Exploring the Accessibility by Using the Hydroxycobalamin Preparations of High Concentration in Treating Methylmalonic Acidemia / 罕见病研究

Methylmalonic acidemia(MMA) is one of the common diseases in hereditary organic acid metabolism disorder. The disorder is mainly treated by using vitamin B12 which comes in various forms.The use of the methylcobalamin and adenosylcobalamin in China cannot meet the needs of children with MMA. Parenteral use of hydroxocobalamin of high concentration has significant advantages in the treatment of MMA. But, the accessibility to hydroxocobalamin is challenging now.Through the supervision and adjustment of hydroxocobalamin, we explored the strategy of using the drugs. Meanwhile, we are considering the oral use of the hydroxocobalamin as supplement to treatment. Solving the challenges of the hydrococobalamin is helpful to meet the treatment of MMA and to provide a new possibility for the use of medication for rare diseases. The improvement in policy and supervision measures will facilitate the development, involvement, and production of hydroxocobalamin, so that the patients will have a good chance of access to the treatment.

The relationship between the level of TAT/PIC and utilization rate of mechanical ventilation in critically ill patients / 西安交通大学学报(医学版)

【Objective】 To investigate the relationship between the level of thrombin-antithrombin complex (TAT)/α2-plasmin inhibitor-plasmin complex (PIC) and the utilization rate of mechanical ventilation (MV) in critically ill patients. 【Methods】 For the cross-sectional study, adult patients who had been admitted to the intensive care unit (ICU) for one day or longer and had a record of the first four tests for thrombosis were enrolled. Age, gender, the results of TAT and PIC, disseminated intravascular coagulation score, treatment, and diagnostic information were retrospectively collected from the hospital information system and laboratory information system. Logistic regression model was used to explore the relationship between TAT/PIC and the MV utilization rate. Interaction analysis and subgroup analysis were conducted to explore whether there was any difference between patients with different age and gender, patients with/without DIC, and with/without infection. 【Results】 A total of 1 176 patients were enrolled in this study. The median of the first TAT/PIC was 15.84 (8.13-33.11) in all the patients. The multivariable Logistic regression model results showed that for every 5 increase in TAT/PIC, the possibility of using MV increased by 2.9% (OR=1.029, 95% CI: 1.008-1.050), and the possibility of using MV in Q3 patients was 1.566 times than that in Q1 patients (OR=1.566, 95% CI: 1.095-2.239); the possibility of using MV in Q4 patients was 2.457 times than that in Q1 patients (OR=2.457, 95% CI: 1.694-3.563). Interaction results showed that the relationship between the level of TAT/PIC and MV usage was different in patients with and without infection (Pinteraction=0.02). Further subgroup analysis showed that in the infected patients (674 cases), the possibility of using MV increased by 5.9% for every 5 increase in TAT/PIC (OR=1.059, 95% CI: 1.022-1.097, P=0.001), while there was no significant difference between different TAT/PIC and MV usage in non-infected patients (502 cases) (OR=1.012, 95% CI: 0.984-1.040, P=0.405). 【Conclusion】 There is a correlation between the level of TAT/PIC and mechanical ventilation in patients with infection in the ICU.

Research on neck dissection for oral squamous-cell carcinoma: a bibliometric analysis / 国际口腔科学杂志·英文版

Neck dissection for oral squamous-cell carcinoma (OSCC) is a clinically controversial issue and has therefore been the subject of abundant research. However, no one has performed a bibliometric study on this topic to date. The aim of this study was to assess the development of research on neck dissection for OSCC in terms of the historical evolution, current hotspots and future directions, particularly including research trends and frontiers from 2010 to 2019. Literature records related to research on neck dissection for OSCC were retrieved from the Web of Science Core Collection (WoSCC). CiteSpace was used as a tool to perform a bibliometric analysis of this topic. The survey included 2 096 papers. "Otorhinolaryngology" was the most popular research area. The most active institutions and countries were Memorial Sloan Kettering Cancer Center and the USA, respectively. Shah J.P. was the most cited author. Among the six identified "core journals", Head & Neck ranked first. The top three trending keywords were 'invasion', 'upper aerodigestive' and 'negative neck'. 'D'Cruz AK (2015)' was the most cited and the strongest burst reference in the last decade. The study evaluated the effect on survival of elective versus therapeutic neck dissection in patients with lateralized early-stage OSCC. The depth of invasion and the management of N0 OSCC were research frontiers in this field. The present study provides a comprehensive bibliometric analysis of research on neck dissection for OSCC, which will assist investigators in exploring potential research directions.

Effects of circadian heart rate variation on short-term and long-term mortality in intensive care unit patients:a retrospective cohort study based on MIMIC-Ⅱ database / 中华危重病急救医学

Objective To investigate the effect of circadian heart rate variation on short-term and long-term mortality in intensive care unit (ICU) patients. Methods A retrospective cohort study was conducted. A total of 32 536 ICU patients were recorded from 2001 to 2008 published by Multiparameter Intelligent Monitoring in Intensive Care Ⅱ(MIMIC-Ⅱ v2.6) in April 2011. The circadian heart rate variation was defined as the ratio of mean nighttime (23:00 to 07:00) heart rate to mean daytime (07:00 to 23:00) heart rate. The 28-day mortality and 1-year mortality were defined as outcome events. The information such as age, gender, ethnicity, first sequential organ failure assessment (SOFA) score, first simplified acute physiology score Ⅰ (SAPSⅠ), usage of sedatives and catecholamines within 24 hours admission of ICU, clinical complications [hypertension, chronic obstructive pulmonary disease (COPD), diabetes with or without complications, congestive heart failure, liver disease, renal failure, etc.], and the complete heart rate records within 24 hours after ICU admission were collected. Cox proportional risk regression models were used to investigate the association between circadian heart rate variation and 28-day mortality and 1-year mortality in ICU patients. Besides, subgroup analysis was also performed in patients with different first SOFA scores. Results Totally 15 382 ICU patients in MIMIC-Ⅱ database were enrolled, excluding the patients without heart rate records or death records, using pacemaker with arrhythmia, without SOFA or SAPSⅠ score records. Finally, 9 439 patients were enrolled in the study cohort. ① Cox regression analysis of the whole patient showed that the higher circadian heart rate variation was correlated with the increased 28-day mortality [hazard ratio (HR) = 1.613, 95% confidence interval (95%CI) was 1.338-1.943, P < 0.001] and 1-year mortality (HR = 1.573, 95%CI was 1.296-1.908, P < 0.001). After adjustment for demographic factors (age, gender and ethnicity), severity of illness (SOFA and SAPS Ⅰ scores), clinical complications (hypertension, COPD, diabetes with or without complications, congestive heart failure, liver disease, renal failure, etc.), and influence of medications (sedatives and catecholamines), the night-day heart rate ratio was also correlated with 28-day mortality (HR = 1.256, 95%CI was 1.018-1.549, P = 0.033) and 1-year mortality (HR = 1.249, 95%CI was 1.010-1.545, P = 0.040). ② According to the SOFA score (median value of 5), the patients were divided into two subgroups, in which 5 478 patients with SOFA score ≤ 5 and 3 961 patients with SOFA score > 5. Cox regression subgroup analysis showed that circadian heart rate variation was related with higher 28-day mortality (HR = 1.430, 95%CI was 1.164-1.756, P = 0.001) and 1-year mortality (HR = 1.393, 95%CI was 1.123-1.729, P = 0.003) in patients with SOFA score > 5. After adjustment for covariates, the 28-day mortality (HR = 1.279, 95%CI was 1.032-1.584, P = 0.025) and 1-year mortality (HR = 1.255, 95%CI was 1.010-1.558, P = 0.040) also increased with the increasing of night-day heart rate ratio in patients with SOFA score > 5. However, the relationships did not exist in patients with SOFA score ≤ 5. Conclusion In ICU patients, the 28-day mortality and 1-year mortality increase with the higher circadian heart rate variation, which indicates that the circadian heart rate variation in ICU patients is positively correlated with the short-term and long-term mortality, especially in patients with relatively severe illness.

Eight-arm polyethylene glycol nanoconjugates for brain targeted delivery of photosensitizer / 中国药科大学学报

@#The aim of this study was to prepare the nanoconjugates for targeted photodynamic therapy of brain cancer by using eight-arm polyethylene glycol(8PEG)as the carrier and cRGD as the targeting ligand, and to investigate the antitumor effect and its mechanism. UV-Vis spectra and confocal microscopy were used for characterization and cellular uptake behavior of nanoconjugates respectively. Alamar Blue assay and Calcein AM/PI staining were applied to investigate the cytotoxocity of nanoconjugates against tumor cells, and tumor spheroid growth curve was used to assess the tumor growth suppression effect. In addition, the generation of reactive oxygen species(ROS), apoptosis and spheroid permeability test was used to reveal the antitumor mechanism of nanoconjugates. The results showed that cRGD-8PEG-IR700 was taken up efficiently by integrin overexpressed U87MG cells, while almost no uptake was found in integrin free NIH/3T3 cells. Remarkable photokilling effect against U87MG cells was only shown in cRGD-8PEG-IR700 group due to the light-induced ROS generation and apoptosis, whereas growth suppression effect was also observed in U87MG spheroids treated with cRGD-8PEG-IR700 plus light owing to the superior penetration ability of targeted nanoconjugates. Hence, tumor-targeted PEG nanoconjugates may provide a promising drug delivery system for photodynamic therapy of cancers.

Effects of circadian heart rate variation on short-term and long-term mortality in intensive care unit patients: a retrospective cohort study based on MIMIC-Ⅱ database / 中华危重病急救医学

Objective@#To investigate the effect of circadian heart rate variation on short-term and long-term mortality in intensive care unit (ICU) patients.@*Methods@#A retrospective cohort study was conducted. A total of 32 536 ICU patients were recorded from 2001 to 2008 published by Multiparameter Intelligent Monitoring in Intensive Care Ⅱ (MIMIC-Ⅱ v2.6) in April 2011. The circadian heart rate variation was defined as the ratio of mean nighttime (23:00 to 07:00) heart rate to mean daytime (07:00 to 23:00) heart rate. The 28-day mortality and 1-year mortality were defined as outcome events. The information such as age, gender, ethnicity, first sequential organ failure assessment (SOFA) score, first simplified acute physiology score Ⅰ (SAPSⅠ), usage of sedatives and catecholamines within 24 hours admission of ICU, clinical complications [hypertension, chronic obstructive pulmonary disease (COPD), diabetes with or without complications, congestive heart failure, liver disease, renal failure, etc.], and the complete heart rate records within 24 hours after ICU admission were collected. Cox proportional risk regression models were used to investigate the association between circadian heart rate variation and 28-day mortality and 1-year mortality in ICU patients. Besides, subgroup analysis was also performed in patients with different first SOFA scores.@*Results@#Totally 15 382 ICU patients in MIMIC-Ⅱ database were enrolled, excluding the patients without heart rate records or death records, using pacemaker with arrhythmia, without SOFA or SAPSⅠ score records. Finally, 9 439 patients were enrolled in the study cohort. ① Cox regression analysis of the whole patient showed that the higher circadian heart rate variation was correlated with the increased 28-day mortality [hazard ratio (HR) = 1.613, 95% confidence interval (95%CI) was 1.338-1.943, P < 0.001] and 1-year mortality (HR = 1.573, 95%CI was 1.296-1.908, P < 0.001). After adjustment for demographic factors (age, gender and ethnicity), severity of illness (SOFA and SAPS Ⅰ scores), clinical complications (hypertension, COPD, diabetes with or without complications, congestive heart failure, liver disease, renal failure, etc.), and influence of medications (sedatives and catecholamines), the night-day heart rate ratio was also correlated with 28-day mortality (HR = 1.256, 95%CI was 1.018-1.549, P = 0.033) and 1-year mortality (HR = 1.249, 95%CI was 1.010-1.545, P = 0.040). ② According to the SOFA score (median value of 5), the patients were divided into two subgroups, in which 5 478 patients with SOFA score ≤ 5 and 3 961 patients with SOFA score > 5. Cox regression subgroup analysis showed that circadian heart rate variation was related with higher 28-day mortality (HR = 1.430, 95%CI was 1.164-1.756, P = 0.001) and 1-year mortality (HR = 1.393, 95%CI was 1.123-1.729, P = 0.003) in patients with SOFA score > 5. After adjustment for covariates, the 28-day mortality (HR = 1.279, 95%CI was 1.032-1.584, P = 0.025) and 1-year mortality (HR = 1.255, 95%CI was 1.010-1.558, P = 0.040) also increased with the increasing of night-day heart rate ratio in patients with SOFA score > 5. However, the relationships did not exist in patients with SOFA score ≤ 5.@*Conclusion@#In ICU patients, the 28-day mortality and 1-year mortality increase with the higher circadian heart rate variation, which indicates that the circadian heart rate variation in ICU patients is positively correlated with the short-term and long-term mortality, especially in patients with relatively severe illness.