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BACKGROUND: Focal liver lesions (FLLs) are a common form of liver disease, and identifying accurate pathological types is required to guide treatment and evaluate prognosis. PURPOSE: To compare and analyze the application effect of contrast-enhanced ultrasound (CEUS) and conventional ultrasound (US) in the clinical diagnosis of focal liver lesions. MATERIAL AND METHODS: A retrospective analysis was performed on 682 patients with space-occupying liver lesions admitted to our hospital between December 2015 and August 2021. Of these, 280 underwent CEUS-guided biopsies and 402 underwent conventional US biopsies, with the results of each biopsy subsequently compared between the two groups. The success rate and accuracy of the biopsies and their relationship with different pathological features were also analyzed. RESULTS: The success rate, sensitivity, diagnostic accuracy, positive predictive value, and negative predictive value of the CEUS group were significantly higher than those of the US group (P < 0.05). Lesion size accuracy in the CEUS group was significantly higher than that in the US group (89.29% vs. 40.55%; P < 0.05). Lesion type accuracy in the CEUS group was significantly higher than that in the US group (86.49% vs. 43.59%), and the difference between the two groups was statistically significant (P < 0.05). The logistic regression analysis indicated that malignant lesions, lesions ≥5 cm, and lesions ≤1 cm were independent factors affecting the success rate of the puncture procedure (P < 0.05). CONCLUSION: The sensitivity, specificity, and diagnostic accuracy of lesion size and type in the CEUS group were higher than those in the US group.
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Meios de Contraste , Sensibilidade e Especificidade , Ultrassonografia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ultrassonografia/métodos , Adulto , Idoso , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Hepatopatias/diagnóstico por imagem , Hepatopatias/patologia , Aumento da Imagem/métodos , Reprodutibilidade dos Testes , Valor Preditivo dos Testes , Adulto JovemRESUMO
Hypoxia is one of the hallmarks of solid tumors, especially in hepatocellular carcinoma (HCC). CircRNAs are reported to be tightly connected to hypoxia and also have essential roles in cancer progression. However, many circRNAs implicated in hypoxia-mediated HCC progression are still unclear and require further exploration. In this study, a hypoxia cell model was structured by exposing cells to hypoxia conditions (1% O2) and normoxia conditions (21% O2) as a control. The effects of hypoxia and normoxia on cell viability, migration, invasion, and glycolysis were examined. The expressions of circRNARTN4IP1 under hypoxia were identified. Finally, molecular mechanisms and biological function of circRTN4IP1 were explored. We confirmed that hypoxia treatment facilitated capacities of proliferation, migration, invasion, and glycolysis in tumor cells. Hypoxia induced a significant increase expression of circRTN4IP1 in cells. Functionally, knockdown of circRTN4IP1 inhibited cell malignant progression and glycolysis under hypoxia HCC cells. Mechanistically, HIF1A targeted the promoter region of circRTN4IP1 and positively regulated the expression of circRTN4IP1. In addition, circRTN4IP1 targeted miR-532-5p/G6PC3 axis. In short, hypoxia induced activation of the HIF1A/circRTN4IP1/miR-532-5p/G6PC3 signaling axis, which promoted proliferation, migration, invasion, and glycolysis of HCC cells. This study may reveal a possible mechanism driving the progression of hypoxia HCC, so as to find potential effective candidates for targeting hypoxia microenvironment therapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , RNA Circular/genética , Glicólise , Hipóxia/genética , MicroRNAs/genética , Microambiente TumoralRESUMO
BACKGROUND AIMS: Human induced pluripotent stem cells (hiPSCs) are becoming increasingly popular in research endeavors due to their potential for clinical application; however, such application is challenging due to limitations such as inferior function and low induction efficiency. In this study, we aimed to establish a three-dimensional (3D) culture condition to mimic the environment in which hepatogenesis occurs in vivo to enhance the differentiation of hiPSCs for large-scale culture and high throughput BAL application. METHODS: We used hydrogel to create hepatocyte-like cell (HLC) spheroids in a 3D culture condition and analyzed the cell-behavior and differentiation properties of hiPSCs in a synthetic nanofiber scaffold. RESULTS: We found that treating cells with Y-27632 promoted the formation of spheroids, and the cells aggregated more rapidly in a 3D culture condition. The ALB secretion, urea production and glycogen synthesis by HLCs in 3D were significantly higher than those grown in a 2-dimensional culture condition. In addition, the metabolic activities of the CYP450 enzymes were also higher in cells differentiated in the 3D culture condition. CONCLUSIONS: 3D hydrogel culture condition can promote differentiation of hiPSCs into hepatocytes. The 3D culture approach could be applied to the differentiation of hiPSCs into hepatocytes for bioartificial liver.
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Técnicas de Cultura de Células/métodos , Diferenciação Celular/efeitos dos fármacos , Hepatócitos/citologia , Hidrogéis/farmacologia , Células-Tronco Pluripotentes Induzidas/citologia , Proliferação de Células/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/metabolismo , Corpos Embrioides/citologia , Endoderma/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Esferoides Celulares/citologia , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismoAssuntos
Carcinoma Hepatocelular , Neoplasias Colorretais , Hepatectomia/métodos , Neoplasias Hepáticas , Fígado , Veia Porta/cirurgia , Adulto , Carcinoma Hepatocelular/secundário , Carcinoma Hepatocelular/cirurgia , Neoplasias Colorretais/secundário , Neoplasias Colorretais/cirurgia , Feminino , Hepatectomia/efeitos adversos , Humanos , Ligadura , Fígado/irrigação sanguínea , Fígado/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-IdadeRESUMO
The adverse effects of exposure to fine particulate matter (PM2.5) on body health have attracted global public attention. However, there is limited research on PM2.5 in animal houses. Numerous studies have indicated that long-term exposure to high levels of PM2.5 can cause damage to multiple systems in animals. Poultry houses are one of the primary sources of PM2.5 emissions. However, there is limited research on the effects of PM2.5 exposure on poultry organisms. This study analyzed the histopathological changes in the lung tissue of poultry under PM2.5 exposure conditions. It used the LC-MS method to analyze the alterations in the serum metabolomic profile of poultry. This study confirmed that long-term exposure to high levels of PM2.5 had significantly reduced the growth performance of poultry. Histopathological slides of the lung tissue in chickens exposed to long-term retention of PM2.5 clearly showed significant damage. Furthermore, the serum metabolome analysis revealed significant changes in the serum metabolic profile of chickens exposed to long-term PM2.5 exposure. Specifically, there were notable alterations in the Glycerophospholipid metabolism, Steroid hormone biosynthesis, and Phenylalanine, tyrosine, and tryptophan biosynthesis pathways.
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Poluentes Atmosféricos , Animais , Poluentes Atmosféricos/análise , Galinhas , Material Particulado/análise , Metaboloma , MetabolômicaRESUMO
In recent years, a series of public health issues caused by the spread of antibiotic resistance have been widely concerned. The indoor air of livestock and poultry houses is considered to be one of the main sources of environmental contamination of ARGs. This study characterized the micro-organisms and ARGs in the air particulate matter of chicken houses using metagenomics. The study successfully detected 761 different subtypes of resistance genes including aminoglycosides, tetracyclines, MLSB etc., 4 types of mobile genetic elements, and various pathogenic microorganisms from the aerosols in the chicken coop environment. The results showed that the abundance of ARGs in the air of the chicken coop was at a relatively high level, correlation network analysis showed that multiple types of ARGs could promote the emergence of antibiotic-resistant bacteria.
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Galinhas , Abrigo para Animais , Animais , Farmacorresistência Bacteriana/genética , Antibacterianos/farmacologia , Microbiologia do Ar , Bactérias/efeitos dos fármacos , Bactérias/genética , Metagenômica , Material Particulado/análise , Genes Bacterianos , Resistência Microbiana a Medicamentos/genéticaRESUMO
INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) is characterized by a dismal prognosis with limited therapeutic alternatives. To explore phosphatase and tension homolog (PTEN) as a biomarker for proteasome inhibition inâICC, we conducted a phase II trial to assess the second-line efficacy of bortezomib in PTEN-deficient advanced ICC patients. METHODS: A total of 130 patients with advanced ICC in our centre were screened by PTEN immunohistochemical staining between 1 July 2017, and 31 December 2021, and 16 patients were ultimately enrolled and treated with single-agent bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day cycle. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1. RESULTS: The median follow-up was 6.55 months (95% confidence interval [CI]: 0.7-19.9 months). Among the 16 enrolled patients, the ORR was 18.75% (3/16) and the disease control rate was 43.75% (7/16). The median progress-free survival was 2.95 months (95% CI: 2.1-5.1 months) and the median overall survival (mOS) was 7.2 months (95% CI: 0.7-21.6 months) in the intent-to-treat-patients. Treatment-related adverse events of any grade were reported in 16 patients, with thrombopenia being the most common toxicity. Patients with PTEN staining scores of 0 were more likely to benefit from bortezomib than those with staining scores > 0. CONCLUSIONS: Bortezomib yielded an encouraging objective response and a favourable OS as a second-line agent in PTEN-deficient ICC patients. Our findings suggest bortezomib as a promising therapeutic option for patients with PTEN-deficient ICC. HIGHLIGHTS: There is a limited strategy for the second-line option of intrahepatic cholangiocarcinoma (ICC). This investigator-initiated phase 2 study evaluated bortezomib in ICC patients with phosphatase and tension homology deficiency. The overall response rate was 18.75% and the overall survival was 7.2 months in the intent-to-treat cohort. These results justify further developing bortezomib in ICC patients with PTEN deficiency.
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Neoplasias dos Ductos Biliares , Bortezomib , Colangiocarcinoma , PTEN Fosfo-Hidrolase , Humanos , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Bortezomib/uso terapêutico , Bortezomib/farmacologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/genética , Adulto , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologiaRESUMO
The outbreak of COVID-19 reminds people that aerosols have an important impact on health. The concentration and composition of microbial aerosol in livestock and poultry houses are closely related to the environmental conditions of livestock and poultry houses, and also related to the healthy growth of livestock and poultry. In our study, 16S and ITS sequencing techniques were used to analyze the relation and difference of bacteria and fungi in the air samples of a chicken house. At the age of 7 to 42 d, the operation classification unit (OTU) numbers of bacteria and fungi identified in our results were 2,398 and 986, respectively, of which the shared OTU numbers were 410 and 141, respectively. At the phylum level, Firmicutes, Proteobacteria, and Actinomycetes were the 3 most abundant bacterial phyla, and Ascomycetes and Basidiomycetes were the top 2 phyla in fungi. At the genus level, 7 differential fungal genera were identified, including Debaryomyces, Trichosporon, Wallemia, Aspergillus, Nigrospora, Fusarium, and Vishniacozyma. Compared with other bacterial genera, Lactobacillus, Cetobacterium, and Romboutsia had the highest abundance (more than 5%). The result showed that the Alpha diversity and Beta diversity of fungi were significantly different in different growing periods. However, only Beta diversity showed significant differences among bacteria. In general, the bacterial and fungal diversity of microbial aerosols in the chicken house increased significantly at the age of 7 to 42 d. And the evenness and richness of airborne fungal communities also increased obviously. In a word, we must pay attention to the complex community composition in the chicken house, this is closely related to animal health and the health of surrounding residents. The cooperation and communication between bacteria and fungi in PM2.5 samples provides a new reference to analyze the influence of microbial aerosol.
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The environmental conditions of chicken houses play an important role in the growth and development of these animals. The chicken house is an essential place for the formation of microbial aerosols. Microbial aerosol pollution and transmission can affect human and animal health. In this work, we continuously monitored fine particulate matter (PM2.5) in the chicken house environment for four weeks and studied the microbial community structure in the aerosols of the chicken house environment through metagenomic sequencing. Our results found that bacteria, fungi, viruses, and archaea were the main components of PM2.5 in the chicken house environment, accounting for 89.80%, 1.08%, 2.06%, and 0.49%, respectively. Conditional pathogens are a type of bacteria that poses significant harm to animals themselves and to farm workers. We screened ten common conditional pathogens and found that Staphylococcus had the highest relative abundance, while Clostridium contained the most microbial species, up to 456. Basidiomycetes and Ascomycota in fungi showed dramatic changes in relative abundance, and other indexes showed no significant difference. Virulence factors (VF) are also a class of molecules produced by pathogenic microbes that can cause host diseases. The top five virulence factors were found in four groups: FbpABC, HitABC, colibactin, acinetobactin, and capsule, many of which are used for the iron uptake system. In the PM2.5 samples, eight avian viruses were the most significant discoveries, namely Fowl aviadovirus E, Fowl aviadovirus D, Avian leukosis virus, Avian endogenous retrovirus EAV-HP, Avian dependent parvovirus 1, Fowl adenovus, Fowl aviadovirus B, and Avian sarcoma virus. The above results significantly improve our understanding of the microbial composition of PM2.5 in chicken houses, filling a gap on virus composition; they also indicate a potential threat to poultry and to human health. This work provides an important theoretical basis for animal house environmental monitoring and protection.
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The prognosis of renal pelvis cancer is poor and therapeutic options are limited, especially for patients with advanced disease. In this report, we present a case of advanced renal pelvis carcinoma in a male patient in his 60s, characterized by an activating mutation in ERBB2. Clinical evaluation resulted in a pathological diagnosis of renal pelvis carcinoma with liver metastasis. Immunohistochemistry staining results suggested that CK, P63, and PAX8 were positively expressed, while Sy, CK7, CK20, S100, PAX8, and HEP1 were negatively expressed. Furthermore, next-generation sequencing results showed an activating mutation in the ERBB2 gene. The patient initially received a trastuzumab-based combination therapy, which led to a significant reduction in ERBB2 mutation frequency and a stable condition after three treatment cycles. However, following continuous treatment for 4 months, the patient developed drug resistance that resulted in disease relapse. Subsequently, the patient received apatinib treatment, but the therapeutic response was not satisfactory. The patient's condition underwent rapid deterioration and he ultimately succumbed to the disease. This case underscores the potential benefit of trastuzumab for treating ERBB2-mutated advanced renal pelvis cancer, but further highlights that overcoming drug resistance remains a crucial challenge for long-term efficacy.
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Neoplasias Renais , Neoplasias Pélvicas , Humanos , Masculino , Mutagênese Insercional , Recidiva Local de Neoplasia/patologia , Neoplasias Renais/patologia , Receptor ErbB-2/genética , Trastuzumab/uso terapêutico , Pelve Renal/patologia , MutaçãoRESUMO
Background: The momentum of robotic surgery is increasing, and it has great prospects in pancreatic surgery. It has been widely accepted and expanding to more and more centers. Robotic distal pancreatectomy (RDP) is the most recent advanced minimally invasive approach for pancreatic lesions and malignancies. However, laparoscopic distal pancreatectomy (LDP) also showed good efficacy. We compared the effect of RDP with LDP using a meta-analysis. Methods: From January 2010 to June 2023, clinical trials of RDP versus LDP were determined by searching PubMed, Medline, and EMBASE. A meta-analysis was conducted to compare the effect of RDP with LDP. This meta-analysis evaluated the R0 resection rate, lymph node metastasis rate, conversion to open surgery rate, spleen preservation rate, intraoperative blood loss, postoperative pancreatic fistula, postoperative hospital stay, 90-day mortality rate, surgical cost, and total cost. Results: This meta-analysis included 38 studies. Conversion to open surgery, blood loss, and 90-day mortality in the RDP group were all significantly less than that in the LDP group (P < .05). There was no difference in lymph node resection rate, R0 resection rate, or postoperative pancreatic fistula between the two groups (P > .05). Spleen preservation rate in the LDP group was higher than that in the RDP group (P < .05). Operation cost and total cost in the RDP group were both more than that in the LDP group (P < .05). It is uncertain which group has an advantage in postoperative hospital stay. Conclusions: To some degree, RDP and LDP were indeed worth comparing in clinical practice. However, it may be difficult to determine which is absolute advantage according to current data. Large sample randomized controlled trials are needed to confirm which is better treatment. PROSPERO ID: CRD4202345576.
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Laparoscopia , Pancreatectomia , Procedimentos Cirúrgicos Robóticos , Humanos , Tempo de Internação , Pancreatectomia/métodos , Fístula Pancreática , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Robótica , Resultado do Tratamento , Pancreatopatias/patologia , Pancreatopatias/cirurgia , Pâncreas/patologia , Pâncreas/cirurgiaRESUMO
Background: Cystectomy accompanied by biliary system reconstruction is an important treatment option for choledochal cysts, but the risk of post-operative complications is high. The most famous long-term complication is anastomotic stricture, whereas non-cirrhotic portal hypertension secondary to cholangiointestinal anastomotic stricture is rare. Case summary: Here we report the case of a 33-year-old female patient with a type I choledochal cyst who underwent choledochal cyst excision with Roux-en-Y hepaticojejunostomy. Thirteen years later, the patient presented with severe esophageal and gastric variceal bleeding, splenomegaly, and hypersplenism. Furthermore, cholangiointestinal anastomotic stricture with cholangiectasis was identified on imaging. A pathological examination of the liver suggested intrahepatic cholestasis, but the fibrosis was mild and inconsistent with severe portal hypertension. Therefore, the final diagnosis was portal hypertension secondary to a cholangiointestinal anastomotic stricture after choledochal cyst surgery. Fortunately, the patient recovered well after endoscopic treatment and dilated cholangiointestinal anastomotic stricture. Conclusion: Choledochal cyst excision with Roux-en-Y hepaticojejunostomy is the recommended standard of care for type I choledochal cysts; however, the long-term risk of cholangiointestinal anastomotic stricture requires consideration. Moreover, cholangiointestinal anastomotic stricture can lead to portal hypertension, and the degree of elevated portal pressure may be inconsistent with the degree of intrahepatic fibrosis.
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To improve the triggering characteristics of the gas switch used for linear transformer driver, a method of corona assisted triggering based on the pre-ionization in switch gaps is proposed and applied to a six-gap gas switch. The principle is demonstrated by electrostatic field analysis and verified by the experimental study on the discharge characteristics of the gas switch. The results indicate that when the gas pressure is 0.3 MPa, the self-breakdown voltage remains about ±80 kV, and its dispersivity is lower than 3%. The effect of corona assisted triggering on the triggering characteristics increases with the higher permittivity of the inner shield. The positive trigger voltage of the switch with the proposed method can be reduced from 110 to 30 kV at a charging voltage of ±80 kV when the jitter is equal to that of the original switch. There are no pre-fire or late-fire when the switch operates continuously for 2000 shots.
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The prognosis of biliary tract cancer (BTC) remains unsatisfactory. This single-arm, phase II clinical trial (ChiCTR2000036652) investigated the efficacy, safety, and predictive biomarkers of sintilimab plus gemcitabine and cisplatin as the first-line treatment for patients with advanced BTCs. The primary endpoint was overall survival (OS). Secondary endpoints included toxicities, progression-free survival (PFS), and objective response rate (ORR); multi-omics biomarkers were assessed as exploratory objective. Thirty patients were enrolled and received treatment, the median OS and PFS were 15.9 months and 5.1 months, the ORR was 36.7%. The most common grade 3 or 4 treatment-related adverse events were thrombocytopenia (33.3%), with no reported deaths nor unexpected safety events. Predefined biomarker analysis indicated that patients with homologous recombination repair pathway gene alterations or loss-of-function mutations in chromatin remodeling genes presented better tumor response and survival outcomes. Furthermore, transcriptome analysis revealed a markedly longer PFS and tumor response were associated with higher expression of a 3-gene effector T cell signature or an 18-gene inflamed T cell signature. Sintilimab plus gemcitabine and cisplatin meets pre-specified endpoints and displays acceptable safety profile, multiomics potential predictive biomarkers are identified and warrant further verification.
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Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/patologia , Cisplatino/uso terapêutico , Desoxicitidina/uso terapêutico , GencitabinaRESUMO
OBJECTIVE: To evaluate the effects of different doses of lactulose on preventing oral morphine-induced constipation. METHODS: From January 2011 to May 2012, a total of 112 patients received oral lactulose solution to prevent morphine-induced constipation at our hospital and their clinical data were retrospectively analyzed. The doses of morphine were adjusted according to the pain scores and lactulose was taken simultaneously. There were 52 males and 60 females. They were randomized into Group 30 ml/d (n = 40), Group 60 ml/d (n = 43) and Group 90 ml/d (n = 29). The incidences of constipation and adverse reactions were obtained at 1 week after the start of medicine. The measurement data were analyzed with analysis of variance. And the enumeration data were analyzed with χ(2), Kruskal-Wallis and Mann-Whitney U tests. RESULTS: The incidence of constipation was 67.5% (27/40) in Group 30 ml/d, 46.5% (20/43) in Group 60 ml/d, and 37.9% (11/29) in Group 90 ml/d. And there were statistical differences (P = 0.036). The incidence of constipation in Group 30 ml was significantly higher than Group 90 ml/d (P = 0.015). No statistical difference existed in the incidence of constipation between Groups 30 ml/d and 60 ml/d (P = 0.054) or Groups 60 ml/d and 90 ml/d (P = 0.471). The incidence of vomiting was 34.5% (10/29) in Group 90 ml/d and it was significantly higher than 10.0% (4/40) in Group 30 ml/d (P = 0.013) and 9.3% (4/43) in Group 60 ml/d (P = 0.009). No statistical difference existed in the incidence of vomiting between Groups 30 ml/d and 60 ml/d (P = 0.915). The incidence of diarrhea was 17.2% (5/29) in Group 90 ml/d and it was significantly higher than 0 (0/40) in Group 30 ml/d (P = 0.007). No statistical difference existed in the incidence of diarrhea between Groups 30 ml/d and 60 ml/d (4.7% (2/43), P = 0.170) or Groups 60 ml/d and 90 ml/d (P = 0.072). CONCLUSION: The correct dosage of lactulose for the prevention of oral morphine-induced constipation is 60 ml/d.
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Constipação Intestinal/prevenção & controle , Lactulose/administração & dosagem , Lactulose/uso terapêutico , Morfina/efeitos adversos , Adulto , Idoso , Constipação Intestinal/induzido quimicamente , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Environmental aerosols in animal houses are closely related to the productive performance and health level of animals living in the houses. Preferable housing environments can improve animal welfare and production efficiency, so it is necessary to monitor and study these environments. In recent years, there have been many large-scale outbreaks of respiratory diseases related to biological aerosols, especially the novel coronavirus that has been sweeping the world. This has attracted much attention to the mode of aerosol transmission. With the rapid development of large-scale and intensive breeding, microbial aerosols have gradually become the main factor of environmental pollution in animal houses. They not only lead to a large-scale outbreak of infectious diseases, but they also have a certain impact on the health of animals and employees in the houses and increase the difficulty of prevention and control of animal-borne diseases. This paper reviews the distribution, harm, and control measures of microbial aerosols in animal house environments in order to improve people's understanding of them.
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BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) and Transarterial chemoembolization (TACE) both showed good local efficacy in advanced or unresectable hepatocellular carcinoma (HCC). We performed a systematic review and meta-analysis to compare the effect of HAIC with TACE in patients with unresectable HCC. METHODS: Clinical trials, which were about HAIC or TACE in Patients with unresectable HCC, were identified by searching PubMed, Medline, and EMBASE from January 2010 to March 2022. A meta-analysis was performed to analyze HAIC in comparison with TACE. Treatment response, 1-year overall survival (OS), 2-year OS and serious adverse events were evaluated in this meta-analysis. RESULTS: This meta-analysis included 6 studies. Objective response rate or Partial response in the HAIC group was significantly more than that in the TACE group (Pâ <â .05). But, stable disease showed no difference between the 2 groups (Pâ =â .52). Disease control rate in the HAIC group was better than that in the TACE group (Pâ <â .05). Progressive disease in the HAIC group was less than that in the TACE group (Pâ <â .05). In 1-year OS, there was no significant deterioration between the 2 groups (Pâ =â .53). There was not significant difference in 2-year OS between the 2 groups (Pâ =â .05). serious adverse events in the HAIC group was significantly less than that in the TACE group (Pâ <â .05). CONCLUSION: To some degree, HAIC may be a better therapeutic method in patients with unresectable HCC than TACE.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Quimioembolização Terapêutica/efeitos adversos , Resultado do Tratamento , Infusões Intra-Arteriais/métodosRESUMO
Extracellular vesicles that are derived from stem cells play an important role in the treatment of disease. To obtain high-quality small extracellular vesicles (sEVs), we optimized the culture conditions of human induced pluripotent stem cells (hiPSCs), the supernatant collection time, and sEVs extraction methods. Firstly, hiPSCs were cultured in extracellular vesicles-production medium (EVs-PM) containing different concentrations (0%, 0.25%, 0.5%, 2%, 5%, and 20%) of extracellular vesicle-depleted knockout serum replacement (ED-KSR), and the culture supernatants were collected continuously for 5 days. Then, the sEVs were isolated, followed by an evaluation of their characteristics. The survival rates of the hiPSCs lines that were cultured in EVs-PM containing 0.5% to 20% ED-KSR were not significantly different (P > 0.05). The survival rates of the hiPSCs in 0.5% ED-KSR after the culture supernatants were continuously collected for day 1, day 3, and day 5 were not statistically significant (P > 0.05). After 5 days of continuous collection of the supernatant, the hiPSCs expressed some pluripotent markers, while SSEA4 and TRA-1-60 expression changed gradually. The sEVs that were extracted by the two methods were all 50-200 nm, double-layered and oval or round cellular vesicles and expressed the marker proteins CD63, TSG101, and HSP70. The characteristics of sEVs extracted on day 1, day 3, and day 5 were almost identical on morphology, size and the relative quantity of annexin V-positive subpopulations. The PKH67 staining showed that the sEVs could be endocytosed by HepG2 cells and aggregated in the cytoplasm. The proliferation experiments showed that the sEVs can promote cell proliferation. In Conclusion, the 0.5% ED-KSR is the optimal concentration, and that the hiPSCs culture supernatant can be continuously collected for 5 days while maintaining high cell viability and some pluripotent characteristics. Both of the methods extraction can be used to obtain biologically active sEVs.
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Técnicas de Cultura de Células/métodos , Vesículas Extracelulares/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Diferenciação Celular , Proliferação de Células , Separação Celular/métodos , Sobrevivência Celular , Técnicas de Cultura/métodos , Vesículas Extracelulares/fisiologia , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismoRESUMO
Aims: To examine the impact of perioperative inhaled corticosteroids (ICS) on length-of-stay (LOS) and costs among patients receiving high-respiratory-risk surgeries.Methods: Adult patients who underwent high-respiratory-risk surgeries in 2015 were identified in the Tianjin Urban Employee Basic Medical Insurance database. Patients were grouped into ICS or non-ICS cohorts according to whether they received ICS during the perioperative period of the index hospitalization. Propensity Score Matching was performed to create matched pairs between two cohorts. The impact of perioperative ICS on LOS and direct medical costs was estimated by negative binomial model and generalized liner model.Results: Eight hundred and twenty-one hospital stays with high-respiratory-risk were selected in the ICS cohort and another 821 stays in the non-ICS cohort were matched. The mean LOS was 13.0 (±0.3) days in the ICS cohort, which was significantly lower than the matched non-ICS cohort. Patients with thorax and ear-nose-throat surgeries had a significant decrease in LOS in the ICS cohort compared to the non-ICS cohort, with a mean decrease of 5.5 and 1.1 days, respectively. In adjusted analyses, perioperative ICS treatment was associated with shorter LOS, lower total, and respiratory-related costs (reductions of 10.1%, 7%, and 5.3%, respectively) after controlling for demographic, clinical, and hospital characteristics.Limitations: Some respiratory risk factors such as living behavior and environment were unable to be captured and respiratory-related costs might be underestimated, limited by claim data. Lastly, caution should be taken when generalizing the results to other populations, as only patients with moderate-to-severe surgeries on the thorax and above were selected in this study.Conclusions: Perioperative ICS treatment was associated with decreased LOS and lower costs for patients undergoing high-respiratory-risk surgeries in China.
Assuntos
Corticosteroides/uso terapêutico , Gastos em Saúde/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/prevenção & controle , Doenças Respiratórias/prevenção & controle , Administração por Inalação , Corticosteroides/administração & dosagem , Fatores Etários , China , Feminino , Humanos , Intubação Intratraqueal , Tempo de Internação/economia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Assistência Perioperatória/economia , Complicações Pós-Operatórias/economia , Pontuação de Propensão , Respiração Artificial/estatística & dados numéricos , Doenças Respiratórias/economia , Fatores de RiscoRESUMO
Chemoembolization for hepatocellular carcinoma (HCC) is often suboptimal due to multiple involved signaling and lack of effective drugs. Arsenic trioxide (ATO) is a potent chemotherapeutic agent, which can target multiple signaling and have substantial efficacy on HCC. However, its usage is limited due to systemic toxicity. Using ATO-eluting beads/microspheres for chemoembolization can have locoregional drug delivery and avoid systemic exposure but will require high drug load, which has not been achieved due to low solubility of ATO. Through an innovative approach, we generated the transiently formed ATO microcrystals via micronization and stabilized these microcrystals by solvent exchange. By encapsulating ATO microcrystals, but not individual molecules, with poly(lactide-co-glycolic acid) (PLGA), we developed microspheres cored with extremely high dense ATO. The molar ratio between ATO and PLGA was 157.4:1 and drug load was 40.1%, which is 4-20 fold higher than that of reported ATO nano/microparticles. These microspheres sustainably induced reactive oxygen species, apoptosis, and cytotoxicity on HCC cells and reduced tumor growth by 80% via locoregional delivery. Chemoembolization on mice model showed that ATO-microcrystal loaded microspheres, but not ATO, inhibited HCC growth by 60-75%, which indicates ATO within these microspheres gains the chemoembolizing function via our innovative approach.