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Objective: As a common chronic inflammatory skin disease, psoriasis seriously affects the physical health and psychological well-being of patients. Various clinical treatments for psoriasis have their own drawbacks, so it is important to find effective and safe drugs. Rehmannioside A (ReA) has anti-inflammatory properties and is the main active ingredient in Fuzhengzhiyanghefuzhiyang decoction (FZHFZY), an herbal compound for the treatment of psoriasis. But no studies have been conducted to determine whether ReA alone can treat psoriasis. Therefore, this study was designed to investigate the effect of ReA in the treatment of psoriasis and its potential mechanism of action. Methods: HaCaT cells were treated with ReA and IL-17A alone for 24 h and 48 h, and the most effective concentrations of ReA and interleukin (IL)-17A were found at 25 µg/mL and 100 ng/mL, respectively. A psoriasis cell model was constructed by stimulating HaCaT cells with IL-17A, followed by intervention with ReA. Cell viability and cell cycle distribution were measured by MTT assay and flow cytometry. The expression levels of keratin family members and chemokines were detected by real-time quantitative PCR (RT-qPCR), the levels of pro-inflammatory cytokines by enzyme-linked immunosorbent assay (ELISA), and key proteins of TRAF6/MAPK signaling pathway by Western blot. Results: ReA weaken cell viability, down-regulate the expression of keratin family members (KRT6 and KRT17), restore cell cycle distribution to normal distribution, inhibit the release of pro-inflammatory cytokines (IL-6, IL-8 and IL-1ß) and lower the expression of chemokines (S100A7, S100A9 and CXCL2) by interfering with the interaction between HaCaT cells and IL-17A. Thus, it exerts an anti-psoriatic effect by reducing the inflammatory response and inhibiting abnormal proliferation of HaCaT cells. Mechanistically, ReA inhibited the TRAF6/MAPK signaling pathway activated by IL-17A stimulation in HaCaT cells. Conclusion: ReA has in vitro anti-psoriatic effects and may be a new therapeutic agent for psoriasis.
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Low-temperature curable negative-tone photosensitive polyimide (n-LTPI) viscous solutions were prepared by dissolving photo-crosslinkable poly (amic ester) (pc-PAE) resin, photophotocrosslinker, photoinitiator, and the heteroaromatic base as curing catalysts, and other additives in organic solvents. Among them, the pc-PAE resin was synthesized by polycondensation of aromatic diacid chloride and diester of 2-ethoxymathacrylate, aromatic diamines in aprotic solvents. After being spun-coated on a silicon wafer surface, soft-baked, exposed to UV light, and developed, the n-LTPI with 2% of imidazole (IMZ) as a curing catalyst produced high-quality photo-patterns with line via resolution of 5 µm at 5 µm film thickness. The photo-patterned polymer films thermally cured at 230 °C/2 h in nitrogen showed 100% of the imidization degree (ID) determined by in situ FT-IR spectroscopy. The thermally cured polymer films exhibited great combined mechanical and thermal properties, including mechanical properties with tensile strength of as high as 189.0 MPa, tensile modulus of 3.7 GP, and elongation at breakage of 59.2%, as well as glass transition temperature of 282.0 °C, showing great potential in advanced microelectronic packaging applications.
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Objectives: To evaluate the effects of paroxetine hydrochloride combined with idebenone on inflammatory factors and antioxidant molecules in the treatment of depression after ischemic stroke. Methods: Randomized controlled trial was adopted on 80 patients with depression after ischemic stroke were randomly divided into two groups, with 40 patients in each group at Xingtai Sanli Health Quannan Clinic from March 17, 2019 to December 20, 2021. Both groups were given basic treatment. On this basis, the control group was treated with paroxetine hydrochloride, while the study group was treated with paroxetine hydrochloride combined with idebenone. The clinical efficacy was evaluated using the Hamilton Rating Scale for Depression (HRSD) before and after treatment. Additionally, the difference in HRSD score after treatment and the improvement in inflammatory factors and antioxidant molecules were compared and analyzed between the two groups. Results: After treatment, the HRSD score of the study group was significantly improved compared with that of the control group (p= 0.00). The effective rate was 82.5% in the study group, which was significantly higher than 62.5% in the control group (p= 0.04). After treatment, TNF-a, CRP and IL-6 in the study group were significantly lower than those in the control group (p= 0.00). Serum SOD, TAC and CAT levels in the study group were significantly higher than those in the control group after treatment (SOD and TAC, p= 0.00; CAT, p= 0.01). The incidence of adverse reactions was 37.5% in the study group and 25% in the control group. Although the incidence of adverse reactions in the study group was higher than that in the control group, the difference was not statistically significant (p= 0.23). Conclusion: Paroxetine hydrochloride combined with idebenone in the treatment of depression after ischemic stroke can significantly improve HRSD score, enhance clinical efficacy, reduce the levels of inflammatory factors, and increase the levels of antioxidant factors, without a significant increase in adverse reactions. Therefore, it is a safe and effective treatment method.
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Background: The clinical efficacy of the third Military Medical University formula (TMMU formula) for fluid resuscitation stage was evaluated to improve the treatment level of adult patients with extensive burns during the shock stage. Methods: Retrospective analysis of the data of 55 patients undergoing fluid resuscitation according to the TMMU formula within six hours after burn injury. The following indicators were collected: (1) demographic and injury information; (2) fluid resuscitation information; (3) efficiency information, including cardiovascular function, liver function, renal function, coagulation function evaluation indicators, blood concentration, and average urine output index. Results: (1) In the first and second 24 hours after injury, the median fluid rehydration coefficient was 1.68 ml/kg·(%) TBSA and 1.15 ml/kg·(%) TBSA, the median ratio of crystal to colloid was 2.24 and 1.67, and the median urine output index was 0.75 ml/kg·h and 1.05 ml/kg·h, respectively. (2) The actual fluid volume during patient resuscitation is higher than the formula calculated volume, and this difference is more obvious in patients with burn area ≥80%. (3) In the second 24 hours, the value of the actual total fluid volume minus the formula total volume in the group with crystal to colloid ratio ≤2 was significantly lower than that in the ratio >2 group. (4) At 24 and 48 hours after injury, the cardiovascular function, liver function, renal function, and coagulation function were better than those before fluid resuscitation. Conclusions: Early application of the TMMU formula for fluid resuscitation in adult patients with extensive burns is safe and effective, but the actual input volume often exceeds the volume calculated by the formula, especially in the second 24 hours after burn injury and in patients with larger burn areas. Increasing the colloid input volume can help reduce the total amount of fluid used for resuscitation.
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With the goal of improving processability of imide oligomers and achieving of high temperature carbon fiber composite, a series of Thermosetting Matrix Resin solutions (TMR) were prepared by polycondensation of aromatic diamine (3,4'-oxybisbenzenamine, 3,4-ODA) and diester of biphenylene diacid (BPDE) using monoester of 4-phenylethynylphthalic acid (PEPE) as end-capping agent in ethyl alcohol as solvent to afford phenylethynyl-endcapped poly(amic ester) resins with calculated molecular weight (Calc'd Mw) of 1500-10,000. Meanwhile, a series of reactive diluent solutions (RDm) with Calc'd Mw of 600-2100 were also prepared derived from aromatic diamine (4,4'-oxybisbenzenamine, 4,4-ODA), diester of asymmetrical biphenylene diacid (α-BPDE) and monoester of 4-phenylethynylphthalic acid (PEPE) in ethyl alcohol. Then, the TMR solution was mixed with the RDm solution at different weight ratios to afford a series of A-staged thermosetting blend resin (TMR/RDm) solutions for carbon fiber composites. Experimental results demonstrated that the thermosetting blend resins exhibited improved melt processability and excellent thermal stability. After being thermally treated at 200 °C/1 h, the B-staged TMR/RDm showed very low melt viscosities and wider processing window. The minimum melt viscosities of ≤50 Pa·s was measured at ≤368 °C and the temperature scale at melt viscosities of ≤100 Pa·s were detected at 310-390 °C, respectively. The thermally cured neat resins at 380 °C/2 h showed a great combination of mechanical and thermal properties, including tensile strength of 84.0 MPa, elongation at breakage of 4.1%, and glass transition temperature (Tg) of 423 °C, successively. The carbon fiber reinforced polyimide composite processed by autoclave technique exhibited excellent mechanical properties both at room temperature and 370 °C. This study paved the way for the development of high-temperature resistant carbon fiber resin composites for use in complicated aeronautical structures.
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OBJECTIVE: To study the effect and safety of G-CSF combined with Plerixafor on the mobilization of peripheral blood hematopoietic stem cells from healthy related donors of allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: It was analyzed retrospectively that the data of peripheral blood hematopoietic stem cells from 33 (observation group) related donors mobilized by G-CSF plus Plerixafor in Hebei Yanda Lu Daopei Hospital from April 2019 to April 2021. Bone marrow and peripheral blood hematopoietic stem cells (PBSCs) of these donors were respectively collected on the fourth and fifth day of G-CSF-induced mobilization. Following the administration of Plerixafor on the night of the fifth day, PBSCs were collected on the sixth day once again. 46 donors using "G-CSF only" mobilization method in the same period were randomly selected as the control and respectively analyzed the differences of CD34+ cell counts on the fifth and the sixth day in two groups. And the donors' adverse reaction to Plerixafor in the form of questionnaire was also observed. Then it was compared that the patients who underwent allo-HSCT in "G-CSF+Plerixafor" group and "G-CSF only" group in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation. RESULTS: CD34+ cells count (M±Q) among PBSCs collected on the fifth and the sixth day in the observation group were (1.71±1.02)×106/kg and (4.23±2.33)×106/kg, respectively. CD34+ cell counts on the sixth day was significantly higher than that of the fifth day (P<0.001); While the counterparts in the control group were (2.47±1.60)×106/kg and (1.87±1.37)×106/kg, respectively. By statistical analysis, CD34+ cell counts on the sixth day was significantly less than that of the fifth day (P<0.001). The adverse reaction to Plerixafor for the donors in the study were all grade 1 or 2 (mild or moderate) according to CTCAE 5.0 and disappeared in a short time. The patients who underwent allo-HSCT in the "G-CSF+Plerixafor" group and "G-CSF only" group were not statistically significant in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation (P>0.1). CONCLUSION: The cell mobilization program of G-CSF combined with Plerixafor is safe and effective for being applied to allo-HSCT. The addition of Plerixafor can significantly increase the number of CD34 postive cells in the PBSC collection. Key wordsãã; ;
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Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos , Trasplante de Células Madre de Sangre Periférica , Antígenos CD34 , Bencilaminas , Ciclamas , Factor Estimulante de Colonias de Granulocitos , Movilización de Célula Madre Hematopoyética , Células Madre Hematopoyéticas , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: Gastroesophageal reflux disease (GERD) is a common digestive disease, could cause extra-esophageal symptoms. Peroral endoscopic cardial constriction with band ligation (PECC-b) is a minimally invasive method for the treatment of GERD in recent years. The goals of this study were to evaluate the clinical efficacy of PECC-b to treat gastroesophageal reflux-related symptoms. METHODS: A retrospective study of patients undergoing PECC-b between January 2017 and December 2018 at a single institution was conducted. All patients confirmed GERD by endoscopy, esophageal PH-impedance monitoring, esophageal manometry and symptom questionnaires. The outcome measures included reflux-related scores, patients' satisfaction and drug independence after 12 months following surgery. RESULTS: A total of 68 patients, with follow-up of 12 months post surgery, were included in the final analysis. The symptom scores were all significantly decreased as compared with preoperation (P < 0.05). The esophageal symptom scores showed a better improvement than extra-esophageal symptoms (P < 0.001). Fifty-three (77.9%) patients achieved complete drug therapy independence and 52 (76.5%) patients were completely or partially satisfied with the symptom relief following surgery. CONCLUSIONS: The PECC-b is a safe, effective and recommended approach for the control of GERD-related symptoms. Further multicenter prospective studies are required to confirm these outcomes.
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Reflujo Gastroesofágico , Constricción , Endoscopía , Monitorización del pH Esofágico , Estudios de Factibilidad , Estudios de Seguimiento , Reflujo Gastroesofágico/cirugía , Humanos , Manometría , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We previously reported that helicid, an active plant monomer of Helicid nilgirica Bedd, had good antidepressant pharmacological activities. However, the potential mechanism of action remains unknown. Current investigation showed the antidepressant-like effects of helicid and its effects on the neurocalcin delta (NCALD) gene, and its mechanism of action through a depression model in rats exposed to chronic unpredictable mild stress (CUMS). We evaluated depression symptoms using the sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST). By silencing NCALD and using rescue experiments, the IL-6, iNOS, IL-1ß, COX-2, and TNF-α levels in the hippocampus or peripheral blood were determined using western blotting and ELISAs. The expression of IKKß, p-IкBα, p-IKKß, NF-кB p65, and IкBα were tested using western blots of the cytoplasmic or nuclear samples. Helicid and silencing NCALD relieved the CUMS-irritated depressive-like actions of rats, which were shown by increased consumption of sucrose, numbers of rearings, total running distance, zone crossings, and reduced immobility times. Helicid or silencing NCALD reversed the CUMS-induced high levels of IL-1ß, COX-2, IL-6, TNF-α, and iNOS in the hippocampus or peripheral blood. Helicid or silencing NCALD also reduced the expressions of p-IκBα and p-IKKß in the cytoplasm and the expression of nuclear NF-κB p 65 in hippocampus, and simultaneously elevated cytoplasmic expressions of IκBα, IKKß, and NF-κB p65 in the hippocampus. Notably, after NCALD overexpression, the biochemical indices of rat helicid administration were reversed. In conclusion, the antidepressant action of helicid was mediated through NCALD in rats of CUMS by repressing hippocampal neuro-inflammation and abating the activation of the IKK/IκBα/NF-κB pathway.
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Antidepresivos/uso terapéutico , Benzaldehídos/uso terapéutico , Depresión/tratamiento farmacológico , Estrés Psicológico/tratamiento farmacológico , Animales , Antidepresivos/farmacología , Benzaldehídos/farmacología , Depresión/metabolismo , Modelos Animales de Enfermedad , Quinasa I-kappa B/metabolismo , Masculino , FN-kappa B/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Estrés Psicológico/metabolismoRESUMEN
Based on our previous research, thirty new 5-amino-1H-1,2,4-triazoles possessing 3,4,5-trimethoxyphenyl moiety were synthesized, and evaluated for antiproliferative activities. Among them, compounds IIa, IIIh, and IIIm demonstrated significant antiproliferative activities against a panel of tumor cell lines, and the promising compound IIIm dose-dependently caused G2/M phase arrest in HeLa cells. Furthermore, analogue IIa exhibited the most potent tubulinpolymerization inhibitory activity with an IC50 value of 9.4 µM, and molecular modeling studies revealed that IIa formed stable interactions in the colchicine-binding site of tubulin, suggesting that 5-amino-1H-1,2,4-triazole scaffold has potential for further investigation to develop novel tubulin polymerization inhibitors with anticancer activity.
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Antineoplásicos/farmacología , Triazoles/farmacología , Moduladores de Tubulina/farmacología , Tubulina (Proteína)/metabolismo , Antineoplásicos/síntesis química , Antineoplásicos/química , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Estructura Molecular , Polimerizacion/efectos de los fármacos , Relación Estructura-Actividad , Triazoles/síntesis química , Triazoles/química , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/químicaRESUMEN
BACKGROUND: Subjective cognitive decline (SCD) has been called the prodromal stage of amnestic mild cognitive impairment (aMCI); however, further investigation is needed to confirm this observation. OBJECTIVE: To define the relationship between SCD and aMCI. METHOD: In this case-control study, we used the feeling-of-knowing in episodic memory (FOK-EM) test to measure the memory-monitoring function of 40 adults with aMCI, 60 with SCD, and 55 healthy controls. RESULTS: The recognition rates of FOK-EM (53.53% ± 7.82%; 55.12% ± 6.08%) and judgment accuracy of the aMCI and SCD groups (γ values 0.21 ± 0.11; 0.30 ± 0.16) were significantly lower than those of the control group (72.32% ± 5.14%; 0.57 ± 0.16) (F = 116.24, P < 0.01; F = 128.57, P < 0.01; F = 73.33, P < 0.01). The scores for correct decision/correct recognition (RR; 27.2 ± 6.43; 29.36 ± 5.16) and correct decision/false recognition (RF; 30.41 ± 5.06; 27.26 ± 4.37) of the aMCI and SCD groups were also significantly lower than those of the control group (49.35 ± 7.13; 11.16 ± 4.35) (FRR = 132.67, P < 0.01; FRF = 131.8, P < 0.01). CONCLUSION: Mild clinical impairments in memory-monitoring function may precede clinically confirmed objective memory impairment in individuals with SCD.
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Disfunción Cognitiva/complicaciones , Trastornos de la Memoria/etiología , Pruebas Neuropsicológicas/normas , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To develop an automated chimeric analysis and reporting platform based on short tandem repeat (STR) and capillary electrophoresis methods for allogeneic hematopoietic stem cell transplantation (allo-HSCT) so as to improve work efficiency. METHODS: Apache, MySQL, PHP and HTML5 were used to build the database and interface. The STR locus geno typing and chimeric analysis logic and flow were set up on the basis of STR rules and capillary electrophoresis. STR genotyping and 194 times of chimeric testing data of 100 patients after allo-HSCT were used to test the platform for automatic STR locus genotyping, chimeric calculation and report generation. RESULTS: The established platform could realize the functions of STR locus customization, STR genotype determination, automatic chimeric analysis, and detection information database management, which can automatically generate an integrated report including multiple sequential chimeric results and trend graphs for the same patient and can be accessed and used simultaneously by different users through different browser interfaces. The results of automated analysis by the platform are completely consistent with that of manual analysis by experienced technicians, and the possibility of manual analysis error is reduced through automation. The time required for automatic analysis using this platform is approximately 1/6-1/5 of manual analysis. CONCLUSION: The automatic analysis platform built in this study is operation stable and reliable in analysis results, which can improve work efficiency and report connotation, thus worthing popularized and applicable.
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Trasplante de Células Madre Hematopoyéticas , Electroforesis Capilar , Genotipo , Humanos , Repeticiones de Microsatélite , Donantes de TejidosRESUMEN
OBJECTIVE: To study the correlation between tumor-associated somatic gene mutation and age in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia transformed from myelodysplastic syndrome (MDS/AML). METHODS: A total of 111 patients primarily diagnosed as MDS or MDS/AML were selected. Bone marrow samples from patients were collected or bone marrow smears prepared at the initial diagnosis were used for detecting the somatic gene mutations of 58 genes related with hematologic tumors by high-throughput gene sequencing. And the correlation of gene mutations with the age of patients was analyzed. RESULTS: The positive rate of total gene mutation was 87.39% (97/111) in 111 patients, and 231 mutations in 28 different genes were detected in the patients with positive gene mutation. The patients of mutation-positive group were significantly older than that of the mutation-negative group (Pï¼0.001). Among the mutation-positive patients, the mutation rate in the senile group (≥60 years) was 100% (14/14), followed by 89.04% (74/85) in the adult group (15-59 years) and 75% (9/12) in the children group (≤14 years). The average number of mutations in the children group, the adult group and the senile group were respectively 1.44, 2.47 and 2.5; the number of mutations in the adult group was greater than that in the children group (Pï¼0.05).The most common mutations in the children group occurred in signal transduction gene (46.15%, 6/13); The most common mutations in both the adult group (22.40%, 41/183) and the senile group (34.29%, 12/35) occurred in epigenetic regulatory gene; the mutation rate of transcription factor gene in the senile group was higher than that in the children group (50.00% vs 8.33%) (Pï¼0.05); the mutation rates of the splicing factor gene in the adult group and the senile group were higher than that in the children group (44.71% vs 8.33%) (Pï¼0.05), (47.06% vs 8.33%) (Pï¼0.05). CONCLUSION: The tumor-associated somatic gene mutations in patients with MDS and MDS/AML are significantly different between the different age groups, especially the children group and the adults group as well as the senile group, suggesting that the occurrence of MDS in children may involve genetic factors that are significantly different from those of adults and the senile.
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Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Adolescente , Adulto , Médula Ósea , Humanos , Persona de Mediana Edad , Mutación , Adulto JovenRESUMEN
OBJECTIVE: To study the epidemiologic characteristics of human herpes virus (HHV) activated infection in the diseases of blood system and patients received allo-HSCT by statistically analyzing the screening results of 8 human herpes viruses (HHVs) of 4164 patients in Hebei Yanda LU Dao-Pei Hospital from 2012 to 2017. METHODS: PCR was used to screen 8 HHVs. RESULTS: Two thousand and fifty-two patients (49.28%) were HHV-positive among 4164 patients screened. Among these patients screened, the infection spectra of 8 human HHVs in hematological diseases as well as patients received allogeneic hematopoietic stem cell transplantation of totally 2994 patients were summarized as follows: the positive rate of EBV (29.49%) was the highest, that of HCMV (23.15%), HHV-6 was 18.77% and HHV-7 was 17.64%, while the remaining 4 HHVs all≤2.1%. The rate of co-infection of various HHVs was significantly higher than that of single infection of HHV among all these disease groups except familial hemophagocytic lymphohistiocytosis, for which single EBV infection was the most common. The differences of positive rates among these 8 human HHVs in hematological diseases as well as patients received allogeneic hematopoietic stem cell transplantation were statistically significant by Chi-square test of R*C tables (χ2=54.99, Pï¼0.05). For each HHV, the differences of positive rates among the above-mentioned disease groups were also statistically significant except HHV-8 (Pï¼0.05). CONCLUSION: The patients with various blood diseases have different activated infection spectra of HHVs. EBV, HCMV, HHV-6 and HHV-7 are most common in HHVs infection. Different HHVs infections correlate with different hematologion diseases.
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Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Infecciones por Herpesviridae , Síndromes de Inmunodeficiencia , ADN Viral , HumanosRESUMEN
Gastroesophageal reflux disease (GERD) is often associated with hiatal hernia (HH). However, the need for fundoplication during hiatal hernia repair (HHR) remains controversial. The objective of this study was to evaluate the effect of HHR with concomitant laparoscopic Nissen fundoplication (HHR-LNF) in HH patients. A total of 122 patients with symptomatic HH were randomized to receive either HHR (n = 61) or HHR-LNF (n = 61). The measures of evaluating outcomes included DeMeester scores (DMS), complications, Reflux Diagnostic Questionnaire and patients' satisfaction 24 months following surgery. Despite comparable values in both groups at randomization, the DMS, total numbers of reflux episodes and percentage of time with pH < 4 were significantly higher in HHR group than in HHR-LNF group (P = 0.017, P = 0.002 and P = 0.019, respectively) at 6 months after surgery. One months postoperatively, complications were higher in the HHR-LNF group than in the HHR group (all P < 0.001), and there was no difference between the two groups at 6 months. By the end of the 2-year follow-up, HHR-LNF group showed a significantly lower reflux syndrome frequency-intensity score and greater percentage of satisfaction compared with HHR group (all P < 0.001). Laparoscopic HHR should be combined with a fundoplication in GERD patients with HH. HHR-LNF is safe and effective, not only improve reflux-related symptom, but also reduce the incidence of complications.
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Fundoplicación , Hernia Hiatal/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The chemical constituents and action targets of Acori Tatarinowii Rhizoma and Curcumae Radix were screened by network pharmacological method,and the mechanism of the combination of Acori Tatarinowii Rhizoma and Curcumae Radix in the treatment of epilepsy was analyzed. All chemical constituents of Acori Tatarinowii Rhizoma and Curcumae Radix were retrieved by TCMSP,and their action targets were screened. Component target PPI network was constructed. Epilepsy-related genes were retrieved from PharmGkb database,and PPI networks of disease targets were drawn by Cytoscape software. Cytoscape software was used to merge the network,screen the core network,and further analyze the gene GO function and KEGG pathway enrichment,which was verified by experimental research. One hundred and five chemical constituents of Acori Tatarinowii Rhizoma and 222 chemical constituents of Curcumae Radix were retrieved. Nineteen compounds were selected as candidate compounds according to OB and DL values. Among them,4 chemical constituents of Acori Tatarinowii Rhizoma and 15 chemical constituents of Curcumae Radix were found. A total of 88 target proteins were retrieved by retrieving TCMSP data,and PPI network was constructed. Through PharmGkb database,29 epilepsy-related genes were retrieved and disease target network was established. Cytoscape software and plug-ins were used for network merging and core network screening,and 69 genes were screened out. Through GO function analysis and KEGG pathway analysis,the mechanism of anti-epilepsy is related to prolactin signaling pathway,HTLV-â infection signaling pathway,MAPK signaling pathway and herpes simplex infection signaling pathway. Further experimental verification showed that the serum prolactin level in epileptic rats was significantly increased. The neurons in hippocampal CA1 area degenerated,necrotized and lost 24 hours after epileptic seizure,and some neuron interstitial edema occurred. The possible mechanism of compatibility of Acori Tatarinowii Rhizoma and Curcumae Radix is related to serum prolactin level,MAPK signaling pathway,HTLV-â infection and herpes simplex infection. The analysis may be related to viral encephalitis caused by HTLV-â virus and herpes simplex infection,which damages nerve cells and causes seizures.
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Acorus/química , Curcuma/química , Medicamentos Herbarios Chinos/farmacología , Epilepsia/tratamiento farmacológico , Animales , Región CA1 Hipocampal/efectos de los fármacos , Región CA1 Hipocampal/patología , Hipocampo , Raíces de Plantas/química , Ratas , Rizoma/químicaRESUMEN
The aim of this study was to investigate whether uric acid (UA) might exert neuroprotection via activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and regulating neurotrophic factors in the cerebral cortices after transient focal cerebral ischemia/reperfusion (FCI/R) in rats. UA was intravenously injected through the tail vein (16 mg/kg) 30 min after the onset of reperfusion in rats subjected to middle cerebral artery occlusion for 2 h. Neurological deficit score was performed to analyze neurological function at 24 h after reperfusion. Terminal deoxynucleotidyl transferase-mediated dNTP nick end labeling (TUNEL) staining and hematoxylin and eosin (HE) staining were used to detect histological injury of the cerebral cortex. Malondialdehyde (MDA), the carbonyl groups, and 8-hydroxyl-2'-deoxyguanosine (8-OHdG) levels were employed to evaluate oxidative stress. Nrf2 and its downstream antioxidant protein, heme oxygenase- (HO-) 1,were detected by western blot. Nrf2 DNA-binding activity was observed using an ELISA-based measurement. Expressions of BDNF and NGF were analyzed by immunohistochemistry. Our results showed that UA treatment significantly suppressed FCI/R-induced oxidative stress, accompanied by attenuating neuronal damage, which subsequently decreased the infarct volume and neurological deficit. Further, the treatment of UA activated Nrf2 signaling pathway and upregulated BDNF and NGF expression levels. Interestingly, the aforementioned effects of UA were markedly inhibited by administration of brusatol, an inhibitor of Nrf2. Taken together, the antioxidant and neuroprotective effects afforded by UA treatment involved the modulation of Nrf2-mediated oxidative stress and regulation of BDNF and NGF expression levels. Thus, UA treatment could be of interest to prevent FCI/R injury.
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Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Infarto Cerebral/tratamiento farmacológico , Infarto Cerebral/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Ácido Úrico/uso terapéutico , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Western Blotting , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Ensayo de Inmunoadsorción Enzimática , Hemo-Oxigenasa 1/metabolismo , Inmunoquímica , Etiquetado Corte-Fin in Situ , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
Hypoxia promotes proliferation and differentiation of neural stem cells from embryonic day 12 rat brain tissue, but the concentration and time of hypoxic preconditioning are controversial. To address this, we cultured neural stem cells isolated from embryonic day 14 rat cerebral cortex in 5% and 10% oxygen in vitro. MTT assay, neurosphere number, and immunofluorescent staining found that 5% or 10% oxygen preconditioning for 72 hours improved neural stem cell viability and proliferation. With prolonged hypoxic duration (120 hours), the proportion of apoptotic cells increased. Thus, 5% oxygen preconditioning for 72 hours promotes neural stem cell proliferation and neuronal differentiation. Our findings indicate that the optimal concentration and duration of hypoxic preconditioning for promoting proliferation and differentiation of neural stem cells from the cerebral cortex are 5% oxygen for 72 hours.
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Mud crab reovirus (MCRV) is the causative agent of a severe disease in cultured mud crab (Scylla paramamosain), which has caused huge economic losses in China. MCRV is a double-stranded RNA virus with 12 genomic segments. In this paper, SDS-PAGE, mass spectrometry and Western blot analyses revealed that the VP12 protein encoded by S12 gene is a structural protein of MCRV. Immune electron microscopy assay indicated that MCRV VP12 is a component of MCRV outer shell capsid. Yeast two hybrid cDNA library of mud crab was constructed and mud crab voltage-dependent anion-selective channel (mcVDAC) was obtained by MCRV VP12 screening. The full length of mcVDAC was 1180 bp with an open reading frame (ORF) of 849 bp encoding a 282 amino acid protein. The mcVDAC had a constitutive expression pattern in different tissues of mud crab. The interaction between MCRV VP12 and mcVDAC was determined by co-immunoprecipitation assay. The results of this study have provided an insight on the mechanisms of MCRV infection and the interactions between the virus and mud crab.