Lipofuscin in brains of patients and mice with epidemic hemorrhagic fever

We have previously shown that the lipofuscin in the brain seems to have in-creased in amount in autopsy cases of epidemic hemorrhagic fever.The purpose of thisstudy was to testify if there is really such an increase.Lipfuscin in 10 sections from everybrain of 10 autopsy cases,stained with Sudan Ⅳ,Sudan black and H.E.,was carefully es-timated and found to be greatly increased as compared with the controls of the same agewithout brain disease.Animal experiment was also conducted on 15 sucking BALB/c miceby I.P.inoculation of 100 LD50（0.05ml）of strain Chen of hemorrhagic fever virus,andon 15 mice without inoculation as controls.No lipofuscin was detected in the controls.However,in the brains of experimental mice,lipofuscin was found to be markedly in-creased,especially in the necrotic cells.The findings suggest that the over-productionand deposition of lipofuscin may be a mild change caused by the virus and its related fac-tors,which might be enhanced by hypotension and shock.

Abnormalities of Cellular Immunoregulation in Patients with Epidemic Hemorrhagic Fever

In this report,a comparative study is made of the function test of spontaneousT suppressor cell（STs）and T Lymphocyte subsets in patients with epidemic hemorrha-gic fever（EHF）.It was found that in the early stages of the disease the activity of STs wasmarkedly lower than that of the controls,while the percentage of CD?+ cells increasedsignificantly,which led to the decrease and reciprocation of CD4/CD8 ratio,and that theactivity of STs was reversely related to the proportion of CD8+ cells on linear regressionanalysis,indicating that the CD8+ cells increased may mainly belong to cytotoxic T cells.It was also shown that the changes of STs function and CD4/CD8 ratio were related tothe abnormalities of serum C3 content and circulating immune complex.The results sug-gest that the disturbance of host cellular immunoregulation may play an important rolein the pathogenesis of EHF.

Pathological changes and viral antigen distribution in the lymphatic tissue of Patients with epidemic hemorrhagic fever

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Study on Biologic Activity for Membrane of Normal Bone Marrow Cells with Infection of Epidemic Hemorrhagic Fever Virus

Using DPH fluorescence probe, the membrane of normal bone marrow cells with infection of epidemic hemorrhagic fever virus (EHFV) was labeled. The membrane lipid fluidity was obviously decreased from the membrane lipid fluorescence polarization. The membrane lipid fluidity of lympho- cyte, monocyte and neutrophilic granulocyte was dynamically observed. After culturing the cells for 1, 6, 24 and 72 h, it was found that all the membrane lipid fluidity of the infected cells was de- creased obviously with the longer the culturing time, the more obvious it. Compared with the normal control groups, there was a significant difference statistically (P<0. 05-0. 01). It was suggested that the decrease of the membrane lipid fluidity of normal bone marrow cell with infection of EHFV had correlation with the degree of virus invading and cellfunction injury.

Epidemic Hemorrhagic Fever in Hubei Frovince,The Peoples Repulic of China: A Clinical and Serological Study

Between July 1975 and April 1980, 71 patients were admitted to the 2ndAttached Hospital of Hubei Provincial Medical College in Wuchang withthe diagnosis of Epidemic Hemorrhagic Fever (EHF). The clinical courseamong these patients was similar to that described for patients with KoreanHemorrhagic Fever, Nephropathica Epidemica of Scandanavia and Hemor-rhagic Fever with Renal Syndrome of the U.S.S.R. The overall mortalitywas 11.2％. Sera obtaincd from some of these patients as well as frompatients admitted to the First Attached Hospital of Hubei Provincial Me-dical College were tested against an antigen associated with Korean He-morrhagic Fever and showed exceedingly high antibody titers. We concludethat EHF in Centfal China represents the same disease process as KoreanHemorrhagic Fever.

Epidemic Characteristics and Spatio-Temporal Patterns of HFRS in Qingdao City,China,2010-2022

Objective This study investigated the epidemic characteristics and spatio-temporal dynamics of hemorrhagic fever with renal syndrome(HFRS)in Qingdao City,China.Methods Information was collected on HFRS cases in Qingdao City from 2010 to 2022.Descriptive epidemiologic,seasonal decomposition,spatial autocorrelation,and spatio-temporal cluster analyses were performed.Results A total of 2,220 patients with HFRS were reported over the study period,with an average annual incidence of 1.89/100,000 and a case fatality rate of 2.52%.The male:female ratio was 2.8:1.75.3%of patients were aged between 16 and 60 years old,75.3%of patients were farmers,and 11.6%had both“three red”and“three pain”symptoms.The HFRS epidemic showed two-peak seasonality:the primary fall-winter peak and the minor spring peak.The HFRS epidemic presented highly spatially heterogeneous,street/township-level hot spots that were mostly distributed in Huangdao,Pingdu,and Jiaozhou.The spatio-temporal cluster analysis revealed three cluster areas in Qingdao City that were located in the south of Huangdao District during the fall-winter peak.Conclusion The distribution of HFRS in Qingdao exhibited periodic,seasonal,and regional characteristics,with high spatial clustering heterogeneity.The typical symptoms of“three red”and“three pain”in patients with HFRS were not obvious.

A Retrospective Study of Continuous Renal Therapy and Anticoagulation in Patients with Hemorrhagic Fever with Renal Syndrome

Objective To observe the application of continuous renal replacement therapy(CRRT) and heparin anticoagulation in patients with HFRS, and to explore a more suitable anticoagulant strategy. Methods Eighty-five severe-type patients(severe group) and 71 critical-type patients(critical group) were enrolled in this study. The frequency of CRRT was compared between the two groups; the frequency of CRRT treated with and without heparin anticoagulation and the frequency of hemorrhage and channel blood clotting induced by the two anticoagulant strategies were observed. Results The frequency of CRRT in the critical group was higher than that in the severe group(P < 0.001). The frequency of CRRT initiated during the overlapping phases in the critical group was significantly higher than that of the severe group(P = 0.032). The total times of CRRT was 103, and 70 of them were treated with heparin anticoagulation. The frequencies of hemorrhage induced by heparin anticoagulation and no heparinization were 16 and 0, respectively, and the frequencies of channel blood clotting were 2 and 4, respectively. Conclusions CRRT has been used extensively in the critical-type patients with HFRS. The heparin anticoagulation and no anticoagulant strategies should be used more rationally in patients treated with CRRT, according to the clinical characteristics of the disease.

CLINICAL REPORT ON 142 CASES (278 EYES) OF AFRICAN EPIDEMIC HEMORRHAGIC CONJUNCTIVITIS TREATED WITH ACUPUNCTURE

This paper introduces the curative effects on 142 cases (278 eyes) of African epi-demic hemorrhagic conjunctivitis treated by acupuncture, and 128 (90. 1%) cases (250 eyes) of allpatients have been improved. Three groups were clinically observed in the present report. There were55 cases (104 eyes) in the first group for body acupuncture, of which 46 (83. 6%) cases were effec-tively treated; In the second group for auricular acupuncture, 34 (91. 6% ) cases (68 eyes) out of 37cases (74 eyes) were improved; There were 50 cases (100 eyes) in the third group for boyauricular-acupuncture, among which 48 (96. 0%) cases (96 eyes) were improved. The curative effects of thethird group were better than those of the other two groups.

Acute Hemorrhagic Fever: Clinical, Epidemiological and Laboratory Aspects in São Toméand Príncipe

Background: In the last 6 months, cases of acute hemorrhagic fever (AHF) have been recorded in Sao Tome and Principe (STP). Objective: To identify the clinical, epidemiological and laboratory parameters associated with AHF cases found in patients hospitalized in STP. Methods: Descriptive and quantitative analysis of AHF cases hospitalized in STP in the period December 2021 to May 19, 2022 through the variables: demographic data;clinical data;laboratory data and clinical outcome. Results: Analyzed 18 of 22 AHF cases, 50% of them male, mean age 33.7 years, 85.7% residing in the 2 largest districts of the country, 66.7% rural workers, administrative near maritime areas, sailors and domestics. 66.7% were healthy individuals. ≥50% had a fever, asthenia/weakness, myalgia, headache, lethargy, nausea, vomiting, and diarrhea. 22.2% to 33.3% had retro-orbital pain, abdominal pain, decreased consciousness, dyspnea/hypoxia, and cough. In a smaller register (5.6% - 11.1%), exanthema, convulsion, arthralgia, low back pain, chills, and chest pain. Bleeding from the digestive tract was found in 72.2%, followed by vaginal (33.3%), urethral (27.8%), nasal (22.2%), and oral (16.7%). 50% had laboratory confirmation for dengue, and another 50% with suspected clinical diagnosis without laboratory confirmation of the etiologic agent. Despite hemorrhage, 66.7% of confirmed cases were hemodynamically non-severe, and 88.9% of suspected cases were severe. Coinfection with malaria is evidenced in 11.1% of cases. 72.2% recovered and 27.8% died (deaths in 55.5% of suspected cases). Case deaths were male (100%), resident foreigners (40%), tool store employees, sailors and students, healthy (80%), and residing in the largest district in the country (60%). All deaths were hospitalized in serious condition, 80% were hospitalized for hemorrhage and shock, with bleeding arising between day 4 - 5 of illness in 60% and hospitalization on day 5 of illness. 60% died within ≤24 hours of hospitalization. 80% died from shock and multi-organ dysfunction and 20% from respiratory failure. Deaths had thrombocytopenia (100%), renal dysfunction (100%) and significantly increased transaminases (100%), anemia (75%) and leukocytosis (66.7%). 20% had a radiological change of pulmonary infiltrates. Conclusion: Our data reveal the complexity of the pathogens causing AHF and suggest the possible presence of other human pathogens usually unknown in the Santomean geographical territory.

The Risk of Severe Acute Kidney Injury Requiring Renal Replacement Therapy in Viral Hemorrhagic Fevers. A Review of Literature

Objective: It demonstrates the correlation of the viral hemorrhagic fever with kidney failure and the treatment as well as the outcome. Method: A PubMed search of the English literature from 1999 to 2019 was performed using “viral hemorrhagic fever, Case Report, Renal Failure” as the subject. The inclusion criteria were the following: 1) case report and case series of two or more patients;2) the report detailed the clinical presentation and reported the status of the renal system;3) the report described the management of renal failure if any;and 4) the etiology of the infection is known and is one of the known agents of viral hemorrhagic fever, listed on the centers of disease control website. We excluded infections related to vaccination related to viral hemorrhagic fever. Result: We found the mean age of these patients was 41.5. The male to female ratio was about 3.5:1. Dengue and Hantaviruses constituted 70.5% of patients. The overall mortality of the study cohort was 32.2%. Half of the patients had acute kidney injury and required renal replacement therapy. The chi-square statistic is 0.41;The p-value is 0.51;The chi-square statistic is 6.4254. Overall mortality was 32.3% in one cohort of 78 patients. The illness goes through several stages [1] [2] of clinical features and some viruses in the group have a high case fatality rate. Conclusions: Early diagnosis with aggressive supportive care is critical for improving clinical outcomes. Renal involvement is common. Amongst the cohort reviewed, of patients who had acute kidney injury, half of the patients required renal replacement support. However, some viruses cause greater kidney injury than others, for instance, kidney injury is more severe in Dengue hemorrhagic fevers when compared to Hantaviruses. Simultaneous management of public health by prevention and control of outbreaks is particularly important.

Crimean-Congo hemorrhagic fever:Pathogenesis,transmission and public health challenges

The dangerous Crimean-Congo hemorrhagic fever virus(CCHFV),an encapsulated negative-sense RNA virus of the family Nairoviridae,is transmitted from person to person via ticks.With a case fatality rate between 10%to 40%,the most common ways that the disease may spread to humans are via tick bites or coming into touch with infected animals'blood or tissues.Furthermore,the transfer of bodily fluids between individuals is another potential route of infection.There is a wide range of symptoms experienced by patients throughout each stage,from myalgia and fever to extreme bruising and excess bleeding.Tick management measures include minimising the spread of ticks from one species to another and from people to animals via the use of protective clothing,repellents,and proper animal handling.In order to prevent the spread of illness,healthcare workers must adhere to stringent protocols.Despite the lack of an authorised vaccine,the main components of treatment now consist of preventative measures and supportive care,which may include the antiviral medicine ribavirin.We still don't know very much about the virus's mechanisms,even though advances in molecular virology and animal models have improved our understanding of the pathogenesis of CCHFV.A critical need for vaccination that is both safe and effective,as well as for quick diagnosis and efficient treatments to lessen the disease's impact in areas where it is most prevalent.Important steps towards lowering Crimean-Congo hemorrhagic fever mortality and morbidity rates were to anticipatethe future availability of immunoglobulin products.

采用自配碳酸氢盐置换液行CRRT治疗流行性出血热合并急性肾功能衰竭1例回顾性分析

目的总结1例流行性出血热(EHF)合并急性肾功能衰竭(ARF)患者采用自配碳酸氢盐置换液行连续性肾脏替代治疗(CRRT)的经验,以期为同类病例的治疗提供参考。方法对2021年4月兰州大学第一医院东岗院区综合内科收治的1例EHF合并ARF患者行内科综合治疗,同时采用自配碳酸氢盐置换液行CRRT,依据动态监测血气分析、电解质、肾功能及凝血指标水平调整自配置换液配方及抗凝剂剂量。结果患者住院治疗14 d出院,出院后30 d复查随访,各项指标均恢复正常。结论在内科综合治疗的同时及时采用自配碳酸氢盐置换液行CRRT是治疗EHF合并ARF的有效方法。

STUDIES ON THE ENVIRONMENT STRUCTURE OF NATURAL NIDI AND EPIDEMIC AREAS OF HEMORRHAGIC FEVER WITH RENAL SYNDROME IN CHINA

The environment structure of natural nidi and epidemic areas of hemorrhagic fever with renal syndrome (HFRS) possesses characteristics of topography, hydrology, climate, soil, vegetation, and animals. The natural nidi and epidemic areas of HFRS are distributed mainly in plain and hilly regions under 500 meters above the sea level; in plentiful-water zones and transitional zones; in temperate zone and subtropical zone of the eastern monsoon region; in the abundant-aluminum soil region and the sial soil region; in the eastern China damp forest region (agricultural districts and northeast forest districts); in the eastern Asia dampness-prefering animal geographic region. Apodemus agrarius and Rattus norvegicus are the thriving animal population, predominant species or common species as well as the main reservoir hosts and sources of infection in the natural nidi and epidemic areas of HFRS.

Application of Conglutinin-ELISA for the detection of Circulating Immune Complexes in Sera of Patients with Epidemic Hemorrhagic Fever.

Conglutinin was extracted and purified from bovine’s sera and was used in ELISA for the detection of circulating immune complexes in the sera of patients suffering from epidemic hemorrhagic fever (EHF). The detected rates of circu-

流行性出血热中医病因病机及诊治要点分析

流行性出血热是由汉坦病毒引起的一种传染病,属中医“疫病”范畴。中医防治流行性出血热疫情疗效明显,但各家寒温迥异的辨治方法亦为后世辨治疫病带来困惑。通过总结资料,从“分类-分期-分证”视角对流行性出血热“因机证治”进行重新审视。从“分类”的角度将其归属于“寒疫”范畴,从“分期”的角度将其分为“热毒-厥脱-肾损-正虚”四个阶段。每个阶段又分多个证型:“热毒”阶段,以寒戾嗜营、热毒损络为核心病机,主要证型有太阳经证、太阳腑证、邪郁少阳证、阳明热盛证、气营两燔证。“厥脱”阶段,以热厥气脱为核心病机,主要证型有热厥气脱证、元气外脱证。“肾损”阶段,以疫毒伤肾为核心病机,分为少尿期和多尿期,少尿期以毒损肾络为要,主要证型有膀胱蓄血证、水热互结证、结胸证、湿阻三焦证等;多尿期以肾虚失摄为要,主要证型有肾虚不固证、余邪未尽证。“正虚”阶段,以气血阴阳的亏虚为核心病机,主要证型有脾肾阳虚和肝肾阴虚等。治疗流行性出血热:热毒期,到气即可凉营;厥脱期,见厥即要固脱;肾损期,少尿务必通腑,多尿补肾缩泉。

基于知信行模式的护理在流行性出血热患者中的应用效果

目的:探讨基于知信行模式的护理在流行性出血热患者中的应用效果。方法:回顾性分析2019年4月至2022年4月该院收治的98例流行性出血热患者的临床资料,根据护理方法不同将其分为对照组和观察组各49例。对照组实施常规护理,观察组实施基于知信行模式的护理。比较两组护理前后疾病认知情况、负性情绪[汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)]评分、症状缓解时间、住院时间及护理满意度。结果:护理后,观察组疾病认知量表中发病原因、临床表现、个人防护和注意事项等维度评分均高于对照组,HAMA、HAMD评分均低于对照组,尿蛋白转阴时间、退热时间、血小板恢复正常时间、血压恢复正常时间及住院时间均短于对照组,差异有统计学意义(P<0.05);观察组护理满意度为95.92%(47/49),高于对照组的83.67%(41/49),差异有统计学意义(P<0.05)。结论:基于知信行模式的护理用于流行性出血热患者可提高其对疾病认知,缓解不良情绪,缩短症状缓解时间和住院时间,提高患者护理满意度。

血必净注射液联合连续性肾替代疗法、白蛋白治疗肾综合征出血热的效果及对炎性因子、相关蛋白表达的影响

目的 探讨血必净注射液联合连续性肾替代疗法、白蛋白治疗肾综合征出血热的效果。方法 选取2022年1月至5月收治的50例肾综合征出血热患者为研究对象,根据随机数字表法将其分为对照组和观察组,各25例。对照组采用连续性肾替代疗法、白蛋白治疗,观察组在对照组基础上联合血必净注射液治疗。比较两组的治疗效果。结果 观察组的治疗总有效率高于对照组,差异具有统计学意义(P<0.05)。治疗后,观察组的白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平低于对照组,差异具有统计学意义(P<0.05)。治疗后,观察组的CD61、热休克蛋白70(HSP70)低于对照组,差异具有统计学意义(P<0.05)。结论 血必净注射液联合连续性肾替代疗法、白蛋白治疗肾综合征出血热的效果显著,可改善炎性因子水平,下调CD61、HSP70表达,值得推广及应用。

流行性出血热患者血清CK-MB、IL-6、IL-10水平与病情程度、预后的关系研究

目的:分析流行性出血热(EHF)患者血清肌酸激酶同工酶(CK-MB)、白细胞介素-6(IL-6)及白细胞介素-10(IL-10)水平与病情程度、预后的关系。方法:回顾性选择2019年6月—2022年6月于南昌市第九医院进行治疗的EHF患者60例作为本次研究对象,按照病情严重程度分为以下三组:轻症组(n=28,轻型、中型患者)、重症组(n=19,重型患者)及危重症组(n=13,危重型患者)。检测其入院后第1、3、7天的CK-MB、IL-6及IL-10水平,分析以上3项实验室检查指标与患者病情严重程度的相关性,并依据90 d预后情况分为存活组与死亡组,分析CK-MB、IL-6、IL-10与EHF患者预后的关系。结果:轻症组入院第1、3、7天血清CK-MB、IL-6、IL-10水平均低于重症组及危重症组(P<0.05),重症组以上指标水平均低于危重症组(P<0.05)。血清CK-MB、IL-6、IL-10水平与病情严重程度成正相关(rs=0.562、0.355、0.301,P<0.05)。60例患者随访90 d发现存活54例,死亡6例,存活组入院后第1、3、7天血清CK-MB、IL-6及IL-10水平均明显低于死亡组(P<0.05);受试者操作特征(ROC)曲线分析显示,入院第1天血清CK-MB、IL-6、IL-10单独及联合检测均对EHF患者预后有预测价值(P<0.05),其中联合检测的预测效能最高,其AUC为0.849,敏感度为98.14%,特异度为59.16%。结论:EHF患者血清CK-MB、IL-6及IL-10水平与病情发展呈正相关,可用于评估病情严重程度及预后,且三者联合时的效能最高。

低分子肝素钠对流行性出血热急性肾衰竭患者临床疗效及肾功能的影响

目的探讨低分子肝素钠对流行性出血热急性肾衰竭患者临床疗效及肾功能的影响。方法选取2016年5月至2021年5月于本院接受治疗的120例流行性出血热急性肾衰竭患者作为研究对象,根据随机数字表法将其分为对照组与观察组,每组60例。对照组使用肝素钠注射液治疗,观察组使用低分子肝素钠注射液治疗。比较两组的治疗效果。结果观察组的少尿期、住院时间短于对照组(P<0.05)。治疗后,两组的血尿素氮(BUN)、肌酐(Cr)水平明显降低,且观察组低于对照组(P<0.05)。治疗后,两组的血钙水平明显升高,血磷、甲状旁腺激素(PTH)水平明显降低,且观察组优于对照组(P<0.05)。透析4 h时,观察组的活化部分凝血活酶时间(APTT)、凝血酶时间(TT)较透析0 h时明显延长,但较透析2 h时明显缩短(P<0.05);透析2、4 h时,对照组的APTT、TT较透析0 h时明显延长(P<0.05);透析2、4 h时,观察组的APTT、TT明显短于对照组(P<0.05)。观察组的血液透析器堵管、心力衰竭、休克发生率低于对照组(P<0.05)。结论低分子肝素钠可提高流行性出血热急性肾衰竭患者的临床效果,缩短少尿期、住院时间,改善肾功能,减少并发症的发生。

2005-2021年中国流行性出血热的流行趋势分析

目的探讨2005-2021年中国流行性出血热(EHF)发病率的长期趋势,为完善EHF的防控措施提供参考依据.方法建立2005-2021年中国EHF发病率数据集.采用Joinpoint回归模型分析全国及各地区、各年龄段EHF发病率变化趋势.结果2005-2021年中国共报告EHF病例192066例,年均发病率为0.8345/10万;死亡1752例,年均死亡率为0.0076/10万,年均病死率为0.9122%.2005-2021年中国出血热发病率总体呈下降趋势,平均年度变化百分比(AAPC)为-5.56%(P=0.017),其中2008年和2012年为出血热发病率趋势变化转折点,2005-2008年间呈下降趋势,年度变化百分比(APC)为-26.92%(P=0.001);2008-2012年呈平稳趋势,APC为10.61%(P=0.224);2012-2021年呈下降趋势,APC为-4.11%(P=0.016).2005-2018年中国报告的出血热病例主要集中在东北部地区,病例数排名前5位(降序)的地区为黑龙江省、陕西省、山东省、辽宁省和吉林省.9个地区的出血热发病率呈下降趋势(均P<0.05),4个地区的出血热发病率呈上升趋势(均P<0.05),其余14个地区出血热发病率呈平稳趋势(均P>0.05);各年龄组均有病例发生,主要集中在25~64岁,占总发病数的79.86%;其中40~44岁年龄组比例最高,占12.75%.7个年龄组的出血热发病率均呈下降趋势(均P<0.05),1~岁组呈上升趋势(P<0.05),其余各年龄组处于平稳状态(均P>0.05).结论2005-2021年中国出血热发病率总体呈下降趋势,但黑龙江省、陕西省、山东省、辽宁省和吉林省等重点地区发病率仍在较高水平,下降幅度较小,流行风险仍存在.应针对重点地区与群体加强防治工作,持续开展病例与当地宿主动物监测;根据当地实际情况制定并落实精准综合防控措施,以降低出血热流行强度、发病率和死亡率.