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1.
Methods Mol Biol ; 2186: 3-10, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32918725

RESUMO

Biological nanopores are an emerging class of biosensors with high-end precision owing to their reproducible fabrication at the nanometer scale. Most notably, nanopore-based DNA sequencing applications are currently being commercialized, while nanopore-based proteomics may become a reality in the near future.Although membrane proteins often prove to be difficult to purify, we describe a straightforward protocol for the preparation of Fragaceatoxin C (FraC) nanopores, which may have applications for DNA analysis and nanopore-based proteomics. Recombinantly expressed FraC nanopores are purified via two rounds of Ni-NTA affinity chromatography before and after oligomerization on sphingomyelin-containing liposomes. Starting from a plasmid vector containing the FraC gene, our method allows the production of purified nanopores within a week. Afterward, the FraC nanopores can be stored at +4 °C for several months, or frozen.

2.
Aging (Albany NY) ; 122020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33027769

RESUMO

The value of combining multiple candidate genes into a panel to improve biomarker performance is increasingly emphasized. Genes associated with WNT signaling are widely-reported to provide prognostic signatures in non-small cell carcinoma (NSCLC). Screening of genes involved in this signaling pathway facilitated selection of an optimal candidate biomarker gene combination and development of an NSCLC prognostic model based on expression of these genes. Risk scores derived from the model performed well in predicting survival; in the training dataset, samples achieving a high risk score exhibit a shorter survival interval (median survival time 34.8 months, 95% CI 31.1-41.0) than did samples achieving a low risk score (median survival time 72.0 months, 95% CI 59.3-87.5, p=2e-11), and exhibited higher oncogene and lower tumor suppressor gene expression. Receiver-operator characteristic curves based on three-year survival demonstrate that the model outperformed clinical prognostic indicators. In addition, the model was validated in four independent cohorts, demonstrating robust NSCLC prognostic value. Correlation analyses reveal that the model offers efficacy independent of other clinical indicators. Gene Set Enrichment Analysis (GSEA) reveals that the model reflects variable tissue functional states relevant to NSCLC biology. In summary, the signature model shows potential as a valuable and robust NSCLC prognostic indicator.

3.
Prostate ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33022763

RESUMO

BACKGROUND: Recent genomic profiling has identified a subtype of prostate cancer (PCa) characterized by two key genetic alterations: missense mutation of speckle-type POZ protein (SPOP) and homozygous deletion of chromodomain helicase DNA-binding protein 1 (CHD1). Mutually exclusive with E26 transformation-specific (ETS) rearrangements, this subtype displays high genomic instability. Previous studies indicate that deficient SPOP or CHD1 alone leads to feeble prostate abnormalities and each protein is involved in DNA damage response (DDR). It remains to be determined whether CHD1 and SPOP cooperate to suppress prostate tumorigenesis and DDR. METHODS: Prostate-specific single or double knockout of Spop and Chd1 was generated with the Cre/loxP system in mice. Wild-type or mutant SPOP (F102C, F133V) overexpression and CHD1 knockdown with short hairpin RNA were created in human benign prostatic hyperplasia cell line BPH1. The levels of DNA damage and homologous recombination repair were measured by immunofluorescence staining of γH2AX and RAD51, respectively. RESULTS: Spop/Chd1 double-knockout mice displayed prostatic intraepithelial neoplasia at both young (3 months) and old (12 months) ages and failed to generate prostate adenocarcinoma. Compared with wild-type or single-knockout mice, the double-knockout prostate harbored moderately higher proliferating cells and dramatically augmented the level of γH2AX staining, although androgen receptor-positive cells and apoptotic cells remained at a similar level. In BPH1 cell line, SPOP mutant overexpression and CHD1 silencing synergistically sensitized the cells to DNA damage by camptothecin, an inducer of double-strand breaks. CONCLUSIONS: Our results indicate that SPOP and CHD1 can synergistically promote repair of naturally occurring or chemically induced DNA damages in prostate epithelial cells. Regarding the progression of the SPOP/CHD1 subtype of PCa, other functionally complementary drivers warrant further identification. The clinical implication is that this subtype of PCa may be particularly sensitive to poly(ADP-ribose) polymerase inhibitors or DNA-damaging agents.

4.
J Chem Phys ; 153(12): 124902, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33003754

RESUMO

As an important physical quantity to understand the internal structure of polymer chains, the structure factor is being studied both in theory and experiment. Theoretically, the structure factor of Gaussian chains has been solved analytically, but for wormlike chains, numerical approaches are often used, such as Monte Carlo simulations, solving the modified diffusion equation. In these works, the structure factor needs to be calculated differently for different regions of the wave vector and chain rigidity, and some calculation processes are resource consuming. In this work, by training a deep neural network, we obtained an efficient model to calculate the structure factor of polymer chains, without considering different regions of wavenumber and chain rigidity. Furthermore, based on the trained neural network model, we predicted the contour and Kuhn lengths of some polymer chains by using scattering experimental data, and we found that our model can get pretty reasonable predictions. This work provides a method to obtain the structure factor for polymer chains, which is as good as previous and more computationally efficient. It also provides a potential way for the experimental researchers to measure the contour and Kuhn lengths of polymer chains.

6.
Clin Cancer Res ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046518

RESUMO

PURPOSE: Patients with alveolar soft part sarcoma (ASPS) are rare and have few treatment options. We assessed the activity of geptanolimab (GB226), a fully humanized PD-1 antibody, for patients with unresectable, recurrent or metastatic ASPS. PATIENTS AND METHODS: We did this multicentre, single-arm, phase 2 study (Gxplore-005,NCT03623581) in patients aged 18-75 years who had unresectable, recurrent or metastatic ASPS at 11 sites in China. Patients received intravenous geptanolimab (3 mg/kg) every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed by independent review committee (IRC) per RECIST 1.1 in the full analysis set population. RESULTS: Between September 6, 2018 and March 6, 2019, we enrolled and treated 37 patients with 23 (62.2%) having received prior systemic treatment. 14 (37.8%, 95% confidence interval [CI] 22.5-55.2) of 37 patients had an objective response assessed by IRC with a 6-month duration of response rate of 91.7%. Median progression-free survival was 6.9 months (95% CI 5.0-not reached) and disease control was achieved in 32 (86.5%, 95% CI 71.2-95.5) patients. Three of 37 patients reported grade 3 treatment-related adverse events (TRAEs), including anaemia, hypophysitis and proteinuria (one each [2.7%]). No grade 4 TRAEs were observed. Two (5.4%) patients discontinued treatment due to TRAE (one with hypophysitis and one with Mobitz type I atrioventricular block). The baseline percentage of CD4+ T cells was adversely associated with patient response ( P =0.031). CONCLUSIONS: Geptanolimab has clinically meaningful activity and a manageable safety profile in unresectable, recurrent or metastatic ASPS.

7.
Aging (Albany NY) ; 122020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33065551

RESUMO

The ongoing outbreak of COVID-19 has been announced by the World Health Organization as a worldwide public health emergency. The aim of this study was to distinguish between severe and non-severe patients in early diagnosis. The results showed that the mortality of COVID-19 patients increased accompanied by age. Host factors CRP, IL-1ß, hs-CRP, IL-8, and IL-6 levels in severe pneumonia patients were higher than in non-severe patients. CD3, CD8, and CD45 counts were decreased in COVID-19 patients. The results of this study suggest that the K-values of CD45 might be useful in distinguishing between severe and non-severe cases. The cut-off value for CD45 was -94.33. The K-values for CD45 in non-severe case were above the cut-off values, indicating a 100% prediction success rate for severe and non-severe cases following SARS-CoV-2 infection. The results confirmed that immune system dysfunction is a potential cause of mortality following COVID-19 infection, particularly for the elderly. CD45 deficiency dysfunction the naïve and memory T lymphocytes which may affects the long-term effectiveness of COVID-19 vaccines. K-values of CD45 might be useful in distinguishing between severe and non-severe cases in the early infection. May be CD45 could increase the diagnostic sensitivity.

8.
Fitoterapia ; : 104757, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33069834

RESUMO

Steriods which are ubiquitous in natural resources are important components of cell membranes and involved in several physiological functions. Steriods not only exerted the anticancer activity through inhibition of various enzymes and receptors in cancer cells, inclusive of aromatase, sulfatase, 5α-reductase, hydroxysteroid dehydrogenase and CYP 17, but also exhibited potential activity against various cancer forms including multidrug-resistant cancer, low cytotoxicity, and high bioavailability. Accordingly, steroids are useful scaffolds for the discovery of novel anticancer agents. This review aims to outline the advances in nature-derived steroids outside cardica glycosides with anticancer potential, covering the articles published between Jan. 2015 and Aug. 2020.

9.
Front Immunol ; 11: 582678, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072129

RESUMO

Background: The extent and depth of BK polyomavirus (BKPyV) infection in renal allograft correlate with prognosis. This study was designed to evaluate the value of urinary sediment double-immunostaining for predicting BKPyV infection in proximal tubular epithelium. Materials and methods: A total of 76 urine sediment cell blocks, as well as the corresponding transplanted kidney tissues with BK polyomavirus associated-nephropathy (BKPyVAN), were evaluated by automatic double-immunostaining with anti-58-kDa Golgi protein (58K, a proximal renal tubular marker) + anti-SV40-T and anti-homogentisate 1, 2-dioxygenase (HGD, a renal tubular marker) + anti-SV40-T. Results: Immunohistochemical staining demonstrated that 58K was expressed in proximal tubular epithelium but not in distal tubular epithelium or transitional epithelium. Of the 76 patients, 28 (36.8%) had urinary 58K(+)/SV40-T(+) cells and HGD(+)/SV40-T(+) cells, 41 (53.9%) had only HGD(+)/SV40-T(+) cells, one (1.3%) had only 58K(+)/SV40-T(+) cells, and six (7.9%) had only 58K(-)/HGD(-)/SV40-T(+) cells. The presence of urinary 58K(+)/SV40-T(+) cells was correlated with BKPyV infection in proximal tubular epithelium (P < 0.001, r = 0.806). The mean extent of SV40-T staining was significantly more extensive in patients with urinary 58K(+)/SV40-T(+) cells than those without urinary 58K(+)/SV40-T(+) cells (21.4 vs. 12.0%, P < 0.001). The positive predictive value, negative predictive value, sensitivity, and specificity of urinary 58K(+)/SV40-T(+) cells for predicting BKPyV infection in proximal tubular epithelium were 89.7% (95% CI: 71.5-97.3%), 91.5% (95% CI: 78.7-97.2%), 86.7% (95% CI: 68.4-95.6%), and 93.5% (95% CI: 81.1-98.3%), respectively. Conclusion: Urinary sediment double-immunostaining with anti-58K and anti-SV40-T is valuable for predicting the extent and depth of BKPyV infection in renal allograft.

10.
Technol Cancer Res Treat ; 19: 1533033820967473, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33073697

RESUMO

MiR-124-3p has been identified as a novel tumor suppressor and a potential therapeutic target in hepatocellular carcinoma (HCC) through regulating its target genes. However, the upstream regulatory mechanisms of mir-124-3p in HCC has not been fully understood. The transcription factor liver X receptor (LXR) plays a critical role in suppressing the proliferation of HCC cells, but it is unclear whether LXR is involved in the regulation of mir-124-3p. In the present study, we demonstrated that the expression of mir-124-3p was positively correlated with that of LXR in HCC, and the cell growth of HCC was significantly inhibited by LXR agonists. Moreover, activation of LXR with the agonists up-regulated the expression of mir-124-3p, and in turn down-regulated cyclin D1 and cyclin-dependent kinase 6 (CDK6) expression, which are the target genes of mir-124-3p. Mechanistically, miR-124-3p mediates LXR induced inhibition of HCC cell growth and down-regulation of cyclin D1 and CDK6 expression. In vivo experiments also confirmed that LXR induced miR-124-3p expression inhibited the growth of HCC xenograft tumors, as well as cyclin D1 and CDK6 expression. Our findings revealed that miR-124-3p is a novel target gene of LXR, and regulation of the miR-124-3p-cyclin D1/CDK6 pathway by LXR plays a crucial role in the proliferation of HCC cells. LXR-miR-124-3p-cyclin D1/CDK6 pathway may be a novel potential therapeutic target for HCC treatment.

11.
Theranostics ; 10(21): 9477-9494, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32863940

RESUMO

Background: Patients with advanced soft tissue sarcomas (STS) have a dismal prognosis with few effective therapeutic options. A defect in the homologous recombination repair (HRR) pathway can accumulate DNA repair errors and gene mutations, which can lead to tumorigenesis. BRCAness describes tumors with an HRR deficiency (HRD) in the absence of a germline BRCA1/2 mutation. However, the characteristics of BRCAness in STS remain largely unknown. Thus, this study aimed to explore the genomic and molecular landscape of BRCAness using whole exome sequencing (WES) in STS, aiming to find a potential target for STS treatment. Methods: WES was performed in 22 STS samples from the First Affiliated Hospital of Sun Yat-sen University to reveal the possible genomic and molecular characteristics. The characteristics were then validated using data of 224 STS samples from The Cancer Genome Atlas (TCGA) database and in vitro data. The analysis of the potential biomarker for BRCAness was performed. Targeted drug susceptibility and combination therapy screening of chemotherapeutics for STS were evaluated in STS cell lines, cell-line-derived xenografts (CDX), and patient-derived xenografts (PDX). Results: Compared with 30 somatic mutation signatures of cancers, high cosine-similarity (0.75) was identified for HRD signatures in the 22 STS samples using nonnegative matrix factorization. Single nucleotide polymorphism indicated a low mutation rate of BRCA1/2 in the 22 STS samples (11.76% and 5.88%, respectively). However, copy number variation analyses demonstrated widespread chromosomal instability; furthermore, 54.55% of STS samples (12/22) carried BRCAness traits. Subsequently, similar genomic and molecular characteristics were also detected in the 224 STS samples from TCGA and in vitro. Poly (ADP-ribose) polymerases (PARP)-1 could be a promising reflection of HRD and therapeutic response. Furthermore, the level of PAR formation was found to be correlated with PARP-1. Subsequently, STS cell lines were determined to be sensitive to PARP inhibitor (PARPi), niraparib. Moreover, based on the screening test of the five common PARPis and combination test among doxorubicin, ifosfamide, dacarbazine, and temozolomide (TMZ), niraparib and TMZ were the most synergistic in STS cell lines. The synergistic effect and safety of niraparib and TMZ combination were also shown in CDX and PDX. Conclusions: BRCAness might be the common genomic and molecular characteristics of majority of STS cases. PARP-1 and PAR could be potential proper and feasible theranostic biomarkers for assessing HRD in patients. STSs were sensitive to PARPi. Moreover, the combination of niraparib and TMZ showed synergistic effect. Niraparib and TMZ could be a promising targeted therapeutic strategy for patients with STS.

12.
Ann Surg Oncol ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929601

RESUMO

OBJECTIVES: This study was designed to investigate the potential additive influence of perioperative blood transfusion (BTF) and postoperative infections on cancer-specific survival (CSS) in patients with stage II/III gastric cancer (GC) after radical gastrectomy. METHODS: The medical records of 2114 consecutive stage II/III GC patients who underwent curative resection and planned to receive adjuvant chemotherapy (AC) were retrospectively reviewed. The independent predictive factors for infections were identified using univariate and multivariate analyses. Cox regression analysis was used to assess any associations between BTF, infection and CSS. RESULTS: A total of 507 (24.0%) received perioperative BTF and 148 (7.0%) developed infections with BTF being identified as an independent predictor for infections. Both BTF and infections independently predicted poor CSS (hazard ratio [HR]: 1.193, 95% confidence interval [CI] 1.007-1.414; HR 1.323, 95% CI 1.013-1.727) and an additive effect was confirmed as patients who had both BTF and infection had even worse CSS. Further stratified analyses showed that complete AC (≥ 6 cycles) could significantly improve CSS in patients who had BTF and/or infection, which was comparable to those without BTF and/or infection (P = 0.496). CONCLUSIONS: Infection was the most common complication after gastrectomy and BTF was identified as an independent risk factor. BTF was associated with shorter CSS in stages II/III GC, independent of infections, and receiving BTF and developing infections had an additive effect that was associated with even worse CSS. However, complete AC could significantly improve CSS in these patients. Thus, strategies designed to ensure the completion of AC, such as neoadjuvant chemotherapy, should be further investigated.

13.
Front Immunol ; 11: 1763, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973745

RESUMO

Background: Studies have shown that plasma donor-derived cell-free DNA (dd-cfDNA) can predict renal allograft antibody-mediated rejection. This study was performed to evaluate the value of urine dd-cfDNA concentration and dd-cfDNA fraction (%) for discriminating BK polyomavirus-associated nephropathy (BKPyVAN) in kidney transplant recipients with urinary BK polyomavirus (BKPyV) infection. Methods: In this retrospective single-center observational study, we enrolled kidney transplant recipients who were diagnosed with urine BKPyV infection between August 2018 and May 2019 at the First Affiliated Hospital of Sun Yat-sen University. Urine dd-cfDNA was measured by using a novel target region capture sequencing methodology. The pathological diagnosis of BKPyVAN was confirmed by anti-SV40-T immunohistochemical staining and classified using the American Society for Transplantation schema. Receiver operating characteristic curve analysis was used to investigate the relations of urine dd-cfDNA and dd-cfDNA% to intrarenal allograft BKPyV infection states. Results: In total, 93 patients were enrolled, including 40 cases of proven BKPyVAN, seven cases of probable BKPyVAN, 23 cases of possible BKPyVAN, and 23 cases of resolving BKPyVAN. Urine dd-cfDNA level in proven BKPyVAN (22.09 ± 21.27 ng/ml) was comparable to that in probable BKPyVAN (15.64 ± 6.73 ng/ml, P = 0.434) but was significantly higher than that in possible BKPyVAN (5.60 ± 3.53 ng/ml) and resolving BKPyVAN (5.30 ± 3.34 ng/ml) (both Ps < 0.05). Urine dd-cfDNA% of proven BKPyVAN (0.71 ± 0.21) was lower than that of probable BKPyVAN (0.91 ± 0.04, P < 0.001), but was significantly higher than that of possible BKPyVAN (0.56 ± 0.30) and resolving BKPyVAN (0.46 ± 0.28) (both Ps < 0.05). For distinguishing biopsy-proven BKPyVAN from biopsy-excluded BKPyVAN, the discrimination capacity of urine dd-cfDNA (AUC: 0.842, 95% CI: 0.735, 0.918) was superior to that of plasma BKPyV DNA load (AUC: 0.660, 95% CI: 0.537, 0.769) with 0.181 (95% CI: 0.043, 0.319) difference between areas under ROC curves (P = 0.010). Conclusion: The elevated urine dd-cfDNA level may help discriminate BKPyVAN in kidney transplant recipients with BKPyV viruria.

14.
BMC Med Inform Decis Mak ; 20(Suppl 9): 223, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32967667

RESUMO

BACKGROUND: Prostate cancer is a very common and highly fatal in men. Current non-invasive detection methods like serum biomarker are unsatisfactory. Biomarkers with high accuracy for diagnostic of prostate cancer are urgently needed. Many lipid species have been found related to various cancers. The purpose of our study is to explore the diagnostic value of lipids for prostate cancer. RESULTS: Using triple quadruple liquid chromatography electrospray ionization tandem mass spectrometry, we performed lipidomics profiling of 367 lipids on a total 114 plasma samples from 30 patients with prostate cancer, 38 patients with benign prostatic hyperplasia (BPH), and 46 male healthy controls to evaluate the lipids as potential biomarkers in the diagnosis of prostate cancer. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database was used to construct the potential mechanism pathway. After statistical analysis, five lipids were identified as a panel of potential biomarkers for the detection of prostate cancer between prostate cancer group and the BPH group; the sensitivity, specificity, and area under curve (AUC) of the combination of these five lipids were 73.3, 81.6%, and 0.800, respectively. We also identified another panel of five lipids in distinguishing between prostate cancer group and the control group with predictive values of sensitivity at 76.7%, specificity at 80.4%, and AUC at 0.836, respectively. The glycerophospholipid metabolism pathway of the selected lipids was considered as the target pathway. CONCLUSIONS: Our study indicated that the identified plasma lipid biomarkers have potential in the diagnosis of prostate cancer.

15.
J Int Med Res ; 48(9): 300060520946871, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32962499

RESUMO

Cases of extrahepatic bile duct carcinoma are mostly adenocarcinomas and extrahepatic bile duct squamous cell carcinomas are rare. We report here a case of choledochal squamous cell carcinoma in a young woman who underwent surgery and chemotherapy. The woman presented with abdominal discomfort. A physical examination showed tenderness in the upper abdomen. Laboratory tests showed elevated direct bilirubin, total bilirubin, and C-reactive protein levels. Abdominal computed tomography and magnetic resonance imaging showed a cystic-solid mixed soft tissue mass in the common bile duct. Pain symptoms in the patient were not relieved and surgical treatment was performed. Postoperative pathological results showed a choledochal cyst complicated by squamous cell carcinoma. The patient was treated by biliary intestinal anastomosis followed by chemotherapy. However, the patient developed liver metastasis and recurrence at a 6-month follow-up. Primary congenital bile duct cysts with squamous cell carcinoma are extremely rare. Surgical resection is the main treatment option for choledochal squamous cell carcinoma. Postoperative chemoradiotherapy can be used, but the efficacy is poor and chemotherapy does not significantly prolong the patient's survival.

16.
J Exp Clin Cancer Res ; 39(1): 186, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32928266

RESUMO

BACKGROUND: Bladder cancer (BC) is a common genitourinary malignancy worldwide. Circular RNAs (circRNAs) participate in cancer development, including BC; thus, the roles of circRNAs in this process have attracted significant attention. METHODS: In this study, high-throughput sequencing was used to analyze circRNA expression profiles in BC tissues. We performed RT-qPCR to determine hsa_circ_0001944 expression in BC tissues. We used fluorescence in situ hybridization (FISH) to detect hsa_circ_0001944 expression and hsa_circ_0001944 subcellular localization in BC tissues. hsa_circ_0001944 expression in BC cells was selectively regulated. We employed CCK8, transwell, and wound healing assays to monitor cell proliferation, invasion, and migration, respectively. We employed the dual-luciferase reporter and RNA pulldown assays to verify the relationships among hsa_circ_0001944, miR-548, and PROK2. We examined the effects of hsa_circ_0001944 on BC cell metastasis and proliferation in vivo using a subcutaneous xenograft model and an intravenous tail injection model in nude mice. RESULTS: The results showed that hsa_circ_0001944 expression was significantly increased in BC samples. Furthermore, high hsa_circ_0001944 expression predicted unfavorable prognoses in BC. Functional assays validated that downregulating hsa_circ_0001944 decreased BC invasion and proliferation in vivo and in vitro. Further studies showed that hsa_circ_0001944 expression promoted BC progression via sponging miR-548 and enhancing PROK2 expression. Luciferase reporter experiments validated the interactions between hsa_circ_0001944, miR-548, and PROK2. This study also found that downregulating miR-548 or overexpressing PROK2 restored BC cell invasion and proliferation after silencing hsa_circ_0001944. CONCLUSIONS: Taken together, we found that hsa_circ_0001944 is a tumor-promoting circRNA in BC that functions as a competing endogenous RNA to regulate PROK2 expression via sponging miR-548.

17.
World J Surg Oncol ; 18(1): 246, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933524

RESUMO

BACKGROUND: At present, amputation was widely adopted for young patients when limb salvage was deemed risky with several surgical strategy such as rotationplasty. However, leg length discrepancies and unfavorable cosmetic results were indispensable complication of this strategy. The purpose of this study was to propose a novel reconstruction strategy and evaluate the early clinical and functional outcomes of the strategy. METHODS: Plastic lengthening amputation (PLA) has been developed by lengthening the stump to preserve one additional distal joint for fixing the artificial limb well. The surgical technique and postoperative management were documented, and the functional outcomes were compared with those of traditional amputation (TA). Six pairs of patients matched for age, sex, location, pathological type, and final prosthesis underwent individually designed plastic lengthening amputation with vascularized autografts or traditional amputation between January 2005 and December 2007. All patients were followed, and the locomotor index and the musculoskeletal tumor society score (MSTS) were used to describe and quantitatively grade limb functional outcomes after amputation. The complications and functional outcomes of the patients taken two kinds of procedures were compared. RESULTS: Twelve patients with osteosarcoma or Ewing's sarcoma of either the femur or tibia were included in the study. Six patients underwent plastic lengthening amputations, three of whom also underwent vascular anastomosis. Patients were followed for an average of 48.17 months; bone healing required an average of 3.3 months. No local recurrence was found. The average postoperative locomotor index functional score of the affected limb was 32.67 ± 5.89 in the plastic lengthening amputation group while was 19.50 ± 7.87 in the traditional amputation group. The MSTS functional scores were 22.67 ± 1.33 and 24.17 ± 1.45 at 6 and 12 months for patients in PLA group while 17.00 ± 1.549 and 17.83 ± 1.64 at 6 and 12 months for patients in TA group. CONCLUSIONS: Plastic lengthening amputations with vascularized autografts could preserve the knee joint to improve the function of the amputated limb in selected bone sarcoma patients.

18.
Skeletal Radiol ; 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32767060

RESUMO

OBJECTIVE: This study observed the distribution of CT attenuation values for T10-L3 vertebral bodies and derived the Hounsfield unit (HU) thresholds using the quantitative computed tomography (QCT) as a reference to predict osteoporosis and normal bone density. METHODS: We included 482 subjects who were scheduled to undergo CT lung cancer screening and pulmonary nodule follow-up from May 2015 to February 2019. The subjects were scanned with the calibration phantom beneath the back while performing a chest CT scan. The volumetric bone mineral density (vBMD) and CT attenuation values of T10-L3 vertebral bodies were measured, and the correlation between the two measurements was analyzed. Receiver operator characteristic (ROC) curves were generated to determine diagnostic optimal thresholds. RESULTS: A total of 2716 vertebral bodies of 457 participants were measured after exclusion screening. CT attenuation value of each plane's vertebral body showed a strong correlation with vBMD. The optimal threshold of > 141 HU was 93.5% sensitive and 86.1% specific for the recognition of normal BMD. The optimal threshold of < 102.4 HU was 96.9% specific and 82.1% sensitive for distinguishing osteoporosis from osteopenia and normal BMD. The average CT attenuation values of vertebral bodies with compressed and normal morphology were 108.9 ± 20.6 and 136.8 ± 32.2 HU, respectively. CONCLUSION: Sagittal reconstruction of the thoracic vertebrae using routine thoracic CT image combined with CT attenuation value measurements of the spine is valuable for predicting bone mineral density in high-risk populations. The mean CT attenuation values of the vertebral bodies with vertebral compression appearance were lower than that of normal vertebral shape.

19.
BMC Microbiol ; 20(1): 243, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762711

RESUMO

BACKGROUND: Escherichia coli always plays an important role in microbial research, and it has been a benchmark model for the study of molecular mechanisms of microorganisms. Molecular complexes, operons, and functional modules are valuable molecular functional domains of E. coli. The identification of protein complexes and functional modules of E. coli is essential to reveal the principles of cell organization, process, and function. At present, many studies focus on the detection of E. coli protein complexes based on experimental methods. However, based on the large-scale proteomics data set of E. coli, the simultaneous prediction of protein complexes and functional modules, especially the comparative analysis of them is relatively less. RESULTS: In this study, the Edge Label Propagate Algorithm (ELPA) of the complex biological network was used to predict the protein complexes and functional modules of two high-quality PPI networks of E. coli, respectively. According to the gold standard protein complexes and function annotations provided by EcoCyc dataset, most protein modules predicted in the two datasets matched highly with real protein complexes, cellular processes, and biological functions. Some novel and significant protein complexes and functional modules were revealed based on ELPA. Moreover, through a comparative analysis of predicted complexes with corresponding functional modules, we found the protein complexes were significantly overlapped with corresponding functional modules, and almost all predicted protein complexes were completely covered by one or more functional modules. Finally, on the same PPI network of E. coli, ELPA was compared with a well-known protein module detection method (MCL) and we found that the performance of ELPA and MCL is comparable in predicting protein complexes. CONCLUSIONS: In this paper, a link clustering method was used to predict protein complexes and functional modules in PPI networks of E. coli, and the correlation between them was compared, which could help us to understand the molecular functional units of E. coli better.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32810279

RESUMO

OBJECTIVES: Long non-coding RNA H19 (lncRNA-H19) is highly expressed in fibroblast-like synoviocytes (FLS) from patients with RA. The present study aimed to clarify the pathological significance and regulatory mechanisms of lncRNA-H19 in FLS. METHODS: Mice with CIA were locally injected with LV-shH19. The progression of CIA was explored by measuring arthritic index (AI), paw thickness (PT) and histologic analysis. The growth and cell cycle of human synoviocyte MH7A were assessed by CCK-8 and flow cytometric analysis. The putative binding sites between lncRNA-H19 and miR-124a were predicted online, and the binding was identified by luciferase assay. RT-qPCR, Western blot and luciferase assay were performed to explore the molecular mechanisms between liver X receptor (LXR), lncRNA-H19, miR-124a and its target genes. RESULTS: The expression of lncRNA-H19 was closely associated with the proliferation of synoviocytes and knockdown of lncRNA-H19 significantly ameliorated the progression of CIA, reflected by decreased AI, PT and cartilage destruction. Notably, lncRNA-H19 competitively bound to miR-124a, which directly targets CDK2 and MCP-1. It was confirmed that lncRNA-H19 regulates the proliferation of synoviocytes by acting as a sponge of miR-124a to modulate CDK2 and MCP-1 expression. Furthermore, the agonists of LXR inhibited lncRNA-H19-mediated miR-124a-CDK2/MCP-1 signalling pathway in synoviocytes. The 'lncRNA-H19-miR-124a-CDK2/MCP-1' axis plays an important role in LXR anti-arthritis. CONCLUSION: Regulation of the miR-124a-CDK2/MCP-1 pathway by lncRNA-H19 plays a crucial role in the proliferation of FLS. Targeting this axis has therapeutic potential in the treatment of RA and may represent a novel strategy for RA treatment.

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