Effect of different vaccine strategies for the control of Japanese encephalitis in mainland China from 1961 to 2020: A quantitative analysis.

BACKGROUND: We aimed to quantify the impact of each vaccine strategy (including the P3-inactivated vaccine strategy [1968-1987], the SA 14-14-2 live-attenuated vaccine strategy [1988-2007], and the Expanded Program on Immunization [EPI, 2008-2020]) on the incidence of Japanese encephalitis (JE) in regions with different economic development levels. METHODS: The JE incidence in mainland China from 1961 to 2020 was summarized by year, then modeled and analyzed using an interrupted time series analysis. RESULTS: After the P3-inactivated vaccine was used, the JE incidence in Eastern China, Central China, Western China and Northeast China in 1968 decreased by 39.80 % (IRR = 0.602, P < 0.001), 7.80 % (IRR = 0.922, P < 0.001), 10.80 % (IRR = 0.892, P < 0.001) and 31.90 % (IRR = 0.681, P < 0.001); the slope/trend of the JE incidence from 1968 to 1987 decreased by 30.80 % (IRR = 0.692, P < 0.001), 29.30 % (IRR = 0.707, P < 0.001), 33.00 % (IRR = 0.670, P < 0.001) and 41.20 % (IRR = 0.588, P < 0.001). After the SA 14-14-2 live-attenuated vaccine was used, the JE incidence in Eastern China and Northeast China in 1988 decreased by 2.60 % (IRR = 0.974, P = 0.009) and 14.70 % (IRR = 0.853, P < 0.001); the slope/trend of the JE incidence in Eastern China and Central China from 1988 to 2007 decreased by 4.60 % (IRR = 0.954, P < 0.001) and 4.70 % (IRR = 0.953, P < 0.001). After the EPI was implemented, the JE incidence in Eastern China, Central China and Western China in 2008 decreased by 10.50 % (IRR = 0.895, P = 0.013), 18.00 % (IRR = 0.820, P < 0.001) and 24.20 % (IRR = 0.758, P < 0.001), the slope/trend of the JE incidence in Eastern China from 2008 to 2020 decreased by 17.80 % (IRR = 0.822, P < 0.001). CONCLUSIONS: Each vaccine strategy has different effects on the JE incidence in regions with different economic development. Additionally, some economically underdeveloped regions have gradually become the main areas of the JE outbreak. Therefore, mainland China should provide economic assistance to areas with low economic development and improve JE vaccination plans in the future to control the epidemic of JE.

Impact of the expanded program on immunization on the incidence of Japanese encephalitis in different regions of Mainland China: An interrupt time series analysis.

In 2008, Mainland China included the Japanese encephalitis (JE) vaccine in the Expanded Program on Immunization (EPI) to control the JE epidemic. However, Northwest China experienced the largest JE outbreak since 1994 in 2018, and the effects of the EPI in different regions are unclear. Therefore, we used an interrupted time series design to evaluate the effects of the EPI in different regions. In this study, ß1 and ß1+ß3 represented the slope or trend of the JE incidence before and after the EPI, respectively; ß2 was the level change of the JE incidence immediately after the EPI; ß3 represented the slope change of the JE incidence before and after the EPI. We found that the JE incidence in all regions showed a decreasing trend before the EPI (ß1<0.000, P<0.05). The JE incidence in Mainland China (ß2=-7.669, P<0.05), East China (ß2=-9.791, P<0.05), Central China (ß2=-10.695, P<0.05), South China (ß2=-6.551, P<0.05) and Southwest China (ß2=-2.216, P<0.05) decreased by 7.669/100,000, 9.791/100,000, 10.695/100,000, 6.551/100,000 and 2.216/100,000 immediately after the EPI, and the EPI had short-term effects on the JE incidence in these regions. The slope of the JE incidence in Mainland China (ß3=0.272, P<0.05), East China (ß3=0.337, P<0.05), Central China (ß3=0.381, P<0.05), South China (ß3=0.254, P<0.05) and Southwest China (ß3=0.081, P<0.05) increased by 0.272, 0.337, 0.381, 0.254 and 0.081 after the EPI, and the EPI had long-term effects on the JE incidence in these regions. The JE incidence in many regions (excluding North China) showed a decreasing trend after the EPI (ß1+ß3 <0.000). Northwest China (GDP from 2008 to 2020 ranked last in Mainland China) and Southwest China (GDP from 2008 to 2020 ranked fifth in Mainland China), with underdeveloped economy, used to be low-epidemic regions of JE, but they have become high-epidemic regions in recent years. Economic development may contribute to the geographic variations in the effects of the EPI. Therefore, it is significant for JE control in Mainland China to increase support for underdeveloped regions and adjust the vaccine strategy according to the new epidemic situation of JE.

Long-Term Neurological Sequelae and Disease Burden of Japanese Encephalitis in Gansu Province, China.

Background and objects: The study aimed to evaluate the long-term neurological sequelae and the disease burden of JE in Gansu, China. Methods: JE patients were included as study population from 2005-2011 in Gansu, and a follow-up survey was conducted in 2007-2014. Pair-matched healthy individuals were selected as controls. All subjects underwent a neurological examination and intelligence quotient (IQ) and memory quotient (MQ) assessments. Then, the disability-adjusted life years (DALYs), and direct and indirect medical expenses were systematic assessed. Results: Forty-four point seven percent of the JE patients had objective neurological deficits, compared with 2.4% of controls. Subnormal intelligence was found in 21.2% of JE subjects, compared with 1.2% control who exhibited a mildly reduced IQ. Abnormal MQ scores were noted in 56.3% JE subjects, compared with only 12.7% controls. Prevalence of each sequelae caused by JE were significantly higher in adults than in younger subjects. Furthermore, median DALY lost due to JE was 9.2 per subject. Median economic cost of JE was approximately $2776.6 per subject and significantly higher in adults than in younger subjects. Findings and Conclusions: JE patients suffered from severe neurological sequelae and high disease burden, resulting in a significant downstream burden for both the patients (especially adults) and the healthcare system.

Network pharmacology assessment of Qingkailing injection treatment of cholestatic hepatitis.

OBJECTIVE: To investigate the targets and mechanisms of action of Qingkailing injection (，QKL) in the treatment of cholestatic hepatitis. METHODS: A network pharmacology method was implemented using drug and disease databases to target QKL and cholestasis hepatitis, respectively. The functional protein association network STRING database was used to construct a protein-protein interaction network using R language and the Bioconductor toolkit. The org.Hs.eg.db and clusterProfiler packages were used for gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, which explored biological functions and pathways of potential targets. Targets were then visualized using Cytoscape 3.6.0 software. RESULTS: We screened 121 compounds in QKL and identified 112 targets for the treatment of cholestatic hepatitis. QKL played a role in the treatment of cholestatic hepatitis through 305 biology process terms, 15 cellular component and 29 molecular function terms. The mechanism of QKL action was mainly related to tumor necrosis factor, mitogen-activated protein kinase, and PI3K-Akt signaling pathways. CONCLUSION: The treatment of cholestatic hepatitis by QKL involved multiple targets, biological functions, and signaling pathways that are closely associated with the disease.

[Contamination Characteristics and Ecological Risk Assessment of Androgens, Glucocorticoids, and Progesterone in the Liusha Bay, South China Sea].

Steroid hormones have been continuously detected and well studied in freshwater bodies in recent years, although information regarding their contamination characteristics in seawater is rare. In this paper, samples were collected in Liusha Bay, South China Sea, and the contamination characteristics, as well as the spatial distribution of 33 steroid hormones, were studied by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The results showed that 7 steroid hormones occurred with concentrations ranging from 0.003 (medroxyprogesterone, MP) to 9.023 ng·L-1(dehydroprogesterone, DGT), and from 0.017 (androsta-1,4-diene-3,17-dione, ADD) to 9.281 ng·g-1 (4-androstene-3,17-dione, AED) in seawater and sediment samples, respectively. The concentrations of detected steroid hormones were higher during wet weather than during the dry weather, and higher in the aquaculture area compared to that in the non-aquaculture area. There were no significant differences in the spatial and temporal distribution of steroid hormones in sediment. Wastewater discharge and additives in aquaculture feeds were the main routes of steroid hormones entering the marine environment. The results of the ecological risk assessment indicated that the AED posed low risk to the marine environment, whereas other steroid hormones posed no risk. Correlation analysis indicated that the concentration distribution of steroid hormones was related to salinity, water temperature, particulate matter (SS), and chemical oxygen demand (COD) in the marine environment. The results of this study contribute to the understanding of the contamination characteristics of steroid hormones in the Liusha Bay area and provide a scientific basis for ecological risk assessment and control.

Occurrence, fate and risk assessment of androgens in ten wastewater treatment plants and receiving rivers of South China.

Androgens are one class of steroids that could cause endocrine disrupting effects in aquatic organisms. However, little information is available about androgens in wastewater treatment plants (WWTPs) with different treatment technologies. Here we investigated the occurrence, removal, and fate of fourteen natural and synthetic androgens in ten WWTPs of Guangdong province, south China. The results showed detection of ten androgens in the influents of the ten WWTPs, with concentrations up to 4650 ng/L (androsta-1,4-diene-3,17-dione). But only three androgens androsta-1,4-diene-3,17-dione, 4-androstene-3,17-dione and 17ß-boldenone were detected in the final effluents of the ten WWTPs, while six androgens androsta-1,4-diene-3,17-dione (N.D. to 43.0 ng/g), 4-androstene-3,17-dione (2.06-42.7 ng/g), epi-androsterone (N.D. to 506 ng/g), testosterone (0.29-4.24 ng/g), 17ß-boldenone (N.D. to 2.05 ng/g) and methyl testosterone (N.D. to 0.70 ng/g) were found in activated sludge. The aqueous phase removal rates for most androgens in the WWTPs exceeded 95% except for 4-androstene-3,17-dione with its removal rates varying between 79.5% and 100%. The removal of androgens in the WWTPs could be attributed mainly to biodegradation while removal by precipitation, volatilization, sludge absorption and oxidation was very limited. Eight androgens were also found in five receiving rivers. The risk quotients of some androgens (androsta-1,4-diene-3,17-dione, 4-androstene-3,17-dione, methyl testosterone, 17α-trenbolone) exceeded 1 in the receiving rivers, showing high risks to aquatic organisms. Further studies are needed to understand the origin of these high risk androgens and ecological effects.

[Analysis on reproductive health status and influencing factors of female workers of pharmaceutical industry in Gansu province].

OBJECTIVE: To understand the reproductive health status of female workers in pharmaceutical industry of Gansu Province, to explore influencing factors, and to propose some reference basis of intervening measures. METHODS: The cluster sampling method was used to study 1801 female workers from 16 pharmaceutical industries in 6 cities (Pingliang, Qingyang, Lanzhou, Dingxi, Zhangye and Jiuquan cities) of Gansu Province. The investigation was performed by interviewing and adopting questionnaires. RESULTS: There were the problems of labor and organization, which included the overtime work, continuous work, standing for long periods, rapid monotonous action assignments, the loading work and a variety of harmful factors in the working environment of the pharmaceutical industry in Gansu Province. There were many problems in the reproductive health status of female workers. The morbidities of abnormal menstruation and breast diseases in female workers were 43.25% and 20.43%. The order of high morbidities was hyperplasia of mammary glands (91.30%), breast adenofibroma (5.43%) and mastitis (2.99%). The order of morbidities for three reproductive system disease was adnexitis (21.57%), cervical erosion (20.06%) and vaginitis (11.09%). The rates of abnormal menstrual cycle, abnormal menstrual amount and cervical erosion increased with the length of service (P < 0.01). The taking breaks, long standing, loading work, exposure to harmful factors were related to abnormal menstruation (P < 0.05). The rapid repeat monotonous action was an important influencing factor for female reproductive system disease (OR = 1.255, 95%CI = 1.031 ∼ 1.528). CONCLUSION: There are relatively serious occupational hazards in the pharmaceutical industry of Gansu Province. The reproductive health status of female workers is not improved. Social public should pay attention to the protection for female workers.