The gut microbial metabolite, 3,4-dihydroxyphenylpropionic acid, alleviates hepatic ischemia/reperfusion injury via mitigation of macrophage pro-inflammatory activity in mice

Hepatic ischemia/reperfusion injury (HIRI) is a serious complication that occurs following shock and/or liver surgery. Gut microbiota and their metabolites are key upstream modulators of development of liver injury. Herein, we investigated the potential contribution of gut microbes to HIRI. Ischemia/reperfusion surgery was performed to establish a murine model of HIRI. 16S rRNA gene sequencing and metabolomics were used for microbial analysis. Transcriptomics and proteomics analysis were employed to study the host cell responses. Our results establish HIRI was significantly increased when surgery occurred in the evening (ZT12, 20:00) when compared with the morning (ZT0, 08:00); however, antibiotic pretreatment reduced this diurnal variation. The abundance of a microbial metabolite 3,4-dihydroxyphenylpropionic acid was significantly higher in ZT0 when compared with ZT12 in the gut and this compound significantly protected mice against HIRI. Furthermore, 3,4-dihydroxyphenylpropionic acid suppressed the macrophage pro-inflammatory response in vivo and in vitro. This metabolite inhibits histone deacetylase activity by reducing its phosphorylation. Histone deacetylase inhibition suppressed macrophage pro-inflammatory activation and diminished the diurnal variation of HIRI. Our findings revealed a novel protective microbial metabolite against HIRI in mice. The potential underlying mechanism was at least in part, via 3,4-dihydroxyphenylpropionic acid-dependent immune regulation and histone deacetylase (HDAC) inhibition in macrophages.

Elevated serum lactic acid level is an independent risk factor for the incidence and mortality of sepsis-associated acute kidney injury / 中华危重病急救医学

Objective:To explore the effect of serum lactic acid (Lac) level on acute kidney injury (AKI) in patients with sepsis and whether Lac level affects the in-hospital mortality of patients with sepsis-associated AKI.Methods:A retrospective cohort study was conducted. Clinical data of patients with sepsis admitted to the internal intensive care unit (ICU) of the First Affiliated Hospital of Guangxi Medical University from March 2014 to June 2019 and the ICU of the Second Affiliated Hospital of Guangxi Medical University from January 2017 to June 2020 were collected. According to the first quartile of Lac within 24 hours of admission to ICU, the patients were divided into Lac ≤ 1.4 mmol/L group (group Q1), Lac 1.5-2.4 mmol/L group (group Q2), Lac 2.5-4.0 mmol/L group (group Q3), and Lac ≥ 4.1 mmol/L group (group Q4). The incidence of sepsis-associated AKI after admission to ICU and hospital mortality were compared among four groups. The effect of elevated Lac on the incidence and mortality of sepsis-associated AKI was investigated by binary Logistic regression analysis. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of Lac on the incidence and mortality of sepsis-associated AKI, and the cut-off value was obtained to analyze the incidence and death risk of sepsis-associated AKI at different Lac levels. Results:A total of 655 sepsis patients were enrolled, of which 330 patients (50.4%) developed AKI and 325 patients (49.6%) did not. Among 330 patients with sepsis-associated AKI, 134 (40.6%) died and 196 (59.4%) survived. With the increase of Lac level, the incidence of sepsis-associated AKI increased gradually (34.5%, 41.0%, 58.4%, 66.3%, respectively, in group Q1- Q4), meanwhile, the in-hospital mortality also increased gradually (23.4%, 29.2%, 33.1%, 43.4%, respectively, in group Q1- Q4), the differences were statistically significant (both P < 0.01). Compared with the non-AKI group, the Lac level in the AKI group was significantly increased [mmol/L: 3.08 (1.84, 5.70) vs. 1.91 (1.20, 3.10), P < 0.01]. After adjustment for factors such as gender (male), site of infection (abdominal cavity), vasoactive drugs, basal mechanical ventilation, mean arterial pressure (MAP), basal renal insufficiency, uric acid, procalcitonin (PCT), platelet count (PLT), basal serum creatinine (SCr) and basal estimated glomerular filtration rate (eGFR), and other influencing factors, multivariate Logistic regression analysis showed that elevated Lac was an independent risk factor for sepsis-associated AKI [odds ratio ( OR) = 1.096, 95% confidence interval (95% CI) was 1.022-1.175, P = 0.010]. Compared with the survival group, the Lac level in the death group was significantly increased [mmol/L: 3.55 (2.00, 6.76) vs. 3.00 (1.70, 4.50), P < 0.01]. After adjusting for age, diabetes, vasoactive drugs, basal eGFR, and other factors, multivariate Logistic regression analysis suggested that increased Lac was an independent risk factor for in-hospital mortality in sepsis-associated AKI patients ( OR = 1.074, 95% CI was 1.004-1.149, P = 0.037). ROC curve analysis showed that the area under the ROC curve (AUC) of Lac for predicting the incidence and mortality of sepsis-associated AKI was 0.653 (95% CI was 0.611-0.694) and 0.593 (95% CI was 0.530-0.656, both P < 0.01), respectively, and the cut-off values were 2.75 mmol/L (sensitivity was 57.8%, specificity was 69.2%) and 5.95 mmol/L (sensitivity was 56.7%, specificity was 83.7%). When the Lac ≥ 2.75 mmol/L, the risk of sepsis-associated AKI was 2.772 times higher than that of < 2.75 mmol/L ( OR = 2.772, 95% CI was 1.754-4.380, P < 0.001). When the Lac ≥ 5.95 mmol/L, the patients with sepsis-associated AKI had a 2.511 times higher risk of in-hospital death than those with Lac < 5.95 mmol/L ( OR = 2.511, 95% CI was 1.378-4.574, P = 0.003). Conclusions:Elevated Lac level is an independent risk factor for the incidence and mortality of sepsis-associated AKI. When Lac ≥ 2.75 mmol/L, the risk of AKI in patients with sepsis increased by 1.772 times; when Lac ≥ 5.95 mmol/L, the risk of in-hospital death in patients with sepsis related AKI increased by 1.511 times.

Progress on pathogenicity research of pks-positive Enterobacteriaceae / 中华检验医学杂志

The pks genomic island encodes non-ribosomal peptide synthase (NRPS), polyketide synthases (PKS), and hybrid NRPS/PKS synthetase. This genomic island is mainly found in the members of the family Enterobacteriaceae, and is especially common in Escherichia coli of phylogroup B2 while frequently coexisting with other virulence factors. The pks-positive E. coli is able to synthesize colibactin, a genotoxic chemical compound. Thus, this pks-positive bacteria may induce the breaking of DNA double-strand and chromosomal instability, which lead to senescence and apoptosis of cells. As a result, pks-positive E. coli is positively associated with the occurrence of diseases such as colorectal neoplasms, neonatal meningitis, and septicemia. Epidemiological studies have also confirmed that pks-positive E. coli is associated with a variety of diseases. However, the exact pathogenic mechanism of pks-positive E. coli is still not understood. Despite its genotoxicity, the pks-positive E. coli also exhibits some positive effects including anti-inflammatory, analgesic, and antibiotic abilities. Therefore, the biological role of pks-positive E. coli is complicated. In this review, an overview of the pks genomic island and its prevalence in Enterobacteriaceae, as well as the biological function of pks-positive E. coli is described, aiming to provide references for further researches.

Host metabolism dysregulation and cell tropism identification in human airway and alveolar organoids upon SARS-CoV-2 infection

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs. The infected cells were ciliated, club, and alveolar type 2 (AT2) cells, which were sequentially located from the proximal to the distal airway and terminal alveoli, respectively. Additionally, RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes, especially lipid metabolism, in addition to the well-known upregulation of immune response. Further, Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.

Human Embryonic Stem Cell-derived Lung Organoids: a Model for SARS-CoV-2 Infection and Drug Test

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we demonstrated that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids. Ciliated cells, alveolar type 2 (AT2) cells and rare club cells were virus target cells. Electron microscopy captured typical replication, assembly and release ultrastructures and revealed the presence of viruses within lamellar bodies in AT2 cells. Virus infection induced more severe cell death in alveolar organoids than in airway organoids. Additionally, RNA-seq revealed early cell response to SARS-CoV-2 infection and an unexpected downregulation of ACE2 mRNA. Further, compared to the transmembrane protease, serine 2 (TMPRSS2) inhibitor camostat, the nucleotide analog prodrug Remdesivir potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model for SARS-CoV-2 infection and drug discovery.

Effect of Heat inactivation on Real-Time Reverse Transcription PCR of the SARS-COV-2 Detection

Real-time reverse transcription PCR (rRT-PCR) is commonly used to diagnose SARS-CoV-2 infection. Heat inactivation prior to nucleic acid isolation may allow safe testing, while the effects of heat inactivation on SARS-CoV-2 rRT-PCR detection result need to be determined. 14 positive nasopharyngeal swab specimens were inactivated at 56{degrees}C for 30min, 56{degrees}C for 60min, 60{degrees}C for 30min, 60{degrees}C for 75min, and 100{degrees}C for 10min, then were detected by rRT-PCR. All 14 heat treated samples remained positive. Another 2 positive nasopharyngeal swab specimens were inactivated at 100{degrees}C for 10min, 100{degrees}C for 30min, and 100{degrees}C for 60min, after which the samples were isolated and detected by rRT-PCR. The range of threshold cycle (Ct) values observed when detecting ORF1a/b was 27.228-34.011 in heat-treated samples, while 25.281-34.861 in unheated samples, and the range of threshold cycle (Ct) values observed at the time of detecting N was 25.777-33.351 in heat-treated samples, while 24.1615-35.433 in unheated samples, on basis of which it showed no statistical difference otherwise a good correlation of Ct values between the heat-inactivated samples and the untreated samples. However, the 2 samples inactivated at 100{degrees}C 30min, 100{degrees}C 60min turned into negative. Heat inactivation at 56{degrees}C for 30min, 56{degrees}C for 60min, 60{degrees}C for 30min, 60{degrees}C for 75min, and 100{degrees}C for 10min shall not affect the detection results of Real-Time Reverse Transcription PCR of the SARS-COV2. Furthermore, it is recommended to inactive nasopharyngeal swab specimens 10min at 100{degrees}C before RNA extraction in consideration of efficiency and reliable results.

Diagnosis of Acute Respiratory Syndrome Coronavirus 2 Infection by Detection of Nucleocapsid Protein

BACKGROUNDNucleic acid test and antibody assay have been employed in the diagnosis for SARS-CoV-2 infection, but the use of viral antigen for diagnosis has not been successfully developed. Theoretically, viral antigen is the specific marker of the virus and precedes antibody appearance within the infected population. There is a clear need of detection of viral antigen for rapid and early diagnosis. METHODSWe included a cohort of 239 participants with suspected SARS-CoV-2 infection from 7 centers for the study. We measured nucleocapsid protein in nasopharyngeal swab samples in parallel with the nucleic acid test. Nucleic acid test was taken as the reference standard, and statistical evaluation was taken in blind. We detected nucleocapsid protein in 20 urine samples in another center, employing nasopharyngeal swab nucleic acid test as reference standard. RESULTSWe developed a fluorescence immunochromatographic assay for detecting nucleocapsid protein of SARS-CoV-2 in nasopharyngeal swab sample and urine within 10 minutes. 100% of nucleocapsid protein positive and negative participants accord with nucleic acid test for same samples. Further, earliest participant after 3 days of fever can be identified by the method. In an additional preliminary study, we detected nucleocapsid protein in urine in 73.6% of diagnosed COVID-19 patients. CONCLUSIONSThose findings indicate that nucleocapsid protein assay is an accurate, rapid, early and simple method for diagnosis of COVID-19. Appearance of nucleocapsid protein in urine coincides our finding of the SARS-CoV-2 invading kidney and might be of diagnostic value.

Study on SARS-COV-2 transmission and the effects of control measures in China

ObjectiveTo reconstruct the transmission trajectory of SARS-COV-2 and analyze the effects of control measures in China. MethodsPython 3.7.1 was used to write a SEIR class to model the epidemic procedure and a back propagation class to estimate the initial true infected number. The epidemic area in China was divided into three parts, Wuhan city, Hubei province (except Wuhan) and China (except Hubei) based on the different transmission pattern. A limitation factor for the medical resource was imposed to model the infected but not quarantined. Credible data source from Baidu Qianxi were used to assess the number of infected cases migrated from Wuhan to other areas. ResultsBasic reproduction number, R0, was 3.6 in the very early stage. The true infected number was 4508 in our model in Wuhan before January 22, 2020. By January 22 2020, it was estimated that 1764 infected cases migrated from Wuhan to other cities in Hubei province. Effective reproductive number, R, gradually decreased from 3.6 (Wuhan, stage 1), 3.4 (Hubei except Wuhan, stage 1) and 3.3 (China except Hubei, stage 1) to 0.67 (Wuhan, stage 4), 0.83 (Hubei except Wuhan, stage 2) and 0.63 (China except Hubei, stage 2), respectively. Especially after January 23, 2020 when Wuhan City was closed, the infected number showed a turning point in Wuhan. By early April, there would be 42073, 21342 and 13384 infected cases in Wuhan, Hubei (except Wuhan) and China (except Hubei) respectively, and there would be 2179, 633 and 107 death in Wuhan, Hubei (except Wuhan) and China (except Hubei) respectively. ConclusionA series of control measures in China have effectively prevented the spread of COVID-19, and the epidemic will end in early April.

Hyperuricemia is an independent risk factor for acute kidney injury in sepsis patients / 中华急诊医学杂志

Objective:To investigate the effect of hyperuricemia on acute kidney injury in sepsis patients.Methods:It is a retrospective cohort study of 459 adult sepsis patients who were admitted to the Department of Intensive Care Unit (ICU) of the First Affiliated Hospital of Guangxi Medical University from March 2014 to June 2019, and the Second Affiliated Hospital of Guangxi Medical University from January 2017 to June 2019. The patients were divided into the hyperuricemia group and the non-hyperuricemia group according to the first serum uric acid level within 24 h after ICU admission, and the incidence of AKI within 7 days after ICU admission was compared between the two groups. The effect of hyperuricemia on sepsis-associated AKI was analyzed by univariate analysis and binary logistic regression analysis.Results:Among the 459 sepsis patients, 81 patients (17.6%) had hyperuricemia, and 127 patients (27.7%) had AKI. The incidence of AKI in the hyperuricemia group and the non-hyperuricemia group were 60.5% (49/81) and 20.6% (78/378), respectively, which showed significantly statistical difference ( χ2=52.954, P<0.01). After adjusting for gender, associated diseases (diabetes, coronary heart disease), sequential organ failure score (SOFA) on the day of ICU admission, the use of diuretics within one week before and after ICU admission, invasive mechanical ventilation, basal renal function, lactic acid, and procalcitonin, binary logistic regression analysis showed that hyperuricemia was an independent risk factor for AKI in sepsis patients ( OR=5.091, 95% CI: 2.768-9.362, P<0.01); For every 1 mg/dL increase in serum uric acid in sepsis patients, the risk of developing AKI increased by 28.4% ( OR=1.284, 95% CI: 1.165-1.414, P<0.01). Conclusions:AKI is a common complication in sepsis patients admitted to ICU, and hyperuricemia is an independent risk factor for AKI in sepsis patients.

Postoperative hypoalbuminemia is an independent risk factor for acute kidney injury after cardiac surgery under cardiopulmonary bypass / 中华肾脏病杂志

Objective:To investigate the effect of postoperative hypoalbuminemia on acute kidney injury (AKI) after cardiac surgery under cardiopulmonary bypass (CPB).Methods:The clinical data of adult patients undergoing cardiac surgery under CPB were retrospectively analyzed. The difference between preoperative and postoperative serum albumin level was compared. The patients were divided into hypoalbuminemia group (≤35 g/L) and non-hypoalbuminemia group (>35 g/L) according to the lowest serum albumin concentration within 48 hours after surgery. The incidence and severity of postoperative AKI were compared between the two groups. Univariate analysis and binary logistic regression analysis were used to evaluate the effect of postoperative hypoalbuminemia on the incidence of postoperative AKI.Results:Among the 749 patients, the serum albumin level after cardiac surgery was significantly lower than that before surgery ( Z=-15.739, P<0.001), and the proportion of patients with hypoalbuminemia increased from 9.6% to 27.6% ( χ2=83.516, P<0.001). Postoperative AKI occurred in 273 patients, including 109 cases (52.7%) in hypoalbuminemia group and 164 cases (30.3%) in non-hypoalbuminemia group. The incidence of AKI in hypoalbuminemia group was significantly higher than that in non-hypoalbuminemia group ( χ2=32.443, P<0.001), and the severity of AKI in hypoalbuminemia group increased than that in non-hypoalbuminemia group ( Z=-2.098, P=0.036), and the time of hospital stay extended ( Z=-2.442, P=0.015). After adjusted by gender, age, preoperative hypoalbuminemia, comorbidities (hypertension, hyperuricemia, diabetes mellitus, cerebrovascular disease), renal insufficiency, preoperative heart function, coronary angiography, CPB time, aorta blocking time, type of heart surgery and postoperative hypotension, binary logistic regression analysis revealed that postoperative hypoalbuminemia was an independent risk factor for CPB-associated AKI ( OR=2.319, 95% CI 1.586-3.392, P<0.001). Conclusions:AKI is a common complication following cardiac surgery under CPB. Serum albumin after CBP is significantly lower than that before CBP, and postoperative hypoalbuminemia within 48 hours after surgery is an independent risk factor for AKI.

Risk factors of mortality in peritoneal dialysis patients / 中国综合临床

Objective To explore the risk factors affecting the death of peritoneal dialysis patients.Methods The clinical data of 275 patients with peritoneal dialysis who place a peritoneal catheter in the Department of Nephrology, First Affiliated Hospital of Guangxi Medical University and had regular peritoneal dialysis for more than 3 months from January 1,2005 to December 31,2015 were retrospectively analyzed.Sixty patients died in the observation group, and 215 patients who continued regular peritoneal dialysis were in the control group.Univariate analysis and two?class logistic regression analysis were used to analyze risk factors for death.Results The composition ratio of the primary disease to diabetic nephropathy in the death group and the control group was 15.0%(9／60) and 5.6%(12／215),respectively,the average age of patients entering peritoneal dialysis was ( 50.6 ± 14.3) years old and ( 45.7 ± 13.2) years old, respectively(t＝－2.518),glomerular filtration rates were 6.0(4.5,9.4) and 5.1(4.2,6.6),respectively, blood potassium is (4.2±0.7) mmol／L and (4.5±0.7) mmol／L,respectively,serum creatinine was 721.0 (585.0,891.3) μmol／L and 847 (723.3,1 033.3) μmol／L,respectively,there were significant differences between the two groups ( t＝2.14, all P＜0.05).Logistic regression analysis indicated that the primary disease was diabetic nephropathy,and the age of admission to peritoneal dialysis,glomerular filtration rate, blood uric acid are risk factors for death in peritoneal dialysis patients.Conclusion Diabetic nephropathy, age,glomerular filtration rate,and blood uric acid level are independent risk factors for death in peritoneal dialysis patients.

Advances in the diagnosis and treatment of Peutz?Jeghers syndrome / 中国综合临床

Peutz?Jeghers syndrome ( PJS) is a rare syndrome characterized by multiple polyps of gastrointestinal tract and black spots of mucosa??The etiology is unclear yet??The main clinical manifestations are digestive tract symptoms and pigmentation of skin and mucosa??The diagnosis mainly depends on clinical manifestations and auxiliary examinations??Multiple gastrointestinal polyps can often be found by endoscopy??Gene testing can often detect mutations of serine／threonine kinase 11 (STK11) or liver kinase B1 (LKB1),which has high diagnostic accuracy??At present,PJS is rarely reported,and there is still a lack of systematic understanding??This paper reviews the incidence,clinical manifestations, auxiliary examinations, diagnosis,treatment and progress of PJS??

Analysis of drug resistance genes and molecular typing of carbapenem-resistant Klebsiella variicola strains / 中华微生物学和免疫学杂志

Objective To investigate the prevalence and drug resistance of clinical Klebsiella vari-icola ( K. variicola ) isolates and to illuminate the mechanism of drug resistance in carbapenem-resistant strains. Methods Clinical K. variicola isolates were identified with matrix-assisted laser desorption/ioniza-tion time-of-flight mass spectrometry ( MALDI-TOF MS ) . The antimicrobial susceptibility profile of these strains was determined using broth microdilution. Resistance genes carried by carbapenem-resistant K. vari-icola strains were detected by PCR with specific primers. Multilocus sequence typing ( MLST) was used for molecular typing. A pan-drug resistant strain which was isolated from cerebrospinal fluid sample was ana-lyzed with whole genome sequencing ( WGS) . Results Twenty-six isolates were identified as K. variicola by MALDI-TOF MS. Results of the antimicrobial susceptibility test showed that there were 15. 4％ (4/26) re-sistant to carbapenem and 11. 5％ (3/26) unsusceptible to tigecycline. These strains were highly suscepti-ble to amikacin and gentamicin, which accounted for 96. 2％ (25/26). As for the third-and fourth-genera-tion cephalosporins, the resistance rate was 23. 1％ (6/26). All of the four carbapenem-resistant isolates carried the resistance genes of blaIMP-4 , qnrA/B and blaTEM , and one of them was also positive for blaNDM-1 gene. The fosfomycin resistance gene, fosA, was detected in three of them. Molecular typing analysis indica-ted these isolates belonged to two sequence types ( ST) of ST357 ( three strains) and ST1737 ( one strain) . Two plasmids were obtained from the pan-drug resistant strain by WGS, including IncFⅡ/FIB( k) type plas-mid (160 kb) that was highly homologous to LMG 23571 plasmid (GenBank: CP013986. 1) and IncHⅠ1B/FIB type plasmid (260 kb) sharing high homology with pIMP4 LL34 (GenBank: CP025964. 1). Be-sides the resistance genes mentioned above, the two plasmids also carried a variety of other genes that media-ted the resistance to aminoglycosides (strB, strA, armA, aac3-Ⅱd, aadA2), macrolides (msrE, mphE), chloramphenicol (catA2), sulfonamides (sulⅠ) tigecycline (tetA variant) and trimethoprim (dfrA16). However, no virulence genes were detected. Conclusions In general, the resistance profile of K. variicola was similar to that of Klebsiella pneumoniae, but the differences were that carbapenem-resistant K. variicola strains mainly belonged to ST357 and the leading causes of resistance were carrying the genes encoding IMP-4 and NDM-1 metalβ-lactamases. WGC analysis revealed that the pan-drug resistant K. variicola strain carried multiple drug resistance genes without virulence determinants, which might be resulted from the evo-lution of drug resistance.

Independent association of preoperative hyperuricemia with acute kidney injury after cardiac surgery with cardiopulmonary bypass / 中华肾脏病杂志

Objective To investigate the impact of preoperative hyperuricemia on acute kidney injury (AKI) after cardiac surgery with cardiopulmonary bypass (CPB).Methods A total of 567 adult patients undergoing cardiac surgery with CPB were enrolled to conduct a retrospective cohort database analysis.The patients were divided into hyperuricemia group and non-hyperuricemia group according to preoperative serum uric acid,and the incidence of AKI in two groups were compared.Binary logistic regression analysis was used to evaluate the relationship between preoperative hyperuricemia and AKI.Results Among 567 patients after cardiac surgery with CPB,hyperuricemia occurred in 303 cases (53.4％),and AKI occurred in 217 cases (38.3％).There was significantdifference in the incidence of AKI between hyperuricemia group and non-hyperuricemia group (44.6％ vs 31.1％,x2=10.874,P=0.001).The duration of intensive care unit (ICU) stay and the length of stay were longer in hyperuricemia group than those in non-hyperuricemia group (both P ＜ 0.05).After adjusting for age,gender,comorbidities (hypertension,diabetes mellitus,cerebrovascular disease),preoperative renal function,preoperative heart function,CPB time,intraoperative aortic block time,type of cardiac surgery and postoperative hypotension,binary logistic regression analysis showed that preoperative hyperuricemia was an independent risk factor of AKI after cardiac surgery with CPB (OR=1.912,95％ CI 1.270-2.879,P=0.002).Conclusion AKI is a common complication following cardiac surgery with CPB,and hyperuricemia is independently associated with CPB-associated AKI.Hyperuricemia may be involved in the pathogenesis of AKI,and intervention before cardiac surgery may be beneficial to prevent postoperative AKI.

The clinical characteristics and risk factors of mixed Candida/bacterial bloodstream infections / 中华急诊医学杂志

Objective To investigate the clinical characteristics and associated risk factors for patients with mixed Candida/bacterial bloodstream infections (BSIs).Methods A retrospective study was conducted in the Second Affiliated hHospital of Zhejiang University School of Medicine from February 2012 to June 2015.The clinical data of cases was collected,and the clinical characteristics,the microbiology data and outcomes in patients with mixed Candida/bacterial BSIs confirmed by blood culture were compared with those with candidaemia.A Logistic regression analysis was performed to investigate the independent risk factors.Results A total of 136 candidaemia cases were analyzed including 40 cases (29.4％) of mixed Candida/boacterial BSIs and 96 cases of candidaemia.Among the 136 candidas strains,the proportion of non-albicans exceeded the albicans (50.7％ vs 49.3％),although the later was still the predominant one.There was no significant difference in the distribution of candidas strains between patients with mixed Candida/bacterial BSIs and patients with candidaemia.In patients with mixed Candida/bacterial BSIs,25 strains (61.0％) of gram-positive cocci and 16 strains (39.0％) of gram-negative bacilli were isolated.Compared with patients with candidaemia,patients with mixed Candida/bacterial BSIs needed longer period of antifungal therapy [12.0 (4.0-25.0)days vs 7.0 (3.0-13.5) days,P=0.027],but the crude 30-day and 90-day mortality did not differ between the two groups (40.0％ vs 32.3％;45.0％ vs 36.5％;both P＞0.05).Univariate analysis revealed that the prior hospital stay,ICU admission at the onset of candidaemia,blood transfusion,human albumin infusion,mechanical ventilation,linezolid use and high SOFA score were related with the occurrence of mixed Candida/bacterial BSIs (all P＜0.05).Multivariate analysis showed that only high SOFA score was the independent risk factor (P=0.003).Conclusions Gram-positive cocci were the predominant species in mixed Candida/bacterial BSIs.Compared with candidaemia,mixed Candida/bacterial BSIs needs a longer ICU stay,a longer hospital stay,and a prolonged antifungal therapy.High SOFA score is the independent risk factor for mixed Candida/ bacterial BSIs.

Patterns of intestinal microbiome imbalance in patients with type 2 diabetes mellitus and diabetes kidney disease / 中华检验医学杂志

Objective To explore the signs of consistent changes of intestinal flora in type 2 diabetes mellitus (T2DM) and diabetes kidney disease (DKD) patients, by studying the key change characteristics of intestinal flora in these patients. Methods Thirty patients with T2DM,twenty-five patients with DKD were involved. Thirty healthy patients with matching age and sex were also involved as the control group. Fecal and serum specimens were collected from both the study group and the control group. High-throughput sequencing technology was used to sequence the 16S rDNA-v4 region of fecal samples;interleukin-6 (IL-6) and C-reactive protein (CRP) were detected by electrochemical luminescence and immunoturbidimetry. Microbiome analysis software QIIME (v1.9.1) was used to analyze the composition and diversity of intestinal flora. Microbial diversity analysis software LEfSe was used to compare intestinal bacteria markers differences between the study group and the healthy control group. The diagnosis model was established by the random forest method. The change characteristics of intestinal flora function were predicted by the PICRUSt. Results The intestinal flora diversity of DM and DKD patients was significantly different from that of the healthy control group (P<0.05). T2DM and DKD patients harbored lots of similar changes. For example, there was a significant decrease in Lachnospira, Faecalibacterium, Roseburia and Coprococcus(P<0.05). However, there was also a disease-specific pattern of imbalance between the two disease. There was a significant increase in Bacteroides in T2DM patients, and in Lactobacillus, Slackia, Anaerotruncus,Haemophilus and Enterococcus in DKD patients. Functional prediction was also confirmed that T2DM and DKD patients had more consistent changes. The correlation analysis between serum inflammatory indicators of T2DM and DKD and bacteria suggested that the decrease of beneficial bacteria in the intestinal tract of T2DM and DKD patients may be the cause of the increase of serum inflammatory indicators. Conclusion T2DM and DKD patients harbored lots of similar changes in intestinal flora, a decrease of bacteria producing butyrate,but there was also a disease-specific change between the two disease,providing a data basis for further studies to evaluate the risk of nephropathy in patients with diabetes by intestinal flora .

Progress of Da Vinci Robot in Surgical Treatment of Gastric Cancer / 中国综合临床

Objective The Da Vinci single－site surgical platform (DVSSP) is an intelligent operation platform widely used worldwide. It possesses 3D vision ,flexible operation and other advantages, so in the field of gastrointestinal surgery, it has been gradually applied to radical gastrectomy, radical gastrectomy, radical resection of colorectal cancer, gastric fundus folding, Heller myotomy, weight loss surgery and small bowel surgery, and the satisfactory clinical effect has been achieved. For gastric cancer surgery, compared with traditional laparoscopy and laparotomy, the robot operation is more accurate, flexible, and has obvious minimally invasive advantages. The intraoperative treatment and postoperative curative effect are better than the traditional laparoscopy. With the support of a large number of clinical cases, DVSSP has been proven to be a new platform for minimally invasive surgery and has considerable value in the field of gastric cancer surgery. However, there is still a long operation time and a high cost of operation. The long－term effect of gastric cancer surgery needs further observation.

Dysbiosis and resilience of gut microbiota in patients with ischemic stroke / 中国神经精神疾病杂志

Objective To investigate the gut microbial characteristics in patients with acute ischemic stroke and resilience of the gut microbiota after a stroke. Methods Ninety-five fecal samples from 28 ischemic stroke patients and 28 fecal samples from 28 healthy volunteers were collected.DNA was extracted from these samples and the bacterial 16S rRNA were amplified through real-time quantitative polymerase chain reaction (qPCR). All PCR products were mixed together and then sequenced using the Illumina Hiseq 2500 platform. Microbiome analysis was implemented in QIIME. Results Patients with acute ischemic stroke showed significantly higher diversity than controls (phylogenetic diversity, P=0.002). The overall composition of the gut microbial communities also differed significantly between acute ischemic stroke patients and healthy controls as indicated by the clear separation in principle coordinate analysis (Adonis test on Bray-Curtis, P<0.001). Stroke patients' intestines had more opportunistic pathogens, such as Enterobacteriaceae, Veillonellaceae and Streptococcaceae, fewer commensal or beneficial genera including Bacteroides and Prevotella. Four weeks after onset, the gut microbiota in stroke patients began to restore, but the alpha diversity declined (P<0.05). Conclusion The present study has revealed the characteristic of gut microbial dysbiosis and recovery in acute ischemic stroke patients.However,the significance of the dynamic gut microbiota in stroke patients needs further study.

Regional variation and diagnosis modeling of gut microbiome for inflammatory bowel diseases / 中华检验医学杂志

Objective To identify microbiome biomarkers in patients with inflammatory bowel disease ( IBD) in different regions and establish predictive models , and to explore the various gut microbiota function in IBD patients .Methods The 16 srRNA gene sequences of 1510 IBD patients and 496 healthy controls were collected from China , the United States ( RISK and PRISM cohort ), Germany, India and Lithuania cohort.QIIME ( v1.9.1) was used to analyze microbiota data.LEfSe was used to identify biomarkers for IBD.Random forest method was used to establish the prediction model to distinguish IBD from HC.PICRUSt was used to predict the functional changes of gut microbiota in IBD patients .Resultsɑdiversity of gut microbial in IBD patients was significantly lower than in HC (Wilcoxon,P<0.05).The gut microbiota of IBD patients was different from HC significantly ( Adonis,P<0.05) in all of the cohort study but Indian.LEfSe analysis showed that the IBD patients from China and the U .S.cohort harbored similar dysbiosis patterns , while those from Lithuania , Germany and India have highly localized dysbiosis patterns.Generally, enterococcus was significantly increased in IBD patients in China , the U.S.and Germany cohort.Enterobacteriaceae was significantly increased in IBD patients in China and the U .S. cohort.Ruminococcus was significantly decreased in the intestines of IBD patients in China , the U.S.and India cohort.When predicting IBD status using machine learning models built on local population , the area under the curve ( AUC) was 86.48％ ±4.91％.Meanwhile, when predicting IBD status using machine learning models built on other populations , China and the U.S.had a relatively high AUC for cross-predicting, whilethe other pairs were failed when cross-applied to each other.The model established based on all samples was used to predict each population ,which showed that China , the United States ( RISK and PRISM cohort ), Germany, Lithuania and India cohorts having AUCs of 90.1％, 82.3％, 79.6％, 61.9％, 65.5％and 54.2％respectively.For functional analysis, in China, the United States (RISK and PRISM cohort ) and India cohort , glutathione metabolism and quinones biosynthesis was significantly increased in IBD patients.In China, Germany and Lithuania cohort , flagella assembly and bacterial motility proteins functions were significantly decreased in the IBD patients .Conclusions The intestinal microbiota of IBD patients from different countries could have consistent dysbiosis patterns , but geographical factors still exert a great effect on the microbiota , which needs to be further explored in subsequent studies .

Detection and epidemiology of mcr-1-positive Escherichia coli strains in Dongyang area of Zhejiang Province / 中华微生物学和免疫学杂志

Objective To investigate the prevalence of mcr-1 gene,a plasmid-mediated polymyxin resistance gene,in Escherichia coli(E.coli) strains isolated in Dongyang of Zhejiang Province and to under-stand the epidemiological characteristics of E.coli strains carrying mcr-1 gene in order to provide local clini-cians with a theoretical basis for prevention and control of the spread of mcr-1-bearing E.coli strains. Meth-ods A total of 315 E.coli strains were collected in the People′s Hospital of Dongyang, Zhejiang Province from January to December 2016. All strains were isolated from specimens of blood,urine,respiratory tract, etc. PCR was performed to detect the genes confering resistance to polymyxin (mcr-1 gene), β-lactamase and carbapenem. Minimal inhibitory concentrations (MIC) of antibiotics against mcr-1-positive strains were determined by micro-broth dilution method. Conjugation test was performed to confirm whether the mcr-1 gene was located on the transferable plasmid. Multilocus sequence typing (MLST) was used for molecular typing of mcr-1-positive strains. Results Five mcr-1-positive strains were identified from 315 E.coli strains with a positive rate of 1.6%. Two out of the five mcr-1-positive E.coli strains contained β-lactamase resist-ance genes,blaTEM-1and blaCTX-M-14. Both of them were resistant to the first, second and third generation of cephalosporins and one was also resistant to cefepime. All of the five mcr-1-positive E.coli strains were sen-sitive to ciprofloxacin and levofloxacin,but resistant to ticarcillin/clavulanic acid. No carbapenem resistance genes were detected. One transconjugant was successfully obtained by transconjugation assay. MLST analysis showed that a total of four sequence types were identified, including ST131 (two strains), ST43 (one strain),ST69 (one strain) and ST349(one strain). Conclusion Only 1.6% of all E.coli strains isolated in Dongyang area of Zhejiang Province carry mcr-1 gene,indicating that there is no epidemic of mcr-1 gene-positive E.coli infection. The coexistence of mcr-1 gene and β-lactamase resistance genes in E.coli strains isolated in Dongyang suggests that local clinicians should avoid antibiotic abuse to prevent the spread of drug-resistant E.coli.