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1.
Nat Methods ; 21(4): 609-618, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38443507

RESUMEN

Precise identification and quantification of amino acids is crucial for many biological applications. Here we report a copper(II)-functionalized Mycobacterium smegmatis porin A (MspA) nanopore with the N91H substitution, which enables direct identification of all 20 proteinogenic amino acids when combined with a machine-learning algorithm. The validation accuracy reaches 99.1%, with 30.9% signal recovery. The feasibility of ultrasensitive quantification of amino acids was also demonstrated at the nanomolar range. Furthermore, the capability of this system for real-time analyses of two representative post-translational modifications (PTMs), one unnatural amino acid and ten synthetic peptides using exopeptidases, including clinically relevant peptides associated with Alzheimer's disease and cancer neoantigens, was demonstrated. Notably, our strategy successfully distinguishes peptides with only one amino acid difference from the hydrolysate and provides the possibility to infer the peptide sequence.


Asunto(s)
Nanoporos , Aminoácidos/química , Péptidos/química , Secuencia de Aminoácidos , Porinas/química , Porinas/metabolismo
2.
Nucleic Acids Res ; 52(7): e39, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38477342

RESUMEN

CRISPR-Cas systems with dual functions offer precise sequence-based recognition and efficient catalytic cleavage of nucleic acids, making them highly promising in biosensing and diagnostic technologies. However, current methods encounter challenges of complexity, low turnover efficiency, and the necessity for sophisticated probe design. To better integrate the dual functions of Cas proteins, we proposed a novel approach called CRISPR-Cas Autocatalysis Amplification driven by LNA-modified Split Activators (CALSA) for the highly efficient detection of single-stranded DNA (ssDNA) and genomic DNA. By introducing split ssDNA activators and the site-directed trans-cleavage mediated by LNA modifications, an autocatalysis-driven positive feedback loop of nucleic acids based on the LbCas12a system was constructed. Consequently, CALSA enabled one-pot and real-time detection of genomic DNA and cell-free DNA (cfDNA) from different tumor cell lines. Notably, CALSA achieved high sensitivity, single-base specificity, and remarkably short reaction times. Due to the high programmability of nucleic acid circuits, these results highlighted the immense potential of CALSA as a powerful tool for cascade signal amplification. Moreover, the sensitivity and specificity further emphasized the value of CALSA in biosensing and diagnostics, opening avenues for future clinical applications.


Asunto(s)
Técnicas Biosensibles , Sistemas CRISPR-Cas , ADN de Cadena Simple , Oligonucleótidos , Humanos , Oligonucleótidos/química , Oligonucleótidos/genética , ADN de Cadena Simple/genética , ADN de Cadena Simple/metabolismo , ADN de Cadena Simple/química , Técnicas Biosensibles/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , ADN/química , ADN/genética , Línea Celular Tumoral , Catálisis
3.
J Med Genet ; 61(5): 459-468, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38296632

RESUMEN

BACKGROUND: Townes-Brocks syndrome (TBS) is a rare genetic disorder characterised by multiple malformations. Due to its phenotypic heterogeneity and rarity, diagnosis and recognition of TBS can be challenging and there has been a lack of investigation of patients with atypical TBS in large cohorts and delineation of their phenotypic characteristics. METHODS: We screened SALL1 and DACT1 variants using next-generation sequencing in the China Deafness Genetics Consortium (CDGC) cohort enrolling 20 666 unrelated hearing loss (HL) cases. Comprehensive clinical evaluations were conducted on seven members from a three-generation TBS family. Combining data from previously reported cases, we also provided a landscape of phenotypes and genotypes of patients with TBS. RESULTS: We identified five novel and two reported pathogenic/likely pathogenic (P/LP) SALL1 variants from seven families. Audiological features in patients differed in severity and binaural asymmetry. Moreover, previously undocumented malformations in the middle and inner ear were detected in one patient. By comprehensive clinical evaluations, we further provide evidence for the causal relationship between SALL1 variation and certain endocrine abnormalities. Penetrance analysis within familial contexts revealed incomplete penetrance among first-generation patients with TBS and a higher disease burden among their affected offspring. CONCLUSION: This study presents the first insight of genetic screening for patients with TBS in a large HL cohort. We broadened the phenotypic-genotypic spectrum of TBS and our results supported an underestimated prevalence of TBS. Due to the rarity and phenotypic heterogeneity of rare diseases, broader spectrum molecular tests, especially whole genome sequencing, can improve the situation of underdiagnosis and provide effective recommendations for clinical management.


Asunto(s)
Anomalías Múltiples , Ano Imperforado , Pérdida Auditiva Sensorineural , Pulgar/anomalías , Factores de Transcripción , Humanos , Mutación , Factores de Transcripción/genética , Síndrome , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/genética , Fenotipo , Proteínas Nucleares/genética , Proteínas Adaptadoras Transductoras de Señales/genética
4.
J Mol Cell Biol ; 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38444183

RESUMEN

Fusion pore opening is a transient intermediate state of synaptic vesicle exocytosis, which is highly dynamic and precisely regulated by the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex and synaptotagmin-1 (Syt1). Yet, the regulatory mechanism is not fully understood. In this work, using single-channel membrane fusion electrophysiology, we determined that SNAREpins are important for driving fusion pore opening and dilation but incapable of regulating the dynamics. When Syt1 was added, the closing frequency of fusion pores significantly increased, while the radius of fusion pores mildly decreased. In response to Ca2+, SNARE/Syt1 greatly increased the radius of fusion pores and reduced their closing frequency. Moreover, the residue F349 in the C2B domain of Syt1, which mediates Syt1 oligomerization, was required for clamping fusion pore opening in the absence of Ca2+, probably by extending the distance between the two membranes. Finally, in Ca2+-triggered fusion, the primary interface between SNARE and Syt1 plays a critical role in stabilizing and dilating the fusion pore, while the polybasic region of Syt1 C2B domain has a mild effect on increasing the radius of the fusion pore. In summary, our results suggest that Syt1, SNARE, and the anionic membrane synergically orchestrate the dynamics of fusion pore opening in synaptic vesicle exocytosis.

5.
Nanoscale ; 16(12): 6087-6094, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38444242

RESUMEN

Membrane proteins are vital resources for developing biosensors. TMEM120A is a membrane protein associated with human pain transmission and lipid metabolism, and recent studies have demonstrated its ability to transport ions and bind to coenzyme A (COA-SH), indicating its potential to develop into a single-molecule sensor based on electrical methods. In this study, we investigated the ion transport properties of TMEM120A and its homolog TMEM120B on an artificial lipid bilayer using single-channel recording. The results demonstrate that both proteins can fuse into the lipid bilayer and generate stable ion currents under a bias voltage. Based on the stable ion transport capabilities of TMEM120A and TMEM120B, as well as the feature of TMEM120A binding with COA-SH, we developed these two proteins into a single-molecule sensor for detecting COA-SH and structurally similar molecules. We found that both COA-SH and ATP can reversibly bind to single TMEM120A and TMEM120B proteins embedded in the lipid bilayer and temporarily block ion currents during the binding process. By analyzing the current blocking signal, COA-SH and ATP can be identified at the single-molecule level. In conclusion, our work has provided two single-molecule biosensors for detecting COA-SH and ATP, offering insights for exploring and developing bio-inspired small molecule sensors.


Asunto(s)
Membrana Dobles de Lípidos , Proteínas de la Membrana , Humanos , Membrana Dobles de Lípidos/química , Proteínas de la Membrana/metabolismo , Coenzima A , Nanotecnología , Adenosina Trifosfato
6.
BMC Med Genomics ; 17(1): 203, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39123271

RESUMEN

BACKGROUND: A comprehensive understanding of the genetic basis of rare diseases and their regulatory mechanisms is essential for human molecular genetics. However, the genetic mutant spectrum of pathogenic genes within the Chinese population remains underrepresented. Here, we reported previously unreported functional ABHD12 variants in two Chinese families and explored the correlation between genetic polymorphisms and phenotypes linked to PHARC syndrome. METHODS: Participants with biallelic pathogenic ABHD12 variants were recruited from the Chinese Deafness Genetics Cohort. These participants underwent whole-genome sequencing. Subsequently, a comprehensive literature review was conducted. RESULTS: Two Han Chinese families were identified, one with a compound heterozygous variant and the other with a novel homozygous variant in ABHD12. Among 65 PHARC patients, including 62 from the literature and 3 from this study, approximately 90% (57 out of 63) exhibited hearing loss, 82% (50 out of 61) had cataracts, 82% (46 out of 56) presented with retinitis pigmentosa, 79% (42 out of 53) experienced polyneuropathy, and 63% (36 out of 57) displayed ataxia. Seventeen different patterns were observed in the five main phenotypes of PHARC syndrome. A total of 33 pathogenic variants were identified in the ABHD12. Compared with other genotypes, individuals with biallelic truncating variants showed a higher incidence of polyneuropathy (p = 0.006), but no statistically significant differences were observed in the incidence of hearing loss, ataxia, retinitis pigmentosa and cataracts. CONCLUSIONS: The diagnosis of PHARC syndrome is challenging because of its genetic heterogeneity. Therefore, exploring novel variants and establishing genotype-phenotype correlations can significantly enhance gene diagnosis and genetic counseling for this complex disease.


Asunto(s)
Ataxia , Catarata , Estudios de Asociación Genética , Monoacilglicerol Lipasas , Linaje , Fenotipo , Polineuropatías , Retinitis Pigmentosa , Humanos , Masculino , Femenino , Ataxia/genética , Catarata/genética , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/patología , Polineuropatías/genética , Monoacilglicerol Lipasas/genética , Mutación , Adulto , Niño , Adolescente , Genotipo
7.
ACS Nano ; 18(12): 9137-9149, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38470845

RESUMEN

Point-of-care monitoring of small molecules in biofluids is crucial for clinical diagnosis and treatment. However, the inherent low degree of recognition of small molecules and the complex composition of biofluids present significant obstacles for current detection technologies. Although nanopore sensing excels in the analysis of small molecules, the direct detection of small molecules in complex biofluids remains a challenge. In this study, we present a method for sensing the small molecule drug gentamicin in whole blood based on the mechanosensitive channel of small conductance in Pseudomonas aeruginosa (PaMscS) nanopore. PaMscS can directly detect gentamicin and distinguish its main components with only a monomethyl difference. The 'molecular sieve' structure of PaMscS enables the direct measurement of gentamicin in human whole blood within 10 min. Furthermore, a continuous monitoring device constructed based on PaMscS achieved continuous monitoring of gentamicin in live rats for approximately 2.5 h without blood consumption, while the drug components can be analyzed in situ. This approach enables rapid and convenient drug monitoring with single-molecule level resolution, which can significantly lower the threshold for drug concentration monitoring and promote more efficient drug use. Moreover, this work also lays the foundation for the future development of continuous monitoring technology with single-molecule level resolution in the living body.


Asunto(s)
Antibacterianos , Nanoporos , Humanos , Ratas , Animales , Antibacterianos/farmacología , Gentamicinas , Nanotecnología , Pseudomonas aeruginosa
8.
Am J Chin Med ; 52(3): 841-864, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38716618

RESUMEN

A high-glucose environment is involved in the progression of diabetes mellitus (DM). This study aims to explore the regulatory effects of quercetin (QUE) on autophagy and apoptosis after myocardial injury in rats with DM. The type 2 DM rat models were constructed using low-dose streptozotocin (STZ) treatment combined with a high-carbohydrate (HC) diet in vivo. Compared with the control group, the body weight was decreased, whereas blood pressure, blood glucose, and the LVW/BW ratio were increased in the diabetic group. The results showed that the myocardial fibers were disordered in the diabetic group. Moreover, we found that the myocardial collagen fibers, PAS-positive cells, and apoptosis were increased, whereas the mitochondrial structure was destroyed and autophagic vacuoles were significantly reduced in the diabetic group compared with the control group. The expression levels of autophagy-related proteins LC3 and Beclin1 were decreased, whereas the expression levels of P62, Caspae-3, and Bax/Bcl-2 were increased in the diabetic group in vitro and in vivo. Moreover, QUE treatment alleviated the cellular oxidative stress reaction under high-glucose environments. The results of immunoprecipitation (IP) showed that the autophagy protein Beclin1 was bound to Bcl-2, and the binding capacity increased in the HG group, whereas it decreased after QUE treatment, suggesting that QUE inhibited the binding capacity between Beclin1 and Bcl-2, thus leading to the preservation of Beclin1-induced autophagy. In addition, the blood pressure, blood glucose, and cardiac function of rats were improved following QUE treatment. In conclusion, QUE suppressed diabetic myocardial injury and ameliorated cardiac function by regulating myocardial autophagy and inhibition of apoptosis in diabetes through the AMPK/mTOR signaling pathway.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Apoptosis , Autofagia , Diabetes Mellitus Experimental , Quercetina , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Autofagia/efectos de los fármacos , Apoptosis/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Quercetina/farmacología , Transducción de Señal/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Masculino , Proteínas Quinasas Activadas por AMP/metabolismo , Ratas Sprague-Dawley , Ratas , Modelos Animales de Enfermedad , Miocardio/metabolismo , Miocardio/patología , Estreptozocina , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/tratamiento farmacológico , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/prevención & control , Fitoterapia , Beclina-1/metabolismo , Estrés Oxidativo/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicaciones
9.
Rev Sci Instrum ; 95(6)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38860831

RESUMEN

Measurement device independent quantum key distribution (MDI QKD) has attracted growing attention for its immunity to attacks at the measurement unit, but its unique structure limits the secret key rate. Utilizing the wavelength division multiplexing (WDM) technique and reducing error rates are effective strategies for enhancing the secret key rate. Reducing error rates often requires active feedback control of wavelengths using precise external references. However, for a multiwavelength laser, employing multiple references to stabilize each wavelength output places stringent demands on these references and significantly increases system complexity. Here, we demonstrate a stable, wavelength-tunable multiwavelength laser with an output wavelength ranging from 1270 to 1610 nm. Through precise temperature control and stable drive current, we passively lock the laser wavelength, achieving remarkable wavelength stability. This significantly reduce the error rate, leading to an almost doubling of the secret key rate compared to previous experiments. Furthermore, the exceptional wavelength stability offered by our multiwavelength laser, combined with the WDM technique, has further boosted the secret key rate of MDI QKD. With a wide wavelength tuning range of 5.1 nm, our multiwavelength laser facilitates flexible operation across multiple dense wavelength division multiplexing channels. Coupled with high wavelength stability and multiple wavelength outputs simultaneously, this laser offers a promising solution for a high-rate MDI QKD system.

10.
Cell Transplant ; 33: 9636897231221887, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38183241

RESUMEN

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory disease characterized by familial and acquired forms. Here, we present the case of a 26-year-old male patient with relapsed/refractory peripheral T-cell lymphoma and concurrent HLH. Whole-exon sequencing revealed germline mutations associated with HLH, including those in critical genes such as CD27 and UNC13D and other germline heterozygous variants (NOTCH2, NOTCH3, IL2RA, TYK2, AGL, CFD, and F13A1). CD107a analyses consistently demonstrated impaired degranulation of cytotoxic T-lymphocytes and natural killer (NK) cells. Examination of the patient's family pedigree revealed that his father and mother harbored UNC13D and CD27 mutations, respectively; his brother carried the same CD27 heterozygous mutation. However, none of them manifested the disease. Despite the missense mutation of CD27 (c.779C>T; p.Pro260Leu) lacking previous documentation in databases, comprehensive analysis suggested non-pathogenic mutations in the CD27 variant, indicating minimal impact on T- and NK-cell functions. These results ultimately supported the option of hematopoietic stem cell transplantation (HSCT) as a successful curative therapeutic approach. As of this report, the patient has remained free of lymphoma and quiescent HLH 15.2 months post-HSCT. This study underscores the efficacy of genetic tests in identifying significant mutations and confirming their etiologies, providing an early basis for treatment decisions and the selection of suitable transplant donors.


Asunto(s)
Linfohistiocitosis Hemofagocítica , Linfoma de Células T Periférico , Masculino , Humanos , Adulto , Mutación de Línea Germinal , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/genética , Linfohistiocitosis Hemofagocítica/terapia , Recurrencia Local de Neoplasia , Mutación , Proteínas de la Membrana
11.
Front Cell Infect Microbiol ; 14: 1366472, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38500502

RESUMEN

Pulmonary Mucormycosis is a fatal infectious disease with high mortality rate. The occurrence of Mucormycosis is commonly related to the fungal virulence and the host's immunological defenses against pathogens. Mucormycosis infection and granulation tissue formation occurred in the upper airway was rarely reported. This patient was a 60-year-old male with diabetes mellitus, who was admitted to hospital due to progressive cough, sputum and dyspnea. High-resolution computed tomography (HRCT) and bronchoscopy revealed extensive tracheal mucosal necrosis, granulation tissue proliferation, and severe airway stenosis. The mucosal necrotic tissue was induced by the infection of Rhizopus Oryzae, confirmed by metagenomic next-generation sequencing (mNGS) in tissue biopsy. This patient was treated with the placement of a covered stent and local instillation of amphotericin B via bronchoscope. The tracheal mucosal necrosis was markedly alleviated, the symptoms of cough, shortness of breath, as well as exercise tolerance were significantly improved. The placement of airway stent and transbronchial microtube drip of amphotericin B could conduce to rapidly relieve the severe airway obstruction due to Mucormycosis infection.


Asunto(s)
Obstrucción de las Vías Aéreas , Mucormicosis , Masculino , Humanos , Persona de Mediana Edad , Anfotericina B/uso terapéutico , Mucormicosis/diagnóstico , Mucormicosis/microbiología , Mucormicosis/patología , Rhizopus oryzae , Necrosis/patología , Obstrucción de las Vías Aéreas/etiología , Obstrucción de las Vías Aéreas/patología , Tejido de Granulación/patología , Tos/patología
12.
Nat Commun ; 14(1): 8390, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-38110352

RESUMEN

Signal transmission in the brain relies on voltage-gated ion channels, which exhibit the electrical behaviour of memristors, resistors with memory. State-of-the-art technologies currently employ semiconductor-based neuromorphic approaches, which have already demonstrated their efficacy in machine learning systems. However, these approaches still cannot match performance achieved by biological neurons in terms of energy efficiency and size. In this study, we utilise molecular dynamics simulations, continuum models, and electrophysiological experiments to propose and realise a bioinspired hydrophobically gated memristive nanopore. Our findings indicate that hydrophobic gating enables memory through an electrowetting mechanism, and we establish simple design rules accordingly. Through the engineering of a biological nanopore, we successfully replicate the characteristic hysteresis cycles of a memristor and construct a synaptic device capable of learning and forgetting. This advancement offers a promising pathway for the realization of nanoscale, cost- and energy-effective, and adaptable bioinspired memristors.


Asunto(s)
Nanoporos , Fenómenos Electrofisiológicos , Semiconductores , Electricidad , Encéfalo
15.
Braz. j. med. biol. res ; 53(8): e9469, 2020. tab, graf
Artículo en Inglés | LILACS, Coleciona SUS (Brasil) | ID: biblio-1132537

RESUMEN

This is a retrospective, single-center observational study to explore the predictors of chest drainage for neonatal pneumothorax. A total of 183 neonates (age ≤28 days) who presented to the Children's Hospital of Soochow University between January 1, 2015 and December 31, 2018 for pneumothorax or developed pneumothorax during a hospital stay were included. Demographic data, clinical presentation, and imaging characteristics of neonatal pneumothorax were collected and analyzed. We used univariate and multivariate logistic regression analyses to determine significant predictors of chest drainage of pneumothorax in neonates. Pneumothorax occurred within 24 h after birth in 131 (71.6%) cases, between 24 and 48 h after birth in 41 (22.4%) cases, and 48 h after birth in 11 (6.0%) cases. Univariate and multivariate logistic regression analyses revealed that lung collapse ≥1/3 on initial chest X-ray (OR 4.99, 95%CI 2.25-11.07), chest retractions (OR 8.12, 95%CI 2.88-22.89), cyanosis (OR 2.25, 95%CI 1.08-4.66), and frothing from mouth (OR 2.49, 95%CI 1.12-5.49) (P<0.05 for all) were significant predictors of the need for chest drainage due to pneumothorax. In conclusion, the thorough evaluation of the above predictive factors can guide treatment and improve patient outcome.


Asunto(s)
Humanos , Masculino , Femenino , Embarazo , Recién Nacido , Neumotórax , Síndrome de Aspiración de Meconio , Estudios Retrospectivos , Disnea , Tiempo de Internación
16.
Braz. j. med. biol. res ; 52(8): e8522, 2019. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1011609

RESUMEN

Pancreaticobiliary maljunction (PBM) is associated with high risk of epithelial atypical growth and malignant transformation of the bile duct or gallbladder. However, overall changes in genetic expression have not been examined in children with PBM. Genome-wide expression was analyzed using peripheral blood samples from 10 children with PBM and 15 pediatric controls. Differentially expressed genes (DEGs) were identified using microarray. Bioinformatics analysis was conducted using Gene Ontology and KEGG analyses. The top 5 in the up-regulated genes in PBM were verified with qRT-PCR. Receiver operator characteristic curve analysis was conducted to evaluate the predictive accuracy of selected genes for PBM. The microarray experiments identified a total of 876 DEGs in PBM, among which 530 were up-regulated and the remaining 346 were down-regulated. Verification of the top 5 up-regulated genes (TYMS, MYBPC1, FUT1, XAGE2, and GREB1L) by qRT-PCR confirmed the up-regulation of MYBPC1 and FUT1. Receiver operating characteristic curve analysis suggested that FUT1 and MYBPC1 up-regulation could be used to predict PBM, with the area under the curve of 0.873 (95%CI=0.735−1.000) and 0.960 (95%CI=0.891−1.000), respectively. FUT1 and MYBPC1 were up-regulated in children with PBM, and could be used as potential biomarkers for PBM.


Asunto(s)
Humanos , Masculino , Lactante , Preescolar , Niño , Conductos Pancreáticos/anomalías , Conductos Biliares/anomalías , Regulación hacia Arriba/genética , Perfilación de la Expresión Génica , Fucosiltransferasas/genética , Neoplasias de los Conductos Biliares/etiología , Proteínas Portadoras/genética , Estudios de Casos y Controles , Análisis por Micromatrices , Dilatación Patológica/complicaciones , Dilatación Patológica/congénito , Neoplasias de la Vesícula Biliar/etiología
17.
Chinese Medical Journal ; (24): 589-593, 2010.
Artículo en Inglés | WPRIM | ID: wpr-314538

RESUMEN

<p><b>BACKGROUND</b>Hemocoagulase Agkistrodon for injection is a single component thrombin which has passed phases I and II clinical trials. The purpose of this phase III clinical trial was to evaluate the effect of Hemocoagulase Agkistrodon on hemostasis and coagulation in abdominal skin and subcutaneous incisions and to assess the safety of this agent in surgical patients.</p><p><b>METHODS</b>This is a phase III, prospective, randomized, double-blind, and controlled multicenter clinical trial including 432 consecutive patients randomized into either a study group (injected with hemocoagulase Agkistrodon at 2 U, n = 324) or a control group (injected with hemocoagulase Atrox, n = 108). The hemostatic time, hemorrhagic volume, hemorrhagic volume per unit area, blood coagulation, and adverse events were measured and compared between the two groups.</p><p><b>RESULTS</b>The mean hemostatic time in the study group was (36.8 +/- 18.7) seconds; the hemorrhagic volume was (3.77 +/- 3.93) g; and the hemorrhagic volume per unit area was (0.091 +/- 0.125) g/cm(2). In the control group, the corresponding values were (38.1 +/- 19.7) seconds, (4.00 +/- 4.75) g, and (0.095 +/- 0.101) g/cm(2), respectively. No significant difference in values existed between the two groups (P > 0.05). Blood coagulation results and hepatic and renal function were also similar between the two groups. Adverse events were reported in two cases, but were deemed non-drug-related.</p><p><b>CONCLUSIONS</b>Hemocoagulase Agkistrodon has good hemostatic and coagulative function and is safe for the use of arresting capillary hemorrhage that occurs while incising the abdomen during surgery.</p>


Asunto(s)
Adolescente , Adulto , Anciano , Animales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Abdomen , Cirugía General , Agkistrodon , Batroxobina , Farmacología , Coagulación Sanguínea , Método Doble Ciego , Medicina Basada en la Evidencia , Hemostasis , Hemostáticos , Farmacología , Estudios Prospectivos
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