1.Exploring Chemical Constituent Distribution in Blood/Brain(Hippocampus) and Emotional Regulatory Effect of Raw and Vinegar-processed Products of Citri Reticulatae Pericarpium Viride
Yi BAO ; Yonggui SONG ; Qianmin LI ; Zhifu AI ; Genhua ZHU ; Ming YANG ; Huanhua XU ; Qin ZHENG ; Yiting HUANG ; Zihan GAO ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):189-197
ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride(CRPV), and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts, as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards, databases, and relevant literature were utilized for compound annotation, with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups, including the blank group, model group, diazepam group(2.5 mg·kg-1), raw CRPV low/high dose groups(0.6, 1.2 g·kg-1), and vinegar-processed CRPV low/high dose groups(0.6, 1.2 g·kg-1), with 10 mice per group. Except for the blank group, all other groups underwent chronic restraint stress(2 h·d-1) for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling, with a total treatment duration of 10 d. Following model-based drug administration, mice underwent open-field, forced swimming, and elevated plus maze tests. After anesthesia with isoflurane, whole brains were collected from each group of mice, and hippocampi were dissected. Reactive oxygen species(ROS) level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei(NeuN) and peroxisome proliferator-activated receptor alpha(PPARα) expressions in hippocampal tissue. Then, pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders, exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV, with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds, including 20 flavonoids, 20 flavonoid glycosides, 3 triterpenes, 3 phenolic acids, 1 alkaloid, and 6 other compounds. Twenty-one components were detected in blood(15 methoxyflavones, 4 flavonoid glycosides, and 2 phenolic acids), with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues(all common to both forms). In regulating emotional disorders, Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology, particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS(P<0.05). ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing, but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway, thereby negatively regulating ROS generation in the hippocampus, reducing oxidative stress, and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards, pharmacodynamic material research, and active drug development of raw and vinegar-processed CRPV.
2.The Influence of COVID-19 Infection on the Mobilization and Collection of Autologous Peripheral Blood Stem Cells in Patients with Multiple Myeloma.
Guo-Rong WANG ; Guang-Zhong YANG ; Yun LENG ; Yin WU ; Ai-Jun LIU ; Wen-Ming CHEN
Journal of Experimental Hematology 2025;33(2):455-462
OBJECTIVE:
To analyze the effect of COVID-19 infection on the mobilization and collection of autologous peripheral blood stem cells in patients with multiple myeloma.
METHODS:
The general baseline data, treatment factors before mobilization collection, collection status, and treatment overview after collection of autologous peripheral blood stem cells at Beijing Chaoyang Hospital affiliated with Capital Medical University from January 1, 2020 to July 15, 2023 were analyzed.
RESULTS:
269 patients underwent mobilization and collection of autologous peripheral blood stem cells. Among them, 32 cases with COVID-19 infection history (COVID-19 group) and 237 cases without COVID-19 infection history (non-COVID-19 group). In the COVID-19 group, 17 cases were treated with chemotherapy (etoposide)+G-CSF, and 15 cases were treated with plerixafor +G-CSF. In the non-COVID-19 group, 214 cases were treated with chemotherapy +G-CSF, 17 cases were treated with plerixafor +G-CSF, and 6 cases were treated with chemotherapy + plerixafor +G-CSF. The number of CD34+ cells, collection success rate, and excellence rate in the COVID-19 group and the non-COVID-19 group were [5.52 (0.94-26.87) vs 4.80 (0.53-37.20)]×106/kg (P =0.610), (93.8% vs 85.2%) (P =0.275), (62.5% vs 49.4%) (P =0.190), respectively. Among 113 patients mobilized with etoposide +G-CSF, the number of CD34+ cells, success rate, and excellence rate collected from COVID-19 infection (17 cases) and non-COVID-19 infection (96 cases) were [7.54 (2.66-26.87) vs 7.78 (2.26-37.20)]×106/kg (P =0.847), (100.0% vs 100.0%) (no P value), (82.4% vs 86.5%) (P =0.655), respectively. Among 32 patients mobilized by plerixafor +G-CSF, the number of CD34+ cells, success rate and excellence rate of COVID-19 infection (15 cases) and non-COVID-19 infection (17 cases) were [3.82 (0.94-7.27) vs 4.11 (0.53-9.05)]×106/kg (P =0.821), (86.7% vs 88.2%) (P =0.893), (40.0% vs 35.3%) (P =0.784), respectively. In 32 patients with COVID-19 infection, the number of CD34+ cells collected by etoposide +G-CSF (17 cases) and plerixafor +G-CSF (15 cases), as well as the success rate and excellence rate were [7.54 (2.66-26.87) vs 3.82(0.94-7.27)]×106/kg (P =0.004), (100.0% vs 86.7%) (P =0.120), (82.4% vs 40.0%) (P =0.014), respectively. By 2023.7.31, 232 patients (86.2%, 232/269) had received transplantation, including 24 patients in the COVID-19 group and 208 patients in the non-COVID-19 group. The median number of CD34+ cells infused in the two groups was [3.67 (2.50-13.44) vs 3.11(1.12-19.89)]×106/kg (P =0.058), the median days of neutrophil engraftment [11(9-13) vs 11(9-17)] (P =0.674), the median days of platelet engraftment [11(0-23), 12(0-43)] (P =0.279), respectively.
CONCLUSION
The history of COVID-19 infection did not affect the PBSC mobilization, collection and transplantation of patients with myeloma. In patients with COVID-19 infection, the results of chemotherapy mobilization with etoposide seems to be better than that of plerixafor mobilization, but further research is needed to clarify.
Humans
;
COVID-19/complications*
;
Multiple Myeloma/complications*
;
Hematopoietic Stem Cell Mobilization
;
Transplantation, Autologous
;
Granulocyte Colony-Stimulating Factor/therapeutic use*
;
Peripheral Blood Stem Cell Transplantation
;
SARS-CoV-2
;
Middle Aged
;
Peripheral Blood Stem Cells
;
Male
;
Female
;
Cyclams
;
Benzylamines
3.Effective therapeutic targeting of tumor lineage plasticity in neuroendocrine prostate cancer by BRD4 inhibitors.
Xiong ZHANG ; Yatian YANG ; Hongye ZOU ; Yang YANG ; Xingling ZHENG ; Eva COREY ; Amina ZOUBEIDI ; Nicolas MITSIADES ; Ai-Ming YU ; Yuanpei LI ; Hong-Wu CHEN
Acta Pharmaceutica Sinica B 2025;15(3):1415-1429
Tumor lineage plasticity (LP) is an emerging hallmark of cancer progression. Through pharmacologically probing the function of epigenetic regulators in prostate cancer cells and organoids, we identified bromodomain protein BRD4 as a crucial player. Integrated ChIP-seq and RNA-seq analysis of tumors revealed, for the first time, that BRD4 directly activates hundreds of genes in the LP programs which include neurogenesis, axonogenesis, EMT and stem cells and key drivers such as POU3F2 (BRN2), ASCL1/2, NeuroD1, SOX2/9, RUNX1/2 and DLL3. Interestingly, BRD4 genome occupancy is reprogrammed by anti-AR drugs from facilitating AR function in CRPC cells to activating the LP programs and is facilitated by pioneer factor FOXA1. Significantly, we demonstrated that BRD4 inhibitor AZD5153, currently at clinical development, possesses potent activities in complete blockade of tumor growth of both de novo neuroendocrine prostate cancer (NEPC) and treatment-induced NEPC PDXs and that suppression of tumor expression of LP programs through reduction of local chromatin accessibility is the primary mechanism of action (MOA) by AZD5153. Together, our study revealed that BRD4 plays a fundamental role in direct activation of tumor LP programs and that its inhibitor AZD5153 is highly promising in effective treatment of the lethal forms of the diseases.
4.Effect of Different Fermentation Conditions on Fungal Community and Chemical Composition of Aurantii Fructus
Zhihong YAN ; Xiumei LIU ; Qiuyan GUAN ; Yonggui SONG ; Zhifu AI ; Genhua ZHU ; Yuhui PING ; Ming YANG ; Qin ZHENG ; Huanhua XU ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):254-262
ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus, in order to obtain the optimal fermentation conditions and flora structure, and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2(ITS2) high-throughput sequencing, combined with fungal community diversity analysis and fungal community structure analysis, were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7, 14, 21 d(numbered Y1-Y3 for the former, and numbered F1-F3 for the latter), respectively. At the same time, the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS), combined with principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA) and compound retention time, parent ions, characteristic fragment ions and other information, the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method, while in the non-pressure-shelf natural fermentation method, there was a significant difference with the fermentation process, and at the genus level, the dominant genus of samples Y1, Y2, Y3 and F2 was Aspergillus, while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable, and the microbial community structure was more stable, which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis, including 70 flavonoids, 38 coumarins, 10 alkaloids, 34 organic acids and 3 other compounds. After fermentation, two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition, multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods, mainly including flavonoids, organic acids and coumarins. Comprehensively, the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable, the species richness was high and the overall content of differential compounds was high, which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation, the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds, and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus, as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.
5.Effect of Different Fermentation Conditions on Fungal Community and Chemical Composition of Aurantii Fructus
Zhihong YAN ; Xiumei LIU ; Qiuyan GUAN ; Yonggui SONG ; Zhifu AI ; Genhua ZHU ; Yuhui PING ; Ming YANG ; Qin ZHENG ; Huanhua XU ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):254-262
ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus, in order to obtain the optimal fermentation conditions and flora structure, and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2(ITS2) high-throughput sequencing, combined with fungal community diversity analysis and fungal community structure analysis, were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7, 14, 21 d(numbered Y1-Y3 for the former, and numbered F1-F3 for the latter), respectively. At the same time, the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS), combined with principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA) and compound retention time, parent ions, characteristic fragment ions and other information, the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method, while in the non-pressure-shelf natural fermentation method, there was a significant difference with the fermentation process, and at the genus level, the dominant genus of samples Y1, Y2, Y3 and F2 was Aspergillus, while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable, and the microbial community structure was more stable, which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis, including 70 flavonoids, 38 coumarins, 10 alkaloids, 34 organic acids and 3 other compounds. After fermentation, two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition, multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods, mainly including flavonoids, organic acids and coumarins. Comprehensively, the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable, the species richness was high and the overall content of differential compounds was high, which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation, the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds, and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus, as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.
6.Chinese expert consensus on emergent treatment of hypothermia(2025 edition)
Wei CHEN ; Lei HE ; Ming YIN ; Tao WAN ; You-Qing TANG ; Ai-Ping WANG ; Yang LI ; Wan-Xian YU
Medical Journal of Chinese People's Liberation Army 2025;50(6):641-655
Hypothermia is a clinical syndrome characterized by core body temperature<35℃,caused by significant heat loss from body surface in cold environment.As a systemic cold injury,it can be lethal if treatment is delayed.Emergent diagnosis and treatment of hypothermia are expected to improve the prognosis of patients.In 2005,the U.S.Army Research Institute of Environmental Medicine(USARIEM)issued guidelines for the prevention and management of cold injuries,but there has been no corresponding standard in China.Therefore,Emergency Branch of Chinese Medical Rescue Association,Emergency Medical Equipment Society of China Association of Medical Equipment,Integrated Rehabilitation Medical Branch of Chinese Medical Rescue Association,and Pre-Hospital Emergency Care Working Committee of Chinese Aging Well Association jointly developed the Chinese Expert Consensus on Emergent Treatment of Hypothermia(2025 edition).The consensus covers the pathophysiology,etiology and epidemiology,diagnosis and severity grading,prehospital treatment,and in-hospital treatment of hypothermia,including 15 recommendations in total,aiming to provide guidance for the relevant clinical rescue work.
7.Screening of Antidepressant Active Components from Curcumae Rhizoma and Its Mechanism in Regulating Nrf2/GPX4/GSH Pathway
Yonggui SONG ; Delin DUAN ; Meixizi LAI ; Yali LIU ; Zhifu AI ; Genhua ZHU ; Huanhua XU ; Qin ZHENG ; Ming YANG ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):211-221
ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma, and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2(Nrf2)/glutathione(GSH) peroxidase 4(GPX4)/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma, including curcumol, curgerenone, curdione, curzerene, curcumenol, curcumenone, dehydrocurdione, isocurcumenol, furanodienone, furanodiene and zederone, were detected using 1,1-diphenyl-2-picrylhydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt(ABTS) radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress(CUMS), and W1118 wild-type male D. melanogaster were randomly divided into blank group, model group, curcumol group, curgerenone group, curdione group, curzerene group, curcumenol group,curcumenone group, dehydrocurdione group, isocurcumenol group, furanodienone group, furanodiene group, zederone group and fluoxetine group(10 μmol·L-1). The treatment groups received a dose of 0.1 g·L-1 of 11 characteristic components from Curcumae Rhizoma, while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test, climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry(LC-MS) was used to detect the levels of 5-hydroxytryptamine(5-HT) and dopamine(DA) in the brain of D. melanogaster, and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators, resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition, a mouse depression model was established by CUMS, and C57BL/6J mice were randomly divided into blank group, model group, low and high dose groups of curzerene(0.5, 1 mg·kg-1), and fluoxetine group(10 mg·kg-1) to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species(ROS) in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate(ATP), superoxide dismutase(SOD), catalase(CAT) and GSH. Transmission electron microscope(TEM) was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein, and Nrf2 inhibitor(ML385) was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction(Real-time PCR) was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals, and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group, the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center(P<0.01), as well as a significant increase in immobility time in the forced swimming and tail suspension tests(P<0.01), and the ROS content in hippocampus significantly elevated(P<0.01), while the ATP content significantly reduced(P<0.01). In the hippocampal neurons of the model group, mitochondrial cristae were disordered, with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased(P<0.05), and the antioxidant enzymes SOD, CAT and GSH contents were also significantly reduced(P<0.05, P<0.01), and the gene expression levels of GPX1, GPX4 and GPX7 were significantly decreased(P<0.01). Compared with the model group, the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center(P<0.05), as well as a significant decrease in immobility time in the forced swimming and tail suspension tests(P<0.05, P<0.01). The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced(P<0.01), while the ATP content was significantly increased(P<0.05). The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated, and the expression level of Nrf2 protein was significantly increased(P<0.05). The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased(P<0.01), while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased(P<0.05), while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.
8.Early predictive value of dynamic contrast-enhanced MRI radiomics combined with Magee equation 3 for pathological response of HR+/HER2-breast cancer after neoadjuvant chemotherapy
Siye LIU ; Ming YANG ; Huiling LI ; Zhaodong AI ; Xiaorong OU ; Jun LIU
Journal of Practical Radiology 2025;41(9):1487-1493
Objective To investigate the predictive value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)radiomics combined with Magee equation 3(ME3)for pathological response following neoadjuvant chemotherapy(NAC)in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR+/HER2-)breast cancer.Methods A ret-rospective analysis was performed on 325 breast cancer patients diagnosed with HR+/HER2-in two hospitals.Patients from the first hospital were randomly divided into training and internal validation sets at a ratio of 7∶3.Patients from the second hospital served as external validation set.The volume of interest(VOI)of breast cancer was delineated on DCE-MRI images.Then the rele-vant radiomics features were extracted and selected,and the Radiomics score(Radscore)was calculated.The statistically significant clinical and pathological features and Radscore were incorporated into a multivariate analysis.The combined radiomics-clinical model and nomogram were established,and the prediction performance was evaluated by using the receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results In the training set,seven radiomics features were selected to construct the radiomics model.ME3 score emerged as the independent factor for pathological complete response(pCR)(P<0.001).By integrating ME3 score and Radscore,a combined radiomics-clinical model was developed.This model demonstrated robust predictive accuracy,with area under the curve(AUC)of 0.88[95%confidence interval(CI)0.80-0.95],0.90(95%CI 0.82-0.98),and 0.82(95%CI 0.70-0.93)in the training,internal validation,and external validation sets,respectively.The nomogram construc-ted from the combined model exhibited excellent discrimination and calibration,with P-values of 0.455,0.312 and 0.062 in the train-ing,internal validation,and external validation sets.Conclusion DCE-MRI radiomics combined with ME3 can be used to predict the pathological response of NAC in HR+/HER2-breast cancer.
9.Chinese expert consensus on emergent treatment of hypothermia(2025 edition)
Wei CHEN ; Lei HE ; Ming YIN ; Tao WAN ; You-Qing TANG ; Ai-Ping WANG ; Yang LI ; Wan-Xian YU
Medical Journal of Chinese People's Liberation Army 2025;50(6):641-655
Hypothermia is a clinical syndrome characterized by core body temperature<35℃,caused by significant heat loss from body surface in cold environment.As a systemic cold injury,it can be lethal if treatment is delayed.Emergent diagnosis and treatment of hypothermia are expected to improve the prognosis of patients.In 2005,the U.S.Army Research Institute of Environmental Medicine(USARIEM)issued guidelines for the prevention and management of cold injuries,but there has been no corresponding standard in China.Therefore,Emergency Branch of Chinese Medical Rescue Association,Emergency Medical Equipment Society of China Association of Medical Equipment,Integrated Rehabilitation Medical Branch of Chinese Medical Rescue Association,and Pre-Hospital Emergency Care Working Committee of Chinese Aging Well Association jointly developed the Chinese Expert Consensus on Emergent Treatment of Hypothermia(2025 edition).The consensus covers the pathophysiology,etiology and epidemiology,diagnosis and severity grading,prehospital treatment,and in-hospital treatment of hypothermia,including 15 recommendations in total,aiming to provide guidance for the relevant clinical rescue work.
10.The efficacy and safety of nebulized inhalation of recombinant human interferon α1b in the treatment of pediatric respiratory syncytial viral associated lower respiratory tract infections: a multicenter, randomized, double-blind, placebo-controlled phase Ⅲ clinical study
Xiaohui LIU ; Baoping XU ; Yunxiao SHANG ; Han ZHANG ; Zhenkun ZHANG ; Guangyu LIN ; Ju YIN ; Aihua CUI ; Guocheng ZHANG ; Zhaoling SHI ; Liwei GAO ; Chunming JIANG ; Junmei BIAN ; Yongjian HUANG ; Rongfang ZHANG ; Xiaomei LIU ; Xiaoqing YANG ; Yu TANG ; Lili ZHONG ; Hongmei QIAO ; Chuangli HAO ; Yuqing WANG ; Qubei LI ; Ling CAO ; Yungang YANG ; Ling LU ; Rongjun LIN ; Xingzhen SUN ; Wei ZHOU ; Qiang CHEN ; Jikui DENG ; Yuejie ZHENG ; Lin ZHAO ; Tao AI ; Xiaohong LIU ; Xiaoxia LU ; Ning JIANG ; Ming LI
Chinese Journal of Applied Clinical Pediatrics 2025;40(3):180-186
Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

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