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BACKGROUND: Understanding factors affecting the infectiousness of influenza cases is crucial for disease prevention and control. Viral shedding is expected to correlate with infectiousness of cases, but it is strongly associated with age and the presence of symptoms. METHODS: To elucidate this complex interplay, we analyze with an individual-based household transmission model a detailed household transmission study of influenza with 442 households and 1710 individuals from 2008 to 2017 in Hong Kong, to characterize the household transmission dynamics and identify factors affecting transmissions. RESULTS: We estimate that age, fever symptoms and viral load were all associated with higher infectiousness. However, by model comparison, the best model includes age and fever as factors affecting individual infectiousness, and estimates that pre-school and school-age children were 317% (95% credible interval (CrI): 103%, 1042%) and 161% (95% CrI: 33%, 601%) more infectious than adults respectively, and patients having fever had 146% (95% CrI: 37%, 420%) higher infectiousness. Adding heterogeneity on individual infectiousness of cases does not improve the model fit, suggesting these factors could explain the difference in individual infectiousness. CONCLUSIONS: Our study clarifies the contribution of age, symptoms and viral shedding to individual infectiousness of influenza cases in households.
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BACKGROUND: Preoperative hematological parameters are predictors of pathological features and recurrence-free survival (RFS) in various malignancies. However, comprehensive studies of preoperative indicators associated with papillary thyroid carcinoma (PTC) are scarce. The present study investigated the association between preoperative indicators and RFS in patients with PTC. Accordingly, we explored the clinical impact of the prognostic nutritional index (PNI) on lymph node metastasis and RFS in patients with PTC. METHODS: A total of 619 PTC patients were retrospectively reviewed between Jan 2013 and Dec 2017. Laboratory values were measured and calculated. Receiver operating characteristic curves were generated to calculate the cutoff value. Univariate and multivariate analyses using the COX proportional hazard model were performed for RFS. The effects of PNI and age on RFS were investigated by the Kaplan-Meier method. Clinical characteristics and PNI were tested with the chi-square test. Univariate and multivariate logistic analyses were conducted to evaluate the predictive value of PNI for lymph node metastasis. RESULTS: In the multivariate Cox analysis, age, PNI and lymph node metastasis were independent prognostic indicators for RFS. The Kaplan-Meier method showed that the lower PNI group and age older than 55 years group displayed poor RFS. A low preoperative PNI was remarkably correlated with age, sex, extrathyroidal invasion, T stage, N stage and TNM stage. PNI was the only preoperative hematological indicator for lateral lymph node metastasis. CONCLUSIONS: Among the preoperative hematological indicators, PNI may serve as a promising and effective predictor for RFS and lateral lymph node metastasis in PTC patients.
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Metástase Linfática , Avaliação Nutricional , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Feminino , Masculino , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/mortalidade , Pessoa de Meia-Idade , Metástase Linfática/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/cirurgia , Adulto , Recidiva Local de Neoplasia/patologia , Idoso , Intervalo Livre de Doença , Adulto Jovem , Estimativa de Kaplan-Meier , Linfonodos/patologia , Estadiamento de Neoplasias , Curva ROCRESUMO
Two novel six-membered perimidocarbene (PIC)-based tetradentate Pt(II) complexes were designed and successfully synthesized. Systematical experimental and theoretical studies suggest that the PIC moiety greatly affects the frontier orbitals, as well as the photophysical and excited-state properties of the Pt(II) complexes. PtYK2 has a broad emission spectrum peaking at 576 nm with a shoulder band at 620 nm, along with a full width at half-maximum (FWHM) value of 100.0 nm at 77 K in 2-MeTHF; however, the emission spectrum is slightly red-shifted with a dominant peak at 610 nm and a FWHM value of 125.0 nm at room temperature in a poly(methyl methacrylate) (PMMA) film. Time-dependent-density functional theory and natural transition orbital analyses reveal that PtYK2 has a 3LC (3πPIC* â πPIC)-dominated character with an unexpectedly negligible contribution of 3MLCT transition (0.68%) in the T1 state, which results in a broad emission spectrum and a relatively low quantum efficiency of 7.4% in the PMMA film.
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OBJECTIVE: This study aimed to assess the long noncoding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) regulatory network in clear cell renal cell carcinoma (ccRCC) by gene expression analyses. MATERIALS AND METHODS: LncRNA, miRNA, and mRNA expression profiles in ccRCC were obtained from The Cancer Genome Atlas. Differentially expressed lncRNAs, mRNAs (cut-off: |log 2 [fold change, FC])| > 2.0 and adjusted P < 0.01) and miRNAs (|log 2FC| > 1.5 and adjusted P < 0.01) were unveiled using R. Cox regression analysis was performed to identify prognostic factors of ccRCC related to overall survival (OS). A protein-protein interaction (PPI) network was constructed for differentially expressed mRNAs (DEmRNAs) by Search Tool for the Retrieval of Interacting Genes (STRING). Key hub genes were screened from top 300 DEmRNAs. LncRNA-miRNA and miRNA-mRNA regulatory network were constructed and combined into the competing endogenous RNA regulatory network. Gene ontology biological terms were screened by STRING; Kyoto Encyclopedia of Genes and Genomes pathways were identified using the "clusterProfiler" package in R. RESULTS: A total of 2331, 1517, and 83 DEmRNAs, lncRNAs, and miRNAs were identified, respectively. Eleven lncRNAs (AC016773.1, HOTTIP, LINC00460, NALCN-AS1, PVT1, TRIM36-IT1, WT1-AS, COL18A1-AS1, LINC00443, LINC00472, and TCL6), three miRNAs (hsa-mir-21, hsa-mir-144, and hsa-mir-155), and three mRNAs (COL4A4, NOD2, and GOLGA8B) were associated with OS. Specifically, four lncRNAs (PVT1, LINC00472, TCL6, and WT1-AS1) and one mRNA (Collagen Type IV Alpha 4 Chain) were verified as independent prognostic factors by Gene Expression Profiling Interactive Analysis. Eleven key hub genes were obtained by PPI analysis. "Cell adhesion molecules (CAMs)," "chemical carcinogenesis," and "cytokine-cytokine receptor interaction" were significantly enriched in the network. CONCLUSION: The findings clarify the pathogenesis of ccRCC and might provide potential therapeutic targets.
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BACKGROUND: The aim of this study was to investigate the regulatory network of lncRNAs as competing endogenous RNAs (ceRNA) in bladder urothelial carcinoma (BUC) based on gene expression data derived from The Cancer Genome Atlas (TCGA). MATERIALS AND METHODS: RNA sequence profiles and clinical information from 414 BUC tissues and 19 non-tumor adjacent tissues were downloaded from TCGA. Differentially expressed RNAs derived from BUC and non-tumor adjacent samples were identified using the R package "edgeR". Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed using the "clusterProfiler" package. Gene ontology and protein-protein interaction (PPI) networks were analyzed for the differentially expressed mRNAs using the "STRING" database. The network for the dysregulated lncRNA associated ceRNAs was then constructed for BUC using miRcode, miRTarBase, miRDB, and TargetScan. Cox regression analysis was performed to identify independent prognostic RNAs associated with BUC overall survival (OS). Survival analysis for the independent prognostic RNAs within the ceRNA network was calculated using Kaplan-Meier curves. RESULTS: Based on our analysis, a total of 666, 1819 and 157 differentially expressed lncRNAs, mRNAs and miRNAs were identified respectively. The ceRNA network was then constructed and contained 59 lncRNAs, 23 DEmiRNAs, and 52 DEmRNAs. In total, 5 lncRNAs (HCG22, ADAMTS9-AS1, ADAMTS9-AS2, AC078778.1, and AC112721.1), 2 miRNAs (hsa-mir-145 and hsa-mir-141) and 6 mRNAs (ZEB1, TMEM100, MAP1B, DUSP2, JUN, and AIFM3) were found to be related to OS. Two lncRNAs (ADAMTS9-AS1 and ADAMTS9-AS2) and 4 mRNA (DUSP2, JUN, MAP1B, and TMEM100) were validated using GEPIA. Thirty key hub genes were identified using the ranking method of degree. KEGG analysis demonstrated that the majority of the DEmRNAs were involved in pathways associated with cancer. CONCLUSION: Our findings provide an understanding of the important role of lncRNA-related ceRNAs in BUC. Additional experimental and clinical validations are required to support our findings.
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OBJECTIVE: To assess the effects of survivin (SVV)in vascular endothelial cells. METHODS: In this study, we applied a gain-of-function approach and ectopically expressed SVV in rat aortic endothelial cells (RAECs) using a SVV-expressing adenovirus. The resulting SVV expression on the steady-state mRNA and protein level in RAECs was determined by reverse transcription quantitative PCR and Western blot, respectively. Cell viability, apoptosis, and migration were assessed in vitro by CCK-8 assay, flow cytometry, and transwell assay, respectively. The effect of SVV on in vivo angiogenesis was evaluated by immunohistochemistry in nude mice. Non-infected RAECs and those infected with GFP-expressing control adenovirus were used as controls. RESULTS: Compared to non-infected or control adenovirus-infected RAECs in vitro, SVV-expressing cells had increased viability and migratory capability, but reduced apoptosis. In vivo, SVV-expressing RAECs were associated with a higher level of angiogenesis. CONCLUSION: SVV is a positive regulator of endothelial cell survival and migration, and thus, stabilizes endothelial cells and stimulates angiogenesis.
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Células Endoteliais/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Neovascularização Fisiológica , Adenoviridae/genética , Animais , Apoptose , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Células Endoteliais/transplante , Feminino , Vetores Genéticos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Associadas aos Microtúbulos/genética , Ratos , Transdução de Sinais , Survivina , Fatores de Tempo , TransfecçãoRESUMO
OBJECTIVES: To assess the safety and efficacy of local anesthetic infiltration around nephrostomy tract on postoperative pain control after percutaneous nephrolithotomy. METHODS: This systematic review was performed based on randomized clinic trials about local anesthetic infiltration around nephrostomy tract on postoperative pain control. The weighted mean difference (WMD), with their corresponding 95% CI, was calculated to compare continuous variables. RESULTS: Our results showed that the consumption of analgesic was less in the experimental group than in the control group (WMD -25.32, 95% CI -48.09 to -2.55, p = 0.003). There was no significant difference between the mean Visual Analog Scale (VAS) in the experimental group than the control group after 6 h while significantly lower after 24 h. The time of first analgesic demand was significantly longer in the experimental group (WMD 2.19, 95% CI 0.98-3.41). There was no significant difference between 2 groups in terms of operation time, hemoglobin (Hb) alteration, and hospital stay. CONCLUSION: Local anesthetic infiltration around nephrostomy tract had similar efficacy in the control group in terms of operation time, Hb alteration, and hospital stay, but offers some potential advantages in terms of analgesia requirement, the time of first analgesic demand, and VAS-24 h. However, good quality and large studies with long-term follow-up are warranted for further research.
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Anestesia Local , Anestésicos Locais/administração & dosagem , Nefrostomia Percutânea , Dor Pós-Operatória/prevenção & controle , Humanos , Nefrostomia Percutânea/efeitos adversos , Dor Pós-Operatória/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Optimizing water allocation is a crucial strategy for water planning in large basins, such as the Yellow River basin. The transforming water supply pattern, triggered by inter-basin water transfer, urges the optimization and refinement of water allocation. Here, we predict the future water demand for different sectors at the provincial level and carry out future water allocation based on a multi-objective allocation model. The results imply that "demand increases in midstream and water deficits in downstream" would persist by 2050, and the demand structure highlights potential sectoral rivalry for water resources in each province. Water transfer will be the "antidote" to water disputes and will account for 19.8% and 34.5% of the water demand in 2030 and 2050, respectively. This study provides a basis for the policymaking of water management and establishes the future allocation pattern from water resources to sectors in each province in the Yellow River basin.
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HOXA transcript at the distal tip (HOTTIP), a lncRNA, induces cell proliferation and cancer progression. However, the expression and function of HOTTIP in renal cell carcinoma (RCC) were rarely reported. The role of the HOTTIP in RCC was explored in this study. HOTTIP expresses higher in RCC tissues than in normal tissues and indicates poor prognosis based on the TCGA database. The over- and low-expression HOTTIP cell line was established in this research to assess the oncogenic function of HOTTIP in RCC progression. Mechanistic analyses revealed that HOTTIP functioned as a competing endogenous RNA (ceRNA) for miR-506. RIP experiment and luciferase assay were performed to explore the mechanisms of the sponge between HOTTIP and miR-506. HOTTIP down-regulation attenuated cell proliferation, migration, and invasion, which could be rescued by miR-506 down-regulation. On the whole, this study revealed that the HOTTIP/miR-506 axis has a dominant impact on RCC progression and potentially provides a novel strategy for RCC diagnosis and therapy.
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Carcinoma de Células Renais , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais , MicroRNAs , RNA Longo não Codificante , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Movimento Celular/genética , Transdução de Sinais/genética , Regulação para BaixoRESUMO
Extending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose. Here, we quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022. We estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21-27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR: 1.66; 95% CI: 1.07, 2.59; p = 0.02) after the first dose. Implementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.
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BACKGROUND: Lichtenstein tension-free mesh repair is the most commonly used technique for open inguinal hernia. However, mesh fixation with sutures to avoid dislocation has been considered as a cause of chronic pain and discomfort. A new self-gripping mesh (Parietene Progrip; Coviden) has been developed, which is making the use of sutureless for inguinal hernia repair. The aim of this systematic review was to compare the outcomes of open Lichtenstein inguinal hernia repair using new self-gripping mesh or sutured mesh. METHODS: PubMed/MEDLINE, CENTRAL, and reference lists were searched for controlled trials of self-gripping mesh versus sutured mesh for open inguinal hernia repair from January 2005 to February 2013. The primary outcomes were chronic pain and recurrence. Secondary outcomes were duration of operation, wound infection, hematoma, seroma formation, postoperative pain, hospital stay, and time to return to work. The methodology was in accordance with the Cochrane Handbook for interventional systematic reviews and written based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: A total of seven studies, representing 1353 patients were included. There was no effect on chronic pain (risk difference -0.02 [95% confidence interval -0.07 to 0.03], P = 0.40) or recurrence (risk difference -0.00 [95% confidence interval -0.01 to 0.01], P = 0.57). No significant differences were noted in terms of secondary outcomes, such as wound infection, hematoma, and seroma formation, between self-gripping and sutured mesh repair. But the mean operative duration was shorter in the self-gripping mesh group than sutured mesh group. CONCLUSIONS: Based on the results, both meshes appear to result in similar postoperation outcomes. Further long-term analysis may guide surgeon selection of adapted mesh for inguinal hernia repair.
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Hérnia Inguinal/cirurgia , Herniorrafia/instrumentação , Herniorrafia/métodos , Telas Cirúrgicas , Técnicas de Sutura , HumanosRESUMO
OBJECTIVE: To systematically review and compare tubeless percutaneous nephrolithotomy (PCNL) with standard PCNL. MATERIALS AND METHODS: We conducted a review of the English language literature on studies involving randomized controlled trials for PCNL. The studies chosen to be included in our review compared tubeless PCNL with standard PCNL and described the advantages of each in the outcomes. Two reviewers independently screened the studies for eligibility, evaluated their quality and extracted the data from the eligible studies, with confirmation by cross-checking. Data were processed using RevMan 5.0. RESULTS: Seven studies involving 1365 cases met the inclusion criteria, and these were included in the meta-analysis. The patients' baseline characteristics were comparable in all the studies. By comparing the four common characteristics, we found no difference in efficacy between the two surgical approaches in terms of mean operation duration and postoperative haematocrit change (P > 0.05). We found that the mean analgesic requirement and number of days in hospital were lower for tubeless PCNL (P < 0.05). CONCLUSIONS: Our results show that tubeless PCNL is a good option in non-complicated cases, with the advantages of reduced hospital stay and little need for postoperative analgesia. There was no difference between the two approaches in operation duration, or haematocrit change after surgery. As only few studies with small study populations were available, more high quality larger trials with longer follow-up are recommended.
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Cálculos Renais/cirurgia , Nefrostomia Percutânea/métodos , Analgesia/estatística & dados numéricos , Humanos , Tempo de Internação/estatística & dados numéricos , Nefrostomia Percutânea/efeitos adversos , Dor Pós-Operatória/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To systematically evaluate the risk of antiplatelet drugs (APs) on bleeding complications in urological surgery. METHODS: Studies were sought and included in this review if they were clinical controlled trials and involved transurethral resection of the prostate (TURP) and prostate puncture biopsy (PPB), which compared preoperative AP withdrawal (control group) with continuing APs (experimental group) and revealed bleeding complications as outcomes. A literature search was conducted of the electronic databases PubMed, Ovid, ScienceDirect and Embase for studies published between 1990 and 2012. Two reviewers independently screened the studies for eligibility, evaluated the quality and extracted the data from the eligible studies, with confirmation by cross-checking. There was evidence of publication bias based on Egger's test and funnel plot. Data were processed using Cochrane Review Manager 5.0 software. RESULTS: Nine studies involving 3,145 cases met the inclusion criteria and were included in the meta-analysis. The baselines of patients' characteristics were comparable in all studies. The meta-analysis results showed that no differences were found in risk of bleeding after (1) TURP (OR 1.26, 95% CI 0.80-2.00, p = 0.32) or (2) PPB (OR 0.89, 95% CI 0.45-1.76, p = 0.73). CONCLUSION: Preoperative APs do not raise the risk of surgical bleeding complications in prostatectomy and PPB. Because of few studies and small samples, more high-quality trials with larger samples and longer follow-ups are proposed.
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Hemorragia/epidemiologia , Complicações Intraoperatórias/epidemiologia , Inibidores da Agregação Plaquetária/administração & dosagem , Próstata/patologia , Próstata/cirurgia , Punções , Ressecção Transuretral da Próstata , Humanos , Masculino , Cuidados Pré-Operatórios , RiscoRESUMO
PURPOSE: Radiotherapy resistance is the main obstacle in the effective treatment of advanced head and neck squamous cell carcinoma (HNSCC). Increasing scientific opinions present that ubiquitin-conjugating enzyme E2C (UBE2C) might be a target gene acting as an oncogene. METHOD: TCGA database was used to analyze the expression of UBE2C in HNSCC patients, and the relationship between UBE2C expression and prognosis. Western blot and RT-PCR were used to assess UBE2C expression before and after radiation. Then, cell viability experiment and colony formation were used to evaluate proliferation after 2 Gy radiation. Cell viability experiment, migration, and invasion were evaluated in the condition of UBE2C knock-down. Western blot and RT-PCR were used to assess the expression of apoptosis and ROS relative gene expression. Then, the xenograft model was used to evaluate the efficacy of radiation combined with UBE2C suppression. RESULT: The expression of UBE2C was high in tumors of patients with HNSCC and relatives with poor prognoses. Si-UBE2C cells showed proliferation inhibited and apoptosis enhanced after radiation. Furthermore, the mechanism of UBE2C in HNSCC radioresistance was explored. We performed RT-PCR to find the 4-HNE, which increases oxidative-stress-relative apoptosis in Si-UBE2C cells after radiation. CONCLUSIONS: Through the RT-PCR, WB, cell viability experiment, migration, invasion, and in vivo experiment, UBE2C was confirmed to downregulate oxidative-stress-relative apoptosis induced by radiation and promote the development of malignant tumor cells.
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Neoplasias de Cabeça e Pescoço , Enzimas de Conjugação de Ubiquitina , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismoRESUMO
BACKGROUND: This study aimed to introduce a novel loop neurorrhaphy technique using an innervated vascularized iliac bone flap (VIBF) with vascularized ilioinguinal nerve (IIN) to reconstruct the inferior alveolar nerve (IAN) and preserve lower lip sensation simultaneously with mandibular reconstruction. METHODS: This study prospectively included patients who underwent mandibular reconstruction using VIBF from May 2018 to April 2020. Subjects were allocated into two groups: (1) Group I; innervated VIBF with loop neurorrhaphy (IIN doubly anastomosed with IAN and mental nerve), (2) Group II (control); conventional VIBF. Evaluation was done with operative time, intraoperative indocyanine green (ICG), lower lip sensory assessment (two-point discrimination [TPD] test and current perception threshold [CPT]), and drooling. RESULTS: Twelve patients were included; 6 in each group, (7 males and 5 females), age ranging from 18 to 57 years (average: 36.75 years). In all cases, intraoperative perfusion of IIN was confirmed by ICG. Group I showed a statistically significant more flap harvesting time compared with group II (mean difference, 5.67 min; P = 0.0091). There was a significant difference in sensory recovery favoring group I (P < 0.05). The TPD results in group I showed an average of 9.8 ± 6.9 mm and 6.2 ± 5.7 mm on operated and non-operated sides, while Group II showed a poor sensory recovery, and the TPD showed an average of 24.6 ± 6.7 mm and 8.4 ± 2.3 mm on operated and non-operated sides. The CPT results showed a significant difference between both groups. In Group I, the extent of drooling was 3.16 ± 0.75, while in Group II, the score was 1.6 ± 0.81, revealing a significant difference favoring Group I. CONCLUSIONS: Concurrent mandibular reconstruction using VIBF and loop neurorrhaphy with vascularized IIN to reconstruct IAN successfully restore lower jaw form and preserve lip sensation.
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Reconstrução Mandibular , Procedimentos de Cirurgia Plástica , Adolescente , Adulto , Feminino , Humanos , Lábio/cirurgia , Masculino , Mandíbula/cirurgia , Nervo Mandibular/cirurgia , Pessoa de Meia-Idade , Retalhos Cirúrgicos , Adulto JovemRESUMO
PURPOSE: Apatinib resistance is the main obstacle to the effective treatment of advanced head and neck squamous cell carcinoma (HNSCC). This study aimed to evaluate the function of Erb-B2 receptor tyrosine kinase 2 (ERBB2) and stimulator of interferon response cGAMP interactor (STING) in apatinib resistance in HNSCC. METHOD: The Cancer Genome Atlas database of HNSCC was used to analyze the relationship between vascular endothelial growth factor receptor 2 (VEGFR2) expression and prognosis. An apatinib resistant (AR) HNSCC cell line was constructed based on the CAL27 cell line. RNA sequencing was performed to explore the differentially expressed mRNAs. Quantitative real-time reverse transcription PCR (qRT-PCR) and western blotting were used to evaluate the expression and phosphorylation level VEGFR2, ERBB2, STING, and related proteins. Apatinib resistance was evaluated by colony formation and cell viability assays. A mouse subcutaneous tumor formation model was established to evaluate the efficiency of combination treatment and vascularization was evaluated by assessing CD31 immunofluorescence. RESULT: The expression of VEGFR2 was high in tumor of patients with HNSCC. Western blotting and qRT-PCR revealed that in AR cells, ERBB2 expression was high, whereas the expression of STING was low. Targeted treatment of ERBB2 using lapatinib could attenuate apatinib resistance. Further research confirmed that overexpressing STING could decrease ERBB2 expression. CONCLUSION: STING could sensitize AR cells to apatinib by decreasing ERBB2 expression. The combination of lapatinib or a STING agonist with apatinib ameliorated acquired apatinib resistance in a synergistic manner.
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Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/metabolismo , Proteínas de Membrana/metabolismo , Piridinas/uso terapêutico , Receptor ErbB-2/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Animais , Linhagem Celular Tumoral , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Interferons , Lapatinib/uso terapêutico , Masculino , Camundongos Endogâmicos BALB C , Nucleotídeos Cíclicos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Xantonas/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
RATIONALE: The free fibular flap is considered the gold standard, particularly for a mandibular defect combined with a significant soft tissue defect. However, the fibular flap has the disadvantages of a lack of height for postoperative dental restoration and donor site skin graft if the skin paddle is wider than 5âcm. The larger bone and soft tissue defects tend to be reconstructed using either a scapula or a combination of iliac artery and radial free flap. Few cases involving reconstruction using chimeric deep circumflex iliac artery perforator flap (DCIAPF) for mandibular defect combined with more significant soft tissue defects have been reported due to perforator variations. We successfully performed oromandibular reconstruction using chimeric DCIAPF. PATIENT CONCERNS: A 56-year-old male patient was admitted due to "constant pain in the gradually enlarged right lower gingival mass since the previous four months." The patient had no other obvious symptoms, and no history of diabetes or hypertension was reported. The patient reported long-term smoking and drinking habits. DIAGNOSES: Computed tomography (CT) revealed a neoplasm in the right buccal space, which is primarily considered a malignancy. The pathological results of a gingival mass biopsy presented squamous cell carcinoma. INTERVENTIONS: No operative contraindications were confirmed after regular tests and examinations were undertaken. The patient underwent a primary extent resection of a 6-cm-long mandible, including mass and suprascapulohyoid neck dissection. The oromandibular defects were then reconstructed with chimeric DCIAPF, simultaneously using the iliac crest bone flap to repair the mandibular lateral segment defect and the skin paddle to repair the intraoral soft tissue defect of 5â×â10âcm. OUTCOMES: The total operating time was five and half hours and blood loss was approximately 500âml. The operation was successful, with no infections or flap loss. Six months postoperatively, CT showed that the iliac crest bone had connected to the alveolar bone of the mandible. The height of the iliac crest bone was sufficient for postoperative dental restoration. The patient healed without obvious complications and no tumor recurrence. LESSONS: Chimeric DCIAPF is an excellent option for mandibular angle or body segment defects combined with significant soft tissue defects.
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Carcinoma de Células Escamosas/cirurgia , Artéria Ilíaca/cirurgia , Neoplasias Mandibulares/cirurgia , Reconstrução Mandibular/métodos , Retalho Perfurante/irrigação sanguínea , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The photothermal agents have been widely developed due to the minimally invasive treatment for targeted tumor photothermal therapy, which is considered to have great potential for antitumor bioapplications. The development of multifunctional photothermal agents is extremely challenging. This work presents a novel photothermal theragnosis agent, i.e., CuGeO3 nanoparticles (CGO NPs), showing intense absorption in the near-infrared (NIR) window and excellent ability of CT imaging. Due to the strong NIR absorption, CGO NPs exhibit excellent photothermal effect with a photothermal conversion efficiency of 59.4%. Moreover, because of the high X-ray attenuation coefficient of germanium, the CGO NPs have a great potential of CT imaging diagnosis in clinical application. Additionally, the CGO NPs show negligible cytotoxicity in vitro and in vivo, indicating that it can be served as an outstanding contrast and anticancer agent in a biosafe way. Our work opens the way for the development of bimetallic copper-based oxides used in photothermal diagnostic agents for cancer treatment.
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Objectives: This study aims to explore the roles of 13 m6A RNA methylation regulators in clear cell renal cell carcinoma (ccRCC), and identify a risk signature and prognostic values of m6A RNA methylation regulators in ccRCC. Materials and Methods: RNA sequence data of ccRCC was obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed of 13 m6A RNA methylation regulators in ccRCC stratified by different clinicopathological characteristics were unveiled using "limma" package in R version 3.6.0. Cox regression and LASSO analyses were conducted to identify the powerful independent prognostic factors in ccRCC associated with overall survival (OS). Protein-protein interaction (PPI) network and correlation analyses of the 13 m6A RNA methylation regulators were performed using "STRING" and R package, respectively. Principal component analysis (PCA) was also done using R. In addition, gene ontology (GO), GSEA and Kyoto Encyclopedia of Genes and Genomes pathways were used to functionally annotate the differentially expressed genes in different subgroups. Results: Most of the 13 m6A RNA methylation regulators are differentially expressed in ccRCC tissue samples stratified by different clinicopathological characteristics in 537 patients. Next, a risk signature for predicting prognosis of ccRCC patients, was established based on two powerful independent prognostic m6A RNA methylation regulators (METTL14 and METTL3). Then, two subgroups (cluster1 and 2) were identified by consensus clustering to the two powerful independent factors and the cluster1 had a poorer prognosis than cluster2. Furthermore, the genes in cluster1 were significantly enriched in cancer-related pathways, biological process, and hallmarks, including "cell adhesion molecules (CAMs)," "leukocyte migration," "Wnt/ß-catenin signaling," and so on. Conclusion: M6A RNA methylation regulators play important roles in the initiation and progression of ccRCC and provide a novel sight to understand m6A RNA modification in ccRCC.
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PURPOSEï¼To compare the osteogenic potential of bone marrow mesenchymal stem cells (BMMSCs) from innervated iliac graft bone flap and traditional one for reconstructing mandibular defects. METHODSï¼Graft bone marrow samples were harvested 1 year after free vascularized iliac reconstruction of mandibular defects, with or without innervation through simultaneous nerve anastomosis. BMMSCs were isolated and cultured in vitro. Colony forming units-fibrosis observation, Brdu incorporation assay, population doubling, Alizarin red staining for in vitro calcified nodule formation and in vivo assay of subcutaneous osteogenesis in nude mice were used to detect BMMSCs proliferation, self-renewal and osteogenic differentiation capabilities, respectively. SPSS 24.0 software package was used for statistical analysis. RESULTSï¼Colony formation, proliferation, population doubling and osteogenic differentiation abilities of BMMSCs from innervated group were significantly higher than those from non-innervated groupï¼P<0.05ï¼. CONCLUSIONSï¼Simultaneous innervation of free vascularized iliac during reconstruction of mandibular defects may maintain self-renewal and osteogenic differentiation potentials of BMMSCs in graft bones, thereby maintaining bone homeostasis and reducing postoperative graft bone resorption.