An interpretable machine learning-based prediction model for risk of death for patients with ischemic stroke in intensive care unit / 南方医科大学学报

OBJECTIVE@#To construct an inherent interpretability machine learning model as an explainable boosting machine model (EBM) for predicting one-year risk of death in patients with severe ischemic stroke.@*METHODS@#We randomly divided the data of 2369 eligible patients with severe ischemic stroke in the MIMIC-Ⅳ(2.0) database, who were admitted in ICU in 2008 to 2019, into a training dataset (80%) and a test dataset (20%), and assessed the prognosis of the patients using the EBM model. The prediction performance of the model was evaluated by calculating the area under the receiver operating characteristic (AUC) curve. The calibration curve and Brier score were used to evaluate the degree of calibration of the model, and a decision curve was generated to assess the net clinical benefit.@*RESULTS@#The EBM model constructed in this study had good discrimination power, calibration and net benefit, with an AUC of 0.857 (95% CI: 0.831-0.887) for predicting prognosis of severe ischemic stroke. Calibration curve analysis showed that the standard curve of the EBM model was the closest to the ideal curve. Decision curve analysis showed that the model had the greatest net benefit rate at the prediction probability threshold of 0.10 to 0.80. The top 5 independent predictive variables based on the EBM model were age, SOFA score, mean heart rate, mechanical ventilation, and mean respiratory rate, whose significance scores ranged from 0.179 to 0.370.@*CONCLUSION@#This EBM model has a good performance for predicting the risk of death within one year in patients with severe ischemic stroke and allows clinicians to better understand the contributing factors of the patients' outcomes through the model interpretability.

Research progress on pathogenesis and treatment of drug-resistant epilepsy / 药学学报

Epilepsy is a chronic nervous system disease, which affects more than 70 million people all over the world. Although more than 30 kinds of antiepileptic drugs (AEDs) have been on the market, about one third of the patients with epilepsy fail to respond to medical treatment, who become drug-resistant epilepsy patients. Identifying the mechanism and developing effective treatment methods for drug-resistant epilepsy have become a hot area in the field of epilepsy research. This review discussed resent advance on the pathogenesis of drug-resistant epilepsy from the transporter hypothesis, neural network hypothesis and target hypothesis, and we also summarized the existing potential treatment methods and research progress of drug-resistant epilepsy, such as surgical resection, deep brain stimulation, ketogenic diet, precise treatment, and traditional Chinese medicine treatment. Our review may provide useful clues for the mechanisms research and clinical treatments of drug-resistant epilepsy.

Safety of butylphthalide and edaravone in patients with ischemic stroke: a multicenter real-world study / 老年心脏病学杂志（英文版）

BACKGROUND@#Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations.@*METHODS@#In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively.@*RESULTS@#81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count.@*CONCLUSIONS@#In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.

Current research status and application prospect of numerical simulation in traditional Chinese medicine drying / 中国中药杂志

With the rapid development of computer technology, numerical simulation has gradually become an important method to study drying process and improve drying equipment. Using computer to simulate the drying process of traditional Chinese medicine(TCM) is characterized by intuitiveness, scientificity, and low cost, which serves as an auxiliary means for technical innovation in TCM drying. This paper summarizes the theories of different drying methods and the research status of numerical simulation in drying, introduces the modeling methods and software of numerical simulation, and expounds the significance of numerical simulation modeling in shortening the research and development cycle, improving drying equipment, and optimizing drying parameters. However, the current numerical simulation method for drying process has problems, such as low accuracy, lack of quantitative indicators for the control of simulation results on the process, and insufficient in-depth research on the mechanism of drug quality changes. Furthermore, this paper put forward the application prospect of numerical simulation in TCM drying, providing reference for the further study of numerical simulation in this field.

Compound Tinglizi Decoction intervenes COPD-associated pulmonary hypertension through regulation of HMGB1-mediated pyroptosis and immune imbalance / 中国中药杂志

This paper aimed to investigate the effects of high mobility group box 1(HMGB1)-mediated pulmonary artery smooth muscle cell pyroptosis and immune imbalance on chronic obstructive pulmonary disease-associated pulmonary hypertension(COPD-PH) in rats and the intervening mechanism of Compound Tinglizi Decoction. Ninety rats were randomly divided into a normal group, a model group, low-dose, medium-dose, and high-dose Compound Tinglizi Decoction groups, and a simvastatin group. The rat model of COPD-PH was established by fumigation combined with lipopolysaccharide(LPS) intravascular infusion, which lasted 60 days. Rats in the low, medium, and high-dose Compound Tinglizi Decoction groups were given 4.93, 9.87, and 19.74 g·kg~(-1) Compound Tinglizi Decoction by gavage, respectively. Rats in the simvastatin group were given 1.50 mg·kg~(-1) simvastatin by gavage. After 14 days, the lung function, mean pulmonary artery pressure, and arterial blood gas of rats were analyzed. Lung tissues of rats were collected for hematoxylin-eosin(HE) staining to observe the pathological changes. Real-time fluorescent quantitative polymerase chain reaction(qRT-PCR) was used to determine the expression of related mRNA in lung tissues, Western blot(WB) was used to determine the expression of related proteins in lung tissues, and enzyme linked immunosorbent assay(ELISA) was used to determine the levels of inflammatory factors in the lung tissues of rats. The ultrastructure of lung cells was observed by transmission electron microscope. The forced vital capacity(FVC), forced expiratory volume in 0.3 second(FEV_(0.3)), FEV_(0.3)/FVC, peek expiratory flow(PEF), respiratory dynamic compliance(Cdyn), arterial partial pressure of oxygen(PaO_2), and arterial oxygen saturation(SaO_2) were increased, and resistance of expiration(Re), mean pulmonary arterial pressure(mPAP), right ventricular hypertrophy index(RVHI), and arterial partial pressure of carbon dioxide(PaCO_2) were decreased by Compound Tinglizi Decoction in rats with COPD-PH. Compound Tinglizi Decoction inhibited the protein expression of HMGB1, receptor for advanced glycation end products(RAGE), pro caspase-8, cleaved caspase-8, and gasdermin D(GSDMD) in lung tissues of rats with COPD-PH, as well as the mRNA expression of HMGB1, RAGE, and caspase-8. Pulmonary artery smooth muscle cell pyroptosis was inhibited by Compound Tinglizi Decoction. Interferon-γ(IFN-γ) and interleukin-17(IL-17) were reduced, and interleukin-4(IL-4) and interleukin-10(IL-10) were incresead by Compound Tinglizi Decoction in lung tissues of rats with COPD-PH. In addition, the lesion degree of trachea, alveoli, and pulmonary artery in lung tissues of rats with COPD-PH was improved by Compound Tinglizi Decoction. Compound Tinglizi Decoction had dose-dependent effects. The lung function, pulmonary artery pressure, arterial blood gas, inflammation, trachea, alveoli, and pulmonary artery disease have been improved by Compound Tinglizi Decoction, and its mechanism is related to HMGB1-mediated pulmonary artery smooth muscle cell pyroptosis and helper T cell 1(Th1)/helper T cell 2(Th2), helper T cell 17(Th17)/regulatory T cell(Treg) imbalance.

Research advances in the size selection of implantable collamer lens / 国际眼科杂志(Guoji Yanke Zazhi)

The implantable collamer lens(ICL)is a widely popular option for the correction of refractive errors. ICL implantation brings a whole new dimension to the vision, from the anterior chamber phakic ICL to the posterior and central hole ICL. Even though there are fewer reported complications, ICL size selection remains challenging due to the differences in device measurements and ICL sizing formulas. With the widening comprehensiveness of ICL implantation and the ongoing development of ophthalmic devices and technologies, particularly the advent of artificial intelligence, more and more indicators such as sulcus-to-sulcus(STS), crystalline lens rise(CLR), angle-to-angle(ATA), the iris pigment end to the iris pigment end(PTP), anterior chamber width(ACW), and anterior chamber angle(ACA)are providing references in the selection of ICL size, this article provides a review of ICL size selection.

Analysis for the short-term efficacy and long-term prognosis of laparoscopic and laparotomy radical resection for gallbladder cancer / 中华外科杂志

Objective: To compare the short-term efficacy and long-term prognosis of laparoscopic and laparotomy radical resection for gallbladder cancer(GBC). Methods: From January 2010 to December 2020,the clinical data and survival information for 133 patients who underwent radical resection of GBC at the Department of Hepatopancreatobiliary Surgery,Zhejiang Provincial People's Hospital,were retrospectively collected. Eighty patients(23 males and 57 females) underwent laparoscopic radical resection and had a median age(M(IQR)) of 66.0(12.8)years(range:28.0 to 82.0 years). Fifty-three patients(45 males and 8 females) who received laparotomy were 63.0(6.0)years old(range:45.0 to 80.0 years old). There were no significant differences in age,gender,body mass index,preoperative albumin,preoperative total bilirubin,N stages,vascular invasion,peri-neural invasion or tumor differentiation between the laparoscopic and laparotomy group(all P>0.05). But there were significant differences in preoperative CA19-9(Z=-2.955, P=0.003), preoperative ALT level(Z=-2.801,P=0.031) and T stage (χ2=19.110,P=0.007) between the two groups. A non-parametric test was used for quantitative data. χ2 test or Fisher exact probability method was used for count data. Results: Patients in the laparoscopic group did not differ from those in the laparotomy group in terms of length of operation,number of lymph node yield,number of positive lymph nodes,the incidence of intraoperative gallbladder rupture,incidence of postoperative bile leakage,abdominal bleeding or abdominal infection,30-day mortality,90-day mortality, the incidence of incision implantation or peritoneal cavity metastasis(all P>0.05). Patients in the laparoscopic group showed less intraoperative bleeding(100.0(200.0)ml vs. 400.0(250.0)ml)(Z=-5.260,P<0.01),fewer days with drainage tube indwelling(6.0(3.8)days vs. 7.0(4.0)days)(Z=-3.351, P=0.001), and fewer postoperative days in hospital(8.0(5.0)days vs. 14.0(7.5)days)(Z=-6.079,P<0.01) than those in the laparotomy group. Patients in the laparoscopic group displayed better overall survival (P<0.01) and progression-free survival (P<0.01). Subgroup analysis for GBC of T1b-T2 and T3 stages revealed comparable overall survival and progression-free survival between the laparoscopic and laparotomy groups (P>0.05). Conclusions: Laparoscopic radical resection can achieve long-term survival for GBC comparable to that with open surgery. Laparoscopic radical resection has advantages over open surgery regarding surgical trauma and postoperative recovery.

Intermittent theta burst stimulation can improve the spatially-delayed responses of working memory / 中华物理医学与康复杂志

Objective:To observe any effect of intermittent theta burst stimulation (iTBS) on the spatially-delayed responses of working memory using cynomolgus macaques.Methods:The working memory of six male cynomolgus macaques (8-9 years old) was trained using a spatially-delayed response task. They were then randomly divided into an iTBS group and a control group, each of 3. The iTBS group was given iTBS at an intensity of 35% of the maximum output, with 2 seconds of stimulation followed by 8 seconds of rest with trains of 50Hz bursts repeated at a frequency of 5Hz over a period of 192 seconds once daily for 5 days, while the control group was given sham iTBS. Before and after the 5 days, the body weight and working memory of each animal were evaluated. The total number of effective feeding episodes, and of effective feeding episodes with short and long delay periods were recorded.Results:There was no significant change in the average body weight of either group before and after the modeling and iTBS intervention. After the intervention the number of total effective feeding cases and those with a short delay period were both significantly higher in the iTBS group than in the control group. However, no significant inter-group differences in the effective feeding cases with a long delay period were observed.Conclusions:iTBS is effective in improving the spatially-delayed responses of working memory, at least in cynomolgus macaques.

Effects of in-house made heat preservation socks on body temperature maintenance in elderly patients undergoing spinal surgery / 中华老年医学杂志

Objective:To examine the effects of in-house made heat preservation socks on body temperature maintenance in elderly patients undergoing posterior approach spinal surgery.Methods:This was a randomized, controlled trial.A total of 84 patients aged 65-75 years treated with posterior approach spinal surgery under general anesthesia were enrolled.Patients were randomly divided into two groups: the experimental group(n=42)and the control group(n=42). The two groups were treated with the same anesthesia procedure.The control group was given routine temperature management, while the experimental group used in-house made heat preservation socks in addition to routine temperature management during the entire surgical process.The anal temperature of patients was dynamically monitored with a disposable body temperature probe, and body temperature, heart rate, mean arterial pressure and oxygen saturation were recorded at the time of anesthesia induction and intubation(T 0), skin incision(T 1), 1 hour into surgery(T 2), 2 hours into surgery(T 3), the end of surgery(T 4), arrival at the post-anesthesia care unit(T 5), immediately after extubation(T 6)and 1 hour after extubation(T 7). The occurrence of intraoperative body temperature lower than 36℃, postoperative extubation time, incidence of shivering, postoperative incision infection rate and average length of stay were recorded.Changes in C-reactive protein and procalctonin levels were recorded. Results:There was no significant difference in sex composition, age, height, weight, body mass index and operative time between the two groups(all P>0.05). From T 2 to T 7, the body temperature of the experimental group was higher than that of the control group[T 2: (36.5±0.5)℃ vs.(36.3±0.3)℃, (36.6±0.6)℃ vs.(36.2±0.4)℃, (36.6±0.6)℃ vs.(36.2±0.4)℃, (36.6±0.6)℃ vs.(36.2±0.4)℃, (36.6±0.6)℃ vs.(36.2±0.4)℃, (36.6±0.5)℃ vs.(36.2±0.3)℃, t=2.229, 3.514, 3.823, 3.790, 3.722, 4.408, P=0.029, 0.001, 0.001, 0.001, 0.001, 0.000]. The incidence of intraoperative body temperature lower than 36 ℃ in the control group was higher than that in the experimental group(47.6% vs.21.4%, χ2=6.372, P=0.012). The incidence of postoperative shivering in the experimental group was lower than that in the control group(21.4% vs.59.5%, χ2=12.649, P<0.001). There was no significant difference between the two groups in postoperative incision infection rate, average length of stay and postoperative inflammatory infection indicators(all P>0.05). Conclusions:For elderly patients undergoing posterior spinal surgery, the in-house made heat preservation socks have favorable effects on body temperature maintenance and help reduce the occurrence of hypothermia and postoperative shivering.

Mechanism of mixed probiotics relieves food allergy in infant mice through the programmed cell death 1/programmed cell death ligand 1 pathway / 中华实用儿科临床杂志

Objective:To investigate the effects of mixed probiotics on food allergy and the underlying mechanism.Methods:BALB/c mice on the 15 th day of pregnancy were randomly (random number table method) classified into the control group, food allergy model group and mixed probiotics group.Mice in the food allergy model and mixed pro-biotics group were subjected to ovalbumin (OVA) sensitization after birth, and those in the mixed probiotics group were then given probiotic solution by gavage from day 21 to day 35.Mice in control group were similarly given 9 g/L saline.Twenty-four hours after the last OVA sensitization, intestinal histopathological sections were prepared to observe intestinal pathological changes.Blood smears were prepared to detect eosinophil count.In addition, serum samples were collected to measure cytokine levels and OVA specific antibodies.The number of dendritic cells (DCs) and regulatory T cells (Tregs) in mouse mesenteric lymph nodes was calculated.Differences among 3 groups were compared by the One- Way ANOVA or Kruskal- Wallis H test. Results:Compared with those of food allergy model group, diarrhea score, the ratio of eosinophils and serum levels of interleukin(IL)-4, IL-5, IL-13, mast cell protease 1 (MCPT-1), and OVA specific antibodies IgE and IgG were significantly lower in mixed probiotics group[(2.00±0.71) points vs.(3.22±0.97) points, (2.28±1.61)% vs.(10.99±2.26)%, (413.68±22.81) ng/L vs.(708.78±27.66) ng/L, (36.64±3.74) ng/L vs.(46.05±4.95) ng/L, (201.37±65.61) ng/L vs.(495.22±96.66) ng/L, (31 924.15±1 177.77) ng/L vs.(36 175.77±618.29) ng/L, (9.10±8.08) ng/L vs.(19.69±0.84) ng/L, (30.50±8.81) ng/L vs.(190.32±6.40) ng/L], while IL-10 level was significantly higher[(164.12±3.88) ng/L vs.(123.90±7.31) ng/L] ( t=3.37, 8.72, 16.07, 3.90, 7.40, 7.95, 3.91, 44.00 and 7.76, respectively, all P<0.01). Compared with those of food allergy model group, programmed cell death ligand 1 (PD-L1) level on the surface of CD 103+ DCs and CD 103+ CD 80-CD 40-DCs, the proportion of Tregs in CD4 + T cells, and the level of programmed cell death 1 (PD-1) on the surface of Tregs were significantly higher in mixed probiotics group[(75.59±0.45)% vs.(45.60±4.73)%, (67.56±1.87)% vs.(37.12±6.07)%, (8.24±0.69)% vs.(6.20±0.66)%, (11.25±3.12)% vs.(4.08±2.33)%]( t=7.88, 4.48, 3.63 and 3.71, all P<0.01). Conclusions:Mixed probiotics can alleviate the symptoms of food allergy and inflammatory response of young rats through mediating Tregs via the PD-1/PD-L1 pathway.

Design and evaluation of ideological and political teaching of Medical Statistics for postgraduates / 上海预防医学

ObjectiveTo design and evaluate the ideological and political teaching in the Medical Statistics as a public basic course for postgraduates in a medical school. MethodsThrough expert consultation， literature review， investigation， we designed the main points in the ideological and political teaching for the Medical Statistics. Students' satisfaction and demand of ideological and political teaching were investigated by a questionnaire. Furthermore， effect of ideological and political teaching was evaluated. ResultsA total of 178 out of 201 graduate students in Grade 2020 in a medical university completed the survey， accounting for 88.56%， with a response rate of 100%. Among them， 84.27% of the students believed it was necessary to implement ideological and political teaching for the Medical Statistics， and 90.45% expected that ideological and political teaching could be combined with case studies. The comparison before and after class showed that the students’ correct understanding of data acquisition has been greatly improved from 78.65% to 100%. In addition， the proportion of those who were dedicated to studying increased from 89.88% to 97.75%. ConclusionThe ideological and political teaching for Medical Statistics can be implemented in combination with case studies. Ideological and political teaching may improve the courses with practical operation of knowledge and skills.

Bioinformatics-based identification of key genes CDC5L and related pathways in osteosarcoma and Ewing's sarcoma / 中国骨伤

OBJECTIVE@#Osteosarcoma(OS) and Ewing's sarcoma (EWS) are the two most common primary malignant bone tumors in children. The aim of the study was to identify key genes in OS and EWS and investigate their potential pathways.@*METHODS@#Expression profiling (GSE16088 and GSE45544) were obtained from GEO DataSets. Differentially expressed genes were identified using GEO2R and key genes involved in the occurrence of both OS and EWS were selected using venn diagram. Gene ontology and pathway enrichment analyses were performed for the ensembl. Protein-protein interaction (PPI) networks were established by STRING. Further, UCSC was used to predict the transcription factors of the cell division cycke 5-like(CDC5L) gene, and GEPIA was used to analyze the correlation between the transcription factors and the CDC5L gene.@*RESULTS@#The results showed that CDC5L gene was the key gene involved in the pathogenesis of OS and EWS. The gene is mainly involved in mitosis, and is related to RNA metabolism, processing of capped intron-containing pre-mRNA, mRNA and pre-mRNA splicing.@*CONCLUSION@#CDC5L, as a key gene, plays a role in development of OS and EWS, which may be reliable targets for diagnosis and treatment of these primary malignant tumors.

Economic Burden of Heart Failure in Asian Countries with Different Healthcare Systems

Background and Objectives@#Heart failure (HF) poses substantial economic burden, primarily driven by high hospitalization and mortality rates. This study aimed to understand the economic burden of HF in 4 Asian countries under varying healthcare systems. @*Methods@#This was a non-interventional, retrospective study conducted in South Korea, Taiwan, Thailand and Malaysia through medical chart review. Eligible patients included those who had either ≥1 hospitalization or ≥2 outpatient visits from January 1st to December 31st, 2014, and at least one year of follow-up. Resource use and direct healthcare costs (adjusted to 2015 USD) of HF were assessed. HF costs for subgroups stratified by age and sex were assessed. @*Results@#A total of 568 patients were recruited from South Korea (n=200), Taiwan (n=200), Thailand (n=100) and Malaysia (n=68). The proportion of patients hospitalized ranged from 20.0% to 93.5% (South Korea 20.0%, Thailand 49.0%, Malaysia 70.6%, and Taiwan 93.5%).The overall annual HF cost per patient was $2,357, $4,513, $3,513 and $1,443 in South Korea, Taiwan, Thailand, and Malaysia, respectively; hospitalized HF care costs were $10,714, $4,790, $7,181 and $1,776, respectively. The length of stay was more than 12.2 days except in Malaysia. No specific trend was observed in subgroup analysis. @*Conclusions@#In Asia, HF poses significant economic burden and hospitalization has emerged as the major cost driver among healthcare costs. A streamlined treatment strategy reducing hospitalization rate can minimize the economic burden.

Economic Burden of Heart Failure in Asian Countries with Different Healthcare Systems

Background and Objectives@#Heart failure (HF) poses substantial economic burden, primarily driven by high hospitalization and mortality rates. This study aimed to understand the economic burden of HF in 4 Asian countries under varying healthcare systems. @*Methods@#This was a non-interventional, retrospective study conducted in South Korea, Taiwan, Thailand and Malaysia through medical chart review. Eligible patients included those who had either ≥1 hospitalization or ≥2 outpatient visits from January 1st to December 31st, 2014, and at least one year of follow-up. Resource use and direct healthcare costs (adjusted to 2015 USD) of HF were assessed. HF costs for subgroups stratified by age and sex were assessed. @*Results@#A total of 568 patients were recruited from South Korea (n=200), Taiwan (n=200), Thailand (n=100) and Malaysia (n=68). The proportion of patients hospitalized ranged from 20.0% to 93.5% (South Korea 20.0%, Thailand 49.0%, Malaysia 70.6%, and Taiwan 93.5%).The overall annual HF cost per patient was $2,357, $4,513, $3,513 and $1,443 in South Korea, Taiwan, Thailand, and Malaysia, respectively; hospitalized HF care costs were $10,714, $4,790, $7,181 and $1,776, respectively. The length of stay was more than 12.2 days except in Malaysia. No specific trend was observed in subgroup analysis. @*Conclusions@#In Asia, HF poses significant economic burden and hospitalization has emerged as the major cost driver among healthcare costs. A streamlined treatment strategy reducing hospitalization rate can minimize the economic burden.

Impact and predictive value of time-dependent acute physiology and chronic health evaluation Ⅱ score on death risk in patients with severe stroke: data analysis based on MIMIC-Ⅲ / 中华危重病急救医学

Objective:To study the influence of time-dependent acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score on 14-day death risk in patients with severe stroke, and to provide reference for clinical diagnosis and treatment.Methods:Data of 3 229 patients with severe stroke were enrolled from Medical Information Mart for Intensive Care-Ⅲ (MIMIC-Ⅲ). According to the main types of stroke, the patients were divided into subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), ischemic stroke (IS) and other groups. According to age, patients were divided into > 60 years old and ≤ 60 years old subgroups. According to the baseline of sequential organ failure assessment (SOFA) score, they were divided into subgroups of > 3 and ≤ 3. The daily measured values of APACHE Ⅱ scores in each patient were recorded. And all-cause death within 14 days after admission to intensive care unit (ICU) was used as the outcome index to obtain the survival status and survival time of patients. Joint models for longitudinal and time-to-event data were established to evaluate the effect of APACHE Ⅱ score measured at multiple time points on the death risk of patients, and a subgroup analysis was performed.Results:Among the joint models, the one which include APACHE Ⅱ score, and the interaction items between APACHE Ⅱ and age showed the better fitting. Further analysis showed that APACHE Ⅱ score was affected by age, gender, hospital admission, baseline SOFA score and smoking history. After controlling for these confounding factors, APACHE Ⅱ score was significantly associated with 14-day all-cause death in patients with severe stroke [hazard ratio ( HR) = 1.48, 95% confidence interval (95% CI) was 1.31-1.66, P < 0.001], which indicated that the risk of death increased by 48% (95% CI was 31%-66%) for each 1-point increase in APACHE Ⅱ score. Subgroup analysis showed that for different types of severe stroke patients, APACHE Ⅱ score had a greater impact on the risk of 14-day death in SAH patients ( HR = 1.43, 95% CI was 1.10-1.85), but had a smaller impact on ICH and IS groups [HR (95% CI) was 1.37 (1.15-1.64) and 1.35 (1.06-1.71), respectively]. There was no significant difference in APACHE Ⅱ score on the risk of 14-day death between the patients aged > 60 years old and those aged ≤ 60 years old [ HR (95% CI): 1.37 (1.08-1.72) vs. 1.35 (1.07-1.70), respectively]. Compared with patients with SOFA score > 3, APACHE Ⅱ score had a greater impact on the risk of 14-day death in patients with SOFA score ≤ 3 [ HR (95% CI): 1.40 (1.16-1.70) vs. 1.34 (1.16-1.55)]. Conclusion:Time-dependent APACHE Ⅱ score is an important indicator to evaluate the risk of death in patients with severe stroke.

Research Advances in the Mechanisms of BRD4 and Its Inhibitors in Hematologic Malignancies--Review / 中国实验血液学杂志

Bromodomain-containing protein 4 (BRD4) is one of the most important members in the bromodomain and extra terminal domain(BET) family, it plays an important role in cellular physiology in human body, such as cell cycles, cell proliferation, and immune response. Recent studies have shown that BRD4 is associated with occurrence and development of acute myeloblastic leukemia, multiple myeloma and lymphoma. The mechanisms of BRD4 in hematologic malignancies including the regulation of c-Myc expression, and participation of the composition of super-enhancer, etc. At present, many kinds of inhibitors have been developed to target inhibit BRD4 for therapy in hematologic malignancies, and some of BRD4 inhibitors have entered phase Ⅱ clinical trials, which suggested that BRD4 inhibitors are expected to become new therapeutic agents for hematologic malignancies. In this review, the research advance of BRD4 and BRD4 inhibitors in hematologic malignancies was summarized briefly.

Development and application of a chemical transformational method for the indirect measurement of ligustilide content in Angelica sinensis / 药学学报

The poor stability of the ligustilide (LIG) makes its quantitation in Angelica sinensis (AS) difficult. This study establishes a chemical conversion method for the determination of ligustilide content in AS and proposes a national pharmacopoeia standard. Mechanical agitation and sonication of a powdered AS extract in a methanol/cyprolamine mixture facilitated the stabilization and transformation of ligustilide. Using an external reference HPLC-DAD method, the cyclopropyl-ligustilide (LIGc) content in the mixture could be determined. The content of ligustilide was greater than 1.0% based on 144 AS specimens including 68 obtained from the originally planted areas of Qinghai and Gansu Province; 55 specimens were obtained from Minxian and Weiyuan County medicine markets, and 21 specimens for which the storage period reached or exceeded 1.5 years. According to the Hong Kong Chinese materis medica standards, the content of ligustilide in AS should not be lower than 0.6%. The developed method could also be applied to the quality control of other Chinese medicinal materials (such as Ligusticum chuanxiong) or Chinese patent medicines in which ligustilide is the main component.

Analysis of two cases of glycogen storage disease type III due to compound heterozygous variants of AGL gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic basis of two children with glycogen storage disease type III (GSD III).@*METHODS@#The probands and their parents were subjected to genetic testing, and the pathogenity of candidate variants was analyzed by using bioinformatic tools.@*RESULTS@#Sequencing has identified compound heterozygous variants of the AGL gene in both children, namely c.1423+1G>A and c.3701-2A>G in case 1, and c.4213_c.4214insA (p.Glu1405Glufs*17) and c.3589-3C>G in case 2. Both children were diagnosed with GSD III. Literature review suggested that the main type variant among Chinese patients with GSD III involve splice sites of the AGL gene, with c.1735+1G>T being the most common. Based on the American College of Medical Genetics and Genomics standards and guidelines,c.1423+1G>A, c.3701-2A>G and c.4213_c.4214insA variants of AGL gene were predicted to be of pathogenic (PVS1+PM2+PM3, PVS1+PM2+PM3, PVS1+PM2+PP5), and c.3589-3C>G variant was predicted to be of uncertain significance (PM2+PM3+PP3).@*CONCLUSION@#The compound heterozygous variants of the AGL gene probably underlay the GSD III in both children. Above findings have enriched the spectrum of genetic variants underlying this disease.

Impact of thymosin α1 as an immunomodulatory therapy on long-term survival of non-small cell lung cancer patients after R0 resection: a propensity score-matched analysis / 中华医学杂志(英文版)

BACKGROUND@#There is limited information about thymosin α1 (Tα1) as adjuvant immunomodulatory therapy, either used alone or combined with other treatments, in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate the effect of adjuvant Tα1 treatment on long-term survival in margin-free (R0)-resected stage IA-IIIA NSCLC patients.@*METHODS@#A total of 5746 patients with pathologic stage IA-IIIA NSCLC who underwent R0 resection were included. The patients were divided into the Tα1 group and the control group according to whether they received Tα1 or not. A propensity score matching (PSM) analysis was performed to reduce bias, resulting in 1027 pairs of patients.@*RESULTS@#After PSM, the baseline clinicopathological characteristics were similar between the two groups. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly higher in the Tα1 group compared with the control group. The multivariable analysis showed that Tα1 treatment was independently associated with an improved prognosis. A longer duration of Tα1 treatment was associated with improved OS and DFS. The subgroup analyses showed that Tα1 therapy could improve the DFS and/or OS in all subgroups of age, sex, Charlson Comorbidity Index (CCI), smoking status, and pathological tumor-node-metastasis (TNM) stage, especially for patients with non-squamous cell NSCLC and without targeted therapy.@*CONCLUSION@#Tα1 as adjuvant immunomodulatory therapy can significantly improve DFS and OS in patients with NSCLC after R0 resection, except for patients with squamous cell carcinoma and those receiving targeted therapy. The duration of Tα1 treatment is recommended to be >24 months.

Flipped classroom teaching:Practice and evaluation / 上海预防医学

Objective To evaluate the feasibility and effectiveness of flipped classroom teaching in medical research design class with more than 50 undergraduate. Methods Using randomized parallel-control study, two classes were chosen for this study:flipped classroom teaching group (i.e.FC group) and traditional teaching group (i.e.control group).Except for different teaching modes, all the other conditions of these two groups remained the same, including learning materials, network reference materials and teaching equipment. Results The FC group had 52 students and the control group had 69 students.After teaching, the final test score on study design in FC group was 11.53 higher (95%CI:4.75-18.32, t=3.37, P=0.001).However, there was no statistically significant difference between the test scores of other medical statistic teaching units (t=0.223, P=0.824). Conclusion FC teaching can be used in large class (more than 50 students) in medical undergraduate education.For flipped classroom teaching with large number of students, teachers should strengthen the arrangement of students′ self-study before class, organize effective team discussion, and make full use of new technologies to support teaching.