Background and purpose:PARP-1 is closely related to malignant tumors. This study aimed to ex-plore the clinical significance of serum level of PARP-1 protein in onset and progression of gastric cancer.Methods:The serum samples from 145 patients with gastric cancer and 112 healthy check-up cases were collected. The serumHP spec-ificity IgA and PARP-1 protein levels were detected using enzyme-linked immunosorbent assay method. The correlation of serum PARP-1 protein levels with clinical characteristics of gastric cancer was analyzed.Results:Compared with healthy people, serum PARP-1 protein levels were significantly higher in gastric cancer patients [(407±139) pg/mLvs(258±120) pg/mL,P=0.014). Serum PARP-1 protein levels were significantly higher inHp(+) gastric cancer patients than those in patients withHp (-) (P<0.001). Serum PARP-1 protein levels were positively correlated with family gastric cancer history (P=0.033) and alcohol intake history (P=0.015) in gastric cancer patients. Compared with serum protein PARP-1 negative patients, PARP-1 protein positive patients had a significantly shorter cancer-free survival (P=0.011). However serum PARP-1 protein level was not found to be an independent risk factor for the overall survival of gastric cancer patients using multivariate COX regression.Conclusion:High expression of serum PARP-1 protein may be involved in the pathogenesis and progression of gastric cancer. Inhibition of PARP-1 may be potential new target for the treatment of gastric cancer.

Aims To study the role of NGF/Trk A sig-naling pathway in Memantine ( MEM) improving APP/PS1 transgenic mice cognitive deficits and to explore its possible mechanisms. Methods Cognitive perform-ance was assessed by Morris water maze( MWM) , pas-sive avoidance test( PAT) and locomotivity test. Aβ1-42 protein levels were determined by immunohistochemis-try. The activities of AChE and ChAT were also exam-ined by ELISA and colorimetry. Western blot was used to detect the expression levels of NGF and its receptor TrkA and the downstream ERK pathway. Results MEM treatment significantly ameliorated the cognitive deficits, dramatically reduced the Aβ1-42 overexpres-sion. MEM increased the activity of choline acetyl-transferase( ChAT) , while decreased that of acetylcho-line esterase( AChE) . Moreover, MEM activiated NGF signaling by increasing the phosphorylation of TrkA fol-lowing the increased phosphorylation of c-Raf, ERK1/2 and downstream effector CREB after MEM treatment. Conclusion MEM treatment may activate the NGF/TrkA signaling in APP/PS1 mice to reduce amyloidosis and cognitive deficits.

Aim To investigate whether EGCG treat-ment ameliorates cognitive deficits in APP/PS1 trans-genic mice and, whether it has the ameliorating effect of p75 NTR signaling to neuronal apoptosis in the hippo-campus of APP/PS1 mice. Methods Morris water maze test and locomotivity test were used to predict be-havioral changes; further TUNEL staining and Fluoro-Jade B staining were applied to confirm the neuronal apoptosis and neuronal degeneration;Western blot was employed to detect protein expression levels of p75 NTR signaling in the hippocampus of APP/PS1 mice. Re-sults EGCG treatment dramatically ameliorated the cognitive impairments, and inhibited the neuronal ap-optosis in the APP/PS1 mice. Moreover, EGCG treat-ment dramatically inhibited the p75 NTR signaling by de-creasing the p75ICD expression, JNK2 phosphorylation, and cleaved-caspase 3 expression. Conclusion EGCG treatment dramatically ameliorates the cognitive impairments, and inhibits the neuronal apoptosis by in-hibiting the p75NTR signaling.

Renal tubular secretion mediated by organic anion transporters(OATs)and the multidrug resistance-associated protein 4(MRP4)is an important means of drug and toxin excretion.Unfortunately,there are no biomarkers to evaluate their function.The aim of this study was to identify and characterize an endogenous biomarker of the renal tubular OATs-MRP4 channel.Twenty-six uremic toxins were selected as candidate compounds,of which kynurenic acid was identified as a potential biomarker by assessing the protein-binding ratio and the uptake in OAT1-,OAT3-,and MRP4-overexpressing cell lines.OAT1/3 and MRP4 mediated the transcellular vectorial transport of kynurenic acid in vitro.Serum kynurenic acid concentration was dramatically increased in rats treated with a rat OAT1/3(rOAT1/3)inhibitor and in rOAT1/3 double knockout(rOAT1/3-/-)rats,and the renal concentrations were markedly elevated by the rat MRP4(rMRP4)inhibitor.Kynurenic acid was not filtered at the glomerulus(99％of albumin binding),and was specifically secreted in renal tubules through the OAT1/3-MRP4 channel with an appropriate affinity(Km)(496.7 μM and 382.2 μM for OAT1 and OAT3,respectively)and renal clearance half-life(ti/2)in vivo(3.7±0.7 h).There is a strong correlation in area under the plasma drug concentration-time curve(AUC0-t)between cefmetazole and kynurenic acid,but not with creatinine,after inhibition of rOATs.In addition,the phase of increased kynurenic acid level is earlier than that of creatinine in acute kidney injury process.These results suggest that albumin-bound kynurenic acid is an appropriate endogenous biomarker for adjusting the dosage of drugs secreted by this channel or predicting kidney injury.

Objective:To study the Epstein-Barr virus (EBV) activity and its clinical characteristics in patients with hemorrhagic fever with renal syndrome (HFRS). Methods:From January 2016 to August 2017, patients with HFRS who were hospitalized in the First Affiliated Hospital of Harbin Medical University were routinely tested by EBV serology, and were divided into two groups according to their presence or absence of EBV infection, namely EBV active group and non-EBV active group. The clinical data between the two groups were compared and analyzed by SPSS 18.0.Results:A total of 188 HFRS patients were enrolled, including 73 cases in EBV active group and 115 cases in non-EBV active group. The EBV active rate of HFRS patients was 38.83% (73/188). The incidences of lumbago [57.53% (42/73) vs 42.61% (49/115)], abdominal pain [42.47% (31/73) vs 20.00% (23/115)], skin and mucosa congestion [57.53% (42/73) vs 39.13% (45/115)], and conjunctiva edema [50.68% (37/73) vs 28.70% (33/115)] in EBV active group were significantly higher than those in non-EBV active group (χ 2 = 3.983, 11.008, 6.083, 9.239, P < 0.05). There were 10, 7 and 43 patients with acute kidney injury (AKI) stage 1, 2 and 3 in EBV active group and 5, 13 and 53 patients in non-EBV active group. Degree of AKI in EBV active group was higher than that in non-EBV active group, and the difference was statistically significant (χ 2 = 12.615, P < 0.05). In EBV active group, the proportion of patients whose renal function recovery over 15 days [23.29% (17/73)] and white blood cell count [11.26 (3.39 ~ 54.23) × 10 9/L] were significantly higher than those in non-EBV active group [6.96% (8/115), 10.03 (2.91 ~ 66.99) × 10 9/L], and the differences were statistically significant (χ 2 = 10.330, Z = - 2.003, P < 0.05). Conclusion:HFRS patients may cause latent EBV activity, complicate their clinical features, cause severe renal damage and prolong the recovery time of renal function.

Objective:To investigate frailty in older patients with comorbidities and explore related risk factors.Methods:A cross-sectional study was conducted with an enrollment of 746 patients aged 65 years or older with comorbidities in the Wanshoulu Road area of Beijing from April 2019 to December 2020.A total of 617 patients with comorbidities were finally included, aged(85.6±4.8)years, including 358 women(58.0%); According to the FRAIL scale, 617 patients with comorbidities were divided into a frail group(156 cases, 25.3%)and a non-frail group(461 cases, 74.7%). Demographic data and information on comorbidities were collected.Univariate and multivariate Logistic regression analyses of risk factors were conducted.Results:Among 617 patients with comorbidities, the common chronic diseases in descending order were hypertension(497 cases, 80.6%), coronary heart disease(375 cases, 60.8%), osteoporosis(357 cases, 57.9%), osteoarthritis(281 cases, 45.5%), type 2 diabetes(211 cases, 34.2%), stroke and/or transient ischemic attack(193 cases, 31.3%), chronic lung disease(144 cases, 23.3%), tumor(133 cases, 21.6%), chronic kidney disease(92 cases, 14.9%), and heart failure(58 cases, 9.4%). Univariate logistic regression analysis showed that age, type 2 diabetes, coronary heart disease, heart failure, chronic lung disease, stroke/transient ischemic attack, cancer and osteoarthritis were influencing factors for frailty( P<0.05). Multivariate logistic regression analysis showed that age, type 2 diabetes, heart failure, chronic lung disease, cancer and osteoarthritis were risk factors for frailty( OR=1.076, 1.806, 3.275, 3.371, 1.640, 2.227, all P<0.05). Conclusions:Old age, type 2 diabetes, heart failure, chronic lung disease, tumor and osteoarthritis are closely related to frailty in elderly patients with comorbidities.Proactive and effective prevention and intervention should be instituted to target risk factors for frailty to reduce the occurrence of adverse outcomes.

Objective:To observe the clinical characteristics and guideline compliance of chronic obstructive pulmonary disease (COPD) patients with initial triple therapy in real-life world.Methods:This study is a cross-sectional study. The subjects of the study were COPD patients admitted to 13 hospitals in Hunan Province and Guangxi Zhuang Autonomous Region from December 2016 to December 2021. The initial treatment was triple inhaled drugs. The data collected included gender, age, diagnosis, body mass index (BMI), history of acute exacerbation (AE) in the past year, pulmonary function, COPD Assessment Test (CAT) score, modified British Medical Research Council Dyspnea Questionnaire (mMRC), inhaled drugs and other indicators. The characteristics and differences of COPD patients before and after 2020 were analyzed.Results:7 184 patients with COPD were enrolled in this study, including 2 409 COPD patients treated with initial triple therapy, accounting for 33.5%(2 409/7 184). Taking January 1st, 2020 as the cut-off point, 1 825 COPD patients (75.8%) received initial treatment with triple inhaled drugs before 2020 and 584 patients (24.2%) after 2020 were included in this study. Compared with COPD patients before 2020, the COPD patients after 2020 had higher FEV 1% [(40.9±15.5 )% vs (39.3±15.5)%, P=0.040], lower CAT [(15.8±6.5)point vs (17.5±6.2)point, P<0.001], less AE in the past year [1(0, 2)times vs 1(0, 2)times, P=0.001] and higher rate of non-AE [255(43.7%) vs 581(37.1%), P=0.006]. In addition, before 2020, patients with COPD were mainly treated with open triple drugs (1 825/1 825, 100%); after 2020, 306 patients (52.4%) received open triple inhaled drugs, and 278 patients (47.6%) received closed triple inhaled drugs. Conclusions:In real-life world, most of patients with COPD treated with triple therapy have severe lung function, obvious symptoms and high risk of acute exacerbation. The real-world prescribing of triple therapy in patients with COPD does not always reflect recommendations in guidelines and strategies, and overtreatment is common. After 2020, prescribing triple therapy for COPD patients is more positive and worse consistency with guideline.