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The abnormal production and/or excretion of uric acid can lead to a disorder in uric acid metabolism, resulting in hyperuricemia, uric acid nephropathy, gouty arthritis, and other diseases related to uric acid metabolism disorder. The clinical incidence of these diseases is increasing year after year, posing a significant threat to public health. In the past, hyperuricemia and gouty arthritis were often considered different diseases, with uric acid nephropathy being a complication of hyperuricemia. However, recent research has challenged this perspective, suggesting that hyperuricemia, uric acid nephropathy, and gouty arthritis are different stages of the same disease, with urate deposition as the common pathological feature. This article offered a comprehensive overview of the current understanding of hyperuricemia, uric acid nephropathy, and gouty arthritis in both traditional Chinese medicine(TCM) and western medicine. It delved into the most up-to-date insights into the involvement of urate deposition in the pathogenesis of uric acid metabolism disorders and highlighted the dominant role of TCM in the prevention and treatment of uric acid metabolism disorders, so as to provide a reference for effective intervention strategies and drug development in uric acid metabolism disorder-related diseases.
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Medicamentos Herbarios Chinos , Hiperuricemia , Medicina Tradicional China , Ácido Úrico , Humanos , Ácido Úrico/metabolismo , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/metabolismo , Medicamentos Herbarios Chinos/uso terapéutico , Artritis Gotosa/metabolismo , Artritis Gotosa/tratamiento farmacológico , Artritis Gotosa/prevención & control , AnimalesRESUMEN
OBJECTIVE: In this study, we investigated the safety and practicability of ultra-fast track anesthesia (UFTA) for endoscopic thoracic sympathectomy (ETS). METHODS: A total of 72 patients with palmar hyperhidrosis undergoing ETS were randomly divided into three groups: the UFTA group (group I), the group undergoing single-lumen tracheal intubation with local infiltration anesthesia technique (group II), and the group undergoing single-lumen tracheal intubation with routine anesthesia (group III). Mean arterial pressure (MAP) and heart rate (HR) were recorded for all three groups at the following six time points: Before anesthetics administration (T0), the time of intubating or inserting laryngeal mask airway (T1), the time of incising skin (T2), the time of disconnecting of the right sympathetic nerve (T3), the time of disconnecting of the left sympathetic nerve (T4), the time of withdrawing the tracheal tube or laryngeal mask airway (T5), and the time of transferring the patient to a post-anesthesia care unit (PACU) (T6). The three groups were compared from the following perspectives: surgery duration; anesthesia recovery duration, that is, the duration from discontinuation of anesthesia to extubating the tracheal tube; the dose of propofol and remifentanil per kilogram body mass per unit time interval (the time at the end of the procedure, which lasted from anesthesia induction to incision suturing); and the visual analog scale (VAS) in the resting state in the PACU. RESULTS: Based on pairwise comparisons, the average HR and average MAP values of the three groups differed significantly from T2 to T6 (p < 0.05). As demonstrated by the correlation analysis between remifentanil and propofol with HR and MAP, the doses of the total amount of remifentanil and propofol were lower, and group I used less remifentanil and propofol than group II. No patient in group I experienced throat discomfort following surgery. Patients in groups II and III experienced a range of postoperative discomfort. The VAS scores of groups I and II were significantly lower than those of group III, with group I lower than group II. CONCLUSION: When utilized in ETS, UFTA can provide effective anesthesia for minor traumas. It is safe, effective, and consistent with the enhanced recovery philosophy of fast-track surgery departments.
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OBJECTIVE: To investigate the relationship between complications of massive cerebral infarction (MCI) and composite inflammatory ratios. STUDY DESIGN: A case-control study. Place and Duration of the Study: Department of Neurology, Affiliated Hospital of Putian University, Putian, China, from January 2019 to November 2021. METHODOLOGY: Eighty-two patients with MCI underwent blood tests within 24 hours of admission. Complications such as cerebral herniation, haemorrhage transformation (HT), and stroke-associated pneumonia (SAP) were evaluated based on imaging examinations. The prognosis was assessed using the modified Rankin Scale score (mRS) at discharge. RESULTS: Among the 82 patients, the cerebral herniation group had higher levels of systemic immune inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) compared to the non-cerebral herniation group. MCI patients who developed HT had higher levels of SII, NLR, mean platelet volume/platelet (MPV/PLT), and platelet-to-lymphocyte ratio (PLR). The SAP group had higher levels of MPV/PLT and NLR compared to the non-SAP group. The poor prognosis group had higher SII and NLR levels but a lower lymphocyte-to-monocyte ratio (LMR) compared to the good prognosis group. CONCLUSION: NLR showed high accuracy in predicting complications and the short-term prognosis of MCI. SII was linked to cerebral herniation, HT, and the short-term prognosis of MCI. MPV/PLT was found to be related to SAP and HT caused by MCI. LMR may act as a protective factor for the short-term prognosis of MCI. KEY WORDS: Massive cerebral infarction, Neutrophil-to-lymphocyte ratio, Systemic immune inflammation index, Prognosis.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Isquemia Encefálica/complicaciones , Estudios de Casos y Controles , Accidente Cerebrovascular/complicaciones , Linfocitos , Pronóstico , Neutrófilos , Infarto Cerebral , Inflamación , Estudios RetrospectivosRESUMEN
Blackleg and soft rot are harmful diseases in potato (Solanum tuberosum) caused by Pectobacterium spp. and Dickeya spp. (Czajkowski et al. 2015). The occurrence of potato blackleg was serious in potato-producing areas around Xiapu County in Fujian Province, China, in 2021 (6 ha) and 2022 (7 ha), with an incidence of approximately 5%, which reached nearly 23%. Three diseased plants were collected to isolate the pathogen. Single colonies from each sampled plant were isolated and streaked onto fresh plates. DNA from three colonies from different plants was PCR amplified with primer pair 27F/1492R (Lane 1991) for the 16S rRNA gene. Since the sequences were identical, we selected strain M2-3 for further analysis. The strain M2-3 was gram-negative, pectolytic on CVP, grew at 37°C and 5% NaCl. The bacterium was positive for phosphatase activity, erythromycin sensitivity, indole production, gelatin liquefaction, malonic utilization, and acid production from, melibiose, raffinose, and arabinose. The bacterium was negative for sucrose, α-methyl glucoside, sorbitol, trehalose, lactose, and sodium citrate (Fujimoto et al. 2018;),although sucrose and lactose did not provide the expected results, there are exception in all species. The genome of strain M2-3 was sequenced and deposited in the NCBI database under accession numbers: CP077422. An Average Nucleotide Identity (ANI) analysis showed that M2-3 clustered with other D. dadantii strains and has a 98.39% identity with D. dadantii strain DSM 18020 (CP023467). The housekeeping genes (recA, dnaX, acnA, gapA, icd, mdh, mtlD and pgi) were amplified with primer pairs designed previously(Fujimoto et al. 2018; Ma et al. 2007) and sequenced. A multilocus sequence analysis (MLSA) was performed by concatenating the 8 gene sequences and constructing a maximum likelihood phylogenetic tree using PhyloSuite version 1.2.1 (Zhang et al. 2020) and IQ-tree version 1.6.8 (Nguyen et al. 2015) software. Strain M2-3 was clustered together with Dickeya dadantii. For the pathogenicity test, three plants per treatment, totaling nine plants, were used. Bacterial suspensions (1×10^8 CFU/mL) were made in a 10mM PBS buffer. 10 µL of M2-3, D. dadantii type strain 18020 (positive control), and buffer (negative control) were injected into the plant stems near the base. Water stains appeared at the site of inoculation after 2 days and they gradually became black and rotten. The leaves became yellow and wilted, and the petiole base rotted within 5 days of inoculation completing the Koch postulate. According to average nucleotide identity and housekeeping gene sequence analysis, strain M2-3 was identified as Dickeya dadantii. Previous studies have reported several pathogens that cause potato blackleg in China, including P. atrosepticum, P. carotovorum, P. brasiliense, P. parmentieri, P. polaris, and P. punjabense (Li-ping et al. 2020; Wang et al. 2021). To the best of our knowledge, this study is the first to report potato blackleg disease caused by Dickeya dadantii in Fujian Province, China. This finding suggests that this pathogen may cause a threat to potato production in Fujian Province.
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Limited resident's participation in the stock market has become a key constraint to the capital market development. Utilizing the 2019 China Household Financial Survey (CHFS) data, our paper designs probit models to examine the peer effects of residents' stock market participation and explore the intermediary mechanisms with a multiple intermediary model. We find that: (1) Resident involvement in stock market decision-making exhibits significant peer effects. (2) Heterogeneity analysis reveals that males and rural residents display more pronounced peer effects than females and urban residents. Additionally, middle-aged residents demonstrate more potent peer effects than their younger and older counterparts, with the intensity of peer effects correlating with education levels. (3)We observe that the peer effects of market participation operate by altering economic expectations and enhancing residents' financial literacy. (4) Further investigation establishes that individuals engaging in stock market investments manifest peer effects when deciding whether to diversify their stock portfolio. This study holds reference value for analyzing the impact of social interaction on financial behaviors and regulating individuals' financial conduct.
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Inversiones en Salud , Modelos Económicos , Humanos , Persona de Mediana Edad , Escolaridad , ChinaRESUMEN
Twin and family studies have established the genetic contribution to idiopathic generalized epilepsy (IGE). The genetic architecture of IGE is generally complex and heterogeneous, and the majority of the genetic burden in IGE remains unsolved. We hypothesize that gene-gene interactions contribute to the complex inheritance of IGE. CNTN2 (OMIM* 615,400) variants have been identified in cases with familial adult myoclonic epilepsy and other epilepsies. To explore the gene-gene interaction network in IGE, we took the CNTN2 gene as an example and investigated its co-occurrent genetic variants in IGE cases. We performed whole-exome sequencing in 114 unrelated IGE cases and 296 healthy controls. Variants were qualified with sequencing quality, minor allele frequency, in silico prediction, genetic phenotype, and recurrent case numbers. The STRING_TOP25 gene interaction network analysis was introduced with the bait gene CNTN2 (denoted as A). The gene-gene interaction pair mode was presumed to be A + c, A + d, A + e, with a leading gene A, or A + B + f, A + B + g, A + B + h, with a double-gene A + B, or other combinations. We compared the number of gene interaction pairs between the case and control groups. We identified three pairs in the case group, CNTN2 + PTPN18, CNTN2 + CNTN1 + ANK2 + ANK3 + SNTG2, and CNTN2 + PTPRZ1, while we did not discover any pairs in the control group. The number of gene interaction pairs in the case group was much more than in the control group (p = 0.021). Taking together the genetic bioinformatics, reported epilepsy cases, and statistical evidence in the study, we supposed CNTN2 as a candidate pathogenic gene for IGE. The gene interaction network analysis might help screen candidate genes for IGE or other complex genetic disorders.
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Contactinas , Epilepsia Generalizada , Epistasis Genética , Redes Reguladoras de Genes , Predisposición Genética a la Enfermedad , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Adulto Joven , Estudios de Casos y Controles , Contactinas/genética , Epilepsia Generalizada/genética , Secuenciación del Exoma , Frecuencia de los GenesRESUMEN
Spinocerebellar ataxias (SCAs) are inherited neurodegenerative diseases characterized by loss of balance, coordination, and slurred speech. Recently, a digenic mode of inheritance of TBP/STUB1 contributing to SCA was demonstrated. The clinical manifestations of SCATBP/STUB1 include not only ataxia but also obvious cognitive and behavioral impairment. Here, we describe a Chinese family with SCATBP/STUB1 and performed a literature search for similar cases. We identified a Chinese family with SCATBP/STUB1 and compare our clinical findings with other cases described in the literature so far. Four individuals in this family have been found to carry SCATBP/STUB1, of which three have clinical manifestations. A heterozygous deletion mutation in the STIP1-homologous and U-box containing protein 1 (STUB1) gene, NM_005861.4:c433_435del(p.K145del), was identified. The proband is a 34-year-old female with progressive dementia and dysarthria. The mother and uncle of the proband first presented with motor abnormalities and gradually developed cognitive impairment. The proband and her uncle showed cerebellar atrophy on MRI. The proband's brother carried digenic variants but was asymptomatic. SCATBP/STUB1 is a novel SCA subtype. The main clinical manifestations are motor, cognitive, and behavioral abnormalities. Brain MRI shows significant cerebellar atrophy and cortical thinning. The independent segregation of TBP and STUB1 alleles should be considered when evaluating patients with cognitive impairment and ataxia.
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Linaje , Ataxias Espinocerebelosas , Proteína de Unión a TATA-Box , Humanos , Femenino , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/diagnóstico por imagen , Proteína de Unión a TATA-Box/genética , Adulto , Masculino , Pueblo Asiatico/genética , Persona de Mediana Edad , Pueblos del Este de AsiaRESUMEN
PURPOSE: Idiopathic generalized epilepsies (IGEs) are a common group of genetic generalized epilepsies with high genetic heterogeneity and complex inheritance. However, the genetic basis is still largely unknown. This study aimed to explore the genetic etiologies in IGEs. METHODS: Trio-based whole-exome sequencing was performed in 60 cases with IGEs. The pathogenicity of candidate genetic variants was evaluated by the criteria of the American College of Medical Genetics and Genomics (ACMG), and the clinical causality was assessed by concordance between the observed phenotype and the reported phenotype. RESULTS: Seven candidate variants were detected in seven unrelated cases with IGE (11.7%, 7/60). According to ACMG, a de novo SLC2A1 (c.376C>T/p.Arg126Cys) variant identified in childhood absence epilepsy was evaluated as pathogenic with clinical concordance. Six variants were assessed to be uncertain significance by ACMG, but then considered causative after evaluation of clinical concordance. These variants included CLCN4 hemizygous variant (c.2044G>A/p.Glu682Lys) and IQSEC2 heterozygous variant (c.4315C>T/p.Pro1439Ser) in juvenile absence epilepsy, EFHC1 variant (c.1504C>T/p.Arg502Trp) and CACNA1H (c.589G>T/p.Ala197Ser) both with incomplete penetrance in juvenile myoclonic epilepsy, and GRIN2A variant (c.2011C>G/p.Gln671Glu) and GABRB1 variant (c.1075G>A/p.Val359Ile) both co-segregated with juvenile myoclonic epilepsy. Among them, GABRB1 was for the first time identified as potential novel causative gene for IGE. SIGNIFICANCE: Considering the genetic heterogeneity and complex inheritance of IGEs, a comprehensive evaluation combined the ACMG scoring and assessment of clinical concordance is suggested for the pathogenicity analysis of variants identified in clinical screening. GABRB1 is probably a novel causative gene for IGE, which warrants further studies.
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Epilepsia Tipo Ausencia , Epilepsia Generalizada , Epilepsia Mioclónica Juvenil , Humanos , Mutación , Secuenciación del Exoma , Epilepsia Generalizada/genética , Inmunoglobulina E/genética , Canales de Cloruro/genética , Proteínas de Unión al Calcio/genética , Factores de Intercambio de Guanina Nucleótido/genéticaRESUMEN
Context: Gout is a chronic disease that imposes a huge financial and health burden on patients, which might diminish quality of life. Qin Jiao, a perennial herb found in northwestern China and Japan, is commonly used for treating various ailments.Objective: This study investigates the effects of Qin Jiao on gout and joint inflammation and elucidates its potential mechanism for gouty arthritis.Materials and methods: Study 1, a literature review was conducted using PubMed, Web of Science, and CNKI to assess the applications of Qin Jiao in arthritis treatment. Study 2 was performed to discover the component targets and gouty disease targets via TCMSP, OMIM, GeneCards and DRUGBANK, and network pharmacology analysis. Study 3, male Sprague-Dawley (SD) rats were divided into normal, model, colchicine, Qin Jiao low-dose (QJL), and Qin Jiao high-dose group (QJH), oral gavage for 40 d. Serum, synovial fluid, and synovial membrane tissue were collected to measure the expression levels of IL-1ß, IL-6, and STAT3.Results: The research also identified potential targets and pharmacological pathways of Qin Jiao for gout treatment. In vivo study demonstrated Qin Jiao can reduce IL-1ß levels in serum and ankle flushing fluid. ELISA analysis confirmed that Qin Jiao significantly reduces the protein expression of IL-6 and STAT3.Discussion and conclusion: Qin Jiao exerts anti-inflammatory effects on gouty arthritis by modulating the IL-6/STAT3 pathway. This study provides a biological basis for the use of Qin Jiao in treating arthritis-related diseases and offers experimental evidence for potential future drug development.
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Artritis Gotosa , Medicamentos Herbarios Chinos , Gota , Humanos , Ratas , Animales , Masculino , Artritis Gotosa/tratamiento farmacológico , Interleucina-6 , Farmacología en Red , Calidad de Vida , Ratas Sprague-Dawley , Gota/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Background: Excessive daytime sleepiness (EDS) is a frequent nonmotor symptoms of Parkinson's disease (PD), which seriously affects the quality of life of PD patients and exacerbates other nonmotor symptoms. Previous studies have used static analyses of these resting-state functional magnetic resonance imaging (rs-fMRI) data were measured under the assumption that the intrinsic fluctuations during MRI scans are stationary. However, dynamic functional network connectivity (dFNC) analysis captures time-varying connectivity over short time scales and may reveal complex functional tissues in the brain. Purpose: To identify dynamic functional connectivity characteristics in PD-EDS patients in order to explain the underlying neuropathological mechanisms. Methods: Based on rs-fMRI data from 16 PD patients with EDS and 41 PD patients without EDS, we applied the sliding window approach, k-means clustering and independent component analysis to estimate the inherent dynamic connectivity states associated with EDS in PD patients and investigated the differences between groups. Furthermore, to assess the correlations between the altered temporal properties and the Epworth sleepiness scale (ESS) scores. Results: We found four distinct functional connectivity states in PD patients. The patients in the PD-EDS group showed increased fractional time and mean dwell time in state IV, which was characterized by strong connectivity in the sensorimotor (SMN) and visual (VIS) networks, and reduced fractional time in state I, which was characterized by strong positive connectivity intranetwork of the default mode network (DMN) and VIS, while negative connectivity internetwork between the DMN and VIS. Moreover, the ESS scores were positively correlated with fraction time in state IV. Conclusion: Our results indicated that the strong connectivity within and between the SMN and VIS was characteristic of EDS in PD patients, which may be a potential marker of pathophysiological features related to EDS in PD patients.
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Introduction: Rheumatoid arthritis (RA) is an immune-mediated disease associated with chronic inflammation of numerous joints. Nyctanthes arbor-tristis (NAT) is a traditional remedy for RA, a chronic inflammatory disorder. Aim: The current project aims to demonstrate the role of the NAT extracts in sub-acute toxicity, pharmacovigilance, and anti-rheumatic biomarkers. Method: Hydroethanolic extract (1:1) of plant leaves was prepared by using the reflux method. The safety of the dose was evaluated in Sprague-Dawley rats, and the anti-inflammatory effects of NAT on RA symptoms, including paw volumes, body weight, arthritic index, withdrawal latency, hematology and serological test, radiology, and histopathology, were evaluated in Freund's complete adjuvant (FCA)-induced arthritis Sprague-Dawley rat models. The inflammatory (TNF-α and COX-2) and anti-inflammatory markers (IL-10) were analyzed in control and experimental groups. Result: The study showed that 500 mg/kg BW NAT leaf extract was found to be least toxic without showing any subacute toxicity symptoms. The pharmacovigilance study highlighted the potential side effects of NAT, such as drowsiness, sedation, and lethargy, at high dosages. Treatment with the plant extract mitigated paw edema, restored the immune organ and body weights, and ameliorated the level of blood parameters such as hemoglobin, red blood cells, platelets, white blood cells, aspartate aminotransferase (AST), alanine transaminase (ALT), C-reactive proteins, and rheumatoid factor. Treatment with the plant extracts also reduced the level of cyclooxygenase 2 and TNF-α and increased the level of IL-10 in the serum of arthritic rats dose-dependently. Radiographic analysis of the ankle joint showed an improvement in the hind legs. Histological examination of the ankle joints revealed that the plant extract treatment decreased pannus formation, inflammation, and synovial hyperplasia in arthritic animals. Conclusion: NAT 500 mg/kg could serve as a promising therapeutic option for the treatment of inflammatory arthritis.
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The roughness of the part surface is one of the most crucial standards for evaluating machining quality due to its relationship with service performance. For a preferable comprehension of the evolution of surface roughness, this study proposes a novel surface roughness prediction model on the basis of the unity of fuse d signal features and deep learning architecture. The force and vibration signals produced in the milling of P20 die steel are collected, and time and frequency domain feature from the acquired signals are extracted by variational modal decomposition. The GA-MI algorithm is taken to select the signal features that are relevant to the surface roughness of the workpiece. The optimal feature subset is analyzed and used as the input of the prediction model. DBN is adopted to estimate the surface roughness and the model parameters are optimized by ISSA. (Reviewer 1, Q1) The separate force, vibration and fusion signal information are brought into the DBN model and the ISSA-DBN model for the prediction of surface roughness, and the results show that the accuracy of the roughness prediction is as follows, respectively DBN: 78.1%, 68.8% and 84.4%, and ISSA-DBN: 93.8%, 87.5% and 100%.
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Rheumatoid arthritis (RA) is an autoimmune disease characterized by bone and joint degeneration. Existing anti-inflammatory chemotherapy drugs offer temporary relief but come with undesirable side effects. Herbal medications have shown positive effects on RA symptoms with minimal adverse reactions. In this study, we investigated the potential of Nyctanthes arbor-tristis (NAT) through in vitro and in silico research. Hydroethanolic extracts of harsingar were prepared using the reflux method, containing alkaloids, phenol, saponin, steroids, proteins, tannins, terpenoids, carbohydrates, glycosides, and flavonoids, which exhibited TPC (98.56 ± 0.46 mg GAE/g) and TFC (34.51 ± 0.45 mg CE/g). LC-MS/MS analyzes the active compounds in the extract. NAT exhibited the best scavenging capabilities at 1 mg/mL in anti-oxidant and anti-arthritic activity. Maximum splenocyte proliferation occurred at 250 µg/mL. In vitro cell splenocyte studies revealed the downregulation of TNF-α and the upregulation of IL-10. Additionally, an in silico study demonstrated that bioactive constituents and targets bind with favorable binding affinity. These findings demonstrate the potential of Nyctanthes arbor-tristis in exerting anti-arthritic effects, as supported by in vitro and in silico studies. Further mechanistic research is necessary to validate the therapeutic potential of all phytoconstituents in RA treatment.
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Artritis Reumatoide , Enfermedades Autoinmunes , Osteoartritis , Humanos , Cromatografía Liquida , Espectrometría de Masas en Tándem , Artritis Reumatoide/tratamiento farmacológicoRESUMEN
Background: This study aimed to evaluate the efficacy of Chinese patent medicines (CPMs) combined with dexrazoxane (DEX) against anthracycline-induced cardiotoxicity (AIC) and further explore their pharmacological mechanism by integrating the network meta-analysis (NMA) and network pharmacology approach. Methods: We searched for clinical trials on the efficacy of DEX + CPMs for AIC until March 10, 2023 (Database: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, China Science and Technology Journal and China Online Journals). The evaluating outcomes were cardiac troponin I (cTnI) level, creatine kinase MB (CK-MB) level, left ventricular ejection fraction (LVEF) value, and electrocardiogram (ECG) abnormal rate. Subsequently, the results of NMA were further analyzed in combination with network pharmacology. Results: We included 14 randomized controlled trials (RCTs) and 1 retrospective cohort study (n = 1,214), containing six CPMs: Wenxinkeli (WXKL), Cinobufotalin injection (CI), Shenqifuzheng injection (SQFZ), Shenmai injection (SM), Astragalus injection (AI) and AI + CI. The NMA was implemented in Stata (16.0) using the mvmeta package. Compared with using DEX only, DEX + SM displayed the best effective for lowering cTnI level (MD = -0.44, 95%CI [-0.56, -0.33], SUCRA 93.4%) and improving LVEF value (MD = 14.64, 95%CI [9.36, 19.91], SUCRA 98.4%). DEX + SQFZ showed the most effectiveness for lowering CK-MB level (MD = -11.57, 95%CI [-15.79, -7.35], SUCRA 97.3%). And DEX + AI + CI has the highest effectiveness for alleviating ECG abnormalities (MD = -2.51, 95%CI [-4.06, -0.96], SUCRA 96.8%). So that we recommended SM + DEX, SQFZ + DEX, and DEX + AI + CI as the top three effective interventions against AIC. Then, we explored their pharmacological mechanism respectively. The CPMs' active components and AIC-related targets were screened to construct the component-target network. The potential pathways related to CPMs against AIC were determined by KEGG. For SM, we identified 118 co-targeted genes of active components and AIC, which were significantly enriched in pathways of cancer pathways, EGFR tyrosine kinase inhibitor resistance and AGE-RAGE signaling pathway in diabetic complications. For SQFZ, 41 co-targeted genes involving pathways of microRNAs in cancer, Rap1 signaling pathway, MAPK signaling pathway, and lipid and atherosclerosis. As for AI + CI, 224 co-targeted genes were obtained, and KEGG analysis showed that the calcium signaling pathway plays an important role except for the consistent pathways of SM and SQFZ in anti-AIC. Conclusions: DEX + CPMs might be positive efficacious interventions from which patients with AIC will derive benefits. DEX + SM, DEX + SQFZ, and DEX + AI + CI might be the preferred intervention for improving LVEF value, CK-MB level, and ECG abnormalities, respectively. And these CPMs play different advantages in alleviating AIC by targeting multiple biological processes.
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Objective: The present study aimed to use bedside ultrasound to evaluate the effects of metoclopramide on gastric motility in patients being treated for trauma in the emergency department. Methods: Fifty patients underwent an ultrasound immediately after attending the emergency department of Zhang Zhou Hospital due to trauma. The patients were randomly divided into two groups: a metoclopramide group (group M, n = 25) and a normal saline group (group S, n = 25). The cross-sectional area (CSA) of the gastric antrum was measured at 0, 30, 60, 90, and 120 min (T = time). The gastric emptying rate (GER, GER=-AareaTn/AareaTn-30-1×100), GER/min (GER divided by the corresponding interval time), gastric content properties, Perlas grade at different time points, T120 gastric volume (GV), and GV per unit of body weight (GV/W) were evaluated. The risk of vomiting, reflux/aspiration, and type of anesthetic treatment were also evaluated. Results: The differences between the two groups in the CSA of the gastric antrum at each time point were statistically significant (p < 0.001). The CSAs of the gastric antrum in group M were lower than those in group S, and the greatest difference between the two groups occurred at T30 (p < 0.001). The differences between the two groups in GER and GER/min were also statistically significant (p < 0.001); those differences in group M were higher than those in group S, and the greatest differences between the two groups occurred at T30 (p < 0.001). There were no obvious change trends in the properties of the gastric contents and the Perlas grades in either group, and the differences between the two groups were not statistically significant (p = 0.97). The differences between the two groups in the GV and GV/W at T120 were statistically significant (p < 0.001), as was the risk of reflux and aspiration at T120 (p < 0.001). Conclusion: When metoclopramide was used in satiated emergency trauma patients, it accelerated gastric emptying within 30 min and reduced the risk of accidental reflux. However, a normal gastric emptying level was not achieved, which can be attributed to the delaying effect of trauma on gastric emptying.
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Epilepsia , Humanos , Virulencia , Epilepsia/genética , Predisposición Genética a la EnfermedadRESUMEN
Gene sub-region encoded protein domain is the basic unit for protein structure and function. The DMD gene is the largest coding gene in humans, with its phenotype relevant to idiopathic generalized epilepsy. We hypothesized variants clustered in sub-regions of idiopathic generalized epilepsy genes and investigated the relationship between the DMD gene and idiopathic generalized epilepsy. Whole exome sequencing was performed in 106 idiopathic generalized epilepsy individuals. DMD variants were filtered with variant type, allele frequency, in silico prediction, hemizygous or homozygous status in the population, inheritance mode, and domain location. Variants located at the sub-regions were selected by the subRVIS software. The pathogenicity of variants was evaluated by the American College of Medical Genetics and Genomics criteria. Articles on functional studies related to epilepsy for variants clustered protein domains were reviewed. In sub-regions of the DMD gene, two variants were identified in two unrelated cases with juvenile absence epilepsy or juvenile myoclonic epilepsy. The pathogenicity of both variants was uncertain significance. Allele frequency of both variants in probands with idiopathic generalized epilepsy reached statistical significance compared with the population (Fisher's test, p = 2.02 × 10-6, adjusted α = 4.52 × 10-6). The variants clustered in the spectrin domain of dystrophin, which binds to glycoprotein complexes and indirectly affects ion channels contributing to epileptogenesis. Gene sub-region analysis suggests a weak association between the DMD gene and idiopathic generalized epilepsy. Functional analysis of gene sub-region helps infer the pathogenesis of idiopathic generalized epilepsy.
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Epilepsia Generalizada , Epilepsia , Humanos , Epilepsia Generalizada/genética , Frecuencia de los Genes , FenotipoRESUMEN
Background: Hyperuricemia (HUA) is a major public health issue with a high prevalence worldwide. Wuling San (WLS) is an effective treatment for HUA. However, the active compounds and the related mechanism are unclear. In this study, we aimed to explore the active compounds and the underlying pharmacological mechanisms of WLS against HUA. Methods: First, a network pharmacology approach was used to detect active compounds of WLS, and potential targets and signaling pathways involved in the treatment of HUA were predicted. Then, a molecular docking strategy was used to predict the affinity between active compounds and key targets. Finally, to verify the prediction, the HUA rat model was established. Results: 49 active compounds with 108 common targets were obtained. Besides, cerevisterol, luteolin, ergosterol peroxide, beta-sitosterol, and sitosterol were identified as key active compounds. In PPI analysis, TNF, IL6, CASP3, PPARG, STAT3, and other 12 core targets were obtained. GO enrichment analysis indicated that WLS was likely to interfere with oxidative stress in the treatment of HUA, and KEGG enrichment analysis indicated multiple inflammation-related signaling pathways possibly involved in the treatment of HUA by WLS, including TNF, and NOD-like receptor, HIF-1, PI3K-Akt, and IL-17 signaling pathways. The results of molecular docking indicated that the active compounds had good binding properties to their key targets. In the validation experiments, WLS significantly reduced the levels of serum uric acid (SUA) and serum malondialdehyde (MDA). Moreover, WLS not only significantly increased the levels of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD), but also inhibited the expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Conclusion: In the present study, we demonstrate that WLS has multicomponent, multitarget, and multi-pathway properties in the treatment of HUA. Its potential capability to reduce SUA could be ascribed to oxidative stress improvement and inflammation inhibition.
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Medicamentos Herbarios Chinos , Hiperuricemia , Animales , Ratas , Simulación del Acoplamiento Molecular , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Ácido Úrico , Estrés Oxidativo , InflamaciónRESUMEN
OBJECTIVE: The aim of this research is to investigate the feasibility of folate receptor-positive circulating tumor cells (FR+CTCs) as a biomarker for the diagnosis of malignant pulmonary nodules and the correlation between clinicopathological factors and FR+CTC levels. METHODS: Patients initially diagnosed with one or more pulmonary nodules from a computed tomography scan were prospectively included. Three milliliters of peripheral blood was collected from each participant for FR+CTC analysis prior to surgery. Clinical and pathological parameters and FR+CTC levels were compared between patients with lung cancer and benign diseases. RESULTS: Six hundred fifty-three patients had lung cancer and the other 124 had benign lung diseases based on pathological examinations of the resected specimens. The median FR+CTC value of the lung cancer group was 12.0 (95% CI 9.6-16.2) FU/3 mL and that of the benign group was 7.2 (95% CI 5.78-11.2) FU/3 mL. The difference was statistically significant (P < 0.0001). In a receiver operating characteristic analysis to distinguish the two groups, the area under curve of FR+CTC was 0.7457 (95% CI 0.6893-0.8021; P < 0.0001) using a cutoff of 8.65 FU/3 mL. The sensitivity was 86.37%, and the specificity was 74.19%. Combined with conventional serum tumor biomarkers, the area under curve was 0.922 (0.499-0.963). The sensitivity was 92.20%, and the specificity was 83.05%. FR+CTC levels were related to tumor staging (P4 < 0.001), the degree of tumor invasion both in single (P = 0.011) and multiple lesions (P = 0.022), pathological subtypes (P = 0.013), and maximum tumor diameter (P = 0.014). CONCLUSIONS: FR+CTC is an effective and reliable biomarker for the diagnosis of lung cancer. Further, FR+CTC level is correlated with tumor staging, degree of invasion, pathological subtypes, and tumor size.