Objective To study the mechanism of adaptive immunity against Rhizopus arrihizus (R. arrihizus) infections. Methods Bone marrow derived dendritic cells (BMDCs) were separated from C57BL/6 mice and Card9-/- mice and then were cultured in vitro. Resting spores and swollen spores of R. arrihizus were in vitro co-cultured with BMDCs with or without Syk inhibition. Secretion of cytokines ( IL-23, IL-1βand IL-12) was analyzed by ELISA after 24 hours of culture. Na?ve T cells derived from C57BL/6 mice were in vitro co-cultured with spore-stimulated BMDCs for four days. Levels of IL-17A and IFN-γ in supernatants of cell culture were analyzed by ELISA. Flow cytometry was performed to analyze T cell differ-entiation. Confocal microscopy was used to observe the images of stained β-glucan on the surface of resting and swollen spores. Swollen spores were co-cultured with Dectin-1, Dectin-2, TLR2 and mannose receptor ( MMR) , and the binding results were analyzed by flow cytometry. Results Swollen spores but resting spores could induce the maturation of BMDCs and promote the secretion of cytokines (IL-23, IL-1βand IL-12). Co-culturing T cells with swollen spore-stimulated BMDCs enhanced their differentiation to Th17 and Th1. In addition, swollen spores promoted the secretion of Th1-related cytokine ( IFN-γ) and Th17-related cytokine (IL-17A). Adding Syk inhibitor to Card9-/-BMDCs or wild type BMDCs significantly inhibited the secretion of cytokines and T cell differentiation, especially in the Card9-/- group. β-glucan was overserved on the surface of swollen spores, but not on resting spores. On the surface of swollen spores existed pathogen associated molecular patterns ( PAMPs) that could bind with Dectin-1 and TLR2. Conclusion Swollen spores of R. arrihizus could active BMDCs to secrete cytokines of IL-23, IL-1β and IL-12 and trigger T cell responses in vitro. The possible mechanism might be associated with β-glucan exposed on the surface of swollen spores that binds with Dectin-1. The responses between BMDCs and R. arrihizus are Syk-Card9-dependent.

Background/Aims: The occurrence and development of hepatitis B virus-associated acute-onchronic liver failure (HBV-ACLF) is closely related to the immune pathway. We explored the heterogeneity of peripheral blood T cell subsets and the characteristics of exhausted T lymphocytes, in an attempt to identify potential therapeutic target molecules for immune dysfunction in ACLF patients. Methods: A total of 83,577 T cells from HBV-ACLF patients and healthy controls were screened for heterogeneity by single-cell RNA sequencing. In addition, exhausted T-lymphocyte subsets were screened to analyze their gene expression profiles, and their developmental trajectories were investigated. Subsequently, the expression of exhausted T cells and their capacity in secreting cytokines (interleukin 2, interferon γ, and tumor necrosis factor α) were validated by flow cytometry. Results: A total of eight stable clusters were identified, among which CD4 + TIGIT + subset and CD8 + LAG-3 + subset, with high expression of exhaust genes, were significantly higher in the HBV-ACLF patients than in normal controls. As shown by pseudotime analysis, T cells experienced a transition from naïve T cells to effector T cells and then exhausted T cells. Flow cytometry confirmed that the CD4 + TIGIT + subset and CD8 + LAG-3 + subset in the peripheral blood of the ACLF patients were significantly higher than those in the healthy controls. Moreover, in vitro cultured CD8 + LAG-3 + T cells were significantly fewer capable of secreting cytokines than CD8 + LAG-3- subset. Conclusions Peripheral blood T cells are heterogeneous in HBV-ACLF. The exhausted T cells markedly increase during the pathogenesis of ACLF, suggesting that T-cell exhaustion is involved in the immune dysfunction of HBV-ACLF patients.

Objective:To observe the antagonism of dexamethasone on radiation bystander effect and its re-transmission in rabbit lymphocytes.Methods:The plasmas of 2 New Zealand rabbits which were irradiated with 6 MV X-ray was taken to prepare the first generation of conditioned medium; the plasmas of 2 unirradiated New Zealand rabbits were taken to prepare the first generation of unconditioned culture medium; The lymphocytes of 5 unirradiated New Zealand rabbits were extracted. The lymphocytes from 5 unirradiated New Zealand rabbits were cocultured with the first generation of unconditioned medium or conditioned medium. After abandoning the culture medium, the lymphocytes were cultured in conventional medium for 24 h. The second generation of unconditioned medium or conditioned medium was taken. The lymphocytes were treated with four medium with or without dexamethasone (1 μg/ml), and the apoptosis rate of lymphocytes was detected by flow cytometry.Results:With or without dexamethasone, the apoptosis rates of lymphocytes treated with the first generation of conditioned medium was significantly higher than that with the first generation of unconditioned medium [without dexamethasone: (21.09±1.60)% vs. (8.06±0.65)%, t = -30.182, P < 0.05; with dexamethasone: (14.96±1.80)% vs. (6.25±0.54)%, t = -16.404, P < 0.05]. Dexamethasone could reduce the apoptosis rates of lymphocytes treated with the first generation of unconditioned medium and the first generation of conditioned medium, and the differences were statistically significant (both P < 0.05). With or without dexamethasone, the apoptosis rates of lymphocytes treated with the second generation of conditioned medium was significantly higher than that with the second generation of unconditioned medium [without dexamethasone: (28.70±2.14)% vs. (12.38±0.67)%, t = -33.351, P < 0.05; with dexamethasone: (20.21±1.96)% vs. (12.53±1.25)%, t = -14.145, P < 0.05]. Dexamethasone could reduce the apoptosis rates of lymphocytes treated with the second generation of conditioned medium ( P < 0.05), but it could not reduce the apoptosis rate of lymphocytes treated with the second generation of unconditioned medium ( P > 0.05). Conclusion:Dexamethasone can antagonize the injury of lymphocytes by radiation bystander effect in vitro, reduce the apoptosis rate of lymphocytes, and can also antagonize the re-transmission of radiation bystander effect.

Objective:To analyze the distribution characteristics of peripheral retinopathy in Chinese patients with diabetic retinopathy (DR).Methods:A cross-sectional study. From January to December 2019, 265 cases of 388 eyes of DR patients diagnosed in the eye examination of Guangdong Provincial People's Hospital were included in the study. Among them, there were 211 eyes in 148 males and 177 eyes in 117 females; the average age was 58.4±12.3 years. Ultra-wide-angle fundus imaging (UWF) examination was performed by Daytona in Aalborg, UK. Use Photoshop to simulate the standard 7-azimuth (S7F) area, which was used as the central retinal area 1-7. The peripheral retinal areas 3-7 (P3-P7) were the adjacent peripheral retinal areas of the central retinal area 3-7, respectively. Divided DR into peripheral lesion predominant type (PPL) and central lesion predominant type (PCL). PPL was defined as at least one peripheral retinal area with more severe disease than its adjacent central area. χ 2 test was performed on the difference of PPL composition ratio in each retinal area of eyes with different DR stages. Results:Among 388 eyes, 200 eyes were PPL (51.5%, 200/388). Compared of PPL composition ratios of eyes with different stages of DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR and proliferative DR were 32 (36.8%, 32/87), 89 (55.3%, 89/161)), 42 (51.9%, 42/81), 37 (62.6%, 37/59), the difference was statistically significant ( χ2=11.440, P=0.010). Comparison of the distribution of PPL in each retinal area in DR eyes: in 200 PPL eyes, areas 3, 4, 5, 6, and 7 have 87, 101, 78, 67, and 38 eyes, respectively. The distribution of PPL in each retinal area in DR eyes was compared, and the difference was statistically significant ( χ2=37.640, P<0.001). Conclusions:PPL accounts for 51.5% of the eyes with DR. The DR stage are more severe, the proportion of PPL is higher. The temporal retinal peripheral lesions are the most common.

Humans ; Psoriasis/drug therapy* ; Registries ; China/epidemiology*

Objectives:To retrieve,evaluate and summarize the contemporary evidence of strategies for weaning from extracorporeal membrane oxygenation(ECMO)of adult patients,and to provide evidence-based reference for clinical practice. Methods:The Web of Science,Embase,Cochrane Library,PubMed,Wanfang Database,CNKI,VIP website,SinoMed,BMJ Best Practice,National Institute for Health and Care Excellence,Joanna Briggs Institute Library,UpToDate and the website of Agency for Healthcare Research and Quality,Society of Critical Care Medicine,American Association of Critical-Care Nurses,European Society of Intensive Care Medicine and Extracorporeal Life Support Organization were researched to collect the literature related to randomized controlled trials,systematic reviews,guidelines,evidence summaries,expert consensuses and clinical decisions in this field.The time limit for the retrieval is from the inception of databases until July 2023. Results:A total of 13 related literature were retrieved,including 4 guidelines,4 expert consensuses,3 clinical decisions and 2 system reviews.Totally 42 evidences were formulated based on retrieved literature,including adequately accessing the ability of gas exchange before weaning from veno-venous ECMO(V-V ECMO)and withdrawing from veno-arterial ECMO(V-A ECMO)as soon as possible when patients's heart function has recovered,involving six aspects such as team composition,anticoagulation measures,assessment before weaning,weaning implementation,cannula and wound management and quality measures. Conclusions:It is suggested to build a professional ECMO team based on the actual hospital situation,to follow the contemporary evidence to standardize the weaning process of patients from ECMO to ensure the patients'safety and improve the outcomes.

OBJECTIVE To screen out the pharmacodynamic substances of Cistanches Herba aqueous extracts, explore the basis of the pharmacodynamic substances and their mechanism of action in the treatment of diabetic nephropathy(DN), based on the spectral relationship between the mass spectral peak areas of different elution sites of Cistanches Herba aqueous extracts and their anti-DN effects. METHODS UPLC-Orbitrap-MS/MS technique was used to characterise the chromatographic peaks; MTT method was used to detect the effects of different elution sites of Cistanches Herba aqueous extract on the proliferation of high glucose and high fat HK-2 cells; grey correlation analysis and partial least squares method were used to analyse the spectral relationship between mass spectrometry peak area and anti-DN activity. MTT method was used to determine the anti-DN activities of the individual components of Cistanches Herba aqueous extract; biochemical kit and ELISA were used to determine the levels of oxidative indicators(SOD, GSH-P) and inflammatory factors(IL-1β, TNF-α, TGF-β); Western blotting was used to detect the expression of apoptosis-related proteins. RESULTS UPLC-Orbitrap-MS/MS technique speculated and identified 72 common compounds; In Cistanches Herba aqueous extracts, water, 20% ethanol, and 40% ethanol-eluted sites differentially increased the proliferation rate of HK-2 cells in a high-sugar, high-fat environment; Partial least squares and grey correlation analyses showed that the constituents of the aqueous extracts of Cistanches Herba with greater anti-DN contributions were 8-epideoxymatricinic acid, geniposidic acid, pinoresinol, betaine and syringin, et al. MTT assay reveals that 8-epi-deoxystrychnic acid and geniposidic acid had significant proliferative effects on HK-2 cells in a high glucose and high fat environment; Biochemical kit and ELISA showed that 8-epideoxystrychnic acid and geniposidic acid were able to up-regulate the activity of SOD and GSH-Px, and at the same time they had an inhibitory effect on the expression of inflammatory factors IL-1β, TNF-α and TGF-β. Western blotting results showed that 8-epideoxystrychnic acid and geniposidic acid were able to down-regulate and up-regulate the markers of dermal mesenchymal transition: α-SMA, Collagen Ⅰ and E-cadherin, and they could exert anti-DN effects by inhibiting the PI3K-Akt pathway. CONCLUSION The two compounds, 8-epideoxystrychnic acid and geniposidic acid, which are screened by the spectroeffective relationship of anti-DN among the many chemical constituents contained in Cistanches Herba, can affect oxidative stress, inflammation and epithelial-mesenchymal transformation of renal tubular cells by inhibiting the PI3K-Akt signalling pathway, and improve renal pathology, degree of fibrosis and renal function, which will be useful for the in-depth study of aqueous extracts of Cistanches Herba in the treatment of DN.

Objective To analyze the disease burden of multidrug-resistant tuberculosis (MDR-TB) in China and regions with different income levels in the world from 1990 to 2019. Methods Using the Global Burden of Disease Study 2019 (GBD2019) results, the changes of the disease burden of MDR-TB in China and regions with different income levels in the world were described and analyzed using the Joinpoint Regression Program 4.8.0.1 software. Results From 1990 to 2019, the age standardized incidence, mortality and DALY rates in China and other areas with different income levels in the world basically showed a trend of first rising and then decreasing at the turning point of the late 20th century and early 21st century, except for low-income areas where the age standardized incidence rate showed an overall upward trend. In 2019, the incidence rate, mortality and DALY rate of MDR-TB in China were 9 times, 6.67 times and 6.89 times higher than those in high-income areas, respectively. The incidence rate in China was 6 times lower than that in low and middle-income areas, while the mortality and DALY rate in China were 26 times and 32.53 times lower than those in low-income areas, respectively. The age standardized incidence, mortality rate and DALY rate of MDR-TB in men were higher than those in women. Risk factors for the burden of MDR-TB disease included alcohol consumption, smoking, and high fasting blood glucose. Conclusion From 1990 to 2019, there are significant regional and gender differences in the disease burden of multidrug-resistant tuberculosis in China and regions with different income levels in the world. Multidrug-resistant tuberculosis is still a major challenge for tuberculosis control in the world. It is necessary to develop more effective control strategies and health care systems to deal with multidrug-resistant tuberculosis.

A 6-year-old girl presented with recurrent skin rash at the initial stage, recent joint pain, and neutrophilia was found during a routine blood test. After a multidisciplinary case discussion, she was diagnosed with chronic neutrophil leukemia, and the symptoms were relieved after hydroxyurea and luxolitinib treatment. She received the allogeneic hematopoietic stem cell transplantation subsequently. At present, she is in stable condition and under follow-up. Chronic neutrophil leukemia is a rare disease, which rarely occurs in children. It is more difficult to diagnose in patients with skin rash as the first manifestation. The diagnosis and treatment of this case reflects the important role of multidisciplinary cooperation in the diagnosis and treatment of difficult and rare diseases.