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PURPOSE: The aim of this study was to determine the genetic cause of early onset autosomal dominant hearing loss segregating in five-generation kindred of Chinese descent and provide preimplantation genetic testing (PGT)for them. METHODS: Clinical examination, pedigree analysis and exome sequencing were carried out on the family. Minigene-based splicing analysis, in vivo RNA analysis and protein structure prediction by molecular modeling were conducted on the candidate variant. PGT for the causative variation and chromosome aneuploidis based on SNP analysis has been used for avoidance of hearing loss in this family. RESULTS: All the affected individuals presented with moderate down-sloping hearing loss and whole-exome sequencing identified a novel splice-site variant c.5383+6T>A in the tested subjects within the TECTA locus. Genotyping of all the 32 family members confirmed segregation of this variant and the hearing loss phenotype in the extended family. Functional analysis of RNA and molecular modeling indicates that c.5383+6T>A is a pathogenic splice-site variant and should be considered as genetic cause of the hearing loss. Furthermore, a successful singleton pregnancy with no variation in TECTA c.5383+6 was established and a healthy male child was born by PGT. CONCLUSION: We have identified a novel variant c.5383+6T>A in TECTA ZA-ZP inter-domain, which could be attributable to the early-onset autosomal dominant hearing loss. The implications of our study are valuable in elucidating the disrupted RNA splicing and uncovering the genetic cause of hearing loss with TECTA pathogenic variants, as well as providing reproductive approaches to healthy offspring.
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The inconsistency between mismatch repair (MMR) protein immunohistochemistry (IHC) and microsatellite instability PCR (MSI-PCR) methods has been widely reported. We aim to investigate the prognosis and the effect of immunotherapy in dMMR by IHC but MSS by MSI-PCR (dMMR&MSS) colorectal cancer (CRC) patients. A microsatellite instability (MSI) predicting model was established to help find dMMR&MSS patients. MMR and MSI states were detected by the IHC and MSI-PCR in 1622 CRC patients (ZS6Y-1 cohort). Logistic regression analysis was used to screen clinical features to construct an MSI-predicting nomogram. We propose a new nomogram-based assay to find patients with dMMR&MSS, in which the MSI-PCR assay only detects dMMR patients with MSS predictive results. We applied the new strategy to a random cohort of 248 CRC patients (ZS6Y-2 cohort). The consistency of MMR IHC and MSI-PCR in the ZS6Y-1 cohort was 95.7% (1553/1622). Both pMMR&MSS and dMMR&MSS groups experienced significantly shorter overall survival (OS) than those in dMMR by IHC and MSI-H by MSI-PCR (dMMR&MSI-H) group (hazard ratio [HR] = 2.429, 95% confidence interval [CI]: 1.89-3.116, p < .01; HR = 21.96, 95% CI: 7.24-66.61, p < .01). The dMMR&MSS group experienced shorter OS than the pMMR&MSS group, but the difference did not reach significance (log rank test, p = .0686). In the immunotherapy group, the progression-free survival of dMMR&MSS patients was significantly shorter than that of dMMR&MSI-H patients (HR = 13.83, 95% CI: 1.508-126.8, p < .05). The ZS6Y-MSI-Pre nomogram (C-index = 0.816, 95% CI: 0.792-0.841, already online) found 66% (2/3) dMMR&MSS patients in the ZS6Y-2 cohort. There are significant differences in OS and immunotherapy effect between dMMR&MSI-H and dMMR&MSS patients. Our prediction model provides an economical way to screen dMMR&MSS patients.
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Neoplasias Colorretais , Reparo de Erro de Pareamento de DNA , Imunoterapia , Instabilidade de Microssatélites , Nomogramas , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/terapia , Neoplasias Colorretais/imunologia , Feminino , Masculino , Prognóstico , Pessoa de Meia-Idade , Reparo de Erro de Pareamento de DNA/genética , Imunoterapia/métodos , Idoso , Imuno-Histoquímica , Adulto , Biomarcadores Tumorais/genéticaRESUMO
Teratomas are congenital malformations that rarely occur in the oral cavity. In the case reported here, fetal magnetic resonance imaging performed at 30 weeks of gestation informed the decision-making of the multidisciplinary management team, who closely followed the pregnancy until the scheduled cesarean delivery at 38 weeks of gestation. After delivery, tracheal intubation was performed to ensure airway patency, and tumor resection was scheduled immediately after ruling out contraindications to surgery based on preoperative examinations, allowing for safe excising of the tumor. Postoperative follow-up at 3 months showed no abnormalities.
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Imageamento por Ressonância Magnética , Neoplasias Bucais , Teratoma , Humanos , Teratoma/congênito , Teratoma/cirurgia , Teratoma/diagnóstico por imagem , Teratoma/diagnóstico , Feminino , Gravidez , Recém-Nascido , Neoplasias Bucais/cirurgia , Neoplasias Bucais/congênito , Neoplasias Bucais/diagnóstico por imagem , Neoplasias Bucais/diagnóstico , Adulto , Diagnóstico Pré-NatalRESUMO
OBJECTIVE: In this study, we aimed to identify differentially expressed heat shock protein (HSP) profiles in the villi and decidua from patients with early missed abortion (EMA). METHODS: By using high-throughput and high-precision parallel reaction monitoring (PRM)-based targeted proteomics techniques, this study examined the abundance of HSPs in the villi and decidua of 10 patients with EMA and 10 controls. Moreover, the abundance of 3 HSPs in the villi of another 22 patients with EMA and 22 controls was verified with Western blotting and immunohistochemistry (IHC). RESULTS: There were potential differences in the abundance of 16 HSPs and 42 polypeptides in human villi and decidua compared with those of the control group. Among them, HSP90AB1, HSPD1 and HSPA13 were downregulated in abundance in villi of patients with EMA, with a statistically significant difference, which was consistent with the verification results of Western blots and IHC. CONCLUSION: Using a PRM-based targeted proteomics technique, this study is the first to screen and quantitatively analyze the expression profile of HSPs in the villi and decidua of patients with EMA. The significant downregulation of HSP90AB1, HSPD1 and HSPA13 was found to have a potentially intimate association with the occurrence of EMA. The findings in our study may provide novel potential research targets related to HSPs for the pathogenesis, prevention and treatment of EMA.
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Nonribosomal peptides (NRPs) are a large family of secondary metabolites with notable bioactivities, which distribute widely in natural resources across microbes and plants. To obtain these molecules, heterologous production of NRPs in robust surrogate hosts like Escherichia coli represent a feasible approach. However, reconstitution of the full biosynthetic pathway in a host often leads to low productivity, which is at least in part due to the low efficiency of enzyme interaction in vivo except for the well-known reasons of metabolic burden (e.g., expression of large NRP synthetases-NRPSs with molecular weights of >100 kDa) and cellular toxicity on host cells. To enhance the catalytic efficiency of large NRPSs in vivo, here we propose to staple NRPS enzymes by using short peptide/protein pairs (e.g., SpyTag/SpyCatcher) for enhanced NRP production. We achieve this goal by introducing a stapled NRPS system for the biosynthesis of the antibiotic NRP valinomycin in E. coli. The results indicate that stapled valinomycin synthetase (Vlm1 and Vlm2) enables higher product accumulation than those two free enzymes (e.g., the maximum improvement is nearly fourfold). After further optimization by strain and bioprocess engineering, the final valinomycin titer maximally reaches about 2800 µg/L, which is 73 times higher than the initial titer of 38 µg/L. We expect that stapling NRPS enzymes will be a promising catalytic strategy for high-level biosynthesis of NRP natural products.
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Antibacterianos , Escherichia coli , Valinomicina/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Vias Biossintéticas , Peptídeo Sintases/genética , Peptídeo Sintases/metabolismo , Peptídeos/metabolismoRESUMO
OBJECTIVE: To assess the diagnostic performance of initial post-therapeutic 131I single-photon emission computed tomography/computed tomography (SPECT/CT) compared with that of reoperation in detecting residual lymph node metastasis (LNM). METHODS: Patients with iodine-avid LNM detected on the initial post-therapeutic 131I SPECT/CT and who underwent reoperative dissection within 6 months were included. LNMs (numbers and locations) detected via both methods were compared. The American Thyroid Association dynamic risk stratification was performed for patients receiving second radioactive iodine therapy after reoperation. RESULTS: Fifty-three patients with 95 iodine-avid LNMs detected by 131I SPECT/CT were enrolled. Fifty-one (96.2%) patients had 212 LNMs confirmed by reoperation (P = .004). The sensitivity and specificity of 131I SPECT/CT in detecting LNM were 44.8% (95/212) and 91.6% (87/95), respectively. The location frequency of residual LNMs found by 131I SPECT/CT was similar to that of reoperation (P = .057). Thirty-two patients received a second radioactive iodine treatment, and 6 (18.8%) patients still had residual iodine-avid LNM on SPECT/CT. Therapeutic response was evaluated by American Thyroid Association dynamic risk stratification in 16 patients. The number of patients with structural incomplete response, biochemical incomplete response, indeterminate response, and excellent response was 4 (23.5%), 4 (23.5%), 5 (29.4%), and 3 (17.6%), respectively. CONCLUSION: 131I SPECT/CT has high specificity but relatively low sensitivity in detecting all residual LNMs. Approximately 80% of patients were rendered structurally disease free after reoperation.
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Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/radioterapia , Câncer Papilífero da Tireoide/cirurgia , Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Reoperação , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/tratamento farmacológico , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Regional odontodysplasia (RO) is a rare developmental abnormality of epithelial and mesenchymal dental tissues. Due to its poorly understood etiology, assessing and discussing related clinical cases of this dental anomaly is crucial to guide professionals in improving its treatment and outcomes. This article aimed to report the case of a 9-year-old male patient who presented to our department with the main complaint of absent eruption of permanent left mandibular quadrant teeth. This is the first case reported in China from a patient with multiple cutaneous nevi on the face and neck, and based on the retrieved clinical and radiographic features, we described and discussed the treatment and etiology of RO.
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Odontodisplasia , Masculino , Humanos , Criança , Odontodisplasia/diagnóstico por imagem , Pescoço , Mandíbula , Erupção DentáriaRESUMO
Previous studies revealed that MQEO (Maqian fruits essential oil), which is extracted from the fruit of Maqian (Zanthoxylum myriacanthum var. Pubescens), had a good anti-inflammatory effect, but the effect on endometriosis inâ vitro remains unknown. In the present study, the inhibitory effects of MQEO against the EESCs (ectopic endometrial stromal cells) were investigated. Cells were treated with a concentration gradient (from 0.025 % to 0.15 %) of MQEO for 24â h and cell viability was detected by CCK-8. In addition, apoptotic rates were investigated using flow cytometry. The effect of MQEO on cell migration was determined by wound-healing and transwell assay. The expression of apoptosis-associated and cell adhesion-related proteins was assessed by western blotting. The transcriptional levels of IL-1, IL-6 and TNF-α were determined by Real-time qPCR. RNA-seq was used to identify the DEGs (differentially expressed genes) in MQEO-pretreated EESCs. We found that the MQEO condition dosage-dependently reduced the cell viability of EESCs. Based on flow cytometry results, the number of apoptotic cells increased significantly with dosage. The wound-healing and transwell results showed that MQEO group exhibited a significantly decreased cell motility and migration ability in comparison with the normal group. Western blotting results showed that MQEO down-regulated the expression of Bcl-2, ICAM-1 (intercellular adhesion molecule 1) and CD44, but up-regulated the cleaved caspase-3 expression in EESCs. What's more, MQEO also inhibited the LPS-induced inflammation in human EECs (endometrial epithelial cells). RNA-seq revealed that 221 DEGs were up-regulated genes and 284 DEGs were down-regulated in MQEO-pretreated EESCs. Our data uncovered the beneficial effects of MQEO in endometriosis and provided new insights into the mechanism of the effect of MQEO on EESCs, suggesting MQEO could be a promising new therapeutic agent for endometriosis.
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Endometriose , Óleos Voláteis , Feminino , Humanos , Lipopolissacarídeos/farmacologia , Óleos Voláteis/farmacologia , Óleos Voláteis/metabolismo , Endometriose/genética , Endometriose/metabolismo , Células Estromais/metabolismo , Células Epiteliais/metabolismoRESUMO
Traditional analytical methods for thalassemia screening are needed to process complicated and time-consuming sample pretreatment. In recent decades, ambient mass spectrometry (MS) approaches have been proven to be an effective analytical strategy for direct sample analysis. In this work, we applied ambient MS with wooden-tip electrospray ionization (WT-ESI) for the direct analysis of raw human blood samples that were pre-identified by gene detection. A total of 319 whole blood samples were investigated in this work, including 100 α-thalassemia carriers, 67 ß-thalassemia carriers, and 152 control healthy samples. Only one microliter of raw blood sample was directly loaded onto the surface of the wooden tip, and then five microliters of organic solvent and a high voltage of +3.0 kV were applied onto the wooden tip to generate spray ionization. Multiply charged ions of human hemoglobin (Hb) were directly observed by WT-ESI-MS from raw blood samples. The signal ratios of Hb chains were used to characterize two main types of thalassemia (α and ß types) and healthy control blood samples. Our results suggested that the ratios of charged ions to Hb chains being at +13 would be an indicator for ß-thalassemia screening.
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Espectrometria de Massas por Ionização por Electrospray , Talassemia beta , Hemoglobinas , Humanos , Íons , Projetos Piloto , Espectrometria de Massas por Ionização por Electrospray/métodos , Talassemia beta/diagnósticoRESUMO
A 51-year-old woman with papillary thyroid cancer (PTC) complained of headache.Physical examination found the tongue derivation torightside. Fluorine-18-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) detected a hypermetabolic soft-tissue mass in the right retropharyngeal carotid space, where the nasopharyngeal carotid segment of right hypoglossal nerve passing inferiorly. The musculature in the right side of tongue was inflammatory instead of fatty infiltration, with hyperintense on T2-weighted image and hypermetabolism on PET. These images together indicated the early phase of hypoglossal nerve palsy caused by PTC invasion.
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Doenças do Nervo Hipoglosso , Neoplasias da Glândula Tireoide , Feminino , Fluordesoxiglucose F18 , Humanos , Doenças do Nervo Hipoglosso/diagnóstico por imagem , Doenças do Nervo Hipoglosso/etiologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Câncer Papilífero da Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/diagnóstico por imagemRESUMO
Natural products are important because of their significant pharmaceutical properties such as antiviral, antimicrobial, and anticancer activity. Recent breakthroughs in DNA sequencing reveal that a great number of cryptic natural product biosynthetic gene clusters are encoded in microbial genomes, for example, those of Streptomyces species. However, it is still challenging to access compounds from these clusters because many source organisms are uncultivable or the genes are silent during laboratory cultivation. To address this challenge, we develop an efficient cell-free platform for the rapid, in vitro total biosynthesis of the nonribosomal peptide valinomycin as a model. We achieve this goal in two ways. First, we used a cell-free protein synthesis (CFPS) system to express the entire valinomycin biosynthetic gene cluster (>19 kb) in a single-pot reaction, giving rise to approximately 37 µg/L of valinomycin after optimization. Second, we coupled CFPS with cell-free metabolic engineering system by mixing two enzyme-enriched cell lysates to perform a two-stage biosynthesis. This strategy improved valinomycin production ~5000-fold to nearly 30 mg/L. We expect that cell-free biosynthetic systems will provide a new avenue to express, discover, and characterize natural product gene clusters of interest in vitro.
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Antibacterianos/biossíntese , Valinomicina/biossíntese , Bioengenharia , Sistema Livre de Células , Escherichia coli/genética , Escherichia coli/metabolismo , Genes Bacterianos , Engenharia Metabólica/métodos , Família Multigênica , Streptomyces/genética , Streptomyces/metabolismoRESUMO
PURPOSE: Some data suggest an association between the single nucleotide polymorphisms AGT T704C, ACE I/D, and AT1R A1166C and preeclampsia, but overall, the data are conflicting; the aim of our study was to discover a more stable and reliable association between these polymorphisms and PE risk. METHODS: A comprehensive literature search for this meta-analysis was conducted. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated to evaluate the strength, and heterogeneity test was conducted. Trial sequential analysis was also performed. RESULTS: A total of forty studies were finally included in our meta-analysis. The AGT T704C polymorphism was associated with PE risk in three genetic models (dominant OR = 1.33, 95%CI = 1.12-1.59; heterozygote OR = 1.26, 95%CI = 1.05-1.52; homozygote OR = 1.44, 95%CI = 1.14-1.83). No heterogeneity was observed in the three genetic models for the ACE I/D polymorphism. For subgroup analysis by geography, no significant association was detected. Significant associations were observed in mixed race, early-onset, late-onset, and more than 200 subgroups for the AT1R A1166C polymorphism; however, only one study was analyzed in these subgroups. CONCLUSIONS: Our results indicated the AGT T704C and ACE I/D polymorphisms were associated with an increased risk of PE. Increased risks were also observed for the two polymorphisms in subgroups including Asians, Europeans, Caucasoid, and Mongoloid. Moreover, an increased PE risk with the ACE I/D polymorphism in the severe PE population was also detected. Regarding the AT1R A1166C polymorphism, weak associations were observed, but further studies are required.
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Angiotensinogênio/genética , Predisposição Genética para Doença , Peptidil Dipeptidase A/genética , Polimorfismo de Nucleotídeo Único , Pré-Eclâmpsia/patologia , Receptor Tipo 1 de Angiotensina/genética , Sistema Renina-Angiotensina , Feminino , Humanos , Metanálise como Assunto , Pré-Eclâmpsia/etiologia , Gravidez , Fatores de RiscoRESUMO
The incidence of colorectal cancer (CRC) is increasing in China. Here, we aimed to evaluate the latest demographic trends and KRAS/BRAF mutations status of Chinese CRC. Five thousand five hundred and forty-six CRC patients diagnosed from 2010 to 2017 were involved. KRAS exon 2 and BRAFV600E mutations were detected by Sanger sequencing and high-resolution melting analysis or allelic-specific probe method. Gene mutation profiles and clinicopathologic characteristics of 5495 patients were analyzed. The joinpoint regression model was used to predict the demographic data in 2018. We found KRAS exon 2 and BRAFV600E mutation rates were 37.7 and 2.8% in CRC patients. Tumors with KRAS exon 2 mutations were more likely to be present in female and patients aged older than 75 years, right colon and have well-differentiated histology. Tumors with BRAFV600E mutations were more likely to be present in the female, right colon and have poorly differentiated histology. From 2010 to 2017, the percentage of colon cancer and tubular adenocarcinoma in CRC increased substantially (from 39.3 to 51.8%, from 78.6 to 93.4%, respectively). The percentage of right colon cancer increased from 18.3 to 20.5%, which predictively may keep at 22.6% in 2018. The rise trends for patients with moderate differentiation tumor or KRAS exon 2 mutated tumor were apparent (from 50.3 to 78.6%, from 32.8 to 39.7%, respectively). In conclusion, in recent 8 years, there is a shift to the colon, especially right colon in the incidence of Chinese CRC. Moreover tubular adenocarcinoma is becoming the primary histology type.
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Adenocarcinoma/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , China/epidemiologia , Neoplasias Colorretais/patologia , Demografia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mutação/genética , Análise de Sequência de DNA , Adulto JovemRESUMO
The effect of ultrasonic assisted extraction (UAE) process on oil recovery from refinery oily sludge was examined in this study. Two types of UAE treatment including UAE probe (UAEP) system and UAE bath (UAEB) system were investigated. Their oil recovery efficiencies were compared to that of mechanical shaking extraction (MSE). Three solvents including cyclohexane (CHX), ethyl acetate (EA), and methyl ethyl ketone (MEK) were examined as the extraction solvents. The influence of experimental factors on oil and solvent recovery was investigated using an orthogonal experimental design. Results indicated that solvent type, solvent-to-sludge (S/S) ratio, and treatment duration could have significant effects on oil recovery in UAE treatment. Under the optimum conditions, UAEP treatment can obtain an oil recovery of 68.8% within 20 s, which was higher than that (i.e., 62.0%) by MSE treatment after 60 min' extraction. UAEB treatment can also obtain a promising oil recovery within shorter extraction duration (i.e., 15 min) than MSE. UAE was thus illustrated as an effective and improved approach for oily sludge recycling.
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Indústrias Extrativas e de Processamento/métodos , Petróleo/análise , Reciclagem , Esgotos/química , Ultrassom , Resíduos Industriais/análise , Modelos Teóricos , SolventesRESUMO
OBJECTIVE: To evaluate the effectiveness and safety of leuprolide acetate in the treatment of endometriosis. METHODS: From Nov. 2007 to Oct. 2012, the patients who confirmed to be endometriosis were randomly divided into test group of 113 cases and control group of 116 cases. The test drug was the sustained-release agent of leuprolide acetate. The control drug was Enantone. The drugs were used for 3 times in total. After treatment, the ovarian mass volumes measured with type-B ultrasound, the scores of the patient's subjective symptoms during non-menstrual and menstruation days, the pelvic signs during non-menstrual days, the changes of hormones [estradiol (E2), FSH, LH], and adverse events were observed. RESULTS: After the treatment, the rate of changes of ovarian mass volume (among them, at 12 weeks after the first injection, the median was -55.83% in the test group, -68.22% in the control group, P = 0.336), the distinct improvement rate of symptom scores and pelvic signs during non-menstrual days [among them, at 12 weeks after the first injection, the rate of lower abdomen pain was 47.5% (48/101) in the test group, 44.0% (44/100) in the control group, P = 0.881], the hormone (E2, FSH, LH) levels [among them, at 12 weeks after the first injection, the serum level of E2, was (33±38) pmol/L in the test group, (38±40) pmol/L in the control group, P = 0.414; the serum level of FSH, was (5.1±2.8) U/L in the test group, (5.3±2.3) U/L in the control group, P = 0.666; the serum level of LH, was (0.6±0.8) U/L in the test group, (0.6±0.9) U/L in the control group, P = 0.907], had no statistically significant difference between the two groups (all P > 0.05). The distinct improvement rate and improvement rate of symptom (lower abdomen pain, low back pain) scores during menstruation days at 12 weeks after the first injection, the rates of lower abdomen pain were 73.9% (34/46), 15.2% (7/46) respectively in the test group, 72.3% (34/47), 2.1% (1/47) respectively in the control group, had statistically significant difference between the two groups (P = 0.026). There was no serious adverse event occurred in both two groups. The incidence rate of adverse event was 33.6% (38/113) in test group, 23.2% (27/116) in control group, there was no significant difference between the two groups (P = 0.082). CONCLUSION: Leuprolide acetate is effective and safe in the treatment of endometriosis.
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Antineoplásicos Hormonais/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Endometriose/tratamento farmacológico , Leuprolida/uso terapêutico , Preparações de Ação Retardada , Método Duplo-Cego , Estradiol , Feminino , Hormônios , Humanos , Resultado do TratamentoRESUMO
INTRODUCTION: Primary tracheal acinic cell carcinoma (ACC) is an exceptionally rare malignancy, posing challenges in understanding its clinical behavior and optimal management. Surgical resection has traditionally been the primary treatment modality, but we present a compelling case of tracheal ACC managed with endotracheal intervention, challenging conventional approaches. PATIENT CONCERNS: A 53-year-old woman presented with shortness of breath, cough, and hemoptysis. Enhanced computed tomography revealed an obstructive tracheal lesion, leading to her referral for further assessment. DIAGNOSIS: Microscopic evaluation, immunohistochemistry, and clinical assessments confirmed primary tracheal ACC, an exceedingly rare condition with limited clinical insights. INTERVENTIONS: We utilized rigid bronchoscopy to perform endotracheal intervention, successfully resecting the tumor and restoring tracheal patency. Postoperatively, the patient received no radiotherapy or chemotherapy. OUTCOMES: The patient achieved complete recovery, with 24-month follow-up examinations indicating no recurrence or metastatic disease. Only minimal scar tissue remained at the resection site. CONCLUSION: This case demonstrates the potential of endotracheal intervention as a curative approach for primary tracheal ACC, minimizing invasiveness and preserving tracheal function. Collaborative research efforts and extensive case reporting are crucial for advancing our understanding of this rare malignancy and optimizing treatment strategies for improved patient outcomes.
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Carcinoma de Células Acinares , Neoplasias da Traqueia , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Traqueia/cirurgia , Neoplasias da Traqueia/patologia , Carcinoma de Células Acinares/cirurgia , Carcinoma de Células Acinares/patologia , Traqueia/cirurgia , Traqueia/patologia , Broncoscopia/métodos , Tomografia Computadorizada por Raios XRESUMO
Robertsonian translocations (ROBs) are the most common structural chromosomal abnormalities in the general population, with an estimated incidence rate of 1/1000 births. In this study, we retrospectively analyzed the cases of ROBs from September 2015 to August 2022 and totally identified ROB carriers from 84,569 specimens karyotyped in a single accredited laboratory in China, including 189 cases of balanced ROBs and 3 of mosaic ROBs. Microsoft Excel and descriptive statistics were used to record and analyze the collected data. The male/female ratio of ROBs is 1/1.29, with der(13;14) and der(14;21) being the main karyotypes. Among the 192 patients, 7 were lost to follow-up, 82 had given birth, and 103 were childless (such as miscarriage, fetal chromosomal abnormalities, in vitro fertilization (IVF) failure, or divorce). A total of 44 amniocenteses were performed in 42 couples; ROB cases with natural pregnancies showed that the normal karyotype and balanced ROBs of fetal accounted for 66.67% (16/24), while the results of assisted pregnancies showed 90.00% (18/20). This study represents the largest collections of ROBs in Jiangxi population and reminder that the ROB carriers can achieve the ideal outcome for pregnancy with the appropriate genetic guidance and assisted reproductive technologies (ART).
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Aborto Espontâneo , Transtornos Cromossômicos , Gravidez , Humanos , Masculino , Feminino , Estudos Retrospectivos , Translocação Genética , Aberrações Cromossômicas , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/epidemiologia , Transtornos Cromossômicos/genética , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/genéticaRESUMO
PURPOSE: Fumarate hydratase-deficient renal cell cancer (FHRCC) is a rare and aggressive form of renal cell carcinoma. The diagnostic value of 68Ga-FAPI PET/CT for FHRCC remains unexplored. Therefore, we compared the potential value of 68Ga-FAPI-04 and 18F-FDG PET/CT in FHRCC. PATIENTS AND METHODS: Patients with FHRCC underwent 68Ga-FAPI-04 and 18F-FDG PET/CT from May 2022 to December 2023. The SUVmax and tumor-to-liver ratio (TLR) of both tracers were compared using the Wilcoxon signed rank test. RESULTS: Eleven patients with 83 lesions were enrolled. The rate of 18F-FDG PET/CT in detecting lesions was higher than that of 68Ga-FAPI-04 PET/CT: primary tumors: 75.0% (6/8) versus 50.0% (4/8); lymph nodes: 94.9% (37/39) versus 89.7% (35/39); and bone lesions: 100.0% (21/21) versus 90.5% (19/21). The median SUVmax of primary and metastatic lesions on 18F-FDG PET/CT was comparable to 68Ga-FAPI-04 PET/CT in semiquantitative analysis (primary lesions: 13.86 vs 16.35, P = 1.000; lymph nodes: 10.04 vs 9.33, P = 0.517; bone lesions: 13.49 vs 9.84, P = 0.107; visceral lesions: 8.54 vs 4.20, P = 0.056). However, the median TLRs of primary and metastatic lesions on 68Ga-FAPI-04 PET/CT were higher than that of 18F-FDG PET/CT (primary lesions: 30.44 vs 5.41, P = 0.010; lymph nodes: 17.71 vs 3.95, P = 0.000; bone lesions: 15.94 vs 5.21, P = 0.000; visceral lesions: 9.26 vs 3.44, P = 0.003). CONCLUSIONS: 18F-FDG PET/CT detected more primary and metastatic FHRCC lesions than 68Ga-FAPI-04 PET/CT. However, the higher TLR in FHRCC on 68Ga-FAPI-04 PET/CT may indicate therapeutic potential in targeting fibroblast activation protein in FHRCC.
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BACKGROUND: This study aimed to investigate the long-term effects of repetitive mild traumatic brain injury (rmTBI) with varying inter-injury intervals by measuring diffusion tensor metrics, including mean diffusivity (MD), fractional anisotropy (FA), and diffusion magnitude (L) and pure anisotropy (q). METHODS: Eighteen rats were randomly divided into three groups: short-interval rmTBI (n = 6), long-interval rmTBI (n = 6), and sham controls (n = 6). MD, FA, L, and q values were analyzed from longitudinal diffusion tensor imaging at days 50 and 90 after rmTBI. Immunohistochemical staining against neurons, astrocytes, microglia, and myelin was performed. Analysis of variance, Pearson correlation coefficient, and simple linear regression model were used. RESULTS: At day 50 post-rmTBI, lower cortical FA and q values were shown in the short-interval group (p ≤ 0.038). In contrast, higher FA and q values were shown for the long-interval group (p ≤ 0.039) in the corpus callosum. In the ipsilesional external capsule and internal capsule, no significant changes were found in FA, while lower L and q values were shown in the short-interval group (p ≤ 0.028) at day 90. The q values in the external capsule and internal capsule were negatively correlated with the number of microglial cells and the total number of astroglial cells (p ≤ 0.035). CONCLUSION: Tensor scalar measurements, such as L and q values, are sensitive to exacerbated chronic injury induced by rmTBI with shorter inter-injury intervals and reflect long-term astrogliosis induced by the cumulative injury. RELEVANCE STATEMENT: Tensor scalar measurements, including L and q values, are potential DTI metrics for detecting long-term and subtle injury following rmTBI; in particular, q values may be used for quantifying remote white matter (WM) changes following rmTBI. KEY POINTS: The alteration of L and q values was demonstrated after chronic repetitive mild traumatic brain injury. Changing q values were observed in the impact site and remote WM. The lower q values in the remote WM were associated with astrogliosis.
Assuntos
Concussão Encefálica , Imagem de Tensor de Difusão , Ratos Sprague-Dawley , Animais , Imagem de Tensor de Difusão/métodos , Ratos , Masculino , Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/complicações , Anisotropia , Doenças Neuroinflamatórias/diagnóstico por imagem , Doenças Neuroinflamatórias/etiologiaRESUMO
Enzymatic cascades have become a green and sustainable approach for the synthesis of valuable chemicals and pharmaceuticals. Using sequential enzymes to construct a multienzyme complex is an effective way to enhance the overall performance of biosynthetic routes. Here we report the design of an efficient in vitro hybrid biocatalytic system by assembling three enzymes that can convert styrene to (S)-1-phenyl-1,2-ethanediol. Specifically, we prepared the three enzymes in different ways, which were cell surface-displayed, purified, and cell-free expressed. To assemble them, we fused two orthogonal peptide-protein pairs (i.e., SpyTag/SpyCatcher and SnoopTag/SnoopCatcher) to the three enzymes, allowing their spatial organization by covalent assembly. By doing this, we constructed a multienzyme complex, which could enhance the production of (S)-1-phenyl-1,2-ethanediol by 3 times compared to the free-floating enzyme system without assembly. After optimization of the reaction system, the final product yield reached 234.6 µM with a substrate conversion rate of 46.9% (based on 0.5 mM styrene). Taken together, our strategy integrates the merits of advanced biochemical engineering techniques, including cellular surface display, spatial enzyme organization, and cell-free expression, which offers a new solution for chemical biosynthesis by enzymatic cascade biotransformation. We, therefore, anticipate that our approach will hold great potential for designing and constructing highly efficient systems to synthesize chemicals of agricultural, industrial, and pharmaceutical significance.