Objective To optimize the culture and fermentation conditions of the Penicillium aurantiocandidum Z12 strain, a fungal strain with molluscicidal actions against Oncomelania hupensis, so as to provide the basis for the research and development of molluscicidal active substances from the P. aurantiocandidum Z12 strain and its fermentation broth and large-scale fermentation. Methods The carbon source, nitrogen source and mineral salts were identified in the optimal culture medium for the P. aurantiocandidum Z12 strain with a single-factor experiment to determine the best fermentation condition for the P. aurantiocandidum Z12 strain. Factors that significantly affected the growth of the P. aurantiocandidum Z12 strain were identified using the Plackett-Burman design, and the best range of each factor was determined using the steepest climb test. Response surface analyses of temperature, pH value, seeding amount and liquid-filling quantity were performed using the Box-Behnken design to create a regression model for fermentation of the P. aurantiocandidum Z12 strain to identify the optimal culture medium. Results Single-factor experiment preliminarily identified the best culture medium and conditions for the P. aurantiocandidum Z12 strain as follows: sucrose as the carbon source at approximately 20 g/L, tryptone as the nitrogen source at approximately 5 g/L, K₂HPO₄ as the mineral salt at approximately 5 g/L, initial pH at approximately 8, temperature at approximately 28 °C, seeding amount at approximately 6%, and liquid-filling quantity at approximately 50 mL/100 mL. Plackett-Burman design showed that factors that significantly affected the growth of the P. aurantiocandidum Z12 strain included temperature (t = −5.28, P < 0.05), seeding amount (t = 5.22, P < 0.05), pH (t = −4.30, P < 0.05) and liquid-filling quantity (t = −4.39, P < 0.05). Steepest climb test showed the highest mycelial growth at pH of 7.5, seeding amount of 8%, and liquid-filling quantity of 40 mL/100 mL, and this condition was selected as the central point of response surface analysis for the subsequent optimization of fermentation conditions. Response surface analyses using the Box-Behnken design showed that the optimal conditions for fermentation of the P. aurantiocandidum Z12 strain included sucrose at 15 g/L, tryptone at 5 g/L, K₂HPO₄ at 5 g/L, temperature at 28.2 °C, pH at 7.5, seeding amount at 10%, and liquid-filling quantity at 35.8 mL/100.0 mL, resulting in 0.132 g yield of the P. aurantiocandidum Z12 strain. Conclusion The optimal culture condition for the P. aurantiocandidum Z12 strain has been identified, and the optimized culture medium and fermentation condition may effectively improve the fermentation yield of the P. aurantiocandidum Z12 strain.

Objective:To explore the spatial and temporal distribution patterns of emerging snail-infested sites in different environmental types in Yunnan Province.Methods:The data of snail-infested sites in Yunnan Province from 1950 to 2014 (from Yunnan Institute for Endemic Diseases Control and Prevention), were collected and sorted out, a spatial and temporal database on the distribution of emerging snail-infested sites were established, and the changes in the spatial and temporal distribution of emerging snail-infested sites in different environments types (ditches, tangerines, paddy fields, dry land, beaches and other environments) were studied by using spatial autocorrelation analysis and scanning statistics analysis.Results:From 1950 to 2014, the annual number of emerging snail-infested sites in Yunnan Province reached a peak (1 730) in 1955 and then showed a fluctuating downward trend. From 1993 to 2014, the number of emerging snail-infested sites remained below 100, and increased to 160 and 131, respectively, in 2004 and 2013. The longest mean duration of 43.85 years was recorded for the beaches environment for emerging snail-infested sites, followed by the paddy fields environment with a mean duration of 37.01 years, and the shortest mean duration of 20.44 years for the tangerines environment. Spatial autocorrelation analysis showed that there was a positive spatial correlation between the duration of emerging snail-infested sites of different environmental types (global Moran's I ranged from 0.43 to 0.64, P < 0.05). Scanning statistics analysis showed that emerging snail-infested sites of different environmental types had spatial and temporal aggregation ( P < 0.001), with 3- 6 clusters of statistically significant aggregation detected respectively. Conclusion:The emerging snail-infested sites in different environments types in Yunnan Province have spatial and temporal aggregation, and it is necessary to strengthen monitoring and prevention and control of the aggregation areas of different environment types to prevent further spread of the snail.

ObjectiveTo explore the positive predictive value （PPV） and false positive （FP） number of screening test in mass testing when the prevalence of infection is low. MethodsAssuming a population of 20 million with the prevalence of disease infection ranging from 0.1% to 5.0%， PPV， true positive （TP） and FP numbers were calculated under different scenarios of combination of sensitivity （99.0%， 99.5%， and 100.0%） with specificity （97.0%， 97.5%， 98.0%， 98.5%， 99.0%， 99.5%， and 99.9%）. ResultsFor low infection prevalence （≤5.0%）， specificity has a greater impact on PPV than sensitivity； with the decrease of infection prevalence， the increase in PPV elevates when the specificity increases. When the infection prevalence is >1.0%， the closer the specificity is to 99.9%， the closer the PPV is to 100.0%. However， when the infection prevalence is <1.0%， the maximum PPV is only about 90.0%. When the infection rate is 0.1%， a screening test with more than 99.0% sensitivity could detect about 20 thousand TP cases in a population of 20 million. Additionally， the FP and PPV are estimated to be 599 thousand and 3.2% if the specificity is 97.0%， and 20 thousand and 50.0% if the specificity is 99.9%. When the infection rate is 1.0%， a screening test with ≥99.0% sensitivity and ≥97.0% specificity could detect about 0.198‒0.200 million TP cases； and the number of FP decreases from 594 thousand to 20 thousand when the specificity increases from 97.0% to 99.9%. When the infection rate is 5.0%， a screening test with ≥99.0% sensitivity and ≥97.0% specificity could detect about 0.99‒1.00 million TP cases； and the number of FP decreases from 570 thousand to 19 thousand when the specificity increases from 97.0% to 99.9%. When the infection prevalence is ≤5.0% in a total population of 20 million， there are about 20，000 FP cases even if the sensitivity and specificity reach the maximum values of 100.0% and 99.9%， respectively. ConclusionWhen the population is large and the infection prevalence is low， in addition to improving the specificity of the screening test in mass testing， the problem of a large number of false positives cannot be ignored.

ObjectiveTo explore the changing trend of negative predictive value and number of false negatives in screening tests under the condition of low infection rate of infectious diseases. MethodsAssuming that the population is 20 million， to calculate the negative predictive value， numbers of true negatives and false negatives of the combination of different sensitivity （75.0%， 80.0%， 85.0%， 90.0%， 95.0%， 99.0%） and specificity （90.0%， 95.0%， 99.0%， 99.9%） when the disease infection rate of the population is 0.10%， 1.0% and 5.0% respectively. ResultsWhen the population infection rate is 0.1%， with the screening test sensitivity ≥75.0% and specificity ≥90.0%， the number of true negatives in 20 million people is about 17.98‒19.96 million. When the sensitivity is 75.0%， the negative predictive value is 99.972%‒99.975%， and the number of false negatives is 5 000； When the sensitivity increases to 99.0%， the negative predictive value is 99.999%， and the number of false negatives decreases to 200. When the population infection rate is 1.0%， a screening test with sensitivity ≥75.0% and specificity ≥90.0% can detect about 17.82‒19.78 million true negatives in 20 million population. When the sensitivity is 75.0%， the negative predictive value is 99.720%‒99.748%， and the number of false negatives is 50 000； When the sensitivity increases to 99.0%， the negative predictive value increases to 99.990%， and the number of false negatives decreases to 2 000. When the population infection rate is 5.0%， with sensitivity ≥75.0% and specificity ≥90.0%， the number of true negatives in 20 million people is about 17.10‒18.98 million； when the sensitivity is 75.0%， the negative predictive value is 98.559%‒98.700%， and the number of false negatives can reach 250 000； When the sensitivity is 99.0%， the negative predictive value increases to 99.942%‒99.947%， and the number of false negatives decreases to 10 000. The lower the infection rate of the population， the fewer false negatives will appear in the screening. ConclusionThe number of false negatives in large-scale screenings increases exponentially with the increase of infection rate. Screenings should be carried out as early as possible in a pandemic of infectious diseases， so as to control the spread of the pandemic as soon as possible.

Poststroke recrudescence (PSR) is a reappear phenomenon in the neurological symptoms of chronic stroke in the setting of toxic metabolic factors. Infection, hyponatremia, and use of benzodiazepine are important precipitants. In this paper, the risk factors, pathogenesis, clinical characteristics, diagnosis and treatment methods of PSR are reviewed to enhance the understanding of the disease among clinicians.

Objective:To analyze the symptom characteristics of Coronavirus Disease 2019(COVID-19) and to improve its prevention by using big data.Methods:Using Baidu Index Platform (http://index.baidu.com) and the website of Chinese Center for Disease Control and Prevention as data resources, we obtained the search volume (SV) of keywords for symptoms associated with COVID-19 from January 1 to February 20 in each year from 2017 to 2020, in Hubei province and other top 10 impacted provinces in China and the epidemic data. Data of 2020 were compared with the previous three years. Data of Hubei province were compared with confirmed cases. The differences and characteristics of the SV of COVID-19-related symptoms, and the correlation between the SV of COVID-19 and new confirmed or suspected cases were analyzed and the hysteresis effects were discussed. R3.6.2 software was used to analyze the data.Results:Compared the data from January 1 to February 20, 2020, with the SV for the same period of previous three years, Hubei′s SV for cough, fever, diarrhea, chest tightness, dyspnea and other symptoms were significantly increased. The total SV of lower respiratory symptoms was significantly higher than that of upper respiratory symptoms ( P<0.001). The SV of COVID-19 in Hubei province was significantly correlated with new confirmed or suspected cases ( rconfirmed=0.723, rsuspected=0.863, all P<0.001). The results of the distributed lag model suggested that the patients who retrieved relevant symptoms on the internet may begin to see a doctor in 2-3 days later and be diagnosed in 3-4 days later. Conclusions:The total SV of lower respiratory symptoms is higher than that of upper respiratory symptoms, and the SV of diarrhea also increases significantly. It warns us to pay attention to not only the symptoms of lower respiratory tract, but also the gastrointestinal symptoms, especially diarrhea in patients with COVID-19. There is a relationship between internet retrieval behavior and the number of new confirmed or suspected cases. Big data have a certain role in the early warning of infectious diseases.

Objective To study epidemic of schistosomiasis in the Qiandao Lake reservoir area,and to provide a reference for prevention and control of schistosomiasis in the construction of large water conservancy projects in the epidemic area of schistosomiasis.Methods The data over the years of snail condition and monitoring of schistosomiasis before and after building the dam,and water conservancy project reconstruction related information were collected.Based on the survey results of the river channel,the lake beach and the dissipation zone in the reservoir area,the influence of Xin'an River water conservancy project on epidemic of schistosomiasis in the Qiandao Lake reservoir area was analyzed,and the epidemic factors of the schistosomiasis in the Three Gorges reservoir were compared and analyzed.Results Before the dam was built,an area of 38 144 000 m2 was examined but Oncomelania was undetected.The Qiandao Lake reservoir area belonged to a non epidemic area of schistosomiasis.After the dam was built,557 cases of schistosomiasis were found in 6 232 immigrants during 1962-1965,resulting in an imported epidemic.In 1970-1980,an area of 379 654 m2 in which Oncomelania was found was examined and snails were mainly distributed in some rice fields and ditches in the end of the reservoir.949 cases of local schistosomiasis were found in the snails.The condition and condition of the snail are gradually controlled through several decades of comprehensive prevention and control.Compared with the epidemic factors of schistosomiasis in Qiandao Lake and the Three Gorges reservoir,the environment of elevation beach and ecologically fragile fluctuation zone coexist in the two reservoir areas.Conclusion From the long-term longitudinal monitoring data of the Qiandao Lake reservoir area and the epidemic regularity of schistosomiasis and the comparison with the ecology of the Three Gorges reservoir,it is concluded that the two reservoir areas will not cause a large range of schistosomiasis epidemic in general,but it does not exclude the possibility of the breeding of the inputting Oncomelania.

OBJECTIVE:To explore the dynamic upwarp state correction coefficient of cyclosporine blood concentration determined by EMIT. METHODS:The dynamic upwarp state of cyclosporine concentration was determined by EMIT. The cyclosporine calibration reagents with concentration of 100 ng/mL was used as the sample to be measured,the 58th and 101st test results were selected to simulate the dynamic upwarp state related coefficients,and the 1st,20th,45th,77th,106th,115th test results were corrected by above coefficients. The difference of correction quality concentration with real quality concentration was investigated. RESULTS:The dynamic upwarp state coefficient [k=(1+0.001 235×n0.419 5)n] and dynamic upwarp state correction coefficient {k′=1/[(1+0.001 235×n0.419 5)n} were obtained. After determination results were corrected,relative error of corrected quality concentration with real quality concentration was within ± 4%.CONCLUSIONS:The obtained dynamic upwarp state correction coefficient can be used for dynamic calibration of cyclosporine quality control concentration,which contribute to correct determination of blood concentration of cyclosporine.

Objective To explore the spatial-temporal characteristics and changing regularities of Schistosoma japonicum in-fections among human from 2004 to 2011. Methods The township level spatial databases of schistosomiasis in Hunan Province from 2004 to 2011 were established,and the related spatial analysis was performed by SPSS 17.0,ArcGIS 10.1 and SaTScan 7.03. Results The schistosome infection rate among human in Hunan Province sharply decreased from 3.0％in 2004 to 0.8％in 2011. However,the rate among residents in parts of some townships in 2011 was still hovering at a higher level (P90=2.12％),and the higher rate was distributed along the Oncomelania hupensis snail ridden areas outside embankment. The auto-correlation analysis showed that the global Moran's I for schistosome infection rate among human was 0.34 to 0.53 from 2004 to 2011,and was higher than the expected value(Z>8.71,P<0.05). The local G statistics indicated that the positive hotspot high-high clustering areas were mainly near the coast of Dongting Lake from 2004 to 2011,and the number of townships with schistosomiasis endemic in the clustering areas reached 30 to 70. The spatial scan analysis showed that the number of townships in the clustering areas ran up to 145 to 183 from 2004 to 2011. Conclusions The schistosome infection rate among human de-creased significantly in Hunan Province from 2004 to 2011. However,the rate in parts of some townships still remains at a com-paratively high level,and there are positive spatial correlation and spatial agglomerations in the schistosome infection rate among human,suggesting that the prevention and control work on schistosomiasis in these areas should be strengthened in the fu-ture.

s] Objective To evaluate the effect of comprehensive schistosomiasis control measures with focus on total removal of cattle and sheep in Junshan District,Yueyang City. Methods The retrospective review and field survey were implemented in the pilot villages in Junshan District. The data of Schistosoma japonicum infection status of human,cattle,sheep and Oncome-lania hupensis snails,and density of snails were gathered and modeled in the period of 2006 to 2016. Results The prevalence of schistosome infection in residents in the pilot villages decreased from 3.44％ in 2006 to 0.59％ in 2012(F = 14.501,P =0.013). After removal of all the cattle and sheep in 2013,the prevalence of schistosome infection in the residents decreased to zero in 2016(F=14.148,P=0.033). The density of living snails decreased from 0.8833/0.1 m2 in 2006 to 0.3088/0.1 m2 in 2012(F=76.250,P=0.005). Conclusion The comprehensive schistosomiasis control strategy with focus on cattle and sheep removal is remarkably effective.