A multi-omics approach to investigate characteristics of gut microbiota and metabolites in hypertension and diabetic nephropathy SPF rat models.

Background: Imbalance in intestinal microbiota caused by microbial species and proportions or metabolites derived from microbes are associated with hypertension, as well as diabetic nephropathy. However, the involvement of the intestinal microbiota and metabolites in hypertension and diabetic nephropathy comorbidities (HDN) remains to be elucidated. Methods: We investigated the effects of intestinal microbiota on HDN in a rat model and determined the abundance of the intestinal microbiota using 16S rRNA sequencing. Changes in fecal and serum metabolites were analyzed using ultra-high-performance liquid chromatography-mass spectrometry. Results: The results showed abundance of Proteobacteria and Verrucomicrobia was substantially higher, whereas that of Bacteroidetes was significant lower in the HDN group than in the sham group. Akkermansia, Bacteroides, Blautia, Turicibacter, Lactobacillus, Romboutsia, and Fusicatenibacter were the most abundant, and Prevotella, Lachnospiraceae_NK4A136_group, and Prevotella_9 were the least abundant in the HDN group. Further analysis with bile acid metabolites in serum showed that Blautia was negatively correlated with taurochenodeoxycholic acid, taurocholic acid, positively correlated with cholic acid and glycocholic acid in serum. Conclusions: These findings suggest that the gut microbiota and metabolites in feces and serum substantially differed between the HDN and sham groups. The F/B ratio was higher in the HDN group than in the sham group. Blautia is potentially associated with HDN that correlated with differentially expressed bile acid metabolites, which might regulate the pathogenesis of HDN via the microorganism-gut-metabolite axis.

Comparison of the effectiveness four years after Homo/Hetero prime-boost with 10 µg HP and 20 µg CHO recombinant hepatitis B vaccine at 1 and 6 months in maternal HBsAg-negative children.

Introduction: Limited data were available on the effectivenessfour years after Homo or Hetero prime-boost with 10 µg Hansenulapolymorpha recombinant hepatitis B vaccine (HepB-HP) and 20 µgChinese hamster ovary cell HepB (HepB-CHO). Methods: A crosssectional study was performed in maternalhepatitis B surface antigen (HBsAg)-negative children whoreceived one dose of 10 µg HepB-HP at birth, Homo or Heteroprime-boost with 10 µg HepB-HP and 20 µg HepB-CHO at 1 and 6months. HBsAg and hepatitis B surface antibody (anti-HBs) fouryears after immunization were quantitatively detected by achemiluminescent microparticle immunoassay (CMIA). Results: A total of 359 children were included; 119 childrenreceived two doses of 10 µg HepB-HP and 120 children receivedtwo doses of 20 µg HepB-CHO, called Homo prime-boost; 120children received Hetero prime-boost with 10 µg HepB-HP and 20µg HepB-CHO. All children were HBsAg negative. The geometricmean concentration (GMC) and overall seropositivity rate (SPR) ofanti-HBs were 59.47 (95%CI: 49.00 - 72.16) mIU/ml and 85.51%(307/359). Nearly 15% of the study subjects had an anti-HBsconcentration < 10 mIU/ml and 5.01% had an anti-HBsconcentration ≤ 2.5 mIU/ml. The GMC of the 20 µg CHO Homoprime-boost group [76.05 (95%CI: 54.97 - 105.19) mIU/ml] washigher than that of the 10 µg HP Homo group [45.86 (95%CI:31.94 - 65.84) mIU/ml] (p = 0.035). The GMCs of the Heteroprime-boost groups (10 µg HP-20 µg CHO and 20 µg CHO-10 µgHP) were 75.86 (95% CI: 48.98 - 107.15) mIU/ml and 43.65(95%CI: 27.54 - 69.18) mIU/ml, respectively (p = 0.041). Aftercontrolling for sex influence, the SPR of the 20 µg CHO Homoprime-boost group was 2.087 times than that of the 10 µg HPHomo group. Discussion: The HepB booster was not necessary in the generalchildren, Homo/Hetero prime-boost with 20 µg HepB-CHO wouldincrease the anti-HBs concentration four years after immunization,timely testing and improved knowledge about the self-pay vaccinewould be good for controlling hepatitis B.

A case of congenital rubella syndrome and epidemiology of related cases in China, 2014-2023.

Rubella is a major cause of congenital defects, and the presence of rubella infection in a pregnant woman may lead to fetal death or congenital defects known as congenital rubella syndrome(CRS). Since China has not yet established a national CRS surveillance system, the true incidence cannot be determined. To understand the disease burden and epidemiological characteristics of CRS cases in China, the article reports the first case of CRS in Quzhou, China, and conducts a retrospective analysis of related cases that have been reported in China over the past decade. Because the availability of rubella-containing vaccines (RCV) was not widespread in China before 2008, women of childbearing age born before 2008 are generally unvaccinated against RCV. Due to the lack of routine CRS monitoring and screening, CRS is underreported in China. Vaccination of nonimmune women of childbearing age with RCV and establishing a sensitive and timely case-based CRS surveillance system can accelerate the elimination of rubella and CRS.

Effectiveness of COVID-19 vaccines against SARS-CoV-2 Omicron variants during two outbreaks from March to May 2022 in Quzhou, China.

Limited data are available on the effectiveness of COVID-19 vaccines used in China in real-world outbreaks - especially against Omicron variants in vaccinated individuals. Two outbreaks of SARS-CoV-2 Omicron variants - the first involving the sub-lineage BA.2 and the second the BA.1 variant - occurred in Quzhou. Infected people and their close contacts were divided according to vaccination status: unvaccinated, partially vaccinated, fully vaccinated, and boosted. The Cox proportional-hazard regression model was used to estimate the evolving hazard for vaccinated individuals after their first immunization. 138 people had been infected with the SARS-CoV-2 Omicron BA.2 variant and 13 with the BA.1 variant. Of the 151 infections, 99.34% (150/151) were mild or asymptomatic and 90.07% (136/151) were vaccine breakthrough cases. The total vaccine effectiveness (VE) of partial, full, and booster vaccinations during the two outbreaks was 47.4% (95%CI: 0-93.1%), 28.9% (95%CI: 0-60.2%), and 27.5% (95%CI: 0-58.3%). The VE of booster vaccination against the Omicron BA.1 variant was higher than that for the BA.2 variant. The cumulative hazard began to increase 220 days after the first immunization. The transmissibility of the Omicron BA.2 variant as for BA.1 did not increase in vaccinated individuals; booster vaccination after a primary course substantially increased protection. Our study found that the SARS-CoV-2 Omicron variant caused less severe illness and that the VE of boosters against the Omicron variant was less than 30%. Timely administration of the booster dose was important, especially for individuals aged over 80 years old.

Current situation and influencing factors of varicella vaccination among left-behind children aged 4-8 years old in Quzhou / 中国学校卫生

Objective@#To understand vaccination coverage and the influencing factors of varicella vaccine (VarV) among left-behind children in Quzhou, which based on protective motivation theory(PMT), so as to provide reference to consolidate VarV vaccination in the next step.@*Methods@#From September to December in 2022, simple random sampling was used to select 628 left-behind children in six counties of Quzhou City. A questionnaire survey on their caregivers was conducted to collect data relating to sociological characteristics and PMT factors, and the influencing factors of VarV were tested by Logistic regression.@*Results@#A total of 628 left-behind children participated in the study. The VarV rate was 69.59%, and 74.83% had received a second dose of VarV. The unvaccinated rate was 30.41%, and caregivers willingness to vaccinate children with VarV was only 10.99%. Logistic regression analysis showed that family relationships, annual household income, number of children in the family, extrinsic rewards and self-efficacy were the influencing factors of VarV among left-behind children ( OR =0.43-3.40， P <0.05). The external reward factor was positively correlated with the vaccination probability ( OR =1.14), and the self-efficacy factor was negatively correlated with the vaccination probability ( OR =0.95).@*Conclusion@#In the context of health education and school promotion, attention should be paid to factors relating to extrinsic rewards and self-efficacy as a means of increasing motivation to seek vaccine protection and improve the use of VarV.

Assessment of mumps-containing vaccine effectiveness by dose during 2006 to 2020 in Quzhou, China.

Mumps cases were reported frequently when a routine dose measles-mumps-rubella(MMR) achieved high coverage in Quzhou. The supplementary immunization activities (SIA) using measles mumps (MM) was conducted to control mumps outbreaks. The effectiveness of one and two doses of mumps-containing vaccine (MuCV) was assessed using surveillance data in this study. Mumps cases and immunization information were retrieved from the National Notifiable Disease Reporting System (NNDRS) and the Zhejiang Provincial Immunization Information System (ZJIIS), respectively. Mumps cases of children born from 2006 to 2010 were included. Vaccine effectiveness by dose was calculated using the screening method. A total of 956 mumps cases were identified, of whom 754 (78.9%) had received one dose of MuCV; 108 (11.3%) had received two doses; 94 (9.8%) were unvaccinated. The coverage of one-dose MuCV in the 2006-2010 birth cohorts ranged from 91.6% to 98.9%. Except the 2009 birth cohort in which the coverage of two doses of MuCV was 55.1%, the others were less than 10%. Vaccine effectiveness (VE) of one dose ranged from 47.4% to 86.0%, while VE of two doses ranged from 64.0% to 92.4%. The VE of one and two doses of MuCV waned over time, but the VE of two doses was consistently higher than that of one dose in the same period. The vaccine schedule with two-dose MMR should be implemented among children in Quzhou. The optimal age for the second dose needs to be further evaluated.

Pain management of nalbuphine and sufentanil in patients admitted intensive care unit of different ages.

BACKGROUND: Pain relief for patients in the intensive care unit (ICU) can improve treatment outcomes and reduce the burden on doctors and nurses. This study aims to report the clinical analgesic and sedative effects of nalbuphine and sufentanil on ICU patients. METHODS: This study retrospectively analyzed the medical records of 87 critically ill patients who received nalbuphine or sufentanil infusion in the ICU, including demographic data, diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE) II, Critical Care Pain Observation Tool (CPOT), Richmond Agitation-Sedation Scale (RASS), systolic and diastolic blood pressure, heart rate and blood oxygen saturation (SpO2). The primary outcomes of this study were CPOT and RASS scores. The secondary outcomes were hemodynamic changes, including systolic blood pressure, diastolic blood pressure, heart rate, and SpO2. The adverse events recorded during pain management, such as hypoxemia, respiration depression and bradycardia, were also collected and analyzed. RESULTS: None of the patients in both groups experienced episode of hypoxemia, respiration depression and bradycardia. However, age-stratified analyses showed that nalbuphine has a better analgesic effect than sufentanil for patients aged ≤ 60 (P < 0.05). In contrast, sufentanil showed a better analgesic effect than nalbuphine for patients aged > 60 ( P < 0.05). Furthermore, nalbuphine has a significantly better sedative effect than sufentanil for patients aged ≤ 60 (P < 0.05). CONCLUSION: ICU patients of different age groups may be suitable for different analgesics. For patients under the age of 60, nalbuphine has better analgesia and sedation than sufentanil, and does not cause respiratory depression and drastic hemodynamic changes.

Comparing the pertussis antibody levels of healthy children immunized with four doses of DTap-IPV/Hib (Pentaxim) combination vaccine and DTaP vaccine in Quzhou, China.

Despite the high coverage of pertussis vaccines in high-income countries, pertussis resurgence has been reported in recent years, and has stimulated interest in the effects of vaccines and vaccination strategies. Immunoglobulin G (IgG) antibodies against pertussis toxoid (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) after immunization with four doses of co-purified or component vaccines were determined by enzyme-linked immunosorbent assay (ELISA). Serological data of PT-IgG geometric mean concentrations (GMCs) over time since vaccination were used to fit the mathematical models. A total of 953 children were included in this study; 590 participants received four doses of the component acellular vaccine and 363 participants received four doses of the co-purified acellular vaccine. The GMCs and the seropositivity rate of pertussis IgG were significantly influenced by the production methods, and the immunogenicity of the component acellular vaccine was superior to that of the co-purified acellular vaccine. The fitted mathematical models for the component acellular vaccine and the co-purified acellular vaccine were Y=91.20e-0.039x and Y=37.71x-0.493, respectively. The initial GMCs of the component acellular vaccine was higher than that of the co-purified acellular vaccine, but both were similar at 72 months after immunization. Pertussis IgG levels waned over time after four doses of acellular pertussis vaccine, regardless of whether component or co-purified vaccine was used. The development and promotion of component acellular pertussis vaccines should be accelerated in China, and booster doses of pertussis vaccine in adolescents, adults, and pregnant women should be employed.

Introduction of Two-Dose Mumps-Containing Vaccine into Routine Immunization Schedule in Quzhou, China, Using Cox-Proportional Hazard Model.

Mumps is a vaccine-preventable disease caused by the mumps virus, but the incidence of mumps has increased among the children who were vaccinated with one-dose measles-mumps-rubella (MMR) in recent years. In this study, we analyzed the influence of different doses of mumps-containing vaccine (MuCV) against mumps using Cox-proportional hazard model. We collected 909 mumps cases of children who were born from 2006 to 2010 and vaccinated with different doses of MuCV in Quzhou during 2006-2018, which were all clinically diagnosed. Kaplan-Meier survival methods and Cox-proportional hazard model were used to estimate the hazard probabilities. Kaplan-Meier curves showed that the cumulative hazard of male and female has no difference; lower hazards were detected among those who were vaccinated with two-dose MuCV, born in 2006, and infected after supplementary immunization activities (SIA). Cox-proportional hazard regression suggested that onset after SIA, born in 2006, and vaccinated with two-dose MuCV were protective factors against infection even after adjusting for potential confounding effects. Our study showed that it was necessary to revise the diagnostic criteria of mumps and identify RT-PCR as the standard for mumps diagnosis in China. We suggested that routine immunization schedule should introduce two doses of MMR and prevaccination screening should be performed before booster immunization in vaccinated populations.

[Influence of ball milling with PTFE plastic tube on carbon isotope ratio measurement of C4 plants.] / èšå››æ°Ÿä¹™çƒ¯å¡‘æ–™ç®¡ç ”ç£¨æ³•å¯¹æµ‹å®šC4æ¤ç‰©ç¢³åŒä½ç´ æ¯”å€¼çš„å½±å“.

Before the measurement of stable carbon isotope signatures (δ13C), plant samples should be well homogenized. Using a ball-mill fitted with poly tetra fluoroethylene (PTFE) plastic tubes is one of the most efficient and convenient methods. However, sample-tube plastic might contaminate plant samples during milling. In this study, a two-factor experiment was carried out using four growth chambers, with different relative humidity of the air (50% and 80%) and δ13C of the air (13C depleted and enriched). Leaf samples of Cleistogenes squarrosa (C4) were milled and homogenized using a ball-mill fitted with PTFE tubes and measured for δ13C, and the results were compared with that of leaf samples milled using metal tubes. Due to plastic contamination, 13C discrimination (Δ13C) of the two groups of plants, which were grown in CO2 with different δ13C and could be assumed as replicates, were significantly different (with an offset of 4.8‰ on average). The contamination led to errors in δ13C of individual leaves up to 8‰. Given the lower Δ13C value of C4 plants (normally about 1‰-8‰) compared with that of C3 plants, such an error caused by plastic contamination far exceeded the acceptable error range. By using a two-member mixing model that was similar to the 'Keeling plot', such errors could be effectively eliminated, and the δ13C of plant samples and pollutants were accurately estimated. Our results showed that the widely applied method of using PTFE tubes for ball-mill homogenization is not suitable for examining Δ13C of C4 plants, as it might lead to large errors. For studies with high precision requirements, samples should be milled in stainless-steel tubes.

Assessing the Changes of Mumps Characteristics with Different Vaccination Strategies Using Surveillance Data: Importance to Introduce the 2-Dose Schedule in Quzhou of China.

BACKGROUND: From 2005 to 2016, the prevention and control of mumps in China have undergone three stages of transition. These include the use of MuCV as a self-supported vaccine, the introduction of one-dose MMR to the Expanded Program on Immunization (EPI), and the administration of two-dose MuCV following supplementary immunization activities (SIAs) using MM. Here, using surveillance data, we assessed the epidemiology of mumps during the three stages. METHODS: Children in Quzhou of China born from 2005 to 2016 and registered in the Zhejiang Provincial Immunization Information System (ZJIIS) were included. We analyzed the epidemic data and calculated incidence and MuCV coverage via birth cohorts. RESULTS: The average incidence of mumps in 2005-2006, 2007-2010, and 2011-2016 was 51.57, 41.02, and 12.53 per 100,000 individuals, respectively. The highest incidence was in children aged 6-14 years from 2005-2016, of which the majority were school students (67.84%). Approximately 90% of the reported outbreaks occurred in school children (primary school/middle school). The seasonal characteristics of mumps were less obvious from 2011 to 2016. The coverage of one-dose MMR in the 2005 birth cohort was 71.38%. For the 2006-2010 birth cohort, the coverage of one-dose MuCV was 96.82% and the coverage of two-dose MuCV was 17.68%. The children born from 2011 to 2016 were only free vaccinated with MMR; the coverage of one-dose MuCV was 99.10%. The mumps incidence in the three birth cohorts significantly declined (X 2 = 805.90, P < 0.001 for trend). Except the children less than two years old, the mumps incidence for the children born from 2006 to 2010 was higher than that for the children born from 2011 to 2016. CONCLUSION: The mumps incidence significantly declined following the introduction of one-dose MMR. The SIA using MM led to a rapid reduction of mumps cases. Therefore, we recommend a two-dose MuCV routine immunization schedule and improved vaccination coverage.

[Protective effect and mechanism of Ribociclib on sepsis induced-acute kidney injury].

OBJECTIVE: To investigate the role of Ribociclib in sepsis induced-acute kidney injury (AKI) and its possible mechanisms. METHODS: (1) Twenty adult male C57BL/6 mice were divided into sham operation group (Sham group; only open the abdomen without ligating or perforating the cecum, administered with sodium lactate buffer 12 hours before the sham operation), Ribociclib control group (administered with 150 mg/kg Ribociclib), cecal ligation and puncture (CLP) group (sepsis model induced by CLP; lactate buffer was given by intragastric administration 12 hours before CLP), and Ribociclib pretreatment group (administered with 150 mg/kg Ribociclib 12 hours before CLP) according to random number table, with 5 mice in each group. Kidneys were harvested 12 hours after the operation. Pathological changes in kidney were observed by hematoxylin-eosin (HE) staining. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in mice kidney homogenate were measured by enzyme linked immunosorbent assay (ELISA). Western Blot was used to detect the expression of cell cycle-related protein phosphorylate retinoblastoma protein (p-Rb), apoptosis-related protein Bcl-2 and Bax. (2) Mouse renal tubular epithelial (TCMK-1) cell line was used for in vitro experiment. The cells were divided into control group, Ribociclib group (treated with 5 µmol/L Ribociclib for 24 hours), lipopolysaccharide (LPS) group (treated with 200 mg/L LPS for 6 hours), Ribociclib+LPS group (replaced with the medium containing 5 µmol/L Ribociclib and 200 mg/L LPS for 6 hours after exposing with 5 µmol/L Ribociclib for 18 hours). Inflammatory cytokines in cell culture medium were detected by ELISA. The expression of p-Rb, Bcl-2 and Bax, autophagy-related proteins microtubule associated protein 1 light chain LC3b (LC3b II, LC3b I) and p62, phosphate protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR) were measured by Western Blot. RESULTS: (1) Animal experiments showed that, compared with the Sham group, the kidney tissue of mice were significantly damaged, the levels of TNF-α and IL-6 were increased, the expressions of p-Rb and Bcl-2/Bax ratio were decreased in kidney tissue in CLP group; but there was no significant difference in indexes between Ribociclib control group and Sham group. Compared with the CLP group, kidney injury in mice pretreated with Ribociclib was significantly ameliorated, the pathological score was significantly decreased (1.48±0.16 vs. 2.68±0.16, P < 0.01), the levels of TNF-α and IL-6 in kidney homogenate were significantly decreased [TNF-α (ng/g): 340.55±34.96 vs. 745.08±58.86, IL-6 (mg/g): 17.33±1.01 vs. 114.20±20.49, both P < 0.01], the expression of p-Rb was furtherly decreased (p-Rb/ß-tubulin: 0.14±0.01 vs. 0.73±0.06, P < 0.01), Bcl-2/Bax ratio was increased (0.89±0.06 vs. 0.62±0.10, P < 0.01). (2) In vitro experiments showed that, compared with the control group, the releases of TNF-α and IL-6 were increased, the expression of p-Rb was decreased, the ratios of Bcl-2/Bax and LC3b II/I were decreased, the expressions of p62, p-AKT and p-mTOR were increased in LPS group; the expression of p-Rb was decreased after Ribociclib treatment in TCMK-1 cells. Compared with the LPS group, TNF-α and IL-6 were decreased [TNF-α (ng/L): 2.73±0.23 vs. 4.96±0.10, IL-6 (ng/L): 36.05±5.83 vs. 53.78±24.08, both P < 0.01], the expression of p-Rb was furtherly decreased (p-Rb/ß-tubulin: 0.25±0.05 vs. 0.65±0.05, P < 0.01), the ratios of Bcl-2/Bax and LC3b II/I were increased (Bcl-2/Bax: 1.01±0.07 vs. 0.73±0.05, LC3b II/I: 2.08±0.31 vs. 1.04±0.01, both P < 0.05), the expressions of p62, p-AKT and p-mTOR were decreased (p62/ß-tubulin: 0.59±0.01 vs. 1.09±0.08, p-AKT/ß-tubulin: 0.61±0.03 vs. 1.20±0.06, p-mTOR/ß-tubulin: 0.50±0.05 vs. 1.15±0.08, all P < 0.01) in the Ribociclib+LPS group. CONCLUSIONS: Ribociclib pretreatment ameliorated sepsis-induced AKI and AKT/mTOR pathway may be involved in the protective role of Ribociclib on kidney.

[Mesophyll conductance to CO2: Methods and current knowledge].

Mesophyll conductance (gm), the total conductance of CO2 diffusion from substomatal cavity to the site of carboxylation within chloroplast, is a major limiting factor for photosynthesis and a key parameter for improving photosynthetic resource use efficiency of crops. Online 13C discrimination method is an important method for plant eco-physiological studies and a well-established method for measuring gm of C3 plants, although it has not been widely used due to challenges in methodology and high demands on experimental facilities. In this review, we summarized the characteristics of commonly used methods for gm, introduced the basic theory of the online 13C discrimination method, namely Farquhar's photosynthetic 13C discrimination model; systematically introduced the practical measurements, equations and the components of facilities; and reviewed the drivers for variation in gm of C3 plants. At the last part, we discussed the outlook of the development of methodology, new experimental protocols, and applications in measurement scenarios.

MiR-214-3p exacerbates kidney damages and inflammation induced by hyperlipidemic pancreatitis complicated with acute renal injury.

AIMS: Acute pancreatitis (AP) is usually complicated with multiple organ insufficiency, including renal injury. Hyperlipidemia is regarded as a risk factor to induce AP. High-fat diet-induced hyperlipidemic pancreatitis (HP) increased nowadays and showed more severe symptoms and complications than other AP. However, detailed mechanisms or mediators involved in HP complicated with acute renal injury were less studied. Here, we aimed to study how miR-214 expresses in the HP and whether miR-214 has functions to regulate pathological kidney damages induced by HP. MAIN METHODS: Sprague-Dawley rats were adopted to establish HP model complicated with acute renal injury through long-term high-fat diet and sodium taurocholic injection. Models were injected with LV-rno-miR-214-3p or LV-anti-rno-miR-214-3p to exogenously regulate miR-214-3p to study its impacts on HP via a series of molecular and histological experiments. KEY FINDINGS: MiR-214-3p was found to be up-regulated in the kidney, pancreas and serum of HP rats and also could intensify the pathological alterations, kidney and pancreas damages and fibrosis induced by HP. Inflammatory response in HP was enhanced when miR-214-3p was overexpressed. Besides, miR-214-3p up-regulation was showed to inhibit PTEN expression but increased P-Akt levels in the HP kidney, which might be a possible mechanism to induce severe symptoms of pancreatitis. Knockdown of miR-214-3p showed opposite effects. SIGNIFICANCE: MiR-214-3p is indicated to exacerbate the tissue damages and inflammatory response caused by HP complicated with acute renal injury, which may provide a novel therapeutic perspective targeting miR-214-3p to treat HP with acute renal injury.

Autophagy Enhancing Contributes to the Organ Protective Effect of Alpha-Lipoic Acid in Septic Rats.

Alpha-lipoic acid (ALA) reportedly has protective effects against sepsis, which is a leading cause of mortality worldwide and is associated with multiple organ dysfunction. The present study aimed to investigate further the possible action mechanisms of ALA. Male Sprague-Dawley rats were subjected to cecal ligation and puncture (CLP) in order to establish a sepsis model. The rats received an oral gavage of 200 mg/kg ALA or saline immediately after surgery. The heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and maximum rising and lowering rates of left ventricular pressure (±dp/dt) were examined for assessing the cardiac function. Blood urea nitrogen (BUN) and serum creatinine levels were assessed for evaluating renal function. Neutrophil gelatinase-associated lipocalin (NAGL) was examined for reflecting acute renal injury. Histopathological alterations of the small intestine were examined by hematoxylin-eosin staining. The ultrastructure of the small intestine and kidney was observed under electron microscopy. The levels of autophagy- and inflammation-associated proteins were determined via western blot analysis. The binding of nuclear factor-kappa B (NF-κB) to DNA was tested via an electrophoretic mobility shift assay. Cell apoptosis was examined using TUNEL staining. ALA treatment improved the survival rate, restored the loss of body weight and pro-inflammatory cytokines production in the serum of CLP-induced septic rats. ALA improved the cardiac and renal functions, downregulated the expression levels of interleukin-1ß, tumor necrosis factor-α, and inducible nitric oxide synthase in the myocardium and small intestine of septic rats. ALA treatment also inactivated the NF-κB signaling pathway in the small intestine. An examination of autophagy showed that ALA increased the LC3II/I ratio, upregulated Atg5, Atg7, and beclin-1 and downregulated p62 protein levels in the myocardium, kidney, and small intestine of septic rats, and further promoted autophagosome accumulation in the kidney and small intestine. In addition, ALA could also reduce cell apoptosis in myocardium, kidney and small intestine tissues. These effects can be completely or party inhibited by 3-MA. Our findings suggest that autophagy enhancing may contribute to the organ protective effect of ALA in septic rats.

The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats.

Sepsis-induced acute kidney injury (AKI) represents a major cause of mortality in intensive care units. Sivelestat, a selective inhibitor of neutrophil elastase (NE), can attenuate sepsis-related acute lung injury. However, whether sivelestat can preserve kidney function during sepsis remains unclear. In this study, we thus examined the effects of sivelestat on sepsis-related AKI. Cecal ligation and puncture (CLP) was performed to induce multiple bacterial infection in male Sprague-Dawley rats, and subsequently, 50 or 100 mg/kg sivelestat were administered by intraperitoneal injection immediately after the surgical procedure. In the untreated rats with sepsis, the mean arterial pressure (MAP) and glomerular filtration rate (GFR) were decreased, whereas serum blood urea nitrogen (BUN) and neutrophil gelatinase-associated lipocalin (NGAL) levels were increased. We found that sivelestat promoted the survival of the rats with sepsis, restored the impairment of MAP and GFR, and inhibited the increased BUN and NGAL levels; specifically, the higher dose was more effective. In addition, sivelestat suppressed the CLP-induced macrophage infiltration, the overproduction of pro-inflammatory mediators (tumor necrosis factor­α, interleukin-1ß, high-mobility group box 1 and inducible nitric oxide synthase) and serine/threonine kinase (Akt) pathway activation in the rats. Collectively, our data suggest that the inhibition of NE activity with the inhibitor, sivelestat, is beneficial in ameliorating sepsis-related kidney injury.

Invasive candidiasis in intensive care units in China: Risk factors and prognoses of Candida albicans and non-albicans Candida infections.

BACKGROUND: To investigate the risk factors and prognoses of patients with invasive Candida albicans and non-albicans Candida (NAC) infection in intensive care units (ICUs) in China. METHODS: Between November 2009 and April 2011, we performed a prospective study of critically ill patients with invasive Candida infection from 67 ICUs across China to compare the risk factors and mortality between patients with C albicans and NAC infection. RESULTS: There were 306 patients with proven invasive Candida; 244 cases (a total 389 Candida isolates) were sent to laboratory for strain identification (C albicans, 40.1%; NAC, 59.9%). More patients admitted for surgery or trauma had NAC infection than C albicans infection. C albicans infection was more common in patients with subclavian vein catheters or peritoneal drainage tubes. Compared with patients with C albicans infection, patients with NAC infection had longer antifungal therapy (P < .001), longer ICU (P = .004) or hospital stay (P = .002), and slightly higher mortality (38.4% vs 29.6%), but the difference was not significant (P = .17). CONCLUSIONS: C albicans remains the most common pathogen in candidiasis in critical care patients. However, the number of NAC infections exceeded C albicans infections. Compared with patients with C albicans infection, patients with NAC infection had heavier disease burdens.

[The effects of fluid resuscitation on oxygenation index and prognosis in early stage of severe acute pancreatitis].

OBJECTIVE: To analyze the correlation between fluid equilibrium and oxygen index in patients at early stage (within 2 weeks) of severe acute pancreatitis (SAP), and to discuss the effects of fluid equilibrium after resuscitation on the prognosis. METHODS: A clinical study was conducted. Ninety-seven patients with SAP admitted into Shengjing Hospital of China Medical University directly or transferred into intensive care unit (ICU) in 24 hours after admission between March 2011 to October 2013 were studied. Finally, 65 patients were enrolled in statistical analysis, and those with termination of treatment prematurely were excluded. The patients received treatment protocol formulated by the same physician in ICU. Patients were divided into improved group and death group according to the outcome. The differences in fluid equilibrium on 1, 2, 3, 7, 14 days after admission of ICU between the two groups were compared. The correlation between fluid equilibrium and oxygen index was analyzed with curve fitting. RESULTS: Among 65 patients enrolled, 53 of them were improved after intensive care and were transferred into ordinary wards. However, 12 patients died in ICU. Patients in the improved group showed delayed positive fluid equilibrium, and some patients even showed negative fluid equilibrium. Patients in death group needed more fluid to achieve fluid equilibrium. There was a significant difference in the need of fluid to reach an equilibrium between improved group and death group [1 day: 1 814.5 (905.2, 2 152.8) mL vs. 3 891.0 (2 524.2, 5 714.5) mL, Z=-3.303, P=0.001; 2 days: 2 469.0 (1 456.0, 3 696.0) mL vs. 6 498.0 (4 617.8, 8 763.5) mL, Z=-4.431, P<0.001; 3 days: 3 234.0 (1 098.0, 4 295.5) mL vs. 9 533.5 (6 748.8, 10 689.0) mL, Z=-4.684, P<0.001; 7 days: 3 234.0 (1 033.0, 5 162.0) mL vs. 13 986.5 (8 045.8, 14 518.0) mL, Z=-4.718, P<0.001; 14 days: 3 234.0 (978.5, 4 924.0) mL vs. 13 436.5 (8 045.8, 14 518.0) mL, Z=-4.769, P<0.001]. There was no correlation between fluid equilibrium and oxygen index in improved patients within 3 days of ICU admission (R² = 0.000, P=0.827), and it fit the logistic curve in a relatively low level after 3 days of ICU admission (R² = 0.036, P<0.001). CONCLUSIONS: Early fluid resuscitation could help maintain hemodynamics stability in SAP patients. Those SAP patients who showed a negative equilibrium in early stage showed a better prognosis, and the fluid equilibrium and oxygen index in improved patients fit the logistic curve after 3 days of ICU admission.

α-Lipoic acid prolongs survival and attenuates acute kidney injury in a rat model of sepsis.

Acute kidney injury is a frequent and serious complication in patients with severe sepsis. α-Lipoic acid (ALA), a naturally occurring dithiol compound, has been shown to possess anti-inflammatory and anti-oxidative properties. In the present study we investigated whether ALA could attenuate acute kidney injury and improve survival in a rat model of sepsis. Rats were subjected to caecal ligation and puncture (CLP) to induce sepsis. α-Lipoic acid (200 mg/kg) was administered by oral gavage either immediately (early treatment) or 12 h after the surgical procedure (delayed treatment). Both early and delayed ALA treatment effectively prolonged survival, improved pathological damage in kidney tissues and reduced serum blood urea nitrogen and creatinine levels in CLP-induced septic rats. Furthermore, early treatment with ALA markedly inhibited the release of tumour necrosis factor-α, interleukin (IL)-6 and IL-1ß into the serum and reduced mRNA and protein expression of inducible nitric oxide synthase and high mobility group box 1 in kidney tissues from CLP-induced rats. Finally, CLP-induced nuclear factor-κB activation in kidney tissues was significantly suppressed by early ALA treatment. Together, the results indicate that ALA is able to reduce mortality and attenuate acute kidney injury associated with sepsis, possibly by anti-inflammatory actions. α-Lipoic acid may be a promising novel agent for the treatment of conditions associated with septic shock.

[Changes in plasma adiponectin concentrations in sepsis and its correlation with the severity of the disease].

OBJECTIVE: To explore the regularity of changes in total adiponectin (APN) and high molecular bodyweight adiponectin (HAP) in sepsis, and its correlation with infection and its role on predicting prognosis. METHODS: A prospective study was conducted. Eighty patients with sepsis in intensive care unit (ICU) of Shengjing Hospital of China Medicine University from June to November in 2011 were enrolled in this study. The plasma APN (both total APN and HAP), procalcitonin (PCT), and endotoxin were determined with enzyme linked immunosorbent assay (ELISA) at 2 hours, 2 days, and 6 days after ICU admission. The acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), and simplified acute physiology score II (SAPS II) scores were recorded, and insulin resistance index was calculated. Twenty healthy volunteers and 21 patients with systemic inflammation response syndrome (SIRS) were enrolled as controls and SIRS group. RESULTS: Plasma total APN and HAP in sepsis patients at 2 hours after ICU admission were significantly decreased compared with control group and SIRS group [total APN: 2.87 (2.28, 3.89) mg/L vs. 6.48±1.53 mg/L, 3.72 (2.67, 4.59) mg/L; HAP: 2.64 (2.07, 3.75) mg/L vs. 5.12±1.98 mg/L, 3.33 (2.23, 4.24) mg/L, P<0.05 or P<0.01]. A negative correlation was found between total APN and HAP in plasma and PCT (total APN r=-0.559, HAP r=-0.530, both P<0.01), but no correlation with endotoxin. Those correlations remained significantly in partial correlation analysis controlled by insulin resistance status. There were significances in APN among sepsis, severe sepsis and septic shock groups, and negative correlations were found between APN and APACHE II, SOFA, and SAPS II scores (total APN r value, -0.868, -0.766, -0.725; HAP r value, -0.859, -0.715, -0.692, all P<0.01). Total APN and HAP in plasma of survivors with sepsis (n=41) was gradually increased following the recovery of the disease (total APN χ(2)=34.520, HAP χ(2)=27.802, both P<0.01) and the level in non-survivors (n=7) was decreased (total APN χ(2)=3.938, HAP χ(2)=3.938, both P>0.05). The significantly negative correlations were found between total APN and HAP at 2 hours after ICU admission and ICU duration (total APN r=-0.275, P=0.014; HAP r=-0.299, P=0.007) and ventilation time (total APN r=-0.393, HAP r=-0.519, both P<0.01). CONCLUSIONS: Plasma total APN and HAP was decreased in septic patients, and negatively correlated with PCT. Plasma total APN and HAP played a role in diagnosis of infection and predicting the outcomes, and correlated with severity of sepsis.