The present study was aimed to investigate whether Gasdermin D (GSDMD)-mediated pyroptosis participated in lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (AKI), and to explore the role of caspase-1 and caspase-11 pyroptosis pathways in this process. The mice were divided into four groups: wild type (WT), WT-LPS, GSDMD knockout (KO) and KO-LPS. The sepsis-associated AKI was induced by intraperitoneal injection of LPS (40 mg/kg). Blood samples were taken to determine the concentration of creatinine and urea nitrogen. The pathological changes of renal tissue were observed via HE staining. Western blot was used to investigate the expression of pyroptosis-associated proteins. The results showed that the concentrations of serum creatinine and urea nitrogen in the WT-LPS group were significantly increased, compared with those in the WT group (P < 0.01); whereas serum creatinine and urea nitrogen in the KO-LPS group were significantly decreased, compared with those in the WT-LPS group (P < 0.01). HE staining results showed that LPS-induced renal tubular dilatation was mitigated in GSDMD KO mice. Western blot results showed that LPS up-regulated the protein expression levels of interleukin-1β (IL-1β), GSDMD and GSDMD-N in WT mice. GSDMD KO significantly down-regulated the protein levels of IL-1β, caspase-11, pro-caspase-1, caspase-1(p22) induced by LPS. These results suggest that GSDMD-mediated pyroptosis is involved in LPS-induced sepsis-associated AKI. Caspase-1 and caspase-11 may be involved in GSDMD cleavage.
Animals ; Mice ; Acute Kidney Injury ; Caspase 1 ; Caspases/metabolism* ; Creatinine ; Lipopolysaccharides ; Mice, Knockout ; Nitrogen ; Sepsis ; Urea ; Gasdermins/metabolism*

Objective To observe the intervention effect of typical hot spring bathing in Guizhou province on joint pain, serum anti-keratin antibody(AKA), anti-perinuclear factor antibody(APF)and anti-cyclic citrullinated peptide antibody(CCP). Methods A total of 160 people with joint pain symptoms from five typical hot spring areas in Guizhou province were selected as the subjects. They were treated with hot spring bathing intervention for 4 weeks, once a day, 5 times a week, 40 to 50 minutes each time. According to the evaluation index of physiotherapy natural mineral water in the Code for Geological Exploration and Evaluation of Natural Warm Mineral Water Resources(GB/T 13727-2016)and geological types, the five typical hot springs were divided into three different types, namely water temperature type hot springs(water temperature > 36 ℃), metasilicate type hot springs(metasilicate > 50 mg/L)and warm mineral spring type hot springs(total dissolved solids > 1 000 mg/L). WHO pain grading standard was used to score the degree of joint pain before and after hot spring bathing intervention. Serum APF, AKA and CCP antibodies were detected by ELISA kit before and after hot spring bathing. Results The joint pain score of the subjects was 2.60±0.60, and the joint pain score of the total population decreased after intervention(0.61±0.57, P < 0.05). Before intervention, the joint pain scores of water temperature type, metasilicic acid type and warm mineral spring type were 2.78±0.96, 1.98±1.15 and 3.31±0.57, respectively. After intervention, the scores of joint pain of the three kinds of hot spring bathing patients all decreased(P < 0.05), and were 0.50±0.65, 0.48±0.74 and 0.85±0.90, respectively. Before intervention, AKA(ng/L)and CCP(μg/mL)antibody levels of the observed subjects were 34.89±16.06 and 107.58±10.40, respectively, which significantly decreased after intervention(both P < 0.05), namely 26.06±10.68 and 102.93±6.01, respectively. AKA(ng/L)was 35.04±20.01 before intervention, but decreased significantly after intervention(26.61±7.54, P < 0.05). AKA(ng/L)and CCP(μg/mL)were 31.09±17.26 and 106.51±10.13 before intervention, respectively. After intervention, the above two antibody indexes significantly decreased(all P < 0.05)to 24.53±13.98 and 98.57±5.68, respectively. Before intervention, the AKA(ng/L), APF(ng/mL)and CCP(μg/mL)antibody levels were 38.40±8.66, 349.46±118.43 and 104.96±9.66, respectively. After intervention, the above three antibody indexes significantly decreased(all P < 0.05). The values were 34.00±7.55, 269.38±127.55 and 101.65±3.04, respectively. Conclusion The typical hot spring bathing intervention in Guizhou province can relieve the symptoms of joint pain, and the three types of hot springs can reduce the levels of AKA, APF and CCP antibodies to different degrees, and the warm mineral spring type of hot spring is better than the other types of hot spring.

Objective:To investigate the different outcomes of two types of acute kidney injury (AKI) according to standard of Kidney Disease: Improving Global Outcomes-AKI (KDIGO-AKI), and to analyze the risk factors that affect the prognosis of intensive care unit (ICU) patients in China.Methods:A secondary analysis was performed on the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a multicenter prospective study involving 3 063 patients in 22 tertiary ICUs in 19 provinces and autonomous regions of China. The demographic data, scores reflecting severity of illness, laboratory findings, intervention during ICU stay were extracted. All patients were divided into pure AKI (PAKI) and acute on chronic kidney disease (AoCKD). PAKI was defined as meeting the serum creatinine (SCr) standard of KDIGO-AKI (KDIGO-AKI SCr) and the estimated glomerular filtration rate (eGFR) at baseline was ≥ 60 mL·min -1·1.73 m -2, and AoCKD was defined as meeting the KDIGO-AKI SCr standard and baseline eGFR was 15-59 mL·min -1·1.73 m -2. All-cause mortality in ICU within 28 days was the primary outcome, while the length of ICU stay and renal replacement therapy (RRT) were the secondary outcome. The differences in baseline data and outcomes between the two groups were compared. The cumulative survival rate of ICU within 28 days was analyzed by Kaplan-Meier survival curve, and the risk factors of ICU death within 28 days were screened by Cox multivariate analysis. Results:Of the 3 063 patients, 1 042 were enrolled, 345 with AKI, 697 without AKI. The AKI incidence was 33.11%, while ICU mortality within 28 days of AKI patients was 13.91% (48/345). Compared with PAKI patients ( n = 322), AoCKD patients ( n = 23) were older [years old: 74 (59, 77) vs. 58 (41, 72)] and more critical when entering ICU [acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score: 23 (19, 27) vs. 15 (11, 22)], had worse basic renal function [eGFR (mL·min -1·1.73 m -2): 49 (38, 54) vs. 115 (94, 136)], more basic complications [Charlson comorbidity index (CCI): 3 (2, 4) vs. 0 (0, 1)] and higher SCr during ICU stay [peak SCr for diagnosis of AKI (μmol/L): 412 (280, 515) vs. 176 (124, 340), all P < 0.01]. The mortality and RRT incidence within 28 days in ICU of AoCKD patients were significantly higher than those of PAKI patients [39.13% (9/23) vs. 12.11% (39/322), 26.09% (6/23) vs. 4.04% (13/322), both P < 0.01], while no significant difference was found in the length of ICU stay. Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate in ICU in AoCKD patients was significantly lower than PAKI patients (Log-Rank: χ2 = 5.939, P = 0.015). Multivariate Cox regression analysis showed that admission to ICU due to respiratory failure [hazard ratio ( HR) = 4.458, 95% confidence interval (95% CI) was 1.141-17.413, P = 0.032], vasoactive agents treatment in ICU ( HR = 5.181, 95% CI was 2.033-13.199, P = 0.001), and AoCKD ( HR = 5.377, 95% CI was 1.303-22.186, P = 0.020) were independent risk factors for ICU death within 28 days. Conclusion:Further detailed classification (PAKI, AoCKD) based on KDIGO-AKI SCr standard combined with eGFR is related to ICU mortality in critical patients within 28 days.

Objective To analyze the role of telehealth?based dialysis registration systems in real?time and dynamic reflection of renal anemia in hemodialysis (HD) patients, and discuss the prospect of its application in dialysis registration management. Methods The Red China project was to build up a dialysis registration system based on the WeChat mobile terminal platform. Demographic and baseline laboratory parameters such as age, gender, primary disease, dialysis age, creatinine were recorded in this system. Hemoglobin (Hb) level was monthly recorded. The platform generated Hb statistics report for each HD center monthly, including the detection rate, target rate and the distribution level of Hb, and released it to physicians through the WeChat terminal of mobile phone. After that, physicians could change the treatment of anemia individually on basis of this report. Here the demographic and baseline laboratory parameters, the detection rate, target rate, the average level and the distribution of Hb from June 2015 to October 2017 after the project launched were analyzed. Results From June 2015 to October 2017, 8392 maintenance HD patients from 28 HD centers in Shanghai were enrolled, of whom 5059(60.3％) were male.The average rate age was (60.5 ± 13.7) years old. Baseline average Hb was (108.3±16.0) g/L. Baseline detection rate and target rate were 54.2％and 47.5％, respectively. After 28 months follow?up, the detection rate of Hb increased from 54.2％ to 73.6％ (P<0.001), the target rate of Hb increased from 47.5％ to 56.1％ (P<0.001), and the level of average Hb rose from (108.3±16.0) g/L to (110.7±16.0) g/L. The difference between average Hb in two consecutive months was less than 1.3 g/L. Conclusions The telehealth?based dialysis registration system can timely report the anemia situation of HD patients, which may improve the awareness rate of anemia, the degree of attention and the compliance of anemia monitoring, so as to improve the detection rate and target rate of Hb and reduce the fluctuation of Hb, which helps to maintain the HD patients to correct anemia in a timely, stable and long?term way. The telehealth?based dialysis registration system, as an improved mode of dialysis registration is a promising way for long?term management of renal anemia in dialysis patients.

OBJECTIVETo investigate the genotypic diversity of Methicillin-resistant Staphylococcus aureus (MRSA) isolated from pigs and retail foods from different geographical areas in China and further to study the routes and rates of transmission of this pathogen from animals to food.

METHODSSeventy-one MRSA isolates were obtained from pigs and retail foods and then characterized by multi-locus sequencing typing (MLST), spa typing, multiple-locus variable number of tandem repeat analysis (MLVA), pulsed-field gel electrophoresis (PFGE), and antimicrobial susceptibility testing.

RESULTSAll isolated MRSA exhibited multi-drug resistance (MDR). Greater diversity was found in food-associated MRSA (7 STs, 8 spa types, and 10 MLVA patterns) compared to pig-associated MRSA (3 STs, 1 spa type, and 6 MLVA patterns). PFGE patterns were more diverse for pig-associated MRSA than those of food-associated isolates (40 vs. 11 pulse types). Among the pig-associated isolates, CC9-ST9-t899-MC2236 was the most prevalent clone (96.4%), and CC9-ST9-t437-MC621 (20.0%) was the predominant clone among the food-associated isolates. The CC9-ST9 isolates showed significantly higher antimicrobial resistance than other clones. Interestingly, CC398-ST398-t034 clone was identified from both pig- and food-associated isolates. Of note, some community- and hospital-associated MRSA strains (t030, t172, t1244, and t4549) were also identified as food-associated isolates.

CONCLUSIONCC9-ST9-t899-MC2236-MDR was the most predominant clone in pigs, but significant genetic diversity was observed in food-associated MRSA. Our results demonstrate the great need for improved surveillance of MRSA in livestock and food and effective prevention strategies to limit MDR-MRSA infections in China.

Animals ; Anti-Bacterial Agents ; pharmacology ; China ; Food Microbiology ; Humans ; Methicillin ; pharmacology ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; genetics ; isolation & purification ; Nose ; microbiology ; Swine ; microbiology

BACKGROUNDUrine output (UO) is an essential criterion of the Kidney Disease Improving Global Outcomes (KDIGO) definition and classification system for acute kidney injury (AKI), of which the diagnostic value has not been extensively studied. We aimed to determine whether AKI based on KDIGO UO criteria (KDIGOUO) could improve the diagnostic and prognostic accuracy, compared with KDIGO serum creatinine criteria (KDIGOSCr).

METHODSWe conducted a secondary analysis of the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a 2-month prospective cohort study (July 1, 2009 to August 31, 2009) involving 3063 patients in 22 tertiary Intensive Care Units in Mainland of China. AKI was diagnosed and classified separately based on KDIGOUOand KDIGOSCr. Hospital mortality of patients with more severe AKI classification based on KDIGOUOwas compared with other patients by univariate and multivariate regression analyses.

RESULTSThe prevalence of AKI increased from 52.4% based on KDIGOSCrto 55.4% based on KDIGOSCrcombined with KDIGOUO. KDIGOUOalso resulted in an upgrade of AKI classification in 7.3% of patients, representing those with more severe AKI classification based on KDIGOUO. Compared with non-AKI patients or those with maximum AKI classification by KDIGOSCr, those with maximum AKI classification by KDIGOUOhad a significantly higher hospital mortality of 58.4% (odds ratio [OR]: 7.580, 95% confidence interval [CI]: 4.141-13.873, P< 0.001). In a multivariate logistic regression analysis, AKI based on KDIGOUO (OR: 2.891, 95% CI: 1.964-4.254, P< 0.001), but not based on KDIGOSCr (OR: 1.322, 95% CI: 0.902-1.939, P = 0.152), was an independent risk factor for hospital mortality.

CONCLUSIONUO was a criterion with additional value beyond creatinine criterion for AKI diagnosis and classification, which can help identify a group of patients with high risk of death.

Acute Disease ; mortality ; Aged ; Creatinine ; blood ; Critical Illness ; mortality ; Female ; Hospital Mortality ; Humans ; Kaplan-Meier Estimate ; Kidney Diseases ; blood ; mortality ; pathology ; urine ; Logistic Models ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Risk Factors

Objective To establish the high performance liquid chroma-tography ( HPLC ) method for determination of the concentration of imi-penem in sputum.Methods HPLC was performed on a C18 column, ( Venusil MP, 4.6 mm ×250 mm, 5 μm).The mobile phase was com-posed of phosphate buffer 10 mmol? L-1 ( pH 7.2 ) and methanol ( with 0.3 mmol? L-1 tetraethyl ammonium bromide ) ( 96∶4 ) .The flow rate was 1 mL? min-1 .Stabilizer was a mixture of 0.5 mmol? L-1 3-mor-pholine propanesulfonic acid buffer ( pH 6.8 ) , glycol and pure water (2∶1∶1).The column temperature was set at 30 ℃.The detection wavelength was set at 300 nm.The flow rate was 1.0 mL? min-1 .And then the specificity , and quantitative lower limit standard curve , preci-sion and recovery rate and stability of the method was investigated . Results A good linearity was shown in the concentration range 0.25-50 μg? mL-1 ( r=0.999 0-0.999 6 ).The limit of quantitation concen-tration of imipenem was 0.25 μg? mL-1 .The intra-day relative stan-dard deviation ( RSD) were 3.29%, 4.94%, 1.35%, and inter -day RSD were 2.57%, 6.15%, 6.98% at 3 concentrations ( 0.3 , 15 , 45μg? mL-1 ) , the extraction recovery of each quality control concentra-tion of the diluted sputum was ( 86.77 ±0.88 )%, ( 98.31 ±0.47 )%and (95.51 ±1.54 )%, respectively. Conclusion The method is simple and accurate .It can be used to determine the concentration of imipenem in sputum .

Objective To investigate the effects of the aqueous extracts of Eclipta Prostrata L.( EPL) on plasma lipid levels and the structure of vascular intima in rats with hyperhomocysteinemia ( Hhcy ) . Methods High L -methionine diet was used to construct HHcy rat model.Fifty SD rats were randomly divided into five groups:normal group, model group, lovastatin group (2 mg? kg -1 ), Eclipta Prostrata L.(EPL) low-and high-doses groups (5, 10 g? kg -1 ).The drags were administrated by intragastric administration once a day . After 8 weeks administration , the level of serum homocysteine ( Hcy ) , total cholesterol (TC) and trigly-ceride ( TG) were detected by biochemical analysis.While nitric oxide (NO), endothelin (ET) and thromboxane B2 ( TXB2 ) were measured by enzyme linked immunosorbent assay (ELISA).The histopathological examination of the thoracic aortas were observed microscopically afterhematoxylin -eosin ( HE ) staining. Results Compared with model group , serum levels of Hcy , TG, TC, ET and TXB 2 were significantly decreased ( P<0.05 ) in EPL groups and lovastatin group , while NO levels were significantly increased ( P<0.05) in high dose EPL group.HE sections showed that the shape of thoracic aortas looks as normal .Conclusion The aqueous extract of EPL could effectively reduce serum Hcy and regulate plasma lipid levels , thus it could alleviate vascular damage .

Clinical breakpoints are used in phaseⅡorⅢclinical trials to categorize microorganisms if susceptibility to new tested antibacterial agents that means the patient infected by the pathogen will be enrolled the study or not.The role of this consensus is to define procedure and required data to setting breakpoints and how to revaluate it in clinical trials.

Objective To evaluate self -made vancomycin quality -control serum used in blood drug concentration monitoring .Methods To prepare 10,20,30 μg·mL-1 vancomycin quality -control serum. The preparation, repeatability, sample stability and clinical application were studied.Results The results of low, medium and high concentra-tion of vancomycin quality-control serum was 98.0%-101.5%.The content change of vancomycin was less than 2% while saved at -30 ℃within 6 months.Conclusion The method for preparation of self-made vancomycin quality-control serum is simple, cost-effective, accurate and reliable, which can be used as daily laboratory quality control saved at -30℃.