The Etiological Study of Three Hunter Syndrome Families in Southern China / 中山大学学报(医学科学版)

ObjectiveTo reveal the molecular pathogenesis of Hunter syndrome in three families in southern China and to clarify the correlation between phenotype and genotype， so as to lay a foundation for future prenatal or preimplantation genetic diagnosis. MethodsOn the basis of initial clinical diagnosis and pedigree analysis， qualitative detection of glycosaminoglycans in urine was performed first， and then anticoagulant blood samples were collected from the children and their relatives. DNA was extracted and the IDS gene sequence was analyzed by PCR and Sanger sequencing. Various methods such as RT-PCR and bioinformatics analysis were used to identify the pathogenicity of the new variants. ResultsThe urine test results of the patients in the three families were all strongly positive（++）. Probands were all male， with hemizygous mutations in IDS gene from their mothers， and the mutation sites were c.615_622delCATACAGT， c.847_848delGT and IVS7 ds+1 G>A， respectively. The cross-species conservation analysis showed that the amino acid of IDS gene mutation site was highly conserved during species evolution. Compared with the normal protein， mutant proteins exhibited significant differences in the predicted results of advanced structure. The variants identified in the three families were classified as pathogenic by ACMG criteria. ConclusionsThe three probands were diagnosed with Hunter syndrome. The c.615_622del（p.Il206Valfs*18）， c.847_848del（p.Val283Alafs*57） and IVS7 ds+1 G>A （p.G336Dfs*12） of IDS gene are all novel pathogenic mutations， which are the underlying causes of morbidity in children. This study has further enriched the mutation spectrum of IDS gene.

O-linked N-acetylglucosamine modification induced by lipopolysaccharide is involved in inflammatory signaling pathway in endothelial cells / 中华危重病急救医学

Objective:To explore whether the lipopolysaccharide (LPS)-induced modification of O-linked N-acetylglucosamine (O-GlcNAc) is involved in the inflammatory signaling pathway of endothelial cells.Methods:Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. Results:Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2 -ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2 -ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2 -ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2 -ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2 -ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2 -ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2 -ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2 -ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. Compared with the blank control group, the phosphorylation level of Akt in the LPS group was increased. Compared with the LPS group, both OGT expression and O-GlcNAc modification were down-regulated after pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor. Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2 -ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2 -ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2 -ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2 -ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2 -ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2 -ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2 -ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. Conclusions:The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. AKT may be involved in the effect of LPS on the inhibition of O-GlcNAc modification.

Efficacy of maintenance electroconvulsive therapy combined with quetiapine treatment for manic episode of bipolar disorder / 中国基层医药

Objective:To investigate the efficacy of maintenance electroconvulsive therapy (MECT) combined with quetiapine treatment for manic episodes of bipolar disorder.Methods:A total of 103 patients with manic episodes of bipolar disorder received treatment in Kangci Hospital of Jiaxing from January 2019 to August 2020 and were included in this study. They were randomly divided into observation ( n = 46) and control groups ( n = 57). The observation group was given MECT combined with quetiapine treatment and the control group was treated with magnesium valproate sustained-release tablets combined with quetiapine. All patients received 4 weeks of treatment. Clinical efficacy, total hospital cost, drug cost during hospitalization, drug proportion, adverse reactions, and scores of the Bech-Rafaelsdn Mania Rating Scale and the Wisconsin Card Sorting Test pre- and post-treatment were compared between the two groups. Results:After 4 weeks of treatment, total response rate was significantly higher in the observation group than in the control group [76.09% (35/46) vs. 56.14% (32/57), χ2 = 4.45, P < 0.05]. In the observation group, total hospital cost, drug cost during hospitalization, and drug proportion were (16074.52 ± 1019.81) yuan, (1374.52 ± 619.81) yuan, and 8.70% respectively, which were not significantly different from those in the control group [(15618.14 ± 1550.34) yuan, (1261.14 ± 750.34) yuan, 10.53%, t = 1.71, 0.82, χ2 = 0.09, all P > 0.05]. After 4 weeks of treatment, Bech-Rafaelsdn Mania Rating score was significantly lower in the observation group than in the control group [(7.36 ± 3.04) points vs. (10.23 ± 2.37) points, t = 5.38, P < 0.001]. The number of wrong responses and the number of perseverative errors in the Wisconsin Card Sorting Test in the observation group were (40.45 ± 3.61) counts and (9.56 ± 1.39) counts, respectively, which were significantly lower than those in the control group [(48.59 ± 4.51) counts, (12.08 ± 1.25) counts, t = 10.17, 9.56, both P < 0.001]. The number of perseverative errors in the Wisconsin Card Sorting Test was significantly higher in the observation group than in the control group [(33.85 ± 2.50) counts vs. (29.71 ± 2.14) counts, t = 8.90, P < 0.001]. There was no significant difference in total incidence of adverse reactions between observation and control groups (21.74% vs. 22.81%, χ2 = 0.01, P > 0.05). Conclusion:MECT combined with quetiapine treatment is highly effective on the manic episodes of bipolar disorder. The combined therapy is worthy of clinical application.

Secondary metabolites from the dandelion-derived endophytic fungus Epicoccum sorghinum 1-2 / 药学学报

The secondary metabolites from the dandelion-derived Epicoccum sorghinum 1-2 were isolated by silica gel and Sephadex gel column chromatography, and semi-preparative high performance liquid chromatography (HPLC). Their structures were identified by comprehensive NMR and MS methods. Their antibacterial activities were determined by filter paper method. Finally, seven compounds were isolated and identified from the fermentation product of E. sorghinum 1-2, including (4R*,5R*,6S*)-4,5-dihydroxy-6-(6'-methylsalicyloxy)-2-methoxymethyl-2-cyclohexen-l-one (1), (4R*,5R*,6S*)-4,5-dihydroxy-6-(6′-methylsalicyloxy)-2-methyl-2-cyclohexen-1-one (2), (4R,5R,6S)-4,5-dihydroxy-6-(6'-methylsalicyloxy)-2-hydroxymethyl-2-cyclohexen-1-one (3), (-)-gabosine E (4), theobroxide (5), 3-chlorogentisyl alcohol (6), and 3-hydroxybenzyl alcohol (7), of which 1-5 are epoxydons, and 6 and 7 are phenolics. Compounds 1 and 2 are new structures reported for the first time. Compound 6 showed significant antibacterial activity against Staphylococcus aureus.

The prognostic value of thymosin β4 expression and preoperative systemic immune-inflammatory index/serum albumin level in early operable non-small cell lung cancer / 中国医师杂志

Objective:To investigate the prognostic value of thymosin β4 (TMSB4X) expression and preoperative systemic immune-inflammatory index/serum albumin (SII/ALB) level in patients with early operable non-small cell lung cancer (NSCLC).Methods:A total of 128 patients with early NSCLC admitted to Zibo Central Hospital from January 2016 to January 2021 were selected. TMSB4X and SII/ALB were detected before surgery, and they were divided into TMSB4X positive group (52 cases) and TMSB4X negative group (76 cases) according to TMSB4X expression. According to the median SII/ALB value, the patients were divided into high SII/ALB group (64 cases) and low SII/ALB group (64 cases). The relationship between TMSB4X, SII/ALB and clinical characteristics in patients with early operable NSCLC was analyzed. The survival curve was drawn by Kaplan-Meier method and the difference of progression free survival (PFS) between TMSB4X positive group and negative group, high SII/ALB group and low SII/ALB group was tested by log-rank. The influencing factors of PFS was analyzed by Cox univariate and multivariate regression.Results:There were difference in lesion site, carcinoembryonic antigen (CEA) and lymphocyte count (LY) between TMSB4X positive group and TMSB4X negative group (all P<0.05). There were significant difference in age, American Joint Committee on Cancer (AJCC) stage, ALB, cytokeratin 19 fragment (CYFRA21-1), CEA, LY, platelet count (PLT) between the high SII/ALB group and the low SII/ALB group (all P<0.05). The median PFS of TMSB4X positive group (17.11 months) was lower than that of TMSB4X negative group (26.64 months) (log rank P<0.001); The median PFS (15.82 months) in the high SII/ALB group was lower than that in the low SII/ALB group (28.24 months) (log rank P<0.0001); Cox univariate analysis showed that lesion location, AJCC stage, ALB, CYFRA21-1, CEA, LY, PLT, TMSB4X, and SII/ALB were all factors influencing PFS in early operable NSCLC patients (all P<0.05); Multivariate analysis showed that AJCC stage, LY, TMSB4X, SII/ALB were independent factors influencing PFS in early operable NSCLC patients (all P<0.05). Conclusions:The expression of TMSB4X and the preoperative level of SII/ALB can be used as prognostic indicators for patients with early operable NSCLC.

Effect of early individualized rehabilitation on patients with severe mechanical ventilation / 中国康复理论与实践

ObjectiveTo explore the effect of early individualized rehabilitation on patients with severe mechanical ventilation. MethodsA total of 36 patients on mechanical ventilation admitted to the ICU of the Second Affiliated Hospital of Anhui Medical University from March, 2019 to February, 2020 were randomly divided into control group (n = 18) and rehabilitation group (n = 18). All the patients completed a rehabilitation assessment within 24 hours of admission, including clinical assessment, state of consciousness and muscle strength assessment. The control group was treated with intensive care routine treatment, including symptomatic treatment of primary disease, nutritional support, placement of normal limbs, active and passive movement of limbs. The rehabilitation group received early individualized rehabilitation in addition., including active and passive limb movements, transfer training, physical factor therapy, and respiratory muscle training after the specific evaluation. The mechanical ventilation duration and ICU length of stay, the hospitalization cost, Richmond Agitation and Sedation Scale (RASS), acute Physiology and Chronic Health Evaluation Ⅱ (APACHEⅡ), and the content of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 were compared. ResultsThere was no significant difference in the weaning rate and hospitalization cost between two groups (P > 0.05). The mechanical ventilation duration and ICU length of stay were less in the rehabilitation group than in the control group (t > 2.067, P < 0.05). After treatment, the score of APACHEⅡ and the content of TNF-α and IL-6 decreased in the control group (t > 2.040, P < 0.05); the score of APACHEⅡ and the content of TNF-α, IL-6 and IL-8 decreased in the rehabilitation group (t > 4.141, P < 0.001); the content of TNF-α, IL-6 and IL-8 was less in the rehabilitation group than in the control group (t > 2.217, P < 0.05). The improvement of all the indexes was better in the rehabilitation group than in the control group (|Z| > 2.104, P < 0.05). ConclusionFor patients on mechanical ventilation, early individualized rehabilitation could improve the sedation, relieve the inflammatory reaction, accelerate the process of weaning, and reduce the length of stay with no extra cost.

Detection of antibodies against SARS-CoV-2 as a serologic marker of infection in patients with COVID-19 / 中国输血杂志

【Objective】 To investigate the diagnostic value of severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) specific antibodies IgM and IgG on coronavirus disease 2019 (COVID-19). 【Methods】 1) The test results of SARS-CoV-2 IgM/IgG antibodies and nucleic acid(NAT), which were tested by colloidal gold test and fluorescent quantitative PCR respectively, were collected from 145 febrile outpatients during early March, 2020, named Fever group, in which retrospective analysis and paired chi-square test were performed. 2) 612 cases of SARS-CoV-2 IgM/IgG antibodies test results, which were done on March 5, 2020, were collected. They were named COVID-19 group (Our hospital was provisionally assigned as a specialized hospital for COVID-19, and 1500 COVID-19 patients admitted to our hospital from February 12, 2020 to March 18, 2020). The SARS-CoV-2 IgM/IgG antibodies and NAT were respectively tested on the 30th and the 60th day after the date of discharge. The clinical application values of the antibodies was clarified by statistical analysis. 【Results】 1) In the fever group, the positive rate of SARS-CoV-2 IgM, IgG and IgM+ IgG antibodies were 26.21% (38/145), 54.48% (79/145) and 26.21% (38/145), respectively(P<0.01), and the positive rate of NAT was 4.14% (6/145), which was lower than that of antibody (P<0.01). One (1/145, 0.69%) positive NAT was implicated in initially negative IgM and IgG antibodies samples. 2) In the COVID-19 group, the positive rate of IgM antibody was low (5%) and IgG antibody was high (65%) during 2~14 days after infection, and stably increased during the 15~56 days [IgM 47.68%(277/581) vs IgG 94.15% (547/581) ], then both decreased after 57 days. The positive rates of IgM antibody and IgG antibody were 45.8% (280/612) and 93.1% (570/612) in 612 patients during hospitalization. 15 patients′ data after dischange were not collected as they were later transferred to Huoshenshan Hospital for treatment. The coronavirus NAT results of the rest 597 COVID-19 patients, tested on the 30th and 60th days after the date of discharge, were negative, and the positive rates of IgG antibody and IgM antibody were still ≥80% and ≥40% respectively at the second month after discharge. 【Conclusion】 IgM, IgG antibody against SARS-CoV-2 can be well detected by Colloidal gold method(Innovita), whose positive rate is higher than that of NAT. IgG antibody is produced earlier than IgM, and it keeps high positive rate and persists for a long time. The combination of colloidal gold antibody test and NAT can improve the diagnose rate of COVID-19 and the exclusion of suspected cases.

Progress of microcirculation research in shock and sepsis from 2000 to 2019 based on knowledge visualization analysis / 中华危重病急救医学

Objective:To explore the progress of microcirculation research in shock and sepsis from 2000 to 2019 based on knowledge visualization analysis.Methods:The literatures related to microcirculation of shock and sepsis published in Web of Science and Wanfang databases were collected from 2000 to 2019. Then, data collected was sorted out and used to make bar charts and curves reflecting the growth trend of the literatures using Excel software. The information about country, institution and author were extracted by CiteSpace 5.0 R1 for generating co-occurring network, to find the main research power and each cooperative relation. This software was also used to analyze the related-keywords and cited reference, so that the map of co-citation reference was drawn subsequently to explore the frontiers and hot spots in this field.Results:There were a total of 2 000 Chinese "papers" or "dissertations", 1 823 English "articles" or "reviews", collected preliminarily. The Chinese literatures were only statistically described for the amounts, institutions and authors, however, all retrieved English literatures were enrolled in the visualization analysis eventually. From 2009 to 2019, the number of English literatures rose steadily; however, the number of Chinese literatures had been sliding since 2011. On terms of quality, the impact factors of most literatures were under 6, lacking high quality ones, and the number remained stable every year. According to the analysis of English literatures, the top three countries that published related papers around the world were Germany ( n = 430), the United States ( n = 401) and Netherlands ( n = 223). In the aspect of research institutions, the University of Amsterdam (Netherlands) ranked first in the Web of Science ( n = 113), while the institution in China with the most publications was the Southern Medical University ( n = 71). According to the analysis of co-occurring author network, there were three major globe scientific groups in which Can Ince, Daniel De Backer and Jean-Louis Vincent contributed most to this research field. The top three authors who published most Chinese papers were Niu Chunyu ( n = 20), Zhao Zigang ( n = 18) and Duan Meili ( n = 13). By generating the co-occurring keyword mapping, the research hot spots mainly focused on "blood flow", "nitric oxide", "hemorrhagic shock" and "perfusion". However, these burst keywords, including "cardiogenic shock", "acute kidney injury", "fluid resuscitation", "sublingual microcirculation", "mortality", "oxidative stress", and "critically ill patient", represented the frontiers in microcirculation research of shock and sepsis field. Finally, the results of co-citation reference analysis showed that "sublingual microcirculation" and "mottling score" were most active, indicating that the research of microcirculation monitoring technology could be considered as a hot spot and also the frontier in this field, which was consistent with the results of co-occurring keywords network. Conclusions:Knowledge visualization analysis can visually exhibit the hot spot and trend of microcirculation research in shock and sepsis. The power was mainly focused on a few developed countries in Europe, and the trend was more inclined to the related microcirculation monitoring technology.

Change of moisture transformation and chemical constituents in drying/rehydration process of fresh Chinese medicines (ginseng) / 中草药

Objective: To study the changes rule of active ingredients content and moisture status during the process of dry (drying/steaming) and rehydration (decoction), which could provide technical support for optimizing the dry/rehydration conditions of Chinese medicine and scientifically determine the end point of the process, and it also provides a new scientific perspective for exploring the differences in fresh/dry/processing of traditional Chinese medicine. Methods: Low-field NMR and imaging techniques (LF-NMR, MRI) were used to determine the change of water with time; The content changes of main composition of ginsenosides in different samples were determined by HPLC. Results: The results of determination of moisture and chemical composition showed that: The fresh ginseng was steamed for 180 min. At this time, the water was saturated, the ginsenosides tended to be stable, and the content of total ginsenosides was high. When fresh ginseng and red ginseng were dried at different temperatures for 12.5 h, they were not completely dried at 40 ℃ hot-air drying; The sun-dried ginseng still contained 3.02% water at 50 ℃ hot-air drying, and the red ginseng has been dried; Both of them have been dried at 60 ℃, but the content of total ginsenosides in ginseng and red ginseng was the highest at 50 ℃. The comprehensive results showed that ginseng and red ginseng were better at 50 ℃ hot-air drying. During rehydration (decocting), the moisture content of the decoction for 60 min was fully saturated and the content of total ginsenosides was higher, better than 30 min and 120 min, which was a better decocting condition. The moisture content and total ginsenosides content of fresh ginseng were higher than those of steaming/drying/decocting ginseng, suggesting that fresh ginseng is great significance for preserving and exerting the basic state of the initial pharmacodynamics of traditional Chinese medicine. Conclusion: In this study, ginseng was used as an example. LF-NMR/MRI and HPLC techniques were used to focus on the changes of moisture and chemical contents during the drying (drying, processing) and rehydration (decocting) of traditional Chinese medicines. It provides a new technical method for the determination of the dry/rehydration end point and the optimization of process conditions for traditional Chinese medicine, and also provides a new scientific basis for the interpretation and exploration of the theory of fresh/drying/processing of traditional Chinese medicine.

Interpretation of Society of Critical Care Medicine and European Society of Intensive Care Medicine of clinical practice guideline on critical illness-related corticosteroid insufficiency in 2017 / 中华危重病急救医学

Great progress of critical illness-related corticosteroid insufficiency (CIRCI) has been made in diagnosis and treatment, but it still has high mortality. Meanwhile, corticosteroids are widely used in critically ill patients. Recently, the Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) published a practice guideline which had updated the diagnosis and management of CIRCI. In order to master and promote the guideline, this article interprets the new guideline to assist Chinese clinicians for better understanding CICRI at a more comprehensive level.

An interpretation of the Second consensus on the assessment of sublingual microcirculation in critically ill patients issued by the European Society of Intensive Care Medicine in 2018 / 中华危重病急救医学

The European Society of Intensive Care Medicine (ESICM) issued the second consensus on the assessment of sublingual microcirculation in critically ill patients. This paper interprets the consensus for clinicians about: what is microcirculation, how to observe microcirculation, and the details of microcirculation images collection and parameters analysis. Besides, this paper illustrates the relationship between microcirculation alternation and shock, it also evaluates the present situation and future development of microcirculation monitoring.

Establishment of an antibacterially effective components fingerprint for quality evaluation of Scutellariae Radix (Huangqin) / 药学学报

A chemical fingerprint is an important mean for quality control of traditional Chinese medicine (TCM); however, there is much redundant information in a conventional fingerprint that can affect its availability and accuracy. In this work, the antibacterial biopotency of Scutellariae Radix (Huangqin, HQ) was determined according to the parallel line method of quantitative response. HPLC was adopted to detect the chemical fingerprint of HQ; Grey relational analysis (GRA) was used to identify the primary effective components. The results showed that the antibacterial biopotency of 15 batches of HQ ranged from 0 to 1 000 U·g-1 and the average potency was 556.29 ± 258.57 U·g-1 (1 U is equivalent to the bacteriostatic activity of 2.25 μg gentamicin). There were 34 characteristic peaks in the fingerprints of the samples and their similarities were 0.255-0.991. Eight components (P33, P30/baicalein, P19/baicalin, P15, P29, P34, P31/wogonin and P28) are positively related to antibacterial biopotency and selected from the top ten components of the grey correlation sequence to define the antibacterially effective components fingerprint of HQ. This fingerprint can clearly distinguish the commodity specification and grade, and can also characterize the morphology, components and the bacteriostatic potency differences of HQ. In summary, we established an antibacterially effective components fingerprint which provides simplified information on the antibacterial activity of Scutellariae Radix and could significantly improve the efficacy, specificity, and discriminative ability of the fingerprint for HQ, and could be a useful reference for the comprehensive quality evaluation of other TCM.

Impact of anemia and chronic kidney disease on the risk of cardiovascular disease and all-cause mortality among diabetic patients / 北京大学学报(医学版)

OBJECTIVE@#To explore the association between anemia and cardiovascular disease and all-cause mortality among diabetic patients, and whether the association is modified by the presence of chronic kidney disease (CKD).@*METHODS@#Physical examination data of 8 563 patients with diabetes who met the inclusion and exclusion criteria between 2010 and 2011 were collected, based on the prospective cohort data of Kailuan study. The deadline of the follow-up was December 31, 2015, and the endpoints comprised all-cause mortality and cardiovascular disease. Survival analysis was performed by Kaplan-Meier method. Cox proportional hazards regression model was used to assess the association between anemia with or without CKD, and cardiovascular events and all-cause mortality after adjustment for confounding factors.@*RESULTS@#The average age of the subjects was (57.3±10.3) years, of whom the patients with anemia accounted for 5.2%. The proportion of the patients with anemia combined with CKD was higher than that of the patients without anemia (27.2% vs. 20.8%, P=0.001). The median follow-up time was 4.9 years (interquartile range: 4.6-5.2 years). During the follow-up period, 559 patients died, and 434 patients had cardiovascular disease. Compared with the patients without anemia, the all-cause mortality rate of the patients with anemia was higher (3 220.3/100 000 person-years vs. 1 257.9/100 000 person-years, P<0.001). There was no statistically significant difference in the incidence of cardiovascular disease between the above two groups (999.8/100 000 person-years vs. 1 081.2/100 000 person-years, P>0.05). The mortality and incidence of cardiovascular disease among the patients with CKD were higher than those of the patients without CKD (2 558.3/100 000 person-years vs. 1 044.0/100 000 person-years, P<0.001; 1 605.9/100 000 person-years vs. 941.6/100 000 person-years, P<0.001). Results of Cox regression model showed that, after adjustment for confounding factors, the all-cause mortality risk increased by 95% in the diabetic patients with anemia (HR=1.95, 95% CI: 1.50-2.54). Anemia and CKD significantly increased the mortality risk among diabetic patients (HR=3.61, 95% CI: 2.48-5.26). The CKD patients without anemia had an increased risk of cardiovascular disease (HR=1.41, 95% CI: 1.13-1.74).@*CONCLUSION@#Anemia is associated with an increased mortality risk in Chinese diabetic patients. Patients with CKD have an increased risk of cardiovascular disease and mortality. The all-cause mortality risk increases significantly in anemia patients with the presence of CKD, which indicates that we should focus on the prevention and treatment of diabetic patients with anemia and CKD.

Accuracy of different methods in predicting fluid responsiveness in septic patients: a comparison between ultrasound, PiCCO and traditional methods / 中华麻醉学杂志

Objective To compare the accuracy of ultrasound,pulse indicator continuous cardiac output monitoring (PiCCO) and traditional methods in predicting fluid responsiveness in septic patients.Methods Forty-six septic patients of both sexes,aged 18-72 yr,requiring mechanical ventilation treatment in the intensive care unit,were enrolled in the study.Venous blood samples were collected for determination of plasma B-type natriuretic peptide (BNP) concentrations by chemiluminescence assay,and central venous pressure (CVP) was recorded.Stroke volume variation (SVVTTE),distensibility index of inferior vena cava (dIVC) and velocity time integral changes of aortic blood flow (△VTI) were measured by ultrasound method.SVVPiCCO and global end-diastolic volume index (GEDVI) were measured by PiCCO method.The patients were divided into negative fluid responsiveness group and positive fluid responsiveness group according to the fluid responsiveness after volume expansion.The receiver operating characteristic curves of the parameters mentioned above in predicting fluid responsiveness were drawn.A consistency check for dIVC,△VTI and SVVPiCCO thresholds was conducted by using Kappa statistics.The agreement between SVVTTEand SVVPiCCO was analyzed by the Bland-Altman analysis.Results There were 24 patients in positive fluid responsiveness group and 22 patients in negative fluid responsiveness group.Compared with negative fluid responsiveness group,the plasma BNP concentration,CVP and GEDVI were significantly decreased,and SVVPiCCO,SVVTTE,dIVC and △VTI were increased before volume expansion in positive fluid responsiveness group (P＜0.05).The area under the curve (95％ confidence interval),sensitivity and specificity of the plasma BNP concentration were 0.894 (0.807-0.981),81.8％ and 79.2％,respectively,of CVP 0.859 (0.752-0.965),81.8％ and 79.2％,respectively,of GEDVI 0.772 (0.628-0.915),72.7％ and 75.0％,respectively,of SVVPiCCO 0.965 (0.922-1.008),95.8％ and 81.8％,respectively,of SVVTTE 0.940 (0.874--1.006),91.7％ and 86.4％,respectively,of dIVC 0.964 (0.920-1.008),83.3％ and 95.5％,respectively,and of △VTI 0.958 (0.909-1.008),87.5％ and 90.9％,respectively.The Kappa value for dIVC threshold and SVVPiCCO threshold was 0.826,and for △VTI threshold and SVVPiCCO threshold was 0.743 (P＜0.01).The mean deviation of SVVTTE and SVVPiCCO was 0.209,95％ confidence interval (-2.967-3.385)％,and the limit of agreement (-2.46-2.62)％ (P＜ 0.05).Conclusion Ultrasound and PiCCO methods can accurately predict fluid responsiveness,have a good agreement and are superior to the traditional method in septic patients.

The ultrasonic monitoring coupled with passive leg raising test for evaluation of fluid responsiveness in critical patients / 中华急诊医学杂志

Objective To explore the value of predicting fluid responsiveness using velocity time index variation (△VTI) and stroke volume variation (△SV) before and after passive leg raising (PLR)monitored by bedside temporary test equipment (TTE).Methods A cohort of 42 patients supported with mechanical ventilation in our hospital admitted from October 2014 to October 2015 were prospectively selected.The hemodynamic variables including heart rate (HR),mean arterial pressure (MAP),central venous pressure (CVP),VTI,SV and other parameters were monitored before and after after undergoing PLR.Fluid resuscitation volume expansion test was carried out after stroke volume index (SVI) monitored by pulse indicator continuous cardiac output monitoring (PICCO).Patients were divided into fluid responsiveness positive group and fluid responsiveness negative group according to presence or absence of SVI ≥ 15％ after fluid resuscitation volume expansion.Results Of 42 patients,22 belonged to fluid responsiveness positive group,20 got into fluid responsiveness negative group.There were no significant differences in basic clinical data between two groups.Before and after PLR,there were no distinct changes in HR and CVP (P ＞ 0.05),while MAP,VTI and SV increased significantly (P ＜ 0.05) after PLR in fluid responsiveness positive group.Contrarily,there were no noticeable changes in MAP and SV after PLR (P ＞ 0.05),but HR,CVP and VTI increased significantly (P ＜ 0.05) in fluid responsiveness negative group.The degrees of △VTI and △SV in fluid responsiveness positive group were much higher than those in fluid responsiveness negative group (P ＜0.05).According to SVI ≥ 15％ monitored by PICCO after fluid resuscitation volume expansion test as a standard,the area under the ROC (AUC) of △VTI between prePLR and post-PLR was 0.75 (95％ CI:O.593-0.907,P ＜ 0.01),the sensitivity and specificity were 63.6％ and 95％ respectively using △VTI 15.6％ as threshold value.The AUC of △SV was 0.844 (95％CI:O.716-0.972,P ＜0.01),the sensitivity and specificity were 81.8％ and 85.0％ respectively using △SV 10.5％ as threshold value.Conclusion △VTI and △SV monitored by TTE before and after PLR could be employed for predicting fluid responsiveness of critical patients under the status of spontaneous respiration.Their value for prediction of critical patients could be further improved by combined employment of these two indexes of variation.

Regulatory effect of the leaves of Rehmannia glutinosa Libosch on intestinal microflora in diabetic nephropathy rats / 药学学报

The aim of this study was to investigate the regulatory effect of the total glycoside extracted from leaves of Rehmannia (TLR) and Dihuangye total glycoside capsule (DTG) on intestinal microflora in diabetic nephropathy rats. Forty-eight rats were randomly divided into the control group (C), model group (M), Huangkui capsule group (0.75 g·kg-1·d-1, HK), irbesartan group (27 mg·kg-1·d-1, YX), TLR low dose group (4.3 g·kg-1·d-1, DHYL), TLR high dose group (7.2 g·kg-1·d-1, DHYH), DTG low dose group (216 mg·kg-1·d-1, JNL), DTG high dose group (360 mg·kg-1·d-1, JNH). Rat model of diabetic nephropathy was induced by intraperitoneal injection of small dose of streptozotocin (45 mg·kg-1, STZ) and feeding high-fat diet and 5% glucose drinking water. After oral administration for two weeks, the 16S rDNA sequencing method was used to study the effects of the TLR and DTG on intestinal flora in diabetic nephropathy rats. The results showed that compared with the control group, the intestinal flora of diabetic nephropathy rats had changed from phylum units to the genus units. Moreover, the proportion of lactobacilli in the intestinal bacteria of the model group was significantly decreased, and the proportion of lactobacilli in the administration group was increased, especially the YX group, TLR low dose group and DTG low dose group. The data suggest that the total glycosides of Rehmannia glutinosa improved the disorder of intestinal flora in STZ-induced diabetic nephropathy rats.

Curative efficacy of compound tanshin injection and acupuncture and moxibustion in treatment of peripheral nerve injury its effects on nerve function / 中国生化药物杂志

Objective To study curative efficacy of compound tanshin injection and acupuncture and moxibustion in treatment of peripheral nerve injury its effects on nerve function.Methods 110 patients of peripheral nerve injury whoreceived therapy from April 2014 to September 2014 in our hospital were selected as research objects,according to the treatment were divided into observation group and control group,observation group using curative efficacy of compound tanshin injection,the control group using compound tanshin injection and low frequency dc therapy.Observe clinical efficacy of the two groups after treatment,compared two groups before and after treatment can motor nerve and sensory nerve nerve conduction velocity,and to evaluate the basic function after treatment.Results After treatment,the observation group total effectiveness 94.5％,obviously higher than the control group total effectiveness 81.8％,significant difference(P< 0.05); Observation group after treatment of nerve function was 80.0％,significantly higher than the control group was 60.0％,significant difference(P<0.05); And after the treatment of motor nerve and sensory nerve conduction velocity observation group were significantly higher than the control group,significant difference(P<0.05).Conclusion Curative of compound tanshin injection and acupuncture and moxibustion in treatment of peripheral nerve injury,can significantly improve patients with nerve function,improve the effect of treatment,and no side effect,is worth popularizing in clinic.

Growth factor composite scaffolds for bone defect repair via immediate implantation of bone defects / 中国组织工程研究

BACKGROUND:Nerve growth factor has been shown to play an important role in bone healing, but little is reported on the effect of growth factor composite scaffolds via the immediate implantation in the repair of canine bone defects. OBJECTIVE:To analyze the effect of nerve growth factor composite scaffolds via the immediate implantation for the repair of canine bone defects. METHODS:Nerve growth factor composited strontium apatite scaffolds were prepared. Canine mandibular defect models were established and divided into three groups, fol owed by implanted with composite scaffold (experimental group), strontium apatite (positive control group), or nothing (blank control group). The three-dimensional CT reconstruction and hematoxylin-eosin staining of canine mandibular bone defects were observed. RESULTS AND CONCLUSION:In the blank control group, there were few new bones surrounding bone defect. Trabecular bones spread from the defect center to the surrounding tissues in the experimental and positive control groups. The bone density, volume, thickness, and implant-bone contact were significantly increased, while the trabecular separation was significantly decreased in the experimental group compared with the positive control and blank control groups (P<0.05), and al above indicators in the positive contro group were significantly higher than those in the blank control group (P<0.05). Hematoxylin-eosin staining showed that in the experimental group, there were a large number of new bones that contacted with the surrounding bones closely, and trabecular bones arranged regularly. In the positive control group, newborn osteoid, trabeculare, and a smal amount of debris were found. In the blank control group, few new bones were connected with the surrounding bones untightly and trabecular bone arranged irregularly. These results indicate that the nerve growth factor composite scaffold can promote the bone regeneration in the canine bone defects after immediate implantation.

Titanium core/bone morphogenetic protein composite materials used to repair alveolar bone defects after immediate implant placement / 中国组织工程研究

BACKGROUND:Now experimental and clinical research on suitable bone substitutes for alveolar bone defects after dental implantation is an issue of concern.OBJECTIVE:To study the therapeutic effect of titanium core/bone morphogenetic protein (BMP) composite material on alveolar bone defects after immediate implant placement.METHODS:Twenty-four New Zealand rabbits were randomly assigned into normal group (no intervention),experimental group or control group.Animal models of bone femoral greater trochanter defect were made in the experimental and control groups.Dental implant and titanium core/BMP composite material were implanted in the experimental group,while dental implant and titanium core were implanted in the control group.Percentage of CD4+,CD8+ T lymphocytes,natural killer cell activity and interleukin 2 level were detected at postoperative 4 weeks;bone mineral density and osteogenesis around the implant were detected at postoperative 16 weeks through X-ray and histological examinations.RESULTS AND CONCLUSION:X-ray results showed that the bone mineral density in the experimental group was significantly higher than that in the control group (P ＜ 0.05).Histological results showed that in the experimental group,different degrees of cell lysis around the composite,more bone cells and bone matrices were found,implant-bone osseointegration formed well,and red-dyed mature bone tissues were detective inside the implant.Compared with the experimental group,lower number of bone cells and fibrocytes were found in the control group.Additionally,the percentage of CD4+ and CD8+ T lymphocytes,natural killer cell activity and interleukin 2 level in the experimental group were significantly lower than those in the control group (P ＜ 0.05).To conclude,the titanium core/BMP composite material can effectively repair alveolar bone defects after immediate implant placement to guide the growth of bone cells.

Incidence, Development, and Prognosis of Diabetic Kidney Disease in China: Design and Methods / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although that glomerulonephritis is the major cause of end-stage renal disease in developing countries such as China, the increasing prevalence of diabetes has contributed to the changing spectrum of predialysis chronic kidney disease. Recent studies have revealed an increased proportion of patients with diabetic kidney disease (DKD) in hemodialysis populations in large cities in China. However, studies regarding the clinical phenotype of DKD in China are extremely limited. The incidence, development, and prognosis of diabetic kidney disease (INDEED) study aims to investigate the incidence, progression, and prognosis of DKD, as well as the associated genetic, behavioral, and environmental factors and biomarkers in patients with DKD in China.</p><p><b>METHODS</b>INDEED study is a prospective cohort study based on all participants with diabetes in the Kailuan study, which is a general population-based cohort study in northern China. Altogether, over 10,000 participants with diabetes will be followed biennially. Questionnaires documenting general characteristics, behavioral and environmental factors, and medical history will be administrated. Anthropometric measurements and a series of laboratory tests will be performed in one central laboratory. The DNA, plasma, and urine samples of every participant will be stored in a biobank for future research.</p><p><b>CONCLUSIONS</b>INDEED study will provide essential information regarding the clinical phenotype and prognosis of patients with DKD in China and will be valuable to identify factors and biomarkers associated with patients with DKD in China.</p>