Toxicological evaluation of Yulangsan polysaccharide in Wistar rats: A 26-week oral gavage study

Although numerous studies have proven the medicinal values of Yulangsan polysaccharide (YLSP), the toxicity of this active ingredient is unknown. In the acute toxicity study, a single oral administration of 24 g/kg YLSP caused neither toxicological symptoms nor mortality, and the LD₅₀ was estimated >24 g/kg. In the chronic toxicity study, we administered doses of 0, 0.6, 1.2 and 2.4 g/kg YLSP in rats by oral gavage for 26 weeks followed by a 3-week recovery period. There was no mortality or remarkable clinical signs observed during this 26-week study. Additionally, there were no toxic differences in the following parameters: body weight, food consumption, hematology, clinical biochemistry, organ weight, and macroscopic findings. There were no adverse effects on histopathology observed in males or female rats treated with YLSP. Based on the results, the no-observed-adverse-effect-level of YLSP in rats is greater than 2.4 g/kg when administered orally for 26 consecutive weeks.     

Cardiovascular effects and mechanisms of sodium-glucose cotransporter-2 inhibitors

Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) are a new type of drug for the treatment of diabetes, and they have been proven to have a good hypoglycemic effect. Several lines of clinical evidence have shown that SGLT2 inhibitors can significantly reduce the risks of atherosclerosis, hospitalization for heart failure, cardiovascular death, and all-cause mortality and delay the progression of chronic kidney disease. Because of the protective effects of SGLT2 inhibitors on the heart and kidney, they are being studied for the treatment of heart failure and chronic kidney disease in patients without diabetes. Therefore, it is necessary for cardiologists, patients with diabetes, and nephrologists to fully understand this type of drug. In this review, we summarize the following three aspects of SGLT2 inhibitors: the recent clinical evidence of their cardiovascular benefits, their mechanisms of action, and their safety.     

Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response

Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4⁺ T cells in the lung. PA-specific CD4⁺ T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity.     

Aflibercept in Combination With FOLFIRI as First-line Chemotherapy in Patients With Metastatic Colorectal Cancer (mCRC): A Phase II Study (FFCD 1302)

BackgroundFOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) + aflibercept improves median overall survival (OS) and progression-free survival (PFS) in patients with previously treated metastatic colorectal cancer (mCRC). Our aim was to investigate efficacy and tolerability of this combination in the first line.Patients and MethodsPatients with untreated documented mCRC received aflibercept plus FOLFIRI every 14 days until progression or unacceptable toxicity in an open, phase II single-arm, multicenter trial. The primary endpoint was the 6-month PFS rate. Secondary endpoints were OS and tolerability. A 2-step Simon design was used with H₀: 55% and H₁= 75%. Data were analyzed in intention to treat.ResultsForty-one patients were included, and 40 were analyzed (1 consent withdrawal) in 9 French centers between October 2014 and February 2017. The median age was 65 years (range, 46-81 years), 55% had ≥ 2 metastatic sites, and 50% and 15% had RAS and BRAF mutations, respectively. Twenty-two (54.5%; 95% confidence interval, 38.9%-68.5%) patients were alive and non-progressive at 6 months. FOLFIRI + aflibercept was considered ineffective, resulting in the cessation of inclusions. The median follow-up was 34 months. The overall response rate was 55%, and the disease control rate was 80%. The median duration of treatment was 5.3 months; the median PFS and OS were 8.2 and 18.6 months, respectively. Grade 3 to 4 adverse events were mainly gastrointestinal (47.5%) and vascular (32.5%). Of the patients, 87.5% had at least 1 dose modification.ConclusionAlthough the primary objective was not met, first-line FOLFIRI + aflibercept for mCRC leads to median PFS and OS close to those reported with classical doublet and targeted agents, but with significant toxicities needing dose reduction.     

The impact of circumferential tumour location on the clinical outcome of rectal cancer patients managed with neoadjuvant chemoradiotherapy followed by total mesorectal excision

AimTo investigate the impact of circumferential tumour location on neoadjuvant chemoradiotherapy (CRT) response and its prognostic value for locally advanced rectal cancer (LARC) patients after CRT and surgery.MethodsA retrospective study was performed on 486 patients with LARC who received neoadjuvant CRT and surgical treatment. The rate of pathological complete response (pCR) and survival among patients with anteriorly, laterally, and posteriorly located tumours were compared. Logistic regression was performed to identify pCR predictors.ResultsThe anterior tumours exhibited the highest pCR rate of 26.7%, which was slightly higher than the 20.0% and 12.3% for lateral and posterior tumours, respectively (P = 0.006). The 5-year Overall survival (OS) rates after CRT were similar among the anterior, lateral, and posterior groups (anterior vs lateral vs posterior: 81.1% vs 89.9% vs 84.1%, P = 0.6368). Multivariate analysis revealed that the circumferential tumour location, post-CRT serum CEA and post-CRT tumour thickness measured by MRI were independently correlated with achieving pCR.ConclusionThis study is the first, to the best of our knowledge, to show that anterior LARC exhibited the highest pCR rate after neoadjuvant CRT. Patients with anterior rectal cancers do not have different prognoses from those with non-anterior cancers if they undergo neoadjuvant CRT.     

Referral patterns and outcomes of a highly specialised pelvic exenteration multidisciplinary team meeting: A retrospective cohort study

IntroductionThe purpose of this study was to review recommendations made from a specialist pelvic exenteration (PE) multidisciplinary team (MDT) and to provide insights as to the impact of the MDT on patient selection and clinical decision making.Materials & methodsA retrospective review was conducted at Royal Prince Alfred Hospital's PE MDT between June 2014 and December 2015. Data was collected from the recorded minutes of MDT meetings. Referral information and clinical data was extracted from individual patient files. Additional data including operative dates and surgical resection margins were collected from electronic medical records.ResultsOf the 183 patients considered for PE during the MDT meeting, 104 (57%) were recommended for surgery. Factors that influenced the recommendation in favour of surgery were referral by a surgeon (P = 0.004), referral from a rural location (P = 0.05) and having locally advanced primary cancer (P < 0.001). Patients who were seen by the unit's surgeon prior to the MDT did not impact on the MDT recommendation nor the decision for or against surgery (P = 0.771). The most common reason for recommendation against PE was unresectable distant metastatic disease (43%).ConclusionsThe PE MDT meeting is a critical step in the patient care pathway and facilitates critical decision making. Anatomically-based contraindications to surgery (i.e. involvement of adjacent organs, bone and neurovascular structures) do not appear to influence MDT decision making regarding resectability.     

Curcumin ameliorates hepatic chronic inflammation induced by bile duct obstruction in mice through the activation of heme oxygenase-1

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