济宁市2001～2003年流行性腮腺炎流行病学分析

目的探讨济宁市2001～2003年流行性腮腺炎(以下简称流腮)疫情动态,控制流腮传播蔓延。方法采用流行病学回顾性调查方法,对济宁市3年流腮报告病例的流行特征进行分析。结果2001～2003年全市共登记流腮病例1431例,占法定传染病报告数的12.70%。全年均有发病,以冬春为主,农村发病明显高于城市,城乡之比为0.41:1,在托儿园所、小学、中学时有多发、暴发疫情。1431例流腮病例中有发热病例1127例,腮腺肿大者1163例,颌下腺肿大者389例,并发症共665例,其中前3位为脑炎372例(55.94%),脑膜炎132例(19.85%),胰腺炎95例(14.29%);男性患病率明显高于女性,男女性别比为2.59:1,以15岁以下儿童发病为主,占该病的96.09%,78.34%的病例集中在6～10岁年龄组,62.47%的患者是小学生。结论6～10岁学龄儿童及农村人口是实施免疫控制策略的重点。     

蟾麝解毒膏治疗流行性腮腺炎180例

采用蟾麝解毒膏外敷治疗流行性腮腺炎180例,并与应用如意金黄散治疗120例作对照。结果：治疗组2天治愈85例,3天治愈71例,4－5天治愈24例;对照组2天治愈46例,3天治愈45例,4－5天治愈29例。两组疗效比较,2、3天治愈率明显差异（x^2=14.83、7.46,P均＜0．01）。     

Activation of PTH1R alleviates epididymitis and orchitis through Gq and β-arrestin-1 pathways

Inflammation in the epididymis and testis contributes significantly to male infertility. Alternative therapeutic avenues treating epididymitis and orchitis are expected since current therapies using antibiotics have limitations associated to side effects and are commonly ineffective for inflammation due to nonbacterial causes. Here, we demonstrated that type 1 parathyroid hormone receptor (PTH1R) and its endogenous agonists, parathyroid hormone (PTH) and PTH-related protein (PTHrP), were mainly expressed in the Leydig cells of testis as well as epididymal epithelial cells. Screening the secretin family G protein–coupled receptor identified that PTH1R in the epididymis and testis was down-regulated in mumps virus (MuV)- or lipopolysaccharide (LPS)-induced inflammation. Remarkably, activation of PTH1R by abaloparatide (ABL), a Food and Drug Administration–approved treatment for postmenopausal osteoporosis, alleviated MuV- or LPS-induced inflammatory responses in both testis and epididymis and significantly improved sperm functions in both mouse model and human samples. The anti-inflammatory effects of ABL were shown to be regulated mainly through the Gq and β-arrestin-1 pathway downstream of PTH1R as supported by the application of ABL in Gnaq^± and Arrb1^−/− mouse models. Taken together, our results identified an important immunoregulatory role for PTH1R signaling in the epididymis and testis. Targeting to PTH1R might have a therapeutic effect for the treatment of epididymitis and orchitis or other inflammatory disease in the male reproductive system.

A total of ∼15% of childbearing–age couples are infertile, and male infertility accounts for nearly 50% of this sterility. Currently, male infertility is not only a personal problem but also becomes a public health issue (1–3). Epididymitis and orchitis, which are inflammatory diseases of the epididymis and testis, respectively, are estimated to account for 6 to 15% of male infertility and thus have attracted increasing attention in recent years (4–6). The current treatment of epididymitis and orchitis mainly relies on antibiotics since the inflammations were commonly caused by bacteria-induced infections. However, antibiotic therapies are known to cause undesired adverse effects. In addition, infection by viruses, such as mumps virus (MuV), cytomegalovirus, and herpes simplex virus, could also lead to epididymitis and orchitis, which are insensitive to regular antibiotic therapies (4, 7, 8). Therefore, novel therapeutic strategies for threating epididymitis and orchitis are needed.The G protein–coupled receptors (GPCRs) are the largest family of membrane proteins with wide-ranging expression and physiologic functions (9–11). Currently, GPCRs account for ∼30% of drug targets with clinical usage, but the physiological and pathological functions of the majority of GPCRs in the male reproduction system are still undefined (3, 12). Therefore, the characterization of functions of GPCRs involved in the regulation of inflammatory responses in the epididymis and testis may provide novel clues for treatments of epididymitis and orchitis. Mammalian GPCR are grouped into five families including Rhodopsin (Class A), Secretin (Class B1), Adhesion (Class B2), Glutamate (Class C), and Frizzled (Class F) (12, 13). The secretin family GPCR, consisting of 15 members, are peptide receptors that bind important endogenous peptide hormones (14–16). The secretin family GPCR and their cognate peptide ligands are implicated as drug targets in many pathologies, such as migraine, cardiovascular disease, diabetes, psychiatric disorders, neurodegeneration, osteoporosis, and inflammation (15–17). Among them, the type 1 parathyroid hormone receptor (PTH1R) primarily mediates skeletal development, bone turnover, and calcium homeostasis through interacting with two endogenous polypeptide ligands, parathyroid hormone (PTH) and PTH-related protein (PTHrP) (18, 19). PTH1R has been found to play an important role in many pathologies, such as osteoporosis, hypoparathyroidism, and cancer-associated hypercalcemia and cachexia (20, 21). Recent RNA sequencing results suggested a high expression of PTH1R in spermatozoa, implying a regulatory role of this receptor in the male reproductive system (22). However, the detailed functions and potential underlying mechanisms still remain unknown.In the present study, we found that PTH1R and its two endogenous ligands, PTHrP and PTH, were expressed in the Leydig cells of testis as well as epididymal epithelial cells. Both messenger RNA (mRNA) and protein levels of PTH1R and its ligands were down-regulated in the testis and epididymis upon MuV- or lipopolysaccharide (LPS)-induced inflammation. Interestingly, abaloparatide (ABL), which is an agonist of PTH1R and a Food and Drug Administration (FDA)–approved drug for postmenopausal osteoporosis (23), significantly alleviated MuV- or LPS-induced inflammation in the testis and epididymis and also enhanced sperm motility of mice. Further studies using Gnaq^± and Arrb1^−/− mice models and cellular approaches elucidated the mechanisms underlying the regulatory role of the PTH1R in the testis and epididymis. Our findings suggest that endogenous PTH1R signaling plays an important immunoregulatory role in the male reproduction system, and PTH1R is a potential therapeutic target for the treatment of epididymitis and orchitis.     

RT-PCR based diagnosis and molecular characterisation of mumps viruses derived from clinical specimens collected during the 1996 mumps outbreak in Portugal

Clinical specimens collected during an outbreak of mumps were characterised by RT-PCR, nested PCR, and nucleotide sequencing. Mumps virus was positively identified in 12/21(57%) saliva, 9/21(43%), throat and 1/33(3%) urine specimens and further sequence comparison revealed that at least six strains of viruses, which differed from 0–9.43% at the nucleotide levels, were co-circulating during the epidemic. However, phylogenetic analysis showed that these viruses grouped with two previously identified lineages which were mostly composed of other European mumps virus isolates. J. Med. Virol. 52:349–353, 1997. © 1997 Wiley-Liss, Inc.     

Influence of Ribavirin on Mumps Virus Population Diversity

Frequent mumps outbreaks in vaccinated populations and the occurrence of neurological complications (e.g., aseptic meningitis or encephalitis) in patients with mumps indicate the need for the development of more efficient vaccines as well as specific antiviral therapies. RNA viruses are genetically highly heterogeneous populations that exist on the edge of an error threshold, such that additional increases in mutational burden can lead to extinction of the virus population. Deliberate modulation of their natural mutation rate is being exploited as an antiviral strategy and a possibility for rational vaccine design. The aim of this study was to examine the ability of ribavirin, a broad-spectrum antiviral agent, to introduce mutations in the mumps virus (MuV) genome and to investigate if resistance develops during long-term in vitro exposure to ribavirin. An increase in MuV population heterogeneity in the presence of ribavirin has been observed after one passage in cell culture, as well as a bias toward C-to-U and G-to-A transitions, which have previously been defined as ribavirin-related. At higher ribavirin concentration, MuV loses its infectivity during serial passaging and does not recover. At low ribavirin concentration, serial passaging leads to a more significant increase in population diversity and a stronger bias towards ribavirin-related transitions, independently of viral strain or cell culture. In these conditions, the virus retains its initial growth capacity, without development of resistance at a whole-virus population level.     

Low immunity against vaccine preventable diseases in Turkish HIV cohort

Background/aimHIV infection increase the risk of serious disease resulting from common vaccine-preventable infections. Vaccinations are particularly important for HIV infected adults. We aimed to investigate the immunity rates against measles, mumps, rubella, hepatitis A, B, and tetanus in newly diagnosed HIV patients. Materials and methodsPatients who admitted to outpatient clinics of three centers with newly diagnosed HIV infection, between 1 January 2015 and 31 June 2017 were included. Measles, mumps, rubella, varicella zoster virus, hepatitis A, hepatitis B, and tetanus antibody levels were measured by commercial diagnostic kits. Demographical and laboratory data of the patients were recorded.ResultsFive hundred and twenty-three patients were enrolled in the study. Of the patients 87% were male (n = 455) and the mean age was 38 ± 13 years. Serology was available for measles 74.2% (388/523), mumps 73.8% (386/523), rubella 77.8% (407/523), hepatitis A 88.5% (463/523), hepatitis B 97.7% (511/523), tetanus 8.6% (45/523), and VZV 79.9% (418/523). Seropositivity was 82% for measles, 75.6% for mumps, 92.1% for rubella. Of the patients whom all three of the components of the MMR vaccine was tested, 37.7% (127/337) were susceptible at least one and needed the vaccine. Mean age was lower in patients who are nonimmune to measles and mumps (p = 0.008). Younger patients were also nonimmune for hepatitis A, while older patients were nonimmune for hepatitis B.ConclusionIn our study we found that rates of nonimmunity can increase up to one third of the patients even though there is a national vaccination program. Nonimmune individuals should be detected and vaccinated in line with recent guidelines and response should be monitored because of the possibility of impaired immunity and possible suboptimal response. National campaigns can be launched for adult immunization and physicians should be aware of the importance of adult immunization.     

French national diagnostic and care protocol for Kawasaki disease

Kawasaki disease (KD) is an acute vasculitis with a particular tropism for the coronary arteries. KD mainly affects male children between 6 months and 5 years of age. The diagnosis is clinical, based on the international American Heart Association criteria. It should be systematically considered in children with a fever, either of 5 days or more, or of 3 days if all other criteria are present. It is important to note that most children present with marked irritability and may have digestive signs. Although the biological inflammatory response is not specific, it is of great value for the diagnosis. Because of the difficulty of recognising incomplete or atypical forms of KD, and the need for urgent treatment, the child should be referred to a paediatric hospital as soon as the diagnosis is suspected. In the event of signs of heart failure (pallor, tachycardia, polypnea, sweating, hepatomegaly, unstable blood pressure), medical transfer to an intensive care unit (ICU) is essential. The standard treatment is an infusion of IVIG combined with aspirin (before 10 days of fever, and for a minimum of 6 weeks), which reduces the risk of coronary aneurysms. In case of coronary involvement, antiplatelet therapy can be maintained for life. In case of a giant aneurysm, anticoagulant treatment is added to the antiplatelet agent. The prognosis of KD is generally good and most children recover without sequelae. The prognosis in children with initial coronary involvement depends on the progression of the cardiac anomalies, which are monitored during careful specialised cardiological follow-up.     

Long-term immunoprotection after live attenuated measles-mumps-rubella booster vaccination in children with juvenile idiopathic arthritis

IntroductionVaccines, especially live attenuated vaccines, in children with JIA pose a great challenge due to both potential lower immunogenicity and safety as a result of immunosuppressive treatment. For many years, in the Netherlands, JIA patients receive a measles-mumps-rubella (MMR) booster vaccine at the age of nine years as part of the national immunization program.ObjectivesTo study long-term humoral immunoprotection in a large cohort of JIA patients who received the MMR booster vaccine while being treated with immunomodulatory therapies at the Wilhelmina Children’s Hospital in Utrecht, the Netherlands.MethodsMMR-specific IgG antibody concentrations in stored serum samples of vaccinated JIA patients were determined with chemiluminescent microparticle immunoassays (CMIA). Samples were analyzed five years after MMR booster vaccination and at last available follow-up visit using both crude and adjusted analyses. Additional clinical data were collected from electronic medical records.ResultsIn total, 236 samples from 182 patients were analyzed, including 67 samples that were available five years post-vaccination, and an additional 169 samples available from last visits with a median duration after vaccination of 6.9 years (IQR: 2.8–8.8). Twenty-eight patients were using biologic disease-modifying antirheumatic drugs (bDMARDS) of whom 96% anti-TNF agents and 4% tocilizumab. Percentages of protective antibody levels against measles after five years were significantly lower for patients who used bDMARD therapy at vaccination compared to patients who did not: 60% versus 86% (P = 0.03). For mumps (80% versus 94%) and rubella (60% versus 83%) this difference did not reach statistical significance (P = 0.11 and P = 0.07, respectively). Antibody levels post-vaccination decreased over time, albeit not significantly different between bDMARD users and non-bDMARD users.ConclusionThe MMR booster vaccine demonstrated long-term immunogenicity in the majority of children with JIA from a large cohort, although lower percentages of protective measles antibody levels were observed in bDMARD users. Hence, it might be indicated to measure antibody levels at least five years after MMR booster vaccination in the latter group and advice an extra booster accordingly.     

基于优劣解距离法、秩和比法和线性插值法的我国儿童保健工作质量综合评价

目的：运用优劣解距离法（TOPSIS法）、秩和比法及线性插值法对2020年全国31个省（区、市）儿童保健工作质量进行综合评价，对比分析3种方法对儿童保健工作质量评价的应用价值，为制定儿童健康发展规划提供参考依据。方法：收集2021年《中国卫生健康统计年鉴》中，全国31个省（区、市）的低出生体重率（%）、围产儿死亡率（‰）、5岁以下儿童低体重患病率（%）等6项反映儿童保健工作质量的常见指标，运用TOPSIS法、秩和比法和线性插值法分别对全国31个省（区、市）的儿童保健工作质量进行评价，采用Spearman相对系数法对3种评价方法的排序结果进行相关性分析。结果：相关性分析结果表明，3种方法的评价结果具有高度的正相关关系，其中，秩和比法和线性插值法排序结果的一致性最好（R=0.968,P<0.01），其次是TOPSIS法和秩和比法（R=0.845,P<0.01），第三是TOPSIS法和线性插值法（R=0.832,P<0.01）。虽然3种方法的评价结果具有高度的正相关关系，但是其评价结果仍有一定的差别。对3种方法评价结果进行综合排序，2020年儿童保健工作质量排名居前3位的省...