou-Mandel interference with photons transmitted by free-space channels. Two typical photon sources, i.e., correlated photon pairs generated in spontaneous parametric down conversion (SPDC) process and weak coherent states, are employed. A visibility of 0.744 ± 0.013 is observed by interfering with two photons generated in the SPDC process, exceeding the classical limit of 0.5. Our results demonstrate that the quantum property of photons remains even after transmission through unstable free-space channels, indicating the feasibility and potential application of free-space-based quantum interference in quantum information processing.

5.
Phytomedicine ; 101: 154110, 2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35487039

RESUMO

BACKGROUND: Renal fibrosis is the final common pathological feature of various chronic kidney diseases (CKD). Despite recent advances, development of new treatments strategy is needed. Emodin (EMO), an important ingredient of Chinese medicine, rhubarb (Polygonaceae Rheum palmatum l.), has been reported to inhibit the development of renal fibrosis effectively. However, the poor oral bioavailability of EMO and the insufficient monotherapy therapy compromise its efficacy. PURPOSE: In order to enhance renal fibrosis therapy of emodin, an innovative combination therapy based on deoxycholic acid-chitosan coated liposomes (DCS-Lips) and in situ colonic gel (IGE) was developed. METHODS: For one, the DCS-Lips were prepared via electrostatic interaction by mixing anionic conventional Lips with cationic DCS, deoxycholic acid conjugated on the backbone of chitosan. The cellular uptake of FITC-labeled DCS-Lips in Caco-2 cell monolayer was evaluated by CLSM and flow cytometry, respectively. Permeability study was carried out using Caco-2 cell monolayer. For another, EMO-loaded in situ colonic gel (EMO-IGE) was prepared by mixing EMO nanosuspensions and plain in situ gel, which was obtained by the cold method. The EMO-IGE was assessed for morphology, gelation temperature, viscosity and in vitro drug release. Finally, the therapeutic efficacy of the combination strategy, oral DCS-Lips formulations and in situ colonic gel, was evaluated in unilateral ureteral obstruction (UUO) rat model. Additionally, 16S rDNA sequencing was performed on rats faces to investigate whether the combination strategy improves the microbial dysbiosis in UUO rats. RESULTS: The prepared DCS-Lips produced small, uniformly sized nanoparticles, and significantly enhanced the cellular uptake and in vitro permeability of EMO compared to non-coated liposomes. Moreover, the EMO-IGE was characterized by short gelation time, optimal gelling temperature, and excellent viscosity. In UUO model, the combination of DCS-Lips (gavage) and IGE (enema) attenuated renal fibrosis effectively. The results of 16S rDNA sequencing illustrated that IGE could restore the gut microbial dysbiosis of UUO rats. CONCLUSION: Overall, the combination of DCS-Lips and EMO-IGE alleviated renal fibrosis effectively, resulting from the improved oral bioavailability of EMO by DCS-Lips and the restoration of gut microbiota by EMO-IGE, thus, presenting an innovative and promising potential for renal fibrosis treatment.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35366078

RESUMO

PURPOSE: The role of the tibial tubercle-posterior cruciate ligament (TT-PCL) and tibial tubercle-trochlear groove (TT-TG) in recurrent patellar instability (RPI) remains unclear. This study aims to confirm the validity of the TT-TG and TT-PCL in predicting RPI and to verify whether the TT-PCL can truly reflect the lateralization of the tibial tubercle. METHODS: A total of 50 patients with RPI and 50 controls were recruited and underwent magnetic resonance imaging examinations. The TT-TG, TT-PCL, and tibial tubercle lateralization (TTL) were measured independently by two authors in a blinded and randomized fashion. T-test was used for parametric variances and the Mann-Whitney U and Chi-square tests were used for non-parametric variances. Pearson's product moment correlation coefficients were calculated to determine correlations between the defined measurements. The intraclass correlation coefficient was used to assess the reliability of the measurements. RESULTS: All defined measurements showed excellent intra- and inter-observer reliability. The TT-TG distance, TT-PCL distance, and TTL were significantly greater in the PI group than in the control group. The AUC was highest for the TT-TG distance compared with that for the TT-PCL distance, and TTL were 0.798, 0.764, and 0.769, with the calculated cut-off value of 12.5 mm, 16.5 mm, and 66.1 percentages. There was a moderate correlation (r = 0.595) between the TT-TG distance and TTL, and a weak correlation (r = 0.430) between the TT-PCL distance and TTL. CONCLUSION: Both the TT-TG distance and TT-PCL distance can be measured with excellent reliability on magnetic resonance imaging. The TT-TG distance, rather than the TT-PCL distance, has a better performance in predicting RPI. Most interestingly, the TT-PCL distance cannot reflect the real lateralization of TT. This study provides new information to evaluate TTL in patients with RPI. LEVEL OF EVIDENCE: III.

7.
Asian J Surg ; 2022 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-35227565

RESUMO

PURPOSE: The efficacy of radiotherapy for treating thymomas is unclear. The goal of this study was to analyze overall survival (OS) and disease-free survival (DFS) among thymoma patients to determine the impact of postoperative radiotherapy (PORT) on thymoma outcomes. METHODS: Recorded cases of thymoma at Xinqiao Hospital were retrospectively analyzed from 1991 to 2019. Data on stage II and III thymomas were extracted from medical records. This study evaluated OS and DFS and compared outcomes between surgery and surgery-plus-radiation groups. The Kaplan-Meier method and Cox regression analysis were used to compare DFS and OS for these groups. RESULTS: Of the 205 patients included in the current study, 142 (69.3%) presented with stage II disease and 63 (30.7%) presented with stage III disease. The median follow-up was 84.3 months. PORT did not statistically significantly improve OS (P = 0.613) and DFS (P = 0.445) in stage II thymoma patients (compared with surgery alone). However, our subgroup analysis showed a statistically significant difference in DFS in patients with stage III thymoma (P = 0.044). CONCLUSION: Although the routine use of postoperative radiotherapy in patients with thymoma does not appear warranted, patients with stage III thymoma may benefit from adjuvant radiation. These findings, if confirmed, will provide valuable information to guide medical decision-making for thymoma treatment.

8.
Front Oncol ; 12: 802683, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35296006

RESUMO

Background: Whether patients with advanced gastric cancer with unresectable synchronous liver metastases require surgical treatment remains a controversial topic among surgeons. Recently, an open-label multicenter, international RCT study show that compared with chemotherapy alone, gastric resection combined with chemotherapy had no survival advantage for advanced gastric cancer with unresectable synchronous liver metastases. A limitation of this study was that gastrectomy for gastric cancers was restricted to D1 lymphadenectomy and no metastatic lesions were removed. Whether D2 gastrectomy plus liver radiofrequency plus postoperative chemotherapy could provide benefits to these patients is worthy of further confirmation by high-level evidence-based medicine. Methods/Design: This study will investigate the efficacy of D2 gastrectomy plus liver radiofrequency plus postoperative chemotherapy compared to chemotherapy alone in a prospective, multicenter, randomized controlled trial that will enroll 200 patients who have advanced gastric cancer with unresectable synchronous liver metastases. The patients will be randomly divided into two groups: the test group (D2 gastrectomy plus liver radiofrequency plus postoperative chemotherapy, n=100) and the control group (chemotherapy alone, n=100). The patients' general information, past medical history, laboratory tests, imaging results, surgery details, and chemotherapy details will be recorded and analysed. The overall survival (OS) will be recorded as primary endpoints. Progression-free survival (PFS) and the total incidence of complications will be recorded as secondary endpoints. Discussion: This study is to establish a multicentre randomized controlled trial to compare the efficacy of D2 gastrectomy plus liver radiofrequency combined with postoperative chemotherapy versus chemotherapy alone. Trial Registration: Chinese Clinical Trial Registry, Approved No. of ethics committee:ChiECRCT20200331. Registered on 15 November 2020. Registration number:ChiCTR2000039964. The study has received full ethical and institutional approval. Advantages and Limitations of this Study: This is the first clinical trial that will provide evidence on the efficacy of D2 gastrectomy plus liver radiofrequency combined with chemotherapy versus chemotherapy alone for the treatment of advanced gastric cancer with unresectable synchronous liver metastases. A prospective RCT with 200 patients who have advanced gastric cancer with unresectable synchronous liver metastases. Clinical Trial Registration: [https://www.chictr.org.cn/], identifier ChiCTR2000039964.

9.
Int J Clin Oncol ; 27(5): 871-881, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35171361

RESUMO

PURPOSE: Clinical evidence of metastasis with ground-glass nodules (GGNs) has been reported, including pulmonary metastasis and distant metastasis. However, the clonal relationships of multiple GGNs at the genetic level remain unclear. EXPERIMENTAL DESIGN: Sixty tissue specimens were obtained from 19 patients with multiple GGN lung cancer who underwent surgery in 2019. Whole exome sequencing (WES) was performed on tissue samples, and genomic profiling and clone evolution analysis were conducted to investigate the genetic characteristics and clonality of multiple GGNs. RESULTS: A total of 15,435 nonsynonymous mutations were identified by WES, and GGNs with shared nonsynonymous mutations were observed in seven patients. Copy number variant (CNV) analysis showed that GGNs in ten patients had at least one shared arm-level CNV. Mutational spectrum analysis showed that GGNs in three patients had similar six substitution profiles and GGNs in fou patients had similar 96 substitution profiles. According to the clone evolution analysis, we found that GGNs in five patients had shared clonal driver gene mutations. Taken together, we identified that 5 patients may have multiple primary GGNs without any similar genetic features, 2 patients may have intrapulmonary metastatic GGNs with ≥ 3 similar genetic features, and the other 12 patients cannot be determined due to insufficient evidences in our cohort. CONCLUSIONS: Our findings suggest that the intrapulmonary metastasis exist in multiple GGNs, but the number of GGNs was not associated with the probability of metastasis. Application of genomic profiling may prove to be important to precise management of patients with multiple GGNs.


Assuntos
Neoplasias Pulmonares , Neoplasias Primárias Múltiplas , Humanos , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Sequenciamento Completo do Exoma
10.
Front Cell Dev Biol ; 10: 830046, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35186935

RESUMO

Background: Almost all lung adenocarcinoma (LUAD) patients with EGFR mutant will develop resistance to EGFR-TKIs, which limit the long-term clinical application of these agents. Accumulating evidence shows one of the main reasons for resistance to EGFR-TKIs is induction of autophagy in tumor cells. Our previous study found that circumsporozoite protein (CSP) in Plasmodium can suppress autophagy in host hepatocytes. However, it is unknown whether CSP-mediated inhibition of autophagy could improve the anti-tumor effect of EGFR-TKIs. Methods: We constructed A549 and H1975 cell lines with stable overexpression of CSP (OE-CSP cells). CCK-8, Lactate Dehydrogenase (LDH), flow cytometry, and colony analysis were performed to observe the effect of CSP overexpression on cell viability, apoptosis rate, and colony formation ratio. The sensitizing effect of CSP on gefitinib was evaluated in vivo using a subcutaneous tumor model in nude mice and immunohistochemical assay. The role of CSP in regulation of autophagy was investigated by laser confocal microscopy assay and western blotting. A transcriptome sequencing assay and real-time polymerase chain reaction were used to determine the levels of mRNA for autophagy-related proteins. Cycloheximide (CHX), MG132, TAK-243, and immunoprecipitation assays were used to detect and confirm proteasomal degradation of LC3B. Results: OE-CSP A549 and H1975 cells were more sensitive to gefitinib, demonstrating significant amounts of apoptosis and decreased viability. In the OE-CSP group, autophagy was significantly inhibited, and there was a decrease in LC3B protein after exposure to gefitinib. Cell viability and colony formed ability were recovered when OE-CSP cells were exposed to rapamycin. In nude mice with xenografts of LUAD cells, inhibition of autophagy by CSP resulted in suppression of cell growth, and more marked apoptosis during exposure to gefitinib. CSP promoted ubiquitin-proteasome degradation of LC3B, leading to inhibition of autophagy in LUAD cells after treatment with gefitinib. When LUAD cells were treated with ubiquitin activating enzyme inhibitor TAK-243, cell viability, apoptosis, and growth were comparable between the OE-CSP group and a control group both in vivo and in vitro. Conclusion: CSP can inhibit gefitinib-induced autophagy via proteasomal degradation of LC3B, which suggests that CSP could be used as an autophagy inhibitor to sensitize EGFR-TKIs.

11.
Ying Yong Sheng Tai Xue Bao ; 33(1): 268-276, 2022 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-35224950

RESUMO

Soil quality of urban green space (UGS) is the basis for ensuring healthy growth of plants and maintaining the healthy ecosystem services for the residents and the sustainable development of city. At present, in order to improve the soil quality of UGS, more attention has been paid to fertility quality and environmental quality, but less to the health quality. We analyzed the concept, connotation, and assessment indicator of soil health quality, summarized the main problems and challenges of soil health quality of UGS. Finally, we put forward the ways and strategies to improve soil health quality of UGS, and prospected future research direction. Our aim was to attract the attention to the soil quality of UGS, especially soil health quality, and the importance of comprehensively improving soil quality of UGS, eventually providing strong technical support for urban sustainable development and eco-city construction.


Assuntos
Ecossistema , Parques Recreativos , Cidades , Solo
12.
J Nanobiotechnology ; 20(1): 55, 2022 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35093073

RESUMO

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) biofilm-associated bacterial infection is the primary cause of nosocomial infection and has long been an ongoing threat to public health. MRSA biofilms are often resistant to multiple antimicrobial strategies, mainly due to the existence of a compact protective barrier; thus, protecting themselves from the innate immune system and antibiotic treatment via limited drug penetration. RESULTS: A hierarchically structured hydrogen sulfide (H2S)-releasing nano-disinfectant was presented, which was composed of a zinc sulfide (ZnS) core as a H2S generator and indocyanine green (ICG) as a photosensitizer. This nano-disinfectant (ICG-ZnS NPs) sensitively responded to the biofilm microenvironment and demonstrated efficient eradication of MRSA biofilms via a synergistic effect of Zn2+, gas molecule-mediated therapy, and hyperthermia. Physically boosted by released H2S and a near-infrared spectroscopy-induced hyperthermia effect, ICG-ZnS NPs destroyed the compactness of MRSA biofilms showing remarkable deep-penetration capability. Moreover, on-site generation of H2S gas adequately ameliorated excessive inflammation, suppressed secretion of inflammatory cytokines, and expedited angiogenesis, therefore markedly accelerating the in vivo healing process of cutaneous wounds infected with MRSA biofilms. CONCLUSION: ICG-ZnS NPs combined with NIR laser irradiation exhibited significant anti-biofilm activity in MRSA biofilms, can accelerate the healing process through deep-penetration and anti-inflammatory effectuation. The proposed strategy has great potential as an alternative to antibiotic treatment when combating multidrug-resistant bacterial biofilms.


Assuntos
Desinfetantes , Staphylococcus aureus Resistente à Meticilina , Infecção dos Ferimentos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios/farmacologia , Biofilmes , Desinfetantes/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Infecção dos Ferimentos/tratamento farmacológico
13.
Int J Surg ; 98: 106219, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34990829

RESUMO

OBJECTIVE: To determine the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) following radical gastrectomy and to identify independent risk factors of CR-POPF. BACKGROUND: CR-POPF and its sequelae are potential complications following radical gastrectomy. The reported incidence of CR-POPF was quite different across various regions, and no consensus was reached. METHODS: Between December 2017 to November 2018, patients who underwent radical gastrectomy from 22 centers across 13 regions in China were prospectively recruited. The primary endpoint was the occurrence of CR-POPF, defined by the International Study Group of Pancreatic Fistula (ISGPF) in 2016. Clinically relevant change and short-term outcomes were recorded to diagnose and grade the POPF. Multivariate regression analyses were performed to identify independent risk factors of clinically relevant postoperative pancreatic fistula (CR-POPF). RESULTS: A total of 2089 cases were analyzed. The incidence of biochemical leakage (BL) and CR-POPF were 19.6% and 1.1% respectively. All CR-POPF patients recovered well after appropriate treatment and no Grade C POPF were recorded. Logistic regression analysis showed pTNM III (OR, 2.940; 95% CI 1.180-7.325; P = 0.021) and LigaSure usage (OR, 6.618; 95% CI 1.847-23.707; P = 0.004) were independent risk factors of CR-POPF. LigaSure usage (OR, 4.817; 95% CI 1.184-19.598; P = 0.028), the drain amylase content (D-AMY) on postoperative day 3 (POD3) ≥5 times the upper limit of normal amylase (OR, 3.476; 95% CI 1.240-9.744; P = 0.018) and open surgery (OR, 2.463; 95% CI 1.003-6.050; P = 0.049) were independent predictors for identifying CR-POPF from BL. CONCLUSION: In rich-experienced gastric cancer centers, there is high prevalence of BL secondary to radical gastrectomy without clinical impact. Fewer patients suffered Grade B POPF, and Grade C POPF was less common. The patients with pTNM III or LigaSure usage were prone to suffer CR-POPF. Surgery procedure, LigaSure usage combined with D-AMY measurement on POD3 are promising for early identification of CR-POPF.


Assuntos
Gastrectomia , Fístula Pancreática , Gastrectomia/efeitos adversos , Humanos , Incidência , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Fístula Pancreática/cirurgia , Pancreaticoduodenectomia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco
14.
Dig Liver Dis ; 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34991975

RESUMO

BACKGROUND: Mucosal healing, the result of endoscopic remission, is associated with prolonged clinical remission and delayed deterioration of Crohn's disease, which is significant and accompanied by reduced hospitalizations and surgeries. Currently, the relationship between ultrasonic parameters and mucosal healing remains controversial. To establish an ultrasonic regression model to evaluate mucosal healing, we conducted this preliminary study using multiple parameters from B-mode ultrasonography, colour Doppler flow imaging and shear wave elastography systematically. METHODS: This study consisted of two single-centre investigations based on development and validation populations who received endoscopies (as the gold standard) and ultrasound. The involved bowel segments were divided into mucosal healing (MH) and nonmucosal healing (NMH) groups according to endoscopic results. Eight ultrasonic parameters were observed, including bowel wall thickness (BWT), mesenteric fat thickness (MFT), median modulus of elasticity (Emean), average shear wave velocity (SWV), Limberg scoring (LG), bowel wall stratification (BWS), ascites (AS) and lymph node enlargement (LN). We developed an ultrasonic regression model in the development phase to evaluate segmental mucosal healing and undertook prospective validation of this model. RESULTS: A total of 124 patients with 380 involved bowel segments from the development and validation cohorts were evaluated. Eight ultrasonic parameters were significantly different between the two groups (P<0.05) in the development phase. Four significant parameters with better AUC performance were selected to establish an ultrasonic regression model to predict mucosal healing. The AUCs of this ultrasonic model were 0.975 and 0.942 in the development and validation cohorts, respectively. CONCLUSION: The multimodal ultrasonic model has the potential to evaluate segmental mucosal healing in Crohn's disease.

15.
Arch Pathol Lab Med ; 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35041745

RESUMO

CONTEXT.­: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are common methods to detect ALK status in inflammatory myofibroblastic tumors (IMTs). However, equivocal ALK FISH signals and inconsistency between FISH and IHC are occasionally observed. OBJECTIVE.­: To study the inconsistency between FISH and IHC, and clarify ALK status in IMT by targeted RNA sequencing (RNAseq). DESIGN.­: In this study, 12 consultation cases preliminarily diagnosed as uncommon IMTs with ALK IHC positivity but FISH negativity, plus 3 ALK-positive and 3 ALK-negative IMTs, were re-analyzed by IHC, FISH, and RNAseq. RESULTS.­: As a result, 1 case with FUS-TFCP2 fusion was detected by RNAseq, which was previously misdiagnosed as IMT. In the other 11 uncommon IMTs, 90.9% (10 of 11) showed equivocal ALK FISH signals, and all were confirmed to harbor ALK fusion by RNAseq, except for 1 failure, suggesting that a low threshold for ALK FISH might be proposed in IMT. Furthermore, RNAseq also identified IGFBP5-ALK in 1 case with ALK IHC positivity but typical FISH negativity, suggesting the possibility of false negatives for ALK FISH. For the typical IMTs, ALK fusion was identified by RNAseq in all 3 ALK-positive IMTs as expected, and additionally FN1-ROS1 fusions were identified in 2 of 3 ALK-negative IMTs. CONCLUSIONS.­: These findings indicated that RNAseq can simultaneously detect multiple gene fusions and provide fusion forms and breakpoints, which is of great value for differential diagnosis, especially for those uncommon IMTs with equivocal FISH findings, or inconsistency between IHC and FISH.

16.
Obesity (Silver Spring) ; 30(1): 172-182, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34889060

RESUMO

OBJECTIVE: The aim of this study was to investigate laparoscopic sleeve gastrectomy (LSG)-induced changes in connectivity between regions involved with reward/antireward and cognitive control and the extent to which these changes persist after surgery and predict sustainable weight loss. METHODS: Whole-brain local functional connectivity density (lFCD) was studied in 25 participants with obesity who underwent resting-state functional MRI before (PreLSG), 1 month after (PostLSG1 ), and 12 months after (PostLSG12 ) LSG and compared with 25 normal-weight controls. Regions with significant time effects of LSG on functional connectivity density were identified for subsequent seed-based connectivity analyses and to examine associations with behavior. RESULTS: LSG significantly increased lFCD in the mediodorsal thalamic nucleus (MD) and in the habenula (Hb) at PostLSG12 compared with PreLSG/PostLSG1 , whereas it decreased lFCD in the posterior cingulate cortex/precuneus (PCC/PreCun) at PostLSG1 /PostLSG12 , and these changes were associated with reduction in BMI. In contrast, controls had no significant lFCD differences between baseline and repeated measures. MD had stronger connectivity with PreCun and Hb at PostLSG12 compared with PreLSG/PostLSG1 , and the increased MD-left PreCun and Hb-MD connectivity correlated with decreases in hunger and BMI, respectively. PCC/PreCun had stronger connectivity with the insula at PostLSG1-12 . CONCLUSIONS: The findings highlight the importance of reward and interoceptive regions as well as that of regions mediating negative emotions in the long-term therapeutic benefits of LSG.


Assuntos
Gastrectomia , Habenula , Núcleo Mediodorsal do Tálamo , Obesidade Mórbida , Cognição/fisiologia , Gastrectomia/métodos , Habenula/anatomia & histologia , Habenula/fisiologia , Humanos , Laparoscopia/métodos , Imageamento por Ressonância Magnética , Núcleo Mediodorsal do Tálamo/anatomia & histologia , Núcleo Mediodorsal do Tálamo/fisiologia , Vias Neurais , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/cirurgia , Resultado do Tratamento , Perda de Peso
18.
Nat Commun ; 12(1): 6283, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725330

RESUMO

Ethylene/polar monomer coordination copolymerization offers an attractive way of making functionalized polyolefins. However, ethylene copolymerization with industrially relevant short chain length alkenoic acid remain a big challenge. Here we report the efficient direct copolymerization of ethylene with vinyl acetic acid by tetranuclear nickel complexes. The protic monomer can be extended to acrylic acid, allylacetic acid, ω-alkenoic acid, allyl alcohol, and homoallyl alcohol. Based on X-ray analysis of precatalysts, control experiments, solvent-assisted electrospray ionization-mass spectrometry detection of key catalytic intermediates, and density functional theory studies, we propose a possible mechanistic scenario that involves a distinctive vinyl acetic acid enchainment enabled by Ni···Ni synergistic effects. Inspired by the mechanistic insights, binuclear nickel catalysts are designed and proved much more efficient for the copolymerization of ethylene with vinyl acetic acid or acrylic acid, achieving the highest turnover frequencies so far for both ethylene and polar monomers simultaneously.

19.
JBMR Plus ; 5(11): e10535, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34761143

RESUMO

The number of total joint replacements (TJRs) in the United States is increasing annually. Cementless implants are intended to improve upon traditional cemented implants by allowing bone growth directly on the surface to improve implant longevity. One major complication of TJR is implant loosening, which is related to deficient osseointegration in cementless TJRs. Although poor osseointegration in aged patients is typically attributed to decreased basal bone mass, little is known about the molecular pathways that compromise the growth of bone onto porous titanium implants. To identify the pathways important for osseointegration that are compromised by aging, we developed an approach for transcriptomic profiling of peri-implant tissue in young and aged mice using our murine model of osseointegration. Based on previous findings of changes of bone quality associated with aging, we hypothesized that aged mice have impaired activation of bone anabolic pathways at the bone-implant interface. We found that pathways most significantly downregulated in aged mice relative to young mice are related to angiogenic, Notch, and Wnt signaling. Downregulation of these pathways is associated with markedly increased expression of inflammatory and immune genes at the bone-implant interface in aged mice. These results identify osseointegration pathways affected by aging and suggest that an increased inflammatory response in aged mice may compromise peri-implant bone healing. Targeting the Notch and Wnt pathways, promoting angiogenesis, or modulating the immune response at the peri-implant site may enhance osseointegration and improve the outcome of joint replacement in older patients. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

20.
Pak J Pharm Sci ; 34(4): 1459-1468, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34799322

RESUMO

First-generation EGFR-TKIs (gefitinib/erlotinib) and second-generation EGFR-TKI (afatinib) have become the current first-line treatments for EGFR-mutated non-small cell lung cancer (NSCLC), however, the effects of using second-generation EGFR-TKIs compared to those of using first-generation EGFR-TKIs as a first-line treatment for NSCLC patients with EGFR mutations remain unknown. We conducted this meta-analysis based on 4 retrospective and 2 randomized controlled studies published between 2016 and 2018. We surveyed the effectiveness of afatinib/dacomitinib and gefitinib/erlotinib as first-line treatments for stage III-IV EGFR-mutated NSCLC patients. The combined hazard ratio (HR) for the progression free survival (PFS) of second-generation EGFR-TKI group versus that first-generation drug group was 0.64 [95% confidence interval (95% CI) 0.55-0.74; P<0.001], demonstrating a superior PFS in the second-generation group. This outcome coincided with the subgroup analyses comparing the PFS of patients with EGFR exon 19 deletion (HR = 0.68 [95% CI 0.55-0.83; P = 0.0002]) or L858R mutation (HR = 0.64 [95% CI 0.51-0.81; p=0.0002]). Meanwhile, second-generation drugs could to significantly improve the time to progression (TTFs) compared to first-generation drugs (HR = 0.81 [95% CI 0.67-0.89; P = 0.03]). Afatinib and dacomitinib may be the superior first-line treatment for advanced NSCLC patients with EGFR mutations.


Assuntos
Afatinib/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib/uso terapêutico , Gefitinibe/uso terapêutico , Genes erbB-1/genética , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/genética , Mutação/genética , Resultado do Tratamento
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