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BACKGROUND: Acute anorectal abscesses of cryptoglandular origin are commonly managed by incision and drainage, which results in fistula development in up to 73% of cases, requiring subsequent definitive fistula surgery. However, given that fistula tracts may already be present at the initial presentation, primary closure of the tract as secondary prevention of fistula formation, using ligation of intersphincteric fistula tract, may be useful. OBJECTIVE: This study aims to examine the feasibility and outcomes of performing intersphincteric exploration with ligation of intersphincteric fistula tract or attempted closure of internal opening for acute anorectal abscesses. DESIGN: This is a retrospective study of patients with acute anorectal cryptoglandular abscesses who underwent surgery between January 2014 and December 2016. SETTINGS: The patients were treated at a tertiary referral center in Thailand. PATIENTS: Eighty-six patients with acute anorectal abscesses without previous surgery were included. INTERVENTIONS: Intersphincteric dissection was performed. Further surgical intervention was dependent on the intersphincteric findings. MAIN OUTCOME MEASURE: The main outcome measure was the 90-day healed rate. RESULTS: Of the 86 patients, 3 had low intersphincteric abscesses, 26 had low transsphincteric abscesses, 25 had anterior high transsphincteric abscesses, 27 had posterior high transsphincteric abscesses, and 5 had high intersphincteric abscesses. Ligation of intersphincteric fistula tract was successfully performed in 66 patients with an identifiable intersphincteric tract. Intersphincteric exploration with attempted closure of the internal opening was performed in the remaining 20 patients. The success rates were 86% and 70%. Unidentified internal opening and intersphincteric pathology were risk factors for nonhealing. No patients reported fecal incontinence postoperatively. LIMITATIONS: The limitation of this study is its retrospective nature and that all operations were performed by a single surgeon; therefore, the results may vary according to the individual surgeon's expertise. CONCLUSIONS: Fistula tract formation was found in most cases of acute anorectal abscesses. Definitive surgery using this strategy provides promising results. See Video Abstract at http://links.lww.com/DCR/B451. EXPLORACIN INTERESFINTRICA CON LIGADURA DEL TRAYECTO EN LA FSTULA INTERESFINTRICA O INTENTO DE CIERRE DEL ORIFICIO INTERNO EN ABSCESOS ANORRECTALES AGUDOS: ANTECEDENTES:Los abscesos anorrectales agudos de origen criptoglandular, comúnmente se manejan mediante incisión y drenaje, lo que resulta en el desarrollo de una fístula hasta en un 73% de los casos, requiriendo posteriormente cirugía definitiva de la fístula. Sin embargo, dado que los trayectos de la fístula ya pueden estar inicialmente presentes, puede ser útil el cierre primario del trayecto, como prevención secundaria en la formación de la fístula, mediante la ligadura del trayecto de la fístula interesfintérica.OBJETIVO:El estudio tiene como objetivo, examinar la viabilidad y los resultados en realizar exploración interesfintérica, con ligadura del trayecto de fístula interesfintérica o intento de cierre del orificio interno para abscesos anorrectales agudos.DISEÑO:Se trata de un estudio retrospectivo de pacientes con abscesos criptoglandulares anorrectales agudos, que fueron operados entre enero de 2014 y diciembre de 2016.AJUSTES:Los pacientes fueron tratados en un centro de referencia terciario en Tailandia.PACIENTES:Se incluyeron 86 pacientes con abscesos anorrectales agudos, sin cirugía previa.INTERVENCIONES:Se realizó disección interesfintérica. La intervención quirúrgica adicional dependió de los hallazgos interesfintéricos.PRINCIPALES MEDIDAS DE RESULTADO:La principal medida de resultado, fue la tasa de cicatrización a 90 días.RESULTADOS:De los 86 pacientes, hubo 3 abscesos interesfintéricos bajos, 26 abscesos transesfintéricos bajos, 25 abscesos transesfintéricos anteriores altos, 27 abscesos transesfintéricos posteriores altos y 5 abscesos interesfintéricos altos. La ligadura del tracto de la fístula interesfintérica, con tracto interesfintérico identificable, se realizó con éxito en 66 pacientes. Se realizó exploración interesfintérica, con intento de cierre del orificio interno en los 20 pacientes restantes. Las tasas de éxito fueron 86% y 70% respectivamente. Orificio interno no identificado y patología interesfintérica, fueron factores de riesgo para la falta de cicatrización. Ningún paciente reportó incontinencia fecal posoperatoria.LIMITACIONES:La limitación de este estudio, es su naturaleza retrospectiva y que todas las operaciones fueron realizadas por un solo cirujano, por lo tanto, los resultados pueden variar según la experiencia de cada cirujano.CONCLUSIONES:En la mayoría de los casos de abscesos anorrectales agudos, se encontró formación de trayectos fistulosos. La cirugía definitiva con esta estrategia, proporciona resultados prometedores. Consulte Video Resumen en http://links.lww.com/DCR/B451.
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Absceso/cirugía , Ligadura/métodos , Enfermedades del Recto/patología , Fístula Rectal/cirugía , Técnicas de Cierre de Heridas/estadística & datos numéricos , Enfermedad Aguda , Adulto , Anciano , Canal Anal/patología , Drenaje/efectos adversos , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Recto/microbiología , Fístula Rectal/epidemiología , Fístula Rectal/etiología , Estudios Retrospectivos , Tailandia/epidemiología , Resultado del TratamientoRESUMEN
Objective: To investigate the therapeutic efficacy of the modified posterolateral approach on tibial plateau fractures. Methods: Forty-four patients with tibial plateau fractures were enrolled in the study and divided into two groups-control and observation-according to the different surgical procedures. The control group underwent fracture reduction via the conventional lateral approach, while the observation group underwent fracture reduction via the modified posterolateral strategy. The depth of tibial plateau collapse, active mobility, and the Hospital for Special Surgery (HSS) score and Lysholm score of the knee joint at 12 months after surgery were assessed in comparison to the two groups. Results: The amount of blood loss (p < 0.01), duration of surgery (p < 0.05), and depth of tibial plateau collapse (p < 0.001) were significantly less in the observation group compared with the control group. In addition, compared with the control group, the observation group exhibited significantly better knee flexion and extension function and significantly higher HSS and Lysholm scores at 12 months after surgery (p < 0.05). Conclusion: The modified posterolateral approach for posterior tibial plateau fractures has less intraoperative bleeding and a shorter operative time compared with the conventional lateral approach. It also effectively prevents postoperative tibial plateau joint surface loss and collapse, promotes the recovery of knee function, and has few postoperative complications and good clinical efficacy. Thus, the modified approach is worth promoting in clinical practice.
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OBJECTIVE: To investigate the effect of the decoction of Fuzheng Jiedu Xiaoji formula (, FJXF) plus chemoembolization (TACE) on primary liver cancer (PLC) in patients, and study the underlying mechanism. METHODS: Patients with PLC who met the inclusion criteria were randomized into case group and control group. The case group was treated with FJXF combined with TACE. The control group was treated with TACE alone. The short-term clinical effect was evaluated; liver biochemistry, liver function index and multidrug resistance-associated indicators were detected. RESULTS: FJXF combined with TACE in the case group significantly increased the disease control rate than TACE alone in the control group (83.3% 61.1%). There was a reduction in the serum alpha-fetoprotein at 8 weeks after treatment in each group, while no difference between the two groups. The same trend can be observed for transaminase and direct bilirubin in both groups. In the case group, it showed a significant increase for albumin at 8 weeks after treatment, while no change in the control group. Multidrug resistance-associated indicators for multidrug resistance protein 1 and p-glycoprotein were upregulated in the case group but remained stable in the control group. CONCLUSIONS: FJXF combined TACE had a better short-term effect than TACE alone in patients with PLC. The potential mechanism was probably associated with alleviated multidrug resistance induced by FJXF. Additionally, FJXF didn't increase the risk of liver damage in the combined therapy.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Medicamentos Herbarios Chinos , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamiento farmacológico , Quimioembolización Terapéutica/efectos adversos , Terapia Combinada , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Overexpression of estrogen receptor ß (ERß) in endometrium contributes to endometriosis (EM) pathogenesis. Trimethylation of the H3 lysine (K) 4 (H3K4me3) in promoters is strongly correlated with gene expression. This study aimed to explore the effects of bisphenol A (BPA) exposure on EM development from the perspective of the regulation of ERß expression in eutopic endometrium via the H3K4me3-related epigenetic pathway. A mouse EM model was established to investigate the effects of BPA. Immortalized human normal endometrial stromal cells (iESCs) were cultured and treated with BPA to explore the underlying mechanism. Eutopic endometria from patients with or without EM were collected and analyzed. Results showed that BPA elevated ERß expression in mouse eutopic endometrium and promoted lesion growth. BPA also promoted WD repeat domain 5 (WDR5) expression and upregulated H3K4me3 levels in the ERß promoter and Exon 1. Further research indicated that WDR5 interacted with tet methylcytosine dioxygenase 2 (TET2), while BPA exposure enhanced the interaction between these two proteins, promoted the recruitment of the WDR5/TET2 complex to the ERß promoter and Exon 1, and inhibited DNA methylation of CpG islands. The WDR5/TET2 interaction was essential for BPA-induced ERß overexpression. Enhanced WDR5/TET2 interaction was also observed in eutopic endometria from EM patients. Further results showed that BPA upregulated WDR5 expression through the G protein-coupled estrogen receptor (GPER)-mediated PI3K/mTOR signaling pathway. In conclusion, our study suggests that BPA exposure promotes EM development by upregulating ERß expression in eutopic endometrium via the WDR5/TET2-mediated epigenetic pathway.
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Endometriosis , Receptor beta de Estrógeno , Animales , Compuestos de Bencidrilo/toxicidad , Proteínas de Unión al ADN , Dioxigenasas , Endometriosis/inducido químicamente , Endometriosis/genética , Endometrio , Epigenómica , Receptor beta de Estrógeno/genética , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular , Ratones , Fenoles , Proteínas Proto-Oncogénicas/genéticaRESUMEN
Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.
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Since the discovery of hepatitis D virus (HDV) in the 1970s, Chinese scholars have started to conduct extensive studies on HDV and hepatitis D (HD). By searching for related articles published on the platforms of Chinese scientific and technological journals and the journals in PubMed database by Chinese scholars, this article comprehensively analyzes and summarizes the advances and scientific findings in HDV and HD by Chinese scholars from basic to clinical research from the perspective of historical development. Over the past years, Chinese scholars have conducted extensive research on the establishment of detection techniques and methods, the construction of infected animal models, the function and application of ribozymes, and clinical diagnosis and manifestation. The research findings in the past 40 years have laid a foundation for further research on the virological characteristics, infection mechanism, and immune response and injury of HDV, the clinicopathological changes of HD, and related antiviral treatment.
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Due to significant innovations in the diagnosis and treatment of hepatitis D virus (HDV), the European Society of Hepatology (EASL) published its first international clinical practice guidelines on the management of individuals with HDV infection in July 2023. The guidelines mainly focus on the six aspects of HDV screening, diagnosis, clinical features and influencing factors, patient monitoring and selection for treatment, therapeutic methods and treatment endpoints. The guidelines give recommendations by answering and elaborating on 13 questions covering these six aspects. In addition, the guidelines also provide the prospect of the future treatment of HDV. The author’s team makes an excerpt of the guidelines and systematically introduces various evaluation points in recommendations and clinical management suggestions, in order to promote the development of clinical management and decision-making for individuals with HDV infection in China.
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BACKGROUND@#Primary malignant bone tumors are uncommon, and their epidemiological features are rarely reported. We aimed to study the incidence and death characteristics of bone tumors from 2000 to 2015.@*METHODS@#Population-based cancer registries submitted registry data to National Central Cancer Registry of China (NCCRC). The data collected from 501 local cancer registries in China were assessed using NCCRC screening methods and criteria. Incidence and mortality rates of primary bone tumor were stratified by age group, gender, and area. Age-standardized incidence and mortality rates were adjusted using the Chinese standard population in 2000 and Segi's world population. The annual percentage change (APC) in rate was calculated using the Joinpoint Regression Program.@*RESULTS@#Data from 368 registries met quality control criteria, of which 134 and 234 were from urban and rural areas, respectively. The data covered 309,553,499 persons. The crude incidence, age-standardized incidence, and crude mortality rates were 1.77, 1.35, and 1.31 per 100,000, respectively. Incidence and mortality rates were higher in males than those in females; they showed downward trends, with declines of 2.2% and 4.8% per year, respectively, and the rates in urban areas were lower than those in rural areas. Significant declining trends were observed in urban areas. Stable trends were seen in rural areas during 2000 to 2007, followed by downward trends. Age-specific incidence and mortality rates showed stable trends in the age group of 0 to 19 years, and downward trends in the age group elder than 19 years.@*CONCLUSIONS@#The incidence and mortality rates of primary malignant bone tumors in rural areas were higher compared to those in urban areas. Targeted prevention measures are required to monitor and control bone tumor incidence and improve the quality of life of affected patients. This research can provide a scientific basis for the prevention and control of bone tumors, as well as basic information for follow-up research.
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Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Adulto Joven , China/epidemiología , Incidencia , Calidad de Vida , Neoplasias Óseas/mortalidad , Pueblos del Este de AsiaRESUMEN
During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.
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Objective:To evaluate the efficacy and safety of the combination of apatinib and S-1 for treatment of patients with advanced gastric cancer, in order to provide clinical therapy reference for advanced gastric cancer.Methods:Clinical trials were retrieved from China National Knowledge Infrastructure (CNKI) , Chinese Science and Technology Journal Database (CSTJ) , Wanfang Medical Network, VIP Journal Database (VIP) , China Biomedical Literature Database (CBMdisc) , Cochrane Library, PubMed, etc., searched from Jan. 2010 to Oct. 2019. The experimental group were given apatinib combined with S-1, and the control group received S-1 monotherapy. Two sets of RCT in patients with advanced gastric cancer were collected. Researchers first screened literature, data extraction and to assess the risk of bias, then made Meta analysis with RevMan5.3 software, the test level was α=0.05.Results:A total of 12 Meta analysis of randomized RCT were selected from the group, including 561 cases of patients. The results showed that objective response rate (ORR) and disease control rate (DCR) of the experimental group was higher than those of the control group [ (RD=0.16, 95% CI: 0.08-0.23, P<0.0001; RD=0.21,95% CI: 0.14-0.29, P<0.00001) ]; There was no significant difference in nausea and vomiting, hand-foot syndrome, fatigue, diarrhea, thrombocytopenia, neutropenia, leukopenia, neuro-toxicity and mucositis between the two groups. The rate of hypertension, proteinuria, hemoglobin of the experimental group decrease was higher than that of the control group [ (OR=6.21, 95% CI: 1.92-20.13, P=0.002; OR = 10.57,95% CI: 5.06-22.04, P<0.00001; OR=2.84, 95% CI:1.25-6.48, P=0.01) ]; and there was a significant heterogeneity in hypertension among them ( P=0.008, I 2=63) . Conclusion:Compared with S-1 alone, the treatment effect of S-1 combined with targeted drug apatinib can significantly improve ORR and DCR of patients with advanced gastric cancer.
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BACKGROUND@#Transplantation of mesenchymal stem cells (MSCs) is a potential therapeutic strategy for cartilage degeneration of osteoarthritis (OA). But controlling chondrogenic differentiation of the implanted MSCs in the joints remains a challenge. The role of kartogenin (KGN) for chondrogenesis of MSCs has been widely reported, however, the mechanism of chondrogenesis has not been elucidated in OA. @*METHODS@#In this study, we investigated the miR-145-5p, TGF-b, Samd4, and p-stat3/stat3 expression in cartilage of OA patients and bone marrow mesenchymal stem cells (BMSCs) treated with KGN or miR-145-5p inhibitor. In addition, the cell proliferation and chondrogenic differentiation in vitro and in vivo of BMSCs treated with KGN was also detected. @*RESULTS@#In OA patients, the expression of miR-145-5p was up-regulated, and the expression of TGF-b, Samd4, and p-stat3/stat3 was inhibited. When the BMSCs treated with miR-145-5p inhibitor, the expression of TGF-b, Samd4, and p-stat3/stat3 was also significantly up-regulated. KGN-treated BMSCs had better proliferation and chondrogenic differentiation by up-regulating the expression of Sox 9, Col-2a1, aggrecan in vitro and in OA by down-regulation of miR-145-5p targeting Smad4 pathway. Moreover, intra-articular injection of KGN-treated BMSCs had a better pain relief effect in OA. @*CONCLUSION@#The double effect on cartilage protection and pain relief indicates a great potential of intra-articular injection of KGN-treated BMSCs for the treatment of OA.
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Objective To observe the expression difference of lncRNA FAL1 in ovarian cancer cells and their drug-resistant cell lines, and to explore the effect and mechanism of lncRNA FAL1 down-regulation on cell chemotherapy resistance. Methods The expression levels of fal1 gene in SKOV3 and COC1 cells and their drug-resistant cell lines were detected by qRT-PCR. fal1 siRNA was transfected to downregulate fal1 gene expression. MTT was used to detect cell proliferation. Transwell method was used to detect cell invasion ability. Plate clone formation test was used to detect cell clone ability, and Western blot was used to detect MDR-1, mpr-1, ABCG2 and phosphorylation levels of p38 MAPK, ERK1/2 and JNK. SKOV3/DDP and COC1/DDP cells transfected with FAL1-siRNA were injected subcutaneously into BALB/c nude mice. The volume and mass of subcutaneous transplanted tumors were measured. Results Compared with SKOV3 and COC1 cells, SKOV3/DDP and COC1/DDP cells were less sensitive to DDP, and the expression levels of FAL1 gene increased (P < 0.01). After transfection with FAL1-siRNA, the sensitivity of SKOV3/DDP and COC1/DDP cells to DDP increased (P < 0.01), and the invasion (P < 0.05) and cloning ability (P < 0.01) decreased. The expression levels of MDR-1, MPR-1, ABCG2 (P < 0.01) and the phosphorylation levels of p38 MAPK, ERK1/2 and JNK (P < 0.05) decreased. The volume and mass of subcutaneous transplanted tumors were significantly reduced (P < 0.01). Conclusion Down-regulation of lncRNA FAL1 could significantly reduce the chemotherapy resistance of cisplatin-resistant ovarian cancer cell lines and inhibit the proliferation of drug-resistant cells in vivo. Its mechanism is related to inhibiting the activation of MAPK signaling pathway.
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BACKGROUND: Increasing studies have shown that acupuncture has a significant effect on the treatment of neurogenic bladder after spinal cord injury, but there is no uniform acupuncture prescription standard for the treatment of this disease. OBJECTIVE: To investigate the rules of selecting acupoints in the treatment of neurogenic bladder after spinal cord injury with acupuncture and moxibustion. METHODS: Clinical literatures related to acupuncture treatment of neurogenic bladder after spinal cord injury were retrieved in China Knowledge Network, WanFang Data, VIP database and China Biology Medicine disc from 1989 to January 2020. Then, we established a database to perform descriptive analysis, relevance principle analysis and cluster analysis of the collected acupuncture prescriptions. RESULTS AND CONCLUSION: A total of 93 articles were included. Data collection and analysis showed that the acupoints and meridians with the highest frequency of neurogenic bladder after acupuncture treatment of spinal cord injury were Zhongji (CV3) (with the frequency of 55) and Bladder Meridian of Foot Taiyang (with the frequency of 161). Relevance principle analysis showed that combination of acupoints with strongest support is Guanyuan (CV4) and Zhongji (CV3). Cluster analysis of acupoints with the frequency ≥ 10 showed that acupoints could be divided into two categories. All these findings indicate that when acupuncture and moxibustion is used to treat neurogenic bladder after spinal cord injury, most of the acupoints along the meridians and local acupoints are selected. The results of relevance principle analysis and cluster analysis obtained from data mining can be used to select acupoints, match acupoints and reuse specific acupoints to improve the therapeutic efficacy.
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The acute-on-chronic liver failure (ACLF) with reactivation of hepatitis B virus (HBV) leads to the difficulty in the treatment and the high mortality rate, but the incidence of HBV reactivation is increasing year by year. There are some high risk factors for the reactivation of HBV, such as the use of rituxan, the glucocorticoid, the chemotherapy, the direct-acting antiviral drugs against hepatitis C virus (HCV) and stopping the nucleot(s)ides analogues against HBV by oneself. The diagnostic criteria, risk factors, risk assessment of ACLF, prevention and management of HBV reactivation are reviewed in this article.
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Objective To investigate the protective effect of ferulic acid on lung function in mice with chronic obstructive pulmonary disease (COPD) and its possible mechanism. Methods Sixty mice were randomly divided into normal control group, COPD model group, Rofloast group and ferulic acid high, medium and low dose groups, each group with 10 rats, and during administration one rat died in the mode group and was eliminated. The COPD model was duplicated by smoking method; the mice in normal control group were fed normally without any treatment. After modeling for 30 days, normal saline begun to be given to the COPD model group and normal control group; the mice in Rofluast group were given Rofluast 65 μg/kg; ferulic acid 160, 80, 40 mg/kg were given to high, middle and low dose groups respectively. The indexes were determined after consecutive 90 days of treatment, the changes of peak inspiratory flow (PIF) rate, peak expiratory flow (PEF) rate and ventilation volume per minute (MV), mean lining interval (MLI), alveolar destruction index (DI), interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α) levels in serum and bronchoalveolar lavage fluid (BALF), the protein expressions and phosphorylation levels of p38 mitogen-activated protein kinases (p38MAPK), extracellular signal-regulated kinase (ERK) and c-Jun amino terminal kinase (JNK) in the pulmonary tissue MAPK signaling pathway were observed in each mouse of various mice groups. Results In the COPD model group, the PIF, PEF, and MV were all significantly lower than those in the normal control group [PIF (mL/s): 2.32±0.18 vs. 3.41±0.12, PEF (mL/s): 2.31±0.22 vs. 2.90±0.15, MV (mL/s): 26.20±2.70 vs. 35.18±2.30); Luofusite and all doses of ferulic acid can increase PIF, PEF, and MV, and the degree of increase in the high dose ferulic acid group was more significant than those in the moderate and low dose ferulic acid groups [PIF (mL/s): 3.24±0.13 vs. 2.88±0.15, 2.51±0.10, PEF (mL/s): 2.81±0.16 vs. 2.66±0.11, 2.58±0.17, MV (mL/s):31.18±1.20 vs. 28.25±2.20, 27.09±1.10]; however, there was no statistical significant difference between the Rofluas group and the ferulic acid groups (all P > 0.05). The levels of the MLI, DI, and inflammatory factors in serum and BALF, and the protein expressions and phosphorylation levels of p38MAPK, ERK, JNK in lung tissue in model group were all significantly higher than those in normal control group [MLI (μm): 52.10±0.26 vs. 21.90±0.14, DI: (60.78±3.32)% vs. (22.47±1.05)%, IL-6 in serum (ng/L): 22.34±4.51 vs. 3.50±1.55, TNF-αin serum (ng/L): 27.11±3.99 vs. 4.66±1.76, IL-6 (ng/L) in BALF: 142.92±20.10 vs. 18.77±4.17, TNF-α(ng/L): 150.16±20.77 vs. 22.01±4.15, P-ERK/ERK (gray value): 0.59±0.03 vs. 0.38±0.05, P-p38MAPK/p38MAPK (gray value): 0.52±0.02 vs. 0.31±0.05, P-JNK/JNK (gray value): 0.56±0.03 vs. 0.25±0.01, all P < 0.05]. The levels of MLI, DI, and inflammatory factors in serum and BALF, p38MAPK, ERK, JNK protein expression and phosphorylation in lung tissue were reduced by Rofluas and various doses of ferulic acid, the reduction levels in the high dose group of ferulic acid were more significant than those in the middle and low dose groups of ferulic acid [MLI (μm): 25.00±0.19 vs. 30.10±0.29, 38.80±0.41, DI: (26.32±3.05)% vs. (29.75±6.17)%, (40.56±5.81)%, IL-6 in serum (ng/L): 9.20±1.87 vs. 12.35±2.16, 18.95±3.12, TNF-α(ng/L): 13.37±2.73 vs. 18.02±2.62, 21.31±3.75, IL-6 (ng/L) in BALF: 64.27±11.72 vs. 99.33±13.02, 120.31±18.02, TNF-α(ng/L): 58.20±10.28 vs. 93.83±16.26, 122.68±14.85, P-ERK/ERK (gray value): 0.43±0.04 vs. 0.46±0.04, 0.52±0.02, P-p38MAPK/p38MAPK (gray value): 0.33±0.03 vs. 0.34±0.03, 0.38±0.02, P-JNK/JNK (gray value): 0.32±0.04 vs. 0.38±0.05, 0.47±0.06). The ferulic acid could improve the inflammatory cell infiltration situation in mice with COPD. Conclusions Ferulic acid can improve pulmonary inflammation in COPD rats. The effective mechanism is possibly related to the inhibition of the protein expressions and phosphorylation levels of the key proteins such as p38MAPK, ERK and JNK in the MAPK signaling pathway.
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Objective To evaluate the effect of tyrosol on myocardial ischemia-reperfusion (I/R) injury in diabetic rats and the role of silent mating-type information regulation 1 (SIRT1)/adenosine monophosphate-activated protein kinase (AMPK)/endothelial nitric oxide synthase (eNOS) signaling pathway.Methods SPF healthy adult male Sprague-Dawley rats,weighing 200-220 g,were intraperitoneally injected with streptozotocin 60 mg/kg to establish the model of diabetes mellitus.Fifty-six diabetic rats were divided into 4 groups (n =14 each) using a random number table method:sham operation group (S group),myocardial I/R group (I/R group),myocardial I/R plus tyrosol group (I/R+T group),and myocardial I/R plus tyrosol plus SIRT1 inhibitor EX527 group (I/R+T+E group).In I/R+T and I/R+T+E groups,tyrosol 20 mg · kg-1 · d-1 was given by gavage for 45 consecutive days,and the equal volume of normal saline was given in the other two groups.In I/R+T+E group,EX527 5 mg · kg-1 · d-1 was intraperitoneally injected for 3 consecutive days before ischemia,and EX527 5 mg/kg was intraperitoneally injected at 20 min before repeffusion.Myocardial I/R was induced by ligation of the left anterior descending branch of coronary artery for 30 min followed by 2-h reperfusion.The myocardial infarct volume was measured by TTC staining.The levels of creatine kinase-MB (CK-MB),lactic dehydrogenase (LDH) and 5-F2t-isoprostane in serum and superoxide dismutase (SOD) in myocardial tissues were detected by enzyme-linked immunosorbent assay.The expression of SIRT1,AMPK,phosphorylated AMPK (p-AMPK),eNOS and p-eNOS was detected by Western blot.Results Compared with S group,the levels of serum CK-MB,LDH and 15-F2t-Isoprostane and myocardial infarction volume were significantly increased,the SOD activity was decreased,and the SIRT1 expression was down-regulated in I/R group,and the levels of serum CKMB,LDH and 15-F2t-Isoprostane and myocardial infarction volume were significantly increased,the SOD activity was decreased,the SIRT1 expression was down-regulated,and the expression of p-AMPK and peNOS was up-regulated in I/R+T and I/R+T+E groups (P<0.05).Compared with I/R group,the levels of serum CK-MB,LDH and 15-F2t-Isoprostane and myocardial infarction volume were significantly decreased,the SOD activity was increased,and the expression of SIRT1,p-AMPK and p-eNOS was up-regulated in I/R+T group (P<0.05),and no significant change was found in the parameters mentioned above in I/R+ T+E group (P>0.05).Compared with I/R+T group,the levels of CK-MB,LDH and 15-F2t-isoprostane in serum and myocardial infarct volume were significantly increased,the SOD activity was increased,and the expression of SIRT1,p-AMPK and p-eNOS was down-regulated in I/R+T+E group (P<0.05).Conclusion Tyrosol can mitigate myocardial I/R injury,and the mechanism may be related to activating SIRT1/AMPK/eNOS signaling pathway and inhibiting oxidative stress response in diabetic rats.
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Viral-encoded microRNAs (miRNAs) have vital roles in the regulation of virus replications and host immune responses. The results of previous studies have indicated that miRNA clusters are involved in the replication and virulence of the pseudorabies virus (PRV), which may potentially lead to immune escape or facilitation of PRV replication. This study's previous research revealed that prv-miR-LLT11a was differentially expressed during PRV infection. The present study's results have demonstrated that prv-miR-LLT11a could significantly inhibit PRV replication. It was further determined that SLA-1 was the target gene of prv-miR-LLT11a, and simultaneously, that overexpression of prv-miR-LLT11a could downregulate the mRNA and protein levels of SLA-1 in a dose-independent manner. Furthermore, the present study also observed that prv-miR-LLT11a can downregulate TAP1 expression. Our findings provide a better understanding of the molecular mechanism involved in the effects of prv-miR-LLT11a on SLA-1 and TAP1 as well as its involvement in immune system evasion of PRV.
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Herpesvirus Suido 1 , Sistema Inmunológico , MicroARNs , Seudorrabia , ARN Mensajero , Naciones Unidas , Virulencia , Replicación ViralRESUMEN
Objective To evaluate the role of classⅠhistone deacetylase (HDAC) in myocardial ischemia-reperfusion (I∕R) injury in diabetic rats and the relationship with adenosine monophosphate-acti- vated protein kinase (AMPK)∕mammalian target of rapamycin (mTOR) signaling pathway. Methods SPF healthy adult male Sprague-Dawley rats, weighing 210-220 g, were used in this study. Type I diabetes mellitus was induced by single intraperitoneal injection of streptozotocin dissolved in citrate buffer 60 mg∕kg, and 8 weeks later the rats with type I diabetes mellitus were used for experiment. Forty-eight diabetic rats were divided into 4 groups (n=12 each) by using a random number table method: sham operation group (group S), myocardial I∕R group (group I∕R), myocardial I∕R plus class I HDAC inhibitor MS-275 group (group I∕R+MS) and myocardial I∕R plus MS-275 plus AMPK inhibitor Compound C group ( group I∕R+MS+CC). Myocardial I∕R was induced by ligation of the left anterior descending branch of the coronary ar-tery for 45 min followed by 180 min of reperfusion in anesthetized rats. In group I∕R+MS, MS-275 10 mg∕kg was intraperitoneally injected once a day for 7 consecutive days, and myocardial I∕R was produced after the end of administration. AMPK inhibitor Compound C 0. 5 mg∕kg was intravenously injected at 30 min before ischemia in group I∕R+MS+CC. Six rats were sacrificed at the end of reperfusion for determina-tion of myocardial infarct size. Another 6 rats were selected at the end of reperfusion and sacrificed for deter-mination of the level of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in serum (by en-zyme-linked immunosorbent assay), expression of AMPK, phosphorylated AMPK ( p-AMPK), mTOR, phosphorylated mTOR (p-mTOR), ubiquitin-binding protein P62 (P62), microtubule-associated protein 1 light chain 3 Ⅰ(LC3 Ⅰ) and LC3Ⅱ in myocardial tissues (by Western blot). The ratios of p-AMPK∕AMPK, p-mTOR∕mTOR and LC3Ⅱ∕Ⅰwere calculated. Results Compared with group S, the myocardial infarct size and levels of serum CK-MB and LDH were significantly increased in I∕R, I∕R+MS and I∕R+M+CC groups, the ratios of p-AMPK∕AMPK and LC3Ⅱ∕Ⅰwere significantly increased, p-mTOR∕mTOR ratio was decreased, and P62 expression was down-regulated in group I∕R+MS (P<0. 05), and no significant change was found in p-AMPK∕AMPK ratio, p-mTOR∕mTOR ratio, LC3Ⅱ∕Ⅰ ratio or P62 expression in I∕R and I∕R+M+CC groups (P>0. 05). Compared with group I∕R, the myocardial infarct size and levels of serum CK-MB and LDH were significantly decreased, the ratios of p-AMPK∕AMPK and LC3Ⅱ∕Ⅰwere in-creased, p-mTOR∕mTOR ratio was decreased, and P62 expression was down-regulated in group I∕R+MS (P<0. 05), and no significant change was found in the parameters mentioned above in group I∕R+M+CC (P>0. 05). Compared with group I∕R+MS, the myocardial infarct size and levels of serum CK-MB and LDH were significantly increased, the ratios of p-AMPK∕AMPK and LC3Ⅱ∕Ⅰ were decreased, p-mTOR∕mTOR ratio was increased, and P62 expression was up-regulated in group I∕R+M+CC ( P<0. 05). Con-clusion Class Ⅰ HDAC is involved in myocardial I∕R injury through enhancing AMPK∕mTOR signaling pathway-regulated level of autophagy in diabetic rats.
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Thromboxane A2 receptors (TPs) widely distribute in different organ systems and localize both on cell membranes and in intracellular structures.TPs are the members of seven-transmembrane G-protein-coupled receptor (GPCR) super family.Historical-ly, the involvement of TPs in platelet functions has received the greatest attention .TPs have the capacity to activate different signaling cascades which regulate platelet shape change , aggregation and secretion response .Currently , anti-platelet drugs primarily act on re-ceptors and /or signaling molecules in activation pathways .The signaling transduction of TPs in platelet contributes to the investigation of the effects of extracts of traditional Chinese medicine on antiplatelet aggregation and the exploration of the action mechanisms .
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Objective To study the different drying technology.on Wudang Lonicerae Flos (Ⅰ) in chlorogenic acid content.Methods Using HPLC method to research the difference in the contents of chlorogenic acid of Wudang Lonicerae Flos (Ⅰ) employing oven-drying method,air-dried method and steamed drying technologies.DIONEX C18 (4.6 mm×250 mm,5 μm) was used.The mobile phases consisted of acetonitrile-0.4% phosphoric acid aqueous solution (17 ∶ 83).The detection wavelengths of chlorogenic acid was 327nm.The flow rate was 0.4 ml/min.The column temperature was 30 ℃.Results The Separation of Chlorogenic acid content was satisfactory.The concentration and peak area showed a good linearity relationship with the range of 0.285-2.850 μg.Precision,repeatability and stability met the requirements.The average recovery was 100.26% with RSD 1.95%.Chlorogenic acid content in the steamed drying Wudang Honeysuckle (Ⅰ) was higher.Conclusions The method of steam drying is better than that of oven-drying method and drying.