Correlative study between the JAK2V617F mutation and thrombosis in patients with myeloproliferative neoplasm.

In this study, we investigated the correlation between the JAK2V617F mutation and thrombosis in patients with myeloproliferative neoplasm (MPN) using real-time fluorescence quantitative PCR. The incidence of thrombus was monitored and blood and coagulation were routinely assayed in patients with MPN. The JAK2V617F mutation was found in 8/68 individuals in the control group (11.8%); it was expressed in 44/68 patients with MPN (64.7%), suggesting that the rate of this mutation was significantly higher in patients with MPN than that in the control group. Twenty-six MPN patients (38.2%) showed symptoms of thrombosis; MPN patients with thrombosis showed a significantly higher rate of the JAK2V617F mutation, were of a greater age, and had higher blood pressure than MPN patients without thrombosis. In addition, the white blood cells (WBC) (21.98 ± 1.95) and platelets (364.68 ± 97.72) were significantly higher in patients, expressing the mutated gene, with polycythemia vera than in the patients without the mutation. The WBC (32.89 ± 4.25) and hemoglobin (161.92 ± 16.19) were significantly increased in the essential thrombocythemia patients with gene mutation compared with the patients without mutation. MPN patients showed higher blood clotting ability than the control subjects; moreover, MPN patients with the JAK2V617F mutation showed higher blood clotting ability than those without the mutation. The findings of this study indicate that the JAK2V617F mutation is correlated with the incidence of thrombosis, and analysis of this mutation has important clinical significance in the diagnosis and treatment of MPN.

Impact of adherence to GOLD guidelines on 6-minute walk distance, MRC dyspnea scale score, lung function decline, quality of life, and quality-adjusted life years in a Shanghai suburb.

We performed a 1-year cluster-randomized field trial to assess the effect of standardized management of chronic obstructive pulmonary disease (COPD) on lung function and quality of life (QOL) measures in patients in China. We used the Global Initiative for Chronic Obstructive Lung Disease (GOLD) treatment guidelines and assessed indexes including pulmonary function, QOL, quality-adjusted life years (QALY), Medical Research Council (MRC) dyspnea scale, 6-min walk distance (6-MWD), number of emergency visits, and frequency of hospitalization. Of a total of 711 patients with chronic cough and asthma, 132 were diagnosed as having COPD and 102 participated in this study [intervention group (N = 47); control group (N = 55)]. We found that adherence to GOLD guidelines had a perceivable impact on 6-MWD, MRC dyspnea scale score, and QOL. The average QALY increased by 1.42/person/year in the intervention group, but declined by 0.95/person/year in the control group. We conclude that standardized management improves disease severity, QOL, and QALY in COPD patients when treatment protocols adhere to GOLD guidelines.

Plasma copeptin and long-term outcomes in acute ischemic stroke.

OBJECTIVE: The identification of patients at highest risk for adverse outcome who are presenting with acute ischemic stroke to the emergency department remains a challenge. This study firstly investigates the long-term prognostic value of the stress marker copeptin in Chinese patients with acute ischemic stroke. METHODS: In a prospective study, copeptin levels were measured using a new sandwich immunoassay on admission in plasma of 245 consecutive patients with an acute ischemic stroke. The prognostic value of copeptin to predict the functional outcome and mortality within one year was compared with the National Institutes of Health Stroke Scale score and with other known outcome predictors. RESULTS: Patients with an unfavorable outcomes and non-survivors had significantly increased copeptin levels on admission (P < 0.0001 and P < 0.0001). Multivariate Cox regression analysis adjusted for common risk factors showed that copeptin was an independent predictor of functional outcome (hazard ratio = 3.88; 95% CI: 1.94-7.77) and non-survivors (hazard ratio = 5.99; 95% CI: 2.55-14.07). The area under the receiver operating characteristic curve of copeptin was 0.75 (95% CI, 0.70-0.82) for functional outcome and 0.867 (95% CI, 0.802-0.933) for mortality. CONCLUSIONS: Copeptin levels are a novel and complementary biomarker to predict functional outcome and mortality 1 year after acute ischemic stroke.

[Clinical analysis of 11 patients with neuroendocrine carcinoma in maxillofacial region].

Objective: To investigate the clinicopathological features, treatment and prognosis of maxillofacial neuroendocrine carcinoma. Methods: A total of 11 patients with maxillofacial neuroendocrine carcinoma diagnosed in the Department of Pathology of The First Affiliated Hospital of Zhengzhou University from December 2010 to July 2022 were retrospectively enrolled, including 8 males and 3 females, aged (65.2±9.5) years (ranged from 49 to 87 years), with a disease course of 0.5 to 6.0 months. The clinicopathological data including head and neck CT, MRI and treatment methods were analyzed. Results: Submandibular gland and maxilla were involved in 3 cases, parapharynx in 2 cases, and face, tongue root and soft palate in 1 case respectively. Clinically, the initial symptom is a rapidly growing painless or tender mass, which may be accompanied by restricted mouth opening, dysphagia, and local numbness after invasion of masticatory muscles and nerves. The tumors were all invasive and low-density, with unclear boundaries from the surrounding tissues. Among the patients, 9 received surgical treatment, and 5 received adjuvant treatment after surgery (2 received chemotherapy, 3 received radiotherapy+chemotherapy). According to the 5th edition of the World Health Organization classification of head and neck tumors in 2022, there were 1 case (1/11) with poorly differentiated large cells and 10 cases (10/11) with poorly differentiated small cells. Histologically, the macrocell type is composed of large cells with rough chromatin, obvious vacuolar nucleolus, protruding nucleolus, and necrosis. The small cell type is dominated by small blue round cells with neuroendocrine characteristics, with active growth and multifocal necrosis. Immunohistochemical staining showed that cytokeratin (CK), epithelial membrane antigen (EMA) and synaptophysin (Syn) were diffusively expressed, 10 cases expressed CD56, 8 cases expressed p63, 6 cases expressed weakly punctated chromograin-A (CgA), and S-100 was not expressed. The Ki-67 index ranges from 20 to 90 percent. By the end of follow-up (0.5 to 127.0 months), 3 patients were alive, and the mean progression-free survival (21.0 months) of postoperative chemoradiotherapy patients was significantly longer than that of surgery and/or chemotherapy alone (3.3 months). Conclusions: Maxillofacial neuroendocrine carcinoma is characterized by low differentiation of small cells, high degree of malignancy and poor prognosis. Radical surgery combined with chemoradiotherapy has better local control effect.

Amyloid-beta immunotherapy for Alzheimer's disease.

Alzheimer's disease (AD) is a progressive, degenerative disorder of the brain and the most common form of dementia among the elderly. As the population grows and lifespan is extended, the number of AD patients will continue to rise. Current clinical therapies for AD provide partial symptomatic benefits for some patients; however, none of them modify disease progression. Amyloid-beta (Abeta) peptide, the major component of senile plaques in AD patients, is considered to play a crucial role in the pathogenesis of AD thereby leading to Abeta as a target for treatment. Abeta immunotherapy has been shown to induce a marked reduction in amyloid burden and an improvement in cognitive function in animal models. Although preclinical studies were successful, the initial human clinical trial of an active Abeta vaccine was halted due to the development of meningoencephalitis in approximately 6% of the vaccinated AD patients. Some encouraging outcomes, including signs of cognitive stabilization and apparent plaque clearance, were obtained in subset of patients who generated antibody titers. These promising preliminary data support further efforts to refine Abeta immunotherapy to produce highly effective and safer active and passive vaccines for AD. Furthermore, some new human clinical trials for both active and passive Abeta immunotherapy are underway. In this review, we will provide an update of Abeta immunotherapy in animal models and in human beings, as well as discuss the possible mechanisms underlying Abeta immunotherapy for AD.

Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS.

AIMS: To investigate the relationships between a known history of diabetes and ambient fasting plasma glucose (FPG) levels with death and morbidity rates in patients with severe acute respiratory syndrome (SARS). METHODS: In this retrospective analysis, the clinical and biochemical characteristics of 135 patients who had died from SARS, 385 survivors of SARS and 19 patients with non-SARS pneumonia were compared. RESULTS: All patients were treated according to a predefined protocol. Before steroid treatment, the mean FPG level was significantly higher in the SARS group (deceased vs. survivors vs. non-SARS pneumonia group: 9.7 +/- 5.2 vs. 6.5 +/- 3.0 vs. 5.1 +/- 1.0 mmol/l, P < 0.01). In the SARS group, the percentage of patients with a known history of diabetes was significantly higher in the deceased patients than in the survivors (21.5% vs. 3.9%, P < 0.01). Among patients with no known history of diabetes and before commencement of steroid therapy, those who had hypoxaemia (SaO(2) < 93%) had higher FPG levels than those who did not have hypoxia in both the survivor (8.7 +/- 4.9 vs. 6.3 +/- 2.1 mmol/l, P < 0.001) and deceased (9.8 +/- 4.8 vs. 7.2 +/- 1.5 mmol/l, P < 0.001) groups. A known history of diabetes [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.4, 6.3; P = 0.005] and FPG > or = 7.0 mmol/l before steroid treatment (OR 3.3, 95% CI 1.4, 7.7, P = 0.006) were independent predictors of death. During the course of the illness, FPG levels were negatively associated with SaO(2) (beta =-0.682 +/- 0.305, P = 0.025, general estimation equation model) in SARS patients. Survival analysis showed that FPG was independently associated with an increased hazard ratio (HR) of mortality (HR = 1.1, 95% CI 1.0, 1.1, P = 0.001) and hypoxia (HR = 1.1, 95% CI 1.0, 1.1, P = 0.002) after controlling for age and gender. CONCLUSIONS: A known history of diabetes and ambient hyperglycaemia were independent predictors for death and morbidity in SARS patients. Metabolic control may improve the prognosis of SARS patients.

[Retention behavior of some polycyclic aromatic hydrocarbons on alkylphosphonate-modified magnesia-zirconia composite stationary phase for reversed-phase liquid chromatography].

An alkylphosphonate-modified magnesia-zirconia composite stationary phase (PZMS) for reversed-phase liquid chromatography was prepared. The reversed-phase chromatographic performance of the new packing material was investigated with some polycyclic aromatic hydrocarbons (PAHs) as solutes. The effect of the methanol content in the mobile phase on the retention of PAHs was examined. The logarithmic capacity factor of PAHs was decreased linearly with increasing volume percent of the methanol in the mobile phase, which is similar to that observed on Zorbax ODS. The capacity factor of PAHs on the new stationary phase was also correlated to their partition coefficient between n-octanol and water (log P). A good linear relationship between them was obtained. These results show that the new material can behave as a reversed-phase packing. The separations of phenanthrene and anthracene, and terphenyl isomers were investigated on the new stationary phase and the Zorbax ODS, respectively. The retention of the solutes on the Zorbax ODS is greater than that on the new stationary phase, but the separation selectivity of the solutes on the new stationary phase is better than that on the Zorbax ODS. The better separation selectivity on the new stationary phase may be contributed from the Lewis acid-base interaction between the solutes and the residual Lewis acid sites on the stationary phase.