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BACKGROUND: It is unclear whether laparoscopic hepatectomy (LH) for hepatolithiasis confers better clinical benefit and lower hospital costs than open hepatectomy (OH). This study aim to evaluate the clinical and economic value of LH versus OH. METHODS: Patients undergoing OH or LH for primary hepatolithiasis at Yijishan Hospital of Wannan Medical College between 2015 and 2022 were divided into OH group and LH group. Propensity score matching (PSM) was used to balance the baseline data. Deviation-based cost modelling and weighted average median cost (WAMC) were used to assess and compare the economic value. RESULTS: A total of 853 patients were identified. After exclusions, 403 patients with primary hepatolithiasis underwent anatomical hepatectomy (OH n=143; LH n=260). PSM resulted in 2 groups of 100 patients each. Although LH required a longer median operation duration compared with OH (285.0 versus 240.0 min, respectively, P<0.001), LH patients had fewer wound infections, fewer pre-discharge overall complications (26 versus 43%, respectively, P=0.009), and shorter median postoperative hospital stays (8.0 versus 12.0 days, respectively, P<0.001). No differences were found in blood loss, major complications, stone clearance, and mortality between the two matched groups. However, the median overall hospital cost of LH was significantly higher than that of OH (CNY¥52,196.1 versus 45,349.5, respectively, P=0.007). Although LH patients had shorter median postoperative hospital stays and fewer complications than OH patients, the WAMC was still higher for the LH group than for the OH group with an increase of CNY¥9,755.2 per patient undergoing LH. CONCLUSION: The overall clinical benefit of LH for hepatolithiasis is comparable or even superior to that of OH, but with an economic disadvantage. There is a need to effectively reduce the hospital costs of LH and the gap between costs and diagnosis-related group reimbursement to promote its adoption.
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Hepatectomia , Laparoscopia , Pontuação de Propensão , Humanos , Hepatectomia/economia , Hepatectomia/métodos , Feminino , Masculino , Laparoscopia/economia , Laparoscopia/métodos , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Hepatopatias/cirurgia , Hepatopatias/economia , Estudos de Coortes , Idoso , Litíase/cirurgia , Litíase/economia , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Complicações Pós-Operatórias/economia , Resultado do TratamentoRESUMO
Asparaginase-associated pancreatitis (AAP) is a severe and potentially life-threatening drug-induced pancreas targeted toxicity in the combined chemotherapy of acute lymphoblastic leukemia among children and adolescents. The toxicological mechanism of AAP is not yet clear, and there are no effective preventive and treatment measures available clinically. Fibroblast growth factor 21 (FGF21) is a secretory hormone that regulates lipid, glucose, and energy metabolism balance. Acinar tissue is the main source of pancreatic FGF21 protein and plays an important role in maintaining pancreatic metabolic balance. In this study, we found that the decrease of FGF21 in pancreas is closely related to AAP. Pegaspargase (1 IU/g) induces widespread edema and inflammatory infiltration in the pancreas of rats/mice. The specific expression of FGF21 in the acinar tissue of AAP rats was significantly downregulated. Asparaginase caused dysregulation of the ATF4/ATF3/FGF21 axis in acinar tissue or cells, and thus mediated the decrease of FGF21. It greatly activated ATF3 in the acinar, which competed with ATF4 for the Fgf21 promoter, thereby inhibiting the expression of FGF21. Pharmacological replacement of FGF21 (1 mg/kg) or PERK inhibitors (GSK2656157, 25 mg/kg) can significantly mitigate the pancreatic tissue damage and reduce markers of inflammation associated with AAP, representing potential strategies for the prevention and treatment of AAP.
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Asparaginase , Fatores de Crescimento de Fibroblastos , Pâncreas , Pancreatite , eIF-2 Quinase , Animais , Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Asparaginase/toxicidade , Pancreatite/induzido quimicamente , Pancreatite/metabolismo , Pancreatite/patologia , Masculino , Ratos , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pâncreas/metabolismo , Camundongos , Ratos Sprague-Dawley , Polietilenoglicóis/toxicidade , Antineoplásicos/toxicidade , Fator 4 Ativador da Transcrição/metabolismo , Fator 4 Ativador da Transcrição/genética , Camundongos Endogâmicos C57BLRESUMO
Inflammatory pain, the most prevalent disease globally, remains challenging to manage. Electroacupuncture emerges as an effective therapy, yet its underlying mechanisms are not fully understood. This study investigates whether adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-regulated silent information regulator 1 (SIRT1) contributes to electroacupuncture's antinociceptive effects by modulating macrophage/microglial polarization in the spinal dorsal horn of a mouse model of inflammatory pain. In this study, mice, introduced to inflammatory pain through subcutaneous injections of complete freund's adjuvant (CFA) in the plantar area, underwent electroacupuncture therapy every alternate day for 30-min sessions. The assessment of mechanical allodynia and thermal hyperalgesia in these subjects was carried out using paw withdrawal frequency and paw withdrawal latency measurements, respectively. Western blot analysis measured levels of AMPK, phosphorylation-adenosine 5'-monophosphate (AMP)-activated protein kinase, SIRT1, inducible nitric oxide synthase, cluster of differentiation 86, arginase 1, and interleukin 10. In contrast to the group treated solely with CFA, the cohort receiving both CFA and electroacupuncture demonstrated notable decreases in both thermal hyperalgesia and mechanical allodynia. This was accompanied by a marked enhancement in AMPK phosphorylation levels. AMPK knockdown reversed electroacupuncture's analgesic effects and reduced M2 macrophage/microglial polarization enhancement. Additionally, AMPK knockdown significantly weakened electroacupuncture-induced SIRT1 upregulation, and EX-527 injection attenuated electroacupuncture's facilitation of M2 macrophage/microglial polarization without affecting AMPK phosphorylation levels. Furthermore, combining electroacupuncture with SRT1720 enhanced the analgesic effect of SRT1720. Our findings suggest that AMPK regulation of SIRT1 plays a critical role in electroacupuncture's antinociceptive effect through the promotion of M2 macrophage/microglial polarization.
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Eletroacupuntura , Hiperalgesia , Humanos , Ratos , Camundongos , Animais , Hiperalgesia/terapia , Hiperalgesia/induzido quimicamente , Proteínas Quinases Ativadas por AMP/uso terapêutico , Microglia , Sirtuína 1 , Ratos Sprague-Dawley , Dor/induzido quimicamente , Analgésicos/uso terapêutico , Adenosina , Macrófagos , Inflamação/induzido quimicamenteRESUMO
BACKGROUND: The aim of this study was to identify the risk factors for postoperative delirium (POD) in elderly patients undergoing heart valve surgery with cardiopulmonary bypass (CPB). METHODS: Elderly patients undergoing elective heart valve surgery with CPB in The First Affiliated Hospital of Wenzhou Medical University between March 2022 and March 2023 were selected for this investigation. They were divided into a POD group and a non-POD group. Their baseline information was collected and recorded, and the patients were subjected to neurocognitive function assessment using the Mini-Mental State Examination and the Montreal Cognitive Assessment scales before surgery. We also recorded their intraoperative indicators such as duration of surgery, duration of CPB, duration of aortic cross-clamp, blood transfusion, and postoperative indicators such as duration of mechanical ventilation, postoperative 24-hour drainage volume, and pain score. Regional cerebral oxygen saturation was monitored intraoperatively by near-infrared spectroscopy based INVOS5100C Regional Oximeter. Patients were assessed for the occurrence of POD using Confusion Assessment Method for the Intensive Care Unit, and logistic regression analysis of risk factors for POD was performed. RESULTS: The study finally included 132 patients, with 47 patients in the POD group and 85 ones in the non-POD group. There were no significant differences in baseline information and preoperative indicators between the two groups. However, marked differences were identified in duration of surgery, duration of CPB, duration of aortic cross-clamp, duration of postoperative mechanical ventilation, postoperative length of stay in cardiac intensive care unit, postoperative length of hospital stay, intraoperative blood transfusion, postoperative pain score, and postoperative 24-hour drainage volume between the two groups (p < 0.05). Additionally, the two groups had significant differences in rScO2 at each intraoperative time point and in the difference of rScO2 from baseline at each intraoperative time point (p < 0.05). Multivariate logistic regression analysis showed that duration of surgery > 285 min (OR, 1.021 [95% CI, 1.008-1.035]; p = 0.002), duration of postoperative mechanical ventilation > 23.5 h (OR, 6.210 [95% CI, 1.619-23.815]; p = 0.008), and postoperative CCU stay > 3.5 d (OR, 3.927 [95% CI, 1.046-14.735]; p = 0.043) were independent risk factors of the occurrence of POD while change of rScO2 at T1>50.5 (OR, 0.832 [95% CI 0.736-0.941]; p = 0.003) was a protective factor for POD. CONCLUSION: Duration of surgery duration of postoperative mechanical ventilation and postoperative CCU stay are risk factors for POD while change of rScO2 at T1 is a protective factor for POD in elderly patients undergoing heart valve surgery with CPB.
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Procedimentos Cirúrgicos Cardíacos , Delírio do Despertar , Humanos , Idoso , Delírio do Despertar/etiologia , Delírio do Despertar/complicações , Ponte Cardiopulmonar/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Fatores de Risco , Valvas Cardíacas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnósticoRESUMO
Bacteria capable of direct ammonia oxidation (Dirammox) play important roles in global nitrogen cycling and nutrient removal from wastewater. Dirammox process, NH3 â NH2 OH â N2 , first defined in Alcaligenes ammonioxydans HO-1 and encoded by dnf gene cluster, has been found to widely exist in aquatic environments. However, because of multidrug resistance in Alcaligenes species, the key genes involved in the Dirammox pathway and the interaction between Dirammox process and the physiological state of Alcaligenes species remain unclear. In this work, ammonia removal via the redistribution of nitrogen between Dirammox and microbial growth in A. ammonioxydans HO-1, a model organism of Alcaligenes species, was investigated. The dnfA, dnfB, dnfC, and dnfR genes were found to play important roles in the Dirammox process in A. ammonioxydans HO-1, while dnfH, dnfG, and dnfD were not essential genes. Furthermore, an unexpected redistribution phenomenon for nitrogen between Dirammox and cell growth for ammonia removal in HO-1 was revealed. After the disruption of the Dirammox in HO-1, more consumed NH4 + was recovered as biomass-N via rapid metabolic response and upregulated expression of genes associated with ammonia transport and assimilation, tricarboxylic acid cycle, sulfur metabolism, ribosome synthesis, and other molecular functions. These findings deepen our understanding of the molecular mechanisms for Dirammox process in the genus Alcaligenes and provide useful information about the application of Alcaligenes species for ammonia-rich wastewater treatment.
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Compostos de Amônio , Compostos de Amônio/metabolismo , Alcaligenes/genética , Alcaligenes/metabolismo , Amônia/toxicidade , Amônia/metabolismo , Águas Residuárias , Nitrogênio/metabolismo , Desnitrificação , Oxirredução , Reatores BiológicosRESUMO
ObjectiveTo understand the influencing factors of work-related injury medical expenses in Kunshan City. Methods The work-related injury data of Kunshan City from 2016 to 2021 were collected from the “Jiangsu Human Resources and Social Security Integration Handling Platform” of Kunshan Municipal Human Resources and Social Security Bureau, and the influencing factors of work-related injury medical expenses were analyzed using quantile regression. Results The median (interquartile range) of per capita work-related injury medical expenses in Kunshan City from 2016 to 2021 was 1 025.6(7 199.1) yuan. The result of 0.50 quantile regression analysis showed that the work-related injury medical expenses of male workers were higher than that of female workers (P<0.01), the work-related injury medical expenses of workers aged 46 and above were higher than those aged 16-<26 (P<0.01), the work-related injury medical expenses of veteran workers were lower than those of new workers (P<0.01), the work-related injury medical expenses of workers in the third, fourth, fifth, and sixth major risk industries were higher than that in the first major risk industry (all P<0.05), the work-related injury medical expenses on lower limb, head and neck, trunk, and multiple injured areas were lower than upper limb injuries (all P<0.01), the work-related injury medical expenses of workers with death, grades 5 to 6, grades 7 to 10, failure to reach grade, and ungraded injuries were lower than those of workers with grades 1 to 4 injuries (all P<0.01), the medical expenses for work-related injuries such as scalds, burns, and scorch were higher than cuts, abrasions, and stabs injuries (P<0.01). Conclusion The influencing factors of the workers' medical expenses for work-related injuries are age, gender, and injured body part. It is necessary to further strengthen the prevention of work-related injuries for males, new workers, workers in the third to sixth major risk industries, and those aged 46 and above. Meanwhile, it is needed to prevent workers from suffering scalds, burns, scorch injuries, upper limb injuries, and high disability grades injuries, to reduce the economic burden on workers and the society.
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Children and adults differ significantly in physiology, biochemistry and immune function, which leads to significant differences in blood transfusion strategies between children and adults. To guide the clinical transfusion practice of pediatric patients and improve the prognosis of children, the National Health Commission organized the formulation and release of the health industry standard Guideline for Pediatric Transfusion (WS/T 795-2022).This paper will briefly introduce some concepts that help understand of the Standard and the preparation process of the Standard, and explain and interpret the preparation of the " scope", " general provisions" and " factors to consider" of the Standard, hoping to contribute to the understanding and implementation of the Standard.
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Immunosuppressant is one of the main preventive measures for rejection after organ transplantation, whereas it may reduce the host response capability to pathogens and increase the risk of infection. In recent years, the application of mesenchymal stem cell (MSC) therapy in the field of solid organ transplantation has attracted widespread attention. Preclinical studies have shown that MSC therapy may prolong the survival time of transplant kidney, induce immune tolerance, accelerate the repair of acute kidney injury and promote the recovery of renal function. Clinical trials have confirmed the safety, tolerance and effectiveness of MSC therapy. Consequently, general characteristics, immunomodulation and tissue repair function of MSC, and the application of MSC in clinical trials of kidney transplantation were reviewed, the unresolved issues were briefly discussed and the prospects for subsequent research were predicted, aiming to provide reference for promoting the application of MSC therapy in clinical kidney transplantation.
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ObjectiveTo explore the impact of subjective vertical perception impairment after stroke on visuospatial cognition, balance, walking and activities of daily living, to investigate the mediating role of visuospatial cognition and lateropulsion. MethodsFrom February to December, 2023, 96 stroke patients were selected from the Rehabilitation Medicine Center of the First Affiliated Hospital of Nanjing Medical University. They were divided into vertical perception impairment group (n = 53) and non-vertical perception impairment group (n = 43). They were assessed with National Institutes of Health Stroke Scale (NIHSS), the Scale for Contraversive Pushing (SCP), Burke Lateropulsion Scale (BLS), Line Bisection Test (LBT), Line Cancellation Test (LCT), Star Cancellation Test (SCT), Subjective Visual Vertical (SVV), Berg Balance Scale (BBS), Holden Functional Ambulation Categories (FAC) and Barthel Index (BI). ResultsScores of SVV orientation, SVV uncertainty, NIHSS, SCT, SCP, BLS, BBS, FAC and BI were worse in the vertical perception impairment group than in the non-vertical perception impairment group (|t| > 2.414, Z = -3.481, P < 0.05). Scores of SVV were correlated with SCT, BLS and BBS (|r| ≥ 0.273, P < 0.05). After controlling for age and gender, SVV orientation score did not directly impact BBS score (β = -0.011, P = 0.920). However, it exerted a partial mediating effect through BLS (effect = -0.173, 95%CI -0.278 to -0.076) and a chain-mediated effect through SCT and BLS (effect = -0.073, 95%CI -0.137 to -0.027), impacting BBS score. ConclusionSubjective vertical perception impairment results in poorer visuospatial cognition, balance, walking and activities of daily living in stroke patients. This influence on balance function is mediated through the mediating effects of visuospatial cognition and lateropulsion.
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ObjectiveTo investigate the effect of modified Baduanjin exercise, as an rehabilitation exercise, on cardiopulmonary function, motor function and activities of daily living in patients with stroke. MethodsFrom January to September, 2023, 42 stroke patients in the Nanjing Qixia District Hospital were randomly divided into control group (n = 21) and experimental group (n = 21). The control group received routine rehabilitation, and the experimental group received modified Baduanjin exercise in addition, for four weeks. They were assessed with peak oxygen uptake (VO2peak), anaerobic threshold (AT), peak oxygen pulse (VO2peak/HR), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak expiratory flow (PEF), Fugl-Meyer Assessment-upper extremities (FMA-UE), Berg Balance Scale (BBS) and modified Barthel Index (MBI) before and after intervention. ResultsVO2peak, AT, and the scores of FMA-UE, BBS and MBI improved in the control group after intervention (|t| > 2.256, |Z| > 2.936, P < 0.05); while VO2peak, AT, VO2peak/HR, FVC, FEV1, PEF, and the scores of FMA-UE, BBS and MBI improved in the experimental group (|t| > 4.390, |Z| > 3.451, P < 0.001); and all the indexes were better in the experimental group than in the control group (|t| > 4.136,|Z| > 2.751,P < 0.01), except the scores of BBS and MBI. ConclusionModified Baduanjin exercise can improve the cardiopulmonary function and upper limb motor function for stroke patients.
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ObjectiveTo investigate the effect of galvanic vestibular stimulation on stroke patients with lateropulsion. MethodsFrom February to October, 2023, 30 stroke patients with lateropulsion in the First Affiliated Hospital of Nanjing Medical University were divided into control group (n = 15) and experimental group (n = 15) randomly. The control group received routine rehabilitation and sham galvanic vestibular stimulation, and the experimental group received routine rehabilitation and true galvanic vestibular stimulation, for two weeks. They were assessed with Scale for Contraversive Pushing (SCP), subjective visual vertical (SVV), Line Cancellation Test (LCT), Star Cancellation Test (SCT), Berg Balance Scale (BBS), Holden Functional Ambulation Category (FAC) and Barthel Index (BI) before and after treatment. ResultsAll the indexes improved in both groups after intervention (|t| > 2.461, Z > 3.000, P < 0.05), except the SVV orientation, SVV certainty and SCT in the control group; while the SCP, SVV certainty, LCT and FAC were better in the experimental group than in the control group (|t| > 2.189, Z = -2.862, P < 0.05), and the differences before and after intervention were better in the experimental group than in the control group (|t| > 2.382, P < 0.05), except LCT. SCP was correlated with SVV orientation, SVV certainty, SCT, BBS, BI and FAC (|r| > 0.381, P < 0.05). ConclusionGalvanic vestibular stimulation can improve the lateropulsion, balance, walking function and activities of daily living in stroke patients, which may be related to improvement for spatial cognitive function, especially vertical perception.
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Objective To analyze the burden of disease attributable to coronary heart disease in adult patients in 2020, to compare the disease burden of patients with coronary heart disease among different sociodemographic indexes (SDI) , and to explore the correlation between the two to provide theoretical guidance for coronary heart disease prevention. Methods The data of 881 adult patients with coronary heart disease in our Hospital in 2020 were collected, and the data, such as illness, morbidity, mortality and disability-adjusted life years (DALY) of adult patients with coronary heart disease were analyzed. Pearson correlation was used to analyze the association between disease burden and sociodemographic index in adult patients with coronary heart disease. Results The prevalence and incidence of adult patients with coronary heart disease were higher in women than in men, while the mortality rate and DALY rate were mainly higher in men than in women. The prevalence, morbidity and mortality rates increased in different age groups, and increased rapidly in the age group of 45 years and beyond. The prevalence of DALY in adult patients with coronary heart disease in different age groups also showed an upward trend, and increased rapidly in the age group of 35 years and beyond. The SDI value of adult patients with coronary heart disease was (0.52±0.16), of which the low SDI value was (0.13±0.05), the medium and low SDI value was (0.34±0.17), the medium SDI value was (0.50±0.14), the medium and high SDI value was (0.82±0.25), and the high SDI value was (0.93±0.13). The chi-square results showed that there were differences in mortality (χ2=12.358, P=0.020) and DALY rate (χ2 =14.557, P=0.011) of adult patients with coronary heart disease between different grades of SDI groups, and the differences were statistically significant. Pearson-related results showed that SDI and DALY rate were negatively correlated in adult patients with coronary heart disease (r=-0.374, P=0.022), and there were gender differences. SDI was negatively correlated with DALY rate in male patients with coronary heart disease (r=-0.489, P=0.017), and SDI was negatively correlated with mortality (r=-0.290, P=0.040) and DALY rate in female patients with coronary heart disease (r=-0.392, P=0.006). Conclusion Burden of disease attributed to coronary heart disease in adult patients varies by sex and it has a negative correlation with SDI, and the improvement of national welfare and education level, that is, the increase of SDI may have a certain effect on reducing the burden of coronary heart disease.
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Objective:To explore the clinical phenotype, diagnosis, treatment and genetic characteristics of infants with lethal mitochondrial trifunctional protein deficiency (MTPD).Methods:The clinical data of one patient with lethal MTPD admitted to the neonatal department of Guilin Maternal and Child Health Hospital were retrospectively analyzed. Relevant literature published up to July 2023 were retrieved from the Chinese Science and Technology Journal database, CNKI, Wanfang Database, Chinese Medical Journal Full-text Database, Chinese Biomedical Journal Literature Database, China Biomedical Literature Database, PubMed, Elsevier ScienceDirect, Embase and BIOSIS Previews with the terms of "mitochondrial trifunctional protein deficiency", "mitochondrial trifunctional protein", "HADHA", "HADHB", "newborn", "infant" and "lethal". Then the characteristics of clinical phenotypes and genetic variations about MTPD infants were summarized.Results:This patient was a 33 +3 week premature male infant who developed symptoms 9 d after birth. The main manifestations were metabolic acidosis, recurrent apnea, shock, cardiomyopathy and heart failure. Blood tandem mass spectrometry reported an increased levels of multiple acylcarnitines, and genetic testing indicated that the patient's HADHB gene had maternal c.527C>G missense mutation and de novo c.1148C>T missense mutation. The infant was diagnosed with lethal MTPD and died 12 d after birth after his family gave up the treatment. There were 29 cases in the total 13 publications that were retrieved. Together with this case, there were 30 cases involved. Among the 16 cases with relatively complete data, 10 cases were male and 15 cases developed symptoms in neonatal period. The main clinical phenotypes were cardiomyopathy, abnormal myocardial enzyme spectrum, heart failure and lactic acidosis or metabolic acidosis. Among the 15 cases with clear age of death, 14 died within 3 months of life. Of the reported patients, only one survived at 8 years of age. 29 cases were confirmed through genetic test, 10 infants had HADHA gene variations and 19 had HADHB gene variations. Only one patient was confirmed by pathological detection and mass spectrometry analysis. Conclusions:MTPD is a rare autosomal recessive genetic disease. Lethal MTPD has an early onset with high mortality. Severe acidosis and heart failure are the most common symptoms in neonatal period. Early detection of acylcarnitine and HADHB, HADHA gene should be performed in highly suspected infants to help early genetic diagnosis and intervention.
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AIM:To elucidate the possible biological mechanism of silica-induced acute lung injury in rats.METHODS:Sixteen Male Sprague-Dawley rats were divided into control and acute silicosis model groups,and instilled intratracheally with 1 mL of normal saline and 50 g/L silica suspension,respectively.After 7 d,the rats were sacrificed for collection of lung tissue and serum.The serum levels of interleukin-1β(IL-1β),IL-18 and tumor necrosis factor-α(TNF-α)were measured by using ELISA.The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)and gasdermin D(GSDMD)were measured by immunohistochemistry.Bacterial DNA was ex-tracted from the lung tissue for 16S ribosomal RNA gene sequencing to characterize changes in the composition of lung flo-ra.The differences in the structure of bacterial flora between control and model groups were analyzed by bioinformatic analy-ses.RESULTS:Immunohistochemical analysis showed that the protein expression levels of NLRP3 and GSDMD were higher in the lungs of the rats in model group.In addition,serum cytokine profiling showed that IL-1β,IL-18 and TNF-α levels were significantly higher in model group.The most abundant bacterial genera in the lung flora of the rats in model group were Bifidobacterium,Clostridium sensu stricto 1,and Parasutterella.The NLRP3 and GSDMD levels in the lung tissue and IL-1β and TNF-α levels in serum were positively correlated with the abundance of Parasutterella.CONCLU-SION:The alterations in lung flora structure and increased inflammation levels may be the actual biological mechanisms underlying silica-induced acute lung injury.The modulation of lung flora may provide a basis for the prevention and treat-ment of silica-induced acute lung injury.
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Polyhydroxybutyrate (PHB) is an attractive biodegradable polymer that can be produced through the microbial fermentation of organic wastes or wastewater. However, its mass production has been restricted by the poor utilization of organic wastes due to the presence of inhibitory substances, slow microbial growth, and high energy input required for feedstock sterilization. Here, Vibrio natriegens, a fast-growing bacterium with a broad substrate spectrum and high tolerance to salt and toxic substances, was genetically engineered to enable efficient PHB production from nonsterilized fermentation of organic wastes. The key genes encoding the PHB biosynthesis pathway of V. natriegens were identified through base editing and overexpressed. The metabolically engineered strain showed 166-fold higher PHB content (34.95 wt %) than the wide type when using glycerol as a substrate. Enhanced PHB production was also achieved when other sugars were used as feedstock. Importantly, it outperformed the engineered Escherichia coli MG1655 in PHB productivity (0.053 g/L/h) and tolerance to toxic substances in crude glycerol, without obvious activity decline under nonsterilized fermentation conditions. Our work demonstrates the great potential of engineered V. natriegens for low-cost PHB bioproduction and lays a foundation for exploiting this strain as a next-generation model chassis microorganism in synthetic biology.
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Glicerol , Poli-Hidroxibutiratos , Vibrio , Glicerol/metabolismo , Fermentação , Hidroxibutiratos/metabolismoRESUMO
Long noncoding RNAs (lncRNAs) play important roles in various signaling pathways in vascular plants. However, the crosstalk between lncRNAs and E3 ubiquitin ligases has been barely reported. In this study, we demonstrate that the lncRNA lncWD83 from rose (Rosa chinensis) 'Old blush' activates flowering by modulating the ubiquitination of the floral repressor MYC2 LIKE (RcMYC2L). Flowering was substantially delayed in rose by virus-induced gene silencing of lncWD83. In an in vitro pull-down assay, lncWD83 associated with PLANT U-BOX PROTEIN 11 (PUB11), a U-box-containing E3 ubiquitin ligase. Seedlings with knocked down RcPUB11 transcripts phenocopied the later-flowering phenotype of lncWD83-silenced seedlings. RcMYC2L physically interacted with RcPUB11 and was ubiquitinated in an RcPUB11-dependent manner in vitro. Accordingly, silencing RcMYC2L fully reversed the later-flowering phenotype resulting from RcPUB11 knockdown. Furthermore, RcMYC2L bound to G-box-related motifs in the FLOWERING LOCUS T (RcFT) promoter and repressed its transcription. However, RcPUB11 alleviated this repression of RcFT expression via proteasomal degradation of RcMYC2L, and lncWD83 enhanced this degradation by associating with RcPUB11. Therefore, lncWD83 promotes flowering by modulating the ubiquitination of the floral repressor RcMYC2L in rose plants. These findings reveal a distinct regulatory mechanism for an lncRNA in facilitating ubiquitin-mediated proteolysis to regulate rose flowering.
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RNA Longo não Codificante , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Flores/fisiologia , Ubiquitinação , Ubiquitina-Proteína Ligases/metabolismo , Proteínas de Plantas/metabolismo , Ubiquitinas/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
BACKGROUND: Acupuncture promotes the recovery of gastrointestinal function and provides analgesia after major abdominal surgery. The effects of transcutaneous electrical acupoint stimulation (TEAS) remain unclear. AIM: To explore the potential effects of TEAS on the recovery of gastrointestinal function after gastrectomy and colorectal resection. METHODS: Patients scheduled for gastrectomy or colorectal resection were randomized at a 2:3:3:2 ratio to receive: (1) TEAS at maximum tolerable current for 30 min immediately prior to anesthesia induction and for the entire duration of surgery, plus two 30-min daily sessions for 3 consecutive days after surgery (perioperative TEAS group); (2) Preoperative and intraoperative TEAS only; (3) Preoperative and postoperative TEAS only; or (4) Sham stimulation. The primary outcome was the time from the end of surgery to the first bowel sound. RESULTS: In total, 441 patients were randomized; 405 patients (58.4 ± 10.2 years of age; 247 males) received the planned surgery. The time to the first bowel sounds did not differ among the four groups (P = 0.90; log-rank test). On postoperative day 1, the rest pain scores differed significantly among the four groups (P = 0.04; Kruskal-Wallis test). Post hoc comparison using the Bonferroni test showed lower pain scores in the perioperative TEAS group (1.4 ± 1.2) than in the sham stimulation group (1.7 ± 1.1; P = 0.04). Surgical complications did not differ among the four groups. CONCLUSION: TEAS provided analgesic effects in adult patients undergoing major abdominal surgery, and it can be added to clinical practice as a means of accelerating postoperative rehabilitation of these patients.
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Capsicum chlorosis virus (CaCV; family Tospoviridae, genus Orthotospovirus) was first reported to infect capsicum (Capsicum annuum) and tomato (Solanum lycopersicum) in Australia in 2002 (McMichael et al., 2002). Subsequently, its infection was detected in different plants including waxflower (Hoya calycina Schlecter) in the United States (Melzer et al. 2014), peanut (Arachis hypogaea) in India (Vijayalakshmi et al. 2016), and spider lily (Hymenocallis americana) (Huang et al. 2017), Chilli pepper (Capsicum annuum) (Zheng et al. 2020), and Feiji cao (Chromolaena odorata) (Chen et al. 2022) in China. Ageratum conyzoides L. (commonly known as goat weed, family Asteraceae) is a natural weed in crop fields distributed in subtropical and tropical areas and a reservoir host of numerous plant pathogens (She et al. 2013). In April 2022, we observed that 90% of plants of A. conyzoides in maize fields in Sanya, Hainan province, China, exhibited typical virus-like symptoms of vein yellowing, leaf chlorosis, and distortion (Fig. S1 A-C). Total RNA was extracted from one symptomatic leaf of A. conyzoides. Small RNA libraries were constructed using the small RNA Sample Pre Kit (Illumina, San Diego, USA) for sequencing with an Illumina Novaseq 6000 platform (Biomarker Technologies Corporation, Beijing, China). A total 15,848,189 clean reads were obtained after removing low-quality reads. Quality-controlled qualified reads were assembled into contigs using Velvet 1.0.5 software with a k-mer value of 17. One hundred contigs shared nucleotide identity ranging from 85.7% to 100% with the CaCV using BLASTn searches online (https://blast.ncbi.nlm.nih.gov/Blast.cgi?). Numerous contigs (45, 34, and 21) obtained in this study were mapped to the L, M, and S RNA segments of the CaCV-Hainan isolate (GenBank accession no. KX078565- KX078567) from spider lily (Hymenocallis americana) in Hainan province, China, respectively. The full-length of L, M, and S RNA segments of CaCV-AC were determined to be 8,913, 4,841, and 3,629 bp, respectively (GenBank accession no. OQ597167- OQ597169). Furthermore, five symptomatic leaf samples were tested to be positive for CaCV using a CaCV enzyme-linked immunosorbent assay (ELISA) kit (MEIMIAN, Jiangsu, China) (Fig. S1-D). Total RNA from these leaves was amplified by RT-PCR with two sets of primer pairs. Primers CaCV-F (5'-ACTTTCCATCAACCTCTGT-3') and CaCV-R (5'-GTTATGGCCATATTTCCCT-3') were used for the amplification of 828 bp fragment from nucleocapsid protein (NP) on CaCV S RNA. While another, primers gL3637 (5'-CCTTTAACAGTDGAAACAT-3') and gL4435c (5'-CATDGCRCAAGARTGRTARACAGA-3') were used for the amplification of 816 bp fragment from RNA-dependent RNA polymerase (RdRP) on CaCV L RNA (Fig. S1-E and -F) (Basavaraj et al. 2020). These amplicons were cloned into the pCE2 TA/Blunt-Zero vector (Vazyme, Nanjing, China) and three independent positive colonies of Escherichia coli DH5α carrying each viral amplicon were sequenced. These sequences were deposited in the GenBank database under accession nos. OP616700-OP616709. Pairwise sequence comparison revealed that nucleotide sequences of NP and RdRP genes of the five CaCV isolates shared 99.5% (812 bp out of 828 bp) and 99.4% (799 bp out of 816 bp) nucleotide identities, respectively. They showed 86.2-99.2% and 86.5-99.1% nucleotide identities with corresponding nucleotide sequences of other CaCV isolates derived from GenBank database, respectively. The highest nucleotide sequence identity (99%) of the CaCV isolates obtained in the study was observed with the CaCV-Hainan isolate. Phylogenetic analysis based on NP amino acid demonstrated that six CaCV isolates (this study = 5 and NCBI database = 1) clustered into one distinct clade (Fig. S2). Our data confirmed for the first time the presence of CaCV naturally infecting A. conyzoides plant in China, which enriches information on the host range and will be helpful for disease management.
RESUMO
Sepsis is a life-threatening organ dysfunction caused by dysregulated body response to infection. It is also one of the major causes of death in critically ill patients. Over the past few years, despite the continuous improvement in the treatment of sepsis, there is no specific treatment, clinical morbidity and mortality are still rising. Therefore, finding effective methods to treat sepsis and reduce mortality is an urgent clinical problem. Histone modification is an epigenetic modification that produces heritable phenotypic changes without altering the DNA sequence. In recent years, many studies have shown that histone modification is closely related to sepsis. This review discusses the mechanism of histone modification in the pathogenesis of sepsis from the aspects of inflammatory factors, signaling pathways, and macrophage polarization, in aimed to provide reference for the clinical treatment of sepsis.