Aim To study the effect of Lacidophilus exopolysaccharides(LAEPS) on immunity. Methods Effects of LAEPS on immunity were investigated by delayed type hypersensitivity reaction, haemolytic plaque assay and macrophage function assay in mice. Results LAEPS ip 7～8 day promoted delayed type hypersensitivity reaction, increased haemolytic plaque and enhanced macrophage function in a dose-dependent manner.Conclusion LAEPS is able to enhances immunity.

Objective To study the effects of pulse high volume hemofiltration (PHVHF) on the changes of Th17 cells (T helper 17 cells) and CD4 + CD25 + reguratory T cells (Treg cells) in peripheral blood of patients with sepsis and to evaluate the clinical value of this intervention. Methods The patients were included in this prospective study as per the criteria of sepsis set by America Chest Physicians College/America Society for Critic Care Medicine in 1992. The patients were excluded: ① immune system disorder, ② acute stroke, ③ myocardial infarction, ④ virus hepatitis,⑤ human immunodeficiency virus infection, ⑥ under immunosuppressive therapy. Forty patients (24 males, 16 females, aged from 25 to 75years) with sepsis in ICU were enrolled from January. 2008 to November. 2010. According to the severity of disease, the patients were divided into three groups; moderate sepsis group (n = 14, 8 males, 6 females) , severe sepsis group (n = 15, 9 males, 6 females) , and septic shock group (n = 11, 7 males, 4 females). The initially clinical data of three groups were comparable. Twenty healthy individuals served as controls. According to the mode of treatment, forty patients were also divided into two groups: conventional treatment group (group A, n= 15) in which patients were treated without PHVHF within 5 days after admission and trial group (group B, n=25) in which patients were treated with pulsed high volume hemofiltration (PHVHF) within 5 days after admission. In group B, high volume hemofiltration (70 mL · kg-1 · h-1) was given to patients for 6 ～ 8 hours, and then conventional continuous vein - vein hemofiltration (35 mL · kg-1 · h-1) for 16 ~ 18 hours. The total length of period for continuum blood scavenging was 24 hours as one cycle. The interval between two cycles of blood scavenging was 24 hours. The changes of Th17 cells and CD4+ CD25 + Treg cells of 40 patients were detected with flow cytometry on the 1st day and the 5th day after admission. The data were analyzed by using SPSS version 13. 0 software. Measurement data were analyzed with Paired-samples t-test, independent-samples t-test or one way ANOVA . Ratio of small samples was compared with fisher's exact test, and the correlation was analyzed by using Pearson correlation analysis. Results The rates of Th17 cells were( 0.91 ±0.38)%, (2.09 ±0. 53)% , (3.90 ±0. 80)% , and ( 1. 85 ±0.35)% in control, moderate sepsis, severe sepsis, and septic shock groups, respectively, while the rates of CD4+ CD25+ Treg cells were (0.39 ±0.23)%, (1. 72 ±0. 59)% , (2.72 ±0. 22)% , and (3. 55 ±0. 51)% , respectively. The rate of Thl7 cells on the 1st day was higher in severe sepsis group than that in other two groups ( P < 0. 05 ) without significant difference between septic shock and moderate sepsis groups ( P > 0. 05). Moreover , the rate of CD4+ CD25 + Treg cells was up - regulated on the 1st day in the following order from high to low: septic shock group > severe sepsis group > sepsis group (P < 0.05). The rates of Th17 cells and CD4 + CD25 + Treg cells in patients of group B decreased in greater degree than that did in patients of group A (P < 0.05 ). Conclusions The changes of Th17 cells and CD4 + CD25 + Treg cells may play an important role in pathogenesis of sepsis, and the pulsed high volume hemofiltration may be one of the effective treatments for the patients with sepsis by regulating the rates of Thl7 cells and CD4 + CD25 + Treg cells.

Objective To observe the effect of exposure of emphysema with intermittent hypoxia on oxidative stress injury of myocardial cells in rats. Methods Sixty male Wistar rats were divided randomly into four experimental groups(each n=15). The normal control group was bred normally. The emphysema group was exposed to cigarette smoke twice a day(once 30 minutes). The intermittent hypoxia(IH)group was exposed to intermittent hypoxia circumstance 8 hours/day,and the emphysema with IH group was exposed to cigarette smoke twice a day (once 30 minutes)and intermittent hypoxia circumstance 8 hours/day. Each group was exposed for 8 weeks. At the beginning of 9 weeks,the blood gas analysis was performed in 5 rats selected randomly from each group,and the rest rats were sacrificed and their hearts and lungs were taken. Under light microscope,the lung tissues stained with hematoxylin-eosin(HE)were examined. The lung pathology and the results of blood gas analysis showed that the emphysema with IH rat model was established successfully. The levels of malonaldehyde(MDA)and superoxide dismutase(SOD)in rat myocardium were measured by enzyme-linked immunosorbent assay(ELISA),and the subunit p22phox mRNA expressions of nicotinamide adenine dinucleotide phosphate(NADPH)-oxidase were detected by real-time reverse transcription-polymerase chain reaction(RT-PCR). Results Compared with the normal group, the MDA levels and p22phox mRNA expressions were increased obviously in emphysema group, IH group and emphysema with IH group〔MDA(μmol/g):2.93±0.54, 3.58±0.63, 4.51±0.72 vs. 1.75±0.56, p22phox mRNA:0.043±0.004,0.067±0.015,0.123±0.016 vs. 0.018±0.002,all P<0.05〕,but the activities of SOD were decreased significantly(U/mg:36.07±4.79,33.51±7.12,24.29±5.36 vs. 46.08±5.12,all P<0.05). In emphysema with IH group,the increase of MDA levels and p22phox mRNA expressions and decrease of SOD levels were more remarkable compared with those in emphysema group and IH group(all P<0.05). The expression of p22phox mRNA was positively correlated with MDA level(r=0.734,P<0.001). Conclusion The myocardial tissue oxidative stress injury in rats induced by emphysema with intermittent hypoxia exposure is more serious than that induced by exposure of either emphysema or intermittent hypoxia alone,NADPH oxidase possibly being the important medium of myocardial cell response to oxidative stress.

Objective To investigate the effect of intermittent hypoxia (IH) with pulmonary emphysema on the ex-pression of hypoxia inducible factor-1α(HIF-1α),Bax and Bcl-2, and the mechanism underlying the role of HIF-1αin he-patocyte apoptosis thereof. Methods Sixty rats were randomly divided into four groups: normal control group, rats were treated normally;IH group, rats were treated by 30 s nitrogen and then 90 s air, and rats were treated by from 9:00-17:00 daily;pulmonary emphysema group, rats were treated by smudging for half an hour, twice a day (8:00 and 18:00);IH with pul-monary emphysema group, rats were treated by 30 s nitrogen and then 90 s air from 9:00-17:00 daily. After exposure four-teen weeks, rats were killed. qRT-PCR assay was conducted to detect the expression of HIF-1α mRNA, Bax mRNA and Bcl-2 mRNA in live tissues. Results The expressions of HIF-1αmRNA, Bax mRNA and Bax/Bcl-2 were significantly higher in IH with pulmonary emphysema group than those in control group,IH group and pulmonary emphysema group (P<0.05). The expression level of Bcl-2 mRNA was significantly lower in IH with pulmonary emphysema group than that of con-trol group and pulmonary emphysema group (P < 0.05), but no significant difference compared with that of IH group (P >0.05). The levels of HIF-1αand Bax were positively correlated with the level of Bax/Bcl-2 (r=0.732 and 0.699),but the lev-els of HIF-1αand Bax were negatively correlated with the level of Bcl-2 (r=-0.705). Conclusion The expression levels of HIF-1αmRNA, Bax mRNA and Bcl-2 mRNA were over-regulated in hepatocytes induced by intermittent hypoxia with pul-monary emphysema. The HIF-1αexpression was correlated with Bax and Bcl-2, suggesting that HIF-1αmay promote the hepatocyte apoptosis through transcriptional co-activators, Bax and Bcl-2.

Objective To explore the diagnostic value of Alzheimer-associated neuronal thread protein(AD7C-NTP)and olfactory function in the differentiation of three types of dementia,and to evaluate their clinical application value.Methods Mini-Mental State Examination (MMSE)and Montreal Cognitive Assessment(MoCA)were applied to evaluate cognitive function of all subjects with Alzheimer disease(AD),frontotemporal dementia (FTLD),or mixed dementia (MD).Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression levels of AD7c-NTP in urine.T&T test method was applied to detect the olfactory function.Spearman rank correlation was used to evaluate the correlation of urine AD7c NTP with MMSE and MoCA scores.Results There was no significant difference in the demographic profile (except age)among three types of dementia of AD,FTLD and MD(F =4.05,P =0.02).Among the three dementia groups,the mean age of the MD group was highest.The statistically significant difference in MMSE scores was found among the three groups(F 3.79,P=0.03),while there was no significant difference inMoCAand NPI scores among the three dementia groups.The levels of the urine AD7c-NTP were different among the three dementia groups,but without statistical significance(H 1.25,P =0.53).Additionally,the FTLD group had the highest urine AD7c NTP level.Spearman rank correlation analysis showed no correlation of AD7c-NTP with MMSE and MoCA(r =0.18,P =0.25;r =0.14,P =0.39,respectively).No differences in olfactory function of the recognition domain(H =3.40,P=0.18)and in the detection domain(H =2.07,P=0.36)were found among three dementia groups of AD,FTLD and MD.Conclusions The level of urine AD7c-NTP is not of clinical significance in differentiating three types of dementia,and it is not correlated with the MMSE and MoCA scores.This study fails to find the clinical value of olfactory function test for distinguishing three types of dementia.

Objective:To investigate the incidence, risk factors and early prognosis of acute kidney injury (AKI) after heart valve surgery in adults, and to provide evidence for the early prevention and treatment of AKI after heart valve surgery.Methods:Clinical data of patients undergoing heart valve surgery from January 2016 to March 2017 were collected retrospectively. Early postoperative AKI was diagnosed and staged according to Kidney Disease Improving Global Outcomes (KDIGO) clinical guidelines for AKI. Patients were divided into AKI group and non-AKI group according to whether AKI occurred within 48 hours after surgery, and the differences in clinical indexes between the two groups were compared and analyzed. Influencing factors for early postoperative AKI were screened by stepwise multivariate logistic regression.Results:A total of 600 patients were enrolled, including 197 patients in the AKI group and 403 patients in the non-AKI group. The incidence of AKI was 32.83%. In the non-AKI and AKI groups, proportion of renal replacement therapy (RRT) during hospitalization, mechanical ventilation time, intensive care unit (ICU) time and proportion of hospital mortality were different (all P<0.001). In the AKI group, 160 patients (81.22%) were in stage I, 33 patients (16.75%) were in stage Ⅱ, and 4 patients (2.03%) were in stage Ⅲ. The proportion of patients receiving RRT, mechanical ventilation time, ICU time, hospital mortality were also different in patients with AKI of different stages (all P<0.05). Logistic regression analysis results showed that males, body mass index≥24.0 kg/m 2, previous history of cardiac surgery, baseline serum creatinine >115 mmol/L, albumin<35 g/L, aortic occlusion time (AOT)>90 min, blood glucose in ICU after operation>11.1 mmol/L, the difference between the highest blood glucose within 48 hours after the operation and the blood glucose at 0 h after the operation≥2 mmol/L, blood lactic acid in ICU after operation>4 mmol/L and maximum vasoactive drug score within 48 hours after surgery>9 were independent influencing factors for early AKI (all P<0.05). Conclusions:The incidence of AKI within 48 hours after heart valve surgery is over 30%. The independent influencing factors include male, overweight/obesity, previous cardiac surgery, preoperative renal insufficiency, hypoproteinemia, long duration of AOT, post-operative stress hyperglycemia, fluctuating blood glucose levels wildly, hyperlactacidemia, and using more vasoactive drugs. AKI after cardiac surgery affects the early prognosis of patients, the later of the stage leads to the worse prognosis.

On January 22, 2020, China National Center for Bioinformation (CNCB) released the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access information resource for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2019nCoVR features a comprehensive integra-tion of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline. Of particular note, 2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and their detailed statistics for each virus isolate, and congregates the quality score, functional annotation,and population frequency for each variant. Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019 (COVID-19), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with NCBI. Collectively, SARS-CoV-2 is updated daily to collect the latest information on genome sequences, variants, hap-lotypes, and literature for a timely reflection, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.

COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF 1ab)of this cluster.Further-more,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introduc-tions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.