Humans ; Consensus ; Immunoglobulin Light-chain Amyloidosis/therapy* ; Heart ; Immunoglobulin Light Chains ; China

Humans ; Adult ; Serum Albumin, Human ; Consensus ; Cardiac Surgical Procedures ; Thoracic Surgery

Objective To investigate the ameliorative effect of salidroside on diabetes retinopathy (DR) rats and its mechanism. Methods Male SD rats were randomly divided into blank group, model group, low-dose and high-dose salidroside treatment groups. Except for the blank group, other groups were modeled by intraperitoneal injection of streptozotocin. After successful modeling, treatment groups were injected intraperitoneally with [50 mg/(kg.d)] and [100 mg/(kg.d)] salidroside respectively, for 4 weeks; the blank group and model group were injected with corresponding doses of saline. ELISA was used to measure the expression levels of antioxidant-related enzyme activity and inflammatory factors in blood glucose and serum of rats in each group. Retinal tissue lesions were detected by HE staining, and the expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) in retinal tissues were detected by immunohistochemical staining. Western blot analysis was used to detect the expression of phosphatidylinositol 3 kinase (PI3K) , nuclear factor κB p65 (NF-κB p65), phosphorylated p38 MAPK (p-p38 MAPK), and phosphorylated protein kinase B (p-AKT) proteins. Results Compared with model group, salidroside could significantly reduce blood glucose level and increase body mass in DR rats. The serum levels of superoxide dismutase (SOD) and catalase (CAT) were significantly increased, while the levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and IL-1β were reduced. The protein expression of VEGF, ICAM-1, NF-κB p65 and p-p38 MAPK was significantly decreased, while the protein expression of PI3K and p-AKT was increased. Conclusion Salidroside can reduce DR in rats by inhibiting oxidative stress and immune inflammatory response, which may be related to the reduction of abnormal expression of VEGF and ICAM-1 and the activation of PI3K/AKT signaling pathway.
Animals ; Male ; Rats ; Blood Glucose ; Diabetes Mellitus ; Inflammation/metabolism* ; Intercellular Adhesion Molecule-1/metabolism* ; NF-kappa B/metabolism* ; Oxidative Stress ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats, Sprague-Dawley ; Retinal Diseases ; Tumor Necrosis Factor-alpha/metabolism* ; Vascular Endothelial Growth Factor A/metabolism*

OBJECTIVES: To investigate the clinical manifestations and laboratory examination results of children with Kawasaki disease complicated by macrophage activation syndrome (KD-MAS), and to provide a basis for identifying early warning indicators for the early diagnosis and treatment of KD-MAS. METHODS: A retrospective study was performed on 27 children with KD-MAS (KD-MAS group) and 110 children with KD (KD group) who were admitted to Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2014 to January 2022. Clinical and laboratory data were compared between the two groups. The receiver operating characteristic (ROC) curve was used to investigate the value of laboratory markers with statistical significance in the diagnosis of KD-MAS. RESULTS: Compared with the KD group, the KD-MAS group had significantly higher incidence rates of hepatomegaly, splenomegaly, incomplete KD, no response to intravenous immunoglobulin, coronary artery damage, multiple organ damage, and KD recurrence, as well as a significantly longer length of hospital stay (<i>Pi><0.05). Compared with the KD group, the KD-MAS group had significantly lower levels of white blood cell count, absolute neutrophil count, hemoglobin, platelet count (PLT), erythrocyte sedimentation rate, serum albumin, serum sodium, prealbumin, and fibrinogen (FIB), a significantly lower incidence rate of non-exudative conjunctiva, and significantly higher levels of C-reactive protein, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase (LDH), and serum ferritin (SF) (<i>Pi><0.05). The ROC curve analysis showed that SF, PLT, FIB, and LDH had high value in the diagnosis of KD-MAS, with areas under the curve (AUC) of 0.989, 0.966, 0.932, and 0.897, respectively (<i>Pi><0.001), and optimal cut-off values of 349.95 μg/L, 159×10⁹/L, 3.85 g/L, and 403.50 U/L, respectively. The combination of SF, PLT, FIB, and LDH had a larger AUC than PLT, FIB, and LDH alone in the diagnosis of KD-MAS (<i>Pi><0.05), but there was no significant difference in the AUC between the combination of SF, PLT, FIB, and LDH and SF alone (<i>Pi>>0.05). CONCLUSIONS KD-MAS should be considered when children with KD have hepatosplenomegaly, no response to intravenous immunoglobulin, coronary artery damage, and KD recurrence during treatment. SF, PLT, FIB, and LDH are of high value in the diagnosis of KD-MAS, especially SF is of great significance in the diagnosis of KD-MAS.
Child ; Humans ; Immunoglobulins, Intravenous ; Macrophage Activation Syndrome/etiology* ; Mucocutaneous Lymph Node Syndrome/diagnosis* ; Retrospective Studies ; Blood Sedimentation ; Hepatomegaly

OBJECTIVES: To develop a risk prediction model for severe adenovirus pneumonia (AVP) in children, and to explore the appropriate timing for intravenous immunoglobulin (IVIG) therapy for severe AVP. METHODS: Medical data of 1 046 children with AVP were retrospectively analyzed, and a risk prediction model for severe AVP was established using multivariate logistic regression. The model was validated with 102 children with AVP. Then, 75 children aged ≤14 years who were considered at risk of developing severe AVP by the model were prospectively enrolled and divided into three groups (A, B and C) in order of visit, with 25 children in each group. Group A received symptomatic supportive therapy only. With the exception of symptomatic supportive therapy, group B received IVIG treatment at a dose of 1g/(kg·d) for 2 consecutive days, before progressing to severe AVP. With the exception of symptomatic supportive therapy, group C received IVIG treatment at a dose of 1 g/(kg·d) for 2 consecutive days after progressing to severe AVP. Efficacy and related laboratory indicators were compared among the three groups after treatment. RESULTS: Age<18.5 months, underlying diseases, fever duration >6.5 days, hemoglobin level <84.5 g/L, alanine transaminase level >113.5 U/L, and co-infection with bacteria were the six variables that entered into the risk prediction model for severe AVP. The model had an area under the receiver operating characteristic curve of 0.862, sensitivity of 0.878, and specificity of 0.848. The Hosmer-Lemeshow test showed good consistency between the predicted values and the actual observations (<i>Pi>>0.05). After treatment, group B had the shortest fever duration and hospital stay, the lowest hospitalization costs, the highest effective rate of treatment, the lowest incidence of complications, the lowest white blood cell count and interleukin (IL)-1, IL-2, IL-6, IL-8, IL-10 levels, and the highest level of tumor necrosis factor alpha (<i>Pi><0.05). CONCLUSIONS The risk model for severe AVP established in this study has good value in predicting the development of severe AVP. IVIG therapy before progression to severe AVP is more effective in treating AVP in children.
Child ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Prospective Studies ; Retrospective Studies ; Adenoviridae Infections/drug therapy* ; Pneumonia, Viral/drug therapy* ; Adenoviridae

OBJECTIVE: To investigate the effect and relative mechanism of Recombinant Human Thrombopoietin (rhTPO) on long-term hematopoietic recovery in mice with acute radiation sickness. METHODS: Mice were intramuscularly injected with rhTPO (100 μg/kg) 2 hours after total body irradiation with ⁶⁰Co γ-rays (6.5 Gy). Moreover, six months after irradiation, peripheral blood, hematopoietic stem cells (HSC) ratio, competitive transplantation survival rate and chimerization rate, senescence rate of c-kit⁺ HSC, and <i>p16i> and <i>p38i> mRNA expression of c-kit⁺ HSC were detected. RESULTS: Six months after 6.5 Gy γ-ray irradiation, there were no differences in peripheral blood white blood cells, red blood cells, platelets, neutrophils and bone marrow nucleated cells in normal group, irradiated group and rhTPO group (P>0.05). The proportion of hematopoietic stem cells and multipotent progenitor cells in mice of irradiated group was significantly decreased after irradiation (<i>Pi><0.05), but there was no significant changes in rhTPO group (P>0.05). The counts of CFU-MK and BFU-E in irradiated group were significantly lower than that in normal group, and rhTPO group was higher than that of the irradiated group(<i>Pi><0.05). The 70 day survival rate of recipient mice in normal group and rhTPO group was 100%, and all mice died in irradiation group. The senescence positive rates of c-kit⁺ HSC in normal group, irradiation group and rhTPO group were 6.11%, 9.54% and 6.01%, respectively (<i>Pi><0.01). Compared with the normal group, the <i>p16i> and <i>p38i> mRNA expression of c-kit⁺ HSC in the irradiated mice were significantly increased (<i>Pi><0.01), and it was markedly decreased after rhTPO administration (<i>Pi><0.01). CONCLUSION The hematopoietic function of mice is still decreased 6 months after 6.5 Gy γ-ray irradiation, suggesting that there may be long-term damage. High-dose administration of rhTPO in the treatment of acute radiation sickness can reduce the senescence of HSC through p38-p16 pathway and improve the long-term damage of hematopoietic function in mice with acute radiation sickness.
Humans ; Mice ; Animals ; Thrombopoietin/metabolism* ; Hematopoietic Stem Cells ; Blood Platelets ; Recombinant Proteins/therapeutic use* ; Radiation Injuries ; RNA, Messenger/metabolism*

Immune thrombocytopenia (ITP) is an immune-mediated acquired hemorrhagic autoimmune disease. At present, the first-line therapeutic drugs for ITP include glucocorticoids and intravenous immunoglobulins. However, about 1/3 of the patients had no response to the first-line treatment, or relapsed after dose reduction or withdrawal of glucocorticoids. In recent years, with the gradual deepening of the understanding on the pathogenesis of ITP, the drugs targeting different pathogenesis continually emerge, including immunomodulators, demethylating agents, spleen tyrosine kinase (SYK) inhibitors and neonatal Fc receptor (FcRn) antagonist. However, most of these drugs are in clinical trials. This review summarized briefly the recent advances in the treatment of glucocorticoids resistance and relapsed ITP, so as to provide reference for the clinical treatments.
Infant, Newborn ; Humans ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; Glucocorticoids/therapeutic use* ; Thrombocytopenia ; Immunoglobulins, Intravenous/therapeutic use* ; Immunologic Factors/therapeutic use*

OBJECTIVES: Restoration of blood circulation within "time window" is the principal treating goal for treating acute ischemic stroke. Previous studies revealed that delayed recanalization might cause serious ischemia/reperfusion injury. However, plenty of evidences showed delayed recanalization improved neurological outcomes in acute ischemic stroke. This study aims to explore the role of delayed recanalization on blood-brain barrier (BBB) in the penumbra (surrounding ischemic core) and neurological outcomes after middle cerebral artery occlusion (MCAO). METHODS: Recanalization was performed on the 3rd day after MCAO. BBB disruption was tested by Western blotting, Evans blue dye, and immunofluorescence staining. Infarct volume and neurological outcomes were evaluated on the 7th day after MCAO. The expression of fibroblast growth factor 21 (FGF21), fibroblast growth factor receptor 1 (FGFR1), phosphatidylinositol-3-kinase (PI3K), and serine/threonine kinase (Akt) in the penumbra were observed by immunofluorescence staining and/or Western blotting. RESULTS: The extraversion of Evans blue, IgG, and albumin increased surrounding ischemic core after MCAO, but significantly decreased after recanalization. The expression of Claudin-5, Occludin, and zona occludens 1 (ZO-1) decreased surrounding ischemic core after MCAO, but significantly increased after recanalization. Infarct volume reduced and neurological outcomes improved following recanalization (on the 7th day after MCAO). The expressions of Claudin-5, Occludin, and ZO-1 decreased surrounding ischemic core following MCAO, which were up-regulated corresponding to the increases of FGF21, p-FGFR1, PI3K, and p-Akt after recanalization. Intra-cerebroventricular injection of FGFR1 inhibitor SU5402 down-regulated the expression of PI3K, p-Akt, Occludin, Claudin-5, and ZO-1 in the penumbra, which weakened the beneficial effects of recanalization on neurological outcomes after MCAO. CONCLUSIONS Delayed recanalization on the 3rd day after MCAO increases endogenous FGF21 in the penumbra and activates FGFR1/PI3K/Akt pathway, which attenuates BBB disruption in the penumbra and improves neurobehavior in MCAO rats.
Animals ; Rats ; Blood-Brain Barrier/metabolism* ; Brain Ischemia ; Claudin-5/metabolism* ; Infarction, Middle Cerebral Artery/metabolism* ; Ischemic Stroke/metabolism* ; Occludin/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats, Sprague-Dawley ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Reperfusion Injury/metabolism*

Objective: To investigate the prognostic value of preoperative inflammatory and nutritional condition detection in the postoperative survival, and establish a prognostic model for predicting the survival of patients with gastric cancer. Methods: The clinicopathological data of 1123 patients with gastric cancer who had undergone radical gastrectomy in Tianjin Medical University Cancer Institute & Hospital from January 2005 to December 2014 were retrospectively analyzed. Patients with history of other malignancy, with history of gastrectomy, who had received preoperative treatment, who died during the initial hospital stay or first postoperative month, and missing clinical and pathological information were excluded. Cox univariate and multivariate analyses were used to identify independent clinicopathological factors associated with the survival of these gastric cancer patients. Cox univariate analysis was used to identify preoperative inflammatory and nutritional indexes related to the survival of patients with gastric cancer after radical gastrectomy. Moreover, the Cox proportional regression model for multivariate survival analysis (forward stepwise regression method based on maximum likelihood estimation) was used. The independent clinicopathological factors that affect survival were incorporated into the following three new prognostic models: (1) an inflammatory model: significant preoperative inflammatory indexes identified through clinical and univariate analysis; (2) a nutritional model: significant preoperative nutritional indexes identified through clinical and univariate analysis; and (3) combined inflammatory/nutritional model: significant preoperative inflammatory and nutritional indexes identified through clinical and univariate analysis. A model that comprised only pT and pN stages in tumor TNM staging was used as a control model. The integrated area under the receiver operating characteristic curve (iAUC) and C-index were used to evaluate the discrimination of the model. Model fitting was evaluated by Akaike information criterion analysis. Calibration curves were used to assess agreement between the predicted probabilities and actual probabilities at 3-year or 5-year overall survival (OS). Results: The study cohort comprised 1 123 patients with gastric cancer. The mean age was 58.9±11.6 years, and 783 were males. According to univariate analysis, age, surgical procedure, extent of lymph node dissection, tumor location, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and nerve invasion were associated with 5-year OS after radical gastrectomy for gastric cancer (all <i>Pi><0.050). Multivariate analysis further identified age (HR: 1.18, 95%CI: 1.03-1.36, <i>Pi>=0.019), maximum tumor size (HR: 1.19, 95%CI: 1.03-1.38, <i>Pi>=0.022), number of examined lymph nodes (HR: 0.79, 95%CI: 0.68-0.92, <i>Pi>=0.003), pT stage (HR: 1.40, 95%CI: 1.26-1.55, <i>Pi><0.001) and pN stage (HR: 1.28, 95%CI: 1.21-1.35, <i>Pi><0.001) as independent prognostic factors for OS of gastric cancer patients. Additionally, according to univariate survival analysis, the preoperative inflammatory markers of neutrophil count, percentage of neutrophils, neutrophil/lymphocyte ratio, platelet/neutrophil ratio and preoperative nutritional indicators of serum albumin and body mass index were potential prognostic factors for gastric cancer (all <i>Pi><0.05). On the basis of the above results, three models for prediction of prognosis were constructed. Variables included in the three models are as follows. (1) Inflammatory model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, and neutrophil-lymphocyte ratio; (2) nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and serum albumin; and (3) combined inflammatory/nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, neutrophil-lymphocyte ratio, and serum albumin. We found that the predictive accuracy of the combined inflammatory/nutritional model, which incorporates both inflammatory indicators and nutrition indicators (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.698),was superior to that of the inflammation model (iAUC: 0.662, 95% CI: 0.673-0.706;C-index: 0.675), nutritional model (iAUC: 0.666, 95% CI: 0.642-0.698, C-index: 0.672), and TNM staging control model (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.658). Furthermore, the combined inflammatory/nutritional model had better fitting performance (AIC: 10 762) than the inflammatory model (AIC: 10 834), nutritional model (AIC: 10 810), and TNM staging control model (AIC: 10 974). Conclusions: Preoperative percentage of neutrophils, NLR, and BMI have predictive value for the prognosis of gastric cancer patients. The inflammatory / nutritional model can be used to predict the survival and prognosis of gastric cancer patients on an individualized basis.
Male ; Humans ; Middle Aged ; Aged ; Female ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/pathology* ; Neoplasm Staging ; Gastrectomy ; Serum Albumin

OBJECTIVE: To evaluate the value of pharmacogenetic testing for improving the efficacy and safety of treatment with cyclosporine, tacrolimus, and cyclophosphamide (CTX) for PLA2R-related membranous nephropathy and for determing individualized and precise treatment plans for the patients. METHODS: A total of 63 patients with PLA2R-related membranous nephropathy hospitalized in the Department of Nephrology at our hospital from January, 2019 to October, 2021 were enrolled in this study. Thirty-three of the patients underwent pharmacogenetic testing before taking the immunosuppressive drugs selected based on the results of genetic screening for sensitive targets, and the other 30 patients were empirically given immunosuppressive drugs according to the guidelines (control group). The clinical efficacy and adverse effects of the immunosuppressive drugs were analyzed for all the patients. The two groups of patients were compared for demographic and biochemical parameters including 24-h urine protein, serum albumin, renal function, and serum anti-phospholipase A2 receptor antibody both before and at 3 months after the beginning of the treatment. RESULTS: Among the 33 patients undergoing pharmacogenetic testing, 51.5% showed a GG genotype for cyclosporine, and 61.6% had an AG genotype for tacrolimus; for CTX, 51.5% of the patients showed a homozygous deletion and 63.6% had an AA genotype. After treatment for 3 months, serum anti-phospholipase A2 receptor antibody, 24-h urine protein, and serum albumin levels were significantly improved in pharmacogenetic testing group as compared with the control group (<i>Pi> < 0.05). CONCLUSION Individualized and precise administration of immunosuppressive drugs based on pharmacogenetic testing better controls proteinuria and serum antiphospholipase A2 receptor antibodies and increases serum albumin level in patients with PLA2R-related membranous nephropathy.
Humans ; Autoantibodies ; Cyclosporine/therapeutic use* ; Glomerulonephritis, Membranous/diagnosis* ; Homozygote ; Immunosuppressive Agents/therapeutic use* ; Pharmacogenomic Testing ; Receptors, Phospholipase A2 ; Sequence Deletion ; Serum Albumin ; Tacrolimus/therapeutic use*