Objective:To analyze the clinical characteristics of warfarin-related nephropathy (WRN).Methods:Medical records of patients with WRN admitted to Linyi People′s Hospital Affiliated to Shandong Second Medical University from January 1, 2020 to December 31, 2024 were collected. The patients′ basic information (gender, age), warfarin medication details (indications, dosage, frequency, etc.), comorbidities, concomitant medication usage, international normalized ratio (INR) and serum creatinine (Scr) test results before and after the occurrence of WRN, as well as the clinical manifestations, interventions, and outcomes of WRN were extracted. The causal relationship between warfarin and renal dysfunction was evaluated according to the Adverse Drug Reaction Reporting and Monitoring Manual. The clinical data of patients were descriptively and statistically analyzed. Results:A total of 11 patients were entered in the analysis, including 7 males and 4 females; the age ranged from 49 to 85 years, with a median age of 70 years, and 9 cases were older than 60 years. The causality evaluation showed that 3 patients were definite and 8 patients were probable. All the 11 patients had at least one comorbidity, including 6 cases of heart failure, 6 cases of hypoproteinemia, 4 cases of chronic kidney disease, 3 cases of hypertension, 3 cases of pulmonary infection, and 1 case of diabetes. Seven patients were treated with warfarin combined with broad-spectrum antibiotics, 6 combined with diuretics, and 3 combined with renin angiotensin system blockers. The time from the highest INR to the highest Scr level was 0-6 days, with a median time of 2 days, and it was ≤2 days in 9 patients. Six patients had bleeding manifestations such as microscopic hematuria, melena, epistaxis, hematochezia, and skin ecchymosis. Among the 11 patients, 10 stopped warfarin immediately and 1 reduced dosage. All patients received different doses of vitamin K 1 according to the INR level. Among the 6 patients of bleeding, 4 received symptomatic treatments such as omeprazole, tranexamic acid, somatostatin, thrombin powder and octreotide, and 2 patients received hemodialysis due to high Scr level. One patient with severe anemia received blood transfusion. After 1-5 days of treatments (with a median time of 2 days), the INR in all patients decreased to <3.00, of which 5 patients continued to take warfarin, 1 changed warfarin to rivaroxaban, and 5 did not continue anticoagulation therapy. After 2 to 14 days of treatments, Scr in 8 patients recovered to the reference value range, and Scr in 3 patients was still at a high level, of which 1 patient died of unexplained cardiac arrest. Conclusions:WRN is a common adverse reaction of warfarin, with or without bleeding. After the occurrence of WRN, the drug should be stopped as soon as possible and symptomatic treatment should be given. The prognosis is generally good, but it may also lead to chronic kidney disease.

Objective:To analyze the clinical characteristics of warfarin-related nephropathy (WRN).Methods:Medical records of patients with WRN admitted to Linyi People′s Hospital Affiliated to Shandong Second Medical University from January 1, 2020 to December 31, 2024 were collected. The patients′ basic information (gender, age), warfarin medication details (indications, dosage, frequency, etc.), comorbidities, concomitant medication usage, international normalized ratio (INR) and serum creatinine (Scr) test results before and after the occurrence of WRN, as well as the clinical manifestations, interventions, and outcomes of WRN were extracted. The causal relationship between warfarin and renal dysfunction was evaluated according to the Adverse Drug Reaction Reporting and Monitoring Manual. The clinical data of patients were descriptively and statistically analyzed. Results:A total of 11 patients were entered in the analysis, including 7 males and 4 females; the age ranged from 49 to 85 years, with a median age of 70 years, and 9 cases were older than 60 years. The causality evaluation showed that 3 patients were definite and 8 patients were probable. All the 11 patients had at least one comorbidity, including 6 cases of heart failure, 6 cases of hypoproteinemia, 4 cases of chronic kidney disease, 3 cases of hypertension, 3 cases of pulmonary infection, and 1 case of diabetes. Seven patients were treated with warfarin combined with broad-spectrum antibiotics, 6 combined with diuretics, and 3 combined with renin angiotensin system blockers. The time from the highest INR to the highest Scr level was 0-6 days, with a median time of 2 days, and it was ≤2 days in 9 patients. Six patients had bleeding manifestations such as microscopic hematuria, melena, epistaxis, hematochezia, and skin ecchymosis. Among the 11 patients, 10 stopped warfarin immediately and 1 reduced dosage. All patients received different doses of vitamin K 1 according to the INR level. Among the 6 patients of bleeding, 4 received symptomatic treatments such as omeprazole, tranexamic acid, somatostatin, thrombin powder and octreotide, and 2 patients received hemodialysis due to high Scr level. One patient with severe anemia received blood transfusion. After 1-5 days of treatments (with a median time of 2 days), the INR in all patients decreased to <3.00, of which 5 patients continued to take warfarin, 1 changed warfarin to rivaroxaban, and 5 did not continue anticoagulation therapy. After 2 to 14 days of treatments, Scr in 8 patients recovered to the reference value range, and Scr in 3 patients was still at a high level, of which 1 patient died of unexplained cardiac arrest. Conclusions:WRN is a common adverse reaction of warfarin, with or without bleeding. After the occurrence of WRN, the drug should be stopped as soon as possible and symptomatic treatment should be given. The prognosis is generally good, but it may also lead to chronic kidney disease.

A 49-year-old male patient received long-term use of warfarin 5 mg once daily orally after the operation of aortic mechanical valve replacement, and the international normalized ratio (INR) was maintained at 1.80~2.50. The patient was treated with amiodarone due to atrial tachycardia, and developed nasal bleeding 1 week later. Laboratory tests showed prothrombin time (PT) 79.7 s, INR 10.17, serum creatinine (Scr) 1 032 μmol/L, and blood urea nitrogen (BUN) 29.4 mmol/L; urine routine examination showed urinary occult blood (+) and urinary protein (±). Considering that it was warfarin-related nephropathy caused by the combination of amiodarone, which can enhance the anticoagulant effect of warfarin, leading to excessive anticoagulation. Warfarin was discontinued and the treatments such as local hemostasis, vitamin K 1, tranexamic acid, Bailing capsules (百令胶囊), lanthanum carbonate chewable tablets, and continuous hemodialysis were given. Five days of drug withdrawal, warfarin was restored. Two weeks later, laboratory tests showed PT 21.0 s, INR 1.82, Scr 179 μmol/L, and BUN 19.0 mmol/L. Renal function indicators were within the reference range at 2 and 6 months of follow-up.

A 49-year-old male patient received long-term use of warfarin 5 mg once daily orally after the operation of aortic mechanical valve replacement, and the international normalized ratio (INR) was maintained at 1.80~2.50. The patient was treated with amiodarone due to atrial tachycardia, and developed nasal bleeding 1 week later. Laboratory tests showed prothrombin time (PT) 79.7 s, INR 10.17, serum creatinine (Scr) 1 032 μmol/L, and blood urea nitrogen (BUN) 29.4 mmol/L; urine routine examination showed urinary occult blood (+) and urinary protein (±). Considering that it was warfarin-related nephropathy caused by the combination of amiodarone, which can enhance the anticoagulant effect of warfarin, leading to excessive anticoagulation. Warfarin was discontinued and the treatments such as local hemostasis, vitamin K 1, tranexamic acid, Bailing capsules (百令胶囊), lanthanum carbonate chewable tablets, and continuous hemodialysis were given. Five days of drug withdrawal, warfarin was restored. Two weeks later, laboratory tests showed PT 21.0 s, INR 1.82, Scr 179 μmol/L, and BUN 19.0 mmol/L. Renal function indicators were within the reference range at 2 and 6 months of follow-up.

【Objective】 To investigate the characteristics of HBV serological markers of NAT reactive blood donors under different HBsAg status. 【Methods】 NAT reactive samples, with HBsAg-, HBsAg+ /retest - and HBsAg+ by single reagent were collected from September 2021 to May 2022 in our laboratory. The TMA non-reactive samples were retested by Roche PCR, then HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc were detected by ECLI for statistical analysis. 【Results】 A total of 66 samples were collected, among which 55 were HBsAg-/NAT+. The positive rate of anti-HBc, anti-HBs+ anti-HBc, anti-HBe+ anti-HBc was 87.3% (48/55), 43.6% (24/55) and 45.5% (25/55), respectively. The positive rate of anti-HBs was 10.9% (6/55) and the overall negative rate was 1.8% (1/55). In 7 HBsAg+ initially/retest -/NAT+ samples, the positive rate of anti-HBc was 100%(7/7), and the positive rate of anti-HBe+ anti-HBc was 71.4%(5/7). In 4 HBsAg+ /NAT+ samples by single reagent, the positive rate of HBsAg+ anti-HBs+ anti-HBe+ anti-HBc was 50% (2/4), and positive rate of anti-HBe+ anti-HBc was100% (4/4). Samples, not reactive to TMA discriminatory and anti-HBc negative, were also non-reactive to individual PCR retest. There were significant differences in the positive rates of anti-HBe+ anti-HBc between HBsAg-/NAT+ samples and HBsAg+ /NAT+ (single reagent) samples (P<0.05). 【Conclusion】 Most HBsAg-/NAT+ blood donors were occult hepatitis B virus infection.The anti-HBe+ anti-HBc positive were correlated with HBV infection status. Non-reactivity discriminated by TMA plus anti-HBc negative do not exclude HBV DNA non-reactivity.

Objective:To investigate the relationship between early international normalized ratio(INR)and overanticoagulation in elderly patients with atrial fibrillation(AF)treated with Warfarin, and to evaluate its clinical value in predicting overanticoagulation.Methods:A total of 470 elderly patients with AF treated with Warfarin for anticoagulation were enrolled retrospectively.INR was detected in the morning of the next day after 3 days and 7 days of Warfarin treatment.According to whether INR was greater than 3.0 after 7 days of Warfarin treatment, the patients were divided into over-anticoagulation group(n=107)and non-over-anticoagulation group(n=363). The general clinical data of the two groups were analyzed.The receiver operating characteristic curve(ROC)was used to evaluate the value of 3-day INR(early INR)level in predicting overanticoagulation.Logistic regression was used to analyze the factors related to overanticoagulation in elderly AF patients receiving Warfarin treatment.Results:The age, initial warfarin dose, early INR and serum aspartate transferase level in the over-anticoagulation group were higher than those in the non-over-anticoagulation group( P<0.05 for all). The proportions of patients with initial Warfarin dose≥2.5 mg, age≥70 years old, body weight≤65 kg, valvular atrial fibrillation, hypoproteinemia, abnormal liver function, and combined use of antibiotics were higher in the over-anticoagulation group than those in the non-over-anticoagulation group( P<0.05 for all). The body weight, serum albumin level and the proportion of diabetes mellitus in the over-anticoagulation group were lower than those in the non-over-anticoagulation group( P<0.05). ROC curve showed that the area under the curve(AUC)of early INR in predicting over-anticoagulation was 0.927(95% CI: 0.900-0.949, P<0.0001), the sensitivity was 82.86% and the specificity was 88.43%, the optimal cutoff value for predicting overanticoagulation was INR≥1.66.Multiple Logistic regression analysis showed that early INR level≥1.66( OR=33.871, P<0.001), initial warfarin dose≥2.5 mg( OR=17.062, P=0.011), body weight≤65 kg( OR=2.824, P=0.002), age≥70 years old( OR=2.678, P=0.003), and abnormal liver function( OR=2.091, P=0.022)were related factors for over-anticoagulation in elderly patients with atrial fibrillation. Conclusions:Early INR level is closely related to overuse of anticoagulation in elderly AF patients receiving Warfarin treatment, which can be regarded as a predictor of overuse of anticoagulation.Early INR level in elderly AF patients receiving warfarin treatment should be monitored to reduce the incidence of anticoagulant overuse.

Objective:To investigate the effect of preoperative use of diuretics on cardiac surgery-associated acute kidney injury(CSA-AKI)in elderly patients.Methods:In this single-center retrospective study, 1 638 patients aged ≥60 years and undergone cardiac surgery(including coronary artery bypass grafting, valve replacement and valvuloplasty)in the Department of Cardiovascular Surgery, Linyi People's Hospital between January 2015 and December 2022 were recruited.The last preoperative serum creatinine(SCr)level was taken as the baseline value, and AKI was diagnosed according to the Kidney Disease Improving Global Outcomes(KDIGO)criteria.Patients were divided into an AKI group and a non-AKI group according to whether AKI occurred after surgery.The clinical characteristics of the two groups were compared, and the effect of preoperative use of diuretics on CSA-AKI was evaluated by multivariate Logistic regression analysis.Results:Of 1638 patients enrolled in the study, 284 patients(17.3%)developed CSA-AKI.Compared with the non-AKI group, there were higher proportions of patients in the AKI group receiving furosemide(62.7% or 178/284 vs.46.2% or 626/1 354, χ2=25.397, P<0.001), spironolactone(70.1% or 199/284 vs.49.9% or 676/1 354, χ2=38.284, P<0.001), and hydrochlorothiazide(8.1% or 23/284 vs.3.5% or 47/1354, χ2=12.288, P<0.001). The number of diuretics in the AKI group was higher than in the non-AKI group[2(0, 2) vs.1(0, 2), Z=-6.381, P<0.001], and the proportion of patients using ≥2 diuretics was higher in the AKI group than in the non-AKI group(70.1% or 199/284 vs.49.0% or 664/1354, χ2=41.652, P<0.001). Multivariate Logistic regression analysis showed that, after adjusting for hypertension, diabetes mellitus, hypoalbuminemia, NYHA functional class Ⅲ/Ⅳ, cardiopulmonary bypass during surgery, operative duration≥6 h, postoperative blood transfusion>600 ml, postoperative use of >3 vasoactive drugs and other variables, preoperative use of ≥2 diuretics remained an independent risk factor for CSA-AKI in elderly patients( OR=1.580, 95% CI: 1.042-2.396, P=0.031). Conclusions:AKI is a common complication after cardiac surgery in elderly patients.Preoperative use of ≥2 diuretics used may be an independent risk factor for CSA-AKI.

【Objective】 To explore the status of HBV infection and low viral load of HBV DNA in blood donor samples implicated in TMA triplex reactive but discriminatory test non-reactive samples. 【Methods】 A total of 51 996 samples were detected by Procleix Panther nucleic acid detection(NAT) system from January 2020 to March 2021, and 86 of them were TMA triplex reactive but discriminatory test non-reactive. HBV serological markers (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc) were detected by electrochemiluminescence. Single-donation(ID) NAT was conducted in some TMA triplex + /discriminatory test-samples using Roche NAT. 【Results】 Out of 86 TMA triplex + /discriminatory test-samples, anti-HBc were positive in 89.53% (77/86), anti-HBe positive in 27.90% (24/86) and anti-HBs positive in 65.12% (56/86). 15 donors carried anti-HBs, anti-HBe and anti-HBc, 34 both anti-HBs and anti-HBc, 1 both anti-HBs/anti-HBe, 8 both anti-HBe/anti-HBc, 6 solo anti-HBs, and 20 solo anti-HBc. The positive rate of HBV serological markers was 97.67% (84/86). HBV DNA in 5 out of the 10 samples was qualitatively detected by Roche ID NAT, and one of them presented HBV DNA < 20 IU/mL. 【Conclusion】 Most TMA triplex + /discriminatory test-samples were occult hepatitis B infection.

BACKGROUND:In recent years, based on high-throughput molecular imaging, integration of genomics, proteomics and computer aided design and the application of correlative “technical chains” have achieved great achievements in the research of breast cancer, lung cancer, gastric cancer, colon cancer, ovarian cancer and melanin tumor. However, there are few researches on oral squamous cel carcinoma. OBJECTIVE:To detect the gene expression profile of the oral squamous cel carcinoma tissue and normal paracarcinoma tissue using DNA chip-based gene expression profile. METHODS:Two samples of oral squamous cel carcinoma tissue and normal paracarcinoma tissue of patients who received treatment at Stomatological Hospital of Guangdong Province of China in 2013 were included in this study. The gene expression profiles of oral squamous cel carcinoma and normal paracarcinoma tissue were determined by the Roche NimbleGen gene expression microarrays. RESULTS AND CONCLUSION: According to screening criteria of differential genes, 7 872 out of 32 448 detected genes were differentialy expressed genes of oral squamous cel carcinoma, which accounts for 24% of the total number of the screening genes. 3 800 genes were up-regulated, and 4 072 were down-regulated. The results confirm that through detection with the help of gene expression profile clip, 7 872 differentialy expressed genes were obtained through DNA chip-based gene expression profiles according to the screening criteria. Thus it can be concluded that the occurrence and development of the tumors are not a result of single or several genes. Previous experiments based on a single or several genes have great limitations. These findings also suggest that the occurrence of tumor is a result of mutual regulatory effects of many genes forming a network, moreover, the interactions of the network is quite complicated.

BACKGROUND:RACK1 is strongly associated with the occurrence and development of oral squamous cel carcinoma. However, the occurrence and development of tumor do not depend on a gene or protein, but a long-term complex process of a network structure of multiple genes and multiple molecules, multi-step, multi-stage joint action. Synergism between tumor genes promotes the formation and development of tumor cel s. Therefore, we cannot limit on a single gene or protein to discover the action mechanism of oral squamous cel carcinoma, but should pay attention on signaling network path related to differential protein or gene, investigate the alterations in related protein or gene expression in the whole signaling pathway, and analyze the action mechanism of the interaction of these molecules.
OBJECTIVE:To screen differential genes related to oral squamous cel carcinoma, construct an interaction network through bioinformatics using STRING database, and provide clues for future tests.
METHODS:In accordance with our previous classic proteomics results and microarray results of oral squamous cel carcinoma, genes with consistent expression and big differences were selected as differential genes. The differential genes were inputted into the database of STRING to find the possible relationship among the protein subunits and to construct network structure of their interaction.
RESULTS AND CONCLUSION:The 19 differential proteins of oral squamous cel carcinoma construct a complicated net work, and the differential proteins interact through these networks. GNB2L1-encoded RACK1 is a node protein and interacts with other differential proteins via WD40 repeated protein (number COG2319) andβ-G protein subunit (number KOG0279). WD40 repeated protein (number COG2319) interacts with 5 differential proteins directly and constructs 10 interacting pathways.β-G protein subunit (number KOG0279) interacts with 8 differential proteins directly, which has 11 interacting pathways. We make a network structure picture based on the interaction of these 19 differential genes by the analysis of the STRING database. The results show that the two subunits of RACK1 protein have direct interaction with 8 differential proteins and have 18 interaction pathways on the picture. As a result, RACK1 is the core protein of the network, suggesting RACK1 is the key node protein in oral squamous cel carcinoma.