Efficacy of physiological seawater nasal irrigation for the treatment of children with SARS-CoV-2 Omicron BA.2 variant infection: a randomized controlled trial.

BACKGROUND: Saline nasal irrigation is an effective therapy for relieving common cold symptoms. This study aimed to investigate and explore the efficacy of physiological seawater nasal irrigation (PSNI) on children with mild and asymptomatic infection with Omicron. METHODS: This randomized controlled trial was conducted in Shanghai, China, and 403 children with mild and asymptomatic infection with Omicron were included. These children were allocated into the PSNI group and the control group. The primary outcome was the duration of viral shedding (DVS), and the secondary outcome was the change in clinical symptoms. RESULTS: The median age of all participants was 5.59 (6.26) years old. The DVS was significantly shorter in the PSNI group [2.40 (1.13)] than in the control group [3.09 (2.14)] (P = 0.014). The multivariable Cox regression model also showed that patients in the PSNI group had an increased probability of shorter DVS compared with patients in the control group [hazard ratio (HR), 1.27; 95% confidence interval (CI), 1.04-1.55; P = 0.017]. Subgroup analysis suggested that the DVS of patients without full vaccination was significantly reduced in the PSNI group. The proportions of runny nose and stuffy nose were apparently reduced in the first three days in the PSNI group or the control group, but there was no evidence showing that PSNI contributes to the benefit compared with the control group. CONCLUSION: PSNI can reduce the DVS of patients with mild and asymptomatic infection with SARS-CoV-2 Omicron BA.2 variant.

Effectiveness of the Shenzhuo formula in the treatment of patients with macroalbuminuria secondary to diabetic kidney disease: protocol update and statistical analysis plan.

BACKGROUND: Diabetic kidney disease (DKD) is a significant complication of diabetes and has garnered considerable attention. Our previous retrospective study indicated that Shenzhuo formula (SZF) potentially reduces macroalbuminuria secondary to DKD. METHODS: This trial is a 24-week, randomized, multicentric, double-blinded, double-dummy clinical trial. A total of 120 patients with DKD will be equally and randomly divided into two groups: SZF+ irbesartan simulator or irbesartan + SZF simulator. The 24-h urinary protein change from baseline to week 24 is the primary outcome measure. The secondary outcome measures include serum creatinine, estimated glomerular filtration rate, urinary albumin excretion rate, improvement in traditional Chinese medicine symptoms, fasting blood glucose, 2-h postprandial plasma glucose, hemoglobin A1c, cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, blood pressure, albumin to creatinine ratio, and the Audit of Diabetes-Dependent Quality of Life 19. Our recruitment began in May 2015; currently, we have recruited 100 participants, with a designed maximum sample size of 120. The interim results were reviewed at N = 60, and continuing recruitment was recommended. This statistical analysis plan includes our approach to missing data imputation, primary and secondary outcomes analyses, and safety endpoints. DISCUSSION: This statistical analysis plan will standardize the clinical trial's statistical analysis and avoid outcome selective reporting bias and data-driven analysis. This trial will provide further clinical evidence regarding the effectiveness of SZF in managing macroalbuminuria secondary to DKD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-ICR-15006311. Registered on 26 May 2013. http://www.chictr.org.cn/showproj.aspx?proj=10862.

Evaluation of the short-term and long-term performance of biological invasion management in the China-Myanmar border region.

Invasive alien species pose great threats to ecological and economic health and cause enormous losses to global ecosystems. The Mikania micrantha management program is a source of great theoretical and practical insights for regional agricultural and forestry development. In this paper, the invasion history and distribution patterns of M. micrantha in the China-Myanmar Border Region are summarized, and the short-term and long-term performance of the current post-border management program are evaluated. A literature survey found that M. micrantha was mainly distributed in 85 townships of five municipalities along the border in China with Myanmar, suggesting an explicit border-crossing scenario of M. micrantha. The M. micrantha management program has produced positive but short-term results due to the conduction of general investigations, establishment of an extensive monitoring network, development of integrated measures, and improvements of public awareness and participation. However, the long-term management performance was hampered by overlapping departmental functions, lagging and unreliable public feedback, inadequate funding, and biased and passive strategies. We suggest that invasive species committees, social media tools, public-private partnership, and forest restoration and conservation and biological control could greatly improve the situation. This regional-scale research provides referential insights for the development of biological invasion management systems in developing economies under transboundary contexts.

Effects of return sludge alkaline treatment on sludge reduction in laboratory-scale anaerobic-anoxic-oxic process.

Three alkaline treatments (pH 10, 11, and 12 for 1 h) were used to treat return sludge alone to reduce sludge production in laboratory-scale anaerobic-anoxic-oxic processes. After 99 days of operation, alkaline treatments at pH 10 and 11 led to accumulative excess sludge production and sludge yield reduction of 18.8%-31.7% and 14.7%-27.8%, respectively. However, alkaline treatment at pH 12 led to system breakdown because of sludge bulking. The alkaline treatment at pH 10 did not affect the chemical oxygen demand and NH4+-N removals of the system and sludge volume index (SVI) of aerobic activated sludge. However, alkaline treatments at pH 11 and 12 obviously deteriorated the wastewater treatment efficiencies and sludge SVI. Although the three treatments increased the effluent pH by 0.08 to 0.38, the effluent pH of three systems were all lower than 9.00. The treatments at pH 10 and 11 increased the specific oxygen uptake rate of activated sludge, whereas the treatment at pH 12 decreased this rate.

Effects of wastewater treatment processes on the sludge reduction system with 2,4-dichlorophenol: Sequencing batch reactor and anaerobic-anoxic-oxic process.

The effects of two wastewater treatment processes (sequencing batch reactor, SBR; and anaerobic-anoxic-oxic, A2O) on sludge reduction with metabolic uncoupler 2,4-dichlorophenol (DCP) were studied in laboratory. The experimental results showed that the reduction of cumulative excess sludge in SBR and A2O was 43.7% and 44.2%, respectively, during the stable stage of the test. The two processes had similar average sludge yield and sludge yield reduction, i.e., 0.306 and 0.305mg of SS/mg chemical oxygen demand (COD), and 16.9% and 17.8%, respectively. The effect of DCP on the wastewater treatment efficiencies (namely, removal of COD, total nitrogen, NH4+-N, and total phosphorus) of the two processes were also similar. SBR was more likely to slightly retard the increase of activated sludge SVI with lesser increase in extracellular polymeric substances and protein/polysaccharide ratio. Although DCP did not dramatically affect the microbial communities of sludge, SBR was more favorable for increasing the activated sludge SOUR and maintaining the primary microorganisms of sludge than A2O.

Tongxinluo improves cognition by decreasing ß-amyloid in spontaneous hypertensive rats.

ß-Amyloid (Aß) accumulation in the brain is the major pathophysiology of Alzheimer disease (AD). Hypertension is a risk factor for AD by promoting Aß deposition. Traditional Chinese medicinal compound tongxinluo (TXL) can improve blood circulation and endothelium-dependent vasodilation. This study investigates the effects of TXL on cognition and Aß using spontaneously hypertensive rats (SHRs). TXL was intragastrically administered to SHRs at low-dose, mid-dose and high-dose for 15, 30 or 60days. Cognition was evaluated with a Morris Water Maze (MWM). Aß in the brain was detected by western blot, ELISA and Thioflavin-S staining. Western blot and RT-PCR were employed to exam the expression of receptor for advanced glycation end products (RAGE), low-density lipoprotein receptor-related protein-1 (LRP-1) and amyloid precursor protein (APP). After TXL treatment for 60days, compared with the vehicle, the number of crossed platform and the time spent in the target quadrant increased in parallel with the increasing length of treatment in MWM. Moreover, the Aß in the hippocampus significantly decreased compared to the vehicle group, both in western blot and ELISA. Additionally, TXL reduced RAGE expression in a dose- and time-depended manner, but LRP-1 expression had no difference between TXL groups and vehicle groups. Furthermore, the ß-secretase expression was significantly decreased compared to the vehicle group, but APP expression had no difference. In conclusion, TXL improved cognition and decreased Aß in SHRs in a dose- and time-dependent manner, the underlying mechanism may involved in inhibiting RAGE and ß-secretase expression.

Amorphous silica nanoparticles trigger vascular endothelial cell injury through apoptosis and autophagy via reactive oxygen species-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling.

Environmental exposure to silica nanoparticles (SiNPs) is inevitable due to their widespread application in industrial, commercial, and biomedical fields. In recent years, most investigators focus on the evaluation of cardiovascular effects of SiNPs in vivo and in vitro. Endothelial injury and dysfunction is now hypothesized to be a dominant mechanism in the development of cardiovascular diseases. This study aimed to explore interaction of SiNPs with endothelial cells, and extensively investigate the exact effects of reactive oxygen species (ROS) on the signaling molecules and cytotoxicity involved in SiNPs-induced endothelial injury. Significant induction of cytotoxicity as well as oxidative stress, apoptosis, and autophagy was observed in human umbilical vein endothelial cells following the SiNPs exposure (P<0.05). The oxidative stress was induced by ROS generation, leading to redox imbalance and lipid peroxidation. SiNPs induced mitochondrial dysfunction, characterized by membrane potential collapse, and elevated Bax and declined bcl-2 expression, ultimately leading to apoptosis, and also increased number of autophagosomes and autophagy marker proteins, such as LC3 and p62. Phosphorylated ERK, PI3K, Akt, and mTOR were significantly decreased, but phosphorylated JNK and p38 MAPK were increased in SiNPs-exposed endothelial cells. In contrast, all of these stimulation phenomena were effectively inhibited by N-acetylcysteine. The N-acetylcysteine supplement attenuated SiNPs-induced endothelial toxicity through inhibition of apoptosis and autophagy via MAPK/Bcl-2 and PI3K/Akt/mTOR signaling, as well as suppression of intracellular ROS property via activating antioxidant enzyme and Nrf2 signaling. In summary, the results demonstrated that SiNPs triggered autophagy and apoptosis via ROS-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling in endothelial cells, and subsequently disturbed the endothelial homeostasis and impaired endothelium. Our findings may provide experimental evidence and explanation for cardiovascular diseases triggered by SiNPs. Furthermore, results hint that the application of antioxidant may provide a novel way for safer use of nanomaterials.

Sarpogrelate inhibits the expression of ICAM-1 and monocyte-endothelial adhesion induced by high glucose in human endothelial cells.

Hyperglycemia is the major cause of diabetic angiopathy. Sarpogrelate hydrochloride is an antiplatelet drug, and expected to be useful in the treatment of chronic arterial occlusive diseases. The aim of our study was to evaluate the possible effects of sarpogrelate hydrochloride on adhesion molecule expression and its underlying mechanism in the prevention and treatment of cardiovascular disorders. Intercellular adhesion molecule-1 (ICAM-1) expression and superoxide dismutase (SOD) activity were determined after endothelial cells were exposed to high glucose in the absence and presence of sarpogrelate hydrochloride. Coincubation of endothelial cells with high glucose for 24 h resulted in a significant increase of monocyte-endothelial cell adhesion and the expression of ICAM-1 (P < 0.01). These effects were abolished by sarpogrelate hydrochloride and sarpogrelate hydrochloride significantly increased SOD activities (40 ± 8 vs. 47 ± 7, n = 8, P < 0.01). The low dose sarpogrelate group (0.1 µM) had significantly higher monocyte-endothelial cell adhesion and the expression of ICAM-1 than medium dose sarpogrelate group (1.0 µM) and high dose sarpogrelate group (10.0 µM) (P < 0.05 for comparison among three groups and P < 0.01 for difference between low and high dose sarpogrelate groups). These findings suggested that sarpogrelate hydrochloride was able to protect vascular endothelium from dysfunction induced by high glucose.

Influence of Fuzheng Huayu Tablet on mental state and social function of patients with post-hepatitis B liver cirrhosis.

OBJECTIVE: To observe the influence of Fuzheng Huayu Tablet on mental state and social activity of patients with post-hepatitis B liver cirrhosis (LC-HB). METHODS: Adopting grouped randomized double-blinded control method, 180 LC-HB patients in 3 research centers were distributed to 2 groups, the treated group and the control group, 90 in each group. Patients in the treated group were administered with FZHYT; while those in the control group treated with conventional therapy combined with placebo, the course for all patients were 6 months. Their mental state and social activity were evaluated before treatment, after 3 months' treatment and at terminal of the 6-month therapeutic course by estimating with Zung self-rating anxiety scale (SAS), self-rating depression scale (SDS) and social deficit screening scale (SDSS). Additionally, the basic demographic materials, liver function, cirrhosis index, hepatic and splenic images, blood coagulation function, etc. in the patients were tested and compared as well. RESULTS: As compared with before treatment, the normal rate of SAS and SDS scores increased and the social deficit rate decreased in the treated group significantly after treatment, showing statistical significance (P<0.05 or P<0.01); while in the control group, change was only shown in the social deficit (P<0.01), inter-group comparisons after treatment showed significant differences in all the three indexes (P<0.05 or P<0.01). Additionally, after treatment, levels of liver function, cirrhosis, blood coagulation function and splenomegaly in the treated group were all improved significantly P<0.05 or P<0.01), and the improvements were better than those in the control group (P<0.01) in levels of total bilirubin (TBIL), albumin (ALB), type IV collagen (IV-C), prothrombin time (PT), prothrombin activity (PTA). CONCLUSION: Most patients of LC-HB have mental disturbance and social activity deficit, which could definitely be improved by intervention with Chinese FZHYT.

Effects of the Ganning formula on liver fibrosis in patients with chronic hepatitis B.

OBJECTIVE: To investigate the clinical efficacy and safety of the Ganning formula for the treatment of liver fibrosis in patients with chronic hepatitis B. METHODS: In a multicenter, randomized, controlled clinical trial, 150 patients with liver fibrosis secondary to hepatitis B virus (HBV) infection were randomly assigned in equal numbers to receive either the Ganning formula (a Chinese herbal decoction; active treatment group) or oral entecavir (control group) for two 3-month courses. Patients were monitored for any treatment-induced changes in liver function test parameters (ALT, AST, and GGT), liver fibrosis markers (LN, HA, IV-C, and PCIII), HBV DNA level, hepatosplenic imaging, quality of life scores, or psychological and social functioning scores. Patients were also observed for any adverse effects. RESULTS: After treatment, patients in both groups experienced significant improvements in liver function, HBV DNA load, hepatosplenic B-mode ultrasonography, quality of life, and psychological and social functioning (P < 0.05 or P < 0.01). Patients receiving the Ganning formula achieved greater improvements in HA, IV-C, quality of life, and psychological and social functioning compared with those on entecavir (P < 0.05 or P < 0.01). There were no abnormal changes in blood tests, urine, feces, renal function, or electrocardiogram. Additionally, no adverse effects were observed in any patients in either group. CONCLUSIONS: The Ganning formula appears to have the potential to inhibit liver fibrosis and therefore improve liver function by inhibiting HBV replication in patients with chronic hepatitis B. Additionally, this formula is helpful in improving quality of life and psychological and social functioning.

Selenium inhibits high glucose-induced cyclooxygenase-2 and P-selectin expression in vascular endothelial cells.

Selenium as a component of glutathione peroxidase may be beneficial in insulin resistance, hence potentially may modify the risk of diabetes and cardiovascular disease. The aim of our study was to evaluate whether selenium can also alter high glucose (HG), advanced glycation end products (AGE), high insulin (HI) and H2O2-induced expression of cyclooxygenase (COX)-2 and P-selectin. Human umbilical vein endothelial cells (HUVECs) were pretreated with selenium and stimulated by HG, AGE, HI and H2O2. Selenium significantly inhibited HG, AGE, HI and H2O2-induced expression of COX-2 and P-selectin. Moreover, selenium also inhibited HG, AGE, HI and H2O2-induced activation of p38 mitogen-activated protein kinase (p38 MAPK), which indicated that the preventive effects of selenium on COX-2 and P-selectin may be associated with p38. Our results indicated that selenium supplementation can reduce HG, AGE, HI and H2O2-induced expression of COX-2 and P-selectin by inhibition of the p38 pathway.

[Mechanisms of algal inhibition by rice straw extract].

An indoor experiment was conducted to investigate the inhibition effects and mechanisms of rice straw extracts to the harmful bloom-forming algae, Microcystis aeruginosa. It was found that there were algae inhibitory chemicals in rice straw. The inhabitation ratio of rice straw extract to Microcystis was 69.3% when stored at a low temperature of - 4 degrees C for 4 days with a concentration of 2.5 g/L. The algal inhibition depends on both chemicals and biological responses from decomposed rice straw extracts. Their relative contributions to the algal inhibition depended on decomposition pathway and time. Algal inhibitory chemicals played more important roles in anaerobic decomposed rice straw extracts than aerobic decomposed ones in the algal-inhibition process. For anaerobically decomposed straw extracts, if stored for 15 and 30 days with the concentration of 1.5 g/L, the inhabitation ratio of rice straw to Microcystis was 83% and 46% respectively. However, for aerobically decomposed straw extracts, the biologic mechanism was more important. The inhibition effects of biologic mechanism increased with the decomposition time. For aerobically decomposed straw extracts, if stored for 15 and 30 days with the concentration of 1.5 g/L, the inhabitation ratio of rice straw to Microcystis was 81% and 93% respectively.

Effects of withdrawal of Xuezhikang, an extract of cholestin, on lipid profile and C-reactive protein: a short-term time course study in patients with coronary artery disease.

OBJECTIVE: C-reactive protein (CRP) is considered a risk factor for coronary artery disease. In addition to its lipid-lowering properties, statin decreases the level of CRP. Abrupt cessation of statin therapy during treatment could increase CRP level independently of the elevation of serum lipids and the incidence of cardiac events in patients with atherosclerotic heart disease. Xuezhikang (XZK), an extract of cholestin, has a marked modulating effect on lipid and CRP concentrations in different study time course. However, no attention has been paid to the changes of lipid profile and CRP concentrations after withdrawal of XZK treatment. This study was designed to explore short-term time course effects on lipid profile and CRP concentrations after withdrawal of XZK treatment in coronary heart disease patients. MATERIALS AND METHODS: Seventy-five consecutive patients with documented coronary heart disease were randomly divided into three groups: 1. Pretreatment with XZK 1,200 mg daily for 6 weeks and then replaced by placebo (XZK discontinued group; n = 25); 2. Treatment with XZK 1,200 mg daily throughout the study (XZK continued group; n = 25); or 3. Placebo (no XZK group; n = 25). Lipid levels (total cholesterol, HDL-C, LDL-C and triglycerides) and CRP were assessed before receiving the XZK therapy, 1 day before discontinuation of XZK, and on days 1, 2, 3, 7 and 14 after discontinuation of XZK, respectively. RESULTS: After 6-week XZK treatment, the fasting total cholesterol, LDL-C, triglyceride and median hs-CRP concentrations decreased, whereas HDL-C concentration increased significantly (p < 0.001, respectively). At day 14 after discontinuation of XZK therapy, total cholesterol (15%), LDL-C (17%) and triglyceride (20%) significantly increased (p < 0.001, respectively), whereas HDL-C level (15%) significantly decreased (p < 0.05). The median level of CRP increased by 11, 65, 128, 103 and 101% on the first, second, third, seventh, and fourteenth day after withdrawal of XZK therapy (p > 0.05, <0.05, <0.001, <0.001, <0.001, compared with 1 day before withdrawal of XZK therapy, respectively). There was a prominent rebound of CRP concentration 3 days after discontinuation of XZK therapy. At this time point, hs-CRP concentration was higher than in the placebo group (p < 0.05). Seven to 14 days after discontinuation of XZK therapy, the hs-CRP concentration declined to a similar level as in the placebo group. No significant correlation was seen between the changes in hs-CRP and lipid profile at all time points. CONCLUSIONS: The level of hs-CRP increases on the second day after withdrawal of XZK and there is a prominent rebound 3 days after discontinuation of XZK therapy. The increase of CRP ends within 7 days, where lipids increase at 14 days after discontinuation of XZK therapy. The results may be clinically important for patients with coronary artery disease.

[Effect of selenium on expression of P38 mitogen-activated protein kinase and monocyte chemoattractant protein-1 in diabetic endothelial cells].

AIM: To study the relationship between P38MAPK and MCP-1 in diabetic HUVEC and the mechanism of anti-atherosclerosis of selenium. METHODS: HUVEC were treated with high concentration of glucose, advanced glycosylation end products (AGE), high concentration of insulin or H(2)O(2) with or without pre-treatment with SB203580 (P38MAPK specific inhibitor) or selenium. The expression of phospho-P38MAPK and MCP-1 in HUVEC was detected by Western blot or RT-PCR, respectively. RESULTS: High concentration of glucose, AGE, high concentration of insulin and H(2)O(2) can activate P38MAPK and increase the expression of MCP-1 in HUVEC. The expression of MCP-1 was inhibited by SB203580. Selenium inhibited the activation of P38MAPK and reduced the expression of MCP-1. CONCLUSION: P38MAPK is an upstream signaling molecule of MCP-1. P38MAPK may be one of the initiating signals of diabetic atherosclerosis. Selenium can inhibit the expression of MCP-1 by repressing P38MAPK signaling pathway and therefore prevent the development of atherosclerosis.