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Tumor microenvironment (TME) is composed of abnormal tumor vasculature, extracellular matrix components, endothelial cells, pericytes, tumor associated fibroblasts, smooth muscle cells and immune cells, which is characterized by hypoxia, acidosis and high interstitial fluid pressure. Hypoxia and acidosis within the TME trigger an adjustment of the extracellular matrix (ECM), a response from neighbor stromal cells (e.g., fibroblasts) and immune cells (lymphocytes and macrophages), inducing tumor growth, angiogenesis, and ultimately, resulting in metastasis. What's more, the components of TME including abnormal tumor vasculature, rich composition of the ECM, and abundant stroma cells impair tumoral distribution and penetration of the drugs. At the same time, this stromal microenvironment plays a vital role in creating an immunosuppressive environment.Over the past years, more and more researches focus on targeting and remolding TME to improve therapeutic effects against tumors. Herein, we reviewed current strategies developed to target and remodel TME, including modulating tumor hypoxia, tumor vasculature, tumor associated fibroblasts, extracellular matrix components, tumor associated macrophage phenotypes and dendritic cells. Also, potential problems and future directions are pointed out in this review.
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Objective To investigate the health-seeking behaviors of imported malaria cases after returning to China, and to investigate the factors affecting the time to initial diagnosis, so as to provide the scientific evidence for early identification of imported malaria cases and prevention of severe cases development and secondary transmission. Methods The individual demographic features, and the disease onset and the time to initial diagnosis of imported malaria cases in Jiangsu Province in 2019 were captured from the National Notifiable Disease Report System and the Information Management System for Parasitic Disease Control in China. The characteristics of health-seeking behaviors and epidemiological features of imported malaria cases were descriptively analyzed, and the factors affecting the time to initial diagnosis of imported malaria cases after returning to China were identified using multivariate logistic regression analysis. Results A total of 244 imported malaria cases were reported in Jiangsu Province in 2019, and the time to initial diagnosis of the cases were 1-12 days, with mean time of (1.53 ± 1.65) days, with median time of one day. The highest number of malaria cases seeking healthcare services were found on the day of developing primary symptoms (76 cases, 31.1%), followed by on the second day (68 cases, 27.9%), on the third day (46 cases, 18.9%), and 54 cases (22.1%) received initial diagnosis 3 days following presence of primary symptoms, including 3 cases with initial diagnosis at more than one week. High proportions of imported malaria cases with a delay in the time to initial diagnosis were seen in migrant workers who returned to China in January (14 cases, 5.7%) and December (13 cases, 5.3%) and those aged between 41 and 50 years (32 cases, 13.1%). Multivariate logistic regression analysis showed relative short time to initial diagnosis among imported malaria cases returning to China on March [odds ratio (OR) = 0.16, P = 0.03, 95% confidence interval (CI): (0.03, 0.85)] and those with a history of overseas malaria parasite infections [OR = 0.36, P = 0.001, 95% CI: (0.19, 0.67)]. Conclusions Timely health-seeking behaviors should be improved among imported malaria cases in Jiangsu Province, patients with a history of overseas malaria infections require faster health-seeking activities.
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Objective To investigate the distribution and density of Culex mosquito populations and the resistance of Culex pipiens pallens to insecticides in Jiangsu Province in 2018 and 2019. Methods During the period from June to October in 2018 and 2019, six counties (districts, cities) were sampled in southern, northern and central Jiangsu Province as surveillance sites. The density of Culex mosquitoes was measured overnight using the light trapping technique. In addition, Culex pipiens pallens mosquitoes were collected from Hai’an of Nantong City and Yandu District of Yancheng City, central Jiangsu Province, and the sensitivity of female first filial generations to dichlorodiphenyltrichloroethane (DDT), malation, proposur, beta cypermethrin and deltamethrin was tested using the standard WHO insecticide susceptibility test assay. Results A total of 104 423 Culex mosquitoes were captured in six surveillance sites of Jiangsu Province in 2018 and 2019, and Culex quinquefasciatus (49.11%), Culex pipiens pallens (28.38%), and Culex tritaeniorhynchus (21.04%) were predominant species. The density of Culex mosquitoes started to increase since early June, peaked in July and tended to be low in late October. Culex pipiens pallens mosquitoes captured from Hai’an was susceptible to malation, while those from Yandu District were moderately resistant to malation. Culex pipiens pallens mosquitoes from both Yandu and Hai’an were moderately resistant to proposur, and were resistant to DDT, beta cypermethrin and deltamethrin. Conclusions Culex quinquefasciatus, Culex pipiens pallens and Culex tritaeniorhynchus are predominant Culex species in Jiangsu Province. Culex pipiens pallens is resistant to DT, beta cypermethrin and deltamethrin in central Jiangsu Province.
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Objective To analyze the epidemiological characteristics of imported cases with Plasmodium ovale infections in Jiangsu Province from 2012 to 2020, so as to provide insights into the development of the imported malaria control strategy in the province. Methods All data pertaining to cases with definitive diagnosis of P. ovale malaria in Jiangsu Province from 2012 to 2020 were captured from the National Notifiable Disease Report System and the Information Management System for Parasitic Disease Control in China, including the date of going abroad and returning to China, time of malaria infections overseas, date of malaria onset, initial diagnosis and definitive diagnosis. All data pertaining to epidemic status were descriptively analyzed. Results A total of 347 cases of P. ovale malaria were reported in Jiangsu Province from 2012 to 2020, with the highest number seen in 2015 (71 cases). All cases were laboratory-confirmed overseas imported malaria cases, accounting for 14.32% of all reported malaria cases in Jiangsu Province during the period from 2012 to 2020. The 5 cities with the highest number of imported P. ovale malaria cases included Lianyungang City (53 cases, 15.27%), Nantong City (44 cases, 12.68%), Huai’an (44 cases, 12.68%), Taizhou City (44 cases, 12.68%) and Yangzhou City (36 cases, 10.37%). The highest number of imported P. ovale malaria cases was reported in October (39 cases, 11.24%), and the lowest number was seen in December (21 cases, 6.05%). P. ovale infections mainly occurred in were Equatorial Guinea (97 cases, 37.95%), Angola (60 cases, 17.29%) and Nigeria (40 cases, 11.53%). The median duration between returning to China and malaria onset was 64 (144) days, and 7.49% (26/347) of all cases developed malaria one year after returning to China. The initial diagnosis of P. ovale malaria was mainly made at county-level medical institutions (117 cases, 33.72%), and the definitive diagnosis was mainly made at city-level medical institutions (122 cases, 35.16%). The correct rate of initial diagnosis of P. ovale malaria increased from 0 in 2012 to 78.26% in 2020, appearing a tendency towards a rise year by year (χ2 = 50.90, P < 0.01). Conclusions Imported P. ovale malaria cases were reported in Jiangsu Province each year from 2012 to 2020, and P. ovale infections predominantly occurred in Africa. Initial and definitive diagnoses of P. ovale malaria were mainly made at city- and county-level medical institutions. Training on the detection ability of malaria parasites is recommended among grassroots microscopists to improve the diagnostic ability of P. ovale malaria, and consolidate the achievements of malaria elimination in Jiangsu Province.
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Objective To analyze the epidemic situation of malaria in Jiangsu Province in 2019, so as to provide the scientific basis for the development of the strategy for the prevention of re-introduction of imported malaria. Methods The malaria case report information, epidemiological case investigation information, epidemic foci investigation and management report in Jiangsu Province in 2019 were collected, and all epidemiological data were descriptively analyzed. Results A total of 244 malaria cases were reported in Jiangsu Province in 2019, and all cases were laboratory-confirmed overseas imported cases, including 4 cases with vivax malaria, 206 cases with falciparum malaria, 12 cases with malariae malaria and 22 cases with ovale malaria. In 2019, there were 12 malaria cases progressing into severe cases in Jiangsu Province, with one death. Nanjing, Nantong, Lianyungang, Taizhou and Changzhou cities contributed the largest number of malaria cases in 2019, with the number of malaria cases accounting for 59.84% of total cases in Jiangsu Province. The infections occurred in Papua New Guinea (2 cases), Pakistan (1 case) and 27 African countries (241 cases), including Angola, the Democratic Republic of the Congo, Nigeria, Equatorial Guinea, Cote d'Ivoire and so on. There were 77 cases (31.55%) with a visit to doctor on the day of onset, and 146 cases (59.84%) within 1 to 3 days after onset. In addition, there were 149 cases (61.06%) with definitive diagnosis at the first visit and 77 cases (31.55%) diagnosed within 1 to 3 days after the visit, and the mean duration from the visit to definitive diagnosis was (0.80 ± 1.59) d, which significantly shortened as compared to that (1.34 d ± 2.59 d) in 2018 (U = 2.53, P < 0.05). Conclusions Intensifying the surveillance and management of imported malaria and improving the diagnostic capability of imported malaria and the treatment of severe malaria cases are required to consolidate the achievements of malaria elimination in Jiangsu Province.
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Objective To analyze the epidemic situation of malaria in Jiangsu Province in 2018, so as to provide scientific evidence for formulating post-elimination malaria surveillance schemes and technical measures in Jiangsu Province. Methods The malaria case report cards, epidemiological individual investigation forms of malaria cases and foci data were collected from Jiangsu Province in 2018, and the epidemic situation of malaria was descriptively analyzed. Results A total of 243 malaria cases were reported in Jiangsu Province in 2018, which increased by 1.67% in relative to in 2017 (239 cases), and these cases included 171 cases with falciparum malaria, 14 cases with vivax malaria, 15 cases with quartan malaria, 42 cases with ovale malaria and a case with mixed infection of P. vivax and P. ovale. All cases were overseas imported, and no local secondary cases were found. The malaria cases were predominantly workers (76.54%). Nantong City (48 cases), Yangzhou City (33 cases) and Taizhou City (22 cases) were the most 3 cities with the largest number of malaria cases across Jiangsu Province. The malaria infections predominantly occurred in African areas (96.30%), and the other 9 cases had infections in Asia (8 cases) and Central America (1 case). There were 125 cases (51.44%) and 91 cases (37.45%) with definitive diagnosis at the day of admission and within 1 to 3 days post-admission, respectively. The percentages of definitive diagnosis at initial diagnosis were 48.27%, 88.76% and 97.30% at township-, county- and city-level medical institutions, respectively, and the percentage of definitive diagnosis at initial diagnosis was significantly lower in township-level medical institutions than in county- (χ2 = 21.47, P < 0.01) and city-level medical institutions (χ2 = 32.86, P < 0.01). Conclusions There are no local malaria cases in Jiangsu Province; however, the number of overseas imported malaria cases remains high in China. In the future, improving the post-elimination malaria surveillance system, enhancing the awareness of malaria prevention and control knowledge among high-risk populations, increasing the diagnostic capability of malaria in medical institutions, and improving the management of imported malaria cases should be performed to consolidate the achievements of malaria elimination.
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Objective To analyze the epidemic situation of malaria in Jiangsu Province in 2018, so as to provide scientific evidence for formulating post-elimination malaria surveillance schemes and technical measures in Jiangsu Province. Methods The malaria case report cards, epidemiological individual investigation forms of malaria cases and foci data were collected from Jiangsu Province in 2018, and the epidemic situation of malaria was descriptively analyzed. Results A total of 243 malaria cases were reported in Jiangsu Province in 2018, which increased by 1.67% in relative to in 2017 (239 cases), and these cases included 171 cases with falciparum malaria, 14 cases with vivax malaria, 15 cases with quartan malaria, 42 cases with ovale malaria and a case with mixed infection of P. vivax and P. ovale. All cases were overseas imported, and no local secondary cases were found. The malaria cases were predominantly workers (76.54%). Nantong City (48 cases), Yangzhou City (33 cases) and Taizhou City (22 cases) were the most 3 cities with the largest number of malaria cases across Jiangsu Province. The malaria infections predominantly occurred in African areas (96.30%), and the other 9 cases had infections in Asia (8 cases) and Central America (1 case). There were 125 cases (51.44%) and 91 cases (37.45%) with definitive diagnosis at the day of admission and within 1 to 3 days post-admission, respectively. The percentages of definitive diagnosis at initial diagnosis were 48.27%, 88.76% and 97.30% at township-, county- and city-level medical institutions, respectively, and the percentage of definitive diagnosis at initial diagnosis was significantly lower in township-level medical institutions than in county- (χ2 = 21.47, P < 0.01) and city-level medical institutions (χ2 = 32.86, P < 0.01). Conclusions There are no local malaria cases in Jiangsu Province; however, the number of overseas imported malaria cases remains high in China. In the future, improving the post-elimination malaria surveillance system, enhancing the awareness of malaria prevention and control knowledge among high-risk populations, increasing the diagnostic capability of malaria in medical institutions, and improving the management of imported malaria cases should be performed to consolidate the achievements of malaria elimination.
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Objective: Cornus officinalis is a commonly used medicinal material in our country. In the study, the CobHLH7 was cloned and analyzed, which might be closely related to the iridoid glycosides synthesis, based on the transcriptome sequencing of Cornus officinalis fruits. Methods The special primers were designed from the both sides of open reading frame of unigene c15204_g1. The total RNA was extracted and reversed transcribed into cDNA. The transcription factor CobHLH7 was cloned through RT-PCR method, and the pMD19-T cloning vector were used for sequencing. A series of bioinformatics analysis of CobHLH7 was performed by software Protparatam, ProtScale, and SOPMA etc. Results The cDNA of CobHLH7 gene was 941bp in length, encoding 266 amino acids with a molecular weight of 29 220 and isoelectric point of 6.32. The analysis of bioinformatics through SOPMA showed that the protein was a neutral unstable protein. Its advanced structure mainly was alpha helix and random coil, and the content of beta turn and extended strand were less. Multiple sequence alignments and phylogenetic trees showed that CobHLH7 protein has high homology with ILR3 of Solanum tuberosum, ILR3-like of model organism Nicotiana attenuate. Conclusion For the first time, the CobHLH7 cDNA sequence was cloned and analyzed successfully from C. officinalis, which would lay the foundation for studying its biological functions deeply.
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To analyze the vector surveillance results during the stage of malaria elimination, so as to provide the evidence for assessing the local transmission risk of imported malaria and carrying out the surveillance work after malaria elimination in Jiangsu Province.From 2011 to 2017, the mosquito population was monitored and human biting rates were calculated by the half overnight human baiting trapping method and overnight lamp trapping method in 7 surveillance sites from June to October. The insecticide resistance level was tested by the force contact method recommended by WHO.A total of 5 106 Anopheles mosquitoes were captured by the half over-night human baiting trapping method in the 7 sites from 2011 to 2017, and all the mosquitoes were identified as Anopheles sinensis. The annual human biting rates were 1.075, 0.786, 1.057, 0.787, 0.790, 1.797 and 1.185 mosquitoes/ (human·hour), respectively. Totally 28 186 Anopheles mosquitoes were caught by the overnight lamp trapping method, and all the mosquitoes were An. sinensis. The densities of Anopheles mosquitoes were 57.950, 50.932, 14.800, 4.405, 58.070, 72.406, and 17.145 mosquitoes/ (night·lamp), respectively. In 2012, the resistance indexes of An. sinensis to deltamethrin, DDT and malathion were at R level in Jiangsu Province.The major vector is An. sinensis and no An. anthropophagus is found in Jiangsu Province. An. sinensis has a high level of resistance to deltamethrin, DDT and malathion.
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To evaluate the implementation effect of the optimization strategy for the use and management of malaria rapid diagnostic testing (RDT) technology in Jiangsu Province, so as to provide the empirical evidence and suggestions for promoting the standardized use of RDT technology.Questionnaire surveys of primary-level health professionals’ RDT-related knowledge, attitude, and practice (KAP) and work satisfaction were conducted in 4 pilot cities in Jiangsu Province before and after the intervention.After the implementation of the intervention, 13.9% of surveyed laboratory technicians, 21.9% of surveyed clinicians and 4.1% of surveyed staff of the centers for disease control and prevention (CDCs) had significant improvements in RDT-related knowledge. About 10.9% of the surveyed laboratory technicians and 25.6% of the surveyed CDC staff improved their attitudes toward RDT technology. About 38.4% of the surveyed laboratory technicians and 10.0% of the surveyed clinicians improved the standardized use of RDT technology. All types of primary-level health professionals had high evaluation in the satisfaction and effectiveness of the optimization strategy. However, the evaluation of the surveyed clinicians was slightly lower than that of the laboratory technicians and CDC staff.The optimization strategy in this project can effectively improve the knowledge, attitude and behavior of all types of primary-level health professionals and help to promote the standardized use of RDT technology.
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To understand the quality of production of blood slides and laboratory personnel’s ability to microscopically examine Plasmodium at Jiangsu Province clinic inspection stations at all levels, so as to provide the evidence for the construction of malaria diagnostic laboratories and the evaluation of malaria elimination effect.After the reexamination of the negative blood slides of the examination stations of the malaria center in each county (district), the negative blood slides of the outpatient inspection station in the district and all the positive blood slides of the direct report of the network from 2011 to 2017, the staining and cleanliness of the blood smears, microscopic examination results and the coincidence rate of positive blood species were comprehensively analyzed.A total of 19 109 checked blood samples were examined. The qualified rates of blood preparation, dyeing and cleanliness were 87.5%, 89.3% and 87.6%, respectively. The quality of reexamined blood slides in different years showed statistically significant difference (all P < 0.05), by using chi-square trend test, and there was a trend of increasing year by year. There was a significant difference in the quality of the reexamined blood slides among the different cities with districts (P < 0.05). In addition, there were 1 860 blood samples from 2012 to 2017, and the total coincidence rate was 87.4% and the coincidence rate of positive blood smear examinations was 98.9%. The species coincidence rates of Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale and mixed infection were 95.4%, 33.3%, 56.0%, 76.5% and 9.1%, respectively (P < 0.05). The total coincidence rates of blood smear reexaminations in different years were 85.0%, 90.1%, 86.0%, 85.3%, 90.0% and 87.6% from 2012 to 2017, respectively, and the difference was not statistically significant (P > 0.05).The quality of blood slides at the primary clinic inspection stations in Jiangsu Province conforms to the standard established by the provincial malaria reference laboratory; however, the ability of Plasmodium species identification is insufficient and needs to be improved.
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Objective To explore the expression characteristics of cytochrome P450(CYP)candidate genes(CYP6M3, CYP6Y1,CYP6P5,CYP4H14,CYP4G17,CYP12F16)in Anopheles sinensis.Methods The samples were collected from dif-ferent developmental stages(eggs,larvae,pupae and adult mosquitoes(females and males)),and different tissues(salivary glands,malpighian tubes,midguts,ovaries,and fat bodies)of An.sinensis and the female adult mosquitoes exposed by differ-ent insecticide doses(0,1.25,3.75,6.25,12.5μg/bottle)and time points(0,5,15,30,60 minutes),then the total RNA was extracted. Quantitative reverse transcription PCR(qPCR)assay was used to analyze the relative expressions of six CYP genes in An.sinensis at different developmental stages,tissues and different insecticide exposure doses and time.Results The expressions of CYP6M3 and CYP6Y1 in the male adult mosquitoes were the highest,the expression of CYP6M3 gene in the males was 35.1 times higher than that in the females,the expression of CYP6Y1 in the males was 61.4 times higher than that in the females;the expression level of CYP4H14 in the larvae was the lowest,the expression of CYP4H14 in the females was 22.5 times higher than that in the fourth instar larvae.The expressions of candidate CYP genes in different tissues of An.sinensis were significantly different,the expression of CYP6M3 in the malpighian tubule was 38.9 times higher than that in the ovary,the ex-pression of CYP6Y1 in the fatbody was 9.1 times higher than that in the ovary,the expression of CYP4G17 was 4.6 times higher than that in the ovary,and the expression of CYP12F16 was 4.4 times higher thanthat in the ovary.The exposure to different in-secticide doses and time showed some induction effects in the expressions of candidate CYP genes,which affected the expres-sions of candidate CYP genes in An.sinensis.Conclusion The expression of candidate CYP genes varies significantly in differ-ent developmental stages and various tissues of An.sinensis,and exposure to deltamethrin at various doses and time points af-fects CYP genes expression in An.sinensis.
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Mosquito is a vector of many infectious diseases,and it is recognized a leading killer of human in the world.After the Belt and Road Initiative launches,more are countries involved and the international communication and cooperation are sig-nificantly growing in China.Therefore,the risk of imported infectious diseases is increasing as well,some mosquito-borne dis-eases which have been well controlled or seldom seen in China,will be more risky to cause locally transmission from imported cases and become the threat to people's health in China.This paper reviews the risk of major imported mosquito borne-diseases to China,and discusses the control strategy as well,so as to provide the suggestion for entry-exit inspection and control of im-ported mosquito-borne diseases in China.