Amelioratory effects of astragaloside IV on hepatocarcinogenesis via Nrf2-mediated pSmad3C/3L transformation.

BACKGROUND: Phosphorylated Smad3 isoforms are reversible and antagonistic, and the tumour-suppressive pSmad3C can shift to an oncogenic pSmad3L signal. In addition, Nrf2 has a two-way regulatory effect on tumours, protecting normal cells from carcinogens and promoting tumour cell survival in chemotherapeutics. Accordingly, we hypothesised that the transformation of pSmad3C/3L is the basis for Nrf2 to produce both pro- and/or anti-tumourigenic effects in hepatocarcinogenesis. Astragaloside IV (AS-IV), the major component of Astragalus membranaceus, exerts anti-fibrogenic and carcinogenic actions. Lately, AS-IV administration could delay the occurrence of primary liver cancer by persistently inhibiting the fibrogenesis and regulating pSmad3C/3 L and Nrf2/HO-1 pathways synchronously. However, effect of AS-IV on hepatocarcinogenesis implicated in the bidirectional cross-talking of pSmad3C/3 L and Nrf2/HO-1 signalling, especially which one contributes palpably than the other still remains unclear. PURPOSE: This study aims to settle the above questions by using in vivo (pSmad3C+/- and Nrf2-/- mice) and in vitro (plasmid- or lentivirus- transfected HepG2 cells) models of HCC. STUDY DESIGN AND METHODS: The correlation of Nrf2 to pSmad3C/pSmad3L in HepG2 cells was analysed by Co-immunoprecipitation and dual-luciferase reporter assay. Pathological changes of Nrf2, pSmad3C, and pSmad3L in human HCC patients, pSmad3C+/- mice, and Nrf2-/- mice were gauged by immunohistochemical, haematoxylin and eosin staining, Masson, and immunofluorescence assays. Finally, western blot and qPCR were used to verify the bidirectional cross-talking of pSmad3C/3L and Nrf2/HO-1 signalling protein and mRNA in vivo and in vitro models of HCC. RESULTS: Histopathological manifestations and biochemical indicators revealed that pSmad3C+/- could abate the ameliorative effects of AS-IV on fibrogenic/carcinogenic mice with Nrf2/HO-1 deactivation and pSmad3C/p21 transform to pSmad3L/PAI-1//c-Myc. As expected, cell experiments confirmed that upregulating pSmad3C boosts the inhibitory activity of AS-IV on phenotypes (cell proliferation, migration and invasion), followed by a shift of pSmad3L to pSmad3C and activation of Nrf2/HO-1. Synchronously, experiments in Nrf2-/- mice and lentivirus-carried Nrf2shRNA cell echoed the results of pSmad3C knockdown. Complementarily, Nrf2 overexpression resulted in the opposite result. Furthermore, Nrf2/HO-1 contributes to AS-IV's anti-HCC effect palpably compared with pSmad3C/3L. CONCLUSION: These studies highlight that harnessing the bidirectional crosstalk pSmad3C/3 L and Nrf2/HO-1, especially Nrf2/HO-1 signalling, acts more effectively in AS-IV's anti-hepatocarcinogenesis, which may provide an important theoretical foundation for the use of AS-IV against HCC.

Progress in DNA-sensing pathways in Epstein-Barr virus infection / 中华微生物学和免疫学杂志

Epstein-Barr virus (EBV) is generally susceptible in human beings and multi-organ systems can be involved in EBV infection, such as blood, respiratory, urinary, digestive and nervous systems. EBV infection also plays an important role in the pathogenesis of related tumors, autoimmune diseases and other diseases, posing a great threat to human health. As a DNA virus, EBV can be sensed by DNA recognition receptors to trigger a series of downstream immune responses. A DNA-sensing pathway consists of DNA sensors, adaptor molecules and downstream effector signals. Double-stranded DNA sensors mainly include absent in melanoma 2-like receptors (ALRs) and cyclic GMP-AMP synthase (cGAS). Adaptors were mainly stimulator of interferon genes (STING) and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). Downstream immune responses mainly involve typeⅠIFN, inflammasomes and proinflammatory cytokines. As a double-stranded DNA virus of the Herpesviridae family, EBV triggers complex innate and adaptive immune responses in the host, especially the sensing pathways mediated by a variety of DNA recognition receptors, which play a key role in host immune defense and pathogen immune evasion. This review made the DNA sensor as the clue to comprehensively summarize the progress in the activation, regulatory mechanism and clinical relevance of DNA-sensing pathways in EBV infection in recent years, aiming to achieve a better understanding of the host innate immune responses during EBV infection and provide an immunological basis for the prevention and treatment of EBV infection-related diseases.

Early identification and influencing factors of post-traumatic stress disorder in high-stress rescue workers / 中华预防医学杂志

Objective: To explore the risk intensity and related influencing factors of post-traumatic stress disorder (PTSD) among high-stress rescue workers, and to provide effective tools for the risk assessment of PTSD in military rescue workers. Method: From June to August 2022, cluster sampling was used to select the high-stress rescue personnel of an Army department as the survey subjects. The acute Stress reaction (ASD) scale and PTSD checklist were used to evaluate the risk of PTSD in military rescue personnel. Multivariate logistic regression were used to analyze the influencing factors of PTSD. Results: The age of 4 460 subjects was (24.38±4.072) years old, including 4 396 males (98.6%). The positive rate of initial screening for ASD was 2.85% (127/4 460). The positive rate of PTSD was 0.67% (30/4 460). Multivariate logistic regression model analysis showed that female, older age, recent trauma exposure history, passive smoking and alcohol consumption were at higher risk of ASD, the values of OR (95%CI) were 4.183 (1.819-9.618), 6.278 (1.363-28.912), 3.094 (1.500-6.379), 2.059 (1.298-3.267) and 2.607 (1.614-4.211), respectively; Lower education level was associated with lower risk of ASD, OR (95%CI) was 0.593 (0.359-0.978); People who are older, thinner, have a history of mental illness, and drink alcohol were at higher risk for PTSD, the values of OR (95%CI) were 20.144 (2.459-165.043), 10.287 (2.218-47.700), 91.104 (8.592-965.980) and 2.866 (1.144-7.180), respectively. Conclusion: Gender, age, education level, passive smoking, alcohol consumption, past history of mental illness and body mass index may be related to the potential risk of PTSD in rescue workers,passive smoking, alcohol consumption, and weight controlling should be focused on to reduce potential risks of PTSD.

Changes and significance of T follicular regulatory cells/T follicular helper cells and related cytokines in peripheral blood of children with dust mite allergic asthma / 中华实用儿科临床杂志

Objective:To explore the changes of T follicular regulatory (T FR) cells/T follicular helper (T FH) cells and their related cytokines in peripheral blood of children with dust mite allergic asthma, and their clinical significance. Methods:A total of 25 children with acute dust mite allergic asthma (the asthma group) in Affiliated Hospital of Jiangnan University from January to December 2021 and 16 age- and sex-matched healthy volunteers (the healthy control group) at the same time were enrolled in the retrospective study.The percentages of peripheral T FR cells and T FH cells of the 2 groups were measured by flow cytometry.The plasma levels of cytokines[interleukin (IL)-10, IL-21] of the 2 groups were assessed by the flow cytometric microsphere-based array technology.The specific IgE (sIgE) levels of dust mites in 2 groups were detected by fluorescence enzyme immunoassay.The percentage of eosinophils in peripheral blood detected by blood cell analyzer.Data between groups were compared by t-test, and the correlation among indicators was analyzed by Spearman rank correlation analysis. Results:The asthma group had evident T FR cells/T FH cells immune imbalance.Compared with the healthy control group, the asthma group had a significantly lower T FR cells level[(0.11±0.03)% vs.(0.13±0.03)%], a significantly higher T FH cells level[(5.07±1.75)% vs.(3.80 ± 1.60)%], and a significantly lower ratio of T FR cells /T FH cells(0.02±0.01 vs.0.05±0.03) ( t=2.29, 2.30, 3.71; all P<0.05). Compared with the healthy control group, the asthma group had a significantly higher IL-21 level[(547.85±195.13) ng/L vs.(404.94±110.41) ng/L], and a significantly lower IL-10 level[(10.18±3.49) ng/L vs.(14.79±5.65) ng/L] ( t=2.60, 3.15; all P<0.05). The ratio of T FR cells/T FH cells in asthma group was negatively correlated with sIgE ( r=-0.444 2, P=0.026 1), but not related to the eosinophil percentage ( r=-0.135 2, P=0.519 3). Conclusions:Children with dust mite allergic asthma suffer from T FR cells/T FH cells subset imbalance.The imbalanced T FR cells, T FH cells and their related cytokines IL-10 and IL-21 may play a role in regulating the production of asthma sIgE.

Comparison of conservative and surgical treatment of testicular appendage torsion in children / 中国医师杂志

Objective:To investigate the clinical efficacy of conservative and surgical treatment of testicular appendage torsion in children and to summarize the experience.Methods:The clinical data of 106 children with testicular appendage torsion admitted in Tengzhou Central People's Hospital Affiliated to Xuzhou Medical University from January 2012 to December 2018 were retrospectively analyzed. According to different therapeutic methods, all the children were divided into conservative group (25 cases) and surgical group (81 cases). The clinical efficacy was compared between the two groups.Results:106 children with testicular appendage torsion were cured. The hospitalization time [(5.61±1.04)d vs (11.32±1.89)d], pain relief time [(9.11±2.56)d vs (68.5±19.87)d], disappearance time of scrotal edema [(5.11±1.08)d vs (10.56±1.50)d] and the utility time of antibiotic [(4.89±1.32)d vs (7.06±1.26)d] in the surgical group were shorter than those in the conservative group, with statistically significant difference(all P<0.05). After 6 months of follow-up, there were no cases of recurrence and discomfort in the two groups. Conclusions:Children with testicular appendage torsion should be actively treated with surgery, which can not only significantly shorten the course of disease, but also reduce the incidence of complications and missed diagnosis. For children who with testicular appendage torsion, surgeries should be performed actively. It can significantly shorten the duration of symptoms, but also reduce the occurrence of complication and the occurrence probability of misdiagnosis.

Genetic diversity of Sparganum isolates from snakes in Hunan Province based on mitochondrial nad4 and nad5 genes / 中国血吸虫病防治杂志

Objective To investigate the genetic diversity and phylogenetic relationship of Sparganum isolates from snakes in Hunan Province. Methods The partial mitochondrial NADH dehydrogenase subunit 4 (pnad4) and NADH dehydrogenase subunit 5 (pnad5) genes were amplified using a PCR assay in 7 Sparganum isolates from snakes in Hunan Province and the amplification product was sequenced. The homology and genetic evolution were investigated using the software DNAMAN 7.0, MegAlign, DnaSP 5.0 and MEGA 5.0. Results The pnad4 and pnad5 gene sequences were approximately 578 bp and 484 bp in length in the 7 Sparganum isolates from Hunan Province, and the percentages of genetic variations were 0 to 2.8% and 0 to 0.8%, respectively. There were 4 haplotypes detected in both the pnad4 and pnad5 genes, with global haplotype diversities of 0.810 ± 0.016 and 0.905 ± 0.011, nucleotide diversities of 0.006 ± 0.005 and 0.004 ± 0.003, and mean nucleotide variations of 3.960 and 1.905, respectively. Phylogenetic analysis showed that all 7 Sparganum isolates from snakes in Hunan Province were clustered into the same branch with Spirometra erinaceieuropaei isolates from different regions/hosts in the world, which belonged to S. erinaceieuropaei, which were close to Diphyllobothrium latum and far from other tapeworms. Conclusion There is a low genetic variation in snake-derived S. erinaceieuropaei isolates from Hunan Province, and both pnad4 and pnad5 genes may be potential molecular genetic markers for identification of S. erinaceieuropaei.

Preliminary study on effect of Gegen Qinlian Decoction on enzyme activity, gene expression and methylation level of FASN in adipose tissue of rats with insulin resistance / 中国中药杂志

To investigate the effect of Gegen Qinlian Decoction(GQD) on enzyme activity, gene expression and methylation level of fatty acid synthase(FASN) in adipose tissue from rats with insulin resistance induced by high-fat diet. The 60% fat-powered high-fat diet was continuously given to male SD rats to induce the insulin resistance model. Then, they were divided into five groups randomly and administrated by gavage every day for 16 weeks with following drugs respectively: 10 mL·kg~(-1)water for control group(C) and insulin resistance model control group(IR), 1.65 g·kg~(-1)GQD per day for low-dose group(GQDL), 4.95 g·kg~(-1)GQD per day for medium-dose group(GQDM), 14.85 g·kg~(-1)GQD per day for high-dose group(GQDH), and 5 mg·kg~(-1) rosiglitazone per day for rosiglitazone group(RGN). Epididymal adipose tissue was taken to determine enzyme activity of FASN by colorimetric method, mRNA expression level of Fasn by quantitative Real-time PCR(Q-PCR) and CpGs methylation level between +313 and +582 by bisulfite sequencing PCR(BSP). These results showed that Fasn expression was significantly lowered in IR model rats compared with the control rats(P<0.01). Enzymatic activity and CpGs methylation level of Fasn in IR group showed downward trends. Low and medium-dose GQD can increase enzyme activity of FASN(P<0.05). Moreover, low-dose GQD increased the total CpGs methylation level of Fasn fragment between +313 and +582 in insulin resistance rats(P<0.05). For GQDM group, the methylation frequency of CpGs at positions +506 and +508(P<0.01) as well as the methylation frequency of CpGs on the binding sites of transcription factorzinc finger protein 161(P<0.05) were significantly increased. The methylation frequency of CpG at +442 position was positively correlated with Fasn expression(P<0.01, r=0.735), and methylation frequencies of CpGs at +345 and +366 positions were positively associated to enzyme activity of FASN respectively(P<0.05, r=0.479; P<0.01, r=0.640). In conclusion, GQD can reverse enzyme activity of FASN and methylation level of Fasn in adipose tissue of insulin resistant rats, and CpG sites at positions +506 and +508 may be the targets of GQD. The methylation level of CpGs at + 345 and + 366 sites were possibly related to FASN activity, while methylation of CpG at + 442 site may be closely correlated with mRNA level of Fasn. In addition, GQD did not significantly change mRNA expression level of Fasn, but effectively reversed enzymatic activity, suggesting that GQD may regulate the post transcriptional expression of Fasn.

Clinical study on Tuina plus umbilical therapy for senile functional constipation / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of Tuina (Chinese therapeutic massage) plus umbilical therapy for senile functional constipation due to Qi deficiency of lung and spleen.Methods: A total of 60 patients who met the inclusion criteria were randomly divided into a control group and an observation group by the random number table method, with 30 cases in each group. The patients in the control group were given lactulose oral solution, while the patients in the observation group were treated with Tuina and umbilical therapy. After two weeks of treatment, the scores of the Wexner continence grading scale (WCGS) and patient assessment of constipation-quality of life questionnaire (PAC-QOL) were observed. The effective rates in the two groups were compared. Results: After two weeks of treatment, the total effective rate in the observation group was 90.0％, while that in the control group was 76.7％, presenting a significant difference between the two groups (P<0.05). There were no significant differences in the WCGS and PAC-QOL scores between the two groups before treatment (P>0.05). After two weeks of treatment, the WCGS and PAC-QOL scores of both groups decreased significantly compared with those before treatment (P<0.05), and the two scores in the observation group were lower than those in the control group (P<0.05). Conclusion: The efficacy of Tuina plus umbilical therapy for senile functional constipation is confirmed. This method can improve patients' quality of life. Its efficacy is better than that of taking lactulose oral solution.

MicroRNA144￣3p targeting histone deacetylase 2 promoting cardiomyocyte hypertrophy and cardiac function damage / 解剖学报

Objective To investigate the role and possible mechanism of microRNA(miR)144-3p in promoting cardiomyocyte hypertrophy. Methods Forty-five C57BL/ 6 mice were divided into control group, myocardial hypertrophy model group (model group), and miR144-3p transfection group (transfection group) according to their transfection method. The cardiac function related indexes of three groups of mice were detected. HE staining was performed on mouse myocardial tissue.The expression of miR144-3p in mouse cardiomyocytes was detected by Real-time PCR. Antinuclear factor (ANF), β-myosin heavy chain (β-MHC), actin α1 (Acta1) and histone deacetylase 2 (HDAC2) were detected by Western blotting in three groups. Results Compared with the control group, the interventricular septal thickness- diastolic(IVSd), interventricular septal thickness-systolic(IVSs), diastolic left ventricular posterior wall thickness(IVPWd), systolic left ventricular posterior wall thickness(IVPWs), ejection fraction(EF), cardiac weight index and left cardiac index of the model group and the transfection group were significantly higher, while systolic left ventricular diameter (LVDs) and diastolic left ventricular diameter(LVDd)were lower (P0. 05). Compared with the control group, the relative expression of miR144-3p in the model group and the transfection group was significantly higher than that in the model group (P<0. 05). Compared with the control group, the expression levels of antinuclear factor, β-myosin heavy chain, Actinα1 and histone deacetylase 2 in the model group and the transfected group were significantly higher (P<0. 05). Conclusion miR144-3p can aggravate cardiac hypertrophy by up-regulating HDAC2 and is expected to become a new therapeutic target.

A key linear epitope for a potent neutralizing antibody to SARS-CoV-2 S-RBD

The spread of SARS-CoV-2 confers a serious threat to the public health without effective intervention strategies1-3. Its variant carrying mutated Spike (S) protein D614G (SD614G) has become the most prevalent form in the current global pandemic4,5. We have identified a large panel of potential neutralizing antibodies (NAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 S6. Here, we focused on the top 20 potential NAbs for the mechanism study. Of them, the top 4 NAbs could individually neutralize both authentic SARS-CoV-2 and SD614G pseudovirus efficiently. Our epitope mapping revealed that 16/20 potent NAbs overlapped the same steric epitope. Excitingly, we found that one of these potent NAbs (58G6) exclusively bound to a linear epitope on S-RBD (termed as 58G6e), and the interaction of 58G6e and the recombinant ACE2 could be blocked by 58G6. We confirmed that 58G6e represented a key site of vulnerability on S-RBD and it could positively react with COVID-19 convalescent patients plasma. We are the first, as far as we know, to provide direct evidences of a linear epitope that can be recognized by a potent NAb against SARS-CoV-2 S-RBD. This study paves the way for the applications of these NAbs and the potential safe and effective vaccine design.

A rapid and efficient screening system for neutralizing antibodies and its application for the discovery of potent neutralizing antibodies to SARS-CoV-2 S-RBD

Neutralizing antibodies (Abs) have been considered as promising therapeutics for the prevention and treatment of pathogens. After the outbreak of COVID-19, potent neutralizing Abs to SARS-CoV-2 were promptly developed, and a few of those neutralizing Abs are being tested in clinical studies. However, there were few methodologies detailly reported on how to rapidly and efficiently generate neutralizing Abs of interest. Here, we present a strategically optimized method for precisive screening of neutralizing monoclonal antibodies (mAbs), which enabled us to identify SARS-CoV-2 receptor-binding domain (RBD) specific Abs within 4 days, followed by another 2 days for neutralization activity evaluation. By applying the screening system, we obtained 198 Abs against the RBD of SARS-CoV-2. Excitingly, we found that approximately 50% (96/198) of them were candidate neutralizing Abs in a preliminary screening of SARS-CoV-2 pseudovirus and 20 of these 96 neutralizing Abs were confirmed with high potency. Furthermore, 2 mAbs with the highest neutralizing potency were identified to block authentic SARS-CoV-2 with the half-maximal inhibitory concentration (IC50) at concentrations of 9.88 ng/ml and 11.13 ng/ml. In this report, we demonstrated that the optimized neutralizing Abs screening system is useful for the rapid and efficient discovery of potent neutralizing Abs against SARS-CoV-2. Our study provides a methodology for the generation of preventive and therapeutic antibody drugs for emerging infectious diseases.

A follow-up study of children infected with SARS-CoV-2 from Western China

BackgroundTo clarify the characteristic and the duration of positive nucleic acid in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including asymptomatic children. MethodsA total of 32 children confirmed with SARS-CoV-2 infection between January 24 and February 12, 2020 from four provinces in Western China were enrolled in this study and followed up until discharge and quarantine 14 days later. ResultsEleven children (34%) were asymptomatic, among whom six children had normal computed tomographic (CT) scan images. Age and gender were not associated with clinical symptoms or the results of CT scan in children infected with SARS-CoV-2. The concentrations of white blood cells and neutrophils were higher in children with asymptomatic infection than in children with clinical symptoms or CT abnormalities. Patients who presented with CT abnormalities had lower D-dimer or lower total bilirubin than those who had normal CT scan but clinical symptoms. All children recovered and no one died or was admitted to the pediatric intensive care unit (PICU). The mean duration of positive SARS-CoV-2 nucleic acid was 15.4 (SD=7.2) days and similar for both asymptomatic children and children with symptoms or CT abnormalities. We found a significant negative correlation between the lymphocyte count and the duration of positive nucleic acid test. ConclusionsChildren with asymptomatic infection should be quarantined for the same duration as symptomatic patients infected with SARS-CoV-2. The clinical significance and mechanism behind the negative correlation between the number of lymphocytes and the duration of positive SARS-CoV-2 needs further study.

Antibody responses to SARS-CoV-2 in COVID-19 patients: the perspective application of serological tests in clinical practice

BackgroundWe aim to investigate the profile of acute antibody response in COVID-19 patients, and provide proposals for the usage of antibody test in clinical practice. MethodsA multi-center cross-section study (285 patients) and a single-center follow-up study (63 patients) were performed to investigate the feature of acute antibody response to SARS-CoV-2. A cohort of 52 COVID-19 suspects and 64 close contacts were enrolled to evaluate the potentiality of the antibody test. ResultsThe positive rate for IgG reached 100% around 20 days after symptoms onset. The median day of seroconversion for both lgG and IgM was 13 days after symptoms onset. Seroconversion of IgM occurred at the same time, or earlier, or later than that of IgG. IgG levels in 100% patients (19/19) entered a platform within 6 days after seroconversion. The criteria of IgG seroconversion and > 4-fold increase in the IgG titers in sequential samples together diagnosed 82.9% (34/41) of the patients. Antibody test aided to confirm 4 patients with COVID-19 from 52 suspects who failed to be confirmed by RT-PCR and 7 patients from 148 close contacts with negative RT-PCR. ConclusionIgM and IgG should be detected simultaneously at the early phase of infection. The serological diagnosis criterion of seroconversion or the >; 4-fold increase in the IgG titer is suitable for a majority of COVID-19 patients. Serologic test is helpful for the diagnosis of SARS-CoV-2 infection in suspects and close contacts.

Clinical observation on acupuncture plus subtle adjustment manipulation of the cervical spine for peripheral facial paralysis / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of acupuncture plus subtle adjustment manipulation of the cervical spine for peripheral facial paralysis.Methods: A total of 60 patients with peripheral facial paralysis who met the screening criteria were selected and divided into two groups according to the method of random number table, with 30 cases in each group. The patients in the acupuncture plus tuina group received routine treatment of acupuncture and subtle adjustment manipulation of the cervical spine, while the patients in the acupuncture group only received the same acupuncture treatment. Assessment of peripheral facial paralysis with integrated traditional Chinese and Western medicine was adopted for rehabilitation assessment. Results: The total effective rate of the acupuncture plus tuina group was 93.3％, while that of the acupuncture group was 70.0％, and there was a significant between-group difference (P<0.05). After treatment, the total scores of rehabilitation assessment in both groups were significantly higher than those before treatment (both P<0.05), and the score of the acupuncture plus tuina group was significantly higher than that of the acupuncture group (P<0.05). Conclusion: The treatment of acupuncture plus subtle adjustment manipulation of the cervical spine can improve the function of facial muscles in patients with peripheral facial paralysis, and its clinical efficacy is better than that of the acupuncture treatment alone.

Protective effect of against oxidative stress in neonatal mice with necrotizing enterocolitis / 南方医科大学学报

OBJECTIVE@#To investigate the protective effect of DSM17938 strain against oxidative stress in a neonatal mouse model of necrotizing enterocolitis (NEC) and explore the possible mechanism.@*METHODS@#Ninety-six 10-day-old neonatal C57BL/6J mice were equally randomized into control group, NEC group, and NEC+ group. The pathological changes of the ileocecal intestinal tissue were evaluated with HE staining and double-blind pathological scoring. The mRNA and protein expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the intestinal tissues were detected using quantitative real-time PCR and ELISA, respectively. Colorimetric assays were used to determine the activity of superoxide dismutase (SOD) and its inhibition rate, malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), and GSSG/ GSH ratio.@*RESULTS@#Compared with those in the control group, the neonatal mice in NEC group showed significant weight loss ( 0.05).@*CONCLUSIONS@# DSM17938 can offer protection against NEC in mice by reducing oxidative stress and increasing antioxidant capacity of the intestinal tissue to suppress intestinal inflammations.

The association of HLA-B27 and Klebsiella pneumoniae in ankylosing spondylitis: A systematic review.

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis of unknown origin. Its autoimmune origin has been suggested but never proven. Several reports have implicated K. pneumoniae as a triggering or perpetuating factor in AS; and the HLA-B27 antigen has also been found in association with AS. But there is no satisfactory explanation of why the presence of HLA-B27 predisposes to AS and the precise role played by K. pneumoniae in the disease has not yet been clarified. However, various studies have shown that the results of molecular, immunological, and microbiological studies could establish the link between K. pneumoniae infections and HLA-B27 in the aetiopathogenesis of AS. In this review, we have examined the evidence linking the interaction between K. pneumoniae infections and HLA-B27 in AS, and tried to exploit the possible mechanisms by which K. pneumoniae infections might induce pathologic processes to develop novel diagnostic criteria. Finally, we have also summarized some dietary regimens that could be helpful in the therapeutic management of AS patients.

A survey of fluid therapy in 2 intensive care units / 中华内科杂志

To explore the present status of fluid therapy and clinical outcome in critically ill patients in intensive care units (ICU).ICU patients consecutively admitted to our ICU were prospectively enrolled.Patients' demographics,laboratory data,fluid record and clinical outcome were collected.Fluid intake quantity of all patients was at peak on the fifth day which was 2 806 (1 997,3 582)ml.From the fourth day in ICU,fluid balance started to benegative as-84 (-1 127,612)ml and gradually increased.Crystalloid solution was the main components.For treatment purposes,medication injections and nutrients were major fluids.Positive correlations were found between total fluid intake quantity,total crystalloid volume,total colloidal volume and hospital stay,ICU stay,duration of intubation (r values as 0.211,0.686,0.282,0.155,0.506,0.174,0.209,0.072,0.292,respectively P＜0.05).Moreover,positive correlations were also demonstrated between total colloidal volume and total bilirubin,direct bilirubin,alanine transaminase,aspartate transaminase,blood urea nitrogen,serum creatinine (r values as 0.196,0.242,0.190,0.335,0.284,0.223,respectively P＜0.05).

Dynamical Analysis of the Inhibitory Effect of Aspirin and Clopidogrel on Platelet Adhesion and Aggregation for Healthy People under Physiological Flow Condition by Microfluidic Chip Technology / 中国医学科学院学报

Objective To explore the inhibitory effect of aspirin and clopidogrel on platelet adhesion and aggregation behaviors under the physiological flow condition using microfluidic chip technology for health volunteers. Methods Peripheral venous blood samples collected from twelve randomly recruited health volunteers were treated with 20 μmol/L acetylsalicylic acid,50 μmol/L 2-methlthioadenosine-5'-monophosphate triethylammonium salt,and their combination,respectively,with untreated blood samples being control group. The blood samples were flowed through a microchannel modified with type I collagen protein at a physiological relevant shear rate of 1000 s for 300 s,while the fluorescent images of platelet aggregations were dynamic captured using a microscope. Based on the images,the platelet coverage rates were calculated and used as quantitative parameters for evaluating platelet adhesion and aggregation behaviors. Results Under a flow condition of 1000 s shear rate,an expected in vivo-like platelet adhesion and aggregation behaviors were observed at the surfaces of collagen proteins for control blood samples. Aspirin alone or clopidogrel alone suppressed platelet adhesion and aggregation at the later period of flow(200-300 s),while the combination of aspirin and clopidogrel reduced the adhesion numbers of platelets at the earlier stage of flow(≤150 s) and compromised the stability of platelet aggregation at the later period of flow(200-300 s). The combination showed synergistic effect in inhibiting platelet aggregation. Furthermore,such inhibitory effect was heterogeneous among 12 volunteers. Conclusion This simple microfluidic technology can offer a new technical platform for analyzing the inhibitory effect of antiplatelet drugs.

Effects of protein PUMA-α on the apoptosis and fibrosis of human peritoneal mesothelial cells induced by high glucose / 解放军医学杂志

Objective To explore the effects of p53 up-regulated modulator of apoptosis (PUMA)-α protein on the apoptosis and fibrosis of human peritoneal mesothelial cells (HPMCs) induced by high glucose.Methods HPMCs were induced by 50mmol/L D type glucose or mannitol for 72 hours respectively,flow cytometry was employed to detect the rate of apoptotic cells,and theexpression levels of apoptosis-and fibrosis-related proteins were detected by Western blotting.The untreated HPMCs were transfected with Lenti-PUMA-α,and the treated cells were transfected with shRNA-PUMA-α,the number of apoptotic cells and the expression levels of apoptosis-and fibrosis-related proteins were detected with the methods mentioned above.Results Flow cytometry showed that the rate of apoptotic HPMCs increased after being induced by high glucose for 72 hours,and Western blotting revealed that the expression levels of pro-apoptotic and pro-fibrotic related proteins increased,but the arrestins of apoptosis and fibrosis-related proteins decreased.Up-regulation of PUMA-α promoted apoptosis and fibrosis,while down-regulation of PUMA-α alleviated apoptosis and fibrosis of HPMCs.Conclusion High glucose may accelerate apoptosis and fibrosis of HPMCs by up-regulating the expression of PUMA-α.

Ultrasound-Assisted Extraction of Pristimerin from Celastrus orbiculatus Using Response Surface Methodology.

This paper describes the ultrasound-assisted extraction (UAE) of pristimerin from Celastrus orbiculatus. Methanol was the most effective for pristimerin extraction, followed by ethanol, ethyl acetate, n-butanol, and water. To optimize the conditions, the Box-Behnken design, a widely used form of response surface methodology, was used to investigate the effects of parameters on UAE. Several variables, such as extraction time, ultrasonic power, extraction temperature, and solvent-to-solid (S/S) ratio were investigated. The highest extraction yield of 1.843 mg/g was obtained using methanol under optimal conditions with an extraction time of 40 min, ultrasonic power of 105 W, an S/S ratio of 40 mL/g, and an extraction temperature of 52°C. The experimental values under optimal conditions agreed well with the predicted values, suggesting that UAE has good potential as an extraction method for pristimerin from C. orbiculatus.