Relationship of miR-126 and miR-325 in serum and vitreous with the severity of proliferative vitreoretinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the relationship of miR-126 and miR-325 in serum and vitreous with the severity of proliferative vitreoretinopathy(PVR).METHODS: A total of 100 cases(100 eyes)with PVR who were treated in our hospital from October 2019 to October 2022 were selected and retrospectively studied. They were divided into a mild group(42 eyes)and a severe group(58 eyes)according to the degree of retinopathy, and another 30 cases(30 eyes)that underwent vitrectomy without retinopathy due to eye trauma in our hospital during the same period were selected as the control group. Fluorescence quantitative PCR was used to detect the expression levels of miR-126 and miR-325 in serum and vitreous; ELISA was used to detect the levels of transforming growth factor β(TGF-β), platelet-derived growth factor(PDGF), vascular endothelial growth factor(VEGF), and tumor necrosis factor α(TNF-α)in serum and vitreous; and Pearson's method was used to analyze the correlation between the serum and vitreous levels of miR-126 and miR-325 correlated with the levels of TGF-β, PDGF, VEGF, and TNF-α; Logistic multifactorial analysis was used to analyze the influencing factors for the occurrence of severe PVR.RESULTS: Compared with the control group, miR-126 levels in serum and vitreous of PVR patients were decreased and lower in the severe PVR group than in the mild PVR group(both P<0.05); miR-325 levels were increased and higher in the severe PVR group than in the mild PVR group(both P<0.05). TGF-β, PDGF, VEGF, and TNF-α levels in serum and vitreous were increased in the severe PVR group compared to the mild PVR group(all P<0.05). The miR-126 levels in serum and vitreous of patients with PVR were negatively correlated with miR-325, TGF-β, VEGF, TNF-α, and PDGF levels(all P<0.05), and miR-325 was positively correlated with TGF-β, VEGF, TNF-α, and PDGF levels(all P<0.05). Logistic regression analysis showed that miR-325, TGF-β, PDGF, and TNF-α were all independent risk factors for the development of severe PVR in serum and vitreous, and miR-126 was an independent protective factor for the development of severe PVR in serum and vitreous(P<0.05).CONCLUSION: With the aggravation of PVR, miR-126 expression in serum and vitreous decreased while miR-325 expression increased and correlated with TGF-β, TNF-α, VEGF, and PDGF.

A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

Effect of Liangxue Huoxue decoction on intestinal flora and NLRP3/caspase-1/GSDMD signaling pathway in mice model of sepsis-induced acute kidney injury / 中华危重病急救医学

Objective:To investigate the effect of Liangxue Huoxue decoction on intestinal flora, intestinal barrier and NOD-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) pyroptosis signaling pathway in mice model of sepsis-induced acute kidney injury (AKI).Methods:The model of AKI was established by cecal ligation and perforation (CLP). Thirty male C57BL/6 mice were randomly divided into sham operation group (Sham group), sepsis group (CLP group) and sepsis+Liangxue Huoxue decoction (CLP+LXHX group), with 10 mice in each group. Mice in Sham group only underwent laparotomy. Two hours before model establishment, mice in CLP+LXHX group were treated with Liangxue Huoxue decoction (6 g/kg) by gavage; mice in Sham group and CLP group were given equal volume of normal saline by gavages. After 24 hours of modeling, all mice were sacrificed under anesthesia, and the colon and kidney tissues and fresh feces in the colon were taken. The pathological changes of kidney and colon were observed by hematoxylin-eosin (HE) staining under light microscope. Real-time polymerase chain reaction (RT-PCR) was used to detect inflammatory factors (interleukins, IL-1β and IL-18) in renal tissue. The expressions of NLRP3, caspase-1 and GSDMD were detected by Western blotting. The changes of intestinal flora in mice were detected by 16S rDNA high-throughput sequencing.Results:Compared with the Sham group, the inflammatory cell infiltration of the kidney tissue was increased and the kidney became vacuolated in CLP group, the mRNA expressions of IL-1β, IL-18, and the protein expressions of NLRP3, caspase-1 and GSDMD were significantly increased in CLP group, the species richness of intestinal microflora decreased significantly, the relative abundance of Enterococcus and Escherichia-Shigella increased significantly, and the relative abundance of Ileibacterium, Alloprevotella, Lachnospiraceae, Klebsiella and Parasutterella increased significantly in CLP group. Compared with CLP group, Liangxue Huoxue decoction can significantly reduce the pathological changes of kidney and colon tissue, reduce the pathological score (1.75±0.43 vs. 3.50±0.50 for kidney tissue, 1.25±0.43 vs. 4.50±0.50 for colon tissue, both P < 0.05), improve the composition of intestinal flora, reduce the relative abundance of Enterococcus and Escherichia-Shigella, and significantly increase the relative abundance of Lactobacillus and Akkermansia. In addition, Liangxue Huoxue decoction can significantly reduce mRNA expressions of IL-1β and IL-18 in kidney tissue [IL-1β mRNA (2 -ΔΔCt): 1.59±0.05 vs. 4.61±0.88, IL-18 mRNA (2 -ΔΔCt): 1.69±0.17 vs. 2.86±0.63, both P < 0.05] and the protein expressions of NLRP3, caspase-1 and GSDMD (NLRP3/GAPDH: 0.71±0.04 vs. 0.89±0.01, caspase-1/GAPDH: 1.04±0.04 vs. 1.48±0.04, GSDMD/GAPDH: 0.90±0.01 vs. 1.41±0.02, all P < 0.05). Conclusions:Liangxue Huoxue decoction has obvious protective effect on AKI induced by sepsis. It can improve intestinal barrier by regulating intestinal flora, thereby inhibiting the activation of NLRP3/caspase-1/GSDMD signaling pathway in kidney tissue and reducing the expression of proptosis-related inflammatory factors.

Revealing the role of gut microbiota in immune regulation and organ damage in sepsis using 16s rRNA and untargeted metabolomics / 中华危重病急救医学

OBJECTIVE@#To analyze the composition and metabolites of gut microbiota in septic rats by fecal 16s rRNA sequencing and untargeted metabolomics, and to preliminarily explore the effect and potential mechanism of gut microbiota and its metabolites on inflammatory response and multiple organ damage in sepsis.@*METHODS@#Ten males healthy male Wistar rats were randomly divided into a sham operated group (Sham group) and sepsis model group (CLP group) using a random number table method, with 5 rats in each group. A rat sepsis model was established by cecal ligation and perforation (CLP) method. The animals were sacrificed 24 hours after modeling, the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung and kidney tissues, and the pathological scores were evaluated. Fecal samples were collected, and 16s rRNA high-throughput sequencing and non-targeted metabolomics were used to screen microbiota, metabolites and potential signal pathways that may play an important role in disease outcomes. Spearman correlation analysis was conducted to jointly analyze the gut microbiota and non-targeted metabolism.@*RESULTS@#Compared with the Sham group, the degree of pathological damage to lung and kidney tissues in the CLP group was significantly increased (lung tissue score: 3.60±0.80 vs. 0.00±0.00, kidney tissue score: 2.40±0.80 vs. 0.00±0.00, both P < 0.01), the level of IL-6 and TNF-α in peripheral blood significantly increased [TNF-α (ng/L): 248.12±55.98 vs. 143.28±36.57, IL-6 (ng/L): 260.26±39.47 vs. 116.01±26.43, both P < 0.05], the species diversity of intestinal flora of rats in the CLP group was significantly reduced, the relative abundance of Morganella, Bacteroides and Escherichia-Shigella were significantly increased, and the relative abundance of Lachnospiraceae NK4A136, Ruminococcus, Romboutsia and Roseburia were significantly reduced. In addition, the biosynthesis and bile secretion of phenylalanine, tyrosine, and tryptophan in the gut microbiota of the CLP group were significantly increased, while the biosynthesis of secondary bile acids was significantly reduced. There was a significant correlation between differential metabolites and differential microbiota.@*CONCLUSIONS@#Sepsis can cause significant changes in the characteristics of gut microbiota and fecal metabolites in rats, which provides a basis for translational research to seek new targets for the treatment of sepsis.

Determination of Calycosin-7-O-β-D-Glucopyranoside and Lobetyolin in Danqi Xinmaikang boiled powders and pieces by quantitative analysis of multi-components by single maker / 国际中医中药杂志

Objective:To establish a quality evaluation method for the simultaneous determination of Calycosin-7-O-β-D-Glucopyranoside and Lobetyolin in Danqi Xinmaikang boiled powders and pieces.Methods:Quantitative analysis of multi-components was performed to determine contents of Calycosin-7-O-β-D-Glucopyranoside and Lobetyolin with Calycosin-7-O-β-D-Glucopyranoside as the reference substance by single-maker (QAMS). The chromatogram conditions were established, with C18 column as solid phase, acetonitrile-water as flowing phase, 268 nm as detecting wavelength, 1.0 ml/min as flowing rate, 30 ℃ as column temperature, and 10 μl as injection volume.Results:The relative correction factor between Calycosin-7-O-β-D-Glucopyranoside and Lobetyolin was 1.14. There was no significant difference of measured values between the external standard method and QAMS ( P>0.05). With Calycosin-7-O-β-D-Glucopyranoside retention time of 1.00, the relative retention time of Lobetyolin was 1.51 and RSD was less than 5%. Conclusion:It is feasible and accurate to evaluate the quality of Danqi Xinmaikang boiled powders and pieces by QAMS.

Efficacy and Safety of Selegiline for Parkinson ’s Disease ：A Reevaluation of Systematic Reviews / 中国药房

OBJECTIVE：To conduct reevaluation of systematic review/Meta-ana lysis on the efficacy and safety of selegiline in the treatment of Parkinson ’s disease （PD）. METHODS ：Retrieved from PubMed ，Embase，Cochrane L ibrary，CNKI，Wanfang database as well as official websites of domestic and foreign health technology assessment institutions ，based on manual retrieval and review of references ，systematic review/Meta-analysis on selegiline alone or combined with other anti-PD drugs （trial group ） versus placebo or blank control or other anti-PD drugs （control group ）were collected. The time limit was from database inception to November 2020. After literature screening and data extraction ，PRISMA statement was adopted to evaluate the quality of the included reports. AMSTAR 2 scale was used to evaluate the methodological quality ，and GRADE method was adopted to evaluate the evidence quality ，the outcome indicators of the included studies were summarised and analyzed. RESULTS ：A total of 12 systematic reviews/Meta-analysis were included ，involving 4 systematic reviews and 8 Meta-analysis；there were 31 outcome indexes in total. PRISMA scores of them ranged from 16.5 to 27.0，including 15.0 to 21.0 for 2 literatures（16.67％）and 22.0 to 27.0 for 10 literatures（83.33％）. Results of AMSTAR 2 scale showed that the methodological qualities of 2 literatures were classed as high quality ，3 as low quality and 7 as very low quality. Results of GRADE evidence quality evaluation showed that 1 evidence quality was high-level ，3 were medium-level ，5 were low-level ，21 were very low-level ，and 1 was no evaluable . The main factors leading to the degradation were bias risk （87.10％），publication bias （77.42％），inaccuracy （51.61％）and incon sistency（41.94％）. In terms of therapeutic efficacy ，compared with control group ，selegiline could improve the total score of UPDRS ，UPDRS Ⅰ score，UPDRS Ⅱ score，UPDRS Ⅲ score and Webster score in patients with Parkinson ’s disease，either monotherapy or in combination with other anti-PD drugs （P＜0.05）. In terms of safety ，there was no significant difference in the incidence of adverse events or mortality between 2 groups（P＞0.05），but the rate of withdrawal due to adverse events was higher（P＜0.05）. CONCLUSIONS ：Selegiline is effective and safe in the treatment of Parkinson ’s disease ，but current methodological quality and evidence quality of included systematic reviews /Meta-analysis are low，which requires further standardization of research methods.

A phase II trial of cytoreductive surgery combined with niraparib maintenance in platinum-sensitive, secondary recurrent ovarian cancer: SGOG SOC-3 study / 부인종양

Background@#In China, secondary cytoreductive surgery (SCR) has been widely used in ovarian cancer (OC) over the past two decades. Although Gynecologic Oncology Group-0213 trial did not show its overall survival benefit in first relapsed patients, the questions on patient selection and effect of subsequent targeting therapy are still open. The preliminary data from our pre-SOC1 phase II study showed that selected patients with second relapse who never received SCR at recurrence may still benefit from surgery. Moreover, poly(ADP-ribose) polymerase inhibitors (PARPi) maintenance now has been a standard care for platinum sensitive relapsed OC. To our knowledge, no published or ongoing trial is trying to answer the question if patient can benefit from a potentially complete resection combined with PARPi maintenance in OC patients with secondary recurrence. @*Methods@#SOC-3 is a multi-center, open, randomized, controlled, phase II trial of SCR followed by chemotherapy and niraparib maintenance vs chemotherapy and niraparib maintenance in patients with platinum-sensitive second relapsed OC who never received SCR at recurrence. To guarantee surgical quality, if the sites had no experience of participating in any OC-related surgical trials, the number of recurrent lesions evaluated by central-reviewed positron emission tomography–computed tomography image shouldn't be more than 3. Eligible patients are randomly assigned in a 1:1 ratio to receive either SCR followed by 6 cyclesof platinum-based chemotherapy and niraparib maintenance or 6 cycles of platinum-based chemotherapy and niraparib maintenance alone. Patients who undergo at least 4 cycles of chemotherapy and must be, in the opinion of the investigator, without disease progression, will be assigned niraparib maintenance. Major inclusion criteria are secondary relapsed OC with a platinum-free interval of no less than 6 months and a possibly complete resection. Major exclusion criteria are borderline tumors and non-epithelial ovarian malignancies, received debulking surgery at recurrence and impossible to complete resection. The sample size is 96 patients. Primary endpoint is 12-month non-progression rate.

Effect of alveolar macrophages phagocytosis on prognosis in patients with acute respiratory distress syndrome caused by abdominal infection: a multicenter study / 中华危重病急救医学

Objective To investigate the effects of alveolar macrophage phagocytosis on prognosis in patients with acute respiratory distress syndrome (ARDS) caused by abdominal infection. Methods ARDS patients caused by severe intra-abdominal infection admitted to intensive care unit (ICU) of Tianjin Fourth Central Hospital, Tianjin Nankai Hospital, Tianjin First Central Hospital and Tianjin Fifth Central Hospital from June 2016 to March 2018 were enrolled. The gender, age, acute physiology and chronic health evaluationⅡ(APACHEⅡ) within 24 hours of admission, neutral red phagocytosis and alkaline phosphatase activity of macrophages in bronchoalveolar lavage fluid, the length of ICU stay, total hospitalization time, hospitalization expenses, and prognosis were recorded. According to the prognosis, the patients were divided into death group and survival group, and the parameters were compared between the two groups. Pearson test was used to analyze the correlation between neutral red phagocytosis function of macrophages and alkaline phosphatase activity and other indicators. The prognosis was analyzed by binary Logistic regression combined with neutral red phagocytosis and alkaline phosphatase activity in patients, and the predictive value of both subjects on prognosis was analyzed by the receiver operating characteristic (ROC) curve. Results Twenty patients were enrolled in the study, with 8 in the death group and 12 in the survival group. Compared with the survival group, the death group was older (years old: 58.50±14.86 vs. 46.67±13.40), APACHEⅡ score was higher (21.50±3.93 vs. 13.58±4.12), neutral red phagocytosis ability and alkaline phosphatase activity of alveolar macrophages were significantly decreased (A value:0.265±0.050 vs. 0.338±0.016; μmol/L: 12.06±1.24 vs. 17.96±3.90), and the length of ICU stay was significantly longer (days: 22.00±14.59 vs. 11.50±3.17), hospitalization cost was significantly increased (10 thousand Yuan:24.17±11.02 vs. 13.44±3.53), the total hospitalization time was shorter (days: 25.25±15.01 vs. 35.67±8.58), and the difference was statistically significant (all P < 0.05). There was no significant difference in gender between the survival group and the death group [male (case): 8 vs. 6, P > 0.05]. The neutral red phagocytosis ability of alveolar macrophages in ARDS patients caused by abdominal infection was negatively correlated with age, APACHEⅡ score and the length of ICU stay (r value was -0.328, -0.572, -0.809, respectively, all P < 0.05); alkaline phosphatase activity was negatively correlated with age, APACHEⅡ score, the length of ICU stay and hospitalization expenses (r value was -0.334, -0.583,-0.470, -0.517, respectively, all P < 0.05). Binary Logistic regression analysis showed that neutral red phagocytosis [odds ratio (OR) = 0.596, 95% confidence interval (95%CI) = 0.212-0.997] and alkaline phosphatase activity (OR = 0.573, 95%CI = 0.339-0.968) were the influencing factors of prognosis (both P < 0.05). ROC curve analysis showed that the AUC of neutral red phagocytosis ability for prognosis of ARDS patients caused by abdominal infection was 0.948, and the sensitivity and specificity were 91.7% and 87.5% when the off-cut value was 0.317. The AUC of alkaline phosphatase for the prognosis of ARDS patients caused by abdominal infection was 0.813; when the cut-off value was 19.72 μmol/L, the sensitivity was 75.0%, and the specificity was 87.5%. Conclusion The alveolar macrophage phagocytosis dysfunction in ARDS patients caused by severe abdominal infection was not only related to the severity of the disease, but also increased the medical burden of patients, and significantly affected the mortality of such patients.

GPA: A Microbial Genetic Polymorphisms Assignments Tool in Metagenomic Analysis by Bayesian Estimation / 基因组蛋白质组与生物信息学报·英文版

Identifying antimicrobial resistant (AMR) bacteria in metagenomics samples is essential for public health and food safety. Next-generation sequencing (NGS) technology has provided a powerful tool in identifying the genetic variation and constructing the correlations between genotype and phenotype in humans and other species. However, for complex bacterial samples, there lacks a powerful bioinformatic tool to identify genetic polymorphisms or copy number variations (CNVs) for given genes. Here we provide a Bayesian framework for genotype estimation for mixtures of multiple bacteria, named as Genetic Polymorphisms Assignments (GPA). Simulation results showed that GPA has reduced the false discovery rate (FDR) and mean absolute error (MAE) in CNV and single nucleotide variant (SNV) identification. This framework was validated by whole-genome sequencing and Pool-seq data from Klebsiella pneumoniae with multiple bacteria mixture models, and showed the high accuracy in the allele fraction detections of CNVs and SNVs in AMR genes between two populations. The quantitative study on the changes of AMR genes fraction between two samples showed a good consistency with the AMR pattern observed in the individual strains. Also, the framework together with the genome annotation and population comparison tools has been integrated into an application, which could provide a complete solution for AMR gene identification and quantification in unculturable clinical samples. The GPA package is available at https://github.com/IID-DTH/GPA-package.

Analysis of 221 Chinese Patent Medicine Instructions Based on the Patient's Concern Survey of Oral Medication / 中国药房

OBJECTIVE:To provide reference for the improvement of Chinese patent medicine instruction.METHODS:The outpatients were selected randomly from a Third Grade Class A hospital.A questionnaire survey was conducted on the attention degree of the outpatients to Chinese patent medicine instructions when taking medicine orally.The concern content label of patients in 221 Chinese patent medicine instructions were counted,analyzed and graded according to survey results.RESULTS:A total of 515 questionnaires were distributed,and 498 effective questionnaires were collected with effective recovery rate of 96.7％.The results of questionnaire survey showed that the highest concern from the patients was usage and dosage (92.4％),followed by attentions and taboos (88.0％,70.3％).The following items were drug interaction,pregnant and lactating women medication,children medication and the elderly medication (56.2％,46.4％,45.2％,42.4％).Among the description of medication methods (usage and dosage) in 221 Chinese patent medicine instructions,203 prescriptions clearly marked medication times (91.9％),160 clearly marked drug dosage (72.4％) and 36 clearly marked medication course (16.3％).In matters of taboos (attentions,taboos,pregnant and lactating women medication,children medication and the elderly medication),124 prescriptions clearly marked population taboos (56.1％),82 clearly marked symptom taboos (37.1％) and 71 clearly marked diet taboos (32.1％).According to the scoring statistics of 221 Chinese patent medicine instructions,there were 52 instructions with score of 6,followed by 47 instructions with score of 8;there were only 4 instructions with full score (12).CONCLUSIONS:At present,related contents of medication methods highly concerned by the patients are well marked in Chinese patent medicine instructions,especially its guidance is basically able to meet the requirements in respect of medication times.The related contents of medication taboos,which is next only to attention degree of medication methods by patients,is poorly marked.Its guidance remains to be improved.

Anti-oxidative damage effect in Schisandrin B in mice of Alzheimer's disease and its mechanism / 吉林大学学报(医学版)

Objective:To investigate the preventive and protective effects of Schisandrin B in the mice of Alzheimer's disease (AD),and to clarify its mechanism.Methods:Fifty Balb/c mice were randomly divided into blank group,model group,pasitive control group,low dose of Schisandrin B group(0.1 g·kg-1)and high dose of Schisandrin B group(0.5 g·kg-1);there were 10 mice in each group.Step-through test was conducted after last administration to detect the latencies and number of errors of the mice in various groups,and the brain tissue was taken.Congo red staining was to detect the morphology changes of cells and neuronal amyloidosis in brain tissue of the mice.The levels of ROS in brain tissue of the mice were tested by Flow Cytometry.The contents of MDA,the levels of LDH,and the activities of CAT,GSH-Px and SOD in brain tissue of the mice were tested by biochemical method.Western blotting method was used to detect the expression levels of signaling pathway proteins Nrf2 and Keap1 in brain tissue of the mice.Results:Compared with model group,the latencies of the mice in low and high dose of Schisandrin B groups were increased (P<0.01) and the number of errors in step-through tests was decreased (P<0.05 or P<0.01).The Congo red staining results showed that compared with model group,the neuronal amyloidosis in brain tissue of the mice in Schisandrin B groups was decreased significantly.Compared with model group,the levels of ROS,LDH and the contents of MDA in brain tissue of the mice in low and high doses of Schisandrin B groups were decreased (P<0.05 or P<0.01),and the activities of CAT,SOD and GSH-Px were increased (P<0.01).Compared with low dose of Schisandrin B group,the content of MDA and the activities of SOD and GSH-Px in brain tissue of the mice in high dose of Schisandrin B group were increased (P<0.001).Compared with model group,the expression level of Nrf2 protein in brain tissue of the mice in low dose of Schisandrin B group was increased (P<0.01),while the expression level of Nrf2 protein in brain tissue of the mice in high dose of Schisandrin B group was decreased (P<0.01);the expression levels of Keap1 protein in brain tissue of the mice in low and high doses of Schisandrin B groups was decreased (P<0.01).Conclusion:Schisandrin B could decrease the level of peroxidation in brain tissue of the mice and reduce the oxidative damage and improve the memory function of the AD mice.The mechanism is related to the activation of Nrf2 signaling pathway which improve the activity of antioxidant enzymes.

Predictive performance of neutrophil gelatinase-associated lipocalin (NGAL) in acute kidney injury in septic patients / 中华急诊医学杂志

Objective To assess the capability of serum and urine neutrophil gelatinase-associated lipocalin (NGAL) in predicting acute kidney injury (AKI) in septic patients.Methods From July 1, 2014 through December 31, 2014, a prospective observational study of septic patients without AKI was carried out in Renmin Hospital, Tianjin Hospital, and Nankai Hospital, Tianjin.The patients with AKI which was developed after admission to intensive care unit (ICU) were assigned to AKI group and the patients without AKI were assigned to non-AKI group.Clinical data and serum and urine sample were collected at the admission, and at 12, 24, 36, 48, 60, 72 ,84 and 96 hours after admission for detecting creatinine and NGAL.The measurement data accorded with normal distribution were used for t test or variance analysis of repeated measures;comparison of measurement data in non-normal distribution was carried out using the Mann-Whitney U test or Fridman test;comparison of count data was performed using Fisher exact probability method.ROC curve of serum or urine NGAL was plotted and the diagnostic values of serum or urine NGAL in predicting AKI were assessed by calculation of the area under the receiver operating characteristic curve (AuROC).Results Fifty septic patients were included.Thirty-five patients were in AKI group and fifteen in non-AKI group.The median age of AKI group was 73 and the median age of non-AKI group was 60 (IQR, 47-82).The urine NGAL (uNGAL) concentration in AKI group was higher than that in non-AKI group at the every interval and serum NGAL (sNGAL) was higher in AKI group than that in non-AKI group at only first twointervals.The uNGAL showed the capability of prediction for AKI progression at the 48 hour (AuROC=0.83,95% CI:0.70-0.97), 36 hours (AuROC=0.75,95%CI:0.59-0.91), 24 hours (AuROC=0.83,95%CI:0.70-0.95), 12 hours (AuROC=0.73,95%CI:0.60-0.88) prior to AKI occurred.The sNGAL showed capability of prediction at the 48 hours (AuROC=0.69,95%CI:0.51-0.88), 36 hours (AuROC=0.69,95%CI:0.52-0.87) prior to AKI occurred.Conclusions The sNGAL and uNGAL both were useful biomarker that predicted development of AKI in early stage.But the performance of sNGAL was slightly inferior to that of uNGAL for predicting development of AKI.

Rapid cryopreservation for Siraitia grosvenorii cells based on cells' capacitance detection / 生物工程学报

A rapid quantitative evaluation method for Siraitia grosvenorii cells was successfully developed based on plant cells' capacitance value detected by a viable cell mass monitor and the cryopreservation of S. grosvenorii suspension cells was optimized. The survival rate of S. grosvenorii cells was quantitatively measured by viable cell mass monitor and 2, 3, 5-triphenyltetrazolium chloride (TTC). An optimum cryoprotectant recipe is that the growth medium contained 10% sucrose and 10% DMSO. The experimental results also showed higher cell survival rates and cell viabilities were achieved when suspension cells were treated with pretreatment of 0.2 mol/L sucrose. With the increase of concentration of sucrose, however, the cell survival rate was decreased. And the cell survival rate represented a bell shape with the increase of pretreatment time. The highest cell survival rate and cell viability were obtained with the 9 h' s pretreatment. In addition, there was a good correlation between the cell survival rate measured by cell recovery test and that measured by viable cell mass monitor, while there were no significant differences in the cell morphology and the ability of mogrosides V production by S. grosvenorii cells cultured in suspension after cryopreservation. Therefore, the evaluation method developed based on the viable cell mass monitor has good feasibility and reliability.

Adequate feeding of early enteral nutrition in critical patients with cancer / 中国实用护理杂志

Objective To describe the adequate feeding of early enteral nutrition in critical patients with cancer, and explore its influencing factors. Methods A retrospective analysis study was performed and 161 patients were involved. Results Nearly 57.14%patients got adequate feeding. The independent risk factors included complications (P < 0.05,OR=2.312,OR 95%CI 1.078-4.958), Acute Physiology and Chronic Health Evaluation Ⅱ (APACHEⅡ) scores (P < 0.05,OR=1.111,OR 95%CI 1.017-1.214) and hypoalbuminemia (P<0.05,OR=2.252,OR 95%CI 1.036-4.892) , and the protective factor was previous enteral nutrition experience (P<0.01,OR=0.123,OR 95%CI 0.021-0.494). Patients who got adequate feeding showed more increase in albumin levels, more decrease in APACHEⅡscores and shorter ICU stays. Conclusions Part of patients got inadequate feeding, due to comprehensive effects of many factors. And adequate feeding may be beneficial to the increase of albumin levels, also helps patients rehabilitate early and shorten the ICU stays.

The diagnostic value of urinary neutrophil gelatinase-associated lipocalin (NGAL) to the acute kidney injured septic rats / 中华急诊医学杂志

Objective ①Observing urinary neutrophil gelatinase-associated lipocalin (uNGAL)'s concentration variation under the intervention of sepsis; ②Evaluatingu NGAL' s diagnostic value for early acute kidney injury (AKI).Method Fifty-six SD (Sprague Dawley) rats were randomly (random number) divided into four groups,including 16 rats in model group (CLG),16 rats in Xuebijing group (XBG),16 rats in Huangqi and Chaihu injection jointly applied group (HCG),and 8 rats in sham operation group (SOG).The septic models in CLG group,HCG group and XBG group were established by cecal ligation and puncture (CLP).Then,the rats in HCG group was treated with intraperitoneal injectionby Huangqi and Chaihu injections; the XBG group was treated with intravenous injection by Xuebijing injection; the SOG group was treated with open surgery without CLP.After the CLP,serial urine and serum samples were obtained at baseline (just prior to operation),6 h,12 h,18 h,24 h,36 h,48 h,and 72 h,and were measured by sCr,uCr,uNa,and uNGAL.The line graph of uNGAL' s concentration variation was plotted,based on the time.Diagnostic characteristics of urinary NGAL in predicting AKI were assessed by calculating the area under the receiver operating characteristic curve (AUC).Results After the CLP,the uNGAL of sepsis model rats increased quickly within 6 hours.The time points of each group model reaching their peak were 6 hours after CLP in CLG groupand 24 hours after CLP in HCG group and XBG group.These groups' uNGAL all decreased quickly after the peak.The cuNGAL of sepsis model rats was increased quickly within 6 hours after CLP,reached its peak at 24 hours after CLP.In CLG group,the line graphs of uNGAL or cuNGAL were almost overlapped.There is little difference in the concentration of uNGAL or cuNGAL at each time point (uNGAL:6h,t=0.691; 12h,t=1.627; 18 h,t=0.511,cuNGAL:6h,t =0.371 ; 12 h,t =0.474; 18 h,t =-1.187.Statistical significance of all above value was P ＞0.05).InXBG group,the line graph of uNGAL and cuNGAL were not overlapped,but difference between uNGAL and cuNGAL concentration at each time point was not significant (uNGAL:6 h,t =1.222 ; 12 h,t =1.178 ; 18h,t=1.272; 24h,t=0.918; 36h,t =0.442.cuNGAL:6 h,t =1.482; 12 h,t =1.314; 18 h,t=1.280; 24 h,t =0.280; 36 h,t =0.467.Statistical significance of all above value was P ＞ 0.05).In HCG group,uNGAL of AKI rats were higher than non-AKI rats at each time points since 6 hours later (6 h,t =2.351,P＜0.05; 12h,t=3.086,P＜0.01; 18h,t=2.535,P＜0.05;24h,t=2.150,P＜0.05;36h,t =2.485,P ＜ 0.05),The average cuNGAL of AKI rats and non-AKI rats have statistical significance at 6h,18 h,and 24 h (6 h,t=3.013.P＜0.01; 18 h,t =4.804,P＜0.01; 24 h,t=2.682,P＜0.05).At 6 h,Uout can increase cuNGAL' s ability of predicting AKI' s occurrence in 24 hours (AUC increased from 0.839 to 0.900,P ＜ 0.05).Conclusions The intervention to the sepsis rats have influence on the secretion volume and secretion sequence of NGAL in rat urine.uNGAL and cuNGAL are good predictor of AKI occurrence in sepsis rats.

Assessment and appraisal of biomarkers in patients with septic kidney injury / 中华急诊医学杂志

Objective To determine the diagnostic significance of serum Cystatin C (Cys C),neutrophil gelatinase-associated lipocalin (sNGAL),urinary kidney injury molecule1 (uKIM-1) and urinary interleukin-18 (uIL-18) in patients with septic acute renal injury.Methods A total of 62 adult patients with sepsis admitted to the Intensive Care Unit over 24 hours in the Tianjin Hospital between August 2012 and March 2013 were divided into acute renal injury group (n =39) and non-acute renal injury group (n =23) according RIFLE diagnostic criteria.Measurements of Cys C,sNGAL,uKIM-1 and uIL-18 were performed.The diagnostic values of the biomarkers were assessed by comparing their levels between the patients of different groups.Results The levels of Cys C (2.27 ± 0.93) μg/L,sNGAL (275.04 ±79.37) μg/L,uKIM-1 (2.52 ± 1.06) μg/L in acute renal injury group were higher than Cys C (1.19 ± 0.77) μg/L,sNGAL (137.51 ± 99.33) μg/L,uKIM-1 (1.27 ± 0.62) μg/L in non-acute renal injury group (P ＜ 0.05).There was no significant difference in uIL-18 between the acute renal injury group (374.87 ± 70.23) ng/L and the non-acute renal injury group (354.09 ± 66.42) ng/L (P ＞ 0.05).The area under ROC curve for diagnostic values of serum Cystatin C,sNGAL and uKIM-1 in acute renal injury were0.84 (0.74-0.95),0.90 (0.79-1.00),0.87 (0.78-0.96).Conclusions CysC,sNGAL and UKIM-1 might be valid as diagnostic biomarkers of septic acute renal injury.

Analysis of Prognostic Risk Factors in Patients with Community Acquired Pneumonia Complicated with Acute Kidney Injury / 天津医药

Objective To explore clinical characteristics and prognostic risk factors in patients with community ac-quired pneumonia(CAP)complicated with acute kidney injury(AKI).Methods In total, 456 CAP patients were included based on the diagnostic guide.According to whether the patients were accompanied with AKI,the patients were divided in-to two groups(non-AKI group and AKI group). AKI group were further divided into risk group, injury group and failure group by RIFLE criteria using admission creatinine.Severity in CAP patients,clinical indexes and prognostic evaluation in-dexes were compared between different groups. Multiple factors were analyzed using Logistic regression model,survival analysis were examined by Kaplan-Meier, which analyzed the risk factors of poor prognosis in CAP patients and the role of RIFLE criteria in prognostic evaluation. Results Thirty percent(135)of the total 456 CAP patients were accompanied with AKI. Patients in AKI group were further divided into risked group (45.2%, 61 patients), injury group (17%, 23 pa-tients) and failure group (37.8%, 51 patients) according to the RIFLE diagnostic criteria using basal creatinine level. Among the 300 patients with PSI gradeⅠtoⅢ,23.3%(70)of patients developed AKI while among 156 patients who are with PSI gradeⅣor over, 65 patients (41.7%) developed AKI(P<0.01).The 30-day mortality of CAP patients accompanied with AKI were increased compared to Non-AKI group(Non-AKI:6.2%;Risk:14.8%;Injury:21.7%;Failure:45.1%).With de-teriorating in RIFLE criteria,the portion of patients who required mechanical ventilation, inotropic support(MV/IS)and re-nal replacement therapy(RRT)increased too. Logistic analysis revealed that AKI,age of 75 years or older and extra-renal or-gan failure were the risk factors of poor prognosis in patients with CAP. The rate of survivors was decreased in the CAP pa-tients accompanied with AKI compared with those who did not.Conclusion There is certain incidence of AKI to compli-cate CAP patients who will have a poor prognosis.RIFLE diagnostic criteria is a valuable tool to evaluate prognosis of CAP patients complicated with AKI.

Effect of Xuebijing Injection on MIF Expression and Acute Kidney Injury in Rats with Sepsis / 天津医药

Objective To investigate the expression of macrophage migration inhibitory factor (MIF) in serum and renal tissue of septic rats with actue kidney injury (AKI), and to explore the effect of Chinese traditional medicine-Xuebijing injection on MIF expression as well as on acute kidney injury in rats with sepsis. Methods Sepsis model was reproduced in rats with cecal ligation and puncture (CLP).Eighty healthy SD rats were randomly divided into three groups:sham operation group(n=16), CLP model group (n=32), and xuebijing group(n=32). All rats were sacrificed at either 2, or 8, or 24 and or 48 hours after operations.MIF mRNA levels in renal tissues of septic rats were semi-quantified by Real-time PCR.The content of MIF in serum was determined by enzyme linked immunosorbent assay (ELISA). Serum creatinine (Cr) contents were measured by automatic biochemistry analyze. Results Compared with sham operation group, transcription of MIF mRNA in renal tissues of model group were significantly enhanced at 8, 24 and 48 hours after operations (P<0.01). Both contents of MIF and creatinine level in serum of model group rose obviously at 24 and 48 hours after operation (P<0.01);Compared with model group, the transcription of MIF mRNA in renal tissues of xuebijing group decrease obviously at 2, 8, 24 and 48 hours (P<0.01) and both contents of MIF and creatinine in serum of xuebijing group drop remarkably at 24 and 48 hours (P<0.01). Conclusion MIF is a kind of late cytokine which might participate in the pathogenesis of AKI in rats with sepsis.Xuebijing injection can inhibit MIF expression, and possess the protective effects on the kidney in rats with sep-sis.

Effects of different blood purification on the prognosis of patients with acute septic kidney injury / 中华急诊医学杂志

Objective To evaluate the different methods of blood purification for acute septic renal injury (AKI) in respect of outcome by using RIFLE(risk,injury,failure,loss and end-stage renal disease)criteria and A-PACHE Ⅱ score. MethodData of 96 patients with ASRI admired to ICU of Tianhe Hospital, Tianjin, from March 2004 to September 2006 were analyzed. Including criteria: 2001 International Sepsis Definitions Conference and 2004 RIFLE criteria of AKI. The methods of blood purification used continuous renal replacement therapy (CRRT, n=54) and imermittent hemodialysis (IHD, n=42).The patients of CRRT group could be classified into stages Ⅰ, Ⅱ and Ⅲ referred to RIFLE criteria. Excel was evaluated to set up clinical data base from documented material. Data were analyzed with SPSS version 11. 5 software. Physical signs, laboratory findings, variation of APACHE Ⅱ score and outcomes of patients were documented evaluated. Data of two groups compared using indepent samples T test, before and after the treatment compared using paired-samples T test, rate compared using chi-square test. Results①There were no statistical differences in APACHE Ⅱ score and creatinine (Cr) between CRRT group and IHD group before treatment (P>0.05). The mortalities of CRRT group and IHD group were 51.9％ and 52.4％, respectively (P>0.05), but the recovery rates of renal function in CRRT group and IHD group were 92.3％ and 65.0％ ,respectively (P< 0.05).②Mean arterial pressure (MAP),oxygen saturation (SpO2) of CRRT group were lower than those of IHD group (P<0.05) and they increased to some extent after treatment (P< 0.05). ③In the patients of stag Ⅰ ,the survival rate was 78.6％, APACHE Ⅱ score was 25.4± 2.5 before treatment, renal function recovery rate was 90.9％ ,and APACHE Ⅱ changed - 13.6 ± 4.3, while those relevant markers in the patients of stage Ⅲ were 38.1％, 36.1 ± 5.7,62.5 ％ and - 7.1 ± 4.2, respectively (P<0.05). ConclusionsThe RIFLE criteria has guiding significance for the early diagnosis and prognosis of ASRI,and the RIFLE and APACHE Ⅲ score may help to choose the optimum opportunity of treatment and the early CRRT as soon as possible after diagnosis can improve the outcome of patients with acute septic renal injury.

Pituitary abscess:a review of 7 cases and some points about its diagnosis / 中国实用内科杂志

Objective To analyze the clinical features,auxiliary examination,diagnosis and treatment of pituitary abscess.Methods A retrospective analysis was done in 7 cases of pituitary abscess.All cases’ final diagnose were confirmed by histopathological results.Results 1.Four cases were diagnosed as primary pituitary abscess,the others 3 cases as secondary pituitary abscess which was associated with pituitary adenoma,pituitary cyst,craniopharyngeal duct tumor respectively.2.Clinical features:Of 7 cases,fever was determined in 6 cases,visual disturbance or temporal hemianopia in 5 cases,headache associated with anorexia and nausea and vomitting in 4 cases.High white blood cell counts was present in 3 cases,high PRL levels in 4 cases.Three cases were associated with hypothyroidism,2 cases with hypoadrenocorticism.MR image showed isointense or hypointense signal on T1WI and isointense or hyperintense signal on T2WI in pituitary abscess.Postcontrast T1WI showed a ring-shaped enhancement.Two cases were diagnosed by MR images and clinical features before surgery,the others by surgical histopathology.3.Treatment:All cases were treated with surgery,followed by antibiotics therapy.After operation all symptoms were improved except for optic nerve function.Conclusion It is suggestive of pituitary abscess when any patient present firstly with fever,headache,visual or eyeshot disturbance,partial or whole hypopituitarism associated with saddle area mass.Earlier diagnosis,timely surgery and postoperative proper antibiotics therapy are the keys to the treatment of pituitary abscess.