Effect of polyethylene glycol 400 on the pharmacokinetics and tissue distribution of baicalin by intravenous injection based on the enzyme activity of UGT1A8/1A9.

Baicalin (BG) is a bioactive flavonoid extracted from the dried root of the medicinal plant, Scutellaria radix (SR) (dicotyledonous family, Labiatae), and has several biological activities. Polyethylene glycol 400 (PEG400) has been used as a suitable solvent for several traditional Chinese medicines (TCM) and is often used as an excipient for the compound preparation of SR. However, the drug-excipient interactions between BG and PEG400 are still unknown. Herein, we evaluated the effect of a single intravenous PEG400 administration on the BG levels of rats using pharmacokinetic and tissue distribution studies. A liver microsome and recombinant enzyme incubation system were used to further confirm the interaction mechanism between PEG400 and UDP-glucuronosyltransferases (UGTs) (UGT1A8 and UGT1A9). The pharmacokinetic study demonstrated that following the co-intravenous administration of PEG400 and BG, the total clearance (CLz) of BG in the rat plasma decreased by 101.60% (p < 0.05), whereas the area under the plasma concentration-time curve (AUC)0-t and AUC0-inf increased by 144.59% (p < 0.05) and 140.05% (p < 0.05), respectively. Additionally, the tissue distribution study showed that the concentration of BG and baicalein-6-O-ß-D-glucuronide (B6G) in the tissues increased, whereas baicalein (B) in the tissues decreased, and the total amount of BG and its metabolites in tissues altered following the intravenous administration of PEG400. We further found that PEG400 induced the UGT1A8 and UGT1A9 enzyme activities by affecting the maximum enzymatic velocity (Vmax) and Michaelis-Menten constant (Km) values of UGT1A8 and UGT1A9. In conclusion, our results demonstrated that PEG400 interaction with UGTs altered the pharmacokinetic behaviors and tissue distribution characteristics of BG and its metabolites in rats.

The polymorphism and geographical distribution of knockdown resistance of adult Anopheles sinensis populations in eastern China.

BACKGROUND: Anopheles sinensis is one of the major malaria vectors in China and other southeast Asian countries, including Vietnam, Cambodia, Thailand. Vector control is considered to be the critical measure for malaria control, while the increasing prevalence of insecticide resistance caused by long-term use of insecticides, especially pyrethroids, is threatening the successful control of An. sinensis. In order to understand the underlying resistance mechanisms involved and molecular basis, the principal malaria vector, An. sinensis from Jiangsu and Anhui provinces, Southeast China, was investigated. METHODS: The adult Anopheles mosquitoes were sampled from multiple sites across Jiangsu and Anhui provinces, and sufficient mosquitoes collected from eleven sites for insecticide susceptibility bioassays. The DIIS4-DIIS6 region of the para-type sodium channel gene was amplified and sequenced, then multiple PCR and Taqman assays were used to assess the frequencies of kdr mutations at the target gene. RESULTS: In the present study, most of the adult An. sinensis populations were pyrethroids resistant, which indicated the presence of kdr resistance mutations in the para-type sodium channel gene. Sequence analyses demonstrated the kdr mutation existed at codon 1014 in Jiangsu and Anhui provinces. In adult An. sinensis, three mutant types (TTT L1014F, TTC L1014F, and TGT L1014C) of kdr alleles were detected, while no wild type (TTG L1014) was observed. The TTC L1014F mutation was first reported in Anhui province. CONCLUSIONS: The highly polymorphic kdr alleles were observed in all the adult An. sinensis populations, which suggested that in-depth studies are required for carrying on insecticide resistance monitoring and specific resistance mechanisms studying into establish effective long-term malaria vector control program in eastern China.

Correction to: The polymorphism and geographical distribution of knockdown resistance of adult Anopheles sinensis populations in eastern China.

Please be advised that since publication of the original article [1] the authors have flagged that they omitted to provide the up-to-date version of Fig. 1 and, as such, the wrong version of Fig. 1 is present in the article.

The first outbreak of measles virus caused by imported genotype D8 in Jiangsu province of China.

Here we reported the outbreak of measles cases caused by the genotype D8 measles virus for the first time in Jiangsu province in China, which was possibly imported by a foreign student from Laos. Throat swab specimens were collected, and used to isolate virus. 634-bp fragment of the N gene and 1854-bp fragment of H gene were amplified by reverse transcription-PCR and sequenced, respectively. Phylogenetic results indicated that they belonged to genotype D8 measles virus. Further epidemiology investigation showed that the adults with D8 measles virus infection did not receive measles vaccine before having measles. In China, almost all D8 genotype MeV only infected those population without receiving measles vaccine immunization. Therefore, it is still necessary to implement the supplement activity of measles immunization target adult with immunity gap.

The first outbreak of measles virus caused by imported genotype D8 in Jiangsu province of China

ABSTRACT Here we reported the outbreak of measles cases caused by the genotype D8 measles virus for the first time in Jiangsu province in China, which was possibly imported by a foreign student from Laos. Throat swab specimens were collected, and used to isolate virus. 634-bp fragment of the N gene and 1854-bp fragment of H gene were amplified by reverse transcription-PCR and sequenced, respectively. Phylogenetic results indicated that they belonged to genotype D8 measles virus. Further epidemiology investigation showed that the adults with D8 measles virus infection did not receive measles vaccine before having measles. In China, almost all D8 genotype MeV only infected those population without receiving measles vaccine immunization. Therefore, it is still necessary to implement the supplement activity of measles immunization target adult with immunity gap.

Severe human infection with a novel avian-origin influenza A(H7N4) virus.

Human infections with influenza H7 subtypes, such as H7N9, have raised concerns worldwide. Here, we report a human infection with a novel influenza A(H7N4) virus. A 68 years-old woman with cardiovascular and cholecystic comorbidities developed rapidly progressed pneumonia with influenza-like-illness as initial symptom, recovered after 23 days-hospitalization including 8 days in ICU. Laboratory indicators for liver and blood coagulation dysfunction were observed. Oseltamivir phosphate, glucocorticoids and antibiotics were jointly implemented, with nasal catheterization of oxygen inhalation for this patient. We obtained the medical records and collected serial respiratory and blood specimens from her. We collected throat, cloacal and/or feces samples of poultry and wild birds from the patient's backyard, neighborhood, local live poultry markets (LPMs) and the nearest lake. All close contacts of the patient were followed up and sampled with throat swabs and sera. Influenza viruses and other respiratory pathogens were tested by real-time RT-PCR, viral culturing and/or sequencing for human respiratory and bird samples. Micro-neutralizing assay was performed for sera. A novel reassortant wild bird-origin H7N4 virus is identified from the patient and her backyard poultry (chickens and ducks) by sequencing, which is distinct from previously-reported avian H7N4 and H7N9 viruses. At least four folds increase of neutralizing antibodies to H7N4 was detected in her convalescent sera. No samples from close contacts, wild birds or other poultry were tested positive for H7N4 by real-time RT-PCR.

Experimental infections of mosquitoes with severe fever with thrombocytopenia syndrome virus.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a newly identified emerging infectious disease, which is caused by a novel bunyavirus (termed SFTSV) in Asia. Although mosquitoes have not been identified as the primary vectors, as revealed by epidemiological surveys, their role in transmitting this SFTSV as a suspicious vector has not been validated. FINDINGS: In this study, we conducted experimental infections of mosquitoes with SFTSV to examine the role of mosquitoes in the transmission of the virus. We did not detect viral replication in Culex pipiens pallens, Aedes aegyptis and Anopheles sinensis as revealed by qRT-PCR assay. In addition, we failed to isolate SFTSV from the Vero cells cultured with suspensions of SFTSV-infected mosquitoes. CONCLUSION: The results of the present study demonstrate little possibility that mosquitoes act as vectors for the emerging pathogen SFTSV.

Economic burden and its associated factors of hospitalized patients infected with A (H7N9) virus: a retrospective study in Eastern China, 2013-2014.

BACKGROUND: H7N9 continues to cause human infections and remains a pandemic concern. Understanding the economic impacts of this novel disease is important for making decisions on health resource allocation, including infectious disease prevention and control investment. However, there are limited data on such impacts. METHODS: Hospitalized laboratory-confirmed H7N9 patients or their families in Jiangsu Province of China were interviewed. Patients' direct medical costs of hospitalization were derived from their hospital bills. A generalized linear model was employed to estimate the mean direct medical costs of patients with different characteristics. RESULTS: The mean direct cost of hospitalization for H7N9 was estimated to be ¥ 71 060 (95 % CI, 48 180-104 820), i.e., US$ 10 996 (95 % CI, 7 455-16 220), and was ¥12 060 (US$ 1 861), ¥136 120 (US$ 21 001) and ¥218 610 (US$ 33 728) for those who had mild or severe symptoms or who died, respectively. The principal components of the total fees differed among patients with different disease severity, although medication fees were always the largest contributors. Disease severity, proportion of reimbursement and family member monthly average income were identified as the key factors that contributed to a patient's direct medical cost of hospitalization. CONCLUSIONS: The direct medical costs of hospitalized patients with H7N9 are significant, and far surpass the annual per capita income of Jiangsu Province, China. The influencing factors identified should be taken into account when developing related health insurance policies and making health resource allocation. TRIAL REGISTRATION: Not applicable. This is a survey study with no health care intervention implemented on human participants.

An Unmanned Aerial Vehicle-Mounted Cold Mist Spray of Permethrin and Tetramethylfluthrin Targeting Aedes albopictus in China.

Aedes albopictus is the primary vector of dengue fever and dengue hemorrhagic fever in China. Although there are previous studies on the application of adulticides to control this species, the application methods have either been back-pack or vehicle-mounted systems. However, many sites are too large to be effectively treated with back-pack sprayers, and the lack of roads restricts the use of vehicle-mounted sprayers. This paper provides the first study of using unmanned aerial vehicles to conduct cold mist sprays on Ae. albopictus habitats. A spray containing 4% permethrin and 1% tetramethylfluthrin was applied at an effective application rate of 9.0 mg/m(2). This method reduced Ae. albopictus populations by more than 90%. The results indicate this novel spray system is a powerful method to achieve a rapid decline of mosquito population in Ae. albopictus habitats in China.

Spatial distribution and risk factors of influenza in Jiangsu province, China, based on geographical information system.

Influenza poses a constant, heavy burden on society. Recent research has focused on ecological factors associated with influenza incidence and has also studied influenza with respect to its geographic spread at different scales. This research explores the temporal and spatial parameters of influenza and identifies factors influencing its transmission. A spatial autocorrelation analysis, a spatial-temporal cluster analysis and a spatial regression analysis of influenza rates, carried out in Jiangsu province from 2004 to 2011, found that influenza rates to be spatially dependent in 2004, 2005, 2006 and 2008. South-western districts consistently revealed hotspots of high-incidence influenza. The regression analysis indicates that railways, rivers and lakes are important predictive environmental variables for influenza risk. A better understanding of the epidemic pattern and ecological factors associated with pandemic influenza should benefit public health officials with respect to prevention and controlling measures during future epidemics.

Epidemiological and clinical characteristics and risk factors for death of patients with avian influenza A H7N9 virus infection from Jiangsu Province, Eastern China.

BACKGROUND: A novel avian influenza A (H7N9) virus has caused great morbidity as well as mortality since its emergence in Eastern China in February 2013. However, the possible risk factors for death are not yet fully known. METHODS AND FINDINGS: Patients with H7N9 virus infection between March 1 and August 14, 2013 in Jiangsu province were enrolled. Data were collected with a standard form. Mean or percentage was used to describe the features, and Fisher's exact test or t-test test was used to compare the differences between fatal and nonfatal cases with H7N9 virus infection. A total of 28 patients with H7N9 virus infection were identified among whom, nine (32.1%) died. The median age of fatal cases was significant higher than nonfatal cases (P<0.05). Patients with older age were more strongly associated with increased odds of death (OR = 30.0; 95% CI, 2.85-315.62). Co-morbidity with chronic lung disease and hypertension were risk factors for mortality (OR = 14.40; 95% CI, 1.30-159.52, OR = 6.67; 95% CI, 1.09-40.43, respectively). Moreover, the presence of either bilateral lung inflammation or pulmonary consolidation on chest imaging on admission was related with fatal outcome (OR = 7.00; 95%CI, 1.10-44.61). Finally, dynamic monitoring showed that lymphopenia was more significant in fatal group than in nonfatal group from day 11 to week five (P<0.05). The decrease in oxygenation indexes were observed in most cases and more significantly in fatal cases after week three (P<0.05), and the value of nearly all fatal cases were below 200 mmHg during our evaluation period. CONCLUSIONS: Among cases with H7N9 virus infection, increased age accompanied by co-morbidities was the risk of death. The severity of lung infection at admission, the persistence of lymphocytopenia, and the extended duration of lower oxygenation index all contributed to worsened outcomes of patients with H7N9 virus infection.

Probable person to person transmission of novel avian influenza A (H7N9) virus in Eastern China, 2013: epidemiological investigation.

OBJECTIVE: To determine whether the novel avian influenza H7N9 virus can transmit from person to person and its efficiency. DESIGN: Epidemiological investigations conducted after a family cluster of two patients with avian H7N9 in March 2013. SETTING: Wuxi, Eastern China. PARTICIPANTS: Two patients, their close contacts, and relevant environments. Samples from the patients and environments were collected and tested by real time reverse transcriptase-polymerase chain reaction (rRT-PCR), viral culture, and haemagglutination inhibition assay. Any contacts who became ill had samples tested for avian H7N9 by rRT-PCR. Paired serum samples were obtained from contacts for serological testing by haemagglutination inhibition assays. MAIN OUTCOMES MEASURES: Clinical data, history of exposure before the onset of illnesses, and results of laboratory testing of pathogens and further analysis of sequences and phylogenetic tree to isolated strains. RESULTS: The index patient became ill five to six days after his last exposure to poultry. The second patient, his daughter aged 32, who provided unprotected bedside care in the hospital, had no known exposure to poultry. She developed symptoms six days after her last contact with her father. Two strains were isolated successfully from the two patients. Genome sequence and analyses of phylogenetic trees showed that both viruses were almost genetically identical. Forty three close contacts of both patients were identified. One had mild illness but had negative results for avian H7N9 by rRT-PCR. All 43 close contacts tested negative for haemagglutination inhibition antibodies specific for avian H7N9. CONCLUSIONS: The infection of the daughter probably resulted from contact with her father (the index patient) during unprotected exposure, suggesting that in this cluster the virus was able to transmit from person to person. The transmissibility was limited and non-sustainable.

[The prospective study of association between C-reactive protein and hypertension in community population].

OBJECTIVE: The aim was to explore the association between high-sensitivity C-reactive protein level at baseline and hypertension in follow-up periods in a Chinese cohort. METHODS: We analyzed data from a cohort established in "Prevention of metabolic syndrome and multi-metabolic disorders in Jiangsu province" in April 2000. A follow-up investigation was carried out for those whose follow up time met 5 years in June 2006. A total of 2035 persons completed investigation and hs-CRP was tested. Subjects with normal baseline blood pressure were classified into four groups(514, 498, 515 and 508 subjects in each group) according to quartiles of hs-CRP level (<1.3, 1.3-1.9, 2.0-3.2 and ≥ 3.3 mg/L). The relationship between the risk of hypertension and baseline level of hs-CRP were analyzed using Cox proportional hazards regression model. RESULTS: The median of follow up time was 6.39 years among the 2035 subjects (926 males and 1109 females). Hypertension incidence was 2378/100 000 person-years, 2942/100 000 person-years, 3693/100 000 person-years and 4390/100 000 person-years in hs-CRP < 1.3, 1.3-1.9, 2.0-3.2 and ≥ 3.3 mg/L groups respectively. Compared to the group of hs-CRP < 1.3 mg/L, the relative risk (RR) (95%CI) of hypertension in groups of hs-CRP 1.3-1.9, 2.0-3.2 and ≥ 3.3 mg/L was 1.22 (0.87-1.72), 1.43 (1.03-2.00), 1.70 (1.21-2.41) respectively, adjusted for sex, age, baseline blood pressure, BMI, smoking, alcohol drinking, physical activity and family history of myocardial infarction and diabetes.When stratified by quartiles of baseline blood pressure, the incidence of hypertension in each group increased with level of hs-CRP.In the group whose baseline SBP < 110 mm Hg (1 mm Hg = 0.133 kPa) , compared to the group of hs-CRP < 1.3 mg/L, RR (95%CI) were 2.24 (1.32-4.03), 2.57 (1.57-4.57) and 3.57 (2.54-5.90) in hs-CRP 1.3-1.9, 2.0-3.2 and ≥ 3.3 mg/L groups respectively.In the group whose baseline DBP < 65 mm Hg, RR (95%CI) were 1.78 (1.03-3.24), 2.74 (1.63-4.93) and 4.13 (2.35-7.27) respectively. CONCLUSION: Inflammation was an important process in the development of hypertension.

A family cluster of infections by a newly recognized bunyavirus in eastern China, 2007: further evidence of person-to-person transmission.

BACKGROUND: Seven persons in one family living in eastern China developed fever and thrombocytopenia during May 2007, but the initial investigation failed to identify an infectious etiology. In December 2009, a novel bunyavirus (designated severe fever with thrombocytopenia syndrome bunyavirus [SFTSV]) was identified as the cause of illness in patients with similar clinical manifestations in China. We reexamined this family cluster for SFTSV infection. METHODS: We analyzed epidemiological and clinical data for the index patient and 6 secondary patients. We tested stored blood specimens from the 6 secondary patients using real time reverse transcription polymerase chain reaction (RT-PCR), viral culture, genetic sequencing, micro-neutralization assay (MNA), and indirect immunofluorescence assay (IFA). RESULTS: An 80-year-old woman with fever, leucopenia, and thrombocytopenia died on 27 April 2007. Between 3 and 7 May 2007, another 6 patients from her family were admitted to a local county hospital with fever and other similar symptoms. Serum specimens collected in 2007 from these 6 patients were positive for SFTS viral RNA through RT-PCR and for antibody to SFTSV through MNA and IFA. SFTSV was isolated from 1 preserved serum specimen. The only shared characteristic between secondary patients was personal contact with the index patient; none reported exposure to suspected animals or vectors. CONCLUSIONS: Clinical and laboratory evidence confirmed that the patients of fever and thrombocytopenia occurring in a family cluster in eastern China in 2007 were caused by a newly recognized bunyavirus, SFTSV. Epidemiological investigation strongly suggests that infection of secondary patients was transmitted to family members by personal contact.

[A prospective study on the association between dyslipidemia and hypertension].

OBJECTIVE: To discuss the risks of hypertension development with relation to the level of lipid variables among populations who had normal blood pressure at baseline study. METHODS: In April 2000, under the support of project "prevention of metabolic syndrome and multi-metabolic disorders in Jiangsu province", a cohort study was performed to obtain the baseline data among 8685 persons from age 34 to 74. In June of 2006, a follow-up investigation was carried out among those who had been in the study for 5 years after the baseline study started. 2603 persons who met the selection criteria and showed normal blood pressure during baseline study, were recruited in this investigation. The interval from the baseline to the follow-up studies was 6.38 years on average. Relationship between the risk of developing hypertension and the baseline level of lipid variables were analyzed. RESULTS: Relations between baseline lipid levels and the incidence of hypertension during the follow-up was discovered. In gender and age adjusted model, the lipid variables were all associated with hypertension (trend test, P<0.01). In multivariable-adjusted model, HDL-C [aRR=0.71 (95%CI: 0.61-0.99)], non-HDL-C [aRR=1.28 (95%CI: 1.14-1.83)], TC/HDL-C ratio [aRR=1.41 (95%CI: 1.25-2.03)] and TG [aRR=1.49 (95%CI: 1.30-2.13)] were again associated with hypertension (trend test, P<0.05). Even the aRR was much weakened after the baseline SBP, DBP were adjusted with Cox model, the significant relation of hypertension to HDL-C, TC/HDL-C ratio and TG still existed. Excluding the two factors of obesity (BMI> or =28) and diabetes which had been recognized in marked linking with hypertension, lipid variables were still associated with hypertension. CONCLUSION: Dyslipidemia might occur before being hypertensive. Hypertension was associated with HDL-C, TC/HDL-C and TG or even exclusion of obesity, diabetes and factors of smoking and drinking or baseline level of SBP, DBP were adjusted.