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1.
DNA Res ; 30(5)2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37788574

ABSTRACT

Characiformes is a diverse and evolutionarily significant order of freshwater fish encompassing over 2,300 species. Despite its diversity, our understanding of Characiformes' evolutionary relationships and adaptive mechanisms is limited due to insufficient genome sequences. In this study, we sequenced and assembled the genomes of four Characiformes species, three of which were chromosome-level assemblies. Our analyses revealed dynamic changes in gene family evolution, repeat sequences and variations in chromosomal collinearity within these genomes. With the assembled genomes, we were not only able to elucidate the evolutionary relationship of the four main orders in Otophysi but also indicated Characiformes as the paraphyletic group. Comparative genomic analysis with other available fish genomes shed light on the evolution of genes related to tooth development in Characiformes. Notably, variations in the copy number of secretory calcium-binding phosphoproteins (SCPP) genes were observed among different orders of Otophysi, indicating their potential contribution to the diversity of tooth types. Our study offers invaluable genome sequences and novel insights into Characiformes' evolution, paving the way for further genomic and evolutionary research in fish.


Subject(s)
Characiformes , Animals , Phylogeny , Characiformes/genetics , Genome , Base Sequence , Genomics
2.
World J Surg ; 47(9): 2221-2229, 2023 09.
Article in English | MEDLINE | ID: mdl-37266695

ABSTRACT

BACKGROUND: To secure surgical margin for hepatic lesion with involvement of the inferior vena cava (IVC), combined radical liver resection and IVC replacement are required. A novel method of replacing IVC by newly customized autologous great saphenous vein (GSV) grafts was introduced by this study. This study aimed at reporting the feasibility and outcome of this novel technique. METHODS: From January 2014 to January 2021, all consecutive patients who underwent concomitant hepatectomy and IVC replacement by autogenous GSV graft were enrolled in this study. Technical insights, intraoperative details, demographic data, postoperative complication, graft patency and survival data were collected and analyzed. RESULTS: Concomitant hepatectomy/autotransplantation (ERAT) with IVC replacement by autogenous GSV graft was successful in 47 patients and there was no 30-day mortality. There were 8 out of the 47 patients whose retrohepatic venae cavae were completely invaded by the lesion and their reconstructed IVCs were totally made from GSV grafts. The other 39 patients whose IVCs were partially invaded had their IVCs reconstructed by both the unaffected part of the IVC wall and newly customized GSV graft. Postoperative complications classified as Clavien-Dindo grade II, III A and III B were observed in 10, 7 and 3 patients, respectively. The median follow-up months were 35 months (29-80 months). No patient developed thrombosis of the graft and 100% patency of the IVC was observed throughout the study. CONCLUSION: In selected patients, hepatectomy/ERAT with IVC replacement by autogenous GSV graft is safe and feasible. The newly customized autologous GVS graft was ideal for reconstruction of the IVC in liver surgery.


Subject(s)
Liver Neoplasms , Vena Cava, Inferior , Humans , Vena Cava, Inferior/surgery , Vena Cava, Inferior/pathology , Liver Neoplasms/surgery , Saphenous Vein/pathology , Hepatectomy/methods , Postoperative Complications/surgery
3.
Asian J Surg ; 46(1): 213-221, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35367096

ABSTRACT

BACKGROUND: The use of artificial or autologous materials for inferior vena cava (IVC) reconstruction is controversial. This study retrospectively explored the effects of different materials on perioperative outcomes. METHODS: This study included 91 patients who underwent IVC reconstruction during liver autotransplantation between 2014 and 2020. A univariate analysis was performed to select variables affecting postoperative morbidity. The effect of IVC reconstruction materials on perioperative outcomes was tested with a multivariable generalized linear model. The effects on postoperative morbidity and operation time were further tested with the multivariate regression analysis based on the generalized estimating equation. Adjusted models were used in all analyses. RESULTS: A median operation time of 710 (633-790) min, a median blood loss of 2200 (1550-3000) mL, an incidence of 33% (30/91) for major morbidities and a median comprehensive complication index (CCI) of 0.0 (0.0-26.2) were observed, with no IVC reconstruction-related complications postoperatively or in the long term. The IVC reconstruction material had no significant effect on postoperative outcomes, while artificial materials significantly increased inpatient cost (191 ± 35 vs. 164 ± 36 k Yuan, p < 0.001). The multivariate regression revealed a significant shift in outcomes of operation time (p = 0.0368). DISCUSSION: Artificial grafts are recommended for IVC reconstruction if cost is not a factor.


Subject(s)
Hepatectomy , Vena Cava, Inferior , Humans , Vena Cava, Inferior/surgery , Transplantation, Autologous , Retrospective Studies , Liver/surgery
4.
Dig Liver Dis ; 55(4): 549-556, 2023 04.
Article in English | MEDLINE | ID: mdl-36002361

ABSTRACT

BACKGROUND: The effect of surgical resection on the long-term outcome of GIST patients with initially diagnosed synchronous hepatic metastases in the targeted therapy era is still uncertain. The main aims of this study were to investigate the role of surgery in the treatment of these patients and establish clinical predictive models for assessing prognosis. METHODS: We identified these patients from the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2018. The selection bias in comparisons was minimized by performing propensity score matching (PSM). The risk factors associated with long-term survival outcomes were identified by a Cox proportional hazards model and thus used to establish the nomograms. Nomograms were validated by concordance indexes (C-indexes), time-dependent receiver operator characteristic (ROC) curves, calibration plots, and decision curve analyses (DCA). RESULTS: Of these 523 eligible patients, there were 187 (35.8%) and 336 (64.2%) patients in the surgical and nonsurgical groups, respectively. Multivariate analysis revealed that surgical resection was an independent prognostic factor for OS (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.44-0.88, p = 0.0068) and CSS (HR 0.51; 95% CI 0.33 - 0.77, p = 0.0016). After PSM, it was found that surgical resection still showed significantly improved OS (5-year 54.9% vs 38.8%, p = 0.028) and CSS (5-year 65.8% vs 50.3%, p = 0.077). In addition, the C-indexes of the nomograms for OS and CSS prediction were 0.692 and 0.705, respectively, and the nomograms showed good consistency. CONCLUSION: This study revealed that surgical resection has a favorable impact on the long-term outcome of patients with synchronous GIST liver metastases, and the nomograms showed remarkable prediction performance for OS and CSS.


Subject(s)
Gastrointestinal Stromal Tumors , Liver Neoplasms , Humans , Gastrointestinal Stromal Tumors/surgery , Neoplasm Staging , Prognosis , Nomograms , Liver Neoplasms/surgery
5.
Oncol Lett ; 24(6): 445, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36420075

ABSTRACT

P38 mitogen-activated protein kinase (MAPK)12 (also known as P38 γ) is critical in the development and progression of various types of tumors. Despite the extensive literature on the subject, further studies are needed to elucidate its role in cancer progression. Here, a comprehensive bioinformatics analysis of a generalized cancer dataset was performed to explore the mechanism of MAPK12 regulation in tumorigenesis. Several tumor datasets and online analytical tools, including HPA, SangerBox, UALCAN, GEPIA2, STRING, ImmuCellAI, and MEXPRESS, were used to analyze the expression information on MAPK12 in several types of cancers. Western blotting and reverse transcription-quantitative PCR were used to verify the protein and mRNA expression levels of MAPK12, respectively, in human normal thyroid cells (HTORI-3) and thyroid carcinoma (THCA) cells. Cytotoxicity and EdU assays were used to verify the promoting effect of MAPK12 on cell proliferation in THCA cells. Analysis of several cancers found that MAPK12 was overexpressed in multiple cancer types. Upregulated MAPK12 mRNA expression levels were correlated with a worse prognosis in patients with several types of cancer. Cytotoxicity and EdU experiments showed that MAPK12 knockdown inhibited THCA cell proliferation. Gene Ontology-Biological Process and Kyoto Encyclopedia of Genes and Genomes analyses showed that the enrichment of MAPK12 genes was related to cell proliferation and the tumor immune microenvironment. These results showed that MAPK12 was closely related to the immune checkpoint, microsatellite instability, and tumor mutational burden and affected the sensitivity of the tumor to immunotherapy. This study showed that MAPK12 may be an immunotherapeutic and promising prognostic biomarker in certain types of tumors.

7.
Front Immunol ; 13: 843408, 2022.
Article in English | MEDLINE | ID: mdl-35693827

ABSTRACT

Macrophages have been reported to exert a crucial role in hepatocellular carcinoma (HCC). This study aimed to explore the macrophage-related genes and establish a macrophage-related signature (MRS) model to predict the overall survival (OS) of patients with HCC based on these genes' expression. We screened the macrophage-related gene module by weighted gene coexpression network analysis (WGCNA), the least absolute shrinkage and selection operator (LASSO) Cox regression analysis was utilized for further selection, and the selected genes were entered into stepwise regression to develop the MRS model, which was further validated in the Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC) datasets. We analyzed the biological phenotypes associated with macrophages in terms of functional enrichment, tumor immune signature, and tumor mutational signature. The patient's response to immunotherapy was inferred by the tumor immune dysfunction and exclusion (TIDE) score, the immunophenotype score (IPS), and the IMvigor210 dataset. A novel MRS model was established based on the LASSO regression coefficients of the genes PON1, IL15RA, NEIL3, HILPDA, PFN2, HAVCR1, ANXA10, CDCA8, EPO, S100A9, TTK, KLRB1, SPP1, STC2, CYP26B1, GPC1, G6PD, and CBX2. In either dataset, MRS was identified as an independent risk factor for OS in HCC patients. Additionally, our research indicated that a high-risk score in the MRS model was significantly correlated with tumor staging, pathological grade, tumor-node-metastasis (TNM) stage, and survival. Several genes of the human leukocyte antigen (HLA) family and immune checkpoints were highly expressed in the high-risk group. In addition, the frequency of tumor mutations was also higher in the high-risk group. According to our analyses, a higher risk score in the MRS model may predict a better response to immunotherapy.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Algorithms , Aryldialkylphosphatase , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/therapy , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Humans , Immunotherapy , Liver Neoplasms/genetics , Liver Neoplasms/therapy , Macrophages/metabolism , Profilins/genetics , Prognosis
8.
Int J Pharm ; 622: 121851, 2022 Jun 25.
Article in English | MEDLINE | ID: mdl-35618178

ABSTRACT

Vulvar candidiasis (VVC) is a vaginitis caused by vaginal mucosa infection of Candida, which greatly impairs women's health. Although there are more and more thiazoles on the market, new classes of antifungal drugs are still missing, it is still challenging to treat azole-resistant candidal vaginitis. We found that L-Se-methylselenocysteine (L-SeMC) could effectively inhibit the growth of Candida albicans, reduce the density and length of the mycelia. To extend the retention time of L-SeMC in the vaginal tract and enhance its therapeutic effect for VVC, a mucoadhesive thermogel (NAC-HA thermogel) was successfully synthesized and prepared. The gelation window was around 29-56 °C for L-SeMC loaded mucoadhesive thermogel (L-SeMC@NAC-HA thermogel), which exhibited a sustained release profile in the in vitro release study and an extended retention time in the vaginal tract. Besides, L-SeMC@NAC-HA thermogel exhibited a good safety profile in the in vivo safety study. The in vivo anti-VVC effect was examined in a rat VVC model and L-SeMC@NAC-HA thermogel significantly reduced the number of Candida albicans in the vaginal secreta, mitigated the vaginal damage and reduced the secretion of proinflammatory factors (TNF-α, IL-1α and IL-ß). Therefore, it is a promising therapy for the clinical treatment of VVC in the near future.


Subject(s)
Candidiasis, Vulvovaginal , Animals , Antifungal Agents , Candida , Candida albicans , Candidiasis, Vulvovaginal/drug therapy , Female , Humans , Rats , Selenocysteine/analogs & derivatives
9.
Microb Drug Resist ; 28(4): 468-483, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35451882

ABSTRACT

Background: Candida albicans catheter-related infection (CRI) is a great challenge in clinic now, mainly due to the difficulty in eradicating the biofilms. Purpose: In this study, the mechanism of the antibiofilm effect of myricetin (MY) on C. albicans was illustrated. A film forming system (FFS) containing MY and miconazole nitrate (MN) was developed, optimized, and evaluated. The anti-infection effect of MY+MN@FFS against C. albicans CRI was investigated in vivo. Study Design and Methods: To clarify the mechanism of the action of MY, the influence of MY on each key process of the formation of C. albicans biofilms was evaluated. To deliver MY and MN into the skin and form a drug reservoir on the surface of the skin, the FFS was used as a carrier and MY+MN@FFS was developed, optimized, and evaluated. After preliminary confirmation of drug safety, a percutaneously inserted C. albicans CRI mouse model was established to investigate the in vivo anti-infection effect of MY+MN@FFS by fluorescence microscopy and scanning electron microscopy on the outer surface of the catheters, hematoxylin/eosin staining, and periodic acid-Schiff staining of the mice skin tissues. Results: MY was found to inhibit the morphological transition of C. albicans and the secretion of exopolysaccharides, resulting in a reduction in biofilms. MY+MN@FFS exhibited excellent properties and no irritation to mice skin. In an in vivo anti-infection study, MY+MN@FFS exhibited an excellent preventive effect against percutaneously inserted C. albicans CRI. Conclusion: MY+MN@FFS might be a potential approach for effectively preventing percutaneously inserted C. albicans CRI in clinic.


Subject(s)
Anti-Infective Agents , Catheter-Related Infections , Animals , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Biofilms , Candida albicans , Catheter-Related Infections/drug therapy , Catheter-Related Infections/prevention & control , Flavonoids , Mice , Miconazole/pharmacology
10.
Clin Infect Dis ; 75(8): 1289-1296, 2022 10 12.
Article in English | MEDLINE | ID: mdl-35271705

ABSTRACT

BACKGROUND: Ex vivo liver resection and autotransplantation (ELRA) has shown promising outcomes in treating end-stage hepatic alveolar echinococcosis (AE). However, the actual benefits and risks remain unclear. This study aims to analyze the benefits and risks of ELRA. METHODS: This retrospective cohort analysis included 228 patients with end-stage hepatic AE who underwent ELRA or nonsurgical treatment between 2014 and 2020. Propensity score matching was used. Long-term survival was compared in the matched cohorts using Kaplan-Meier curves generated with the log-rank test. Short-term mortality in entire cohort was predicted based on the nonsurgical group, and the interaction between the predicted mortality risk and observed mortality was tested. Risk factors for postoperative major morbidity in the ELRA group were evaluated using logistic regression analyses. RESULTS: The long-term overall survival of the ELRA group was superior to that of the nonsurgical group (82.1% vs 19.1%, 5-year survival). Regarding short-term outcomes, the basic risk of 12-month mortality exerted a significant effect on the benefit of ELRA in entire cohort (per 1%, odds ratio, 1.043; 95% confidence interval [CI]: 1.007-1.082; P = .021). Patients with a predicted 12-month mortality risk >75% would significantly benefit from ELRA. Combined resection (hazard ratio [HR], 3.32; 95% CI: 1.01-10.99; P = .049) and overall surgery time (per hour, HR, 1.41; 95% CI: 1.09-1.82; P = .009) were identified as independent risk factors for postoperative major morbidity. CONCLUSIONS: ELRA was significantly beneficial in selected patients with end-stage AE compared with nonsurgical treatment. The timing of conducting ELRA remarkably affected the short-term risk of mortality and should be carefully determined.


Subject(s)
Echinococcosis, Hepatic , Liver Transplantation , Echinococcosis , Echinococcosis, Hepatic/etiology , Echinococcosis, Hepatic/surgery , Humans , Liver Transplantation/adverse effects , Retrospective Studies , Risk Assessment , Transplantation, Autologous/adverse effects
13.
Front Surg ; 8: 753968, 2021.
Article in English | MEDLINE | ID: mdl-34917647

ABSTRACT

Background: This retrospective study aimed to evaluate the safety and learning curve of ex vivo liver resection and autotransplantation (ELRA). Methods: A total of 102 consecutive end-stage HAE patients who underwent ELRA between 2014 and 2020 in West China Hospital were enrolled. The primary endpoint was major postoperative complications (comprehensive complication index, CCI > 26). The ELRA learning curve was evaluated using risk-adjusted cumulative sum (RA-CUSUM) methods. The learning phases were determined based on RA-CUSUM analysis and tested for their association with intra- and post-operative endpoints. Results: The median surgery time was 738 (659-818) min, with a median blood loss of 2,250 (1,600-3,000) ml. The overall incidence of major morbidity was 38.24% (39/102). Risk-adjusted cumulative sum analysis demonstrated a learning curve of 53 ELRAs for major postoperative complications. The learning phase showed a significant association with the hemodynamic unstable time (HR -30.29, 95% CI -43.32, -17.25, P < 0.0001), reimplantation time (HR -13.92, 95% CI -23.17, -4.67, P = 0.004), total postoperative stay (HR -6.87, 95% CI -11.33, -2.41, P = 0.0033), and postoperative major morbidity (HR 0.25, 95% CI 0.09, 0.68, p = 0.007) when adjusted for age, disease course, liver function, and remote metastasis. Discussion: Ex vivo liver resection and autotransplantation is feasible and safe with a learning curve of 53 cases for major postoperative complications.

14.
Infect Drug Resist ; 14: 4887-4901, 2021.
Article in English | MEDLINE | ID: mdl-34848980

ABSTRACT

BACKGROUND: Sarcopenia and visceral adiposity have been shown to be associated with postoperative complications in numerous diseases. However, their effects on the postoperative complications of end-stage hepatic alveolar echinococcosis (HAE) patients undergoing ex vivo liver resection and autotransplantation (ELRA) remain unclear. METHODS: This retrospective study included 101 end-stage HAE patients who underwent ELRA from January 2014 to August 2020. We measured the skeletal muscle and adipose tissue of all patients at the level of the third lumbar vertebra on plain abdominal computed tomography (CT) images and subsequently derived an equation via least absolute shrinkage and selection operator (LASSO) regression analysis to calculate the sarcopenia score. Univariate and multivariate regression were performed to reveal the relationship between major postoperative complications and perioperative clinical data, and the obtained nomogram was validated with the bootstrapping method. RESULTS: The sarcopenia score was constructed as a personalized indicator to evaluate sarcopenia and visceral adiposity in each patient. Logistic regression analysis finally selected duration from primary diagnosis to obvious symptoms (OR=1.024, 95% CI, 1.007-1.042), surgical time (OR=1.003, 95% CI, 0.999-1.007) and sarcopenia score (OR=4.283, 95% CI, 1.739-10.551) as independent risk factors for predicting major postoperative complications following ELRA for end-stage HAE patients. The area under the receiver operating characteristic curve (AUROC) of 0.807 (95% CI, 0.720-0.895) and the calibration curve for this prediction model were satisfactory. CONCLUSION: The sarcopenia score, which systematically evaluates the skeletal muscle and adipose tissue of end-stage HAE patients, was a significant predictive factor for major postoperative complications of ELRA. Relevant interventions should be conducted for those who have a high risk of postoperative complications according to the nomogram.

15.
Cancer Manag Res ; 13: 7463-7477, 2021.
Article in English | MEDLINE | ID: mdl-34611440

ABSTRACT

BACKGROUND: Spontaneous rupture bleeding is a fatal hepatocellular carcinoma (HCC) complication and a significant determinant of survival outcomes. This study aimed to develop and validate a novel artificial neural network (ANN)-based survival prediction model for patients with spontaneous HCC rupture after transcatheter arterial embolization (TAE). METHODS: Patients with spontaneous HCC rupture bleeding who underwent TAE at our hospital between January 2010 and December 2018 were included in our study. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to screen clinical variables related to prognosis. We incorporated the above clinical variables identified by LASSO Cox regression into the ANNs model. Multilayer perceptron ANNs were used to develop the 1-year overall survival (OS) prediction model for patients with spontaneous HCC ruptured bleeding in the training set. The area under the receiver operating characteristic curve and decision curve analysis were used to compare the predictive capability of the ANNs model with that of existing conventional prediction models. RESULTS: The median survival time for the whole set was 11.8 months, and the 1-year OS rate was 47.5%. LASSO Cox regression revealed that sex, extrahepatic metastasis, macroscopic vascular invasion, tumor number, hepatitis B surface antigen, hepatitis B e antigen, tumor size, alpha-fetoprotein, fibrinogen, direct bilirubin, red blood cell, and γ-glutamyltransferase were risk factors for OS. An ANNs model with 12 input nodes, seven hidden nodes, and two corresponding prognostic outcomes was constructed. In the training set and the validation set, AUCs for the ability of the ANNs model to predict the 1-year OS of patients with spontaneous HCC rupture bleeding were 0.923 (95% CI, 0.890-0.956) and 0.930 (95% CI, 0.875-0.985), respectively, which were higher than that of the existing conventional models (all P < 0.0001). CONCLUSION: The ANNs model that we established has better survival prediction performance.

16.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(9): 1086-1092, 2021 Sep 15.
Article in Chinese | MEDLINE | ID: mdl-34523271

ABSTRACT

OBJECTIVE: To formulate the classification criteria of femoral intertrochanteric fractures based on irreducibility or not in order to predict the difficulty of fracture recovery. METHODS: A clinical data of 244 patients with closed femoral intertrochanteric fractures admitted between January 2017 and March 2020 was retrospectively analyzed. There were 116 males and 128 females with an average age of 77.9 years (range, 45-100 years). The cause of injury included falling in 190 cases, traffic accident in 36 cases, smashing in 13 cases, and falling from height in 5 cases. The time from injury to operation was 1-14 days (mean, 3.6 days). According toAO/Orthopaedic Trauma Association (AO/OTA) classification, the fractures were classified as type 31-A1 in 38 cases, type 31-A2 in 160 cases, and type 31-A3 in 46 cases. According to whether the recovery difficulty occurred after intraoperative closed traction reset, the patients were divided into reducible-group and irreducible-group; combined with the literature and preoperative imaging data of two groups, the classification criteria of femoral intertrochanteric fractures was formulated based on the irreducibility or not. The 244 fractures were classified by the doctors who did not attend the operation according to the classification criteria, predicted the difficulty of fracture reduction, and compared with the actual intraoperative reduction situation. RESULTS: The 244 patients were divided into reducible-group ( n=164, 67.21%) and irreducible-group ( n=80, 32.79%) according to the intraoperative difficulty of reduction. Comparing the imaging data and characteristics of the two groups, and formulating the classification criteria of femoral intertrochanteric fractures based on irreducibility or not, the fractures were mainly divided into two categories of irreducibility and reducibility. The fractures of irreducibility category was divided into typesⅠ-Ⅴ, among which type Ⅲ was divided into subtypes 1-4; the fractures of reducibility category was divided into typesⅠand Ⅱ. Compared with the actual intraoperative evaluation results, the total accuracy rate of the doctors who did not attend the operation was 81.15% (198/244) based on the classification criteria of femoral intertrochanteric fractures. The accuracy rate of irreducibility category was 65.74% (71/108), and the reducibility category was 93.38% (127/136). All patients were followed up 13-25 months, with an average of 17.6 months. All fractures healed except 2 cases died of infection. CONCLUSION: The classification criteria of femoral intertrochanteric fractures based on irreducibility or not can accurately predict the reducible cases preoperatively, and most of the irreducible cases can be correctly predicted in a wider way. But the classification criteria still need to be further improved and supplemented.


Subject(s)
Femoral Fractures , Fracture Fixation, Intramedullary , Hip Fractures , Aged , Bone Nails , Female , Femoral Fractures/surgery , Hip Fractures/surgery , Humans , Male , Retrospective Studies , Treatment Outcome
17.
Hepatol Res ; 51(11): 1164-1169, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33991153

ABSTRACT

AIMS: Molecular profiling of hepatocellular carcinoma (HCC) has helped identify actionable genomic alterations that could guide therapeutic decision-making and clinical trial enrollment. However, in clinical practice, next-generation sequencing (NGS) is not extensively used in routine clinical care to identify patients with HCC who are likely to benefit from genome-directed targeted therapies. METHODS: Here, we describe the case of a 66-year-old man with advanced HCC. After rapid progression on transarterial chemoembolization, the tissue sample obtained from biopsy was subjected to NGS to verify whether precision therapy was an option. RESULTS: Our analysis revealed high MET amplification. The patient received crizotinib (250 mg, bid) and showed a remarkable response. CONCLUSIONS: Our case report suggests NGS could help identify patients with high MET amplification in HCC who were likely to benefit from MET inhibitors; moreover, this requires further investigation in clinical trials.

18.
Biomater Sci ; 9(7): 2571-2583, 2021 Apr 07.
Article in English | MEDLINE | ID: mdl-33589891

ABSTRACT

Corneal neovascularization (CNV) is one of the most important causes of visual impairment worldwide. Dasatinib, a poorly water-soluble tyrosine kinase inhibitor with dual Src family kinase and platelet derived growth factor receptor inhibiting capability, has great potential in the treatment of CNV. In this study, dasatinib was successfully encapsulated into a nanostructured lipid carrier (Dasa-NLC) and the size was approximately 78 nm with a small polydispersity index. The NLC increased the solubility of dasatinib by more than 1220 times, sustained the drug release, reduced the ocular toxicity and facilitated its penetration into the cornea. Dasa-NLC significantly inhibited the proliferation, migration and tube formation of HUVEC cells, the three most important angiogenesis-related cellular changes of the CNV. Next, the in vivo anti-CNV effect of Dasa-NLC was evaluated using an alkaline burned mice CNV model, in which the development of the CNV and pathological changes of the cornea were significantly inhibited. The immunohistochemistry analysis indicated that Dasa-NLC could inhibit both the expression and activation of Src family kinase, a key component in the angiogenesis cascade. Therefore, Dasa-NLC showed considerable promise in the treatment of CNV.


Subject(s)
Corneal Neovascularization , Nanostructures , Animals , Corneal Neovascularization/drug therapy , Dasatinib , Drug Carriers , Lipids , Mice , Particle Size
19.
GigaByte ; 2021: gigabyte32, 2021.
Article in English | MEDLINE | ID: mdl-36824335

ABSTRACT

The Bicolor Angelfish, Centropyge bicolor, is a tropical coral reef fish. It is named for its striking two-color body. However, a lack of high-quality genomic data means little is known about the genome of this species. Here, we present a chromosome-level C. bicolor genome constructed using Hi-C data. The assembled genome is 650 Mbp in size, with a scaffold N50 value of 4.4 Mbp, and a contig N50 value of 114 Kbp. Protein-coding genes numbering 21,774 were annotated. Our analysis will help others to choose the most appropriate de novo genome sequencing strategy based on resources and target applications. To the best of our knowledge, this is the first chromosome-level genome for the Pomacanthidae family, which might contribute to further studies exploring coral reef fish evolution, diversity and conservation.

20.
Ann Transl Med ; 8(21): 1398, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33313143

ABSTRACT

BACKGROUND: Skeletal muscle depletion and excessive visceral adipose tissue have been shown to be independent risk factors for postoperative complications (PCs) in various diseases. However, their impact on surgical PCs in hepatic alveolar echinococcosis (HAE) is still unknown. METHODS: We retrospectively reviewed the clinical data of HAE patients who underwent liver resection at our hospital between January 2008 and December 2018. We segmented skeletal muscle and adipose tissue and measured the area of skeletal muscle tissue and adipose tissue at the level of the third lumbar vertebra by manual tracing from preoperative plain computed tomography (CT) images. Sarcopenia features were selected to construct a formula based on the least absolute shrinkage and selection operator (LASSO) logistic regression model in the primary set. Then, integrating the results of multiple clinicopathologic characteristics, we built a nomogram for predicting major PCs in HAE. The results were validated using bootstrap resampling and clinical data from other HAE centers in western China. RESULTS: The sarcopenia score is based on the personalized levels of the five features from the primary set (n=233). In the multivariate logistic analysis of the primary set, the independent factors for PCs were γ-glutamyl transferase (GGT), and surface area of hepatectomy, which were integrated into the nomogram combined with sarcopenia score. The model had a good prediction capability with a C-index of 0.84 (95% CI, 0.72-0.96). The calibration plot for the probability of PCs showed an optimal agreement between the nomogram predictions and actual observations in the primary and validation sets. CONCLUSION: Our study showed that sarcopenia score was significantly correlated with PCs in patients with HAE. In addition, we constructed a prognostic nomogram for predicting complications in HAE patients after liver surgery. The nomogram displayed excellent discrimination and calibration. Improving the nutritional status and physical health of patients before surgery might reduce the incidence of postoperative complications for the high-risk patients.

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