1.Incremental effectiveness of two-dose of mumps-containing vaccine in chidren
Chinese Journal of School Health 2025;46(6):883-887
Objective:
To evaluate the incremental vaccine effectiveness (VE) of two dose of the mumps containing vaccine (MuCV) in chidren, so as to provide a basis for optimizing mumps immunization strategies.
Methods:
A 1∶2 frequency matched case-control study was conducted by using reported mumps cases in childcare centers or schools from Lu an, Hefei, Ma anshan and Huainan cities of Anhui Province from September 1, 2023 to June 30, 2024, as a case group(383 cases). And healthy children in the same classroom were selected as a control group(766 cases). The MuCV immunization histories of participants were collected to estimate the incremental VE of the second dose of MuCV against mumps. Group comparisons were performed using the Chi square test or t-test. For matched case-control pairs, the Cox regression model was employed to calculate the odds ratio (OR) with 95% confidence interval (CI) for two dose MuCV vaccination and to estimate the incremental vaccine effectiveness (VE).
Results:
There were no statistically significant differences between the case and control groups regarding gender, age, dosage of MuCV vaccination and the time interval since the last dose vaccination( χ 2/t=0.05, 0.20, 0.94, -0.02, P >0.05). The proportions of the case and control groups vaccinated with two doses of MuCV were 26.63% and 29.37%, respectively, and the overall incremental VE of the second dose of MuCV was 40.73% (95% CI=3.03%-63.77%, P <0.05). Subgroup analyses revealed that the incremental VE for children with a period of ≥1 year between the two doses of MuCV was 54.13% (95% CI=1.90%-78.56%, P <0.05), while for children with a period of <1 year, it was 30.63% (95% CI=-28.59%-62.58%, P >0.05). The incremental VE of the second dose of MuCV was 30.36% (95% CI=-25.95%-61.50%, P >0.05) in kindergarten children and 66.73% (95% CI=14.92%-86.99%, P <0.05) in elementary and secondary school students. The incremental VE was 28.78% (95% CI=-27.46%-60.21%, P >0.05) within five years of the last dose of MuCV vaccination and 66.07% (95% CI=-41.56%-91.87%, P >0.05) for vaccinations administered beyond five years.
Conclusions
The second dose of MuCV may offer additional protection for children; however, extending the interval between two dose of MuCV (<1 year) has shown limited incremental protective effects. Therefore, it is crucial to consider optimizing current immunization strategies for mumps.
2.Mechanism of Cigarette Smoke-induced Injury to Alveolar Epithelial Cells
Jian-Lu TIAN ; Hong-Juan WANG ; Huan CHEN ; Hong-Wei HOU ; Qing-Yuan HU
Progress in Biochemistry and Biophysics 2024;51(9):2144-2155
Smoking is the leading preventable risk factor for disease and death worldwide. Tobacco and its smoke contain a complex mix of over 9 500 chemical substances, including oxidative gases, heavy metals, and 83 known carcinogens. Long-term smoking is a significant risk factor for respiratory diseases such as acute lung injury, emphysema, and pulmonary fibrosis. Damage to alveolar epithelial cells (AECs) is a common pathological feature in these smoking-related lung diseases. AECs, which line the surface of the alveoli, play a crucial role in preventing overexpansion or collapse, secreting cell factors and surfactants, containing abundant mitochondria, and being essential for lung tissue maturation, gas exchange, metabolism, and repair after damage. Damage to these cells can lead to pulmonary edema and alveolar collapse. Cigarette smoke (CS) can disrupt alveolar epithelial cell function through various pathways, resulting in cell death, tissue damage, and the development of lung diseases.This review summarizes recent research on the damage caused by CS to AECs, showing that CS can promote cell death and damage through induction of oxidative stress, autophagy, endoplasmic reticulum stress, mitochondrial dysfunction, inflammation, and epithelial-mesenchymal transition. It also affects the proliferative function of alveolar type II epithelial cells. The review highlights that CS-induced oxidative stress is a key factor in causing various types of damage, with TRP ion channels serving as important triggers. Inhibiting CS-induced oxidative damage can significantly prevent cell death and subsequent diseases such as pulmonary emphysema. The activation of the same pathway induced by CS can lead to different types of cell damage, potentially encouraging the development of different diseases. CS can either directly induce or indirectly promote cell inflammation through endoplasmic reticulum stress, mitochondrial dysfunction, and senescence. There are interconnected relationships between these mechanisms, and SIRT1 is an important protein in preventing CS-induced AECs damage. Increasing SIRT1 activity can alleviate CS-induced autophagy, endoplasmic reticulum stress, and senescence in various cell damages; its substrate NAD+ is already used clinically, and its effectiveness in COPD treatment deserves further exploration. The impact of CS on cells varies based on concentration: lower concentrations stimulate stress responses or apoptosis, while higher concentrations lead to apoptosis or necrosis through various mechanisms, ultimately impairing lung epithelial function. When external stimuli exceed the cells’ self-healing capacity, they can cause damage to cells, lung epithelial barriers, and alveoli, promoting the development of related lung diseases. Key proteins that play a protective role may serve as potential targets to mitigate cell damage.This review provides insights into the various mechanisms through which CS induces damage to AECs, covering important transcription factors, DNA repair proteins, and membrane channel proteins, paving the way for the study of new mechanisms and pathways. However, there are still unanswered questions, such as the need for further exploration of the upstream pathways of CS-induced autophagy in AECs and the intrinsic mechanisms of CS in enhancing the stem cell properties of AECs and its relationship to the occurrence of lung cancer.It is expected that this article will provide a theoretical basis for future research on the mechanisms of lung epithelial cell damage caused by CS or its individual components and inspire clinical strategies for the prevention and treatment of smoking-related lung diseases.
3.Zuoguiwan Prevent Decreased Ovarian Reserve in Prenatal Stressed Offspring Rats via TLR4/NF-κB p65 Signaling Pathway
Yinjuan LYU ; Weiheng ZHANG ; Siyi CHEN ; Wenjing TIAN ; Jian GONG ; Yuhao MENG ; Huan HE ; Xiaocui JIANG ; Min ZHAO ; Min XIAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):67-76
ObjectiveTo observe the effect of Zuoguiwan on ovarian reserve in the female offspring rat model of prenatal stress (PS) and explore the mechanism based on Toll-like receptor 4/nuclear factor-κB p65 (TLR4/NF-κB p65) signaling pathway. MethodThirty-two pregnant rats were prepared and randomized into four groups (n=8): control, model, Zuoguiwan (18.9 mg·kg-1), and vitamin E (1.44 mg·kg-1). Except the control group, the other three groups were subjected to chronic unpredictable mild stress (CUMS) from day 11 of pregnancy, and the modeling was accompanied by gavage with corresponding drugs until delivery. The PS model was evaluated by the sucrose preference test, open field test, and serum corticosterone (CORT) level. The estrous cycle was monitored and the morphological changes in the ovarian tissue were observed. The serum levels of estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and anti-Mullerian hormone (AMH) in the 75-day-old offspring rats were measured by enzyme-linked immunosorbent assay (ELISA) to evaluate the ovarian reserve. The ovary and uterus indices were calculated. The serum levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). The morphology of the ovarian tissue in the offspring on the day of birth and day 75 after birth was observed by hematoxylin-eosin staining. The transport of NF-κB p65 to the nucleus in the ovaries of the 75-day-old offspring was detected by the immunofluorescence (IF) assay. The expression of TLR4, NF-κB p65 and other related proteins in the ovarian tissue was determined by Western blot. ResultCompared with the control group, the model group showed reduced primordial follicles in the offspring on the day of birth (P<0.01) as well as disturbed estrous cycle, decreased ovary index and uterus index (P<0.01), reduced corpus luteum, increased atretic follicles (P<0.01), lowered serum levels of AMH and E2 (P<0.01), elevated serum levels of LH, FSH, IL-1β, and TNF-α (P<0.05, P<0.01), and up-regulated protein levels of TLR4, NF-κB p65, recombinant myeloid differentiation factor 88 (MyD88), and phosphorylated NF-κB inhibitor (p-IκBα) (P<0.01) in the 75-day-old offspring rats. Compared with the model group, Zuoguiwan and vitamin E increased the primordial follicles in the offspring on the day of birth (P<0.01). Moreover, they resumed the estrous cycle, increased the ovary and uterine indices (P<0.05, P<0.01) and corpus luteum (P<0.01), reduced atretic follicles (P<0.01), elevated the serum levels of AMH and E2 (P<0.05, P<0.01), lowered the serum levels of LH, FSH, IL-1β, and TNF-α (P<0.05, P<0.01), and down-regulated the expression of TLR4, NF-κB p65, MyD88, and p-IκB-α (P<0.05, P<0.01) in the 75-day-old offspring. ConclusionZuoguiwan can improve the ovarian reserve in the offspring rat model of congenital kidney deficiency by regulating the TLR4/NF-κB p65 signaling pathway.
4.Environmental hygiene and healthcare-associated infection:a time-series study based on generalized additive model
Kai LIN ; Kun CHEN ; Jian-Bing WANG ; Fang-Hua FAN ; Hui LIANG ; Fang CHEN ; Kai-Ling JIN ; Wen-Jie CHU ; Wei-Guo CHEN ; Huan SHAN
Chinese Journal of Infection Control 2024;23(7):798-805
Objective To quantitatively analyze the impact of environmental hygiene on the occurrence of health-care-associated infections(HAI).Methods Monitoring data of HAI and environmental hygiene from a tertiary first-class hospital from January 2018 to December 2022 were collected,and the impact of environmental bacterial colony forming unit(CFU)on the occurrence of HAI was analyzed by a time-series generalized additive model.Results The single-contamination model showed a significant positive correlation between HAI and staff's hand bacterial CFU(β1=0.009,P=0.012).For an increase of 1 interquartile range(IQR)in the monthly mean CFU per dish(MCFU/Dish)of staffs'hand,the incidence of HAI increased by 13.28%(95%CI:2.82%-24.81%).Subgroup and lag effect analysis showed that when the monthly MCFU/Dish(after hand disinfection)of staffs'hand in-creased by one IQR,the excess risk(ER)of HAI for the month(lag0)was 16.26%(95%CI:15.45%-17.09%).In the multi-contamination model,the correlation between surface contamination and HAI was also statistically sig-nificant.Conclusion There is a significant correlation between hospital environmental hygiene and the occurrence of HAI.
5.Genetic Subtypes and Pretreatment Drug Resistance in the Newly Reported Human Immunodeficiency Virus-Infected Men Aged≥50 Years Old in Guangxi.
Ning-Ye FANG ; Wen-Cui WEI ; Jian-Jun LI ; Ping CEN ; Xian-Xiang FENG ; Dong YANG ; Kai-Ling TANG ; Shu-Jia LIANG ; Yu-Lan SHAO ; Hua-Xiang LU ; He JIANG ; Qin MENG ; Shuai-Feng LIU ; Qiu-Ying ZHU ; Huan-Huan CHEN ; Guang-Hua LAN ; Shi-Xiong YANG ; Li-Fang ZHOU ; Jing-Lin MO ; Xian-Min GE
Acta Academiae Medicinae Sinicae 2023;45(3):399-404
Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ2=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male
;
Humans
;
Middle Aged
;
Reverse Transcriptase Inhibitors/therapeutic use*
;
HIV Infections/drug therapy*
;
Drug Resistance, Viral/genetics*
;
China/epidemiology*
;
Mutation
;
HIV-1/genetics*
;
Protease Inhibitors/therapeutic use*
;
Genotype
6.Analysis and evaluation of bioactive constituents from different parts of Epimedium brevicornum.
Jia XUE ; Hai-Jie CHEN ; Yong-Yi ZHOU ; Jia-Huan YUAN ; Zhi-Chen CAI ; Nan WU ; Cui-Hua CHEN ; Xun-Hong LIU ; Li-Si ZOU ; Sheng-Xin YIN ; Wei YANG ; Jian-Ming CHENG
China Journal of Chinese Materia Medica 2023;48(13):3448-3461
A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 μm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.
Chromatography, High Pressure Liquid
;
Epimedium
;
Tandem Mass Spectrometry
;
Chromatography, Liquid
;
Multivariate Analysis
7.The Effects and Regulatory Mechanism of Targeting CXC Chemokine Receptor 1/2 Combined with Ara-C on the Malignant Biological Behaviors of U937 Cells of Acute Myeloid Leukemia.
Yan-Quan LIU ; Jian-Zhen SHEN ; Yue YIN ; Yu-Ting CHEN ; Hui YANG ; Huan-Wen TANG
Journal of Experimental Hematology 2023;31(2):364-376
OBJECTIVE:
To investigate and analyze the effect of CXC chemokine receptor 1/2 (CXCR1/2) targeting inhibitor Reparixin combined with cytarabine (Ara-C) on the malignant biological behaviors of acute myeloid leukemia cells and its effect on the expression of the CXCR family, while exploring the accompanying molecular mechanism, providing scientific basis and reference for new molecular markers and targeted therapy for AML.
METHODS:
Acute myeloid leukemia U937 cells were treated with different concentrations of Reparixin, Ara-C alone or in combination, and the cell morphology was observed under an inverted microscope; Wright-Giemsa staining was used to detect cell morphological changes; CCK-8 method was used to detect cell proliferation; the ability of cell invasion was detected by Transwell chamber method; the ability of colony formation was detected by colony formation assay; cell apoptosis was detected by Hoechst 33258 fluorescent staining and Annexin V/PI double-staining flow cytometry; monodansylcadaverine(MDC) staining was used to detect cell autophagy; the expression of apoptosis, autophagy and related signaling pathway proteins was detected by Western blot and the expression changes of CXCR family were detected by real-time quantitative polymerase chain reaction (qRT-PCR).
RESULTS:
Reparixin could inhibit the proliferation, invasion, migration and clone formation ability of U937 cells. Compared with the single drug group, when U937 cells were intervened by Reparixin combined with Ara-C, the malignant biological behaviors such as proliferation, invasion and colony formation were significantly decreased, and the levels of apoptosis and autophagy were significantly increased (P<0.01). After Reparixin combined with Ara-C intervenes in U937 cells, it can up-regulate the expression of the pro-apoptotic protein Bax and significantly down-regulate the expression of the anti-apoptotic protein Bcl-2, and also hydrolyze and activate Caspase-3, thereby inducing cell apoptosis. Reparixin combined with Ara-C could up-regulate the expressions of LC3Ⅱ and Beclin-1 proteins in U937 cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P<0.01). MDC result showed that the green granules of vesicles increased significantly, and a large number of broken cells were seen (P<0.01). Reparixin combined with Ara-C can significantly inhibit the phosphorylation level of PI3K, AKT and NF-κB signaling molecule, inhibit the malignant biological behavior of cells by inhibiting the activation of PI3K/AKT/NF-κB pathway, and induce programmed cell death. Ara-C intervention in U937 cells had no effect on the expression of CXCR family (P>0.05). The expression of CXCR1, CXCR2, and CXCR4 mRNA could be down-regulated by Reparixin single-agent intervention in U937 cells (P<0.05), and the expression of CXCR2 was more significantly down-regulated than the control group and other CXCRs (P<0.01). When Reparixin and Ara-C intervened in combination, the down-regulated levels of CXCR1 and CXCR2 were more significant than those in the single-drug group (P<0.01), while the relative expressions of CXCR4 and CXCR7 mRNA had no significant difference compared with the single-drug group (P>0.05).
CONCLUSION
Reparixin combined with Ara-C can synergistically inhibit the malignant biological behaviors of U937 cells such as proliferation, invasion, migration and clone formation, and induce autophagy and apoptosis. The mechanism may be related to affecting the proteins expression of Bcl-2 family and down-regulating the proteins expression of CXCR family, while inhibiting the PI3K/AKT/NF-κB signaling pathway.
Humans
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U937 Cells
;
Cytarabine/therapeutic use*
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Receptors, Interleukin-8A
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NF-kappa B
;
Proto-Oncogene Proteins c-akt
;
Phosphatidylinositol 3-Kinases
;
Leukemia, Myeloid, Acute/genetics*
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Apoptosis
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Cell Proliferation
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Apoptosis Regulatory Proteins
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Cell Line, Tumor
8.Experimental Study on the Mechanism of Mangiferin Inhibiting Malignant Biological Characteristics of Multiple Myeloma and Exerting Anticancer Effect.
Yan-Quan LIU ; Yue YIN ; Yu-Ting CHEN ; Jian-Zhen SHEN ; Huan-Wen TANG
Journal of Experimental Hematology 2023;31(3):794-800
OBJECTIVE:
To investigate the effect of pure Chinese herbal extract Mangiferin on the malignant biological behaviors of multiple myeloma (MM) cells, and to analyze the molecular mechanism of the anti-myeloma effect of Mangiferin, so as to provide experimental basis for MM replacement therapy.
METHODS:
U266 and RPMI8226 of human MM cell lines were intervened with different concentrations of Mangiferin. Cell proliferation was detected by CCK-8 method. Annexin V/PI double staining flow cytometry was used to detect cell apoptosis. Western blot was used to detect the expression of apoptosis and related signaling pathway proteins, and real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of matrix metalloproteinase (MMP) and CXC chemokine receptor (CXCR) family.
RESULTS:
Mangiferin could inhibit the proliferation activity of U266 and RPMI8226 cells and induce cells apoptosis. After Mangiferin intervened in U266, RPMI8226 cells for 48 h, the expression of Bcl-2 family pro-apoptotic protein Bax was up-regulated, while the expression of survivin and Bcl-xL proteins was down-regulated and caspase-3 was hydrolyzed and activated to promote cell apoptosis, besides, the expression of Bcl-2 protein in U266 cells was also significantly down-regulated to induce apoptosis (P<0.05). After Mangiferin intervenes in MM cells, it can not only increase the expression level of tumor suppressor p53, but also induce programmed cell death of MM cells by inhibiting the expression of anti-apoptotic molecules and down-regulating the phosphorylation levels of AKT and NF-κB. In addition, after the intervention of Mangiferin, the expressions of CXCR4, MMP2 and MMP9 in U266 cells were down-regulated (P<0.05), while there is no effect on the expressions of CXCR2, CXCR7 and MMP13 (P>0.05). However, the expressions of CXCR4, MMP9, and MMP13 in RPMI8226 cells were down-regulated (P<0.01), the expression of MMP2 was weakly affected, and the expression of CXCR2 and CXCR7 was basically not affected (P>0.05).
CONCLUSION
Mangiferin can inhibit the proliferation and induce apoptosis of MM cells, and its mechanism may be related to inhibiting the activation of NF-κB signaling pathway, affecting the expression of Bcl-2 family proteins, and inhibiting the expression of core members of MMP and CXCR family.
Humans
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Matrix Metalloproteinase 2
;
Matrix Metalloproteinase 9
;
Matrix Metalloproteinase 13
;
Cell Line, Tumor
;
NF-kappa B
;
Multiple Myeloma/pathology*
;
Cell Proliferation
;
Apoptosis
;
Proto-Oncogene Proteins c-bcl-2
9.Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF).
Feng XU ; Yuan BIAN ; Guo Qiang ZHANG ; Lu Yao GAO ; Yu Fa LIU ; Tong Xiang LIU ; Gang LI ; Rui Xue SONG ; Li Jun SU ; Yan Ju ZHOU ; Jia Yu CUI ; Xian Liang YAN ; Fang Ming GUO ; Huan Yi ZHANG ; Qing Hui LI ; Min ZHAO ; Li Kun MA ; Bei An YOU ; Ge WANG ; Li KONG ; Jian Liang MA ; Xin Fu ZHOU ; Ze Long CHANG ; Zhen Yu TANG ; Dan Yu YU ; Kai CHENG ; Li XUE ; Xiao LI ; Jiao Jiao PANG ; Jia Li WANG ; Hai Tao ZHANG ; Xue Zhong YU ; Yu Guo CHEN
Chinese Journal of Internal Medicine 2023;62(4):374-383
Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male
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Female
;
Humans
;
Aged
;
Natriuretic Peptide, Brain
;
Simendan/therapeutic use*
;
Non-ST Elevated Myocardial Infarction
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Heart Failure/drug therapy*
;
Peptide Fragments
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Arrhythmias, Cardiac
;
Biomarkers
;
Prognosis
10.Clinical analysis of allergen reactivity and atopic disease history in 168 patients with chronic inducible urticaria
Qiquan CHEN ; Minmin KONG ; Xianjie YANG ; Huan WANG ; Jian LI ; Mingwang ZHANG ; Zhiqiang SONG
Chinese Journal of Dermatology 2023;56(6):496-503
Objective:To analyze the relationship between allergen reactivity, atopic disease history and clinical features in patients with chronic inducible urticaria (CIndU) .Methods:A retrospective analysis was conducted on clinical data and follow-up results from 168 patients with CIndU in the Department of Dermatology, Southwest Hospital of Army Medical University from June 2014 to June 2015. Associations were analyzed between allergen reactivity, atopic disease history and clinical characteristics (including patient global assessment [PGA] scores, pruritus intensity, dermatology life quality index [DLQI], proportions of cases with complicated angioedema, natural course, etc.) in patients with different CIndU subtypes. Chi-square test, Mann-Whitney U test and Kaplan-Meier survival analysis were used for statistical analysis. Results:Among the 168 patients with CIndU, 117 were diagnosed with symptomatic dermographism (SD) , 32 with cold contact urticaria (CCU) , 5 with heat contact urticaria (HCU) , and 14 with cholinergic urticaria (CholU) ; there were 46 (39.3%) , 14 (43.8%) , 3, and 9 patients with positive skin prick test (SPT) among the patients with SD, CCU, HCU and CholU respectively, and no significant difference was observed in the positive rate of SPT among patients with different CIndU subtypes ( χ2 = 3.86, P = 0.283) . The SPT-positive CIndU patients showed significantly increased PGA scores, pruritus scores, DLQI scores and proportions of cases with complicated angioedema compared with the SPT-negative patients (all P<0.05) ; the CIndU patients with a personal or family history of atopic diseases also showed significantly increased PGA and DLQI scores compared with those without (both P < 0.05) . For different CIndU subtypes, the pruritus scores, PGA scores, DLQI scores, and proportions of cases with complicated angioedema were significantly higher in the SPT-positive SD patients than in the SPT-negative SD patients (all P < 0.05) ; the DLQI scores were significantly higher in the SPT-positive CholU patients than in the SPT-negative CholU patients ( Z = -2.28, P = 0.019) ; the pruritus scores were significantly higher in the CCU patients with a personal or family history of atopic diseases than in those without ( Z =-2.41, P = 0.022) . Conclusion:The allergen reactivity and atopic disease history of CIndU patients were associated with disease severity, pruritus intensity, quality of life, and the proportion of cases with complicated angioedema, but their relationship with the natural course of CIndU needs to be confirmed by further studies.


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