1.Herbal Textual Research on Houttuyniae Herba in Famous Classical Formulas
Dan ZHAO ; Changgui YANG ; Chuanzhi KANG ; Chenghong XIAO ; Zhikun WU ; Hongliang MA ; Jiwen WANG ; Xiufu WAN ; Sheng WANG ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):250-259
This article systematically analyzes the historical evolution of the name, medicinal parts, origin, harvesting, processing and other aspects of Houttuyniae Herba(HH) by referring to the medical books, prescription books and other documents of the past dynasties, combined with the research materials related to modern and contemporary times, in order to provide a basis for the development of famous classical formulas containing this herb. In ancient literature, HH was often referred to as "Ji" and "Jicai", the name of "Ji" was first recorded in Mingyi Bielu during the Han and Wei dynasties, and the name of Yuxingcao was first seen in Lyuchanyan Bencao during the southern Song dynasty and has continued to this day. The origin of HH used throughout history is consistent, all of which are the whole herb or aboveground parts of Houttuynia cordata in Saururaceae family. HH recorded throughout history has a wide range of production areas, mostly self-produced self-marketing. In ancient times, fresh HH was often used as medicine by pounding its juice without involving any processing steps. Both fresh and dried products can be used as medicine, the fresh products uses the whole plant, while the dried products uses the aboveground parts, which are cleaned, selected and processed before use. Fresh products are harvested regardless of season, while dried products are harvested in both summer and autumn, with summer as the best. In ancient times, there were no specific requirements for the quality of HH, while in modern times, "intact stems and leaves with a strong fishy smell" are preferred. In addition, the medicinal properties of HH have undergone significant changes from ancient to modern times. In the early period, it was believed that its medicinal property was slightly warm, until the 1977 edition of Chinese Pharmacopoeia officially changed it to slightly cold. Both ancient and modern literature states that HH can be used for the treatment of carbuncle and malignant sores, Lyuchanyan Bencao for the first time introduced HH fresh juice can relieve summer heat, since Diannan Bencao recorded that it can be used for lung carbuncle, and gradually developed into the first choice for the treatment of lung carbuncle. Based on the research results, it is suggested that fresh herb or dried aboveground parts of H. cordata are used as medicine when developing famous classical formulas.
2.Seroprevalence and influencing factors of low-level neutralizing antibodies against SARS-CoV-2 in community residents
Shiying YUAN ; Jingyi ZHANG ; Huanyu WU ; Weibing WANG ; Genming ZHAO ; Xiao YU ; Xiaoying MA ; Min CHEN ; Xiaodong SUN ; Zhuoying HUANG ; Zhonghui MA ; Yaxu ZHENG ; Jian CHEN
Shanghai Journal of Preventive Medicine 2025;37(5):403-409
ObjectiveTo understand the seropositivity of neutralizing antibodies (NAb) and low-level NAb against SARS-CoV-2 infection in the community residents, and to explore the impact of COVID-19 vaccination and SARS-CoV-2 infection on the levels of NAb in human serum. MethodsOn the ground of surveillance cohort for acute infectious diseases in community populations in Shanghai, a proportional stratified sampling method was used to enroll the subjects at a 20% proportion for each age group (0‒14, 15‒24, 25‒59, and ≥60 years old). Blood samples collection and serum SARS-CoV-2 NAb concentration testing were conducted from March to April 2023. Low-level NAb were defined as below the 25th percentile of NAb. ResultsA total of 2 230 participants were included, the positive rate of NAb was 97.58%, and the proportion of low-level NAb was 25.02% (558/2 230). Multivariate logistic regression analysis indicated that age, infection history and vaccination status were correlated with low-level NAb (all P<0.05). Individuals aged 60 years and above had the highest risk of low-level NAb. There was a statistically significant interaction between booster vaccination and one single infection (aOR=0.38, 95%CI: 0.19‒0.77). Compared to individuals without vaccination, among individuals infected with SARS-CoV-2 once, both primary immunization (aOR=0.23, 95%CI: 0.16‒0.35) and booster immunization (aOR=0.12, 95%CI: 0.08‒0.17) significantly reduced the risk of low-level NAb; among individuals without infections, only booster immunization (aOR=0.28, 95%CI: 0.14‒0.52) showed a negative correlation with the risk of low-level NAb. ConclusionsThe population aged 60 and above had the highest risk of low-level NAb. Regardless of infection history, a booster immunization could reduce the risk of low-level NAb. It is recommended that eligible individuals , especially the elderly, should get vaccinated in a timely manner to exert the protective role of NAb.
3.Expression of lymphocyte subsets in the bone marrow of patients with acute myeloid leukemia and its influence on prognosis
Jinhong NIE ; Jiebing XIAO ; Yingchun SHAO ; Chenghui LI ; Lu GAO ; Xiao MA ; Xiaojin WU ; Ziling ZHU
Chinese Journal of Blood Transfusion 2025;38(7):902-908
Objective: To explore the correlation between the composition of bone marrow lymphocyte subsets and the clinical attributes observed in de novo AML patients, as well as their influence on prognosis. Methods: A detailed study was carried out on a cohort of 191 de novo acute myeloid leukemia patients who were admitted to our medical center between October 2022 and September 2024. In addition, a group of 24 patients with iron deficiency anemia individuals was carefully chosen as the control cohort. The proportions of lymphocyte subsets within the bone marrow of de novo AML patients were analyzed. Furthermore, an in-depth analysis was performed to investigate the association between the expression levels of these subsets in de novo AML patients and their clinical attributes, as well as their prognostic implications. Results: The proportion of CD19
and CD56
lymphocytes within the bone marrow of de novo AML patients significantly diminished compared to the control cohort (8.5% vs 13.2% P<0.05, and 15.5% vs 18.0%, P<0.05). Conversely, no significant discrepancies were observed in the CD3
, CD3
CD4
, and CD3
CD8
lymphocyte percentages between the AML patients and control group (71.7% vs 72.1%, 32.5% vs 33.7% and 32.8% vs 35.7%, P>0.05). When analyzing the relationships between lymphocyte subsets within the bone marrow of de novo patients and their respective clinical characteristics, patients aged 60 years and above exhibited diminished percentages of CD3
CD8
lymphocytes in the bone marrow compared to their younger counterparts (31.6% vs 34.1%, P<0.05), while the CD56
lymphocyte subsets demonstrated an increased prevalence (17.2% vs 14.4%, P<0.05). Furthermore, patients with leukocytosis (WBC≥100×10
/L) presented lower levels of CD3
and CD3
CD4
lymphocytes in the bone marrow compared with those without it (65.3% vs 72.9% P<0.05, and 28.9% vs 33.2%, P<0.05), respectively. The AML1-ETO fusion gene-positive cohort exhibited a higher prevalence of CD3
CD8
lymphocytes in the bone marrow than in the negative group (38.2% vs 32.3%, P<0.05), whereas the FLT3-ITD mutation-positive group presented a decreased prevalence of CD56
lymphocytes compared with the negative group (12.4% vs 16.8%, P<0.05). In addition, the NPM1 mutation-positive group demonstrated lower levels of CD3
CD8
lymphocytes in the bone marrow than in the negative group (29.1% vs 33.3%, P<0.05). Variables such as tumor protein p53(TP53) mutation positive, the absence of hematopoietic stem cell transplantation, and CD3
CD4
lymphocyte proportions below 25% were identified as independent adverse prognostic indicators for AML patients (P<0.05). Conclusion: The pathogenesis of AML is closely associated with an imbalance in bone marrow lymphocyte subsets. The FLT3-ITD mutation potentially contributes to the dysregulation of CD56
lymphocyte subset expression. The AML1-ETO fusion gene and NPM1 mutation are implicated in the abnormal expression of CD3
CD8
lymphocytes within the bone marrow. Moreover, the percentage of CD3
CD4
lymphocytes in the bone marrow serves as a prognostic factor for de novo AML patients.
4.Expression of lymphocyte subsets in the bone marrow of patients with acute myeloid leukemia and its influence on prognosis
Jinhong NIE ; Jiebing XIAO ; Yingchun SHAO ; Chenghui LI ; Lu GAO ; Xiao MA ; Xiaojin WU ; Ziling ZHU
Chinese Journal of Blood Transfusion 2025;38(7):902-908
Objective: To explore the correlation between the composition of bone marrow lymphocyte subsets and the clinical attributes observed in de novo AML patients, as well as their influence on prognosis. Methods: A detailed study was carried out on a cohort of 191 de novo acute myeloid leukemia patients who were admitted to our medical center between October 2022 and September 2024. In addition, a group of 24 patients with iron deficiency anemia individuals was carefully chosen as the control cohort. The proportions of lymphocyte subsets within the bone marrow of de novo AML patients were analyzed. Furthermore, an in-depth analysis was performed to investigate the association between the expression levels of these subsets in de novo AML patients and their clinical attributes, as well as their prognostic implications. Results: The proportion of CD19
and CD56
lymphocytes within the bone marrow of de novo AML patients significantly diminished compared to the control cohort (8.5% vs 13.2% P<0.05, and 15.5% vs 18.0%, P<0.05). Conversely, no significant discrepancies were observed in the CD3
, CD3
CD4
, and CD3
CD8
lymphocyte percentages between the AML patients and control group (71.7% vs 72.1%, 32.5% vs 33.7% and 32.8% vs 35.7%, P>0.05). When analyzing the relationships between lymphocyte subsets within the bone marrow of de novo patients and their respective clinical characteristics, patients aged 60 years and above exhibited diminished percentages of CD3
CD8
lymphocytes in the bone marrow compared to their younger counterparts (31.6% vs 34.1%, P<0.05), while the CD56
lymphocyte subsets demonstrated an increased prevalence (17.2% vs 14.4%, P<0.05). Furthermore, patients with leukocytosis (WBC≥100×10
/L) presented lower levels of CD3
and CD3
CD4
lymphocytes in the bone marrow compared with those without it (65.3% vs 72.9% P<0.05, and 28.9% vs 33.2%, P<0.05), respectively. The AML1-ETO fusion gene-positive cohort exhibited a higher prevalence of CD3
CD8
lymphocytes in the bone marrow than in the negative group (38.2% vs 32.3%, P<0.05), whereas the FLT3-ITD mutation-positive group presented a decreased prevalence of CD56
lymphocytes compared with the negative group (12.4% vs 16.8%, P<0.05). In addition, the NPM1 mutation-positive group demonstrated lower levels of CD3
CD8
lymphocytes in the bone marrow than in the negative group (29.1% vs 33.3%, P<0.05). Variables such as tumor protein p53(TP53) mutation positive, the absence of hematopoietic stem cell transplantation, and CD3
CD4
lymphocyte proportions below 25% were identified as independent adverse prognostic indicators for AML patients (P<0.05). Conclusion: The pathogenesis of AML is closely associated with an imbalance in bone marrow lymphocyte subsets. The FLT3-ITD mutation potentially contributes to the dysregulation of CD56
lymphocyte subset expression. The AML1-ETO fusion gene and NPM1 mutation are implicated in the abnormal expression of CD3
CD8
lymphocytes within the bone marrow. Moreover, the percentage of CD3
CD4
lymphocytes in the bone marrow serves as a prognostic factor for de novo AML patients.
5.Risk factor analysis of carbapenem-resistant enterobacteriaceae infection based on machine learning
Chunhai XIAO ; Shuang LIANG ; Xianglu LIU ; Juanfang WU ; Huimin MA ; Shan ZHONG
International Journal of Laboratory Medicine 2024;45(1):79-83
Objective To explore the machine learning model and risk factor analysis for hospital infection caused by carbapenem-resistant enterobacteriaceae(CRE).Methods The clinical data of totally 451 patients infected with extended-spectrum β-lactamases(ESBL)producing Enterobacteriaceae treated in the hospital from 2018 to 2022 were retrospectively collected.The patients were divided into CRE group(115 cases)and sensitive group(336 cases)according to the susceptibility of carbapenem.Four machine learning methods in-cluding Logistic regression analysis,random forest,support vector machine,and neural network were used to build prediction models and receiver operating characteristic curve was used to evaluate.Based on the predic-tion model with the best performance,risk factors for CRE infection were analyzed.Results Random forest model had the best performance,with the area under the curve of 0.952 3.The risk factors for predicting CRE infection by the random forest model included 15 clinical data items,namely fever for more than 3 days,cere-bral injury,drainage fluid sample,trunk surgery,first-level or special-level nursing,ICU treatment,procalcito-nin,anti-anaerobic bacteria,the use of third-generation cephalosporins,age,pre-albumin,creatinine,white blood cell count,and albumin.Conclusion The CRE prediction model developed in this study has good predic-tive value and the risk factors have guiding significance for the early prevention and treatment of CRE infec-tion in clinical practice.
6.Clinical study of skin bridge preopening window drainage in enhanced recovery of mixed hemorrhoids surgically treated with external dissection and internal ligation
Chongfu WU ; Haitao XIAO ; Min MA ; Feng LI ; Shenghong GAN ; Xuexue WU
Journal of Clinical Surgery 2024;32(2):203-205
Objective To investigate the clinical application of skin bridge preopening window drainage in enhanced recovery of mixed hemorrhoids surgically treated with external dissection and internal ligation.Methods A total of 620 patients with mixed hemorrhoids surgically treated with external dissection and internal ligation were retrospectively analyzed from March 1,2021-February 28,2022.Patients were divided into the observation group(n=304)and the control group(n=316)according to the single and even numbers randomly generated at the time of admission.In the observation group,on the basis of conventional operation and drug treatment in the control group,most of them chose to implement preopening window drainage of the skin bridge according to the intraoperative evaluation of the anal skin bridge according to the unified evaluation criteria.Symptom-sign scoring scale used to evaluate the anal edema and pain after the operation.To compare and analyze differences in anal edema,anal pain and the postoperative hospital stay between the observation group and the control.Results The average daily edema scores of the observation group and the control group were 0.56 and 1.2 points,respectively.The average daily edema score of the observation group was lower than that of the control group,with the statistically significant differences(P<0.05).The average daily pain scores of the observation group and the control group were 0.6 and 1.201+0.289 points,respectively.The average daily pain score of the observation group was lower than that of the control group,with the statistically significant differences(P<0.05).The average hospitalization days of the observation group and the control group were 8 days and 10 days,respectively.The average length of stay in the observation group was less than that in the control group,with the statistically significant differences(P<0.05).Conclusion Skin bridge preopening window drainage can effectively relieve the degree of anal edema and pain in patients with mixed hemorrhoids surgically treated with external dissection and internal ligation,improve clinical efficacy,shorten the postoperative hospital stay.It has practical value and clinical significance for enhanced recovery.
7.Hydroxysafflor yellow A intervenes astrocyte lipocalin 2 expression after cerebral ischemia/reperfusion injury
Kexin LIU ; Lijuan SONG ; Yige WU ; Guangyuan HAN ; Zhuyue MIAO ; Ruheng WEI ; Baoguo XIAO ; Cungen MA ; Jianjun HUANG
Chinese Journal of Tissue Engineering Research 2024;28(7):1063-1069
BACKGROUND:Ischemic stroke is a serious threat to human health.After ischemia and hypoxia,astrocyte expresses lipocalin-2 in large amounts to aggravate brain injury,but the specific mechanism is not clear.Hydroxysafflor yellow A has anti-ischemia,anti-oxidation,anti-thrombosis and anti-inflammatory effects.However,whether hydroxysafflor yellow A affects the expression of lipocalin-2 in astrocytes after cerebral ischemia and hypoxia and its mechanism are not clear. OBJECTIVE:To investigate the effect and mechanism of hydroxysafflor yellow A on the expression of lipocalin-2 in astrocytes after cerebral ischemia and reperfusion. METHODS:(1)Thirty adult SD rats were randomly divided into three groups:sham operation group,middle cerebral artery occlusion and reperfusion group,and hydroxysafflor yellow A group.The middle cerebral artery occlusion and reperfusion model was established in the latter two groups,and hydroxysafflor yellow A group was intraperitoneally injected with 12 mg/kg hydroxysafflor yellow A after reperfusion.Longa score was used to evaluate the degree of neurological impairment.Infarct volume was determined by TTC staining.JAK2/STAT3 pathway and lipocalin-2 expression were detected by western blot assay and immunofluorescence.Levels of interleukin 1β,interleukin 6 and tumor necrosis factor α were detected by ELISA.(2)Astrocytes were divided into four groups:Normal group,glucose-oxygen deprivation group,hydroxysafflor yellow A group and AG490 group.In the latter three groups,glucose-oxygen deprivation and glucose-oxygen recovery models were established.Astrocytes were treated with 75 μmol/L hydroxysafflor yellow A and 10 μmol/L tyrosine phosphorylation inhibitor AG490 for 8 hours during glucose-oxygen deprivation,respectively.The mechanism of hydroxysafflor yellow A on lipocalin-2 was further verified. RESULTS AND CONCLUSION:(1)Compared with the sham operation group,cerebral infarction was significantly increased in the middle cerebral artery occlusion and reperfusion group,accompanied by aggravated neurological impairment(P<0.01).Hydroxysafflor yellow A treatment could reduce cerebral infarction volume and improve neurological function(P<0.01).(2)The expressions of p-JAK2,p-STAT3 and lipocalin-2 in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A treatment reduced the expressions of JAK2,STAT3 and lipocalin-2(P<0.01).(3)The expression levels of interleukin 1β,interleukin-6 and tumor necrosis factor α in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A inhibited the expressions of interleukin 1β,interleukin-6 and tumor necrosis factor α(P<0.01).(4)In vitro,the expressions of p-JAK2,p-STAT3 and lipocalin-2 in the glucose-oxygen deprivation group were significantly higher than those in the normal group(P<0.01).After adding AG490,the phosphorylation of JAK2 and STAT3 decreased,and the expression of lipocalin-2 was inhibited(P<0.01).The results suggest that hydroxysafflor yellow A may inhibit the expression of lipocalin-2 in astrocytes after ischemia and hypoxia by regulating the JAK2/STAT3 signaling pathway,thereby reducing brain injury.
8.Transcranial direct current stimulation at different targets for Parkinson's disease:a network Meta-analysis
Yulin YANG ; Wanpeng CHANG ; Jiangtao DING ; Hongli XU ; Xiao WU ; Boheng XIAO ; Lihong MA
Chinese Journal of Tissue Engineering Research 2024;28(11):1797-1804
OBJECTIVE:To systematically evaluate the efficacy of transcranial direct current stimulation on the motor function of patients with Parkinson's disease,and to compare the efficacy of transcranial direct current stimulation at different targets on the motor function of patients with Parkinson's disease,so as to provide a theoretical basis for the target selection of transcranial direct current stimulation in clinical practice. METHODS:Cochrane Library,PubMed,Web of Science,CNKI,VIP,WanFang Data were retrieved for randomized controlled trials on the improvement of motor function in patients with Parkinson's disease by transcranial direct current stimulation published from the database inception to January 2023.The keywords were"Parkinson,transcranial direct current stimulation"in English and Chinese.The quality of the included studies was evaluated using the Cochrane 5.1.0 risk of bias assessment tool and the PEDro scale.Meta-analysis of outcome indicators was performed using RevMan 5.4 and Stata 17.0 software. RESULTS:Fifteen randomized controlled trials were finally included,and the PEDro scale showed that all were high-quality or very high-quality studies.Meta-analysis showed that transcranial direct current stimulation significantly improved Unified-Parkinson Disease Rating Scale part III score[mean difference(MD)=-2.49,95%confidence interval(CI):-4.42 to-0.55,P<0.05),step frequency score(MD=0.07,95%CI:0.03-0.11,P<0.05)and step speed score(MD=0.02,95%CI:0.00-0.05,P<0.05),but not for Berg Balance Scale scores(MD=2.57,95%CI:-0.74 to 5.87,P>0.05).Network Meta-analysis probability ranking:In terms of Unified-Parkinson Disease Rating Scale part III scores,the probability ranking results of target stimulation efficacy were dorsal lateral prefrontal cortex(52.4%)>primary motor cortex(45.8%)>central point of the brain(1.8%)>conventional rehabilitation(0%);in terms of gait frequency scores,the probability probability ranking results of target stimulation efficacy were cerebellum(50.1%)>central point of the brain(45.8%)>dorsal lateral prefrontal cortex(3.9%)>primary motor cortex(0.2%)>conventional rehabilitation(0%);in terms of gait speed scores,the probability ranking results of target stimulation efficacy were cerebellum(64.8%)>dorsal lateral prefrontal cortex(23.8%)>central point of the brain(9.4%)>primary motor cortex(1.7%)>conventional rehabilitation(0.4%);in terms of Berg Balance Scale scores,the probability ranking results of target stimulation efficacy were cerebellum(77.4%)>dorsal lateral prefrontal cortex(20.7%)>central point of the brain(0.7%)>conventional rehabilitation(0.2%). CONCLUSION:Transcranial direct current stimulation significantly improves motor function of patients with Parkinson's disease,with better motor coordination in the dorsolateral prefrontal cortex and better walking and balance in the cerebellum.
9.Pharmacokinetics of JS026 and JS026-JS016 for single intravenous administration in healthy volunteers
Yan TIAN ; Hui-Jing YE ; Jing-Jing WANG ; Nan-Yang LI ; Juan MA ; Xi TAN ; Fan WU ; Jie WANG ; Shu-Yan YU ; Xiao-Jie WU ; Jin-Jie HE ; Jing ZHANG ; Wen-Hong ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(15):2251-2255
Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.
10.Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China
Yun SONG ; Ying HE ; Xin Xue LU ; Mei Xiao ZHANG ; Lin XIAO JIANG ; Qing SONG ; Yong Xue HUANG ; Xia Hong MA ; Cheng Peng YU ; Yang Wu ZHU
Biomedical and Environmental Sciences 2024;37(2):178-186
Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and protection. Methods Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120 after the first immunization.Additionally,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death status.In a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28 and 42 after the first immunization. Results A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P<0.05).The groups 0-3-7-14,0-3-7-21,and 0-3-7-28 showed no statistically significant difference(P>0.05)in RVNAs levels at any time point.The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05). Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14-28 d)on the immunization potential.

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