1.Multicenter retrospect analysis of early clinical features and analysis of risk factors on prognosis of elderly patients with severe burns
Qimin MA ; Wenbin TANG ; Xiaojian LI ; Fei CHANG ; Xi YIN ; Zhaohong CHEN ; Guohua WU ; Chengde XIA ; Xiaoliang LI ; Deyun WANG ; Zhigang CHU ; Yi ZHANG ; Lei WANG ; Choulang WU ; Yalin TONG ; Pei CUI ; Guanghua GUO ; Zhihao ZHU ; Shengyu HUANG ; Liu CHANG ; Rui LIU ; Yongji LIU ; Yusong WANG ; Xiaobin LIU ; Tuo SHEN ; Feng ZHU
Chinese Journal of Burns 2024;40(3):249-257
Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.
2.Clinical efficacy of Da Vinci robot-assisted superior mediastinum lymph node dissection around recurrent laryngeal nerve
Xiaofeng DUAN ; Jie YUE ; Xiaobin SHANG ; Zhao MA ; Chuangui CHEN ; Chen ZHANG ; Zuoyu CHEN ; Hongjing JIANG
Chinese Journal of Digestive Surgery 2023;22(S1):1-6
Objective:To investigate the clinical efficacy of Da Vinci robot-assisted superior mediastinum lymph node dissection around recurrent laryngeal nerve.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 404 patients with esophageal cancer who underwent Da Vinci robot-assisted esophagectomy in Tianjin Medical University Cancer Hospital and Institute from June 2017 to June 2022 were collected. There were 349 males and 55 females, aged (62±8)years. Observation indicators: (1) intraoperative conditions; (2) postoperative conditions; (3) comparison of clinical features in patients who were admitted in different time periods. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the one way ANOVA. Measurement data with skewed distribution were represented as M(IQR), and comparison among multiple groups was conducted using the Kruskal-Wallis H test. Count data were described as absolute numbers or percentages, and com-parison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Intraoperative conditions. The operation time, volume of intraoperative blood loss, the total number of lymph node dissected, the number of thoracic lymph node dissected, left recurrent laryngeal nerve lymph node dissection rate, the number of left recurrent laryngeal nerve lymph node dissected, left recurrent laryngeal nerve lymph node metastasis rate, right recurrent laryngeal nerve lymph node dissection rate, the number of right recurrent laryngeal nerve lymph node dissected, right recurrent laryngeal nerve lymph node metastasis rate were (306±56)minutes,200(100)mL, 29.9±13.1, 18.5±9.7, 78.47%(317/404), 4.0(3.0), 17.35%(55/317), 94.55%(382/404), 3.0(2.0), 21.20%(81/382). (2) Postoperative conditions. The tumor histopathological type (squamous cell carcinoma, neuroendocrine carcinoma, adenocarcinoma, carcinosarcoma, adenosquamous carcinoma, malignant melanoma), incidence rate of overall complications, cases with recurrent laryngeal nerve paralysis, cases with pulmonary complications, cases with anastomotic fistula, cases with incision infection, cases with chylothorax, cases with arrhythmia, cases with deep vein thrombosis, cases with other complications, incidence of re-admission to the intensive care unit, duration of postoperative hospital stay, 90-day mortality were 377, 11, 7, 5, 3, 1, 27.48%(111/404), 8.91%(36/404), 10.64%(43/404), 6.93%(28/404), 0.99%(4/404), 2.48%(10/404), 1.73%(7/404), 0.50%(2/404), 1.98%(8/404), 6.93%(28/404), 16(11)days, 0.50%(2/404). (3) Comparison of clinical features in patients who were admi-tted in different time periods. The number of patients who were admitted from June 2017 to May 2018, from June 2018 to May 2019, from June 2019 to May 2020, from June 2020 to May 2021, from June 2021 to June 2022 was 40, 56, 57, 116, 135, respectively. There were significant differences in age, tumor histopathological type, pT staging, neoadjuvant therapy, operation time, volume of intra-operative blood loss, the total number of lymph node dissected, the number of thoracic lymph node dissected, left recurrent laryngeal nerve lymph node dissection rate, the number of left recurrent laryngeal nerve lymph node dissected, the number of right recurrent laryngeal nerve lymph node dissected, incidence rate of overall complications among patients who were admitted in different time periods ( P<0.05). Conclusion:The Da Vinci robot-assisted superior mediastinum lymph node dissection around recurrent laryngeal nerve is safe and feasible, which can achieve good short-term efficacy.
3.Study on improvement mechanism of caudatin on liver injury in rats
Zhihui CHANG ; Yang BU ; Qian LIU ; Qian MA ; Jie SONG ; E SUN ; Yingjie WEI ; Yi LUO ; Xiaobin TAN
China Pharmacy 2023;34(5):531-536
OBJECTIVE To investigate the improvement mechanism of caudatin on liver injury of rats. METHODS SD rats were randomly divided into blank group, model group, caudatin low-dose and high-dose groups (25, 50 mg/kg), with 6 rats in each group. Diethylnitrosamine (DEN) was injected intraperitoneally three times per week for eight weeks to establish liver injury model of rats. At 5th week of modeling, the rats received relevant medicine or 0.5% sodium carboxymethylcellulose intragastrically for 4 weeks. The levels of liver function indexes [alanine transaminase (ALT), aspartate transaminase (AST), total protein (TP) and total bilirubin (TBI)] and inflammatory factors [interleukin (IL-6), tumor necrosis factor α (TNF-α), IL-1β] in serum were detected; the histopathological morphological changes of rat liver were observed; the positive protein expressions of nuclear factor κB (NF-κB) and 78 kDa glucose regulatory protein (Grp78) in liver tissue were also determined; the expressions of endoplasmic reticulum stress-related protein Grp78, C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6) and inositol requiring enzyme 1α (IRE1α) and the level of protein kinase R-like endoplasmic reticulum kinase robertluoyi@126.com (PERK) in liver tissue were detected. RESULTS Compared with blank group, serum levels of ALT, AST, TBI, IL-6, TNF-α and IL-1β and positive expressions of NF-κB and Grp78 in liver tissue as well as protein expressions of Grp78, CHOP, ATF6 and IRE1α, PERK protein phosphorylation level were all increased significantly in model group (P<0.05), while the serum level of TP was decreased significantly (P<0.05). The disordered structure of liver lobule, swollen liver cells, unclear intercellular boundary were observed and accompanied by inflammatory cell infiltration. Compared with model group, most of the above indexes were significantly reversed in caudatin groups (P<0.05); the structure of hepatic lobule was relatively complete and clear, the cells were arranged orderly, and the infiltration of inflammatory cells was also reduced. CONCLUSIONS Caudatin has a significant improvement effect against DEN-induced liver injury in rats, the mechanism of which may be associated with inhibiting endoplasmic reticulum stress and inflammatory reaction.
4.Analyzing and monitoring real-world clinical safety of ensartinib for the treatment of patients with ALK-positive non-small cell lung cancer
Xiaobin YUAN ; Yang WANG ; Min YANG ; Pengxiang WU ; Zhilin SHEN ; Yongbin MA ; Lieming DING
Journal of International Oncology 2023;50(3):150-156
Objective:To evaluate the safety of ensartinib in the treatment of anaplastic lymphoma kinase (ALK) -positive non-small cell lung cancer (NSCLC) in the real-world clinical setting.Methods:Clinical data of 2 221 patients with ALK-positive locally advanced or metastatic NSCLC who received ensartinib treatment (225 mg/d) from December 16, 2020 to December 16, 2021 were collected and analyzed to assess drug adverse reactions in all population including elderly patients (≥ 65 years old) .Results:Among the total 2 221 patients, 511 patients (23.01%) experienced adverse events, including 8 patients (0.36%) who experienced serious adverse events. Adverse events led to dose modification in 67 patients (3.02%) and discontinuation in 18 patients (0.81%). The common adverse events were rash (407/2 221, 18.33%), pruritus (41/2 221, 1.85%), constipation (41/2 221, 1.85%), and facial edema (31/2 221, 1.40%). Thirty-six patients (1.62%) experienced ≥grade 3 adverse events. After symptomatic treatment of 511 patients with adverse reactions, 50 patients (9.78%) were healed, 271 patients (53.03%) were improved, 120 patients (23.48%) were persisted, and 70 patients (13.71%) were unknown due to loss of follow-up or other reasons. Forty-three patients (1.94%) reported 57 unintended adverse reactions. Among the 599 elderly patients, 116 patients (19.37%) experienced adverse events, including 1 patient (0.17%) who experienced serious adverse events. Adverse events led to dose modification in 25 patients (4.17%) and discontinuation in 5 patients (0.83%). The common adverse events of elderly patients were rash (88/599, 14.69%), constipation (14/599, 2.34%), facial edema (12/599, 2.00%), and pruritus (10/599, 1.67%). Twelve patients (2.00%) experienced ≥grade 3 adverse events. Among the 116 elderly patients with adverse reactions following the symptomatic treatment, 11 patients (9.48%) were healed, 58 patients (50.00%) were improved, 28 patients (24.13%) were persisted, and 19 patients (16.39%) were unknown due to loss of follow-up or other reasons. During the treatment, 1 patient (0.05%) experienced grade 2 interstitial lung disease, and no patient died due to adverse events.Conclusion:Ensartinib has a favorable safety profile in the real-world populations, with the most frequent adverse events being rash, mostly mild, and low incidence of ≥grade 3 adverse events. Overall, adverse reactions were tolerable and manageable.
5.Risk factors analysis and risk prediction model construction and validation of cognitive dysfunction after brain trauma
Xijun HAO ; Ping LEI ; Xiaobin MA ; Changxiang CHEN
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(1):37-44
Objective:To analyze the independent risk factors for the occurrence of post-traumatic cognitive dysfunction, construct a prediction model for the risk factors of post-traumatic cognitive dysfunction, and verify the effectiveness of the risk prediction model, so as to provide a clinical tool for early prediction of the risk of post-traumatic cognitive impairment.Methods:Part I: patients with brain trauma (training set with 556 subjects) who were hospitalized in 21 tertiary and secondary hospitals from Tangshan, Cangzhou and Chengde cities of Hebei province were retrospectively collected from February to May 2021 for Montreal cognitive assessment, and 33 influencing factors (general data, symptoms and signs, laboratory and imaging parameters) were obtained obtained through literature research.The patients were divided into case group and control group according to whether they had cognitive impairment or not, and univariate and multivariate analysis were used to screen independent risk factors.Part Ⅱ: a binary Logistic regression equation was used to construct a cognitive impairment prediction model, the visualization model of line graph is presented.Part Ⅲ: brain trauma patients (260 subjects of the validation set) hospitalized in the aforementioned 21 hospitals from August to October 2021 were collected as a prospective validation population for the prediction model of cognitive impairment, and the grouping basis of case group and control group was the same as before.And the risk factors between the two groups were compared.The receiver operating characteristic curve(ROC), calibration curve and clinical applicability of the model were drawn to evaluate the effectiveness of the model for internal and external verification of the model.Results:Binary Logistic regression analysis showed that the risk factors for post-traumatic cognitive dysfunction were basal ganglia injury, severe injury, amnesia experience after injury, frequent headache after injury, upper limb dysfunction after injury, age ≥ 60 years, and education level of elementary school or below.Visual nomograms showed that the experience of amnesia after injury, frequent headache after injury, upper limb dysfunction, and degree of injury among the symptom factors were the factors that contributed greatly to the risk of traumatic brain injury cognitive impairment in this model.Predictive model discrimination using area under curve(AUC) values of the area under the ROC curve showed that internal validation and external validation were 0.868 and 0.885 for R language analysis and 0.868 and 0.901 for SPSS analysis, respectively.The curve after model calibration almost coincided with the reference line, Hosmer-Lemeshow test P>0.05.The two decision curve analysis (DCA) curves drawn by the clinical applicability of the model were higher than the two extreme curves, predicting that traumatic brain injury patients with cognitive impairment could benefit from the predictive model, and there was a net benefit rate in the range of Pt about 0.1-0.8, when Pt reached about 0.1 until the approximate 1.0 composite evaluation model. Conclusion:Risk factors such as experience of amnesia after injury, frequent headache after injury, upper limb dysfunction, and degree of injury are predicting factors contributed to the risk of cognitive impairment in traumatic brain injury, and their prediction models have good predictive effect, high predictive accuracy and good clinical applicability, which can be applied in clinical diagnosis.
6.Correlation between blood pressure indexes and prognosis in sepsis patients: a cohort study based on MIMIC-III database.
Xiaobin LIU ; Yu ZHAO ; Yingyi QIN ; Qimin MA ; Yusong WANG ; Zuquan WENG ; Feng ZHU
Chinese Critical Care Medicine 2023;35(6):578-585
OBJECTIVE:
To investigate the correlation between early-stage blood pressure indexes and prognosis in sepsis patients.
METHODS:
A retrospective cohort study was conducted on the medical records of patients diagnosed with sepsis from 2001 to 2012 in the Medical Information Mart for Intensive Care-III (MIMIC-III) database. Patients were divided into survival group and death group according to the 28-day prognosis. General data of patients and heart rate (HR) and blood pressure at admission to ICU and within 24 hours after admission were collected. The blood pressure indexes including the maximum, median and mean value of systolic index, diastolic index and mean arterial pressure (MAP) index were calculated. The data were randomly divided into training set and validation set (4 : 1). Univariate Logistic regression analysis was used to screen covariates, and multivariate Logistic stepwise regression models were further developed. Model 1 (including HR, blood pressure, and blood pressure index related variables with P < 0.1 and other variables with P < 0.05) and Model 2 (including HR, blood pressure, and blood pressure index related variables with P < 0.1) were developed respectively. The receiver operator characteristic curve (ROC curve), precision recall curve (PRC) and decision curve analysis (DCA) curve were used to evaluate the quality of the two models, and the influencing factors of the prognosis of sepsis patients were analyzed. Finally, nomogram model was developed according to the better model and effectiveness of it was evaluated.
RESULTS:
A total of 11 559 sepsis patients were included in the study, with 10 012 patients in the survival group and 1 547 patients in the death group. There were significant differences in age, survival time, Elixhauser comorbidity score and other 46 variables between the two groups (all P < 0.05). Thirty-seven variables were preliminarily screened by univariate Logistic regression analysis. After multivariate Logistic stepwise regression model screening, among the indicators related to HR, blood pressure and blood pressure index, the HR at admission to ICU [odds ratio (OR) = 0.992, 95% confidence interval (95%CI) was 0.988-0.997] and the maximum HR (OR = 1.006, 95%CI was 1.001-1.011), maximum MAP index (OR = 1.620, 95%CI was 1.244-2.126), mean diastolic index (OR = 0.283, 95%CI was 0.091-0.856), median systolic index (OR = 2.149, 95%CI was 0.805-4.461), median diastolic index (OR = 3.986, 95%CI was 1.376-11.758) were selected (all P < 0.1). There were 14 other variables with P < 0.05, including age, Elixhauser comorbidity score, continuous renal replacement therapy (CRRT), use of ventilator, sedation and analgesia, norepinephrine, norepinephrine, highest serum creatinine (SCr), maximum blood urea nitrogen (BUN), highest prothrombin time (PT), highest activated partial thromboplastin time (APTT), lowest platelet count (PLT), highest white blood cell count (WBC), minimum hemoglobin (Hb). The ROC curve showed that the area under the curve (AUC) of Model 1 and Model 2 were 0.769 and 0.637, respectively, indicating that model 1 had higher prediction accuracy. The PRC curve showed that the AUC of Model 1 and Model 2 were 0.381 and 0.240, respectively, indicating that Model 1 had a better effect. The DCA curve showed that when the threshold was 0-0.8 (the probability of death was 0-80%), the net benefit rate of Model 1 was higher than that of Model 2. The calibration curve showed that the prediction effect of the nomogram model developed according to Model 1 was in good agreement with the actual outcome. The Bootstrap verification results showed that the nomogram model was consistent with the above results and had good prediction effects.
CONCLUSIONS
The nomogram model constructed has good prediction effects on the 28-day prognosis in sepsis patients, and the blood pressure indexes are important predictors in the model.
Humans
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Cohort Studies
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Retrospective Studies
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Blood Pressure
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Intensive Care Units
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ROC Curve
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Sepsis/diagnosis*
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Prognosis
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Critical Care
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Norepinephrine
7.Visual analysis of the current research status and development of burn-related coagulation dysfunction
Qimin MA ; Yusong WANG ; Wenjia HOU ; Xiaobin LIU ; Tuo SHEN ; Feng ZHU
Chinese Journal of Burns 2023;39(4):356-363
Objective:To conduct a visual analysis of the literature on burn-related coagulation dysfunction and to explore the current research status, evolution process, hot topics, and future research trends in burn-related coagulation dysfunction at home and abroad.Methods:The bibliometrics method was used. The literature on burn-related coagulation dysfunction which were published in Web of Science and China National Knowledge Internet databases from January 1, 1950 to May 1, 2022, and met the inclusion criteria were retrieved for publication volume analysis. The literature on burn-related coagulation dysfunction were retrieved as above in the core collection of Web of Science and China National Knowledge Internet databases, and CiteSpace 5.8.R3 software was used to perform co-occurrence analysis, cluster analysis, and literature co-citation analysis of key words. Results:A total of 501 and 235 literature on burn-related coagulation dysfunction were retrieved from Web of Science database and China National Knowledge Internet database, respectively. The literature on burn-related coagulation dysfunction emerged from 1975 and 1950, respectively, in China and abroad, which were gradually increased later. The frequency and centrality of Chinese key words such as 烧伤, 凝血功能, 血小板 were high in 235 literature in China National Knowledge Internet database, and the frequency and centrality of key words such as burn, coagulation, and deep vein thrombosis were high in 340 literature in the core collection of Web of Science database. In China National Knowledge Internet database, the top 6 Chinese key words in terms of burst intensity were 烧伤患者, 临床意义, 烧伤面积, 凝血功能, 预后, 血小板, and the first 3 among which were burst key words in the early stage; and in the core collection of Web of Science database, the key words with higher burst intensity were disseminated intravascular coagulation and pulmonary embolism, which were the burst key words in the early stage. The representative clustering labels in China National Knowledge Internet database were #0 烧伤, #1 休克, and #2 并发症, etc., and the representative clustering labels in the core collection of Web of Science database were #0 risk, #1 surgical patient, and #2 sepsis. Early researches in China National Knowledge Internet database and the core collection of Web of Science database focused on the presence of burn-related coagulation dysfunction itself, while the late researches focused on the relationship between burn-related coagulation dysfunction and inflammation, immunity, coagulation in general, and wounds. From 2010 onwards, there were a large number of core cited literature in the core collection of Web of Science database, and the prevention and treatment of vein thromboembolism was the most popular research direction in recent years. The researches on optimization and standardization of diagnostic methods and the overall mechanism of burn-related coagulation dysfunction would be the main research directions in the future. Conclusions:The research hotspots and evolution processes of burn-related coagulation dysfunction at home and abroad have both similarities and differences, and the current research hotspot is the relationship between coagulation and inflammation, immunity. With researches increasingly deepening, the researches on optimization and standardization of diagnostic methods and the overall mechanism of burn-related coagulation dysfunction will be the main research directions in the future.
8.Research on the Necessity and Feasibility of Current Medical Device Supervision Legislation.
Chinese Journal of Medical Instrumentation 2022;46(4):433-437
This paper studies the necessity of the current legislation on the supervision of medical devices in China from the perspectives of strengthening administration according to law, protecting public health, perfecting the legal system of medicine and promoting the development of the medical device industry. This study analyzes and summarizes the legislative experiences and forms in the field of medical device regulation in the United States, the European Union, Japan and other countries and regions, at present, the conditions of carrying out the legislation of medical device supervision in China are quite mature, and some policy suggestions are put forward for the enactment of the law of medical device management in China.
Equipment and Supplies
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European Union
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Feasibility Studies
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Industry
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Medical Device Legislation
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United States
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United States Food and Drug Administration
9.A novel inhibitor of ARfl and ARv7 induces protein degradation to overcome enzalutamide resistance in advanced prostate cancer.
Yan LI ; Ya CHU ; Guangjiang SHI ; Xiaobin WANG ; Wanli YE ; Chun SHAN ; Dajia WANG ; Di ZHANG ; Wei HE ; Jingwei JIANG ; Shuqian MA ; Yuhong HAN ; Zhili ZHAO ; Shijia DU ; Zhen CHEN ; Zhiyu LI ; Yong YANG ; Chen WANG ; Xi XU ; Hongxi WU
Acta Pharmaceutica Sinica B 2022;12(11):4165-4179
Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.
10. Preventive Effect of Panax notoginseng Saponins Combined With Bacillus subtilis on Colorectal Cancer Based on Microbiome
Xiaobin LIU ; Yichao DUAN ; Mengya MA ; Xueling ZHANG ; Ruyue GUO ; Xueling REN
Chinese Journal of Gastroenterology 2022;27(3):135-143
Background: Dysregulation of intestinal flora is a key risk factor for colorectal cancer (CRC). In recent years, traditional Chinese medicine preparations and probiotics have been increasingly applied in the prevention of CRC. Aims: To investigate the preventive effect of Panax notoginseng saponins (PNS) combined with Bacillus subtilis on CRC. Methods: Thirty female BALB/c mice were randomly divided into normal control group (NC group), model group, PNS group, Bacillus subtilis group and PNS combined with Bacillus subtilis group (PaB group). CRC mice model was constructed by azoxymethane (AOM)/dextran sulfate sodium (DSS) method. During the experiment, the mice were weighed, and disease activity index (DAI) score was evaluated. The length of colorectum and tumor number were measured. Serum interleukin (IL) - 6 and IL - 10 contents were determined by ELISA. 16S rRNA sequencing was used to analyze the composition of intestinal flora. Results: Compared with model group, DAI score was significantly decreased (P<0.001), colorectal length was significantly increased (P<0.001), number of tumor was significantly decreased (P<0.001), tumor volume was significantly decreased (P<0.01), serum IL-6 content was significantly decreased (P<0.000 1), and serum IL-10 content was significantly increased in PaB group (P<0.000 1). The results of intestinal flora sequencing showed that Simpson index was significantly decreased in PaB group than in model group (P<0.05), Shannon index and Chao index were significantly increased (P<0.05), abundance of Bacteroidota was significantly increased (P<0.01), abundances of Firmicutes, Helicobacter and Oscillibacter were significantly decreased (P all <0.05), abundance of Lactococcus was significantly increased (P<0.05). Conclusions: The combination of PNS and Bacillus subtilis can effectively alleviate the occurrence of CRC caused by AOM/DSS, and its mechanism may be related to the improvement of composition of intestinal microbial community.

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