Cerebral blood vessels and perfusion in the pediatric brain death: five cases studied by neuroimaging.

PURPOSE: To detect the cerebral blood vessels and perfusion using neuroimaging modalities including computed tomography angiography (CTA), computed tomography perfusion (CTP), and arterial spin labeling (ASL) in children with brain death (BD). METHODS: According to the current children's BD criteria, 5 children (3 males, 2 females, mean age of 5.65 years) with BD were enrolled from January 2019 to December 2020. The imaging features of CTA, CTP, and ASL were evaluated to analyze the visualization of important intracranial blood vessels and the states of the cerebral blood flow (CBF) and cerebral blood volume (CBV) related to the region of interest (ROI) brain tissue during the two clinical assessments for BD. RESULTS: The "4-point scale" scoring system of CTA was applied to evaluate BD and no negative results were detected. The CTP results of the 5 children suggested the cessation of cerebral circulation with 100% positive results. The ranges of CBF and CBV were 0.00-9.52 ml/100 g/min (mean value 4.95 ± 1.69 ml/100 g/min) and 0.00-1.34 ml/100 g (mean value 0.36 ± 0.20 ml/100 g), respectively. One patient also underwent ASL examination, which demonstrated a significant reduction in whole brain perfusion, indicating the absence of cerebral circulation. The CBF values of the brainstem, basal ganglia, and prefrontal lobe were 11.61 ± 1.49 ml/100 g/min, 7.81 ± 2.42 ml/100 g/min, and 9.94 ± 2.01 ml/100 g/min, respectively. CONCLUSION: Neuroimaging examinations particularly CTA and CTP reveal well the hemodynamic and cerebral blood vessels changes of BD, which can be used as supplementary supportive evidence for the declaration of brain death in children.

[Association between risk factors during maternal pregnancy and the neonatal period and childhood bronchial asthma].

OBJECTIVE: To study the association of the risk factors during maternal pregnancy and the neonatal period with childhood bronchial asthma. METHODS: A total of 306 children with asthma (asthma group) and 250 healthy children (control group) were enrolled. Their clinical data during the neonatal period and the maternal data during pregnancy were retrospectively studied. RESULTS: The univariate analysis showed that there were significant differences in the rates of maternal use of antibiotics during pregnancy, use of antibiotics and probiotics during the neonatal period, preterm birth, cesarean section, low birth weight, and breast feeding (>6 months) between the asthma and control groups (P<0.05). The multivariate logistic regression analysis showed that use of antibiotics during pregnancy (OR=3.908, 95%CI: 1.277-11.962), use of antibiotics during neonatal period (OR=24.154, 95%CI: 7.864-74.183), preterm birth (OR=8.535, 95%CI: 2.733-26.652), and cesarean section (OR=4.588, 95%CI: 2.887-7.291) were independent risk factors for childhood asthma. The use of probiotics during the neonatal period (OR=0.014, 95%CI: 0.004-0.046) and breast feeding (>6 months) (OR=0.161, 95%CI: 0.103-0.253) were protective factors for childhood asthma. CONCLUSIONS: The early prevention of childhood asthma can be improved by reducing the use of antibiotics during pregnancy, reducing cesarean section, avoiding abuse of antibiotics during the neonatal period, trying breast feeding and taking probiotics in early stage.

Subject-Specific Fully-Coupled and One-Way Fluid-Structure Interaction Models for Modeling of Carotid Atherosclerotic Plaques in Humans.

BACKGROUND: Hemodynamics play an important role in the development and progression of carotid atherosclerosis, and may be important in the assessment of plaque vulnerability. The aim of this study was to develop a system to assess the hemodynamics of carotid atherosclerotic plaques using subject-specific fluid-structure interaction (FSI) models based on magnetic resonance imaging (MRI). MATERIAL AND METHODS: Models of carotid bifurcations (n=86 with plaques from 52 patients, n=14 normal carotids from 12 participants) were obtained at the Department of Radiology, Beijing Tian Tan Hospital between 2010 and 2013. The maximum von Mises stress, minimum pressure, and flow velocity values were assessed at the most stenotic site in patients, or at the carotid bifurcations in healthy volunteers. Results of one-way FSI were compared with fully-coupled FSI for the plaques of 19 randomly selected models. RESULTS: The maximum von Mises stress and the minimum pressure and velocity were significantly increased in the stenosis group compared with controls based on one-way FSI (all P<0.05). The maximum von Mises stress and the minimum pressure were significantly higher and the velocity was significantly lower based on fully coupled FSI compared with on-way FSI (all P<0.05). Although there were differences in numerical values, both methods were equivalent. The maximum von Mises stress of vulnerable plaques was significantly higher than stable plaques (P<0.001). The maximum von Mises stress of the group with fibrous cap defect was significantly higher than the group without fibrous cap defect (P=0.001). CONCLUSIONS: The hemodynamics of atherosclerotic plaques can be assessed noninvasively using subject-specific models of FSI based on MRI.

[Treatment of rheumatoid arthritis by Yangxue Tongluo Recipe combined with immunosuppressive agents: a clinical observation].

OBJECTIVE: To observe the therapeutic effect of Yangxue Tongluo Recipe (YTR) combined with immunosuppressive agents in the treatment of rheumatoid arthritis (RA). METHODS: Totally 88 RA patients were randomly assigned to the treatment group [47 cases, YTR combined Methotrexate (MTX) + Leflunomide (LEF) treatment] and the control group (41 cases, MTX + LEF therapy). All patients received 12-week treatment. Clinical symptoms and signs, laboratory tests [erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and C reactive protein (CRP)], and adverse reactions were observed before and after treatment. RESULTS: The total effective rate was 91.5% (43/47 cases) in the treatment group, and the total effective rate was 75.6% (31/41 cases) in the control group. There was statistical difference between the two groups (P < 0.05). The morning stiffness, the rest pain, the number of tender joints, the number of swollen joints, tender joint index, swollen joint index, ESR, RF, and CRP were significantly improved in the two groups after treatment (P < 0.01). Besides, clinical symptoms and signs, ESR, RF, and CRP were more improved in the treatment group after treatment, when compared with those in the control group (P < 0.05). Gastrointestinal discomfort was the main adverse reaction in the two groups, but the occurrence was lower in the treatment group than in the control group (P > 0.05). CONCLUSIONS: The clinical efficacy of YTR combined MTX + LEF in the treatment of RA was better than using Western medicine alone. It was more safe with less adverse reactions.

Do magnetic resonance imaging manifestations of skeletal system improve after treatment of Gaucher disease?

OBJECTIVES: Skeletal lesions are the most serious complications of Gaucher disease (GD). The pathological changes of skeletal system are complex, which seriously affects the quality of life. The aim was to investigate whether the skeletal system improved in quantitative imaging after treatment with enzyme replacement therapy (ERT). METHODS: Magnetic resonance imaging (MRI) of the vertebrae and femur was performed in 40 patients and 34 healthy volunteers. The scan sequences include iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation (IDEAL-IQ) and intravoxel incoherent motion imaging (IVIM). Statistical data were analyzed by using t-test. RESULTS: As for the fat fraction (FF) and R2*, there were significant differences in FF and R2* of vertebrae and left femur. As for the standard apparent diffusion coefficient (sADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*) and fraction of fast apparent diffusion coefficient (f) of vertebrae and femur. Only D of vertebrae, sADC and f of left femur and sADC of right femur had statistical difference. CONCLUSION: The quantitative imaging of skeletal system lesions have certain characteristics. The lesions in the skeletal system of patients treated with ERT has been improved to some extent, but it is still different from that in normal people.

Efficacy and safety of glucocorticoids therapy for IgA nephropathy: a meta-analysis of randomized controlled trials.

BACKGROUND: Published reports examining the efficacy and safety of glucocorticoids for preserving renal function in immunoglobulin A nephropathy (IgAN) have yielded conflicting results. To systematically evaluate the efficacy and safety of glucocorticoids agents for IgAN, we conducted a meta-analysis of the published randomized controlled trials (RCTs). METHODS: MEDLINE, EMBASE, the Cochrane Library and article reference lists were searched for RCTs that compared glucocorticoids with placebo and any other non-immunosuppressive agents for treating IgAN. The quality of the studies was evaluated with the method of the intention-to-treat analysis and allocation concealment, as well as with the Jadad method. Meta-analyses were performed on the outcomes of proteinuria and renal survival and adverse events in patients with IgAN. RESULTS: Seven RCTs involving 386 patients were included in the review. Four RCTs reported renal survival data with Kaplan-Meier survival curves. Overall, glucocorticoid agents had statistically significant effects on improved renal survival (HR 0.20, 95% CI 0.20 to 0.39) and reduction of proteinuria (standardized mean difference SMD, -0.51; 95% CI -0.73 to -0.29) when compared with the control group. Tests for heterogeneity showed no difference in effect among the studies. In general, glucocorticoid agents were well tolerated. Patients receiving glucocorticoids therapy did not have an increased risk of development of type 2 diabetes mellitus, hypertension or Cushingoid adverse effects, while glucocorticoids were associated with a significant increase in the risk of gastrointestinal tract adverse events. CONCLUSIONS: The current cumulative evidence suggests that glucocorticoids have statistically significant effects on protecting renal function and reduction of proteinuria in patients with IgAN, but we should be careful for its gastrointestinal tract reaction. In general, glucocorticoids agents are a promising medication and should be investigated further.

[Effect of shenmai injection on patients suffering from malnutrition-inflammation complex syndrome during the maintenance hemodialysis].

OBJECTIVE: To investigate the effect of Shenmai Injection (SMI) on patients undergoing maintenance hemodialysis (MHD) suffered from malnutrition-inflammation complex syndrome (MICS). METHODS: Forty patients undergoing MHD were randomly allocated into two groups, the SMI group and the control group, 20 in each group. They were treated for three months. Blood levels of albumin (Alb), high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6) and interleukin 1beta (IL-1beta) as well as stomatologic parameters were measured before and after treatment. Meantime, the modified subjective global analysis of nutrition (SGAN) was used to assess patients' nutritional status, and the quantitative scoring system was adopted to get the malnutrition score (MS). RESULTS: In the SMI group after treatment, levels of MS, hs-CRP, IL-6 and IL-1beta were lowered, levels of Alb, body weight, and SSF were increased significantly (P <0.05 or P <0.01); as compared with those in the control group, MS, hs-CRP and IL-6 were lower, while SSF and Alb were higher (P<0.05 or P< 0.01). Levels of IL-6 and IL-1beta, either in the SMI group or in the control group, were all higher than normal range (P<0.05). Correlation analysis showed significant correlation presented between MS value with levels of Alb (P<0.01) and IL-6 (P <0.05), also between IL-6 and Alb (P<0.05). CONCLUSION: SMI can reduce the blood levels of hs-CRP, IL-6 and IL-1beta in patients undergoing MHD, improve their nutritional indices, suggesting that it could alleviate the MICS in these patients.

Regulatory effect of Langchuang serial recipes on T-lymphocyte subsets Th and Tc in patients with systemic lupus erythematosus.

OBJECTIVE: To study the principle of clearing Fei (), cooling blood, and detoxification as well as nourishing yin and moisening Fei (abbr. as CCD-NM) in regulating the levels of peripheral T-lymphocyte subsets Th and Tc cells to explore its mechanism for lowering the incidence of infection in patients with systemic lupus erythematosus (SLE). METHODS: Sixty SLE patients without complicated infection were assigned to the treatment group and the control group, 30 in each group. The control group was treated with Western medicine alone, while the treatment group was treated with the same program of Western medicine, but additionally administered with either Langchuang No.1 (I) or 2 (II), serial concerted Chinese recipes, applied respectively in patients in the active stage or in the resting stage. The total time of treatment for both groups was 1 year. Further, a healthy control group was set up with 20 healthy subjects. The expressions of Th1, Th2, and Tc1 and Tc2 cells in peripheral blood were detected and compared with those in the healthy control group. RESULTS: (1) As compared with the healthy control group, ratios of Th1/Th2 and Tc1/Tc2 in SLE patients, whether complicated with infection or not, were significantly lower (P<0.05 or P<0.01). (2) Comparison between patients with complications and those uncomplicated with infection showed that the two ratios and Th1 expression were lower and Tc2 was higher in the former than those in the latter (all P<0.05). (3) Ratios of Th1/Th2 and Tc1/Tc2 increased after treatment in patients of both the treatment group and the control group (P<0.05 and P<0.01), but the changes in the treatment group were more significant (P<0.05). CONCLUSION: The principle of CCD-NM could regulate the Th and Tc subsets toward equilibrium in SLE patients, which might be one of the mechanisms of action for alleviating complicated infection.

[Clinical research on effect of TCM treatment beginning with Fei in treating systemic lupus erythematosus for reducing incidence of complicated infection].

OBJECTIVE: To observe the effect of TCM treatment beginning with Fei in reducing the incidence of complicated infection and the antibiotic utilization rate in patients with systemic lupus erythematosus (SLE). METHODS: One hundred and ten SLE patients were randomly assigned to 2 groups equally, the control group treated with the conventional Western medicinal treatment and the treated group treated with the same conventional treatment and SLE I formula (in active stage) or SLE II formula (in silent period) additionally. RESULTS: After 3-month and 6-month treatment, the total effective rate was 83.64% , 87.27% in the treated group, and 78.18%, 81.82% in the control group respectively, showing insignificant difference between the two groups. It lowered in both groups after 1-year treatment, however, which in the treated group (78.18%) was higher than that in the control group (60.00%, P < 0.05). But the difference became insignificant again after 2-year treatment, it being 87.27% in the treated group and 72.73% in the control group. The incidence of complicated infection and antibiotic utilization rate in the 2-year treatment was 23.6%, 55.0% respectively in the treated group, markedly lower than those (50.9% and 100%) in the control group respectively (P < 0.01). CONCLUSION: TCM treatment beginning with Fei could decrease the incidence of complicated infection and the antibiotic utilization rate in SLE patients.

NADPH oxidase-dependent formation of reactive oxygen species contributes to transforming growth factor ß1-induced epithelial-mesenchymal transition in rat peritoneal mesothelial cells, and the role of astragalus intervention.

OBJECTIVE: To investigate the role of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidasedependent formation of reactive oxygen species (ROS) in the transforming growth factor ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) in rat peritoneal mesothelial cells (RPMCs), and the effect of Astragalus injection (AGI) intervention. METHODS: Primary RPMCs were cultured to the second generation in vitro. After synchronization for 24 h, the cells were randomly assigned to the following groups: control (Group A), AGI (2 g/mL; Group B), TGF-ß1 (10 ng/mL; Group C), TGF-ß1 (10 ng/mL) + AGI (2 g/mL; Group D; pretreated for 1 h with AGI before TGF-ß1 stimulation). Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis were employed to evaluate the mRNA and protein expression of the NADPH oxidase subunit p67phox, α-smooth muscle actin (α-SMA) and E-cadherin. The dichlorofluorescein-sensitive cellular ROS levels were measured by a fluorometric assay and confocal microscopy. RESULTS: TGF-ß1 significantly induced NADPH oxidase subunit p67phox mRNA and protein expression in RPMCs, as well as inducing the production of intracellular ROS. AGI inhibited this TGF-ß1-induced up-regulation by 39.3% and 47.8%, respectively (P<0.05), as well as inhibiting the TGF-ß1-induced ROS generation by 56.3% (P<0.05). TGF-ß1 also induced α-SMA mRNA and protein expression, and down-regulated E-cadherin mRNA and protein expression (P<0.05). This effect was suppressed by AGI (P<0.05). CONCLUSIONS: NADPH oxidase-dependent formation of ROS may mediate the TGF-ß1-dependent EMT in RPMCs. AGI could inhibit this process, providing a theoretical basis for AGI in the prevention of peritoneal fibrosis.

Optimized project of traditional Chinese medicine in treating chronic kidney disease stage 3: a multicenter double-blinded randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Stage 3 is the key phase of chronic kidney disease. Traditional Chinese medicine (TCM) has been used for the treatment of chronic kidney disease. But a large sample trial is desirable. MATERIALS AND METHODS: A total of 578 Chinese patients with primary glomerulonephritis in CKD stage 3 were randomly assigned to three groups: patients received TCM (TCM group), benazepril (Ben group), TCM combined with benazepril (TCM+Ben group). Patients were followed up for 24 weeks. The primary endpoint was the time to the composite of 50% increased of serum creatinine, end stage renal disease or death. RESULTS: eGFR in the TCM and the TCM+Ben group were improved (week 24 vs. baseline, P<0.05) while eGFR in the Ben group was decreased (week 24 vs. baseline, P>0.05). 24h urinary protein excretion (UP) and urinary albumin/creatinine (UAlb/Cr) were decreased in the TCM+Ben (week 24 vs. baseline, P<0.05) and the Ben group (week 24 vs. baseline, P>0.05). UP and UAlb/Cr were increased in the TCM group to week 12, then were stable (week 24 vs. baseline, P<0.05). The hemoglobin in the TCM group was also improved (week 24 vs. baseline, P<0.05). The accumulative survival rate in the TCM+Ben group was higher than that in the TCM group and the Ben group (P=0.044). Side effects in the TCM group were the lowest in these groups (P<0.05). The patients with dry cough in the TCM+Ben group and the Ben group were increased as compared with the TCM group (P<0.05). Hyperkalemia happened less frequently in the TCM group as compared with the other two groups (P=0.052). CONCLUSIONS: For the patients with CKD stage 3, TCM can improve eGFR and hemoglobin with lower side effects. Benazepril significantly decreased the proteinuria. Chinese medicine integrated with benazepril can ameliorate renal function and decrease proteinuria synergistically.

Systemic lupus erythematosus complicated with femoral head ischemic necrosis treated by Chinese medicine therapy for activating blood and dredging collaterals method.

OBJECTIVE: To observe the effect and mechanism of Chinese medicine therapy for activating blood and dredging collaterals (ABDC) on treating systemic lupus erythematosus complicated with avascular necrosis of the femoral head (SLE-ANFH). METHODS: Thirty-four patients (51 joints) with SLE-ANFH were assigned by a random number table to two groups: 22 patients (32 joints) in the treatment group and 12 patients (19 joints) in the control group. All received Western medical conventional treatment for anti-inflammation and immunosuppression, but an additional Chinese medicine decoction prescribed based on ABDC principle was administered to patients in the treatment group. The observation on the patients' condition and therapeutic effect lasted for 3 years. RESULTS: The patients' conditions in the two groups, as assessed by Association for Research Circulation Osseous (ARCO) staging, were similar before treatment. After treatment, comparison between groups showed significant difference (P<0.05), and the raised Harris functional scores in the treatment group were higher than that in the control group (P<0.01). The post-treatment symptom improving rate in the treated group was 72.73%, which was higher than that in the control group (50.00%, P<0.05). Moreover, the former was superior in improving hematologic and hemorrheologic parameters in terms of prolonging activated partial thromboplastin time, lowering whole blood middle/low shear viscosity, and plasma viscosity (P<0.05 or P<0.01). Two patients in the control group but none in the treatment group received hip joint replacement operation during the observation period. CONCLUSIONS: Chinese medicine ABDC therapy could effectively alleviate clinical symptoms and improve joint function of patients with SLE-ANFH. The mechanism may be related to its effects on improving high coagulation manner and trend for getting embolism.

The imbalance between regulatory and IL-17-secreting CD4+ T cells in lupus patients.

It has been well recognized that a deficit of numbers and function of CD4+CD25+Foxp3+ cells (Treg) is attributed to the development of some autoimmune diseases; however, there are controversial data regarding the suppressive effect of Treg cells on the T cell response in systemic lupus erythematosus (SLE). Additionally, IL-17-producing cells (Th17) have been recently emerged as a new pathogenic cell, but their role in lupus remains unclear. In this study, we studied the connection between Treg and Th17 cells in lupus patients. We observed that, while Treg or Th17 cells alone were not correlated to SLE development, the ratio of Treg to Th17 cells in active SLE patients is significantly lower than that in inactive SLE patients and healthy controls, and we also found corticosteroid treatment increased the ratio of Treg to Th17 cells in active SLE patients. Moreover, this ratio is inversely correlated with the severity of active SLE. The present study indicates that active SLE appears to exist as an imbalance between Treg and Th17 cells. Correction of this Treg/Th17 imbalance may have therapeutic impact for patients with SLE.

Neutralization of IL-4 and IFN-γ Facilitates inducing TGF-ß-induced CD4(+)Foxp3(+) Regulatory Cells.

It has been well recognized that TGF-ß is able to induce CD4(+)CD25(+)Foxp3(+) suppressor/regulatory T (iTreg) cells and IL-2 facilitates iTreg induction and expansion, however, only half of TGF-ß-induced CD4(+)CD25(+) cells express Foxp3 and remaining CD4(+)CD25(+)Foxp3- cells may represent effector cells. Whether other factor(s) can increase Foxp3 expression by CD4(+)CD25(+) cells induced with TGF-ß is still unclear. Here we show that addition of exogenous IFN-γ or IL-4 diminished the ability of TGF-ß to induce Foxp3 expression and IL-2 failed to rescue this decreased Foxp3 expression. Conversely, neutralization of IFN-γ and IL-4 significantly enhanced the ability of TGF-ß to induce Foxp3 and develop the suppressive activity, indicating that different cytokine profiles affect the differentiation of CD4(+)CD25(+)Foxp3(+) subset induced by TGF-ß. These results show that combination of antibodies against IFN-γ and IL-4 and TGF-ß enhances the efficacy of generation and function of iTreg cells and may therefore provide a novel therapeutic strategy for the treatment of autoimmune and other chronic inflammatory diseases.