1.Construction of an index system for assessment of schistosomiasis transmission risk following natural disasters
Jingye SHANG ; Chenghang YU ; Zisong WU ; Xianhong MENG ; Huirong XU ; Chaofu WANG ; Bin ZHENG ; Shizhu LI ; Yang LIU
Chinese Journal of Schistosomiasis Control 2026;38(1):60-68
Objective To construct an index system for assessment of schistosomiasis transmission risk following natural disasters such as rainstorms, floods, earthquakes, mudslides, and landslides, so as to provide insights into rapid identification of schistosomiasis transmission risk post-disasters and formulation of targeted schistosomiasis control strategies. Methods An initial framework for the index system for assessment of schistosomiasis transmission risk following natural disasters was drafted through literature review, brainstorming, and focus group discussions. Two rounds of expert correspondence consultations were conducted using the Delphi method to refine and finalize the system, and the degrees of expert activeness, authority and endorse ment, and consensus were evaluated. In addition, the weights of each index were calculated using the analytic hierarchy process. Results A total of 18 experts participated in the consultation. The expert positive coefficients were 100.00% and 94.44% for two rounds of consultations, with authority coefficients of 0.92 and 0.94, respectively. The coefficients of coordination on the index importance, rationality and operability were 0.209, 0.185, 0.222 and 0.407, 0.214, 0.257 for two rounds of consultations, respectively, and all consistency tests were statistically significant (χ2 = 246.771 to 505.278, all P values < 0.001). Following two rounds of expert consultations, an index system consisting of 6 first-level indicators, 15 second-level indicators, and 49 third-level indicators was ultimately constructed. In terms of first-level indicators, “disaster situation”, “previous epidemics”, “healthcare guarantee”, “response capacity” and “emergency recovery” had the highest weights, each at 18.18%. Regarding second-level indicators, “Schistosoma japonicum infections in animals”, “S. japonicum infections in snails” and “medical treatment” had the highest weights, each at 7.35%. In terms of third-level indicators, ten items had the highest weights, including “identification of schistosomiasis cases”, “detection of S. japonicum infections in wild feces”, “detection of S. japonicum infections in snails”, “reserves of schistosomiasis diagnostic/testing reagents and consumables”, “reserves of chemotherapy agents for human and animal schistosomiasis”, “reserves of cercariacides”, “periodical surveillance on schistosomiasis”, “identification of schistosomiasis transmission risk and timely response”, “normal provision of diagnosis and treatment services” and “post-disaster schistosomiasis surveillance”, each at 2.40%. Conclusion A scientific, systematic, and practical index system has been constructed for assessment of schistosomiasis transmission risk following natural disasters, which may provide insights into rapid post-disaster identification of schistosomiasis transmission risk, formulation of targeted schistosomiasis control strategies and optimization of resource allocation.
2.PCSK9 promotes mitochondrial dysfunction to accelerate the process of abdominal aortic aneurysm
Man LI ; Yanyu CHEN ; Mengdie XIA ; Qian XU ; Yating ZHOU ; Huayu ZHANG ; Lushan LIU ; Zhihan TANG ; Juan PENG
Chinese Journal of Arteriosclerosis 2025;33(3):209-218
Aim To explore the impact and mechanism of proprotein convertase subtilisin kexin 9(PCSK9)on the progression of abdominal aortic aneurysm(AAA).Methods 6~8 week old ApoE-/-mice were selected to estab-lish the AAA model.Angiotensin Ⅱ(Ang Ⅱ)was continuously infused through subcutaneous implantation of a micro-os-motic pump.The mice were fed with high-fat diet and killed after 28 days.The expression of PCSK9 in abdominal aor-tic smooth muscle cells was detected by immunohistochemistry and immunofluorescence in normal abdominal aortic blood vessels and AAA samples in human and mice.Primary cultured murine vascular smooth muscle cells(mVSMC)of C57BL/6 mice were treated with different concentrations of AngⅡ for 24 h,and the expression of PCSK9 mRNA and pro-tein was detected.PCSK9 overexpression and knockdown cell models were established,and mitochondrial reactive oxygen species(mtROS),mitochondrial membrane potential(MMP),mitochondrial permeability transition pore(MPTP)open-ing,and Z-DNA binding protein 1(ZBP1)protein expression were detected.Bioinformatics was used to analyze the dif-ferential expression of multiple single-cell sequencing datasets to obtain the key differentially expressed genes,and to study their expression and role in AAA.Results Immunohistochemistry and immunofluorescence results showed that PCSK9 expression in human and mouse AAA increased(P<0.01),and co-localized with smooth muscle.Ang Ⅱ promoted PCSK9 expression in mVSMC in a concentration-dependent manner,the 2.0 μmol/L Ang Ⅱ group showed a 2.9-fold and 1.1-fold increase in the expression of PCSK9 mRNA and protein,respectively(P<0.01),with the most significant effect observed.After successfully constructing PCSK9 overexpression and PCSK9 interference mVSMC models,PCSK9 overex-pression led to an increase in intracellular mtROS,a decrease in MMP,an increase in MPTP opening,and a decrease in cellular activity(P<0.01);PCSK9 knockdown could reduce Ang Ⅱ induced increase in mtROS,decrease in MMP and MPTP opening;compared with the siNC+Ang Ⅱ group,the siPCSK9+Ang Ⅱ group showed a decrease in mtROS and an in-crease in the fluorescence brightness of MMP and MPTP(P<0.05).Bioinformatics analysis revealed that ZBP1 was a core differentially expressed gene in AAA.Immunohistochemistry and immunofluorescence results showed that ZBP1 ex-pression in human and mouse AAA tissues increased,and co-localized with smooth muscle.Western blot results showed that PCSK9 overexpression or treatment with 2.0 μmol/L Ang Ⅱ could increase ZBP1 protein expression(P<0.01),while PCSK9 knockdown could alleviate the increased ZBP1 expression caused by AngⅡ(P<0.05).Conclusion PCSK9 may induce mitochondrial damage in smooth muscle cells,activate downstream molecule ZBP1 to cause cell damage,and promote the development of AAA.
3.PCSK9 promotes mitochondrial dysfunction to accelerate the process of abdominal aortic aneurysm
Man LI ; Yanyu CHEN ; Mengdie XIA ; Qian XU ; Yating ZHOU ; Huayu ZHANG ; Lushan LIU ; Zhihan TANG ; Juan PENG
Chinese Journal of Arteriosclerosis 2025;33(3):209-218
Aim To explore the impact and mechanism of proprotein convertase subtilisin kexin 9(PCSK9)on the progression of abdominal aortic aneurysm(AAA).Methods 6~8 week old ApoE-/-mice were selected to estab-lish the AAA model.Angiotensin Ⅱ(Ang Ⅱ)was continuously infused through subcutaneous implantation of a micro-os-motic pump.The mice were fed with high-fat diet and killed after 28 days.The expression of PCSK9 in abdominal aor-tic smooth muscle cells was detected by immunohistochemistry and immunofluorescence in normal abdominal aortic blood vessels and AAA samples in human and mice.Primary cultured murine vascular smooth muscle cells(mVSMC)of C57BL/6 mice were treated with different concentrations of AngⅡ for 24 h,and the expression of PCSK9 mRNA and pro-tein was detected.PCSK9 overexpression and knockdown cell models were established,and mitochondrial reactive oxygen species(mtROS),mitochondrial membrane potential(MMP),mitochondrial permeability transition pore(MPTP)open-ing,and Z-DNA binding protein 1(ZBP1)protein expression were detected.Bioinformatics was used to analyze the dif-ferential expression of multiple single-cell sequencing datasets to obtain the key differentially expressed genes,and to study their expression and role in AAA.Results Immunohistochemistry and immunofluorescence results showed that PCSK9 expression in human and mouse AAA increased(P<0.01),and co-localized with smooth muscle.Ang Ⅱ promoted PCSK9 expression in mVSMC in a concentration-dependent manner,the 2.0 μmol/L Ang Ⅱ group showed a 2.9-fold and 1.1-fold increase in the expression of PCSK9 mRNA and protein,respectively(P<0.01),with the most significant effect observed.After successfully constructing PCSK9 overexpression and PCSK9 interference mVSMC models,PCSK9 overex-pression led to an increase in intracellular mtROS,a decrease in MMP,an increase in MPTP opening,and a decrease in cellular activity(P<0.01);PCSK9 knockdown could reduce Ang Ⅱ induced increase in mtROS,decrease in MMP and MPTP opening;compared with the siNC+Ang Ⅱ group,the siPCSK9+Ang Ⅱ group showed a decrease in mtROS and an in-crease in the fluorescence brightness of MMP and MPTP(P<0.05).Bioinformatics analysis revealed that ZBP1 was a core differentially expressed gene in AAA.Immunohistochemistry and immunofluorescence results showed that ZBP1 ex-pression in human and mouse AAA tissues increased,and co-localized with smooth muscle.Western blot results showed that PCSK9 overexpression or treatment with 2.0 μmol/L Ang Ⅱ could increase ZBP1 protein expression(P<0.01),while PCSK9 knockdown could alleviate the increased ZBP1 expression caused by AngⅡ(P<0.05).Conclusion PCSK9 may induce mitochondrial damage in smooth muscle cells,activate downstream molecule ZBP1 to cause cell damage,and promote the development of AAA.
4.Study on the Reaction Impurities Between Bromhexine Hydrochloride and Excipients in Bromhexine Hydrochloride Injection
Zhili ZENG ; Zhongli WU ; Baolin LIU ; Fei JIA ; Jinfang LOU ; Lushan YU
Chinese Journal of Modern Applied Pharmacy 2024;41(3):378-385
OBJECTIVE
To identify, synthesize and analyze the structure of unknown impurities unique to bromhexine hydrochloride injection and set the impurities as known impurity to control.
METHODS
The structure of unknown impurities was derived through two-dimensional liquid chromatography tandem mass spectrometry(2DLC-HRMS/MS), and the source of impurities was derived based on the product's prescription process. The mechanism of impurities generation was analyzed, and impurity monomers were obtained through directional synthesis. The structure of impurities was confirmed using techniques such as 2DLC-HRMS/MS and nuclear magnetic resonance. Finally, HPLC was used to verify the analysis method of impurities.
RESULTS
It was confirmed that such impurities were produced in a reaction between bromhexine and the excipient glucose. The correction factor of the two impurities were 2.2 and 2.4, the analytical method was specific and reproducible.
CONCLUSION
Name the two injection specific impurities as impurity 1 and impurity 2 respectively, and use them as known impurities to be included in the standard, calculate the impurity content using the self control and correction factor method. This study is of great significance in guiding the impurity control of bromhexine hydrochloride injection and the screening of excipient glucose.
5.Investigation and analysis of acute poisoning of organic fluorine mixed gas in a fluorine polymerization plant
Xiawen ZHENG ; Zhen NIE ; Sifeng LIU ; Zhao ZHENG ; Lushan WANG ; Shiming LAI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(3):184-187
In January 2021, an acute chemical poisoning incident occurred at a fluorine polymerization plant. Through the analysis of the occupational health situation of the enterprise, combined with the clinical manifestations of the poisoned patients and the laboratory examination results, it was determined that the incident was an acute poisoning incident caused by the inhalation of organic fluorine mixed gas in the fluorine polymerization plant. Subsequently, it was clarified that the accident was caused by the illegal operation of the employees of the fluorine polymerization plant, which caused the discharge of the organic fluorine mixed gas containing high concentration of octafluoroisobutene, resulting in the poisoning of the on-site construction personnel. In order to avoid the occurrence of similar incidents, enterprises should implement the main responsibility of safety production, regularly organize supervision and inspection, eliminate illegal operations, conduct safety education and training for the staff of the unit and outsourced staff, and improve the emergency rescue ability of sudden poisoning incidents.
6.Investigation and analysis of acute poisoning of organic fluorine mixed gas in a fluorine polymerization plant
Xiawen ZHENG ; Zhen NIE ; Sifeng LIU ; Zhao ZHENG ; Lushan WANG ; Shiming LAI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(3):184-187
In January 2021, an acute chemical poisoning incident occurred at a fluorine polymerization plant. Through the analysis of the occupational health situation of the enterprise, combined with the clinical manifestations of the poisoned patients and the laboratory examination results, it was determined that the incident was an acute poisoning incident caused by the inhalation of organic fluorine mixed gas in the fluorine polymerization plant. Subsequently, it was clarified that the accident was caused by the illegal operation of the employees of the fluorine polymerization plant, which caused the discharge of the organic fluorine mixed gas containing high concentration of octafluoroisobutene, resulting in the poisoning of the on-site construction personnel. In order to avoid the occurrence of similar incidents, enterprises should implement the main responsibility of safety production, regularly organize supervision and inspection, eliminate illegal operations, conduct safety education and training for the staff of the unit and outsourced staff, and improve the emergency rescue ability of sudden poisoning incidents.
7.Risk factors of stroke-associated pneumonia for patients with mild to moderate acute ischemic stroke
Ting DENG ; Jingmian CHEN ; Xiaomeng LIU ; Xiaohua YAO ; Lushan LIU ; Wei HE ; Tong ZHANG ; Haitao LU
Chinese Journal of Rehabilitation Theory and Practice 2023;29(6):708-713
ObjectiveTo explore the risk factors of stroke-associated pneumonia (SAP) for patients with mild to moderate acute ischemic stroke (AIS). MethodsFrom October, 2016 to December, 2019, 321 patients with mild to moderate AIS in Beijing Bo'ai Hospital were collected and divided into SAP group (n = 71) and non-SAP group (n = 250) according to whether they were complicated with SAP. Gender, age, time from symptom onset to admission, systolic pressure, diastolic pressure, scores of National Institutes of Health Stroke Scale (NIHSS) at admission, and medical history were recorded. Laboratory indexes including the count of white blood cell and platelet, levels of D-dimer, hypersensitive C-reactive protein (hs-CRP) and α-hydroxybutyrate dehydrogenase (α-HBDH) were measured. ResultsUnivariate analysis showed that age, NIHSS score, history of hypertension, atrial fibrillation, prior cerebral infarction, the count of white blood cell and platelet, the levels of D-dimer, hs-CRP and α-HBDH were the influencing factors of SAP (P < 0.2). Multivariate Logistic regression showed that age > 70 years old (OR = 7.121, 95%CI 3.493 to 14.514, P < 0.001), NIHSS score > 4 (5 to 10, OR = 4.861, 95% CI 2.412 to 9.797, P < 0.001), the count of platelet > 300×109/L (OR = 6.978, 95% CI 1.864 to 26.128, P = 0.004), and the level of D-dimer > 1.0 mg/L (OR = 3.036, 95% CI, 1.518 to 6.071, P = 0.002) were the risk factors of SAP. The model fitted the original data well (HL = 1.509,P = 0.680) and appeared a good prediction (AUC = 0.847, 95% CI 0.796 to 0.898, P < 0.001). ConclusionAge > 70 years old, NIHSS score > 4 (5 to 10), the count of platelet > 300×109/L and the level of D-dimer > 1.0 mg/L were the risk factors of SAP for patients with mild to moderate AIS.
8.Changes and predictive value of plasma histone H4 levels in patients with septic cardiomyopathy
Na SHANG ; Shubin GUO ; Huizhen LIU ; Na WANG ; Lushan LIU ; Junyu LI
Chinese Journal of Emergency Medicine 2022;31(2):197-202
Objective:To observe the changes of serum histone H4 level and its predictive value in patients with septic cardiomyopathy.Methods:A prospective study was conducted. A total of 147 patients with sepsis and septic shock were collected in emergency department. The general data were recorded. Transthoracic echocardiography and plasma histone H4 were conducted within 24 hours and 7 days after admission.The scores of sequential organ failure assessment(SOFA), acute physiology and chronic health evaluationⅡ(APACHEⅡ), and nutritional risk screening 2002 (NRS2002) were evaluated within 24 hours. According to whether septic cardiomyopathy occurred, the patients were divided into two groups, and dynamic changes of histone H4 on the first and seventh day of the two groups were observed. The factors influencing the occurrence of septic cardiomyopathy were analyzed by multivariate logistic regression. The prediction ability of serum histone H4 on septic cardiomyopathy was evaluated by receiver operating curve (ROC).Results:The incidence of septic cardiomyopathy was 28.6% (42 / 147). The level of histone H4 in septic cardiomyopathy group was higher than that in non septic cardiomyopathy group ( Z = 4.449, P < 0.001), and dynamic detection showed that the level of histone H4 on the seventh day was lower than that on admission ( Z=3.057, P=0.002). Multivariate logistic regression showed that the high serum histone H4 level [Odd Ratio( OR)=1.337, 95% confidence interval (95% CI) was 1.173-1.522, P < 0.001], SOFA ( OR= 1.474, 95% CI 1.227-1.769, P < 0.001), older age ( OR = 1.074, 95% CI 1.019-1.132, P = 0.008) were independent risk factors for septic cardiomyopathy. The area of ROC curve for serum histone H4 to predict septic cardiomyopathy was 0.729 ( P < 0.001), the predictive cut-off value was 10.81 ng/ml, which yielded a sensitivity 0.524 and a specificity of 0.914. Conclusions:The level of histone H4 showed dynamic change in septic cardiomyopathy, and high serum histone H4 level has a good predictive value for the occurrence of septic cardiomyopathy.
9.Relationship between sleep quality and slow-flow in patients with acute coronary syndrome during percutaneous coronary intervention and its impact on clinical prognosis
Lushan CHEN ; Xiaoming LEI ; Ping′an CHEN ; Jian LIU ; Shaonan LI ; Yishan LUO
Journal of Chinese Physician 2022;24(2):246-249,255
Objective:To investigate the relationship between sleep quality and slow-flow in patients with acute coronary syndrome during percutaneous coronary intervention(PCI) and its impact on clinical prognosis.Methods:200 patients with ACS hospitalized in the cardiology department of Guangzhou First People's Hospital from January 2017 to October 2018 were selected. The Pittsburgh Sleep Quality Index (PSQI) was measured before elective PCI, and the sleep breathing of patients was monitored by micro motion sensitive mattress sleep monitoring system (MSMSMS). The patients were divided into normal sleep group (68 cases, PSQI≤7 points) and sleep disorder group (132 cases, PSQI>7 points). The levels of plasma endothelin-1 (ET-1) and nitric oxide (NO) were measured. The " slow-flow" that took place during PCI were also recorded. Major cardiac adverse events (MACE) of patients took placed during 12 months follow-up periods were recorded and compared between two groups.Results:Compared with normal sleep group, patients in sleep disorder group had higher ratio of sleep apnea-hypopnea syndrome (SAHS), hypoxemia and lower deep sleep (25.00% vs 10.29%, 25.76% vs 11.76%, 66.67% vs 48.53%, all P<0.05); lower level of NO and higher level of ET-1 [(28.65±3.26)μmol/L vs (30.24±4.08)μmol/L; (21.17±3.08)pg/ml vs (18.90±2.95)pg/ml, P<0.05]; more slow-flow events took place during PCI in sleep disorder group than normal sleep group (16.67 vs 5.88%, P<0.05); After 12 months of follow-up, Kaplan-Meier survival analysis showed patients of the two groups had significantly different cumulative non-events survival rates (19.70% vs 7.35%, Log rank=5.06, P=0.025). Conclusions:Sleep disorder increase the slow-flow phenomenon during PCI in patients with ACS and affect the clinical prognosis.
10.Establishment and evaluation of clinical diagnostic scoring system for septic cardiomyopathy
Na SHANG ; Huizhen LIU ; Na WANG ; Junyu LI ; Yahui WANG ; Lushan LIU ; Shubin GUO
Chinese Critical Care Medicine 2021;33(12):1409-1413
Objective:To establish a clinical diagnostic scoring system for septic cardiomyopathy (SCM) and evaluate its diagnostic efficacy.Methods:A prospective cohort study was performed. Patients with sepsis and septic shock admitted to the department of emergency of China Rehabilitation Research Center were enrolled from January 2019 to December 2020. The baseline information, medical history, heart rate (HR), mean arterial pressure (MAP), body temperature and respiratory rate (RR) on admission were recorded. Laboratory indexes such as white blood cell count (WBC), hypersensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and blood lactic acid (Lac) were measured. Transthoracic echocardiography was conducted within 24 hours and on the 7th after admission. Sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluationⅡ(APACHEⅡ), and nutritional risk screening 2002 scale (NRS2002) were also assessed. The patients were divided into two groups according to whether SCM occurred or not. The risk factors of SCM were screened by univariate and multivariate Logistic regression. The cut-off value of continuous index was determined by receiver operator characteristic curve (ROC curve) and discretized concerning clinical data. The regression coefficient β was used to establish the corresponding score, and the clinical diagnostic score system of SCM was established. The diagnostic value of the model was evaluated by ROC curve.Results:In total, 147 patients were enrolled in the study and the incidence of SCM was 28.6% (42/147). Univariate Logistic regression analysis showed the risk factors of SCM included: ① continuous indicators: age, NT-proBNP, RR, MAP, Lac, NRS2002, SOFA, APACHEⅡ; ② discrete indicators: shock, use of vasoactive drugs, history of coronary heart disease, acute kidney injury (AKI). Multivariate Logistic regression analysis after discretization of above continuous index showed that age≥87 years old, NT-proBNP≥3 000 ng/L, RR≥30 times/min, Lac≥3 mmol/L and SOFA≥10 points were independent risk factors for SCM [age ≥87 years: odds ratio ( OR) = 3.491, 95% confidence interval (95% CI) was 1.371-8.893, P = 0.009; NT-proBNP≥3 000 ng/L: OR = 2.708, 95% CI was 1.093-6.711, P = 0.031; RR≥30 times/min: OR = 3.404, 95% CI was 1.356-8.541, P = 0.009; Lac≥3 mmol/L: OR = 3.572, 95% CI was 1.460-8.739, P = 0.005; SOFA≥10 points: OR = 8.693, 95% CI was 2.541-29.742, P = 0.001]. The clinical diagnostic score system of SCM was established successfully, which was composed of age≥87 years old (1 point), NT-proBNP ≥ 3 000 ng/L(1 point), RR≥30 times/min (1 point), Lac≥3.0 mmol/L (1 point), SOFA≥10 points (2 points), and the total score was 6 points. ROC curve analysis showed the cut-off value of the scoring system for diagnosing SCM was 3 points, the area under ROC curve (AUC) was 0.833, 95% CI was 0.755-0.910, P < 0.001, with the sensitivity of 71.4%, and specificity of 86.7%. Conclusion:The clinical diagnostic scoring system has good diagnostic efficacy for SCM and contributes to early identification of SCM for clinicians.


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