Phloretin targets SIRT1 to alleviate oxidative stress, apoptosis, and inflammation in deep venous thrombosis.

Deep vein thrombosis (DVT) is a type of venous thromboembolism posing a serious threat to health on a global scale. Phloretin is a potential natural product that has a variety of pharmacological activities. Besides, some Chinese medicines reported that deacetylase sirtuin (SIRT)1 treats DVT by anti-inflammatory and anti-platelet production. However, the specific binding targets and binding modes have not been elaborated. The present study was to investigate whether phloretin attenuates DVT in model rats and oxidized low­density lipoprotein (ox­LDL) induced human umbilical vein endothelial cells (HUVECs), and to explore its potential target. The results revealed that the treatment of phloretin, especially pretreatment of it elevated tissue plasminogen activator (t-PA), superoxide dismutase (SOD), prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), and cell apoptosis proteins whereas it suppressed plasminogen activator inhibitor (PAI), malondialdehyde (MDA), reactive oxygen species (ROS), fibrinogen (FIB) in DVT rats and cells. Concurrently, phloretin inhibited collagen type I alpha 1 (COL1A1), transforming growth factor-ß1 (TGF-ß1), and inflammatory factors while it enhanced nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase 1 (HO-1). In addition, 20 µM phloretin exerted powerful effective protection in HUVECs with DVT model. Later, the surface plasmon resonance (SPR) confirmed that phloretin has a high affinity with SIRT1. Furthermore, siRNA-SIRT1 transfection abolished the protective effect of phloretin against ox­LDL­induced DVT in HUVECs, indicating that phloretin targets SIRT1 to alleviate oxidative stress, cell apoptosis, and inflammation in DVT rats and HUVECs. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00207-y.

Clinical characteristics of snakebite patients attending a tertiary hospital in Hangzhou, southeast China.

BACKGROUND: Venomous snakebite is a neglected yet an important public health problem in China, and few studies have focused on them so far. The aim of this study is to investigate clinical characteristics of snakebites patients in a tertiary hospital in Hangzhou, southeast China. METHODS: A total of 416 snakebite cases were included in this retrospective study. The data were collected from the medical records including demographics, clinical manifestations, management and outcomes. RESULTS: Of the 416 patients with venomous snakebites, 248 were male, and the average age was 54.6 years. The majority of cases occurred in rural in May to September. Out of all the venomous bites, Gloydius brevicaudus accounted for the highest percentage (55.3%). Hands were the most vulnerable site to snakebites (47.4%). Patients had clinical manifestations of pain (100%), swelling (100%), wound necrosis (25.7%), hemorrhagic blister (18.3%), and blister (8.7%). Three hundred and ninety-two patients received antivenom administration, and most were treated within six hours after bites. Twenty-six patients received surgical treatments, and 90 patients developed venom-induced consumption coagulopathy. No deaths have occurred in this study. CONCLUSION: Hangzhou is one of the regions with high affecting of snakebites in China. The results of this study will increase the understanding of the clinical characteristics of venomous snakebites in Hangzhou area.

Bacteriological Studies of Venomous Snakebite Wounds in Hangzhou, Southeast China.

Snakebite is a common occurrence in Hangzhou, and identifying bacteria in wounds is very important for snakebite treatment. To define the pattern of wound bacterial flora of venomous snakebites and their susceptibility to common antibiotics, we reviewed the medical charts of patients admitted with snakebite at Hangzhou TCM Hospital from January 2019 to December 2020. A total of 311 patients were enrolled in this study. Among them, bacteria culture was positive in 40 patients, and 80 organisms were isolated. The most frequent pathogens were Morganella morganii and Staphylococcus aureus. According to the results of susceptibility testing, a majority of the isolates were resistant to some common first-line antibiotics, such as ampicillin, ampicillin/sulbactam, amoxicillin/clavulanic acid, cefoxitin, and cephazolin. Quinolones, however, have shown a better antibacterial effect. In conclusion, snakebite wounds involve a wide range of bacteria. Fluoroquinolones, such as levofloxacin and ciprofloxacin, could be an alternative for empirical treatment in patients with snakebite when the effect of other antibiotics is poor.

A high value of fibrinogen in immunoglobulin A nephropathy patients is associated with a worse renal tubular atrophy/interstitial fibrosis score.

PURPOSE: The purpose of our study was to investigate the relationship between serum fibrinogen value and renal tubular atrophy/interstitial fibrosis in immunoglobulin A nephropathy patients with eGFR ≥90 ml/min/1.73 m2 . PATIENTS AND METHODS: Of 359 patients diagnosed with immunoglobulin A nephropathy after renal biopsy were enrolled in this retrospective study. Demographic, histopathological features, and clinical data were collected. The relationships among these factors were analyzed by using Student's t test, Mann-Whitney U test, Kruskal-Wallis test, Chi-square test, or Fisher's exact test, where appropriate. The logistic regression analysis was performed to examine the independent risk factors. RESULTS: Of 176 immunoglobulin A nephropathy patients with eGFR ≥90 ml/min/1.73 m2 were included in this study, and patients were classified into low fibrinogen (fibrinogen <304.6 mg/dl) and high fibrinogen (fibrinogen ≥304.6 mg/dl) groups, respectively. High fibrinogen groups had advanced age, a higher classification of renal tubular atrophy/interstitial fibrosis, and higher levels of systolic pressure, D-dimer, 24 h urine protein quantitation, nag enzyme. Multivariate logistic analysis showed that fibrinogen (OR = 1.018) was significantly associated with tubular atrophy/interstitial fibrosis. CONCLUSION: Among patients with immunoglobulin A nephropathy, the higher levels of fibrinogen and uric acid may mean a higher score of tubular atrophy/interstitial fibrosis, which suggests the renal biopsy should be performed for these patients as early as possible to defined pathological classification, even though there is no obvious abnormal change in the test of renal function.

Critical lower extremity ischemia after snakebite: A case report.

BACKGROUND: Globally, the estimated annual incidence of snakebites is approximately 5 million, and approximately 100000 deaths occur from snakebites annually. Local tissue reaction, haemorrhagic clotting disorder, nephrotoxicity, and neurotoxicity are very common effects of snake envenomation, but other rarer complications, such as thrombosis, may also occur as a result of underlying disease. In the treatment of snakebite patients, attention should be paid to the patient's underlying diseases to avoid serious and catastrophic consequences secondary to snakebite. CASE SUMMARY: We report a 69-year-old man with critical right lower extremity pain after left foot snakebite 10 d prior without intermittent claudication or atrial fibrillation history. He was diagnosed with acute right lower extremity arterial thrombosis, which may have been caused by coagulopathy after snakebite and lower extremity atherosclerotic occlusive disease. Lower extremity computed tomography angiography at another hospital revealed that the aortoiliac and femoral arteries had neither filling defects nor atherosclerosis, but the right popliteal artery was occluded 2.3 cm below the tibial plateau. The patient received emergency catheter-directed thrombolysis, but amputation was carried out 11 d after admission because the patient had been admitted to the hospital too late to save the extremity. CONCLUSION: Acute ischaemia of the lower extremity due to snakebite is a rare event, and physicians should bear in mind the serious complications that may occur, especially in patients with atherosclerotic disease.

The Prognostic Value of Preoperative Geriatric Nutritional Risk Index in Patients with Pancreatic Ductal Adenocarcinoma.

PURPOSE: Patients with malignancy are more likely to develop nutritional problems. The Geriatric Nutritional Risk Index (GNRI) is a new prognostic index for evaluating nutritional status. The objective of this study was to assess if preoperative GNRI could be a prognostic factor for patients with pancreatic ductal adenocarcinoma (PDAC) who underwent radical surgery. PATIENTS AND METHODS: This study included 282 consecutive patients with incident pancreatic ductal adenocarcinoma who were treated with radical surgery. The Cox regression analysis was performed to calculate the overall survival (OS) and assess the prognostic factors. A nomogram was developed based on the results of the multivariate analysis, and the predictive accuracy of the nomogram was assessed. RESULTS: Among the 282 patients, there are 117 males and 165 females. The patients had a mean age of 58.7 ±13.5 years, with the median follow-up time of 72.9 months (interquartile range, 0.7 to 115.2 months). They were classified into abnormal (GNRI ≤ 98) and normal (GNRI > 98) GNRI groups, respectively. Multivariate Cox analysis showed that age (HR = 1.023), drinking history (HR = 1.453), tumor grade (HR = 1.633), TNM stage (HR = 1.921), and GNRI (HR = 1.757) were significantly associated with OS. Based on the above variables, the nomogram was established. The concordance index (C-index) and time-dependent receiver operating characteristics curve (tdROC) showed the nomogram was superior to TNM grade and tumor grade in predicting the OS of patients with PDAC. CONCLUSION: GNRI could be a useful prognostic indicator in patients with PDAC who received surgery. Based on the GNRI and the other clinical indicators, we developed a nomogram model that can provide an accurate estimation of OS in patients with PDAC after radical surgery.

A sample model established by S-index predicting overall survival after curative resection of primary hepatocellular carcinoma.

PURPOSE: Prognostic prediction after curative resection of primary hepatocellular carcinoma (PHCC) remains an arduous task. The S-index calculated from γ-glutamyl transpeptidase, albumin, and platelets is reported to predict the severity of liver fibrosis. We constructed a nomogram for predicting the survival probability of PHCC based on a new indicator, the S-index, combined with other routine clinical parameters. PATIENTS AND METHODS: We selected 490 patients with PHCC postradical surgery at the First Affiliated Hospital of Wenzhou Medical University between January 2007 and January 2014. The subjects were randomly allocated into the training cohort and the validation cohort in the ratio 7:3 by the digital method. Important variables screened by univariate analysis were included in multivariate analysis to obtain independent risk factors for predicting the prognosis of PHCC. The construction of the nomogram was based on Cox proportional hazard regression models. The concordance index (C-index) was used in the nomogram for evaluating the model performance for prognosis. We drew time-dependent receiver operating characteristic curves to compare our model with other staging systems. RESULTS: The nomogram based on six independent risk factors after multivariate analyses had good predictive power after radical surgery of PHCC. In the training and validation groups, the C-index of the nomogram was highly consistent for evaluating survival from PHCC. Compared with the traditional scoring system, the areas under time-dependent receiver operating characteristic curves were 0.7382, 0.7293, and 0.7520 for 1-, 3-, and 5-year overall survival, respectively. In summary, the nomogram showed excellent results in terms of prognosis of PHCC. CONCLUSION: Based on the S-index and the other clinical indicators, we developed a precise nomogram that predicts the survival probability of patients with PHCC after radical surgery. This tool can provide effective information for surgeons and patients.