A comparative study of the effects of citrate and heparin anticoagulation on coagulation function and efficacy in children with septic shock undergoing continuous blood purification / 中华危重病急救医学

Objective:To compare the effects of citrate and heparin anticoagulation on coagulation function and efficacy in children with septic shock undergoing continuous blood purification (CBP), and to provide guidance for CBP anticoagulation in children with septic shock.Methods:A case control study was conducted. Thirty-seven children with septic shock admitted to the pediatric intensive care unit (PICU) of the First Affiliated Hospital of Gannan Medical University from July 2019 to September 2022 were enrolled as the research subjects. The patients were divided into citrate local anticoagulation group and heparin systemic anticoagulation group according to different anticoagulation methods. The baseline data, the level of coagulation indicators [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib), D-dimer] before treatment and 1 day after weaning from CBP, serum inflammatory mediators [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), hypersensitivity C-reactive protein (hs-CRP), procalcitonin (PCT)], bleeding complications during CBP and 7-day mortality were collected.Results:A total of 37 cases were enrolled finally, including 17 cases with citric acid local anticoagulation and 20 cases with heparin systemic anticoagulation. There was no statistically significant difference in general data such as gender, age, and body weight of children between the two groups. There were no statistically significant differences in baseline levels of coagulation indicators and inflammatory mediators before treatment of children between the two groups. One day after weaning from CBP, both groups showed varying degrees of improvement in coagulation indicators compared with those before treatment. Compared with before treatment, the PT of the heparin systemic anticoagulation group was significantly shortened after 1 day of weaning (s: 11.82±2.05 vs. 13.64±2.54), APTT and TT were significantly prolonged [APTT (s): 51.54±12.69 vs. 35.53±10.79, TT (s): 21.95±4.74 vs. 19.30±3.33], D-dimer level was significantly reduced (mg/L: 1.92±1.58 vs. 4.94±3.94), with statistically significant differences (all P < 0.05). While in the citrate local anticoagulation group, only APTT was significantly prolonged after treatment compared with that before treatment (s: 49.28±10.32 vs. 34.34±10.32, P < 0.05). There were no statistically significant differences in other coagulation indicators compared with before treatment. Compared with the citric acid local anticoagulation group, the PT of the heparin systemic anticoagulation group was significantly shortened after treatment (s: 11.82±2.05 vs. 13.61±3.05, P < 0.05), and the D-dimer level was significantly reduced (mg/L: 1.92±1.58 vs. 3.77±2.38, P < 0.01). The levels of inflammatory mediators in both groups were significantly reduced 1 day after CBP weaning compared with those before treatment [citric acid local anticoagulation group: hs-CRP (mg/L) was 12.53±5.44 vs. 22.65±7.27, PCT (μg/L) was 1.86±1.20 vs. 3.30±2.34, IL-6 (ng/L) was 148.48±34.83 vs. 202.32±48.62, TNF-α (ng/L) was 21.38±7.71 vs. 55.14±15.07; heparin systemic anticoagulation group: hs-CRP (mg/L) was 11.82±4.93 vs. 21.62±8.35, PCT (μg/L) was 1.90±1.08 vs. 3.18±1.97, IL-6 (ng/L) was 143.81±33.41 vs. 194.02±46.89, TNF-α (ng/L) was 22.44±8.17 vs. 56.17±16.92, all P < 0.05]. However, there was no statistically significant difference between the two groups (all P > 0.05). There was no statistically significant difference in bleeding complication during CBP and 7-day mortality in children between the citrate local anticoagulation group and the heparin systemic anticoagulation group (5.9% vs. 30.0%, 17.6% vs. 20.0%, both P > 0.05). Conclusions:Heparin for systemic anticoagulation and regional citrate anticoagulation can significantly reduce the levels of IL-6, TNF-α, hs-CRP and PCT in children with septic shock, and relieve inflammatory storm. Compared with citric acid local anticoagulation, heparin systemic anticoagulation can shorten the PT and reduce the level of D-dimer in children with septic shock, which may benefit in the prevention and treatment of disseminated intravascular coagulation (DIC).

Isolation and quantification of a 17-epi-dammarane triterpenoid rhuslactone from roots of Rhus chinensis and its preventive effects on coronary heart disease and thrombosis in zebrafish / 中国中药杂志

Based on mass spectrometry(MS)-guided separation strategy, compound 1 was obtained from the roots of Rhus chinensis. By comprehensive analysis of high resolution-electrospray ionization-mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) data, and quantum chemical calculation of NMR(qcc-NMR) parameters, compound 1 was elucidated as rhuslactone, a 17-epi-dammarane triterpenoid with a rare 17α-side chain. An HPLC-ELSD method for its quantification in R. chinensis was established and adopted for the quantification of rhuslactone in different batches of R. chinensis. Rhuslactone displayed a good linear relationship within the range of 0.021 3-1.07 μmol·mL~(-1 )(r=0.997 6), and the average recovery was 99.34% [relative standard deviation(RSD) 2.9%). Moreover, the results of the evaluation test of the preventive effects of rhusalctone on coronary heart disease(CHD) and thrombosis showed that rhuslactone(0.11 nmol·mL~(-1)) significantly alleviated heart enlargement and venous congestion and increased cardiac output(CO), blood flow velocity(BFV), and heart rate, thereby reducing thrombus formation in zebrafish with CHD. The effects of rhuslactone on CO and BFV were superior to that of digoxin(1.02 nmol·mL~(-1)), and its effect on improving heart rate was comparable to that of digoxin. This study provides experimental references for the isolation, identification, quality control, and application of rhuslactone from R. chinensis against CHD. It is worth mentioning that this study has discussed some omissions in the determination of the stereochemistry of C-17 in dammarane triterpenoids in the present coursebook Chemistry of Chinese Medicine and some research papers, that is, the compound may be 17-epi-dammarane triterpenoid. This paper has also proposed steps for the establishment of C-17 stereochemistry.

The discussion of related issues in the efficacy evaluation of COVID-19 vaccine / 中华预防医学杂志

The COVID-19 swept across the countries and regions all over the world in the past one year. The marketing of an effective and safe COVID-19 vaccine is expected to control the spread of the disease. A placebo-controlled field efficacy trial is generally considered in the pivotal study of COVID-19 vaccine to observe whether it is able to reduce the incidence rate of the disease effectively. This paper is to introduce and discuss the considerations in study design and the choice of endpoint, statistical evaluation methods, primary estimand choosing and the strategies to various intercurrent events in the COVID-19 efficacy trials.

Clinical characteristics and epidemiological analysis of pathogenic bacteria of severe abdominal infection in surgical intensive care unit / 中华危重病急救医学

Objective:To study the clinical characteristics of patients with severe abdominal infection and the epidemiological characteristics of pathogenic bacteria in a hospital, to provide a basis for rational use of antibiotics and reduce the drug resistance rate of pathogens.Methods:A retrospective analysis was performed on 237 patients with abdominal disease as the primary disease admitted to the surgical intensive care unit (ICU) of the First Affiliated Hospital of Guangxi Medical University from January 1st, 2017 to December 31st, 2019. They were divided into two groups according to whether abdominal infection occurred or not. The clinical features of patients in both groups were analyzed, including gender, age, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, chronic underlying diseases, primary abdominal site, abdominal trauma or bleeding, multiple organ dysfunction syndrome (MODS) involving organs and surgical treatment. At the same time, the bacterial origin, bacterial distribution and antibiotics sensitivity test results of patients with abdominal infection were recorded.Results:Abdominal infection occurred in 141 of the 237 patients and did not occur in the remaining 96 patients. There were no statistically significant differences between the abdominal infection group and the non-abdominal infection group in terms of gender, age, chronic underlying diseases, etiology and trauma. The APACHE Ⅱ score in the abdominal infection group was obviously higher than that of the non-abdominal infection group (24.0±8.1 vs. 17.1±5.8, P < 0.01). Incidences of abdominal bleeding, MODS involving four or more organs, surgery and the times of surgery ≥ 3 in the abdominal infection group were significantly higher than those in the non-abdominal infection group (36.2% vs. 17.7%, 20.6% vs. 1.0%, 84.4% vs. 21.9%, 9.3% vs. 0%, all P < 0.05). Among the 141 patients with abdominal infection, 107 obtained positive microbial culture results, and a total of 133 pathogenic strains were detected, including 115 strains of bacteria (86.5%) and 18 strains of fungi (13.5%). The main source of bacteria was abdominal drainage (46.1% of non-bloody specimens and 13.9% of bloody specimens). Among the 115 bacteria, Gram-negative (G -) bacteria were the most common (72.2%) and Gram-positive (G +) bacteria accounted for 27.8%. Escherichia coli and Acinetobacter baumannii were the top two G - bacteria (40.9% and 13.9%, respectively), and enterococcus faecalis accounted for the largest proportion of G + bacteria (7.8%). The pathogenic bacteria of abdominal infection were sensitive to tigacycline. Conclusions:The patients with abdominal infection in our hospital had high APACHE Ⅱ score, more organs failure and were easily complicated with intraperitoneal hemorrhage and required surgical intervention and even repeated surgery. The pathogenic bacteria in patients with abdominal infection in ICU were mainly G - bacteria, and the rate of multi-drug resistance of Acinetobacter baumannii was high. Empirical anti-infective treatment should be started as soon as possible according to the microbial spectrum of the region until the pathogenic bacteria results are obtained. Broad-spectrum antimicrobial therapy and combined antimicrobial therapy are recommended for the healthcare acquired abdominal infection in hospital.

Modeling the Long-term Antibody Response and Duration of Immune Protection Induced by an Inactivated, Preservative-free Hepatitis A Vaccine (Healive) in Children / 生物医学与环境科学（英文）

Objective@#Long-term seroprotection the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus (HAV). Due to documented difficulties during decade-long follow-ups after receiving vaccines, statistical-modeling approaches have been applied to predict the duration of immune protection.@*Methods@#Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children (1-8 years old) following a 0, 6 months vaccination schedule, a power-law model accounting for the kinetics of B-cell turnover, as well as a modified power-law model considering a memory-B-cell subpopulation, were fitted to predict the long-term immune responses induced by HAV vaccination (Healive or Havrix). Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted.@*Results@#A total of 375 participants who completed the two-dose vaccination were included in the analysis. Both models predicted that, over a life-long period, participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix. Additionally, consistent with previous studies, more than 90% of participants were predicted to maintain seroconversion for at least 30 years. Moreover, the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination.@*Conclusions@#Based on the results of our modeling, Healive may adequately induce long-term immune responses following a 0, 6 months vaccination schedule in children induction of memory B cells to provide stable and durable immune protection.

Effects of ulnar styloid and sigmoid notch fractures on postoperative wrist function of patients with distal radius fracture / 北京大学学报(医学版)

OBJECTIVE@#To study the effects of ulnar styloid and sigmoid notch fractures on postoperative wrist function in patients with distal radius fracture.@*METHODS@#In total, 139 patients treated for distal radius fracture in the Department of Orthopedic Trauma at Peking University People's Hospital from Jan. 2006 to June 2016 were selected for outpatient follow-ups. Evaluation was based on Sartiento's modification of the Gartland and Werley scores. Efficacy was assessed with wrist pain as the focus.@*RESULTS@#The excellent and good efficacy rate was 97.1% (excellent: n=107, 77.0%; good: n=28, 19.4%; and fair: n=4, 2.9%). Gender, age, and whether the ulnar styloid fracture achieved union did not significantly impact the scores (P>0.05). The scores of the basal fracture group were significantly different (P=0.001). Internal fixation of ulnar styloid fracture was associated with a significant difference in scores (P=0.005). The effect of sigmoid notch fracture was also associated with a significant difference in scores (P=0.024). This study included 22 cases of ulnar wrist pain, and the overall incidence of ulnar wrist pain was 15.8%. Gender, age, whether the ulnar styloid fracture achieved union, and whether internal fixation was conducted for ulnar styloid fracture and sigmoid notch fracture had no significant effect on the occurrence of ulnar wrist pain (P>0.05). The incidence of ulnar wrist pain was higher in basal fractures than that in tip fractures. Among ulnar styloid fractures, the union rate of basal fracture was higher than that of tip fractures. The union rates of basal fracture and tip fracture were significantly different (P<0.001). Basal fractures were significant risk factors for ulnar wrist pain (P=0.028). Basal fracture of the ulnar styloid group and sigmoid notch fracture group had poor wrist function scores. Wrist function score improved significantly after internal fixation of ulnar styloid fracture. The incidence of ulnar wrist pain was higher in basal fracture group. The union rate in basal fracture group was higher than in tip fracture group.@*CONCLUSION@#The overall effect of surgical treatment of distal radius fracture is satisfactory. Ulnar styloid basal fracture and sigmoid notch fracture are risk factors for postoperative wrist dysfunction in patients with distal radius fracture, and the basal fracture is one of the risk factors of ulnar wrist pain. The union rate of ulnar styloid basal fractures is better than that of tip fractures. Internal fixation of ulnar styloid fracture can improve wrist function.

Large- scale prospective clinical study on prophylactic intervention of COVID-19 in community population using Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules / 中国中药杂志

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.

Mild hypothermia can delay the occurrence of post-stroke infection: a propensity score matched-cohort study / 中华危重病急救医学

Objective To evaluate the effect of mild hypothermia on the incidence of post-stroke infection and explore the relationship between mild hypothermia and outcome of stroke patients by using propensity score matching. Methods Patients hospitalized in department of intensive care unit (ICU), neurology and neurosurgery in the First Affiliated Hospital of Guangxi Medical University due to stroke from March 2012 to April 2018 were retrospectively analyzed. According to whether or not mild hypothermia was provided, they were divided into the normal thermic group (NT group) and mild hypothermia treatment group (MHT group). The MHT group patients were matched with the NT group patients by the propensity score matching method at a ratio of 1:1. The observation period was within the first 7 days after admission. Baseline characteristics including age, gender, type of stroke, comorbidities, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score and Glasgow coma score (GCS) on admission, surgical operation, dysphagia, invasive procedures and outcomes of these patients had been analyzed. The primary outcome was incidence of post-stroke infection, and the secondary outcomes included the time of initial infection (TII, the duration from stroke to initial infection), hospital mortality, sequential organ failure assessment (SOFA) at discharge, incidence of complications such as arrhythmia, coagulation dysfunction and multiple organ dysfunction syndrome (MODS). Results 201 stroke patients were enrolled, 41.8％ (84/201) of whom underwent mild hypothermia. Comparison with NT group before matching, there were more males in MHT group (71.4％ vs. 56.4％), the proportion of surgical operation, mechanical ventilation, deep vein catheterization and gastric catheterization were higher (78.6％ vs. 54.7％, 84.5％ vs. 39.3％, 90.5％ vs. 37.6％, 98.8％ vs. 70.9％), and so as incidence of infection (90.5％ vs. 72.6％), in-hospital mortality (27.4％ vs. 12.8％) and TII [hours: 62.00 (35.25, 93.00) vs. 42.00 (28.50, 69.50)]. All the differences were statistically significant (all P < 0.05). Fifty-three patients in the MHT group were matched with 53 patients in the NT group. After matching, there was no significant difference in 15 baseline characteristics between two groups.Significant differences in infection and hospital mortality between the MHT group and NT groups disappeared (92.5％ vs. 88.7％, 22.6％ vs. 26.4％, both P > 0.05), while TII of MHT group was longer than that of the NT group [hours:62.00 (40.75, 92.25) vs. 40.00 (28.00, 63.00), P = 0.000]. There were no statistically significant differences in SOFA score or complications between the two groups either before or after matching. Conclusion Mild hypothermia had no significant effect on the incidence of post-stroke infection and hospital mortality, it could delay the occurrence of infection and provide longer duration of treatment.

Power Analysis and Sample Size Determination for Crossover Trials with Application to Bioequivalence Assessment of Topical Ophthalmic Drugs Using Serial Sampling Pharmacokinetic Data / 生物医学与环境科学（英文）

OBJECTIVE@#To develop methods for determining a suitable sample size for bioequivalence assessment of generic topical ophthalmic drugs using crossover design with serial sampling schemes.@*METHODS@#The power functions of the Fieller-type confidence interval and the asymptotic confidence interval in crossover designs with serial-sampling data are here derived. Simulation studies were conducted to evaluate the derived power functions.@*RESULTS@#Simulation studies show that two power functions can provide precise power estimates when normality assumptions are satisfied and yield conservative estimates of power in cases when data are log-normally distributed. The intra-correlation showed a positive correlation with the power of the bioequivalence test. When the expected ratio of the AUCs was less than or equal to 1, the power of the Fieller-type confidence interval was larger than the asymptotic confidence interval. If the expected ratio of the AUCs was larger than 1, the asymptotic confidence interval had greater power. Sample size can be calculated through numerical iteration with the derived power functions.@*CONCLUSION@#The Fieller-type power function and the asymptotic power function can be used to determine sample sizes of crossover trials for bioequivalence assessment of topical ophthalmic drugs.

Clinical and radiological results of thoracic and lumbar fracture and dislocation treated with posterior transforaminal decompression and interbody fusion / 中国骨伤

OBJECTIVE@#To evaluate the clinical and radiological results of patients with thoracic and lumbar fracture and dislocation treated by posterior transforaminal decompression and interbody fusion.@*METHODS@#From June 2010 to June 2017, posterior transforaminal decompression, interbody fusion combined with pedicle screw fixation were performed in 21 patients with thoracic and lumbar fracture and dislocation. Their clinical and radiological data were collected and retrospectively analyzed, including 15 males and 6 females, aged from 25 to 58 years with an average of 45 years old. According to the criterion of American Spinal Injury(ASIA), preoperative neurological function was graded A in 3 cases, B in 7 cases, C in 6 cases, D in 4 cases and E in 1 case. Operative time and intraoperative blood loss and correlative complications were recorded. And VAS score, ODI and Cobb angle were evaluated before and after surgery. The improvement of neurological function was also analyzed at the final follow-up. Intervertebral bony fusion was observed during the follow-up by CT three-dimensional reconstruction.@*RESULTS@#The operative time was 150 to 240 min with an average of (192±47) min. The intraoperative blood loss was 380 to 750 ml with an average of(603±120) ml. Dura sac tearing and cerebral fluid leakage occurred in 3 cases and were repaired during operation; superficial wound infection occurred in 1 case, and got healing after dressing change. The postoperative follow-up duration was 24 to 45 months with an average of(37.0±9.5) months. VAS score was improved from preoperative 8.9±0.4 to immediately postoperative 4.2±1.3(<0.05). At the final follow-up, VAS score decreased further to 3.6±0.8. ODI was decreased from preoperative (95.30±3.52)% to (32.51±6.30)% at the final follow-up (<0.05). Cobb angle was corrected from preoperative (21.2±8.8)° to immediately postoperative(2.3±3.1)° (<0.05). At the final follow-up, Cobb angle was (3.2±2.5)°, showing no significant difference with immediately postoperative value. The neurological function was grade A in 3 cases, B in 3 cases, C in 5 cases, D in 6 cases and E in 4 cases at the final follow-up. All the patients got solid intervertebral bone fusion in 8 to 13 months after operation, with an average fusion time of (10.3±2.5) months.@*CONCLUSIONS@#For the patients with thoracic and lumbar fracture and dislocation mainly involving intervertebral disc and endplate plane, posterior transforaminal decompression and interbody fusion not only is less invasive, but also can effectively reconstruct spinal three column and obtain good biomechanical stability. And, it is beneficial for the good recovery of neurological function.

Mild hypothermia can delay the occurrence of post-stroke infection: a propensity score matched-cohort study / 中华危重病急救医学

Objective@#To evaluate the effect of mild hypothermia on the incidence of post-stroke infection and explore the relationship between mild hypothermia and outcome of stroke patients by using propensity score matching.@*Methods@#Patients hospitalized in department of intensive care unit (ICU), neurology and neurosurgery in the First Affiliated Hospital of Guangxi Medical University due to stroke from March 2012 to April 2018 were retrospectively analyzed. According to whether or not mild hypothermia was provided, they were divided into the normal thermic group (NT group) and mild hypothermia treatment group (MHT group). The MHT group patients were matched with the NT group patients by the propensity score matching method at a ratio of 1∶1. The observation period was within the first 7 days after admission. Baseline characteristics including age, gender, type of stroke, comorbidities, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score and Glasgow coma score (GCS) on admission, surgical operation, dysphagia, invasive procedures and outcomes of these patients had been analyzed. The primary outcome was incidence of post-stroke infection, and the secondary outcomes included the time of initial infection (TII, the duration from stroke to initial infection), hospital mortality, sequential organ failure assessment (SOFA) at discharge, incidence of complications such as arrhythmia, coagulation dysfunction and multiple organ dysfunction syndrome (MODS).@*Results@#201 stroke patients were enrolled, 41.8% (84/201) of whom underwent mild hypothermia. Comparison with NT group before matching, there were more males in MHT group (71.4% vs. 56.4%), the proportion of surgical operation, mechanical ventilation, deep vein catheterization and gastric catheterization were higher (78.6% vs. 54.7%, 84.5% vs. 39.3%, 90.5% vs. 37.6%, 98.8% vs. 70.9%), and so as incidence of infection (90.5% vs. 72.6%), in-hospital mortality (27.4% vs. 12.8%) and TII [hours: 62.00 (35.25, 93.00) vs. 42.00 (28.50, 69.50)]. All the differences were statistically significant (all P < 0.05). Fifty-three patients in the MHT group were matched with 53 patients in the NT group. After matching, there was no significant difference in 15 baseline characteristics between two groups. Significant differences in infection and hospital mortality between the MHT group and NT groups disappeared (92.5% vs. 88.7%, 22.6% vs. 26.4%, both P > 0.05), while TII of MHT group was longer than that of the NT group [hours: 62.00 (40.75, 92.25) vs. 40.00 (28.00, 63.00), P = 0.000]. There were no statistically significant differences in SOFA score or complications between the two groups either before or after matching.@*Conclusion@#Mild hypothermia had no significant effect on the incidence of post-stroke infection and hospital mortality, it could delay the occurrence of infection and provide longer duration of treatment.

A phase Ⅲ multi-center clinical trial on safety and efficacy of a domestic plasma derived factor Ⅸ for the treatment of patients with hemophilia B / 中华血液学杂志

Objective: To evaluate the efficacy and safety of a domestic human plasma derived coagulation Factor Ⅸ concentrate (pd-FⅨ) in patients with hemophilia B. Methods: The study was a multicenter, open-label and single-arm study. The efficacy of pd-F Ⅸ was evaluated by objective performance criteria. The doses of pd-FⅨ were calculated according to the bleeding symptom and disease severity. The infusion efficiency of pd-FⅨ and improvement of bleeding symptoms were measured at 30 minutes and (24±4) h after the first infusion, respectively. Adverse events were recorded. Viral infection and FⅨ inhibitor were detected 90 d after the first infusion. Results: All 36 subjects with hemophilia B were enrolled in the study. The median age of these patients was 31 years old and the median injection doses were 4 (1-17) times. The hemostatic effect of 27/36 (75.00%) and 9/36 (25.00%) acute bleeding events were rated as "excellent" and "better" , respectively. The recovery rate was 111.92% (65.55%-194.28%) at 30 minutes after infusion of FⅨ. There was no adverse event related to FⅨ. No reactivation of HBV, HCV or HIV and FⅨ inhibitor was detected at 90-104 d after the first FⅨ infusion. Conclusion: This domestically made human plasma derived FⅨ concentrate is safe and effective in the treatment of acute bleeding in patients with hemophilia B. Clinical trial registration: China food and Durg Administration, 2016L08027.

Hypocalcemia is an "accelerator" for the death of patients with nervous system injury / 中华危重病急救医学

In clinical diagnosis and treatment, the occurrence of hypocalcemia during severe nervous system damage is not uncommon but is easily neglected so that delayed treatment, further injurie and even death. It can provide theoretical support for the evaluation of the early identification in calcium ion imbalance and the development of standard calcium ion monitoring program for patients with critical disease by integrating the clinical symptoms induced by low blood calcium based on severe nervous system injury and analyzing the correlation among them.

Effects of mild hypothermia on pulmonary vascular permeability in patients with acute respiratory distress syndrome / 中华危重病急救医学

Objective To study the influence of mild hypothermia on pulmonary vascular permeability in patients with acute respiratory distress syndrome (ARDS) induced by infection.Methods A prospective randomized controlled trial was conducted.Patients with ARDS induced by infection satisfied criteria including age 18-70 years,endotracheal intubation and mechanical ventilation (MV),and without severe coagulation disorder admitted to intensive care unit (ICU) of the First Affiliated Hospital of Guangxi Medical University from May 2012 to November 2015 were enrolled,excluding tumor,burn,cardiac disease,vascular disease,and endovascular surgery within 3 months.The patients enrolled were randomly divided into non-temperature controlled group and mild hypothermia group.The primary diseases in all patients were treated according to the treating principles,including respiratory support,integrated treatment of organ support and symptomatic treatment.Besides,the patients in the mild hypothermia group were administered with systemic hypothermia,and the patients' core body temperature (nasopharyngeal temperature) was rapidly decreased to 34-35 ℃ within 1 hour.Acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score,oxygenation index (PaO2/FiO2),extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) in two groups at 1,24,48,and 72 hours after treatment or core temperature up to standards were monitored respectively.Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of vascular endothelial growth factor (VEGF) in venous blood as well as tumor necrosis factor-α (TNF-α) and surfactant apoprotein A (SP-A) in bronchoalveolar lavage fluid (BALF),and circulating endothelial cell (CEC) was counted.The duration of mechanical ventilation and 7-day survival rate were recorded.Results Fifty-six patients were enrolled,with 32 in non-temperature controlled group and 24 in mild hypothermia group.There was no difference in baseline variables including gender,age,APACHE Ⅱ score,PaO2/FiO2 between two groups.APACHE Ⅱ score,EVLWI,PVPI,VEGF,CEC,and TNF-α in both groups were gradually increased with treatment time prolongation,and PaO2/FiO2 and SP-A were gradually decreased.Compared with non-temperature controlled group,APACHE Ⅱ score (16.34±4.27 vs.19.24 ± 5.95),EVLWI (mL/kg:12.17 ± 2.26 vs.12.39 ± 4.71),PVPI (15.40 ± 10.95 vs.16.08 ± 10.24),VEGF (ng/L:127.92 ± 31.49 vs.159.12 ± 40.67),CEC (cells/μL:4.15 ± 1.79 vs.5.70 ± 2.38),and TNF-α (ng/L:147.18 ± 48.85 vs.257.17 ±40.84) in mild hypothermia group were significantly decreased from 24 hours (all P ＜ 0.05),and PaO2/FiO2 [mmHg (1 mmHg =0.133 kPa):175.03± 12.64 vs.162.53 ± 14.15] and SP-A (μg/L:80.85 ± 16.18 vs.62.06 ± 17.28) were significantly increased (both P ＜ 0.05),the duration of mechanical ventilation was significantly shortened (days:10.38 ± 1.50 vs.15.74 ± 3.06,P ＜ 0.01),and 7-day survival rate was significantly increased (75.0％ vs.46.9％,P ＜ 0.05).Conclusion Mild hypothermia can reduce the pulmonary vascular permeability,and improve pulmonary function in early phase in patients with ARDS,as well as shorten the duration of mechanical ventilation,and decrease short-term mortality.

Prevention and handling of missing data in clinical trials / 药学学报

Missing data is a common but unavoidable issue in clinical trials. It not only lowers the trial power, but brings the bias to the trial results. Therefore, on one hand, the missing data handling methods are employed in data analysis. On the other hand, it is vital to prevent the missing data in the trials. Prevention of missing data should take the first place. From the perspective of data, firstly, some measures should be taken at the stages of protocol design, data collection and data check to enhance the patients' compliance and reduce the unnecessary missing data. Secondly, the causes of confirmed missing data in the trials should be notified and recorded in detail, which are very important to determine the mechanism of missing data and choose the suitable missing data handling methods, e.g., last observation carried forward (LOCF); multiple imputation (MI); mixed-effect model repeated measure (MMRM), etc.

Importance of data management with statistical analysis set division / 药学学报

Testing of hypothesis was affected by statistical analysis set division which was an important data management work before data base lock-in. Objective division of statistical analysis set under blinding was the guarantee of scientific trial conclusion. All the subjects having accepted at least once trial treatment after randomization should be concluded in safety set. Full analysis set should be close to the intention-to-treat as far as possible. Per protocol set division was the most difficult to control in blinded examination because of more subjectivity than the other two. The objectivity of statistical analysis set division must be guaranteed by the accurate raw data, the comprehensive data check and the scientific discussion, all of which were the strict requirement of data management. Proper division of statistical analysis set objectively and scientifically is an important approach to improve the data management quality.

Effect of hypothermia on TLR2/MyD88 signal pathway in lung tissue in rats with acute lung injury induced by lipopolysaccharide / 中华危重病急救医学

Objective To investigate the effect of hypothermia on the expression Toll-like receptor 2 (TLR2),myeloid differentiation factor 88(MyD88),nuclear factor-κBp65(NF-κBp65),plasminogen activator inhibitor-1(PAI-1)in the TLR2/MyD88 pathway in rats with acute lung injury(ALI)induced by lipopolysaccharide (LPS)inhalation. Methods Ninety male Sprague-Dawley(SD)rats were randomly divided into control group (n=18),hypothermia group(n=24),temperature controlled group(n=24),and temperature-uncontrolled group(n=24). The ALI model was reproduced by 0.5 mL/kg LPS intratracheal instillation,while only normal saline was instilled intratracheally for control group. Arterial blood was collected and physical cooling was started 1 hour after instillation. The body temperature was lowered to 32-34 ℃in hypothermia group and 36-37 ℃in temperature controlled group,and no intervention was used for temperature-uncontrolled group and control group. The arterial blood gas was determined in all the groups before and 1 hour after instillation of saline or LPS and 1,6, 12 hours after intervention. Rats were sacrificed respectively at 1,6 and 12 hours after temperature control therapy, the morphological changes in lung tissue were observed under light microscope. The protein expression of PAI-1 in bronchoalveolar lavage fluid(BALF)was determined by enzyme linked immunosorbent assay(ELISA). TLR2 mRNA and MyD88 mRNA transcriptional level were determined by reverse transcription-polymeras chain reaction (RT-PCR). NF-κBp65 protein level was determined by Western Blot. Results After instillation of LPS,the oxygenation index(PaO2/FiO2)of each group was decreased obviously,the damage of lung tissues was aggravating,the lung injury score was increased significantly,PAI-1 protein in BALF and the expressions of TLR2 mRNA,MyD88 mRNA, NF-κBp65 protein in lung tissues were increased obviously. Each index was improved by therapeutic Hypothermia, the effect of which was best in using a cooling period in the 1-6 hours,while might be benefit at 6-12 hours. Compared with temperature controlled group,PaO2/FiO2(mmHg,1 mmHg=0.133 kPa)at 1 hour and 6 hours of hypothermia group was improved(1 hour:402.49±38.61 vs. 324.36±28.93,6 hours:349.72±98.20 vs. 284.35±13.68, both P<0.01),the lung injury score at 1,6 and 12 hours were significantly decreased(1 hour:6.04±0.74 vs. 7.96±0.65,6 hours:9.09±0.80 vs. 13.13±1.02,12 hours:10.79±1.42 vs. 13.42±0.68,all P<0.01),the PAI-1 protein(ng/L)in BALF at 1,6 and 12 hours were significantly decreased(1 hour:121.36±4.62 vs. 197.74±9.42, 6 hours:230.53±10.76 vs. 294.06±16.60,12 hours:270.48±13.20 vs. 319.40±10.24,all P<0.01),TLR2 mRNA and MyD88 mRNA expressions(2-ΔΔCt)in the lung tissues at 1,6 and 12 hours were significantly decreased (TLR2 mRNA 1 hour:2.18±0.26 vs. 3.04±0.39,6 hours:4.09±0.29 vs. 4.90±0.35,12 hours:6.02±0.43 vs. 7.10±0.54;MyD88 mRNA 1 hour:2.25±0.41 vs. 3.04±0.30,6 hours:5.67±0.55 vs. 7.01±0.76,12 hours:7.14±0.60 vs. 8.87±0.54,all P<0.01),NF-κBp65 protein expression(A value)at 6 hours and 12 hours was significantly decreased(6 hours:0.31±0.08 vs. 0.53±0.12,12 hours:1.05±0.17 vs. 1.76±0.35,both P<0.01). There was no difference in each index between temperature controlled group and temperature-uncontrolled group. Conclusion Hypothermia can down-regulate the expression of TLR2 mRNA,MyD88 mRNA,NF-κBp65 protein and PAI-1 in the TLR2/MyD88 pathway to protect lung tissue of rats with ALI induced by LPS inhalation from injury.

Application of the China Infectious Diseases Automated-alert and Response System in Guangxi, 2009-2011 / 中华流行病学杂志

<p><b>OBJECTIVE</b>To analyze and further improvement the application of the China Infectious Diseases Automated-alert and Response System (CIDARS) in Guangxi Zhuang Autonomous Region.</p><p><b>METHODS</b>Results related to the amount of signal, proportion of signal responded, time to signal response, manner of signal verification and on each signal of Guangxi in CIDARS from 2009 to 2011 were described. Performance was compared between the periods of pre/ post the adjustment of parameters in CIDARS on December 10, 2010.</p><p><b>RESULTS</b>A total of 29 788 signals were generated on 16 infectious diseases in the system in Guangxi. 100% signals had been responded with the median time to response as 1.5 hours. The average amount of signal per county per week was 1.7;with 624 signals(2.09%)verified as suspected outbreaks preliminarily and 191 outbreaks of 9 diseases were finally confirmed by further field investigation. The sensitivity of CIDARS was 89.25% , and the timeliness of detection was 2.8 d. After adjusting the parameter of CIDARS, the number of signals reduced, and the sensitivity and timeliness of detection improved for most of the diseases.</p><p><b>CONCLUSION</b>The signals of CIDARS were responded timely, and the performance of CIDARS might be improved by adjusting the parameters of early-warning model, which helped enhance the ability of outbreaks-detection for local public health departments. However the current proportion of false positive signals still seemed to be high, suggesting that both the methods and parameters should be improved, according to the characteristics of different diseases.</p>

The application of China Infectious Diseases Automated-alert and Response System in Zhejiang province, 2012 / 中华流行病学杂志

<p><b>OBJECTIVE</b>To analyze and evaluate the application of China Infectious Diseases Automated-alert and Response System(CIDARS)in Zhejiang province.</p><p><b>METHODS</b>Data through the monitoring program in 2012 was analyzed descriptively and compared with the incidence data in the same period as well information related to public health emergency events.</p><p><b>RESULTS</b>A total of 14 292 signals were generated on 28 kinds of infectious diseases in the system, in Zhejiang province. 100% of the signals had been responded and the median time to response was 0.81 hours. 123 signals (0.86%)were preliminarily verified as suspected outbreaks and 33 outbreaks were finally confirmed by further field investigation, with a positive ratio of 0.23% . Information related to regional distribution showed significant differences which reflecting a positive correlation between the numbers of diseases and the time of early-warning(r = 0. 97, P < 0.01). Distribution of information related to different types of diseases was also significantly different, showing a positive correlation between the prevalent strength of the disease and the amount of information in a specific area(r = 0.80, P < 0.01).</p><p><b>CONCLUSION</b>CIDARS had a good performance which could be used to assist the local public health institutions on early detection of possible outbreaks at the early stage. However, the effectiveness was different for different regions and diseases.</p>

Study on the relationship between urinary albumin and serum bilirubin in patients with type 2 diabetes mellitus / 中国医师进修杂志

Objecttve To explore the relationship between urine albumin and serum bilirubin in patients with type 2 diabetes mellitus.Methods A total of 435 patients with type 2 diabetes mellitus from June 2011 to May 2012 were divided into 3 groups according to 24 hours urinary albumin excretion rate (UAER):normal albuminuria group (UAER ≤ 20 μg/min) in 217 cases; microalbuminuria group (UAER 21-199 μg/min,early diabetic nephropathy group) in 107 cases; great albuminuria group (UAER ≥200 μ g/min,clinical diabetic nephropathy group) in 111 cases.The difference of serum bilirubin level was compared among 3 groups.The risk factors were analyzed by multiple factors unconditional Logistic stepwise regression analysis.Results The serum total bilirubin,direct bilirubin and indirect bilirubin was (9.55 ± 3.48),(2.44 ± 1.03) and (7.11 ± 3.51) μ mol/L in clinical diabetic nephropathy group,which was lower than that in early diabetic nephropathy group[(10.92 ± 3.70),(2.71 ± 1.15),(8.23 ± 3.71) μ mol/L]and normal albuminuria group [(14.67 ±4.59),(2.86 ± 1.34),(11.84 ±4.48)μmol/L],and there was significant difference (P ＜0.05).Unconditional Logistic stepwise regression analysis showed that the correlation existed between glycosylated hemoglobin,blood uric acid,high density lipoprotein cholesferol and total bilirubin and diabetic nephropathy.Serum total bilirubin,high density lipoprotein cholesferol was protective factor,glycosylated hemoglobin,blood uric acid was risk factor.Conclusion High serum bilirubin level is conducive to fight oxidative stress,reduce inflammation,prevent lipid peroxidation,and suppress or delay the occurrence and development of diabetic nephropathy.