The synthetic biology matures to promote the heterologous biosynthesis of the well-known drug paclitaxel that is one of the most important and active chemotherapeutic agents for the first-line clinical treatment of cancer. This review focuses on the construction and regulation of the biosynthetic pathway of paclitaxel intermediates in both Escherichia coli and Saccharomyces cerevisiae. In particular, the review also features the early efforts to design and overproduce taxadiene and the bottleneck of scale fermentation for producing the intermediates.

Objective To explore the rationality of correcting urinary iodine (UI) concentration by using urine specific gravity (U-SG).Methods Weighing method and refractometer method were used respectively to measure specific gravity of 10-30 g/L mass concentration of different inorganic salts (sodium chloride,sodium sulfate,ammonium biphosphate) and organic matters(urea,glucose,glycine) aqueous solution,and urine plus 10-30 g/L sodium chloride or urea.UI concentrations in urine samples of 27 pregnant women respectively were expressed by direct method,weighing method U-SG correction and refractometer method U-SG correction.One random urine sample was collected for six batches in different seasons from children aged 8-10 and pregnant women for determination of U-SG and UI concentration.UI concentration was determined by arsenic cerium catalytic spectrophotometry (WS/T 107-2006).Results ①Measured by weighing method,specific gravity of inorganic salt (sodium chloride,sodium sulfate,ammonium biphosphate) aqueous solution was significantly greater than that of organic matters (urea,glucose,glycine) aqueous solution which had the same mass concentration.The specific gravity of 10 g/L sodium chloride aqueous solution was 1.008,and that of 30 g/L urea solution was 1.006.②Measured by weighing method,10 g/L sodium chloride was added to 3 urine samples separately.Accordingly the increases of USG were 0.006,0.008 and 0.007,respectively.Otherwise,the increases of U-SG were 0.003,0.002 and 0.004,respectively,when adding 10 g/L urea.~he median results of UI concentrations in urine samples from 27 pregnant women were 106.4,165.2 and 211.8 μg/L,respectively,expressing obtained by direct method,weighing method USG correction and refractometer method U-SG correction.④The determination results of six batches urine collected from children aged 8-10 in different seasons,the median results of U-SG measured by refractometer method were 1.019 0-1.021 2,the median UI concentration results obtained by direct method and refractometer method U-SG correction were 134.5-181.7 μg/L and 157.7-190.4 μg/L.The determination results of six batches urine samples of pregnant women in different seasons,the median results of U-SG measured by refractometer method were 1.013 4 -1.017 1,the median UI concentration results obtained by direct method and refractometer method U-SG correction were 96.2-138.9 μg/L and 135.2-181.6 μg/L.Conclusions The change of sodium chloride concentration in urine is the most important reason for the change of U-SG.In China,the main source of UI is the intake of edible iodized salt.Iodized salt intakes directly affect the U-SG and UI concentration.If the U-SG is used to correct the UI concentration,there will be a phenomena that the lower intake of iodized salt the lower U-SG.So the UI concentration was falsely increased significantly after correction.Conversely higher intakes of iodized salt caused higher U-SG.The UI concentration was falsely reduced significantly after correction.Therefore,U-SG cannot be used to correct the UI concentration.

Objective To establish a method for determination of iodine in urine with no need for base urine match by inductively coupled plasma mass spectrometry (ICP-MS).Methods The diluent which contains 2.5 g/L N2H4·2HCl-1.0 g/L NH4C1-0.50％HC1-2.0％C2H5OH were used to eliminate the matrix interference in determination of iodine in urine by ICP-MS.The standard solutions and the urine samples were all diluted in a ratio of 19:1 (diluents:sample) before testing.The methodological evaluation of this new method was done through standard curve linearity,sample detection limit,precision and accuracy in determining urinary iodine.And the determine results were compared with the current urinary iodine arsenic cerium catalytic spectrophotometry standard method (WS/T 107.1-2016,hereinafter referred to as the standard method).Results The linear range of the calibration curve was 0-1 000 μ.g/L and the linear correlative coefficient was 0.999 9.The detection limit for urinary iodine was 0.4 μg/L (0.25 ml of urine was tested).Precision:The average coefficient of variation (CV)was 0.8％ with a range of 0.2％-1.7％ (n =6) when measuring 33 urine samples with iodine concentration of 26.5-854.4 μμg/L.Accuracy:The iodine standard of 40-400 μg/L was added for recovery test.The average recovery was 99.6％ with a range of 94.3％-103.4％ when measuring 24 urine samples with iodine concentration of 26.5-858.3 μg/L.The test results of 8 urinary iodine national standard materials with iodine concentration ranged from 64.5 to 883.0 μg/L were all within the given value range and the relative deviations were all below 3.0％ (n =12).No significant difference was found between the results of the 51 urine samples determined by the standard method (WS/T 107.1-2016) and the new method (t =0.836,P ＞ 0.05).Conclusions The new method to determine iodine in urine with no need for base urine match is successful established.This method has wide linear range,high sensitivity,good precision,accuracy and anti-interference ability,and is easy to be used and quickly to be analyzed of the test results,and is suitable for widely application in determining urinary iodine.

Community-acquired pneumonia(CAP) is one of the leading causes of death in children under 5 years of age.Early identification and clarification of its severity and appropriate therapeutic measures can improve survival, but there are limitations in the existing laboratory indices applied to diagnose CAP.Therefore, it is still necessary to find new and highly specific biomarkers that can identify the etiology and predict the severity of the disease before it worsens in children, and provides a basis for more effective therapeutic measures.Metabolomics provides a new way to search for biomarkers and pathogenesis through qualitative and quantitative analysis of metabolite changes in biological samples.This review summarized the latest research progress on metabolomics in childhood CAP, hoping to provide ideas for the early diagnosis and treatment of childhood CAP.

Objective To analyze genetic testing and prenatal diagnosis of two pedigrees with X-linked ichthyosis.Methods Karyotyping,bacterial artificial chromosomes-on-BeadsTM (BoBs),fluorescence in situ hybridization (FISH) and single nucleotide polymorphism array (SNP-array) were used to detect amniotic fluid and peripheral blood specimens of two pedigrees,one with and one without known family history of ichthyosis.Clinical data was collected and analyzed as well.Results (1) The pedigree without known family history:Prenatal BoBs showed that the XC1 probe of fetus Ⅳ-12 was from 0.36 to 0.50,suggesting the presence of microdeletion.SNP-array analysis of gravida Ⅲ-13 showed a 1.68 Mb copy number deletion at Xp22.31 and four missing Online Mendelian Inheritance in Man (OMIM) genes (HDHD1,STS,VCX and PNPLA4).Fetal SNP-array revealed a deletion of arr[hg19] Xp22.31 (6 455 151-8 135 644)× 0,indicating a maternally inherited one.FISH analysis verified the deletion in STS gene in fetus Ⅳ-12,whose karyotype was 46,XY.The gravida's female cousin (Ⅲ-21) and nephew (Ⅳ-14) also had STS gene deletion,which size was the same as that from the gravida and the fetus.Fetus (Ⅳ-12) was delivered at term by cesarean section with normal skin,but an extensive white scales appeared on the abdomen one week after birth and the symptom was aggravated when the weather was dry.The infant was followed up to eight months old and no other clinical symptoms were found.(2) The pedigree with known family history:SNP-array revealed that a 1.2 Mb copy number deletion at Xp22.31 and four missing OMIM genes (HDHD1,STS,VCX and PNPLA4) were detected in pregnant women (Ⅲ-21),proband (Ⅳ-16) and fetus (Ⅳ-17).FISH analysis of the fetus verified the deletion in STS gene.The karyotype of the fetus was 46,XY.Fetus Ⅳ-17 was delivered at term by cesarean section with normal skin,but white scales widely appeared on the abdomen ten days after birth.The infant was followed up to four months old and no other clinical symptoms were found.Conclusion Molecular genetic techniques such as BoBs,FISH and SNP array are used in combination in this study to provide genetic testing and prenatal diagnosis to two XLI pedigrees,which is helpful for clinical diagnosis and genetic counseling.

Objective:To summarize the clinical characteristics of children with Mycoplasma pneumoniae pneumonia(MPP) complicated with pleural effusion, and explore the effect of mixed adenovirus infection on children with MPP complicated with pleural effusion.Methods:The clinical data of children with MPP complicated with pleural effusion diagnosed in Children′s Medical Center at the First Affiliated Hospital of Hunan Normal University (Hunan Provincial People′s Hospital) from January 2013 to December 2019 were collected.MPP cases were divided into single infection group and mixed infection group according to whether mixing adenovirus infection.The clinical characteristics were compared between two groups.Results:A total of 180 children with MPP complicated with pleural effusion were included, the male to female ratio was 1.22∶1 (99/81), the age was 66.13 (44.35, 83.98) months, and the most common cases were children over 5 years old (55.56%). The length of hospitalization was 9.00 (7.00, 12.00) days.Fever (93.33%) and cough (98.33%) were the most common clinical manifestations, and mild increases in C-reactive protein, erythrocyte sedimentation rate and D-dimer were the most common laboratory results.Among included children, right pleural effusion was the most common (54.44%), bilateral pleural effusion accounted for 26.67%, and left pleural effusion accounted for 18.89%.Compared with single infection group, the mixed infection group had a longer hospital stay, a higher proportion of oxygen intake, a higher proportion of gamma globulin use, and a higher value of lactate dehydrogenase and aspartate aminotransferase.The results of multivariate Logistic regression analysis showed that compared with single infection group, although the mixed infection group had a higher proportion of gamma globulin use (36.54% vs.10.93%, P<0.05), the length of hospital stay, clinical manifestations, laboratory examination, chest CT and fiberoptic bronchoscopy showed no statistically significant difference between two groups. Conclusion:MPP complicated with pleural effusion is more common in children over 5 years old, especially in the right side.Mild increases of C-reactive protein, erythrocyte sedimentation rate, and D-dimer are more common.The clinical features of MPP complicated with pleural effusion are similar between mixed adenovirus infection group and single infection group.

Objective To explore the spatial-temporal characteristics of influenza epidemic in Hubei from 2009 to 2020, and make short-term prediction to provide reference for influenza prevention and control strategies. Methods Time series seasonal decomposition model and geographic spatial analysis method were used to analyze spatial-temporal evolution characteristics of influenza prevalence in Hubei during 2009-2020. LSTM neural network model was used to predict the monthly influenza incidence from 2020 to 2023. Results Influenza was mainly prevalent in the end of winter and the beginning of spring (December to March) were periods of high influenza incidence. In recent years, the influenza pandemic has shown an increasing trend. Influenza epidemic was characterized by significant spatial differentiation, with ^“A-shaped point-axis structure^” surrounding counties were more severe . The epidemic center of gravity experienced a spatial evolution process from west to east and from north to south. LSTM neural network model predicted that although the influenza incidence rate from January 2020 to December 2023 is lower than that in 2019, it is still at a high level, and shows a peak epidemic in winter and spring. Conclusion Influenza epidemic in Hubei is characterized by a high epidemic period in late winter and early spring, and the southeast of Hubei is the key epidemic area. It is suggested that publicity and prevention and control should be strengthened according to people, time and place, and key populations and areas should be encouraged to receive influenza vaccines in advance.

Objective To analyze the epidemiological characteristics of measles, predict the incidence trend of the disease, and provide reference for the development of measles prevention and elimination strategies. Methods Descriptive analysis, seasonal index method, clustering analysis and ARIMA model were used for data analysis and trend prediction. Results The average annual incidence of measles in 2005-2018 was 3.01/100,000. It was at a low level after 2009, and rebounded in 2018. The seasonal index of March-June was greater than 1, which was the month of high incidence. The incidence of men was higher than that of women. The 0-3 years old and 10-30 years old groups had a high incidence, and the population was mainly scattered children, students, and nursery children. The areas with high incidence were mainly northwestern and southeastern Hubei. ARIMA (0,1,0) (0,1,1) was the optimal model. The prediction analysis showed that the incidence rate in 2019 will be 1.26/100 000. Conclusion After the implementation of booster immunization, the measles epidemic in Hubei Province was at a low level, but it fluctuated greatly in recent years and is currently showing a rising trend. The incidence was high in spring. Cases were ^"biphasic shift^" in groups 0-3 years old and 10-30 years old. Occupational distribution was consistent with the characteristics of high incidence in the age group. The mountain areas with poor sanitary conditions and economic backwardness, and regions with large population bases and high floating populations had a high incidence. The ARIMA model had good applicability in predicting the trend of measles incidence, which shows measles will continue to rise in 2019.

Objective To explore spatial clustering of mumps in Hubei Province during 2010-2020, and to provide evidence for mumps prevention and control. Methods The surveillance data of mumps during 2010-2020 in Hubei Province was obtained from the national infectious diseases reporting information system. Trend surface analysis and spatial autocorrelation analysis of mumps incidences at county/district levels were performed using ArcGIS10.5 software. Results Mumps incidence rates in Hubei Province during 2010-2018 ranged from 8.70 per 100 000 to 44.99 per 100 000. The trend surface analysis showed that mumps incidences gradually decreased from west to east, and was low in the middle and high at the north-south direction. Global spatial autocorrelation showed that there were positive spatial correlations in every year except 2012 and 2014 (Morans I> 0, P <0.05). Local autocorrelation analysis showed that the hotspots of mumps incidences varied every year from 2010 to 2020. Conclusions According to the spatial analysis, mumps incidences had obvious spatial clustering in Hubei Province. The hotspots were mainly concentrated in the northwestern region of Hubei, but the hot spots also extended to the urban areas of eastern, central and northern Hubei. It is necessary to take appropriate prevention and control measures in the high-incidence areas.

Objective To analyze the epidemiological characteristics and incidence trend of gonorrhea in Hubei Province, and to provide reference for scientific formulation of prevention and control measures. Methods Based on the surveillance data of gonorrhea from 2010 to 2021, three-way distribution and ARIMA model were used for data analysis and incidence prediction. Results From 2010 to 2021, the reported incidence rate fluctuated between 3.01/100 000-7.07/100 000, and the average annual reported incidence rate was 4.62/100 000. The reported incidence rate showed the characteristics of ^“first fall and then rise, and then fall and rise again^”, and the peak incidence period was from June to December. The male to female ratio of reported cases was 5.78:1, and the number of reported cases in the age group of 20-39 years old accounted for 62.43% of the total number of cases. The reported cases were mainly housework and unemployed, farmers, and unknown occupation. The severity of the regional incidence was divided into 5 categories by the Q-type clustering, and the most serious category included Shennongjia Forest District, Huangshi City, and Wuhan City. The ARIMA model predicted the incidence rate to be in good agreement with the actual incidence rate, with a predicted number of 3 343 cases in 2022. Conclusion At present, gonorrhea in Hubei Province is still at a high prevalence level. There are obvious differences in gender, age, occupation, and regional distribution. The ARIMA model is suitable for predicting the incidence of gonorrhea, and it is predicted that the incidence will increase slightly in 2022.