AIM:To investigate the antiviral effica-cy and mechanism of Qingre Xiaoyanning(QRXYN)in vivo,and provide experimental basis for their prevention and treatment of influenza A virus.METHODS:We constructed a mouse model infect-ed with influenza A H3N2 virus.To evaluate the therapeutic effect of QRXYN on influenza A virus,we measured the body weight changes,pathologi-cal changes in lung tissue,hemagglutination titer,and viral load in mouse.To evaluate the possible mechanism of QRXYN's anti influenza A virus infec-tion,we used the ELISA to measure the levels of TNF-α,IL-1β,IL-4,IFN-γ,and vascular cell adhesion molecule-1(VCAM-1)in mouse bronchoalveolar Ia-vage fluid;used flow cytometry to assess the pro-portions of macrophages(F4/80),helper T lympho-cytes(CD4+T lymphocytes),and natural killer(NK)cells in lung tissue;and used Western blotting to detect the expression of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MYD88),inhibitor of kappa B kinase-β(IKK-β),NF-kappa-B inhibitor al-pha(IκBα),and phospho-IKB alpha(p-IκBα)in lung tissue.RESULTS:Compared to the model group,both Oseltamivir and QRXYN can alleviate the se-verity of lung tissue lesions in mice,decrease the blood coagulation titer and viral load of mouse lung tissue(P＜0.01),lower the levels of TNF-α,IL-4,and VCAM-1 in bronchoalveolar lavage fluid(P＜0.05,P＜0.01),reduce the proportion of macro-phages(P＜0.05,P＜0.01),and increase the propor-tion of CD4+T lymphocytes and NK cells(P＜0.05,P＜0.01).Additionally,oseltamivir can reduce the ex-pression of MYD88 protein in mouse lungs(P＜0.05),while QRXYN can decrease the expression of IKK-β and P-IκBα proteins in mouse lungs(P＜0.05).CONCLUSION:QRXYN have good in vivo antiviral ef-fects against the influenza A virus,and their mecha-nism may be related to the regulation of the immu-nologic function and NF-κB signal pathway.

AIM:To investigate the antiviral effica-cy and mechanism of Qingre Xiaoyanning(QRXYN)in vivo,and provide experimental basis for their prevention and treatment of influenza A virus.METHODS:We constructed a mouse model infect-ed with influenza A H3N2 virus.To evaluate the therapeutic effect of QRXYN on influenza A virus,we measured the body weight changes,pathologi-cal changes in lung tissue,hemagglutination titer,and viral load in mouse.To evaluate the possible mechanism of QRXYN's anti influenza A virus infec-tion,we used the ELISA to measure the levels of TNF-α,IL-1β,IL-4,IFN-γ,and vascular cell adhesion molecule-1(VCAM-1)in mouse bronchoalveolar Ia-vage fluid;used flow cytometry to assess the pro-portions of macrophages(F4/80),helper T lympho-cytes(CD4+T lymphocytes),and natural killer(NK)cells in lung tissue;and used Western blotting to detect the expression of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MYD88),inhibitor of kappa B kinase-β(IKK-β),NF-kappa-B inhibitor al-pha(IκBα),and phospho-IKB alpha(p-IκBα)in lung tissue.RESULTS:Compared to the model group,both Oseltamivir and QRXYN can alleviate the se-verity of lung tissue lesions in mice,decrease the blood coagulation titer and viral load of mouse lung tissue(P＜0.01),lower the levels of TNF-α,IL-4,and VCAM-1 in bronchoalveolar lavage fluid(P＜0.05,P＜0.01),reduce the proportion of macro-phages(P＜0.05,P＜0.01),and increase the propor-tion of CD4+T lymphocytes and NK cells(P＜0.05,P＜0.01).Additionally,oseltamivir can reduce the ex-pression of MYD88 protein in mouse lungs(P＜0.05),while QRXYN can decrease the expression of IKK-β and P-IκBα proteins in mouse lungs(P＜0.05).CONCLUSION:QRXYN have good in vivo antiviral ef-fects against the influenza A virus,and their mecha-nism may be related to the regulation of the immu-nologic function and NF-κB signal pathway.

Objective:To investigate the prognostic and immunotherapeutic significance of androgen receptor V1 (ARV1) in colorectal cancer (CRC) and to explore its mechanism in CRC progression.Methods:The relationship between ARV1 expression and CRC prognosis was analyzed using data from The Cancer Genome Atlas Program (TCGA). Gene ontology (GO) analysis was performed to identify potential mechanisms through which ARV1 regulates CRC progression. Multiple public databases were used to analyze the correlation between ARV1 and immune cell infiltration and to predict the sensitivity of ARV1 to immunotherapy and chemotherapeutic drugs. Immunohistochemical validation was conducted using postoperative specimens from 199 CRC patients, and clinical correlations were analyzed.Results:ARV1 expression was significantly lower in CRC tissues compared to normal tissues ( P<0.001). Patients with high ARV1 expression exhibited better overall survival than those with low expression ( P=0.016). Clinical analysis indicated that ARV1 serves as an independent prognostic factor in CRC, and its expression was associated with age and clinical stage (all P<0.01). GO analysis revealed that ARV1 influenced multiple pathways in CRC. Immune-related analysis demonstrated that ARV1 participated in regulating immune cell infiltration in CRC. Drug sensitivity analysis showed differences in responses to various chemotherapeutic agents between high and low ARV1 expression groups ( P<0.01). In immunotherapy, significant differences in Immunophenotype Score (IPS) were observed between high and low ARV1 expression groups in PD1-negative/CTLA4-negative patients ( P<0.05). Immunohistochemical results from 199 CRC patients confirmed that low ARV1 expression was associated with poorer prognosis ( P<0.001). Conclusions:ARV1 expression affects CRC prognosis and may serve as a potential novel biomarker for immunotherapy in CRC.

Objective:To investigate the prognostic and immunotherapeutic significance of androgen receptor V1 (ARV1) in colorectal cancer (CRC) and to explore its mechanism in CRC progression.Methods:The relationship between ARV1 expression and CRC prognosis was analyzed using data from The Cancer Genome Atlas Program (TCGA). Gene ontology (GO) analysis was performed to identify potential mechanisms through which ARV1 regulates CRC progression. Multiple public databases were used to analyze the correlation between ARV1 and immune cell infiltration and to predict the sensitivity of ARV1 to immunotherapy and chemotherapeutic drugs. Immunohistochemical validation was conducted using postoperative specimens from 199 CRC patients, and clinical correlations were analyzed.Results:ARV1 expression was significantly lower in CRC tissues compared to normal tissues ( P<0.001). Patients with high ARV1 expression exhibited better overall survival than those with low expression ( P=0.016). Clinical analysis indicated that ARV1 serves as an independent prognostic factor in CRC, and its expression was associated with age and clinical stage (all P<0.01). GO analysis revealed that ARV1 influenced multiple pathways in CRC. Immune-related analysis demonstrated that ARV1 participated in regulating immune cell infiltration in CRC. Drug sensitivity analysis showed differences in responses to various chemotherapeutic agents between high and low ARV1 expression groups ( P<0.01). In immunotherapy, significant differences in Immunophenotype Score (IPS) were observed between high and low ARV1 expression groups in PD1-negative/CTLA4-negative patients ( P<0.05). Immunohistochemical results from 199 CRC patients confirmed that low ARV1 expression was associated with poorer prognosis ( P<0.001). Conclusions:ARV1 expression affects CRC prognosis and may serve as a potential novel biomarker for immunotherapy in CRC.

Alcoholic liver disease(ALD)is the most frequent liver disease worldwide,resulting in severe harm to personal health and posing a serious burden to public health.Based on the reported antioxidant and anti-inflammatory capacities of scutellarin(SCU),this study investigated its protective role in male BALB/c mice with acute alcoholic liver injury after oral administration(10,25,and 50 mg/kg).The results indicated that SCU could lessen serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels and improve the histopathological changes in acute alcoholic liver;it reduced alcohol-induced malondialdehyde(MDA)content and increased glutathione peroxidase(GSH-Px),catalase(CAT),and superoxide dismutase(SOD)activity.Furthermore,SCU decreased tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-1β messenger RNA(mRNA)expression levels,weakened inducible nitric oxide synthase(iNOS)activity,and inhibited nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome activation.Mechanistically,SCU suppressed cytochrome P450 family 2 subfamily E member 1(CYP2E1)upregulation triggered by alcohol,increased the expression of oxidative stress-related nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)pathways,and suppressed the inflammation-related degradation of inhibitor of nuclear factor-κB(NF-κB)-α(IκBα)as well as activation of NF-κB by mediating the protein kinase B(AKT)and p38 mitogen-activated protein kinase(MAPK)pathways.These findings demonstrate that SCU protects against acute alcoholic liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and suppressing inflammation by regulating the AKT,p38 MAPK/NF-κB pathways.

BACKGROUND: The clinical importance of hypokalemia is likely underrecognized in Chinese dialysis patients, and whether its clinical effect was mediated by serum albumin is not fully elucidated. This study aimed to explore the association between serum potassium and mortality in dialysis patients of a Chinese nationwide multicenter cohort, taking albumin as a consideration. METHODS: This was a prospective nation-wide multicenter cohort study. Restricted cubic splines were used to test the linearity of serum potassium and relationships with all-cause (AC) and cardiovascular (CV) mortality and a subsequent two-line piecewise linear model was fitted to approach the nadir. A mediation analysis was performed to examine relations of albumin to potassium and mortalities. RESULTS: A total of 10,027 patients were included, of whom 6605 were peritoneal dialysis and 3422 were hemodialysis patients. In the overall population, the mean age was 51.7 ± 14.8 years, 55.3%(5546/10,027) were male, and the median dialysis vintage was 13.60 (4.70, 39.70) months. Baseline serum potassium was 4.30 ± 0.88 mmol/L. After a median follow-up period of 26.87 (14.77, 41.50) months, a U-shape was found between potassium and mortality, and a marked increase in risk at lower potassium but a moderate elevation in risk at higher potassium were observed. The nadir for AC mortality risk was estimated from piecewise linear models to be a potassium concentration of 4.0 mmol/L. Interestingly, the significance of the association between potassium and mortality was attenuated when albumin was introduced into the extended adjusted model. A subsequent significant mediation by albumin for potassium and AC and CV mortalities were found ( P < 0.001 for both), indicating that hypokalemia led to higher mortality mediated by low serum albumin, which was a surrogate of poor nutritional status and inflammation. CONCLUSIONS Associations between potassium and mortalities were U-shaped in the overall population. The nadir for AC mortality risk was at a potassium of 4.0 mmol/L. Serum albumin mediated the association between potassium and AC and CV mortalities.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; East Asian People ; Hypokalemia/etiology* ; Kidney Failure, Chronic/mortality* ; Potassium/blood* ; Prospective Studies ; Renal Dialysis ; Serum Albumin/analysis*

Objective:To analyze the clinical phenotype and molecular pathogenesis of nine patients with hereditary factor Ⅴ (FⅤ) deficiency.Methods:Nine patients with hereditary FⅤ deficiency who were admitted to the Institute of Hematology and Blood Diseases Hospital from April 1999 to September 2019 were analyzed. The activated partial thromboplastin time, prothrombin time, and FⅤ procoagulant activity (FⅤ∶C) were measured for phenotypic diagnosis. High-throughput sequencing was employed for the F5 gene mutation screening, Sanger sequencing was adopted to confirm candidate variants and parental carrying status, Swiss-model was used for three-dimensional structure analysis, and ClustalX v.2.1 was used for homologous analysis.Results:The FⅤ∶C of the nine patients ranged from 0.1 to 10.6. Among them, eight had a hemorrhage history, with kin/mucosal bleeding as the most common symptom (three cases, 37.5%) , whereas one case had no bleeding symptom. There were five homozygotes and four compound heterozygotes. A total of 12 pathogenic or likely pathogenic mutations were detected, of which c.6100C>A/p.Pro2034Thr, c.6575T>C/p.Phe2192Ser, c.1600_1601delinsTG/p. Gln534*, c.4713C>A/p.Tyr1571*, and c.952+5G>C were reported for the first time.Conclusion:The newly discovered gene mutations enriched the F5 gene mutation spectrum associated with hereditary FⅤ deficiency. High-throughput sequencing could be an effective method to detect F5 gene mutations.

Objective:To explore the correlation between serum 25-hydroxyvitamin D3 [25(OH)D3] level and peritoneal dialysis (PD) associated peritonitis, and provide a new idea for the prevention and treatment of peritonitis.Methods:In this single-center retrospective cohort study, patients who were≥18 years old and were treated with regular PD≥3 months in PD center from January 1, 2014 to September 30, 2018 were recruited, except those who had a history of malignant tumors or systemic infectious diseases, transferred from permanent hemodialysis (HD) or failed kidney transplantation. Baseline data including demographic characteristics as well as clinical and biochemical data were collected. All the patients were followed up until death, transfer to HD, kidney transplantation, transfer to other centers or the end of our study (December 31, 2018), and were divided into low tertile [serum 25(OH)D3 ≤12μg/L], middle tertile[12 μg/L17 μg/L] according to the baseline serum 25(OH)D3 level. Multivariate adjusted Poisson model was used to evaluate the association between serum 25(OH)D3 level and PD related peritonitis.Results:A total of 642 patients were enrolled in our study, of whom 341 were male (53.12%) , and the age was (47.58±14.10) years old. The serum 25(OH)D3 level was (13.83±6.41) μg/L. As for the primary disease, 67.19% were chronic glomerulonephritis. During a median 42(19, 59) months follow-up period, 232 peritonitis occurred in 139 patients. After adjusting for confounders, including gender, age, albumin, body mass index(BMI), calcium-phosphorus product, intact parathyroid hormone (iPTH), diabetes, charlson index and drug use, multivariate Poisson regression analysis showed that the risk of peritonitis in the middle tertile and the low tertile was 92% (95% CI 0.62-1.38, P= 0.690) and 1.74 times (95% CI 1.19-2.54, P=0.004) of the high tertile respectively. The difference between the low tertile and the high tertile was statistically significant. Conclusions:The level of serum 25(OH)D3 is closely related to the occurrence of PD associated peritonitis. Low level serum 25(OH)D3 is an independent risk factor for peritonitis in PD patients.

Objective:To explore the prevalence and risk factors of exit-site infection (ESI) in elderly peritoneal dialysis (PD) patients.Methods:The status of exit-site was evaluated in elderly PD patients (≥60 years) who had catheter insertion in our center between January 1, 2009 and December 31, 2013, with follow-up for 1 year or withdrawing from peritoneal dialysis in this period. The patients were divided into ESI and non-ESI group. The data was collected including demographics, clinical features, and nursing care methods of the exit-site.Results:A total of 247 patients were recruited in this study, aged (68.6±6.2) years, among whom there were 132 male (53.4%) and 119 diabetes (48.2%). Median follow-up time was 12.0 months. Thirty-two patients had 34 episodes of ESI with a rate of 82.5 patient-months per episode (0.15 episodes per year). Coagulase-negative Staphylococcus was the main pathogen, accounting for 35.3% of the ESI. No bacterial growth was found in 8.8%. The exit-site nursing care status included that poor compliance of exit-site care 23.5%, poor catheter immobilization 62.3%, history of catheter-pulling injury 9.7%, mechanical stress on exit-site 5.3%, improper frequency of nursing care 29.6%, mupirocin usage 13.8%, patients taking exit-site care 26.7%, exit-site caregiver instability 16.6%. There were no differences in demographic (such as age, gender, primary disease, etc) and laboratory data (hemoglobin, serum albumin, blood potassium, etc) between the ESI and non-ESI groups. Poor compliance with exit-site care ( HR=2.352, 95% CI 1.008-5.488, P=0.048), poor catheter immobilization ( HR=3.074, 95% CI 1.046-9.035, P=0.041) and exit-site caregiver instability ( HR=2.423, 95% CI 1.004-5.845, P=0.049) were significantly correlated with increased risk of ESI. Conclusions:The prevalence of ESI in elderly PD patients was 0.15 episodes per year. Educating PD patients to improve the compliance with exit-site care, maintain catheter immobilization and do exit-site care by a stable and trained caregiver may reduce ESI events in elderly PD patients.

Objective:To explore the effect of continuous quality improvement (CQI) on reducing the incidence of peritoneal dialysis (PD)-related peritonitis in patients within the first year of PD initiation.Methods:The patients who received catheter placement from January 2006 to December 2016 in our hospital were enrolled in this study. All patients were divided into four groups: pre-CQI group patients who initiated PD treatment from 2006 to 2007 (before CQI phase, group A), CQI Ⅰphrase patients who initiated PD treatment from 2008 to 2010 (group B), CQI Ⅱ phrase patients who initiated PD treatment from 2011 to 2013 (group C), and CQI Ⅲ phrase patients who initiated PD treatment from 2014 to 2016 (group D). The method of plan, do, check and act (PDCA) was conducted to decrease the incidence of PDRP. All the patients were followed up for 12 months or until they withdrew from PD in this period. Poisson analysis was used to compare the incidence of PDRP among the groups.Results:There were 2 383 PD patients recruited in this study, including 346 cases in group A, 850 cases in group B, 688 cases in group C and 499 cases in group D, with an age of (47.1±15.8) years, among whom 59.1% of the patients were male, and 21.4% with diabetes. The follow-up time was (10.9±2.8) months. Compared with group A, the incidence of PDRP was lower than that in group C (0.156 episodes/patient year vs 0.234 episodes/patient year, P=0.020); the incidence of gram positive PDRP decreased (0.052, 0.049, 0.054 episodes/patient year vs 0.104 episodes/patient year, all P<0.05) in group B, C, D; the incidence of gram negative PDRP increased in group B, then decreased in group C and group D (all P>0.05). Cox regression analysis indicated that CQI was independently associated with the incidence of gram positive PDRP ( HR=0.526, 95% CI 0.349-0.792, P=0.002). Conclusion:CQI can effectively reduce the incidence of gram positive PDRP in patients within the first year of PD initiation.