Polyphyllin I alleviates lipopolysaccharide-induced inflammation reduces pyroptosis in BEAS-2B and HPAEC cells by inhibiting NF-KB signaling

Polyphyllin I is an active steroidal saponin isolated from Paris polyphylla with anti-cancer and anti-inflammatory properties. The present study investigates the role of polyphyllin I in acute lung injury. Firstly, the human bronchial epithelial cells (BEAS-2B) and human pulmonary artery endo-thelial cells (HPAEC) were stimulated with increasing concentrations of lipopolysaccharide at 2, 5, and 10 μg/mL. The treatment with lipopolysaccharide reduced the cell viabilities of BEAS-2B and HPAEC, downregulated superoxide dismutase (SOD) and glutathione (GSH), and up-regulated myeloperoxidase (MPO) and malondialdehyde (MDA). Moreover, the levels of TNF-α, I L-1β, and IL-6 were also up-regulated in lipopolysaccharide-treated BEAS-2B/HPAEC cells. Secondly, the lipopolysaccharide-treated cells were then incubated with different concentrations of polyphyl-lin I. Incubation with polyphyllin I enhanced the cell viabilities of lipopolysaccharide-treated BEAS-2B/HPAEC, up-regulated levels of SOD and GSH, and reduced MPO and MDA. Moreover, polyphyllin I reduced TNF-α, I L-1β, and IL-6 in lipopolysaccharide-treated BEAS-2B/HPAEC cells. Thirdly, the up-regulation of GSDMD-N, pro-caspase-1, and cleaved caspase-1 proteins in lipo-polysaccharide-treated BEAS-2B/HPAEC cells were decreased by polyphyllin I. Polyphyllin I increased the protein expression of GSDMD-D in the lipopolysaccharide-treated BEAS-2B/HPAEC cells, and inhibited the translocation of GSDMD from cytoplasm to plasma membrane. Lastly, polyphyllin I reduced the expression of p-p65 in lipopolysaccharide-treated BEAS-2B/HPAEC cells. The over-expression of p65 counteracted with the inhibitory effects of polyphyllin I on oxi-dative stress and inflammation in lipopolysaccharide-treated BEAS-2B. In conclusion, polyphyllin (AU)

Predictive values of ALBI and EZ-ALBI scores for early survival of recipients with liver failure after liver transplantation / 器官移植

Objective To evaluate the predictive values of albumin-bilirubin (ALBI) and easy albumin-bilirubin (EZ-ALBI) scores for early survival (postoperative 3 months) of recipients with liver failure after liver transplantation. Methods Clinical data of 137 recipients diagnosed with liver failure and underwent liver transplantation were retrospectively analyzed. The optimal cut-off values of preoperative ALBI, EZ-ALBI and MELD scores to predict early survival of recipients with liver failure after liver transplantation were determined by the area under the receiver operating characteristic (ROC) curve. The risk factors of early death of recipients with liver failure after liver transplantation were identified by univariate and multivariate Cox regression analyses. The effects of different ALBI and EZ-ALBI levels upon early prognosis of recipients with liver failure after liver transplantation were analyzed. Results The optimal cut-off values of ALBI, EZ-ALBI and MELD scores were 0.21, -19.83 and 24.36, and the AUC was 0.706, 0.697 and 0.686, respectively. Univariate Cox regression analysis showed that preoperative alanine aminotransferase(ALT)≥50 U/L, aspartate aminotransferase(AST)≥60 U/L, ALBI score≥0.21 and EZ-ALBI score≥-19.83 were the risk factors for early postoperative death of recipients with liver failure after liver transplantation (all P < 0.05). Multivariate Cox regression analysis demonstrated that preoperative ALBI score≥0.21 was an independent risk factor for early postoperative death of recipients with liver failure after liver transplantation (P < 0.05). According to the optimal cut-off value of ALBI score, the early survival rates in the ALBI < 0.21 (n=46) and ALBI≥0.21(n=91) groups were 93.5% and 64.8%, and the difference was statistically significant (P < 0.05). According to the optimal cut-off value of EZ-ALBI score, the early survival rates in the EZ-ALBI < -19.83(n=60) and EZ-ALBI≥-19.83(n=77) groups were 88.3% and 63.6%, and the difference was statistically significant (P < 0.05). Conclusions Preoperative ALBI score is of high predictive value for early survival of recipients with liver failure after liver transplantation, which could be utilized as a reference parameter for selecting liver transplant recipients.

Genomic evidence for divergent co-infections of SARS-CoV-2 lineages

Recently, patients co-infected by two SARS-CoV-2 lineages have been sporadically reported. Concerns are raised because previous studies have demonstrated co-infection may contribute to the recombination of RNA viruses and cause severe clinic symptoms. In this study, we have estimated the compositional lineage(s), tendentiousness, and frequency of co-infection events in population from a large-scale genomic analysis for SARS-CoV-2 patients. SARS-CoV-2 lineage(s) infected in each sample have been recognized from the assignment of within-host site variations into lineage-defined feature variations by introducing a hypergeometric distribution method. Of all the 29,993 samples, 53 (~0.18%) co-infection events have been identified. Apart from 52 co-infections with two SARS-CoV-2 lineages, one sample with co-infections of three SARS-CoV-2 lineages was firstly identified. As expected, the co-infection events mainly happened in the regions where have co-existed more than two dominant SARS-CoV-2 lineages. However, co-infection of two sub-lineages in Delta lineage were detected as well. Our results provide a useful reference framework for the high throughput detecting of SARS-CoV-2 co-infection events in the Next Generation Sequencing (NGS) data. Although low in average rate, the co-infection events showed an increasing tendency with the increased diversity of SARS-CoV-2. And considering the large base of SARS-CoV-2 infections globally, co-infected patients would be a nonnegligible population. Thus, more clinical research is urgently needed on these patients.

Research progress of immune checkpoint inhibitors in the treatment of lung cancer / 国际肿瘤学杂志

In recent years, immune checkpoint inhibitors are a milestone in the treatment of lung cancer. There are many kinds of immune checkpoints, which are closely related to the efficacy and drug resis-tance of immunotherapy, including programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), killer cell immunoglobulin-like receptor (KIR), T cell immunoglobulin and ITIM domain (TIGIT), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), etc. PD-1/PD-L1 inhibitors have been approved by China National Medical Products Administration and U. S. Food and Drug Administration for the first-line treatment of lung cancer, which can improve overall survival and progression-free survival of patients. The double immunotherapies of CTLA-4 inhibitors or TIGIT inhibitors combined with PD-1/PD-L1 inhibitors also achieve good results, however, more serious adverse events may occur.The KIR and TIM-3 targets are closely related to the drug resistance of immunotherapy.

The cellular immunotherapy of integrated photothermal anti-oxidation Pd-Se nanoparticles in inhibition of the macrophage inflammatory response in rheumatoid arthritis

Reducing the inflammatory response is a major goal in the therapy of rheumatoid arthritis (RA). Herein, we integrated palladium nanoparticles (Pd NPs) with selenium nanoparticles (Se NPs) and obtained a multiple nanosystem (Pd@Se-HA NPs) that could simultaneously scavenge hydroxyl radicals (⋅OH) and provide a photothermal effect. The Pd@Se-HA NPs were constructed by a simple self-assembly method in which Se NPs were electrostatically bonded to Pd NPs; hyaluronic acid (HA) was linked to the NPs by ester bonding to provide macrophage targeting ability. The experiments show that the combined therapy of eliminating ⋅OH with Se NPs and utilizing PTT with Pd NPs could effectively reduce the inflammatory response in macrophages more effectively than either individual NP treatment. In addition, the outer layer of HA could specifically target the CD44 receptor to enhance the accumulation of Pd@Se NPs at the lesion, further enhancing the therapeutic effect. After treatment for 15 days, the Pd@Se-HA NPs nearly eliminated the inflammatory response in the joints of mice in an induced RA model, and prevented joint damage and degradation.

Efficacy and Safety of Eplerenone in the Treatment of Essential Hypertension ：Reevaluation of Systematic Review/Meta-analysis / 中国药房

OBJECTIVE：To reeval uate the systematic review/Meta-analy sis of efficacy and safety of eplerenone in the treatment of essential hypertension. METHODS ：Retrieved from PubMed ，Embase，Cochrane Library ，Web of Science ，Wanfang database，CNKI，VIP，systematic review/Meta-analysis about eplerenone in the treatment of essential hypertension were collected from the inception to June 24th，2021. After literature screening and data extraction ，the quality of included literatures were evaluated with PRISMA statement ；methodology quality of included literatures were evaluated with AMSTAR 2 scale；GRADE method was adopted to evaluate the evidence quality of outcome measures. Efficacy and safety index evaluation of included literatures were summeried. RESULTS ：A total of 8 systematic reviews/Meta-analyses were included ，involving 5 systematic reviews and 3 Meta-analysis，including 73 outcome indicators. PRISMA scores ranged from 7.5 to 23.5，including 6 literatures （75.0％）with≤15 points，1（12.5％）with ＞15-＜21 points and 1（12.5％）with ≥21 points. The results of AMSTAR 2 evaluation indicated that the methodological quality of 2 studies was low ，and that of 6 studies was very low . GRADE quality evaluation results showed that there were 3 high quality indicators ，24 medium quality indicators and 46 low or very low quality indicators；the factors contributed to downgrading evidence quality were limitation ，inconsistency，imprecision and publication bias. In terms of efficacy ，compared with placebo ，eplerenone could significantly reduce clinical blood pressure （CBP）and 24-hour ambulatory blood pressure （ABP）. Its effect in reducing CBP was significantly better than other antihypertensive drugs or equivalent to other antihypertensive drugs. The effects of eplerenone on reducing clinical systolic blood pressure was not as good as spironolactone and enalapril ，or bett er than calcium channel blocker ，enalapril and angiotensin receptor antag onist，or equivalent to calcium channel blocker and enalapril ；the effect of eplerenone on reducing clinical diastolic blood pressure was not as good com as spironolactone ，calcium c hannel blocker and enalapril ，or as good as enalapril ，but better than angiotensin receptor antagonist. In terms of safety ，there was no significant difference in the incidence of ADR ，serious ADR or hyperkalemia caused by eplerenone ，compared with placebo ，or the incidence of ADR was higher than that of placebo. There was no statistical significance in the incidence of ADR or serious ADR ，compared with other antihypertensive drugs. CONCLUSIONS ：Efficacy and safety of eplerenone in the treatment of essential hypertension was good ，but in view of the poor methodological quality of systematic reviews or Meta-analysis and the low or very low level of outcome indicator evidence ，the authenticity and effectiveness of the conclusion will be reduced ，so that those indcaters should be interpreted carefully.

Comparative transcriptome analysis reveals the intensive early-stage responses of host cells to SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a widespread outbreak of highly pathogenic COVID-19. It is therefore important and timely to characterize interactions between the virus and host cell at the molecular level to understand its disease pathogenesis. To gain insights, we performed high-throughput sequencing that generated time-series data simultaneously for bioinformatics analysis of virus genomes and host transcriptomes implicated in SARS-CoV-2 infection. Our analysis results showed that the rapid growth of the virus was accompanied by an early intensive response of host genes. We also systematically compared the molecular footprints of the host cells in response to SARS-CoV-2, SARS-CoV and MERS-CoV. Upon infection, SARS-CoV-2 induced hundreds of up-regulated host genes hallmarked by a significant cytokine production followed by virus-specific host antiviral responses. While the cytokine and antiviral responses triggered by SARS-CoV and MERS-CoV were only observed during the late stage of infection, the host antiviral responses during the SARS-CoV-2 infection were gradually enhanced lagging behind the production of cytokine. The early rapid host responses were potentially attributed to the high efficiency of SARS-CoV-2 entry into host cells, underscored by evidence of a remarkably up-regulated gene expression of TPRMSS2 soon after infection. Taken together, our findings provide novel molecular insights into the mechanisms underlying the infectivity and pathogenicity of SARS-CoV-2.

Mutations, Recombination and Insertion in the Evolution of 2019-nCoV

BackgroundThe 2019 novel coronavirus (2019-nCoV or SARS-CoV-2) has spread more rapidly than any other betacoronavirus including SARS-CoV and MERS-CoV. However, the mechanisms responsible for infection and molecular evolution of this virus remained unclear. MethodsWe collected and analyzed 120 genomic sequences of 2019-nCoV including 11 novel genomes from patients in China. Through comprehensive analysis of the available genome sequences of 2019-nCoV strains, we have tracked multiple inheritable SNPs and determined the evolution of 2019-nCoV relative to other coronaviruses. ResultsSystematic analysis of 120 genomic sequences of 2019-nCoV revealed co-circulation of two genetic subgroups with distinct SNPs markers, which can be used to trace the 2019-nCoV spreading pathways to different regions and countries. Although 2019-nCoV, human and bat SARS-CoV share high homologous in overall genome structures, they evolved into two distinct groups with different receptor entry specificities through potential recombination in the receptor binding regions. In addition, 2019-nCoV has a unique four amino acid insertion between S1 and S2 domains of the spike protein, which created a potential furin or TMPRSS2 cleavage site. ConclusionsOur studies provided comprehensive insights into the evolution and spread of the 2019-nCoV. Our results provided evidence suggesting that 2019-nCoV may increase its infectivity through the receptor binding domain recombination and a cleavage site insertion. One Sentence SummaryNovel 2019-nCoV sequences revealed the evolution and specificity of betacoronavirus with possible mechanisms of enhanced infectivity.

Prediction of receptorome for human-infecting virome

The virus receptors are key for the viral infection of host cells. Identification of the virus receptors is still challenging at present. Our previous study has shown that human virus receptor proteins have some unique features including high N-glycosylation level, high number of interaction partners and high expression level. Here, a random-forest model was built to identify human virus receptorome from human cell membrane proteins with an accepted accuracy based on the combination of the unique features of human virus receptors and protein sequences. A total of 1380 human cell membrane proteins were predicted to constitute the receptorome of the human-infecting virome. In addition, the combination of the random-forest model with protein-protein interactions between human and viruses predicted in previous studies enabled further prediction of the receptors for 693 human-infecting viruses, such as the Enterovirus, Norovirus and West Nile virus. As far as we know, this study is the first attempt to predict the receptorome for the human-infecting virome and would greatly facilitate the identification of the receptors for viruses.

Effect of early enteral feeding on clinical outcome in critically ill patients with hemodynamic instability / 中华急诊医学杂志

objective:To investigate the tolerability of early enteral nutrition (EN), and to further explore the association of early EN with clinical outcome in critically ill patients with hemodynamic instability.Methods:The adult patients from Zhejiang Provincial People’s Hospital with an expected admission to ICU for at least 24 h were consecutively recruited from May 2014 to May 2016, and all clinical, laboratory, and survival data were prospectively collected. The AGI grade was daily assessed on the first week of ICU admission. Enteral nutrition (EN) started after 6 h of hemodynamic stability (MAP ≥ 65 mmHg) when the patients took vasoactive medication. The patients were divided into three groups based on the timing of EN initiation: early EN group (EN initiation within 48 h of ICU admission), late EN group (EN initiation at more than 48 h of ICU admission), and no initiation of enteral feeding within 7 days of ICU admission.Results:Of 201 patients enrolled, the mean age was 65.3 ± 16.4 years, APACHE II score was 22.4 ± 6.85, and 191 patients (95.0%) took mechanical ventilation. There were no differences in high gastric residual volume, diarrhea, and gastrointestinal (GI) bleeding between the early EN group and late EN group ( P>0.05). Whereas, patients in the no initiation of EN within 7 days of ICU admission had a lower prevalence of gastric residual volume (16.7% vs. 33.3%, P=0.05), but higher prevalence of GI bleeding (47.2% vs. 26.1%, P=0.02). Compared with those in the late EN group and in no initiation of EN within 7 days of ICU admission, patients in the early EN group had lower 28- (30.4% vs. 47.9% vs. 55.6%, P=0.01) and 60-day mortality rates (38.0% vs. 53.4% vs. 63.9%, P=0.017). Multivariate Cox regression analysis showed that the timing of EN initiation on the admission to ICU (early EN vs. late EN, χ 2≥5.83, P<0.05; early EN vs. no initiation of EN, χ 2≥7.90, P<0.01), serum creatinine ( χ 2=5.06, P<0.05), plasma albumin ( χ 2≥6.41, P<0.01), AGI grade ( χ 2≥8.15, P<0.01), and APACHE II score ( χ 2≥9.62, P<0.01) were independent predictors for 28- and 60-day mortality. Conclusions:Early EN on admission to ICU could be tolerated, and is significantly associated with lower risk of 28- and 60-day mortality in critically ill patients with vasoactive medication to maintain hemodynamic stability.

Influence of N-acetylcysteine on FEV1, VC, DLCO, PaO2 in patients with chronic obstructive pulmonary disease and pulmonary interstitial fibrosis / 中国基层医药

Objective@#To investigate the influence of N-acetylcysteine on forced expiratory volume in one second(FEV1), vital capacity(VC), diffusion capacity of lung carbon monoxide(DLCO), arterial oxygen partial pressure(PaO2) in patients with chronic obstructive pulmonary disease(COPD) and pulmonary interstitial fibrosis.@*Methods@#From January 2015 to July 2017, 140 COPD patients complicated with pulmonary interstitial fibrosis in the People's Hospital of Shanxi Province were chosen as study objects, and they were divided into control group and research group according to the digital table, with 70 cases in each group.The control group was treated with routine treatment, while the research group was treated with N-acetylcysteine.After treatment, the treatment effects, VC, FEV1, PaO2, DLCO, TGF-β and VEGF between the two groups were compared.@*Results@#The total effective rate of the research group was 82.86%(58/70), which of the control group was 58.57%(41/70), the difference was statistically significant (χ2=9.968, P<0.05). Before treatment, the pulmonary function between the two groups had no statistically significant difference(t=0.082, 0.028, 0.421, 0.155, all P>0.05). After treatment, the FEV1[(59.03±15.02)% vs.(53.35±13.71)%], VC[(69.95±11.83)% vs.(65.21±11.65)%], DLCO[(68.92±11.56)% vs.(64.01±11.34)%] and PaO2[(68.79±5.38)mmHg vs.(62.37±6.14)mmHg]of the research group were higher than those of the control group, the differences were statistically significant (t=2.337, 2.389, 2.537, 6.580, all P<0.05). Before treatment, the TGF-β and VEGF levels between the two groups had no statistically significant differences(t=1.230, 0.016, all P>0.05). After treatment, the VEGF[(0.32±0.04)ng/L vs.(0.44±0.05)ng/L] and TGF-β[(271.16±35.21)ng/L vs.(345.13±39.08)ng/L] levels of the research group were lower than those of the control group, the differences were statistically significant (t=11.765, 15.680, all P<0.05). There was no statistically significant difference in the incidence rate of adverse reactions between the two groups(1.43% vs 4.28%, χ2=2.323, P>0.05).@*Conclusion@#Large dose of N-acetylcysteine can effectively improve the TGF-β and VEGF levels of COPD patients complicated with pulmonary interstitial fibrosis, and promote its pulmonary function, with good safety.

Biliary complications and recovery of liver function after liver transplantation from citizen's deceased donors versus standard criteria donors / 中华肝胆外科杂志

Objective To investigate the biliary complications and recovery of liver function after liver transplantation from citizen's deceased donors (DCD) versus standard criteria donors (SCD).Method The clinical data of 269 patients who underwent orthotopic liver transplantation from January 2009 to December 2016 at the Fuzhou General Hospital were collected.197 livers were from SCD and 72 from DCD.Propensity score matching (PSM) was used to compare the biliary complications and recovery of liver function after liver transplantation in the two groups.Results PSM matched 61 pairs of patients.There were 10 (16.4％) and 8 (13.1％) biliary complications in the DCD and the SCD groups,respectively,with no significant difference between them (P ＞ 0.05).The recovery of liver function was significantly delayed in the DCD group when compared with the SCD group.The levels of ALT,AST,GGT and AKP in the DCD group were significant different on the postoperative first,third,fifth,seventh and fourteenth day (P ＜ 0.05).At 30 days after surgery,there was no significant difference in liver function between the two groups.Conclusions Liver grafts from DCD had a significant impact on the recovery of liver function.When compared with the SCD group,the DCD group recovered significantly slower in liver function.There was no significant increase in the incidence of biliary complications.

Liver transplantation for treatment of hilar cholangiocarcinoma with a report of three Cases / 国际外科学杂志

Objective To investigate the feasibility of liver transplantation in the treatment of inoperable hilar cholangiocarcinoma. Methods The clinical data for 3 patients with unresectable hilar cholangiocarcinoma who underwent liver transplantation in the Department of Hepatobiliary Surgery of Fuzhou General Hospital of People's Liberation Army from January 2006 to December 2012 were retrospectively analyzed. The patients were followed up by phone, outpatient service, and hospitalization. The starting point of the follow-up was the operation date. The patients death was the end point. The clinical and pathological features, postoperative survival, tumor recurrence, and prognostic factors were observed. The follow-up deadline was December 2017. Results All 3 patients underwent classical orthotopic liver transplantation using retrograde perfusion through inferior vena cava and no perioperative deaths occurred. All 3 patients were followed up for 10 to 132 months. During the follow-up period, of 1 patient who died of tumor recurrence, the pathological TNM stage was T4a N1 M0, and both had Union for International Cancer Control stage Ⅳa, and the tumor-free survival time was 3 months, and the survival time was12 months. Of 1 patient who died of other causes, the pathological TNM stage was T3N1 M0, and both had Union for International Cancer Control stage Ⅲ, and the tumor-free survival time was 12 months, and the survival time was12 months. One case as of the end of follow-up, the patient has survived for 132 months, the pathological TNM staging was T2a NOM0, and both had Union for International Cancer Control stage Ⅱ. Conclusions Lymph node positive and high pathological TNM stage were poor prognosis factor for hilar cholangiocarcinoma who underwent liver transplantation. Patients with early hilar cholangiocarcinoma who don't have lymph node metastasis are expected to benefit from liver transplantation.

Clinical value of the conventional liver function test in liver reserve function assessment for large hepatocellular carcinoma / 国际外科学杂志

Objective To study the clinical value of the conventional liver function tests in liver reserve function assessment for large hepatocellular carcinoma.Methods The clinicopathological data of 113 patients with ChildPugh A hepatocellular carcinoma who underwent radical resection with large hepatocellular carcinoma in the Department of Hepatobiliary Surgery of Fuzhou General Hospital of People's Liberation Army from January 2014 to December 2016 were retrospectively analyzed.The patients were divided into two groups according to the recovery of postoperative liver function,which 105 patients recovered well and 8 patients had hepatic decompensation among them.The liver function index of two groups were analyzed.Measurement data with approximately normal distribution were represented by and groups were compared using t test;measurement data with skewed or uneven disstribution were represented by M (range)and group werecompared using Man-Whitney U test;count data were compared using Fisher exact test;risk factors for postoperative liver dysfunction were analyzed using Logistic single factor and multivariate and ROC curve were drawn.Results Preoperative prothrombin time,international standardization ratio,platelet,prealbumin,total bilirubin,alkaline phosphatase,γ-glutamyl transpeptidase comparison between the two groups were statistically significant (Z =-1.983,-2.180,-2.608,-2.007,-3.577,-2.228,-2.575,P ＜ 0.05).Logistic univariate analysis showed that platelet,total bilirubin and prealbumin were the risk factors for the recovery of liver function of radical resection hepatic decompensation with large hepatocellular carcinoma.Logistic multivariate regression analysis showed that preoperative high total bilirubin and low preabumin were independent risk factors of radical resection hepatic decompensation with large hepatocellular carcinoma.Logistic univariate analysis showed that preoperative high total bilirubin and low prealbumin were not risk factors of radical resection liver failure with large hepatocellular carcinoma.The area under the curve of total bilirubin was 0.880,P =0.000,95％ CI:0.808-0.953,the sensitivity was 87.5％,specificity was 84.8％ and the area under prealbumin curve was 0.769,P =0.011,95％ CI:0.648-0.891,sensitivity was 75.2％,specificity was 77.5％ by the ROC curve.The best threshold of total bilirubin and prealbumin after radical resection with large hepatocellular carcinoma were 17.55 μmol/L and 0.18 g/L respectively by the ROC curve.Conclusion The Child-Pugh A patients in radical resection hepatic decompensation with large hepatocellular carcinoma recover well when the preoperative liver function is as follows:total bilirubin ＜ 17.55 μmol/L and prealbumin ≥0.18 g/L.

Correlation between shock index and severity of septic shock and its prognostic value / 中华危重病急救医学

Objective To discuss the correlation between shock index (SI) and severity and the values to forecast the prognosis in patients with septic shock. Methods 127 patients with septic shock admitted to intensive care unit (ICU) of Zhejiang Provincial People's Hospital from January 1st, 2016 to October 31st, 2017 were enrolled, and they were divided into survival group and death group according to the outcomes after 28-day hospitalized. The vital signs, laboratory indexes, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ), sequential organ failure assessment (SOFA), lactate clearance rate (LCR) of 3 hours after fluid resuscitation, and shock index on admission (SI1) and shock index of 3 hours after fluid resuscitation (SI2) were compared between the two groups. The correlation among SI and APACHE Ⅱ, SOFA, LCR was analyzed. The receiver operating characteristic curve (ROC) was drawn to evaluate the prognostic value of SI in patients with septic shock. Results A total of 127 patients were included, 52 in survival group (40.9%) and 75 in death group (59.1%). The SI1, SI2, APACHE Ⅱ and SOFA in the death group were significantly higher than those in the survival group (SI1: 1.62±0.46 vs. 1.35±0.32, SI2: 1.36±0.24 vs. 0.93±0.15, APACHEⅡ:17.5±4.0 vs. 13.6±3.5,SOFA: 9.5±2.3 vs. 6.3±1.5), and LCR was significantly lower than that in the survival group [(14.4±5.2)% vs. (28.6±8.6)%], with statistically significant differences (all P < 0.01). The correlation analysis showed that SI1was significantly positively correlated with APACHEⅡ (r = 0.458, P = 0.000) and SOFA (r = 0.535, P = 0.000), SI2was also significantly positively correlated with APACHEⅡ (r = 0.624, P = 0.000) and SOFA (r = 0.656, P = 0.000), while SI1and SI2were significantly negatively correlated with LCR (r values were -0.348, -0.435, both P = 0.000), and the SI2were more remarkable. ROC curve analysis showed that the area under ROC curve (AUC) of SI1for predicting the prognosis of septic shock was 0.720 [95% confidence interval (95%CI) = 0.620-0.831, P < 0.05]; when SI1= 1.68, the sensitivity, specificity, Yoden index, positive predictive value and negative predictive value were 79.5%, 65.6%, 0.451, 0.759 and 0.636, respectively. The AUC of the SI2to predict prognosis of septic shock was 0.826 (95%CI =0.739-0.826, P < 0.05); when SI2= 1.37, the sensitivity, specificity, Yoden index, positive predictive value and negative predictive value were 85.7%, 87.6%, 0.733, 0.893 and 0.902, respectively. Conclusion Compared with SI1, SI2was more correlated with the severity in patients with septic shock and it had more values to predict prognosis.

Relationship Between Blood Triglyceride Level and Brachial-ankle Pulse Wave Velocity in Relevant Population / 中国循环杂志

Objective: To investigate the relationship between blood triglyceride (TG) level and brachial-ankle pulse wave velocity (baPWV) in relevant population. Methods: A total of 22622 participants in Kailuan area were enrolled and divided into 4 ranks: Stroke rank, n=5219, Aged rank n=1754, Pregnancy hypertension Rank, n=1561and Peripheral vascular diseases rank, n=14088. All participants finished baPWV examination. The relationship between TG and baPWV was studied by partial correlation analysis, the impact of TG on baPWV was assessed by multivariate linear regression and multivariate Logistic regression analysis. Results: There were 21713 subjects finally enrolled for cohort study and 909 subjects excluded for missing TG information. With elevated TG levels, the average baPWV and the detection rate of baPWV≥1400 cm/s showed the increasing trend. Partial correlation analysis presented that TG level was positively related to baPWV, r=0.235; with adjusted age and gender, TG was still positively related to baPWV, r=0.080. Logistic regression analysis indicated that with other adjusted confounding factors, compared with the first quartile of TG, the second quartile, third quartile and fourth quartile of TG were the risk factors for baPWV≥1400 cm/s, OR=1.161, 95% CI (1.035-1.302), OR=1.312, 95% (1.165-1.476) and OR=1.652, 95% CI (1.463-1.865) respectively. Conclusion: Blood TG level was positively and independently related to baPWV in relevant population.

The association between feeding intolerance and clinical outcome in critically ill patients admitted to ICU: a multi-center prospective, observational study / 中华急诊医学杂志

Objective To investigate the prevalence of feeding intolerance (FI),and to explore the FI within 7 days of ICU admission in association with clinical outcome in critically ill patients.Methods The adult patients from 14 general ICUs in Zhejiang Province with an expected admission to ICU for at least 24h were recruited from March 2014 to August 2014,and all clinical,laboratory,and survival data were prospectively collected.The AGI (acute gastrointestinal injury) grade was daily assessed based on gastrointestinal (GI) symptoms,feeding details and organ dysfunction within the first week of ICU stay.The intra-abdominal pressures (IAP) was measured using AbViser device.Results Of 550 patients enrolled,418 were assessed in GI symptoms and feeding details within 7 days of ICU stay.The mean age and SOFA score were (65.1 ± 18.3) years and (8.96 ±4.10),respectively.Of them,355 patients (84.9％) were under mechanical ventilation support,and 37 (8.85％) received renal replacement therapy.The mean length of time for enteral feeding was (30.8 ±26.2) h,and the prevalence of FI on the 3rd and 7th day of ICU stay accounted for 39.2％ and 25.4％,respectively.Compared to those with FI within 7 days of ICU stay,the patients without FI had higher rate of successively weaning from mechanical ventilation (21.3％ vs.5.7％,P =0.003) and higher rate of withdrawal of vasoactive medication (45.5％ vs.20.0％,P =0.037),as well as lower mortality rate of 28-day (24.4％ vs.38.7％,P =0.004) and 60-day (29.6％ vs.44.3％,P =0.005).In multivariate Cox regression model with adjustment for age,sex,participant center,serum creatinine and lactate,AGI grade on the first day of ICU stay,and comorbidities,the FI within 7 days of ICU stay (x2 ≥ 7.24,P ＜ 0.01) remained to be independent predictors for 60-day mortality.After further adjusted for SOFA score,the FI within 7 days of ICU stay (HR =1.71,95％ CI:1.18-2.49;P =0.006) and AGI grade on the first day of ICU stay (HR =1.33,95 ％ CI:1.07-1.65;P =0.009) could provide independent prognostic values of 60-day mortality.Conclusions There is high rate of FI occurred within 7 days of ICU stay,and is significantly associated with worse outcome.In addition,this study also provides evidence to further support that measurement of gastrointestinal dysfunction could increase value of SOFA score in outcome prediction for the risk of 60-day mortality.

Correlation between long time systolic blood pressure variability and short time systolic blood pressure in aged population / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the correlation between long time systolic blood pressure variability(SBPV)and short time SBPV in aged population.</p><p><b>METHODS</b>A total of 752 subjects aged ≥60 years of Kailuan Group who took part in 2006-2007, 2008-2009, 2010-2011 and 2012-2013 health examination were included by cluster sampling method.Long time SBPV was calculated by standard deviation of mean systolic blood pressure measured in 2006-2007, 2008-2009, 2010-2011 and 2012-2013, standard deviation represents short time systolic blood pressure which is derived from 24 hour ambulatory blood pressure monitoring. The observation population was divided into three groups according to the third tertiles of the time systolic blood pressure variability: the first point(<9.09 mmHg (1 mmHg=0.133 kPa)), second point (≥9.09 mmHg, and <14.29 mmHg), and third point (≥14.29 mmHg). Multivariate logistic regression analysis was used to analyze the correlation between long time systolic blood pressure variability and short time systolic blood pressure.</p><p><b>RESULTS</b>(1) The participants' age were (67.0±5.7) years old (284 women). (2) The 24 hours and daytime SSD were (14.7±4.0) mmHg, (14.7±3.5) mmHg, (15.7±4.4) mmHg (P=0.010) and (14.1±4.4) mmHg, (14.2±3.5) mmHg and (15.4±4.6) mmHg (P<0.001) according to the tertiles of long time systolic blood pressure variability, respectively, nighttime SSD were (12.0±4.4) mmHg, (11.8±4.8) mmHg and (11.9±4.9) mmHg (P=0.900). (3) Multiple logistic regression analysis showed that the tertiles of long time SSD was the risk factor for increasing daytime SSD>14.00 mmHg (OR=1.51, 95%CI: 1.03-2.23, P=0.037), but not a risk factor for increasing 24 hours SSD>14.41 mmHg (OR=1.10, 95%CI: 0.75-1.61, P=0.639) and nighttime SSD>11.11 mmHg (OR=0.98, 95%CI: 0.67-1.42, P=0.899).</p><p><b>CONCLUSION</b>Increased long time SBPV is a risk factor for increasing daytime SBPV.</p>

Expression levels and significance of semaphorin3A and matrix metalloproteinase 14 in NSCLC / 中华胸心血管外科杂志

Objective To investigate the correlation between the expression levels of semaphorin3A and MMP14,and their subsequent prognostic significance in nonsmall cell lung cancer(NSCLC).Methods The expression of semaphorin3A and MMP14 protein levels was analyzed in 94 cases of NSCLC tissues and in 80 cases of normal lung tissues,using immunohistochemistry(IHC).Correlation and survival analysis were used to further investigate their association and prognostic value.The correlation analysis using Pearson test,and log-rank test for survival analysis.Results The NSCLC tissues exhibited a lower expression of semaphorin3A and a higher expression of MMP14 than in the control lung tissues.The downregulation of semaphorin3A and upregulation of MMP14 may promote pleural invasion,lymph node metastasis,vascular invasion and proliferating cell nuclear antigen expression.The expression of semaphorin3A was correlated with the maximum diameter of tumor.There was a negative correlation between the protein expression levels of semaphorin3A and MMP14 in NSCLC tissues.Conclusion The data suggest that lower expression of semaphorin3A and a higher expression of MMP14 may promote occurrence and development in NSCLC and that the combined detection of semaphorin3A and MMP14 protein may be a helpful tool in predicting the prognosis of NSCLC.

The exploration of experimental pathology teaching under the idea of translational medicine / 中华医学教育探索杂志

The basic medicine teaching must meet the clinical application,while the clinical practice should be timely feedback to basic medical teaching,which is the embodiment of the idea in the translational medicine.The experimental teaching is an important part of modern pathology teaching.We actively improve the experiment course and deepen the basic concept of translational medicine in the medical education development by adopting such approaches as using the problem-based learning method(PBL) to promote the link between basic courses and clinical pathology,integrating and optimizing the teaching content to promote the knowledge mastery and conducting molecular pathology research to promote the implementation of translational medicine.