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Gut-derived IgA + plasma cells are the key to intestinal mucosal immunity.The intestinal flora and diet regulate the production of gut-derived IgA + plasma cells, which not only play an immune role in the intestinal mucosa, but also migrate to tissues or organs outside the intestine to regulate immune and inflammatory reactions by relying on the production of IgA antibodies or the secretion of cytokines and other non-antibody effects, and act as a protective or pathogenic factor in various diseases.The pathogenic effect of intestinal mucosal immune imbalance in IgA nephropathy (IgAN) has been a concern.IgA + plasma cells increase in intestinal lamina propria of high serum IgA mice with the increase of abnormally glycosylated IgA1.The long-lived plasma cells increase, and interleukin-6 is inhibited in IgAN patients.However, it remains unclear whether gut-derived IgA + plasma cells migrate to kidneys to promote disease progression.This article reviews the relevant research progress on the immunopathologic effects and mechanisms of gut-derived IgA + plasma cells in the intestinal mucosa of IgAN.
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Iron (Fe) isotope geochemistry in rivers is crucial for comprehending surficial weathering and geochemical cycle mechanisms. Lancang River is an important channel for material transport between the Tibet Plateau and the oceans of Southeast Asia. In this study, Fe contents and Fe isotope (δ56Fe) compositions in the suspended particulate matter (SPM) are investigated to discuss the rock weathering processes in the Lancang River Basin. The δ56Fe values of SPM range from 0.01 to 0.21 , with an average of 0.12 , close to the average δ56Fe value of continental crust (0.07 ). The results indicate that the fractionation of Fe isotopes is limited caused of weathering process in the Lancang River Basin. Due to the interception of dense dams in the middle and lower reaches (1000-2000 m), the dissolved oxygen (DO) values of river water and the Fe contents of SPM remain at a relatively highest level, whereas the δ56Fe values in SPM are more positive. The positive correlation between chemical index of alteration (CIA) values and the Fe contents suggest that Fe in the tributary SPM may represent the weathering degree of their source areas. The increase of DO in the mainstream water may promote the decomposition and dissolution of SPM, thus increasing the contents of Fe in the remaining SPM, and causing slight positive fractionation of Fe in SPM. This study presents a complete analysis of the Fe isotope's potential utility in identifying the source of SPM. In addition, the Fe isotope may represent some alterations encountered by SPM throughout the runoff process.
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The application of artificial intelligence (AI) has been considered a revolutionary change in drug discovery and development. In 2020, the AlphaFold computer program predicted protein structures for the whole human genome, which has been considered a remarkable breakthrough in both AI applications and structural biology. Despite the varying confidence levels, these predicted structures could still significantly contribute to structure-based drug design of novel targets, especially the ones with no or limited structural information. In this work, we successfully applied AlphaFold to our end-to-end AI-powered drug discovery engines, including a biocomputational platform PandaOmics and a generative chemistry platform Chemistry42. A novel hit molecule against a novel target without an experimental structure was identified, starting from target selection towards hit identification, in a cost- and time-efficient manner. PandaOmics provided the protein of interest for the treatment of hepatocellular carcinoma (HCC) and Chemistry42 generated the molecules based on the structure predicted by AlphaFold, and the selected molecules were synthesized and tested in biological assays. Through this approach, we identified a small molecule hit compound for cyclin-dependent kinase 20 (CDK20) with a binding constant Kd value of 9.2 ± 0.5 µM (n = 3) within 30 days from target selection and after only synthesizing 7 compounds. Based on the available data, a second round of AI-powered compound generation was conducted and through this, a more potent hit molecule, ISM042-2-048, was discovered with an average Kd value of 566.7 ± 256.2 nM (n = 3). Compound ISM042-2-048 also showed good CDK20 inhibitory activity with an IC50 value of 33.4 ± 22.6 nM (n = 3). In addition, ISM042-2-048 demonstrated selective anti-proliferation activity in an HCC cell line with CDK20 overexpression, Huh7, with an IC50 of 208.7 ± 3.3 nM, compared to a counter screen cell line HEK293 (IC50 = 1706.7 ± 670.0 nM). This work is the first demonstration of applying AlphaFold to the hit identification process in drug discovery.
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Ketogenic diet (KD) has been applied to the treatment of epilepsy for the last century, although it has been underestimated due to the complicated preparation for beginners and the emergence of antiepileptic drugs.Due to the limitations of the mechanism of drug treatment of epilepsy, and the pathogenesis of epilepsy is complex, the incidence of drug-resistant epilepsy has not improved with the development of drugs over the years.KD plays an anti-epileptic and neuroprotective role through a variety of mechanisms, which is also effective to refractory epilepsy.As a result, KD has been emphasized again.Classical KD has high fat content and complicated operation.When the training is not fine enough, many patients cannot understand and qualify the operation.To overcome the disadvantages of the conventional KD, a modified KD has been developed that is closer to a normal diet structure and has a good tolerance, namely the low glycemic index treatment (LGIT). LGIT is featured by a slightly higher intake of carbohydrates, simplified meal preparation, improved taste and tolerance.This review aims to describe the mechanism, clinical outcomes and indications of LGIT in children with refractory epilepsy.
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ObjectiveTo screen the preparation technology of Baoyuan chewable tablets and to preliminarily elucidate its anti-fatigue effect and mechanism. MethodTaking encapsulation rate of volatile oil, extract rate and extraction rate of active ingredients as indexes, single factor test and orthogonal test were used to optimize the volatile oil inclusion, aqueous decoction and formulation molding processes of Baoyuan chewable tablets. ICR rats were randomly divided into the blank group, model group, Gaoshan Hongjingtian oral liquids group(6.01 mL·kg-1) and and Baoyuan chewable tablets low, medium, and high dose groups(2.1, 4.2, 8.4 g·kg-1), 8 mice in each group, and were administered by gastric gavage at the corresponding dose once a day, the blank and model groups were given equal volume of saline for 15 d. After the last administration for 30 min, the mice were loaded with 5% of the body mass of lead at the tail and swam until exhaustion to establish the fatigue model, and the weighted swimming time of the mice in each group was recorded, meanwhile, the muscle tissues of the mice were sliced, stained by hematoxylin-eosin(HE) and subjected to pathological observation, and the levels of blood urea nitrogen(BUN), lactic acid(LA), liver glycogen(LG), activities of lactate dehydrogenase(LDH) and creatine kinase(CK) in the serum were determined. ResultThe optimal inclusion process of cinnamon oil in Baoyuan chewable tablets was 10∶1 for β-cyclodextrin-volatile oil, and inclusion at 50 ℃ for 2 h with saturated aqueous solution method. The optimal water extraction process was to extract twice, adding 10 times of water to extract for 50 min for the first time, and adding 9 times of water to extract for 40 min for the second time. The ratio of the extract of Baoyuan chewable tablets with microcrystalline cellulose, maltodextrin, mannitol, citric acid, magnesium stearate was 63∶13∶8∶17∶17∶1∶1, the tablets were pressed by wet granulation, the each tablet weight was 1.2 g, and the hardness was 60-80 N. Compared with the model group, Baoyuan chewable tablets low, medium, and high dose groups could significantly prolong the exhaustion time of mice in weight bearing swimming(P<0.05, P<0.01), and improve the exercise endurance of the body, and the results of HE staining showed that all dose groups of Baoyuan chewable tablets could significantly improve the muscle tissue damage caused by exercise, significantly reduce the levels of BUN, LA and the activities of LDH and CK in serum(P<0.01), and significantly increase the content of LG(P<0.05, P<0.01). ConclusionThe optimized preparation process of Baoyuan chewable tablets is stable and feasible, and the preparation can improve exercise endurance by increasing the LG level in liver tissue, and relieve muscle soreness by accelerating the removal of LA from the body, and reduce CK and LDH activities to exert anti-fatigue effects.
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Objective: To understand the epidemiological characteristics of tick-borne infectious diseases (TBID) and the risk factors of severe illness and death in Hubei Province from 2016 to 2021. Methods: Based on the incidence data of fever with thrombocytopenia syndrome (SFTS), tsutsugamushi disease, typhus and other TBID reported during 2016-2021, the epidemiological analysis was conducted. Field investigation results of TBID in areas with high incidence in 2021, logistic regression analysis of population characteristics, epidemiological history and other factors were used to explore the risk factors of severe and fatal cases. In the field vector investigation, free ticks and surface ticks of the host animals in the cases' home and surrounding grassland were monitored and detected. Results: A total of 3 826 TBID cases were reported in Hubei from 2016 to 2021, of which 71.30% (2 728/3 826) were SFTS, 13.04% (499/3 826) were tsutsugamushi disease and 15.66% (599/3 826) were typhus. A total of 44 cases died in 6 years; the fatality rate was 1.15% (44/3 826). In the peak seasons of incidence from May to July, the cases in people engaged in agriculture related work accounted for 84.61% (3 237/3 826). The incidence rate in women was higher than that in men, and the cases aged ≥50 years accounted for 81.02% of the total (3 100/3 826), and the incidence rate increased with age (P<0.001). The TBID cases were distributed in 86 counties and districts in 16 prefectures (municipality). The incidence rates of different areas had significant differences (P<0.05), and there was a certain spatial-temporal clustering and expasion. Bovis microplus and Haemaphysalis longicornis were captured in the field, and the positive rates in host animals and grassland ticks were 10.94% (7/64) and 40.00% (2/5), respectively. Univariate logistic regression analysis results showed that age ≥50 years and leukocyte <2.0×109/L were risk factors for severe illness and death. Conclusions: The TBID reported in Hubei were mainly SFTS, tsutsugamushi disease and typhus. In order to reduce the incidence of TBID, it is necessary to strengthen the prevention and control in women aged ≥50 years and reduce field exposure and tick bites during the epidemic period.
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Animales , Femenino , Tifus Epidémico Transmitido por Piojos , Tifus por Ácaros/epidemiología , Síndrome de Trombocitopenia Febril Grave , Garrapatas , Enfermedades Transmisibles , Phlebovirus , China/epidemiología , Enfermedades por Picaduras de Garrapatas/epidemiologíaRESUMEN
Objective: To understand the current situation of long working hours exposure of couriers in Zhejiang Province, and to analyze the influence of long working hours exposure levels on their occupational stress and depression symptoms, and provide a basis for promoting the physical and mental health of couriers. Methods: From September to December 2021 , 1159 couriers from Zhejiang Express Transport Companies were selected as respondents by cluster sampling, and their basic information were collected. The occupational stress and depression symptoms of the couriers were assessed using the Core Occupational Stress Scale (COSS) and the Patient Health Questionnaire-9 (PHQ-9). The effects of long work hours (>48 h per week) on the occupational stress and depression symptoms of the couriers were analyzed. Results: The average age of 1159 courier in Zhejiang Province was (33.24±8.42) years, the average weekly working hours were (63.21±18.77) h, and 75.15% (871/1159) were long-term workers. The detection rates of occupational stress and depression symptoms in courier were 32.44% (376/1159) and 32.53% (377/1159), respectively. There were significant differences in the detection rates of occupational stress and depression symptoms among couriers with different ages, educational background, marital status, monthly average income, length of service, position or post, shift status, drinking status, and average weekly working hours (P <0.05). The adjusted logistic regression analysis showed that, after adjusting for the influence of confounding factors such as age, educational background, marital status, monthly average income, length of service, position or post, shift status and drinking status, compared with the weekly working hours ≤48 h, weekly working hours of 63-77 h, 78-92 h, ≥93 h were the risk factors for occupational stress (OR=1.547, 95%CI: 1.019-2.350; OR=1.886, 95%CI: 1.184-3.006; OR=2.338, 95%CI: 1.188-4.062) and depression symptoms (OR=1.897, 95%CI: 1.258-2.860; OR=2.041, 95%CI: 1.290-3.230; OR=4.978, 95%CI: 2.551-9.715) of couriers (P<0.05) . Conclusion: Long working hours could increase the risk of occupational stress and depression symptoms among couriers. It is necessary to arrange working hours reasonably to reduce the occurrence of occupational stress and depression symptoms of couriers.
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Humanos , Depresión/psicología , Estrés Laboral/psicología , Salud Mental , Factores de Riesgo , Satisfacción en el Trabajo , Encuestas y CuestionariosRESUMEN
Objective: To analyze the immunological characteristics and antibody changes of patients infected with the Omicron BA.1 and evaluate the possibility of secondary infection. Methods: A total of 104 patients infected with Omicron BA.1 in the Jinnan District of Tianjin from January 8 to February 2, 2022, were included in the study. The control group and case group were matched 1∶1 based on age, sex and vaccination status. Serum was collected from the case group and control group at 3, 6 and 9 months after infection. The serum levels of interleukin4 (IL-4), IL-5 and interferon-gamma (IFN-γ), as well as the positive rates of IgG, IgG1 and IgG2, were detected by ELISA. Results: The highest concentration of IFN-γ in the case group at 6 months after infection was 145.4 pg/ml, followed by a decrease in concentration. The concentrations of IL-4 and IL-5 began to decrease at 6 months after infection (all P<0.001). There was no significant difference in the IgG2 positive rate between the case group and the control group at 6 months after BA.1 infection. However, at 9 months, there was a significant decrease compared to the control group (P=0.003). The ratio of IFN-γ/IL4 at 3 months after infection in the case group was lower than that in the control group (P<0.001). There was no significant difference in the ratio between the case group and the control group at 9 months after infection. Conclusion: The cellular immune function has been impaired at 3 months after infection with BA.1, and the specific cellular immune and humoral immune functions decrease significantly after 6 months, and the risk of secondary infection increases.
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Adulto , Humanos , Inmunidad Humoral , Coinfección , Interleucina-4 , Interleucina-5 , Inmunoglobulina G , Interferón gammaRESUMEN
Objective: To analyze the immunological characteristics and antibody changes of patients infected with the Omicron BA.1 and evaluate the possibility of secondary infection. Methods: A total of 104 patients infected with Omicron BA.1 in the Jinnan District of Tianjin from January 8 to February 2, 2022, were included in the study. The control group and case group were matched 1∶1 based on age, sex and vaccination status. Serum was collected from the case group and control group at 3, 6 and 9 months after infection. The serum levels of interleukin4 (IL-4), IL-5 and interferon-gamma (IFN-γ), as well as the positive rates of IgG, IgG1 and IgG2, were detected by ELISA. Results: The highest concentration of IFN-γ in the case group at 6 months after infection was 145.4 pg/ml, followed by a decrease in concentration. The concentrations of IL-4 and IL-5 began to decrease at 6 months after infection (all P<0.001). There was no significant difference in the IgG2 positive rate between the case group and the control group at 6 months after BA.1 infection. However, at 9 months, there was a significant decrease compared to the control group (P=0.003). The ratio of IFN-γ/IL4 at 3 months after infection in the case group was lower than that in the control group (P<0.001). There was no significant difference in the ratio between the case group and the control group at 9 months after infection. Conclusion: The cellular immune function has been impaired at 3 months after infection with BA.1, and the specific cellular immune and humoral immune functions decrease significantly after 6 months, and the risk of secondary infection increases.
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Adulto , Humanos , Inmunidad Humoral , Coinfección , Interleucina-4 , Interleucina-5 , Inmunoglobulina G , Interferón gammaRESUMEN
Objective: In this study, the aim was to investigate the inhibitory effect of 6,6′-bieckol on the migration and epithelial-mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) cells, and explore its potential molecular mechanisms. Methods: Cell migration was measured using a CCK8, wound healing, and transwell migration assay. Apoptosis was determined using an Annexin V/propidium iodide staining. Western blotting and immunofluorescence were used to examine the expression level of apoptosis-related proteins and EMT marker proteins. Results: The results showed that 6,6′-bieckol inhibited migration and induced apoptosis of NSCLC cells. Furthermore, 6,6′-bieckol had significantly up-regulated the E-cadherin and down-regulated Snail1 and Twist1 transcriptional levels. 6,6′-Bieckol might inhibit TGF-β-induced EMT by down-regulating Snail1 and Twist1 and up-regulating E-cadherin in lung cancer cells. Conclusion: It is suggested that 6,6′-bieckol has the potential to be developed as a therapeutic candidate for lung cancer.
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OBJECTIVE@#To explore the genetic basis for a Chinese patient with retinitis pigmentosa (RP).@*METHODS@#Whole exome sequencing (WES) was carried out to screen potential variant in the proband. Candidate variants were determined by taking consideration of clinical phenotype. Sanger sequencing was used to verify the variant in the proband and his parents.@*RESULTS@#The proband was found to harbor compound heterozygous variants of c.8G>A (p.Cys3Tyr) and c.958_959insA (p.Arg320Glnfs*29) in the C2ORF71 gene, which has derived from his father and mother, respectively. Both variants were unreported previously. Based on the ACMG guidelines, they were predicted to be likely pathogenic and pathogenic, respectively.@*CONCLUSION@#The novel compound heterozygous variants of the C2ORF71 gene probably underlay the pathogenesis of RP in the proband. Above finding has enriched the spectrum of C2ORF71 gene mutations and facilitated genetic counseling for the family.
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Humanos , Pueblo Asiatico/genética , China , Mutación , Linaje , Retinitis Pigmentosa/genética , Secuenciación del ExomaRESUMEN
OBJECTIVE@#To compare the therapeutic effect on type 2 diabetes mellitus (T2DM) complicated with angina pectoris of coronary heart disease between the combined therapy of acupuncture and western medication and the simple administration of western medication.@*METHODS@#A total of 134 patients with T2DM and angina pectoris of coronary heart disease were randomly divided into two groups, i.e. an acupuncture plus medication group (67 cases, 3 cases dropped off) and a medication group (67 cases, 4 cases dropped off). The routine western medication was used according to symptoms in the patients of both groups. In the acupuncture plus medication group, on the base of medication, acupuncture was applied to Jianshi (PC 5), Quchi (LI 11), Neiguan (PC 6), etc. The needles were retained for 20 min in each treatment and 3 treatments of acupuncture were required weekly. The treatment was given consecutively for 8 weeks in the two groups. Separately, before and after treatment, the symptom scores of TCM were observed and the indexes were detected, including glycolipid metabolism [fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), glucosylated hemoglobin (HbA1c), triacylglycerol (TG) and total cholesterol (TC)], islet β cell function [homeostasis model assessment-β (HOMA-β), homeostasis model assessment-IR (HOMA-IR), fasting insulin (FINS) and insulin sensitivity index (ISI)], cardiac function indexes [cardiac output (CO), early diastolic peak velocity/late diastolic peak velocity (E/A), left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF)], as well as electrocardiogram QT dispersion (QTd). Besides, the clinical therapeutic effects were compared between the two groups.@*RESULTS@#After treatment, the TCM symptom scores and the values of FPG, 2hPG, HbA1c, TG, TC, HOMA-IR, FINS, E/A and LVEDD as well as QTd were all lower than those before treatment in the two groups (@*CONCLUSION@#The combined therapy of acupuncture and medication is effective in treatment of T2DM complicated with angina pectoris of coronary heart disease. Such therapy effectively improves glucolipid metabolism, islet β cell function, cardiac function and myocardial blood supply. Its curative effect is better than the simple administration of western medicine.
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Humanos , Terapia por Acupuntura , Angina de Pecho/etiología , Glucemia , Enfermedad Coronaria/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
Objective: To compare clinical characteristics of sporadic gastrinoma and multiple endocrine neoplasia type 1 (MEN1)-related gastrinoma. Methods: A retrospective cohort study was conducted. Patients with clinical manifestations of Zollinger-Ellison syndrome, pathological diagnosis as neuroendocrine neoplasm (NEN) and complete clinical and follow-up data were enrolled. Patients with only high gastric acid secretion but without evidence of NEN, or with other concurrent non-NEN tumors were excluded. According to the above criteria, the clinicopathological data of 52 cases of gastrinoma diagnosed from April 2003 to December 2020 in the First Affiliated Hospital, Sun Yat-sen University, were collected. Patients who met the diagnostic criteria of gastrinoma and met one of the following conditions were diagnosed as MEN1-related gastrinoma: (1) the presence of pathogenic mutations in the MEN1 gene confirmed by genetic testing; (2) NENs involving two or more endocrine glands, namely, pituitary, parathyroid, thymic, pancreatic, and adrenal NENs; (3) NEN and at least one first-degree relatives diagnosed as MEN1. The remaining gastrinomas were defined as sporadic gastrinoma. Student's t test and chi-square test were used for statistical analysis. Clinicopathological characteristics, endoscopic findings, imaging characteristics, treatment, and prognosis of sporadic and MEN1-related gastrinoma were compared. Results: Among 52 patients with gastrinoma, 33 were sporadic gastrinoma and 19 were MEN1-related gastrinoma. The common symptoms of both sporadic and MEN1-related gastrinomas were diarrhea (24/33, 72.7%; 17/19, 89.5%) and abdominal pain (19/33, 57.6%; 9/19, 47.4%). Compared with sporadic gastrinoma, MEN1-related gastrinoma needed longer time for diagnosis [(7.4±4.9) years vs. (3.9±5.2) years, t=-2.355, P=0.022), were more likely multiple tumors [47.4% (9/19) vs. 15.2% (5/33), χ(2)=6.361, P=0.012], had smaller diameter [(1.7±1.0) cm vs. (3.1±1.8) cm, t=2.942, P=0.005), presented the lower tumor grade [G1: 83.3% (15/18) vs. 39.4% (13/33); G2: 11.1% (2/18) vs. 54.5% (18/33); G3: 5.6% (1/18) vs. 6.1% (2/33), Z=-2.766, P=0.006], were less likely to have serum gastrin which was 10 times higher than normal [11.8% (2/17) vs. 56.0% (14/33), χ(2)=8.396, P=0.004], had higher probability of complication with type 2 gastric neuroendocrine tumors (g-NET) [31.6% (6/19) vs. 3.0%(1/33), χ(2)=6.163, P=0.013], and had lower rate of liver metastasis [21.1% (4/19) vs. 51.5% (17/33), χ(2)=4.648, P=0.031). There was no obvious difference between sporadic gastrinomas and MEN1-related gastrinomas in endoscopic findings. Both types presented enlarged and swollen gastric mucosa under the stimulation of high gastric acid, and multiple ulcers in the stomach and duodenum could be seen. Gastrinoma with type 2 g-NET presented multiple polypoid raised lesions in the fundus and body of the stomach. (68)Ga-SSR-PET/CT scan had a 100% detection rate for both types while (18)F-FDG-PET/CT scan had a higher detection rate for sporadic gastrinoma compared with MEN1-related gastrinoma [57.9% (11/19) vs. 20.0% (3/15), χ(2)=4.970, P=0.026]. Among the patients with sporadic gastrinoma, 19 received surgical treatment, 1 underwent endoscopic submucosal dissection, 8 underwent transcatheter arterial embolization (TAE), and 5 underwent surgery combined with TAE. Among patients with MEN1-related gastrinoma, 13 received surgical treatment, and the other 6 received conservative treatment. The median follow-up of all the patients was 21.5 (1-129) months, and the 5-year survival rate was 88.4%. The 5-year survival rate of patients with sporadic and MEN1-related gastrinomas was 89.5% and 80.0% respectively (P=0.949). The 5-year survival rate of patients with and without liver metastasis was 76.2% vs. 100%, respectively (P=0.061). Conclusions: Compared with sporadic gastrinoma, MEN1-related gastrinoma has longer diagnosis delay, smaller tumor diameter, lower tumor grading, lower risk of liver metastasis, and is more likely to complicate with type 2 g-NET, while there is no difference in survival between the two tumor types.
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Humanos , Gastrinoma/genética , Neoplasia Endocrina Múltiple Tipo 1/genética , Neoplasias Pancreáticas/genética , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios RetrospectivosRESUMEN
Objective:To explore the role of receptor-interaction protein 3 (RIP3) in regulating the infiltration of monocytes/macrophages into the liver in autoimmune hepatitis (AIH).Methods:From January to June in 2018, at Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, 10 AIH patients who underwent liver biopsy were enrolled, and at the same time, 5 age and gender matched individuals with normal liver function and hepatic cyst were selected as control. The infiltration of monocytes/macrophages in the liver tissues was observed by immunofluorescence detection in the patients with AIH and controls. Raw264.7 macrophages were divided into control group, lipopolysaccharide group and lipopolysaccharide+ RIP3 inhibitor GSK872 (GSK872) group. The expression of RIP3, mixed lineage kinase domain like pseudokinase ( MLKL), tumor necrosis factor ( TNF)- α, interleukin ( IL)-6, IL-1 β, nod-like receptor protein 3 ( NLRP3), CC motif chemokine ligand ( CCL)2 and CCL5 at mRNA levels were detected by quantitative polymerase chain reaction (qPCR). Raw264.7 macrophages were also divided into control group, lipopolysaccharide group and lipopolysaccharide + dexamethasone group. The relative expression of TNF- α, NLRP3, RIP3 and MLKL at mRNA level in macrophage were detected by qPCR. Twenty-four 6-week-old female C57BL/6 mice were chosen to establish AIH mice model and were randomly divided into control group, concanavalin A (ConA) group, ConA+ dexamethasone group and ConA+ GSK872 group (6 mice in each group). After the mice were executed, the peripheral blood and liver tissues were collected. The histopathology of mice liver were observed and the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. The expression of CCL2 and CC motif chemokine receptor 2 ( CCR2) at mRNA level were detected by qPCR. The proportion of macrophages in mice livers were analyzed by flow cytometry. The independent sample t test and one-way analysis of variance were performed for statistical analysis. Results:The percentages of CD68 positive macrophages and MAC387 positive infiltrated mononuclear macrophages in livers of AIH patients were both higher than those of controls ((0.84±0.21)% vs. (0.09±0.03)%, (0.79±0.13)% vs. (0.03±0.01)%), and the differences were statistically significant ( t=3.00 and 4.84; all P<0.05). The expression of RIP3, MLKL, TNF- α, IL-6, IL-1 β, NLRP3, CCL2 and CCL5 at mRNA level of lipopolysaccharide group were all higher than those of control group and lipopolysaccharide+ GSK872 group (1.64±0.16 vs. 1.07±0.07 and 0.63±0.11; 10.45±1.37 vs. 1.10±0.33 and 1.51±0.63; 5.43±0.59 vs. 0.94±0.06 and 2.59±0.45; 204.20±30.73 vs. 1.26 ±0.19 and 111.40±11.62; 20 848.00±362.00 vs. 1.09 ±0.26 and 10 940.00±566.60; 7.47±1.17 vs. 1.09±0.09 and 3.79±0.89; 68.03±5.15 vs. 1.14±0.19 and 14.09±2.62; 5 935.12±96.20 vs. 1.43±0.46 and 673.50±49.10), and the differences were all statistically significant ( t=3.11, 5.21, 6.65, 6.55, 7.57, 3.96, 6.60, 3.06, 8.83, 4.08, 5.46, 2.56, 12.97, 10.16, 25.34 and 14.99; all P<0.05). The expression of TNF- α, NLRP3, RIP3 and MLKL at mRNA level of lipopolysaccharide group were all higher than those of control group and lipopolysaccharide+ dexamethasone group (8.85±1.43 vs. 1.44±0.43 and 3.63±0.63; 6.42±0.86 vs. 0.99±0.12 and 2.07±0.17; 1.72±0.21 vs. 0.93±0.09 and 0.43±0.07; 6.87±0.85 vs. 1.62±0.31 and 1.41±0.29), and the differences were all statistically significant ( t=4.95, 3.33, 6.24, 4.95, 3.04, 5.11, 5.77 and 6.07, all P<0.05). The mice liver of ConA group showed obviously inflammatory cells infiltration and hepatocytes necrosis. The serum ALT and AST levels of ConA group were both higher than those of control group, ConA+ dexamethasone group and ConA+ GSK872 group ((2 569.00±45.44) U/L vs. (49.38±9.07), (103.00±14.07) and (759.30±34.99) U/L; (3 335.00±88.79) U/L vs. (108.50±18.10), (460.00±97.40) and (1 573.85±36.06) U/L), the serum ALT and AST levels of ConA+ dexamethasone group were both lower than those of ConA+ GSK872 group, and the differences were all statistically significant ( t=5.54, 5.42, 3.90, 4.63, 4.16, 3.79, 6.70 and 2.71; all P<0.05). The expression of CCL2 and CCR2 at mRNA levels in mice liver of ConA group were both higher than those of control group, ConA+ dexamethasone group and ConA+ GSK872 group (92.64±10.57 vs. 0.78±0.15, 5.64±1.00 and 9.47±2.06; 5.73±0.39 vs. 0.98±0.22, 2.18±0.22 and 2.98±0.33), and the differences were all statistically significant ( t=7.66, 7.24, 5.87, 8.71, 8.58 and 5.45; all P <0.01). The proportion of CD45 + CD11b + F4/80 + total macrophages and CD45 + CD11b hiF4/80 lo infiltrated macrophages in mice livers of ConA group were both higher than those of control group, ConA+ dexamethasone group and ConA+ GSK872 group (0.86±0.02 vs. 0.73±0.03, 0.68±0.02 and 0.72±0.03; 0.56±0.02 vs. 0.08±0.02, 0.11±0.01 and 0.08±0.01), however the proportion of CD45 + CD11b loF4/80 hi liver macrophages (Kupffer cells) was lower than those that of control group, ConA+ dexamethasone group and ConA+ GSK872 group (0.24±0.03 vs. 0.58±0.04, 0.52±0.07 and 0.56±0.07), and the differences were all statistically significant ( t=4.27, 5.90, 3.89, 18.70, 19.87, 20.52, 7.35, 3.82 and 3.87, all P<0.05). Conclusions:The number of macrophages incread in the livers of AIH patients. RIP3 signaling mediates the migration of monocytes/macrophages infiltration in immune hepatitis, which may be a potential therapeutic target for AIH.
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BACKGROUND: 100âmg rectal nonsteroidal anti-inflammatory drugs (NSAIDs) and pancreatic stents both significantly reduce the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Direct comparison of randomized controlled trials (RCTs) between them in high-risk patients is absent. We conducted this network meta-analysis to indirectly compare the efficacies of 100âmg rectal NSAIDs and pancreatic stents in preventing post-ERCP pancreatitis (PEP) in high-risk patients and help us decide which is preferred in clinical practice. METHODS: A comprehensive search was done to identify RCTs published in English full-text. Interventions included 100âmg rectal NSAIDs (diclofenac or indomethacin) and pancreatic stents. Only studies with high-risk patients of PEP were included. Meta-analyses of NSAIDs and pancreatic stents were conducted respectively. A network meta-analysis using the Bayesian method was performed. RESULTS: We included 14 RCTs, 8 on pancreatic stents and 6 on 100âmg rectal NSAIDs in high-risk patients. There was no direct comparison between them. After excluding an outlier study on NSAIDs (nâ=â144), meta-analyses showed they both significantly and statistically reduced the incidence of PEP in high-risk patients (pancreatic stents: nâ=â8 studies, random-effects risk ratio (RR)0.41, 95%CI 0.30-0.56, Iâ=â0%; NSAIDs: nâ=â5 studies, random-effects RR 0.37, 95%CI 0.25-0.54, Iâ=â0%). And network meta-analysis showed efficacy of 100âmg rectal NSAIDs was equal to pancreatic stents (random-effects RR 0.94, 95%CI 0.50-1.8). CONCLUSIONS: The efficacy of 100âmg rectal NSAIDs (diclofenac or indomethacin) seems equally significant to pancreatic stents in preventing PEP in high-risk patients. Considering the cost-effectiveness and safety, 100âmg diclofenac or indomethacin may be preferred.
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Antiinflamatorios no Esteroideos/uso terapéutico , Colangiopancreatografia Retrógrada Endoscópica , Pancreatitis/prevención & control , Administración Rectal , Antiinflamatorios no Esteroideos/administración & dosificación , Humanos , Complicaciones Posoperatorias/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , StentsRESUMEN
Objective:To explore the clinical characteristics of liver function of patients with autoimmune liver disease (AILD) complicated with gallbladder stone (GS), so as to guide clinical practice.Methods:From November 2009 to October 2018, at General Hospital of Tianjin Medical University, the clinical data of 386 patients with AILD were retrospectively analyzed. According to the relevant diagnostic criteria, 208 cases of autoimmune hepatitis (AIH), 129 cases of primary biliary cholangitis (PBC) and 49 cases of PBC-AIH overlap syndrome were screened out. The incidence, clinical characteristics and the changes of laboratory indicators including albumin, alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT) of AILD patients complicated with GS were analyzed. Chi-square test, t test and rank sum test were performed for statistical analysis. Results:There was no significant difference in the incidence between AILD, AIH, PBC and PBC-AIH overlap syndrome patients complicated with GS (32.9%, 127/386; 28.8%, 60/208; 36.4%, 47/129 and 40.8%, 20/49; respectively; P>0.05). Gallstones of AILD patients complicated with GS mostly were multiple and small stones with maximum diameter <1 cm (45.7%, 58/127 and 57.7%, 60/104, respectively). The age of initial diagnosis, the proportion of liver cirrhosis at inital diagnosis and the levels of ALP and GGT were higher in AILD patients complicated with GS than those of AILD patients without GS ((60.5±11.5) years vs. (57.6±11.5) years; 53.5%, 68/127 vs. 42.1%, 109/259; 154.00 U/L (89.00 U/L, 257.00 U/L) vs. 125.00 U/L (86.00 U/L, 212.00 U/L); 169.00 U/L (79.00 U/L, 343.00 U/L) vs. 128.60 U/L (48.00 U/L, 284.00 U/L); respectively); however the albumin level was lower than that of AILD patients without GS ((36.46±7.30) g/L vs. (38.34±7.58) g/L), and the differences were statistically significant ( t=-2.361, χ2=4.506, Z=-2.192, -2.443, t=2.322; all P<0.05). The incidence of GS in AILD patients≥60 years old was higher than that AILD patients<60 years old (37.6%, 73/194 vs. 28.1%, 54/192), and the difference was statistically significant ( χ2=3.948, P=0.047). The incidence of GS in AILD patients and AIH patients complicated with liver cirrhosis was higher than that in patients without liver cirrhosis (38.4%, 68/177 vs. 28.2%, 59/209; 35.7%, 35/98 vs. 22.7%, 25/110; respectively), and the differences were statistically significant ( χ2=4.506 and 4.259, P=0.034 and 0.039). Conclusions:AILD patients complicated with GS are common, most are multiple and small stones. When complicated with GS, the initial diagnosis may be delayed and the rate of liver cirrhosis at initial diagnosis may increase. The incidence of GS is high in AILD patients with older age and liver cirrhosis.
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Objective:To construct a systematic identification system of Anemonis Flaccidae Rhizoma, and to evaluate the comprehensive quality of Anemonis Flaccidae Rhizoma from 16 regions in China, so as to lay a foundation for its origin selection and clinical medication safety. Method:The authenticity of Anemonis Flaccidae Rhizoma was quickly identified by traditional identification method and DNA barcode molecular identification technology, and HPLC-UV was used to determine the contents of 5 active ingredients in Anemonis Flaccidae Rhizoma. All high pressure chromatographic separations were performed with a Welch Ultimate XB-C18 column (4.6 mm×250 mm, 5 μm), the mobile phase consisted of acetonitrile-0.01% trifluoroacetic acid aqueous solution (30∶70) at a flow rate of 1.0 mL·min-1. The detection wavelength was set at 210 nm and the column temperature was maintained at 30 ℃. Result:The authenticity of Anemonis Flaccidae Rhizoma could be precisely and rapidly identified by ribosomal DNA internal transcribed spacer 2 (ITS2) sequence and traditional identification methods. BLAST comparative analysis found that medicinal materials from 16 areas were all Anemone flaccida. Based on the contents of multi-index components, it was shown that the total content of 5 triterpenoid saponins in Anemonis Flaccidae Rhizoma from Banqiao, Enshi, Hubei was the highest (10.59%), followed by Hezhang, Bijie, Guizhou (6.28%) and Duzhenwan, Changyang, Hubei (5.64%). Conclusion:DNA barcoding can be used as an effective supplement to the traditional identification technology, it can ensure the authenticity of Anemonis Flaccidae Rhizoma and the safety of clinical use. The comprehensive evaluation of multi-index components of HPLC and cluster analysis show that the quality of medicinal materials in Enshi, Changyang, Wufeng of Hubei, Bijie of Guizhou and Jinfoshan of Chongqing is superior, which can be considered as important origin of Anemonis Flaccidae Rhizoma.
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Since the outbreak of the COVID-19 at the end of December 2019, Hubei province has actively adopted a series of prevention and control measures such as “quarantine, treatment, testing, and containment”, and have basically blocked the spread of COVID-19. However, with the development of overseas epidemics and the occurrence of case clusters in local areas, we not only face the threat of imported cases, but also face the urgent need to resume normal work and daily life. This puts forward higher requirements for regular prevention and control of COVID-19. Therefore, we should more deeply understand the significance of regular prevention and control as well as the epidemic situation in our province, summarize experience and lessons, and adhere to the prevention and control strategy of “government-led, group-specialist combination, and specialized-oriented”. Meanwhile, it is necessary to implement the working requirement that combines regular prevention and control surveillance with rapid emergency response to local COVID-19 outbreaks. Furthermore, we should establish a regular multi-point trigger early warning mechanism for COVID-19, strengthen the reserve of emergency supplies and carry out training and drills on epidemic prevention and control across the province to make full preparations for the coming autumn and winter epidemics. The most important is to reform the system of disease prevention and control and public health, comprehensively improve the ability of prevention and treatment, and promote the modernization of public health governance.
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Objective To explore the optimal combination of parameters for the maximum spatial cluster size and maximum temporal cluster size of scan statistics. Methods The daily incidence data of hand-foot-and-mouth disease (HFMD) in Jingzhou in 2016 was collected as data source. The maximum spatial cluster sizes were set to 50%, 40%, 30%, 20%, and 10% of the population at risk. The maximum temporal cluster sizes were set to 7d, 14d, 30d, and 60d. A total of 20 parameter setting schemes were formed and spatial-temporal scanning was conducted one by one. The areas where the number of towns covered by the scanning area was less than 25 were selected, and the clustered epidemic of hand-foot-mouth disease can be detected at the same time in Xiejiaping Town of Songzi City and Sanzhou Town of Jianli County. The combination of large LLR and RR values was the optimal parameter setting. Results When the spatial windows were set to 20% of the population at risk, and the temporal windows were set to 30d, a total of 6 aggregation areas were detected. The number of covered townships was less than 25, and the clustered epidemic of Xiejiaping Township and Sanzhou Town were successfully detected. The LLR and RR values of the detected aggregation area were relatively large. This combination was the optimal parameter setting. Conclusion The combination of different parameters has a significant impact on the results of spatial-temporal scan statistics. It is recommended that parameters be optimized before applying this method.
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Objective To understand the epidemiological characteristics of the novel coronavirus diseases 2019 (COVID-19), and to scientifically guide the prevention and control of COVID-19 in Hubei Province. Methods All COVID-19 cases reported online in Hubei Province as of March 31, 2020 were extracted from Hubei's Infectious Disease Information System. The epidemic curve, age and sex characteristics, and spatiotemporal distribution characteristics of the COVID-19 cases were analyzed. Results As of March 31, 2020, a total of 70 764 cases were reported in Hubei Province, including 49 195 confirmed cases. A total of 4 579 deaths occurred among the confirmed cases, and the reported case fatality rate was 6.47%. The peak of the onset of symptoms occurred from January 20 to February 14, 2020. The sex ratio of male to female of the confirmed cases was 0.99: 1, and most were 30-69 years old. The cases diagnosed before January 5 were mainly reported by Wuhan City. From January 6 to January 31, all counties and districts in the province reported that the incidence of confirmed COVID-19 cases began to rise, and about 50% counties reported that the morbidity rate of confirmed COVID-19 cases was over 10 cases per 100 000. The morbidity rate of COVID-19 cases rose rapidly between February 1-15, and then gradually reached its peak after February 16. Conclusion Wuhan City of Hubei Province first discovered and reported the COVID-19 outbreak. The onset of symptoms peaked in January 20 to February 14, and the 30-69 years old group was the key population. Many measures such as restricting personnel movement, reducing contact, and strengthening health education played an important role in controlling the outbreak of COVID-19 in Hubei.