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Reducing low-value care is a key measure to optimize service model for cancer patients and improve the quality of and value of care.We summarizes the conceptual connotation of low-value medical services for cancer patients,compares the relevant measurement indicators at home and abroad,explains the logic of low-value medical services use for cancer patients at the three levels of"individual-institution-system",and proposes strategies for reducing low-value medical services for cancer patients in five aspects:construction of service value framework,dissemination of evaluation results,connection of drug access mechanisms,moni-toring of cancer care services,and empowering shared decision-making.
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Objective:To investigate the regulatory effects of ring finger protein 43 (RNF43) on CD8 + T cell-mediated anti-tumor immune reaction in melanoma. Methods:RNF43 gene was over-expressed and knockdown in mouse melanoma cells line B16-OVA by lentivirus infection; In vivo proliferation of mouse melanoma cells line B16-OVA in the Lv-Ctrl-OE, Lv-RNF43-OE, Lv-Ctrl-KD and Lv-RNF43-KD groups was detected by subcutaneous tumorigenesis assay in mice, and the expression levels of CD8 + T cells perforin and interferon γ (IFN-γ) in tumor immune microenvironment of melanoma were detected by flow cytometry; The expression levels of β-catenin and programmed death-ligand 1 (PD-L1) mRNA in cells were detected by quantitative real-time PCR assay; The effect of RNF43 on the transcriptional regulation of PD-L1 was detected by dual-luciferase reporter gene assay. Results:Stable RNF43 over-expressing and RNF43 knockdown mouse melanoma cells lines Lv-RNF43-OE and Lv-RNF43-KD were successfully constructed. The results of subcutaneous tumorigenesis experiment in mice showed that the tumor mass of the Lv-RNF43-OE group was (0.08±0.06) g, which was significantly smaller than that of the Lv-Ctrl-OE group [ (1.04±0.52) g], with a statistically significant difference ( t=3.71, P=0.032) ; The tumor mass of Lv-RNF43-KD group was (1.94±0.29) g, with no statistically significant difference ( t=-1.70, P=0.164) compared with that of the Lv-Ctrl-KD group (1.15±0.74) g. The flow cytometry results showed that the fluorescence intensity of CD8 + T cell perforin in the Lv-RNF43-OE group was 9 034 ± 2 628, which was significantly higher than that in the Lv-Ctrl-OE group (3 847 ±1 637), with a statistically significant difference ( t=-3.35, P=0.015) ; The fluorescence intensity of CD8 + T cell perforin in the Lv-RNF43-KD group was 966±247, which was significantly lower than that in the Lv-Ctrl-KD group (2 226±646), with a statistically significant difference ( t=3.16, P=0.034) ; The fluorescence intensity of IFN-γ of CD8 + T cell in the Lv-RNF43-OE group was 2 422±429, which was significantly higher than that of 1 688±324 in the Lv-Ctrl-OE group, with a statistically significant difference ( t=-2.73, P=0.034) ; The fluorescence intensity of IFN-γ of CD8 + T cell in the Lv-RNF43-KD group was 614 (454, 863), with a statistically significant difference ( Z=-1.96, P=0.050) compared with 1 159 (1 152, 2 068) in the Lv-Ctrl-KD group. The results of quantitative real-time PCR showed that the relative expression level of β-catenin mRNA in the Lv-RNF43-OE group was 0.67±0.16, which was significantly lower than that of 1.00±0.11 in the Lv-Ctrl-OE group, with a statistically significant difference ( t=2.98, P=0.041) ; The relative expression level of PD-L1 mRNA in the Lv-RNF43-OE group was 0.32±0.09, which was significantly lower than that of 1.00±0.09 in the Lv-Ctrl-OE group, with a statistically significant difference ( t=9.13, P=0.001). The results of the dual-luciferase reporter gene assay showed that the PD-L1 promoter luciferase activity in the pCMV6-NC, RNF43, RNF43+β-catenin and β-catenin groups were 1.00±0.00, 0.84±0.00, 1.49±0.00 and 1.57±0.03 ( F=2 218.33, P<0.001). Further pairwise comparison showed that compared with the pCMV6-NC group, PD-L1 promoter luciferase activity was significantly lower in the RNF43 group ( P<0.001) and significantly higher in the RNF43+β-catenin and β-catenin groups ( P<0.001; P=0.003) ; compared with the RNF43 group, PD-L1 promoter luciferase activity was significantly higher in the RNF43+β-catenin group ( P<0.001) . Conclusion:RNF43 may reduce the expression of PD-L1 mRNA in melanoma by inhibiting the expression of β-catenin and promote CD8 + T cell-mediated anti-tumor immune reaction.
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Objective:In order to put forward relevant measures and suggestions to improve the quality of the Investigator-Initiated Trials of oncology in medical institutions.Methods:Through literature research, comparative study, combined with the implementation and management of investigator initiated trials, the current status and challenges of the administration of these trials were analyzed.Results:Investigator-Initiated Trials of oncology become increasingly important. However, its quality is poor compared with Industry-Sponsored Trials due to insufficient funds and lack of effective supervision. Besides, four main challenges as follows were identified: lack of clinical research professionals, the quality concerns of ethical review in some institutions, insufficient funding for clinical research, and imperfect quality management system.Conclusions:Based on the actual needs of IITs of oncology, medical institutions should strengthen the talent cultivation, establish electronic information management platform, increase project support, strengthen scientific research supervision and deepen the awareness of risk prevention to improve the quality of investigator initiated trials.
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Objective:To compare the changes of morphology of pharynx in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and healthy individuals during oral or nasal breathing, and explore the relevant influencing factors. Methods:Twenty-nine adult patients with OSAHS and 20 non-snoring controls underwent MRI to obtain upper airway structural measurements while the subjects were awake and during mouth breathing with a nasal clip.The following were analyzed. ①The changes of upper airway structure of oral and nasal respiration in non-snoring control/OSAHS patients were observed; ②The differences and influencing factors of upper airway structure changes between OSAHS patients and controls were compared during breathing. Results:The control group consisted of 15 males and 5 females, with an apnea-hypopnea index (AHI)<5 events/h, while the OSAHS group comprised 26 males and 3 females with an AHI of 40.4±23.1 events/h and the mean lowest arterial oxygen saturation (LSaO2) was 79.5% ±10.0%. In the both groups, the vertical distance between the mandible and the posterior pharyngeal wall decreased (P<0.05); The long axis of tongue body decreased (P<0.05), and the contact area between tongue and palate decreased. There was no significant change in the total volume of the retropalatine(RP) and retroglossal(RG) airway in the control group (P>0.05). However, the minimum cross-sectional area and volume of the RP airway in OSAHS decreased (P<0.001). The lateral diameters of uvula plane in OSAHS decreased during mouth breathing, which was contrary to the trend in the control group (P=0.017). The AHI of patients was positively correlated with the reduction of the volume of the RP airway during oral breathing (P=0.001); The reduction of the distance between the mandible and the posterior pharyngeal wall was positively correlated with the length of the airway (P<0.001). Conclusion:Mouth breathing leads to the shortening of the long axis of the tongue, the reduction of the contact area between the soft palate and the tongue, vertical distance between the mandible and the posterior pharyngeal wall, and the cross-sectional area of the epiglottis plane. These changes vary between OSAHS patients and controls. During mouth breathing, the diameters, areas and volumes of the RP area decreased, and were more significant in severe cases.
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Masculino , Adulto , Femenino , Humanos , Respiración por la Boca , Apnea Obstructiva del Sueño/cirugía , Faringe/cirugía , Paladar Blando , Úvula/cirugía , SíndromeRESUMEN
Objective:To analyze the current situation of Investigator-Initiated Trials in medical and health institutions in Shandong Province, the problems in the process of conducting clinical research, and put forward proposals for the establishment of a clinical research management system with effective supervision, sound systems and supporting services, taking into account the progress of the projects since the pilot work was carried out.Methods:A questionnaire was created, an online survey was conducted, a database was set up, a status analysis was conducted and a post-launch analysis of the progress of the pilot was carried out using the National Medical Research Registry Information System, culminating in recommendations using the literature summary method and empirical analysis.Results:Statistical analysis of the questionnaire found that 29.39% of the institutions have a dedicated clinical research management department, and 75.97% of the institutions have a management approach. 25.52%, 40.30%, and 43.07% of institutions established biobanks, clinical research centers, and follow-up centers. There was a statistically significant difference in the establishment of clinical research centers, biobanks, and follow-up centers in secondary and tertiary medical institutions ( P<0.05). The number of general clinical research projects filed, the number of submissions and the number of ethics committees filed in the filing system have all increased significantly after the pilot work, with growth percentages of 126%, 141% and 62% respectively. Conclusions:Shandong Province clinical research pilot work has begun to bear fruit, the current clinical research project still exists in the lack of special funding support, perfect service platform and system support and training system to be improved and other issues.
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As a complex reaction, biological consequences of the Maillard reaction (MR) on dietary proteins need to be deciphered. Despite previous studies on the structural and antigenic properties of ovalbumin (OVA) by MR, associated changes induced by specific MR intermediates and their downstream products are largely unknown. This study focused on the impacts of glycation by α-dicarbonyl compounds (α-DCs), intermediates of MR and precursors of advanced glycation end-products (AGEs), on the structural and IgE-binding properties of ovalbumin (OVA) under simulated heating. Methylglyoxal (MGO), glyoxal (GO), and butanedione (BU) were selected as typical α-DCs to generate glycated OVA with different AGE-modifications (AGE-Ms). The results showed that reactions between OVA and α-DCs generated OVA-AGE with various degrees of modification and conformational unfolding, and the reactivity of α-DCs followed the order GO > MGO > BU. Depending on the precursor type, the levels of 10 specific AGEs were verified, and the amounts of total AGEs increased with heating temperature and α-DC dosage. Compared to native OVA, glycated OVA showed reduced IgE-binding levels but with sRAGE-binding ligands, the extent of which was associated with the contents of total AGEs and Nε-carboxymethyllysine, and changes in certain protein conformational structures. High-resolution mass spectrometry further identified different AGE-Ms on the Lys and Arg residues of OVA, confirming variations in the glycation sites and their associations with the immunoreactive epitopes of OVA under different conditions.
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Proteínas en la Dieta/química , Glioxal , Calor , Inmunoglobulina E , Ovalbúmina/química , Productos Finales de Glicación Avanzada , PiruvaldehídoRESUMEN
Cervical cancer active targeting nano drug delivery system delivers drug-loaded nanoparticles to cancer cells in a targeted way through specific ligand-receptor interaction, which has the advantages of reducing adverse drug reactions and improving drug efficacy. It is of great significance to understand the active targeting nano drug delivery system for cervical cancer to explore new carriers, drugs and targets.
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The SARS-CoV-2 pandemic poses an unprecedented public health crisis. Accumulating evidences suggest that SARS-CoV-2 infection causes dysregulation of immune system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced by SARS-CoV-2 in animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could reduce inflammatory response and rescue the pneumonia with substantial reduction of viral titers in SASR-CoV-2 infected animals. Remarkably, Paquinimod treatment resulted in 100% survival of mice in a lethal model of mouse coronavirus (MHV) infection. A novel group of neutrophils that contributed to the uncontrolled inflammation and onset of COVID-19 were dramatically induced by coronavirus infections. Paquinimod treatment could reduce these neutrophils and regain antiviral responses, unveiling key roles of S100A8/A9 and noncanonical neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention.
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As a neurological disorder, epilepsy has affected over 65 million people all over the world because of the unforeseeable seizures it might cause. However, in-depth understandings of the pathogenesis of epilepsy and effective treatments for the disease are still lacked. Recent discoveries suggest that autophagy, as an endogenous self-cleansing pathway in mammals, might be involved in the onset of epilepsy. Our study assumes that a non-histone DNA binding protein, high mobility group box-1 (HMGB1), formerly considered as a crucial inflammatory factor, may mediate the autophagy of neurons in epileptic mouse brain. To verify this hypothesis, pilocarpine induced epilepsy mouse model was constructed. The mice were treated with HMGB1 antibody for 4 weeks after the initial epileptic seizure. Behavioral test results suggested a recovery of learning ability and memory in epileptic mice when treated with HMGB1 antibody. Pathological changes in hippocampus were inspected under microscopes and hippocampus damages caused by seizures in mouse with epilepsy such as increased intracellular space were alleviated by HMGB1 antibody treatment. Moreover, the expressions of the proteins involved in autophagy pathways were detected by immunofluorescence staining and western blot. microtubule-associated protein 1A/1B-light chain 3 (LC3), Beclin 1, autophagy protein-5 (ATG5), and ATG7 levels were significantly decreased by HMGB1 antibody while the level of p62 was increased. TdT-mediated dUTP Nick-End Labeling (TUNEL) illustrated that cell apoptosis induced by seizures in hippocampus was mitigated by HMGB1 antibody. In conclusion, we propose that HMGB1 may induce increased autophagy in epilepsy mouse model.
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Anticuerpos/farmacología , Autofagia/efectos de los fármacos , Epilepsia/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Epilepsia/inducido químicamente , Proteína HMGB1/efectos de los fármacos , Proteína HMGB1/metabolismo , Ratones , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Pilocarpina/farmacología , Convulsiones/tratamiento farmacológico , Convulsiones/metabolismoRESUMEN
Objective@#To explore the clinical and radiological features of myelin oligodendrocyte glycoprotein (MOG) antibody associated disease.@*Methods@#The clinical data of 22 MOG antibody associated disease cases treated in the Department of Neurology, Qilu Hospital of Shandong University from January 2017 to June 2019 were retrospectively analyzed. The clinical data of MOG antibody associated disease were summarized, including clinical and imaging features.@*Results@#Of the 22 included patients with MOG antibody associated disease, the average age was 38.5 years, 13 were male and nine were female. Among them, 11 cases manifested as aquaporin-4 (AQP4)-negative neuromyelitis optica spectrum disorder (NMOSD), four cases optic neuritis, two cases transverse myelitis, one case acute disseminated encephalomyelitis (ADEM), two cases cortical encephalitis and two cases vestibular neuronitis. Magnetic resonance imaging (MRI) results showed that multiple anatomical areas were involved. Among the nine patients with optic nerve involvement, five patients had longitudinally extensive optic nerve lesions, which were longitudinally enhanced. In eight patients, MRI lesions in the spinal cord showed mostly long or short segments involvement, involving 2-5 spinal cord segments. Five cases involved the cervical spinal cord, six cases involved the thoracic spinal cord, and one case involved the lumbar spinal cord. Brain MRI abnormalities were found in 13 cases and the lesions were mostly patchy and point-shaped. MRI lesions demonstrated T2 hyperintensity and some of them could be strengthened, which may involve the basal ganglia, thalamus, radiographic crown, frontal temporal lobe, brain stem and other parts. Among them, 16 patients were sensitive to high-dose intravenous/oral methylprednisolone in the acute phase. Seven patients had recurrence after two months to two years of follow-up.@*Conclusions@#MOG antibody associated disease include multiple manifestations. Among them, AQP4-negative NMOSD is the most common form. The clinical manifestations of patients showed diversity. Imaging is characterized by multiple parts involvement such as optic nerve, spinal cord, and brain. Most patients are sensitive to high-dose intravenous/oral methylprednisolone, and have a good prognosis in the acute phase, but some patients may relapse.
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Leishmaniasis is a prevalent cause of death and animal morbidity in underdeveloped countries of endemic area. However, there is few vaccine and effective drugs. Antimicrobial peptides are involved in the innate immune response in many organisms and are being developed as novel drugs against parasitic infections. In the present study, we synthesized a 5-amino acid peptide REDLK, which mutated the C-terminus of Pseudomonas exotoxin, to identify its effect on the Leishmania tarentolae. Promastigotes were incubated with different concentration of REDLK peptide, and the viability of parasite was assessed using MTT and Trypan blue dye. Morphologic damage of Leishmania was analyzed by light and electron microscopy. Cellular apoptosis was observed using the annexin V-FITC/PI apoptosis detection kit, mitochondrial membrane potential assay kit and flow cytometry. Our results showed that Leishmania tarentolae was susceptible to REDLK in a dose-dependent manner, disrupt the surface membrane integrity and caused parasite apoptosis. In our study, we demonstrated the leishmanicidal activity of an antimicrobial peptide REDLK from Pseudomonas aeruginosa against Leishmania tarentolae in vitro and present a foundation for further research of anti-leishmanial drugs.
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Krüppel-like factors (KLFs) play extremely important roles in genesis and development of tumors. Simultaneously, KLFs have been proven to affect the proliferation, differentiation and migration of hepatocellular carcinoma cells. Nine members in the KLFs family (KLF2, KLF4, KLF5, KLF6, KLF8, KLF9, KLF10, KLF14 and KLF17) are involved in the occurrence and development of hepatocellular carcinoma in various ways as an oncogene and tumor suppressor gene. Therefore, the KLFs family will hopefully become biological therapeutic targets for hepatocellular carcinoma.
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Objective:To investigate the effects of long-chain non coding RNA (lncRNA) XIST on the proliferation and migration of pancreatic cancer PANC1 cells, and clarify the targeting relationship between lncRNA XIST and miR-101/enhancer of zeste homologz(EZH2).Methods:Ninety cases of pancreatic cancer surgically resected and pathologically confirmed in the first hospital of Jiaxing city from July 2010 to September 2018 and its corresponding paracarcinoma normal tissue were collected. PANC1 cells were divided into sh-XIST group, SH control group, MiR control group and miR-101 group. The expression of LncRNA XIST and miR-101 in pancreatic cancer tissue and PANC1 cells in each group were detected by fluorescence quantitative PCR. The relationship between the expression of LncRNA XIST and miR-101 and the clinicopathological parameters of tumor was analyzed. The proliferation and migration ability of PANC1 cells in each group were analyzed by CCK8 method and transwell chamber test. The EZH2 expression level of PANC1 cells in each group were analyzed by western blot. PANC1 cells in each group was inoculated into BALB/C nude mice with a cell density of 3×10 6 cells/100 μl and the tumor volume was measured. The relationship between LncRNA XIST and its miR-101 and targeting gene EZH2 were analyzed by bioinformatics and double luciferase reporter genes. Results:Compared with the paracancerous tissues, the level of LncRNA XIST in pancreatic cancer tissue was significantly increased 2.89±0.42 vs (1.12±0.22, P<0.05), and the level of miR-101 was significantly decreased 0.32±0.12 vs (1.25±0.22, P<0.05), and the differences were statistically significant ( P<0.05). LncRNA XIST expression in pancreatic cancer tissue was obviously increased along with higher differentiation degree, advanced TNM stage and lymph node metastasis, while miR-101 was greatly decreased. Compared with the cells in the sh-control group, the expression level of LncRNA XIST in the sh-XIST group was significantly decreased (0.34±0.18 vs 1.21±0.27). Compared with miR-control cells, the level of miR-101 cells in miR-101 group significantly increased (2.94±0.31 vs 1.54±0.29 ), and the differences were statistically significant ( P<0.05). After 72 h cell culture, the light absorption value at 450 nm in sh-control group, sh-XIST group, miR-control group and miR-101 group was 1.98±0.24, 1.21±0.20, 1.87±0.21 and 1.11±0.17; the number of transmembrane cells were (74.25±6.79 ), (29.11±5.17), (61.27±5.19) and (20.47±4.58)per 200 times visual field; the cell proliferation activity and migration ability in sh-XIST group were significantly decreased than sh-control group, miR-101 group and miR-control group and the xenograft tumor grew obviously slowly, all the differences were statistically significant (all P<0.05). Conclusions:LncRNA XIST can target miR-101/EZH2, regulating the proliferation and migration of pancreatic cancer cells, which promotes the occurrence and development of pancreatic cancer.
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Objective To explore the clinical and radiological features of myelin oligodendrocyte glycoprotein (MOG) antibody associated disease.Methods The clinical data of 22 MOG antibody associated disease cases treated in the Department of Neurology,Qilu Hospital of Shandong University from January 2017 to June 2019 were retrospectively analyzed.The clinical data of MOG antibody associated disease were summarized,including clinical and imaging features.Results Of the 22 included patients with MOG antibody associated disease,the average age was 38.5 years,13 were male and nine were female.Among them,11 cases manifested as aquaporin-4 (AQP4)-negative neuromyelitis optica spectrum disorder (NMOSD),four cases optic neuritis,two cases transverse myelitis,one case acute disseminated encephalomyelitis (ADEM),two cases cortical encephalitis and two cases vestibular neuronitis.Magnetic resonance imaging (MRI) results showed that multiple anatomical areas were involved.Among the nine patients with optic nerve involvement,five patients had longitudinally extensive optic nerve lesions,which were longitudinally enhanced.In eight patients,MRI lesions in the spinal cord showed mostly long or short segments involvement,involving 2-5 spinal cord segments.Five cases involved the cervical spinal cord,six cases involved the thoracic spinal cord,and one case involved the lumbar spinal cord.Brain MRI abnormalities were found in 13 cases and the lesions were mostly patchy and point-shaped.MRI lesions demonstrated T2 hyperintensity and some of them could be strengthened,which may involve the basal ganglia,thalamus,radiographic crown,frontal temporal lobe,brain stem and other parts.Among them,16 patients were sensitive to high-dose intravenous/oral methylprednisolone in the acute phase.Seven patients had recurrence after two months to two years of follow-up.Conclusions MOG antibody associated disease include multiple manifestations.Among them,AQP4-negative NMOSD is the most common form.The clinical manifestations of patients showed diversity.Imaging is characterized by multiple parts involvement such as optic nerve,spinal cord,and brain.Most patients are sensitive to high-dose intravenous/oral methylprednisolone,and have a good prognosis in the acute phase,but some patients may relapse.
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Objective:To investigate the clinical features, imaging features, gene diagnosis, treatment and prognosis of autosomal dominant lateral temporal epilepsy (ADLTE) with heterozygous RELN mutation.Methods:Clinical data of an ADLTE family caused by a heterozygous mutation in the RELN gene diagnosed in September 2019 at Qilu Hospital of Shandong University were collected. The clinical characteristics of ADLTE were analyzed, and literature review was conducted.Results:The male proband, 22 years old, was admitted with the clinical manifestations including seizures begun at temporal lobe, which specifically manifested as a sudden emergence of binaural hum, lasting for more than 10 seconds, and the symptoms can self-recover quickly. Half a month later, generalized tonic-clonic seizures attacked subsequently after a similar auditory aura. There were no abnormal findings in interictal electroencephalography (EEG) and magnetic resonance imaging (MRI). Following the family history, his father had similar auditory symptoms around the age of 20, and occasional secondarily generalized tonic-clonic seizures appeared. Antiepileptic drug can control better. The whole exome sequencing of three people in the family revealed that both the proband and his father had NM-005045: c.6068T>C heterozygous mutation in the RELN gene.Conclusions:ADLTE mostly occurs in juveniles or early adulthood. The main clinical manifestations are focal seizures with auditory auras, which can be followed by generalized tonic-clonic seizures. There are no abnormal findings in the interictal EEG and MRI. ADLTE is sensitive to drug treatment and has good clinical prognosis. The study identified a novel heterozygous mutation NM-005045: c.6068T>C in RELN gene, which is responsible for the development of ADLTE.
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Objective:To explore how to enhance the strength of science and technology of research-oriented hospital using goal management, thereby effectively promoting the construction and development of research hospitals.Methods:This paper studies the goal management measures and their effectiveness through data analysis, analyzes the problems of scientific research, goal management measures and changes in scientific research before and after the implementation measures over the years.Results:The goal management significantly enhances the scientific and technological strength. Total amount of research funding kept increasing year by year. Goal accountability management effectively improve the participation in individual scientific research activities. The implementation of high-quality papers goal management has a significant role in promoting the researchers to publish their achievements in domestic journals with international influence.Conclusions:Goal management plays an important role in the improvement of the scientific and technological strength of the hospital, which can effectively promote the construction and development of the research-oriented hospitals connotation. Goal management can serve as a powerful grasper for the research-oriented hospital to improve the scientific research capacity.
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Trichomonas vaginalis is responsible for the prevalence of trichomoniasis, which may be one of the most epidemic nonviral sexually transmitted pathogens. Extracellular traps (ET) are a unique form of innate immunity against infection; they bind to and kill microorganisms. However, the effect of T. vaginalis on ET release in the human monocytic cell line THP-1 remains unclear. In the present study, the morphology of ET derived from THP-1 in response to T. vaginalis was observed by scanning electron microscopy (SEM). The results demonstrated ET entangling T. vaginalis. Then, the colocalization of histone (H3) and myeloperoxidase (MPO) with DNA was observed via fluorescence confocal microscopy. Colocalization revealed the classic characteristics of DNA decorated with H3 and MPO. T. vaginalis significantly increased reactive oxygen species (ROS) and THP-1-derived ET. In addition, we measured the levels of lactic dehydrogenase (LDH) and the phosphorylation of the P38 and ERK1/2 MAPK signaling pathways. The results indicated that the formation of ET induced by T. vaginalis was related to phosphorylation of the P38 and ERK1/2 MAPK signaling pathways but not to LDH levels. These data confirmed the phenomenon of THP-1-derived ET being triggered by T. vaginalis in vitro; this process may play a pivotal role in innate immunity during defense against T. vaginalis infection.
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Trampas Extracelulares/inmunología , Monocitos/inmunología , Tricomoniasis/inmunología , Trichomonas vaginalis/fisiología , Línea Celular , Trampas Extracelulares/parasitología , Humanos , Inmunidad Innata , Sistema de Señalización de MAP Quinasas , Peroxidasa/inmunología , Especies Reactivas de Oxígeno/inmunología , Tricomoniasis/parasitologíaRESUMEN
OBJECTIVE: To explore the role of clinical pharmacist in individualized treatment for osteosarcoma patients with periprosthetic joint infection (PJI). METHODS: An osteosarcoma patient was admitted to our hospital and then suffered from PJI after operation. Clinical pharmacist adjusted the initial anti-infection plan and carried out pharmaceutical care according to the results of patients’ etiology and drug sensitivity. According to the PK-PD principle, combined with the therapeutic drug monitoring (TDM), the dose of antibiotics was adjusted. With the occurrence of ADR, the antibiotic therapeutic regimen was adjusted again. RESULTS: The patient was administrated cefotiam for empiric therapy initially after the diagnosis of PJI. After obtaining the results of etiology and drug sensitivity, the clinical pharmacist suggested that vancomycin sensitive to penicillin-resistant Staphylococcus epidermidis should be used for targeted anti-infection treatment. After adjusting the dosage according to the steady-state valley concentration, the patient had slight liver function damage, accompanied with chest tightness and shortness of breath. After analysis, the clinical pharmacist considered the adverse drug reactions related to vancomycin, and again suggested that the patient should be treated with teicoplanin. After the doctor adopted the treatment plan recommended by the clinical pharmacist, PJI of the patient was effectively controlled, and the adverse reaction symptoms disappeared. The patient was effectively cured for PJI and discharged eventually. During the treatment period, the clinical pharmacist also carried out medication education for the drugs used by the patient. CONCLUSIONS: Clinical pharmacist should master the principle of antibiotic drug PK-PD theory and evaluate the clinical efficacy and safety of anti-infective drugs dynamically based on the guidance of TDM, so as to develop individualized anti-infection therapeutic regimen for osteosarcoma patient with PJI, improve the effect of clinical treatment and guarantee the safety of drug use.
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The present study was performed to investigate the seroprevalence and risk factors for Dirofilaria immitis infection in cats from Liaoning province, northeastern China. From October 2014 to September 2016, sera of 651 cats, including 364 domestic cats and 287 feral cats (332 females and 319 males) were assessed. They were tested for the presence of D. immitis antigen using SNAP Heartworm RT test kit. In this population, the average prevalence was 4.5%. Age and rearing conditions (feral or domestic) were found to be associated with the prevalence of D. immitis. The prevalence was significantly higher in feral cats compared with domestic cats (8.4% vs 1.4%, P 0.05), but older cats (≥3 years old) showed a statistically higher prevalence compared with younger cats ( 0.05), all these results suggest that outdoor exposure time may be one of the most important factors for D. immitis prevalence in cats. Results reveal that D. immitis are prevalence in domestic and feral cats in northeastern China, which indicates that appropriate preventive measures should be taken to decrease the incidence of feline heartworm disease in Liaoning province, northeastern China.
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Animales , Gatos , Femenino , Humanos , Masculino , China , Dirofilaria immitis , Dirofilaria , Dirofilariasis , Incidencia , Prevalencia , Factores de Riesgo , Estudios SeroepidemiológicosRESUMEN
Objective:To investigate the expression change of voltage-gated calcium channels(VGCC) in the facial nucleus motoneurons of adult rats after facial nerve injury.Methods:The facial motor nucleus was localized by retrograde labeling with a fluorescent dye,Dil,and identified by Nissl staining.The facial nerve injury model was established by amputation of the main trunk of left facial nerve.Exposure of the right facial nerve without nerve transection was used as the control.Rats were sacrificed at 3,7,14 and 28 days after injury respectively(n =10),the brainstem containing facial nucleus were collected,the expression of P/Q,N,L,R-type calcium channel α1A,α1B,α1C and α1E subunits was examined by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR).Results:Immunohistochemistry results show that whereas α1A,α1E subunits levels did not vary compared with control group 3,7,14,28 days after injury(P >0.05),α1B and α1C subunits immunoreactivity decreased in the motoneurons after injury,a sharp decrease was detected at 14 days after injury(P < 0.01),thereafter returned to the control level at 28 days after axotomy(P >0.05).The expression of α1B and α1C mRNA was down-regulated,especially 14 days after the injury(P <0.01),and then recovered to normal level at 28 days (P > 0.05).In addition,there was no significant difference of α1A and α1E subunits and their correspoding mRNA between operated group and control group at all time points(P > 0.05).Conclusion:VGCC is involved in facial nerve injury and down-regulation of N-type and L-type calcium channels may be one of the role.