Vaporization of perfluorocarbon attenuates sea-water-drowning-induced acute lung injury by deactivating the NLRP3 inflammasomes in canines.

Seawater-drowning-induced acute lung injury (SD-ALI) is a life-threatening disorder characterized by increased alveolar-capillary permeability, an excessive inflammatory response, and refractory hypoxemia. Perfluorocarbons (PFCs) are biocompatible compounds that are chemically and biologically inert and lack toxicity as oxygen carriers, which could reduce lung injury in vitro and in vivo. The aim of our study was to explore whether the vaporization of PFCs could reduce the severity of SD-ALI in canines and investigate the underlying mechanisms. Eighteen beagle dogs were randomly divided into three groups: the seawater drowning (SW), perfluorocarbon (PFC), and control groups. The dogs in the SW group were intratracheally administered seawater to establish the animal model. The dogs in the PFC group were treated with vaporized PFCs. Probe-based confocal laser endomicroscopy (pCLE) was performed at 3 h. The blood gas, volume air index (VAI), pathological changes, and wet-to-dry (W/D) lung tissue ratios were assessed. The expression of heme oxygenase-1 (HO-1), nuclear respiratory factor-1 (NRF1), and NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasomes was determined by means of quantitative real-time polymerase chain reaction (qRT-PCR) and immunological histological chemistry. The SW group showed higher lung injury scores and W/D ratios, and lower VAI compared to the control group, and treatment with PFCs could reverse the change of lung injury score, W/D ratio and VAI. PFCs deactivated NLRP3 inflammasomes and reduced the release of caspase-1, interleukin-1ß (IL-1ß), and interleukin-18 (IL-18) by enhancing the expression of HO-1 and NRF1. Our results suggest that the vaporization of PFCs could attenuate SD-ALI by deactivating NLRP3 inflammasomes via the HO-1/NRF1 pathway.

Colonoscopy Combined with Me-Nbi to Observe the Canceration Characteristics of Colon Polyps and the Correlation of RHOC Protein Expression.

The current study was carried out to analyze the characteristics of colon polyps canceration observed by colonoscopy combined with ME-NBI (Magnifying Endoscopy combined with Narrow-Band Imaging) and its correlation with RhoC (Ras homolog gene family, member C) protein expression. For this purpose, A total of 300 patients with colorectal polyps and cancerous lesions (192 colorectal polyps and 200 cancerous lesions) who were treated in the digestive endoscopy room of the hospital and underwent colonoscopy were selected, and they were divided into polyp group and malignant lesion according to the diagnosis results. groups, 150 cases in each group. There were 75 patients with non-adenomatous polyps and 75 patients with adenomatous polyps in the polyp group; 75 patients with high-grade neoplasia and cancerous changes in the malignant group. The microvascular structure and surface structure of the lesions were observed by colonoscopy, and the correlation between microvascular morphological characteristics and RhoC protein expression was analyzed. Results showed that the probability of positive RhoC protein expression in the polyp group was significantly lower than that in the malignant transformation group, and the difference was statistically significant (P<0.05). In the malignant transformation group, the positive rate of RhoC expression in mucosal and submucosal superficial infiltration of 150 patients with colon polyp carcinoma was lower than that in submucosal deep infiltration, and the difference was statistically significant (P<0.05). NICE (National Institute for Clinical Excellence) type 2 was diagnosed as colorectal superficial submucosal The sensitivity, specificity, and accuracy of colorectal submucosal invasion were 73.1%, 84.6%, and 83.2%, respectively; the sensitivity, specificity, and accuracy of NICE type 3 in diagnosing colorectal submucosal invasion were 74.6%, 96.8%, and 92.7%, respectively. . Type 2 and type 3 lesions with cancerous features in NICE classification were correlated with the expression of RhoC protein (P<0.05). In conclusion, NICE classification under colonoscopy combined with magnifying colonoscopy has a good effect on colorectal lesions. Differential diagnostic value, RhoC protein is highly expressed in colon cancer and is closely related to the occurrence of colon cancer and the depth of lesion invasion. With the progression of colorectal adenomas, the expression of RhoC protein in the lesions gradually increased.

Clinical outcome is distinct between radiological stricture and endoscopic stricture in ileal Crohn's disease.

OBJECTIVES: Differences in clinical adverse outcomes (CAO) based on different intestinal stricturing definitions in Crohn's disease (CD) are poorly documented. This study aims to compare CAO between radiological strictures (RS) and endoscopic strictures (ES) in ileal CD and explore the significance of upstream dilatation in RS. METHODS: This retrospective double-center study included 199 patients (derivation cohort, n = 157; validation cohort, n = 42) with bowel strictures who simultaneously underwent endoscopic and radiologic examinations. RS was defined as a luminal narrowing with wall thickening relative to the normal gut on cross-sectional imaging (group 1 (G1)), which further divided into G1a (without upstream dilatation) and G1b (with upstream dilatation). ES was defined as an endoscopic non-passable stricture (group 2 (G2)). Strictures met the definitions of RS (with or without upstream dilatation) and ES were categorized as group 3 (G3). CAO referred to stricture-related surgery or penetrating disease. RESULTS: In the derivation cohort, G1b (93.3%) had the highest CAO occurrence rate, followed by G3 (32.6%), G1a (3.2%), and G2 (0%) (p < 0.0001); the same order was found in the validation cohort. The CAO-free survival time was significantly different among the four groups (p < 0.0001). Upstream dilatation (hazard ratio, 1.126) was a risk factor for predicting CAO in RS. Furthermore, when upstream dilatation was added to diagnose RS, 17.6% of high-risk strictures were neglected. CONCLUSIONS: CAO differs significantly between RS and ES, and clinicians should pay more attention to strictures in G1b and G3. Upstream dilatation has an important impact on the clinical outcome of RS but may not be an essential factor for RS diagnosis. CLINICAL RELEVANCE STATEMENT: This study explored the definition of intestinal stricture with the greatest significance for the clinical diagnosis and prognosis of patients with CD, and consequently provided effective auxiliary information for clinicians to formulate strategies for the treatment of CD intestinal strictures. KEY POINTS: • The retrospective double-center study showed that clinical adverse outcome is different between radiological strictures and endoscopic strictures in CD. • Upstream dilatation has an important impact on the clinical outcome of radiological strictures but may not be an essential factor for diagnosis of radiological strictures. • Radiological stricture with upstream dilatation and simultaneous radiological and endoscopic stricture were at increased risk for clinical adverse outcomes; thus, closer monitoring should be considered.

High TXNIP expression accelerates the migration and invasion of the GDM placenta trophoblast.

INTRODUCTION: Our previous study has proofed the glucose sensitive gene-thioredoxin-interacting protein (TXNIP) expression was up in the placenta of the patients with gestational diabetes mellitus (GDM), but the pathological mechanisms underlying abnormal TXNIP expression in the placenta of patients with GDM is completely unclear and additional investigations are required to explain the findings we have observed. In the present study, we simulated the high TXNIP expression via introducing the Tet-On "switch" in vitro, approximate to its expression level in the real world, to explore the following consequence of the abnormal TXNIP. METHODS: The expression and localization of TXNIP in the placenta of GDM patients and the health control was investigated via immunofluorescent staining, western blot and RT-qPCR. Overexpression of TXNIP was achieved through transfecting Tet-on system to the human trophoblastic cell line-HTR-8/Svneo cell. TXNIP knockout was obtained via CRISPR-Cas9 method. The cell phenotype was observed via IncuCyte Imaging System and flow cytometry. The mechanism was explored via western blot and RT-qPCR. RESULTS: The expression level of TXNIP in the GDM placenta was nearly 2-3 times higher than that in the control. The TXNIP located at trophoblastic cells of the placenta. When the expression of TXNIP was upregulated, the migration and invasion of the cells accelerated, but cell apoptosis and proliferation did not changed compared with the control group. Furthermore, the size of the TetTXNIP cells became larger, and the expression level of Vimentin and p-STAT3 increased in the TetTXNIP cells. All the changes mentioned above were opposite in the TXNIP-KO cells. CONCLUSIONS: Abnormal expression of TXNIP might be related to the impairment of the GDM placental function, affecting the migration and invasion of the placental trophoblast cells through STAT3 and Vimentin related pathway; thus, TXNIP might be the potential therapeutic target for repairing the placental dysfunction deficient in GDM patients.

Preoperative computed tomography enterography-based radiomics signature: A potential predictor of postoperative anastomotic recurrence in patients with Crohn's disease.

BACKGROUND: More than half of patients with Crohn's disease (CD) require at least one surgery for symptom management; however, approximately half of the patients may experience postoperative anastomotic recurrence (PAR). OBJECTIVES: This study aims to develop and validate a preoperative computed tomography enterography (CTE)-based radiomics signature to predict early PAR in CD. DESIGN: A total of 186 patients with CD (training cohort, n = 134; test cohort, n = 52) who underwent preoperative CTE and surgery between January 2014 and June 2020 were included in this retrospective multi-centre study. METHODS: 106 radiomic features were initially extracted from intestinal lesions and peri-intestinal mesenteric fat, respectively; significant radiomic features were selected from them and then used to develop intestinal or mesenteric radiomics signatures, using the least absolute shrinkage and selection operator and a Cox regression model. A radiomics-based nomogram incorporating these signatures with clinical-radiological factors was created for comparison with a model based on clinical-radiological features alone. RESULTS: 68 of 134 patients in training cohort and 16 of 52 patients in test cohort suffered from PAR. The intestinal radiomic signature (hazard ratio [HR]: 2.17; 95% confidence interval [CI]: 1.32-3.58; P = 0.002) and mesenteric radiomic signature (HR: 2.19; 95% CI: 1.14-4.19; P = 0.018) were independent risk factors for PAR in the training cohort as per a multivariate analysis. The radiomics-based nomogram (C-index: 0.710; 95% CI: 0.672-0.748) yielded superior predictive performance than the clinical-radiological model (C-index, 0.607; 95% CI: 0.582-0.632) in the test cohort. Decision curve analysis demonstrated that the radiomics-based nomogram outperformed the clinical-radiological model in terms of clinical usefulness. CONCLUSIONS: Preoperative mesenteric and intestinal CTE radiomics signatures are potential non-invasive predictors of PAR in postoperative patients with CD.

Efficiency and safety analysis of Plerixafor combined with granulocyte colony-stimulating factor on autologous hematopoietic stem cell mobilization in lymphoma / 中华血液学杂志

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.

The effect of omega-3 polyunsaturated fatty acids on stroke treatment and prevention: a systematic review and meta-analysis / El efecto de los ácidos grasos poliinsaturados omega-3 en el tratamiento y la prevención del accidente cerebrovascular: una revisión sistemática y metaanálisis

Background: in recent years, n-3 PUFAs have been confirmed to be associated with cardiovascular and cerebrovascular diseases, but the link between n-3 PUFAs and stroke remains controversial. Objective: this study aimed to evaluate the association between n-3 PUFAs and stroke. Methods: we performed a comprehensive search of the following electronic databases: PubMed, Embase, Cochrane Library, Web of Science and CNKI. Literature screening and quality assessment were performed according to inclusion and exclusion criteria. Cochrane's tool was used to assess the methodological components of each study, and the Stata 15.1 software was used to perform the meta-analysis. Results: a total of 18 RCTs were included, and the meta-analysis showed no differences in vascular disease-related death between the n-3 PUFA and control groups (RR, 0.95, 95 % CI: 0.89 to 1.01, p = 0.114 > 0.05). However, there was a significant difference in the lower n-3 PUFA dose subgroup (RR, 0.93, 95 % CI: 0.87 to 0.99, p = 0.034 < 0.05). Oral administration of n-3 PUFAs did not significantly reduce the risk of the following cerebrovascular accidents: stroke (RR = 1.00, 95 % CI: 0.93 to 1.07, p = 0.983 > 0.05), ischemic stroke (RR = 0.99, 95 % CI: 0.896 to 1.094, p = 0.841 > 0.05), hemorrhagic stroke (RR = 1.249, 95 % CI: 0.939 to 1.662, p = 0.127 > 0.05) and TIA (RR = 1.016, 95 % CI: 0.882 to 1.170, p = 0.824 > 0.05). The levels of TC (SMD, -0.167, 95 % CI: −0.193 to -0.141, p = 0 < 0.05) and TG (SMD, -0.065, 95 % CI: -0.087 to -0.042, p = 0 < 0.05) in the n-3 PUFA group were significantly decreased, but no significant improvement in the LDL (SMD, 0.022, 95 % CI: 0.005 to 0.040, p = 0.889 > 0.05) and HDL (SMD, 0.008, 95 % CI: -0.009 to 0.025, p = 0.368 > 0.05) levels was observed. Conclusion: this systematic review and meta-analysis suggests that treatment with low-dose n-3 PUFAs can reduce cerebrovascular disease-related death. After the oral administration of n-3 PUFAs (AU)

Antecedentes: en los últimos años se ha confirmado que los AGPI n-3 se relacionan con las enfermedades cardiovasculares y cerebrovasculares, pero el vínculo entre los AGPI n-3 y el ictus sigue siendo objeto de controversia. Objetivo: este estudio se propuso evaluar la relación entre AGPI n-3 e ictus. Métodos: se realizaron búsquedas en las siguientes bases de datos electrónicas: PubMed, Embase, Cochrane Library, Web of Science y CNKI. Se utilizó la herramienta de Cochrane para evaluar los componentes metodológicos de cada estudio y el software Stata para el metanálisis. Resutados: se incluyeron 18 ECA y el metanálisis no mostró diferencias en cuanto a la muerte relacionada con enfermedades vasculares entre los grupos de AGPI n-3 y de control (RR: 0,95, IC del 95 %: 0,89 a 1,01). Sin embargo, hubo una diferencia significativa en el subgrupo de dosis más baja de AGPI n-3 (RR: 0,93, IC del 95 %: 0,87 a 0,99). La administración oral de AGPI n-3 no redujo significativamente el riesgo de los siguientes accidentes cerebrovasculares: ictus (RR = 1,00, IC 95 %: 0,93 a 1,07), ictus isquémico (RR = 0,99, IC 95 %: 0,896 a 1. 094), ictus hemorrágico (RR = 1,249, IC 95 %: 0,939 a 1,662) y AIT (RR = 1,016, IC 95 %: 0,882 a 1,170). Los niveles de TC (DME: -0,167, IC del 95 %: -0,193 a 0,141) y TG (DME -0,065, IC del 95 %: -0,087 a -0,042) en el grupo de AGPI n-3 se redujeron significativamente, pero no hubo una mejora significativa en los niveles de LDL (SMD: 0,022, IC 95 %: 0,005 a 0,040) y HDL (SMD: 0,008, IC 95 %: -0,009 a 0,025). Conclusiones: esta revisión sistemática y metaanálisis sugiere que el tratamiento con PUFA n-3 en dosis bajas puede reducir la muerte relacionada con la enfermedad cerebrovascular. Después de la administración oral de PUFA n-3, los niveles de TC y TG disminuyeron significativamente, pero los PUFA n-3 no impidieron la aparición de accidentes cerebrovasculares ni mejoraron los niveles de LDL o HDL (AU)

Research progress of histidine-based tumor-targeting drug delivery systems / 药学学报

As a basic amino acid, histidine has a pKa close to the acidity of the tumor microenvironment, thus the charge and solubility of histidine are able to vary as the pH changes. Under a neutral environment, histidine is not charged and exhibits hydrophobic properties, while it can be protonated and becomes hydrophilic when exposed to mildly acidic pH, such as tumor microenvironment. Therefore, histidine is widely used in the design of drug delivery systems to target the mildly acidic pH of tumor microenvironment. This article reviews the recent progresses of histidine-based tumor-targeting drug delivery systems, and summarizes the principles on promoting internalization and tuning drug release by taking advantage of histidine. Finally, we point out the common issues on histidine application and illustrate its future prospects.

Identification of two novel poleroviruses and the occurrence of Tobacco bushy top disease causal agents in natural plants.

Tobacco bushy top disease (TBTD) is a devastating tobacco disease in the southwestern region of China. TBTD in the Yunnan Province is often caused by co-infections of several plant viruses: tobacco bushy top virus (TBTV), tobacco vein distorting virus (TVDV), tobacco bushy top virus satellite RNA (TBTVsatRNA) and tobacco vein distorting virus-associated RNA (TVDVaRNA). Through this study, two new poleroviruses were identified in two TBTD symptomatic tobacco plants and these two novel viruses are tentatively named as tobacco polerovirus 1 (TPV1) and tobacco polerovirus 2 (TPV2), respectively. Analyses of 244 tobacco samples collected from tobacco fields in the Yunnan Province through RT-PCR showed that a total of 80 samples were infected with TPV1 and/or TPV2, and the infection rates of TPV1 and TPV2 were 8.61% and 29.51%, respectively. Thirty-three TPV1 and/or TPV2-infected tobacco samples were selected for further test for TBTV, TVDV, TBTVsatRNA and TVDVaRNA infections. The results showed that many TPV1 and/or TPV2-infected plants were also infected with two or more other assayed viruses. In this study, we also surveyed TBTV, TVDV, TBTVsatRNA and TVDVaRNA infections in a total of 1713 leaf samples collected from field plants belonging to 29 plant species in 13 plant families and from 11 provinces/autonomous regions in China. TVDV had the highest infection rates of 37.5%, while TVDVaRNA, TBTV and TBTVsatRNA were found to be at 23.0%, 12.4% and 8.1%, respectively. In addition, TVDV, TBTV, TBTVsatRNA and TVDVaRNA were firstly detected of co-infection on 10 plants such as broad bean, pea, oilseed rape, pumpkin, tomato, crofton weed etc., and 1 to 4 of the TBTD causal agents were present in the samples collected from Guizhou, Hainan, Henan, Liaoning, Inner mongolia and Tibet autonomous regions. The results indicated that TBTD causal agents are expanding its host range and posing a risk to other crop in the field.

Occurrence of COVID-19 Symptoms During SARS-CoV-2 Infection Defines Waning of Humoral Immunity.

Approximately half of the SARS-CoV-2 infections occur without apparent symptoms, raising questions regarding long-term humoral immunity in asymptomatic individuals. Plasma levels of immunoglobulin G (IgG) and M (IgM) against the viral spike or nucleoprotein were determined for 25,091 individuals enrolled in a surveillance program in Wuhan, China. We compared 405 asymptomatic individuals who mounted a detectable antibody response with 459 symptomatic COVID-19 patients. The well-defined duration of the SARS-CoV-2 endemic in Wuhan allowed a side-by-side comparison of antibody responses following symptomatic and asymptomatic infections without subsequent antigen re-exposure. IgM responses rapidly declined in both groups. However, both the prevalence and durability of IgG responses and neutralizing capacities correlated positively with symptoms. Regardless of sex, age, and body weight, asymptomatic individuals lost their SARS-CoV-2-specific IgG antibodies more often and rapidly than symptomatic patients did. These findings have important implications for immunity and favour immunization programs including individuals after asymptomatic infections.

Effects of different corticosteroid doses and durations on smoke inhalation-induced acute lung injury and pulmonary fibrosis in the rat.

Excessive inflammation induced by cytokine storm and coagulation disorders is considered the primary characteristic of smoke inhalation-induced acute lung injury (SI-ALI). Glucocorticoids such as methylprednisolone (MP) are commonly used to treat patients with inflammatory diseases; however, the management of ALI or acute respiratory distress syndrome (ARDS) remains controversial. We explored the effects of different MP doses and durations in a rat SI-ALI model. SI-ALI model rats had a high mortality rate and severe lung injury with proinflammatory, procoagulant, and pro-fibrotic changes. We found that a medium MP dose (4 mg/kg) markedly improved survival rates compared with low (0.4 mg/kg) and high (40 mg/kg) doses in the acute phase. A medium dose significantly attenuated lung injury, and reduced proinflammatory cytokine production and neutrophil infiltration into alveoli. Both medium and high MP doses improved coagulation and fibrinolysis conditions compared with low-dose MP. We also explored the effect of different durations of MP treatment on attenuating fibrotic changes in late-phase SI-ALI. Pro-fibrotic chemokine levels were gradually increased, followed by an increase in collagen and fibrin deposition after smoke inhalation. Three and 7-day MP treatments significantly attenuated this process, which was reflected by a reduction in pro-fibrotic chemokine levels. There was no significant difference between 3- and 7-day treatments. We report that a medium MP (4 mg/kg) dose significantly reduced inflammation and coagulation disorders, as well as acute-phase mortality. Three-day MP treatment may sufficiently attenuate fibrotic changes in late-phase SI-ALI.

Coculture with bone marrow­derived mesenchymal stem cells attenuates inflammation and apoptosis in lipopolysaccharide­stimulated alveolar epithelial cells via enhanced secretion of keratinocyte growth factor and angiopoietin­1 modulating the Toll­like receptor­4 signal pathway.

Acute lung injury (ALI) is a common, costly and potentially lethal disease with characteristics of alveolar­capillary membrane disruption, pulmonary edema and impaired gas exchange due to increased apoptosis and pulmonary inflammation. There is no effective and specific therapy for ALI; however, mesenchymal stem cells (MSCs) have been demonstrated to be a potential option. Lipopolysaccharide (LPS) is a highly proinflammatory molecule that is used to mimic an in vivo inflammatory and damaged state in vitro. The present study investigated the effect of bone marrow­derived MSCs on an LPS­induced alveolar epithelial cell (A549 cell line) injury and its underlying mechanisms by a Transwell system. It was identified that a high LPS concentration caused a decrease in cell viability, increases in apoptosis, inflammatory cytokine release and NF­κB activity, disruption of the caspase­3/Bcl­2 ratio, upregulation of Toll­like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and toll­interleukin­1 receptor domain­containing adaptor inducing interferon (TRIF) expression, and facilitation of TLR4/MyD88 and TLR4/TRIF complex formation in A549 cells. Coculture with MSCs attenuated all of these activities induced by LPS in A549 cells. In addition, an increased level of keratinocyte growth factor (KGF) and angiopoietin­1 (ANGPT1) secretion from MSCs was observed under inflammatory stimulation. KGF and/or ANGPT1 neutralizing antibodies diminished the beneficial effect of MSC conditioned medium. These data suggest that MSCs alleviate inflammatory damage and cellular apoptosis induced by LPS in A549 cells by modulating TLR4 signals. These changes may be partly associated with an increased secretion of KGF and ANGPT1 from MSCs under inflammatory conditions. These data provide the basis for development of MSC­based therapies for ALI.

Hepatitis B virus infection: Defective surface antigen expression and pathogenesis.

Hepatitis B virus (HBV) infection is a global public health concern. HBV causes chronic infection in patients and can lead to liver cirrhosis, hepatocellular carcinoma, and other severe liver diseases. Thus, understanding HBV-related pathogenesis is of particular importance for prevention and clinical intervention. HBV surface antigens are indispensable for HBV virion formation and are useful viral markers for diagnosis and clinical assessment. During chronic HBV infection, HBV genomes may acquire and accumulate mutations and deletions, leading to the expression of defective HBV surface antigens. These defective HBV surface antigens have been found to play important roles in the progression of HBV-associated liver diseases. In this review, we focus our discussion on the nature of defective HBV surface antigen mutations and their contribution to the pathogenesis of fulminant hepatitis B. The relationship between defective surface antigens and occult HBV infection are also discussed.

CD4 T cell loss and Th2 and Th17 bias are associated with the severity of severe fever with thrombocytopenia syndrome (SFTS).

Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease caused by a novel bunyavirus with high mortality. Immune suppression is thought to be crucial in disease progression. However, data on immune responses during SFTS are scarce. This study aimed to evaluate the changes in CD4 T-cell subsets throughout the entirety of infection and analyse their relationships with disease severity in SFTS patients. In parallel with CD4 T-cell depletion, decreased Th1, Th2 and Treg numbers, but comparable Th17-cell numbers, were observed in deceased patients compared with those in surviving patients. Additionally, increased Th2 and Th17-cell percentages in the residual CD4 T-cell population led to aberrant Th2/Th1 and Th17/Treg ratios, which were positively correlated with disease severity. Collectively, our data indicated that CD4 T-cell deficiency, Th2 and Th17 bias were closely correlated with the severity of SFTS, indicating therapeutic potential of early immune interventions to ameliorate disease severity.

Dynamic changes in the immunological characteristics of T lymphocytes in surviving patients with severe fever with thrombocytopenia syndrome (SFTS).

OBJECTIVE: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality. T cell deficiency has recently been described, but the changes in T cell functionality during acute SFTS virus (SFTSV) infection and the mechanisms leading to T lymphocyte death remain largely unknown. This study was conducted to evaluate T cell functionality and the expression of apoptotic/proliferation and activation/inhibition markers during acute SFTSV infection. METHODS: Twenty-eight surviving SFTS patients were sequentially sampled during their entire hospital stay. SFTSV RNA copies were investigated using real-time RT-PCR. The expression levels of apoptotic markers (annexin V and CD95) and proliferation and activation markers (Ki-67, HLA-DR, and CD25) and the expression levels of programmed cell death-1 (PD-1), interferon gamma (IFN-γ), and granzyme B in T cells were evaluated by flow cytometry for the SFTS patients. RESULTS: In parallel with T cell depletion, higher annexin V and CD95 expression was observed in SFTS patients. Additionally, the expression levels of Ki-67, HLA-DR, CD25, and PD-1 and the levels of IFN-γ and granzyme B in T lymphocytes were markedly increased in the SFTS patients. CONCLUSIONS: T cell proliferation, activation, and functional enhancement were apparent despite the observation of T cell apoptosis, suggesting that these processes are involved in the complex protective response to SFTSV infection.

Application of Virtual Reality in Burn Rehabilitation(review) / 中国康复理论与实践

This article reviewed the application of virtual reality in motor functional training,management of pain,psychological therapy,and so on,and discussed the further development in China.

Hepatic amyloidosis disease: clinic analysis of six cases / 中国医师进修杂志

Objective To summarize the clinical characteristics of hepatic amyloidosis disease by analyzing the data of this disease. Methods Six cases of hepatic amyloidosis out of 32 cases of amyloidosis were selected and the patients clinical characteristics, laboratory tests, treatments and prognosis were analyzed retrospectively. Results All the patients presented weight loss, fatigue, hepatomegaly as well as proteinuria. Four patients had splenomegaly and 3 patients had ventricular hypertrophy. The levels of alkaline phosphatase(ALP)and γ-glutamyl transpeptidase(GGT)in all patients elevated 1.5 times more than the upper limit of normal.Three of them performed immunoglobulin electrophoresis,and the results of which were abnormal.All of them did involved organ biopsy,including liver(3 cases)and kidney(3 cases).All of them demonstrated amyloid deposition.None of them suffered bleeding and death during the biopsy. Organ pathology assessing was not enough. Prognostic markers included hyperbilirubinemia,ALP more than 500 U/L,B type natriuretic peptides,plasma cells clone,β2 microglobulin and other organ function. Conclusions The patients with hepatic amyloidosis disease present hepatomegaly with different sizes and mildly abnormal liver test(mainly with elevated GGT and ALP). Most cases have multiple organs pathology including kidney, spleen and heart. Laboratory test often shows hyperlipidemia and abnormal serum free light chain.It is always confirmed by pathology.

Stem cell models for commercialization / 中国组织工程研究

BACKGROUND: Stem cells are the potentially immortal cells capable of self-renewal, which are essential to the mystery of human development and aging, and are also the core of research for regenerative medicine. OBJECTIVE: To summarize the biological characteristics of embryonic stem cells, adult stem cells and induced pluripotent stem cells, to review the clinical and commercial applications in stem cell therapy and drug screening, and to analyze the problems and prospects in stem cell industry. METHODS: We searched relevant articles about stem cell models in PubMed and CNKI databases during 1995 to 2017 on internet, and took"stem cells, embryonic stem cells, adult stem cells, induced pluripotent stem cells, stem cell therapy, drug screening" as the keywords in English and Chinese, respectively. RESULTS AND CONCLUSION: According to the origin, stem cell models are divided into three types: embryonic stem cells, adult stem cells and induced pluripotent stem cells. Different types of stem cells have their unique biological advantages. Embryonic stem cells can generate all somatic cell types, but the application is limited by ethical disputes. As for adult stem cells, there are the most extensive and in-depth, studies as the well as the most prevalent and mature applications. Induced pluripotent stem cells have similar characteristics as embryonic stem cells, and furthermore their use avoids source restriction, moral and ethical controversies, bringing new opportunities for stem cell application. Stem cell-based cell therapy has shown successful achievement. There have been a few commercial products about adult stem cells-based cell therapy; in the meanwhile both embryonic stem cells and induced pluripotent stem cells are making their way into clinical trials. In addition, pluripotent stem cells hold great promise for the specific drug screening because they enable scientists to establish a variety of cell and disease models in vitro.

Analysis of adverse reactions' factors to Danhong injection--nested case control study by using hospital centralized monitoring data / 中国中药杂志

To study the adverse reactions' factors to Danhong injection in the real world. A multi-center, large sample and prospective hospital centralized monitoring method was adopted, and 30 888 cases of Danhong injection from 37 national 3A hospitals were collected to carry out a nested case control design study. These cases were divided into adverse reaction group and non-adverse group. Single factor logistic regression and multiple factor logistic regression were used to analyze data, and investigate the correlation between adverse reaction and gender, allergy history, methods of administration, and combined drug use. One hundred and eight cases of adverse reactions in 30 888 patients were determined, with an incidence of 0.35%. The results showed that Danhong injection combined with other medication(potassium mendoxine magnesium, thymic peptide, celecoxib, fumarate bisoprolol) with history of adverse reactions including scephalosporin allergy and proprietary Chinese medicine allergies had more adverse reactions than the control group(<0.05, estimated coefficient>0), indicating that these six factors were the risk factors for the adverse reaction of Danhong injection. The adverse reaction of Danhong injection combined with the aspirin was less than that in the control group(<0.05, estimated coefficient<0), indicating that the aspirin was a non-risk factor for the adverse reaction of Danhong injection. All the above results indicate that the adverse factors to Danhong injection include scephalosporin allergy, patent Chinese medicine allergy, Danhong injection combined with medication(potassium mendoxine magnesium, thymic peptide, celecoxib, fumarate bisoprolol), suggesting special attention shall be paid in clinical application.

Paralemmin-3 contributes to lipopolysaccharide-induced inflammatory response and is involved in lipopolysaccharide-Toll-like receptor-4 signaling in alveolar macrophages.

Alveolar macrophages (AMs) are the first line of defense against foreign stimulation in alveoli, and they participate in inflammatory responses during acute lung injury (ALI). Previous studies indicated that paralemmin-3 (PALM3) expression is induced by lipopolysaccharides (LPS) and may be involved in LPS-Toll-like receptor 4 (TLR4) signaling in alveolar epithelial cells. The aim of the present study was to investigate the effect of PALM3 on LPS-induced inflammation and its underlying mechanisms in rat AMs. For this purpose, the authors detected the expression of PALM3 in AMs by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting following LPS stimulation. Following this, a recombinant adenovirus expressing short hairpin RNA (shRNA) for PALM3 was constructed, as well as a recombinant adenovirus carrying the rat PALM3 gene to modulate the expression of PALM3 in rat AMs. At 48 h after transfection, the PALM3 expression in AMs was detected by RT-qPCR and western blotting. The levels of several cytokines and the activity of nuclear factor-κB and interferon regulatory factor 3 in AMs were measured after LPS stimulation. The localization of PALM3 and LPS-TLR4 signaling adaptor molecules in AMs was analyzed by confocal microscopy, and the physical interactions of PALM3 with these adaptors were assessed by co-immunoprecipitation assays. LPS induced PALM3 expression in AMs and that PALM3 expression promoted the LPS-induced inflammatory response, while PALM3 downregulation suppressed the LPS-induced inflammatory response in AMs. In addition, the results demonstrated that PALM3 could interact with TLR4, myeloid differentiation factor 88, interleukin (IL)-1 receptor associated kinase-1, tumor necrosis factor receptor associated factor-6, and Toll-IL-1 receptor containing adapter molecule-2 in AMs after LPS stimulation. These results suggested that PALM3 contributes to the LPS-induced inflammatory response and participates in LPS-TLR4 signaling in AMs. These data may provide the basis for the development of novel targeted therapeutic strategies of treating ALI.