Investigation on prevalence of Schistosoma japonicum infections in wild mice in Shitai County, Anhui Province, 2018 / 中国血吸虫病防治杂志

Objective To investigate the prevalence of Schistosoma japonicum infection in wild mice in Shitai County, Anhui Province, so as to provide insights into precise control of the source of S. japonicum infections. Methods Wild mice were captured using the trapping method for three successive nights at snail-infested settings from Jitan Village of Jitan Township, and Shiquan Village and Xibai Village of Dingxiang Township, Shitai County, Anhui Province in June and October, 2018. All trapped wild mice were sacrificed and liver and mesenteric vein specimens were collected for detection of S. japonicum eggs using microscopy, while the fecal samples in mouse intestines were collected for identification of S. japonicum infections using Kato-Katz technique. In addition, the population density of trapped wild mice was estimated and the prevalence of S. japonicum infection was calculated in trapped wild mice. Results A total of 376 wild mice were trapped from three villages in Shitai County. The population density of trapped wild mice was 9.1% (376/4 124), and the prevalence of S. japonicum infection was 24.2% (91/376) in trapped wild mice. The highest prevalence of S. japonicum infection was detected in Shiquan Village of Dingxiang Township (30.1%), and the lowest prevalence was seen in Xibai Village of Dingxiang Township; however, there was no significant difference in the prevalence of S. japonicum infection in trapped wild mice among three villages (χ2= 4.111, P > 0.05). In addition, there was no significant difference in the prevalence of S. japonicum infection in wild mice captured between on June (26.8%, 34/127) and October (22.9%, 57/249) (χ2 = 0.690, P = 0.406). The trapped wild mice included 6 species, including Rattus norvegicus, Niviventer niviventer, R. losea, Apodemus agrarius, Mus musculus and N. coning, and the two highest prevalence of S. japonicum infection was detected in R. losea (34.9%, 22/63) and R. norvegicus (31.2%, 44/141). Conclusions The prevalence of S. japonicum infections is high in wild mice in Shitai County, and there is a natural focus of schistosomiasis transmission in Shitai County.

Investigation on newly emerging and re-emerging snail habitats in Anhui, 2017-2021 / 中国热带医学

@#Abstract: Objective　To understand the changes of newly emerging and re-emerging snail areas in Anhui from 2017 to 2021 and analyze its related influencing factors, so as to provide scientific basis for formulating snail control strategies. 　　Methods　According to the historical snail survey data, the information of newly emerging and re-emerging snails from 2017 to 2021 were collected, the causes for the formation of newly emerging and re-emerging snails flourish environments were investigated and analyzed retrospectively. Results During 2017-2021, in Anhui, the area with newly emerging snails was respectively 840.41 hm2, 559.14 hm2 (66.53%) in lake and marshland areas and 281.27 hm2 (33.47%) in hilly areas; the area of re-emerging snails was respectively 1 176.87 hm2, 669.39 hm2 (56.88%) in lake and marshland areas and 507.48 hm2 (43.12%) in hilly and mountainous areas. The sum of newly emerging snail area in Chizhou, Anqing and Wuhu accounted for 89.35% of all, the sum of re-emerging snail area accounted for 88.82%. In 2021, the areas with newly emerging and re-emerging snails peaked at 611.52 hm2 and 976.84 hm2, respectively. The newly emerging and re-emerging snail habitats were mainly distributed in the transmission interruption areas, accounting for 65.54% and 84.30%, respectively. The newly emerging and re-emerging snail habitats were mainly found in fluvial marsh, accounting for 65.54% and 52.12%, respectively. In recent 5 years, the longest time interval of re-emerging snails was more than 50 years. The main causes of newly emerging snails were natural factors such as flood disaster and snail drift along river system. Natural factors, such as flood disaster and snail drift along river system, were the main reasons for the newly emerging snail habitats, accounting for 71.44% and 21.75%, respectively. Human factors, such as soil extraction from snail habitats, construction of water conservancy facilities, farmland abandonment and seedling transplanting, could also lead to the newly emerging snail habitats. Flood disaster was the main cause of re-emerging snail habitats, accounting for 72.29%. In addition, the re-emerging snail habitats were caused by historical snail residue, soil collection in snail habitats for construction projects, land abandonment, seedling transplanting, prohibition of snail control in ecological protection areas, and construction of water conservancy facilities. Conclusions　Flood disaster is an important factor for snail newly emerging and re-emerging. Human factors such as engineering construction and seedling transplanting are also easy to cause snail newly emerging and re-emerging. In order to timely detect and deal with newly emerging and re-emerging snail habitats and prevent snail diffusion, it is necessary to investigate snail distribution after flood disaster, the routine monitoring of historical snail habitats should be strengthened; in engineering construction and seedling transplanting, the disposal of soil with snails should be done well.

SARS-CoV-2 with transcription regulatory sequence motif mutation poses a greater threat / 南方医科大学学报

OBJECTIVE@#To analyze the mutations in transcription regulatory sequences (TRSs) of coronaviruss (CoV) to provide the basis for exploring the patterns of SARS-CoV-2 transmission and outbreak.@*METHODS@#A combined evolutionary and molecular functional analysis of all sets of publicly available genomic data of viruses was performed.@*RESULTS@#A leader transcription regulatory sequence (TRS-L) usually comprises the first 60-70 nts of the 5' UTR in a CoV genome, and the body transcription regulatory sequences (TRS-Bs) are located immediately upstream of the genes other than ORF1a and 1b. In each CoV genome, the TRS-L and TRS-Bs share a specific consensus sequence, namely the TRS motif. Any changes of nucleotide residues in the TRS motifs are defined as TRS motif mutations. Mutations in the TRS-L or multiple TRS-Bs result in superattenuated variants. The spread of super-attenuated variants may cause an increase in asymptomatic or mild infections, prolonged incubation periods and a decreased detection rate of the viruses, thus posing new challenges to SARS-CoV-2 prevention and control. The super-attenuated variants also increase their possibility of long-term coexistence with humans. The Delta variant is significantly different from all the previous variants and may lead to a large-scale transmission. The Delta variant (B.1.617.2) with TRS motif mutation has already appeared and shown signs of spreading in Singapore, which, and even the Southeast Asia, may become the new epicenter of the next wave of SARS-CoV-2 outbreak.@*CONCLUSION@#TRS motif mutation will occur in all variants of SARS-CoV-2 and may result in super-attenuated variants. Only super-attenuated variants with TRS motif mutations will eventually lose the abilities of cross-species transmission and causing outbreaks.

Platelet-Derived Growth Factor Receptor-α Subunit Targeting Suppresses Metastasis in Advanced Thyroid Cancer In Vitro and In Vivo

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

Research advances on stimulator of interferon genes (STING) and its agonists / 药学学报

As a key signal transduction molecule involved in the innate immune response, stimulator of interferon genes (STING) is triggered by cytosolic DNA from pathogen and host origins, and plays an important role in inducing the secretion of type I interferons and proinflammatory cytokines, thereby defending against viral and intracellular bacterial infections and regulating the production of spontaneous antitumor immune responses in vivo. Thus, STING agonists have shown useful therapeutic effects for pathogen infection and cancer. In the past decade research on STING and its agonists has progressed rapidly. Here, we summarize recent advances in the structure and activation of STING and the mechanism of the cGAS-STING pathway. In particular, we review research advances of STING agonists, analyze the crystal structure of STING in complex with its agonists and the structure-activity relationship of STING agonists, and summarize the strong challenges of developing STING agonists.

Platelet-Derived Growth Factor Receptor-α Subunit Targeting Suppresses Metastasis in Advanced Thyroid Cancer In Vitro and In Vivo

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

Mechanisms of rapamycin on regulating rat mesangial cell proliferation and cell cycle through mTORC1/p70S6K pathways / 药学学报

To explore the affect and mechanisms of rapamycin on mesangial cell proliferation and cell cycle, rat mesangial cells (HBZY-1) were cultured and divided into the six groups: normal; normal with platelet derived growth factor (PDGF) 20 ng·mL-1; PDGF + rapamycin 1, 10, 100, 1 000 nmol·L-1. The cell proliferation was measured by MTT in 24 and 48 h; flow cytometry was used to detect the cell cycle phase. Western blot was performed to determine cyclin D1,cyclin E, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), p27, p70S6K/p-p70S6K protein expression. The p27 mRNA was detect by Real-time PCR. The results showed that rapamycin significantly suppressed PDGF induced glomerular mesangial cells (MCs) proliferation in a dose and time-dependent manner, but with the dose increased (1 to 1 000 nmol·L-1), the time dependence gradually weakened. Rapamycin inhibited mesangial cell proliferation and arrested the cell cycle in the G0/G1 phase. PDGF at 20 ng·mL-1 significantly increased the expression of cyclin D1, cyclin E and CDK2, CDK4 (P < 0.05), but rapamycin did not affect the expression of cyclin D1, cyclin E and CDK2, CDK4. Rapamycin can significantly inhibited p70S6K phosphorylation, up-regulated the expression of p27 protein and mRNA. Collectively, rapamycin has the effect of inhibiting the glomerular mesangial cells proliferation of mesangial cells by regulating the transcription of p27 mRNA, increasing its protein expression through the mTORC1/p70S6K pathway, resulting in decreased activity of cyclin-CDK, and blocking cell cycle in G0/G1 phase.

Endemic situation of schistosomiasis in national surveillance sites of Anhui Province from 2015 to 2018 / 中国血吸虫病防治杂志

Objective To analyze the endemic situation of schistosomiasis in national surveillance sites of Anhui Province from 2015 to 2018, so as to provide scientific evidence for schistosomiasis control and prevention in Anhui Province. Methods According to the National Schistosomiasis Surveillance Programme (2014 version), a total of 51 national schistosomiasis surveillance sites were assigned in Anhui Province in 2015, and Schistosoma japonicum infections in humans and livestock and snail distribution were monitored from 2015 to 2018. Results A total of 89 638 local residents and 42 609 mobile populations received serological screening of schistosomiasis in 51 national surveillance sites of Anhui Province from 2015 to 2018, and the sero-prevalence of S. japonicum infections was 1.41% to 3.69% in local residents and 0.84% to 2.13% in mobile populations, respectively. There were 5 egg-positive local residents and 1 egg-positive mobile populations detected in 2015, with occupations of farmers and fishermen. There were 6 405 livestock detected for S. japonicum infections, and no egg-positives were identified. Among an area of 12 661 hm2 surveyed in the national schistosomiasis surveillance sites of Anhui Province from 2015 to 2018, the areas of snail habitats were 2 461.27 to 2 628.96 hm2, andthemeandensityoflivingsnailswas 0.3757 to 0.4330 snails/0.1 m2, with no S. japonicum infections identified in snails. Conclusions The endemic situation of schistosomiasis is at a low level in Anhui Province; however, the risk of schistosomiasis transmission remains in local regions of the province. The construction of the surveillance-responsesystemshouldbereinforcedtoconsolidatetheachievementsofschistosomiasis control in Anhui Province.

Spatiotemporal distribution of Oncomelania hupensis snail habitats in Anhui Province / 中国血吸虫病防治杂志

Objective To investigate the spatiotemporal distribution of Oncomelania hupensis snails and infected snails in the endemic areas of schistosomiasis in Anhui Province. Methods Based on the snail survey data in Anhui Province in 2016, the distribution of snails and infected snails were analyzed, and the spatial distribution of snails and spatial cluster patterns of infected snails were investigated in snail habitats in Anhui Province from 1950 to 2016. Results A total of 22 757 snail habitats and 5 004 infected snail habitats were identified in Anhui Province from 1950 to 2016, which appeared single-peak and double-peak patterns, with an inflection point seen in 1970. There were 141 000 hm2 historically accumulative snail habitats, 88.08% of which were firstly identified from 1950 to 1979, and totally 114 500 hm2 snail habitats were eradicated, 77.17% of which were eradicated from 1970 to 1999. There were 4 830 snail habitats identified until 2016, in which 1 051 were once detected with infected snails. In addition, 78.12% of current snail habitats had been present for over 40 years, and infected snails had been eliminated in 65.75% of the infected snail habitats within 10 years. There was a spatial autocorrelation of the living snail density in current snail habitats in Anhui Province (Moran’s I = 0.196, Z = 139.63, P < 0.001), and local hotspot analysis showed spatial clusters of living snails density in snail habitats, with high-value clusters in south of the Yangtze River and low-value clusters in north of the Yangtze River. The 21 high-value clusters of living snail density with statistical significance were distributed along the Yangtze River basin and its branches. Spatiotemporal scan analysis revealed spatiotemporal clusters of infected snails in 4 current snail habitats. Conclusions The current snail habitats have been present for a long period of time, and snails are difficult to be eliminated by chemical treatment alone, which requires the combination of environment improvements. There are spatial clusters of living snail density in current snail habitats in Anhui Province. The epidemic factors and risk of human and animal infections still remain in some clusters of historical infected snail habitats revealed by spatiotemporal scan analysis, which should be consid- ered as the key target areas for snail control in Anhui Province.

Application of infrared camera technique in investigation of wild animals as infectious source of schistosomiasis / 中国血吸虫病防治杂志

Objective To investigate the species and activities of wild animals infected with schistosome in hilly and mountain areas by using an infrared camera technique, so as to provide the evidence for the surveillance of schistosomiasis in these areas. Methods Six infrared cameras were selected and placed in 6 environments of the risk monitoring points of schistosomiasis in Shitai County in Anhui Province. The species and activities of the wild animals in the 6 environments were observed through the photographs and videos taken by the cameras. Results Through 5 day’s monitoring, 3 wild mammals, such as voles, hares and wild boars, were found in 4 monitoring environments, of which voles were found at 2 environments with snails, and hares, wild boars and voles were found in 2 environments adjacent to environments with snails respectively. The monitoring showed that the vole activity was most frequent in the monitored environment. Conclusion The use of infrared camera technique has a good effect in the investigation of wild animal infectious source of schistosomiasis, and it is also suitable for the monitoring work in other types of environments.

Investigation of Oncomelania hupensis snails in Anhui Province in 2016 / 中国血吸虫病防治杂志

Objective To investigate the status of Oncomelania hupensis snails in Anhui Province in 2016, so as to provide the evidence for formulating the 13th Five-Year Plans for Schistosomiasis Control. Methods In 2016, a snail survey was conducted in Anhui Province according to the National Programme of the Oncomelania Snail Survey, covering all snail habitats or historical snail habitats and suspected environments of snail breeding, and the results of the survey were analyzed. Results In 2016, 22 848 environments were surveyed, and no schistosome-infected snails were found. There were 17 927 historical snail habitats in whole province, among which, the environments without changes, changed partly and changed completely accounted for 71.2%, 19.3% and 9.5%, respectively. The area of historical snail habitats was 1.410 billion m2. There were 4 830 environments with snail habitats covering an area of 0.265 billion m2 in 38 counties of 7 cities, including newly emerging area of 1 287.65 hm2 and reemerging area of 1 375.32 hm2. The density of living snails was 0.392 0 snails/0.1 m2, and the rate of frame with living snails was 12.93%. The type of marshland and lake regions, and the type of hilly and mountainous regions accounted for 22.4% and 77.6% of number of snail habitats, and accounted for 86.7% and 13.3% of areas of snail habitats, respectively. Among the different types of vegetation in snail habitats, grass was superior owe to accounting for 82.2% of the number of snail habitats, 57.3% of the area with snail habitats, and the highest density of living snails (0.413 9 snails/0.1 m2). Among the different types of environments in snail habitats, the ditch was superior owe to accounting for 56.8% of the number of snail habitats, the highest density of living snails (0.570 3 snails/0.1m2) and the highest rate of frame with living snails (18.57%), and the beach was superior owe to accounting for 87.8% of the area with snail habitats. In Anhui Province, the first year of snails and schistosome-infected snails being found was 1950 and 1952, respectively, and the latest year of schistosome-infected snails being found was 2012. The map showed that the most environments with snail habitats were distributed along the Yangtze River in Anhui Province. Conclusion For the first time, the investigation has built the database and map of snail spatial distribution, which truly reflect the historic and current status of snail distribution in Anhui Province and can provide the evidence for formulating the 13th Five-Year Plans for Schistosomiasis Control and improving the schistosomiasis prevention and control work in the future.

Investigation of Oncomelania hupensis snails in Anhui Province in 2016 / 中国血吸虫病防治杂志

Objective To investigate the status of Oncomelania hupensis snails in Anhui Province in 2016, so as to provide the evidence for formulating the 13th Five-Year Plans for Schistosomiasis Control. Methods In 2016, a snail survey was conducted in Anhui Province according to the National Programme of the Oncomelania Snail Survey, covering all snail habitats or historical snail habitats and suspected environments of snail breeding, and the results of the survey were analyzed. Results In 2016, 22 848 environments were surveyed, and no schistosome-infected snails were found. There were 17 927 historical snail habitats in whole province, among which, the environments without changes, changed partly and changed completely accounted for 71.2%, 19.3% and 9.5%, respectively. The area of historical snail habitats was 1.410 billion m2. There were 4 830 environments with snail habitats covering an area of 0.265 billion m2 in 38 counties of 7 cities, including newly emerging area of 1 287.65 hm2 and reemerging area of 1 375.32 hm2. The density of living snails was 0.392 0 snails/0.1 m2, and the rate of frame with living snails was 12.93%. The type of marshland and lake regions, and the type of hilly and mountainous regions accounted for 22.4% and 77.6% of number of snail habitats, and accounted for 86.7% and 13.3% of areas of snail habitats, respectively. Among the different types of vegetation in snail habitats, grass was superior owe to accounting for 82.2% of the number of snail habitats, 57.3% of the area with snail habitats, and the highest density of living snails (0.413 9 snails/0.1 m2). Among the different types of environments in snail habitats, the ditch was superior owe to accounting for 56.8% of the number of snail habitats, the highest density of living snails (0.570 3 snails/0.1m2) and the highest rate of frame with living snails (18.57%), and the beach was superior owe to accounting for 87.8% of the area with snail habitats. In Anhui Province, the first year of snails and schistosome-infected snails being found was 1950 and 1952, respectively, and the latest year of schistosome-infected snails being found was 2012. The map showed that the most environments with snail habitats were distributed along the Yangtze River in Anhui Province. Conclusion For the first time, the investigation has built the database and map of snail spatial distribution, which truly reflect the historic and current status of snail distribution in Anhui Province and can provide the evidence for formulating the 13th Five-Year Plans for Schistosomiasis Control and improving the schistosomiasis prevention and control work in the future.

Gastrointestinal leiomyoma with interstitial cells of Cajal: mimicker of gastrointestinal stromal tumor / 中华病理学杂志

Objective@#To study clinical and pathologic characteristics of leiomyomas of the gastrointestinal tract, and to investigate the distribution characteristics of interstitial cells of Cajal ( ICCs ) in gastrointestinal leiomyomas.@*Methods@#One hundred and forty-seven cases of leiomyomas of gastrointestinal tract were collected at the Second Affiliated Hospital of Zhengzhou University from June 2012 to June 2017. Clinical and pathologic findings were analyzed, combined with immunohistochemistry, Alcian blue-osafranin staining and molecular study.@*Results@#The age of patients ranged from 13-82 years with mean age of 52 years. Male to female ratio was about 1∶2. Histologically, all tumors were composed of ovoid to spindle cells arranged in short intersecting fascicles. All tumors were diffusely and strongly positive for smooth muscle antibodies, desmin and h-caldesmon by immunohistochemical staining. A prominent interspersed subpopulation of elongated/dendritic-like cells with CD117 and DOG1 positivity (accounting for 1% to 30% of all tumor cells) and negative for Alcian blue-osafranin staining was identified in all esophageal leiomyomas, 16 of 20 (80%) gastric leiomyomas and 3 of 12 small bowel leiomyomas, but none in colonic/rectal leiomyomas. Mutational analysis in 16 cases showed absence of mutation in exons 9, 11, 13 or 17 of C-KIT and exons 12 or 18 of PDGFRA.@*Conclusions@#ICCs are identified in esophageal and gastric leiomyomas, as well as in small percentage of intestinal leiomyomas. Such findings may bring significant diagnostic pitfalls for misdiagnosis as gastrointestinal stromal tumor. Careful attention to the distribution of CD117 and DOG1 positive cells and molecular mutation analysis of C-KIT and PDGFRA may be necessary to establish the correct diagnosis.

Breeding and genotype identification of Arrb2 gene knockout mice / 中国药理学通报

Aim To explore the optimal way of breeding and genotype identification of Arrb2 knockout mice, and to find a simple and quick polymerase chain reaction ( PCR) method for the genotyping of Arrb2 knockout mice. Methods Breeding homozygote genotype of Arrb2 gene knockout mice were copula-ted with wild-type C57BL/6J mice, and then the heterozygous mating were used for mating. The growth and development of off-spring were observed. The genomic DNA was extracted from the tail of two-week-old mice. PCR was employed to amplify the Arrb2 gene fragment, and electrophoresis was used to present the gene type. Results The breeding and reproducing were successful and three genotype offspring, including wild-type,heterozygous and homozygous knockout mice were obtained. Agarose gel electrophoresis results showed the size of PCR prod-ucts was about 186 bp and 224 bp, which was consistent with the expected target gene fragment, and identified Arrb2 gene knockout mice of different genotypes successfully. Western blot analysis demonstrated the lack ofβ-arrestin2 protein in the major organs from Arrb2 -/ - mice compared with Arrb2 +/ + and Arrb2 +/ - mice. Conclusions It is feasible to obtain the homo-zygous Arrb2 knockout mice by inbreeding heterozygotes. It is simple, rapid and reliable to identify mouse genetype by PCR.

Relationship between clinical features in 371 cases of colorectal polyps with fecal occult blood and CEA / 重庆医学

Objective To investigate the basic clinical features in 371 cases of colorectal polyps and its relationship with fecal occult blood and carcinoembryonic antigen(CEA).Methods The retrospective analysis was performed on 371 inpatients with colo-rectal polyps.The relationship among gender,number of polyps and polyps anatomical site in different ages of patients was investi-gated,and the relationship between fecal occult blood and CEA with polyp canceration was analyzed by 1.5?3.0 years follow-up. Results Among 371 cases of colorectal polyps,the female patients were gradually increased and single polyp was gradually de-creased along with the age increase;due to different ages,there was the statistically significant difference in the polyp locations (χ2 =9.759,P=0.045);the distribution difference of the patients with polyp canceration among three age groups was statistically significant(χ2 =5.138,4.107,13.153,P<0.05).The cases of fecal occult blood positive and CEA abnormal increase were gradual-ly increased with age increasing(χ2 =15.544,11.959,P<0.01);with the number of polyps increasing,the cases of fecal occult blood positive showed the increasing trend(χ2 =14.043,P=0.001);the canceration rate in colorectal polyp cases of fecal occult blood positive and CEA abnormal increase was significantly higher than that in the cases of fecal occult blood negative and CEA normal range(χ2 =40.165,43.249,all of P< 0.001).Conclusion The fecal occult blood test and CEA detection results have a certain significance to the follow up for preventing colorectal polyps canceration.

Mitochondrial Autophagy and NLRP3 Inflammasome in Pulmonary Tissues from Severe Combined Immunodeficient Mice after Cardiac Arrest and Cardiopulmonary Resuscitation / 中华医学杂志(英文版)

<p><b>Background</b>The incidence of cancer, diabetes, and autoimmune diseases has been increasing. Furthermore, there are more and more patients with solid organ transplants. The survival rate of these immunocompromised individuals is extremely low when they are severely hit-on. In this study, we established cardiac arrest cardiopulmonary resuscitation (CPR) model in severe combined immunodeficient (SCID) mice, analyzed the expression and activation of mitochondrial autophagy and NLRP3 inflammasome/caspase-1, and explored mitochondrial repair and inflammatory injury in immunodeficiency individual during systemic ischemia-reperfusion injury.</p><p><b>Methods</b>A potassium chloride-induced cardiac arrest model was established in C57BL/6 and nonobese diabetic/SCID (NOD/SCID) mice. One hundred male C57BL/6 mice and 100 male NOD/SCID mice were randomly divided into five groups (control, 2 h post-CPR, 12 h post-CPR, 24 h post-CPR, and 48 h post-CPR). A temporal dynamic view of alveolar epithelial cells, macrophages, and neutrophils from bronchoalveolar lavage fluid (BALF) was obtained using Giemsa staining. Spatial characterization of phenotypic analysis of macrophages in the lung interstitial tissue was analyzed by flow cytometry. The morphological changes of mitochondria 48 h after CPR were studied by transmission electron microscopy and quantified according to the Flameng grading system. Western blotting analysis was used to detect the expression and activation of the markers of mitochondrial autophagy, NLRP3 inflammasome, and caspase-1.</p><p><b>Results</b>(1) In NOD/SCID mice, macrophages were disintegrated in BALF, and many alveolar epithelial cells were shed at 48 h after resuscitation. Compared with C57BL/6 mice, the ratio of macrophages/total cells peaked at 12 h and was significantly higher in NOD/SCID mice (31.17 ± 4.13 vs. 49.69 ± 2.43, t = 14.46, P = 0.001). After 24 h, the results showed a downward trend. Furthermore, a large number of macrophages were disintegrated in the BALF. (2) Mitochondrial autophagy was present in both C57BL/6 and NOD/SCID mice after CPR, but it began late in the NOD/SCID mice. Compared with C57BL/6 mice, phos-ULK1 (Ser) expression was significantly lower at 2 h and 12 h after CPR (2 h after CPR: 1.88 ± 0.36 vs. 1.12 ± 0.11, t = -1.36, P < 0.01 and 12 h after CPR: 1.52 ± 0.16 vs. 1.05 ± 0.12, t = -0.33, P < 0.01), whereas phos-ULK1 (Ser) expression was significantly higher at 2 h and 12 h after CPR in NOD/SCID mice (2 h after CPR: 1.28 ± 0.12 vs. 1.69 ± 0.14, t = 1.7, P < 0.01 and 12 h after CPR: 1.33 ± 0.10 vs. 1.94 ± 0.13, t = 2.75, P < 0.01). (3) Furthermore, NLRP3 inflammasome/caspase-1 activation in the pulmonary tissues occurred early and for only a short time in C57BL/6 mice, but this phenomenon was sustained in NOD/SCID mice. The expression of the NLRP3 inflammasome increased modestly in the C57 mice, but the increase was higher in the NOD/SCID mice than in the C57BL/6 mice, especially at 12, 24, 48 h after CPR (48 h after CPR: 1.46 ± 0.13 vs. 2.97 ± 0.19, t = 5.34, P = 0.001). The expression of caspase-1-20 generally followed the same pattern as the NLRP3 inflammasome.</p><p><b>Conclusions</b>There is a regulatory relationship between the NLRP3 inflammasome and mitochondrial autophagy after CPR in the healthy mice. This regulatory relationship was disturbed in the NOD/SCID mice because the signals for mitochondrial autophagy occurred late, and NLRP3 inflammasome- and caspase-1-dependent cell injury was sustained.</p>

In silico investigation of agonist activity of a structurally diverse set of drugs to hPXR using HM-BSM and HM-PNN / 华中科技大学学报（医学）（英德文版）

The human pregnane X receptor (hPXR) plays a critical role in the metabolism, transport and clearance of xenobiotics in the liver and intestine. The hPXR can be activated by a structurally diverse of drugs to initiate clinically relevant drug-drug interactions. In this article, in silico investigation was performed on a structurally diverse set of drugs to identify critical structural features greatly related to their agonist activity towards hPXR. Heuristic method (HM)-Best Subset Modeling (BSM) and HM-Polynomial Neural Networks (PNN) were utilized to develop the linear and non-linear quantitative structure-activity relationship models. The applicability domain (AD) of the models was assessed by Williams plot. Statistically reliable models with good predictive power and explain were achieved (for HM-BSM, r (2)=0.881, q LOO (2) =0.797, q EXT (2) =0.674; for HM-PNN, r (2)=0.882, q LOO (2) =0.856, q EXT (2) =0.655). The developed models indicated that molecular aromatic and electric property, molecular weight and complexity may govern agonist activity of a structurally diverse set of drugs to hPXR.

Validation of zebrafish embryo toxicity evaluation method / 中国药理学与毒理学杂志

OBJECTIVE In this study,nine different levels of known teratogenic embryos toxic com-pounds (aceta minophen,methi mazole,indo metacin,methotrexate,ascorbic acid,isoniazid,penicillin G,saccharin ,5-fluorouracil )were used to validate the established evaluation method of zebrafish e mbryo develop mental toxicity in our laboratory via zebrafish e mbryonic develop ment toxicity tests. METHODS By water bath method,zebrafish embryos of post-fertilization 2 h (2 hpf)were exposed to different concentrations of compounds.Observe and record the nu mber of malformations and dead e mbryo in 24,48,72,144 hpf.After three parallel experiments,get EC50 ,LC50 through software and calculate the teratogenic indices (TI =LC50 /EC50 )of the positive drug and recorded it as teratogens.If there is no teratogenic index recorded it as non-teratogens.Co mpare the results with the existing animal experiments and clinical trials to obtain the sensitivity and specificity.RESULTS Based on the results, exposure to aceta minophen (TI =2.07),methi mazole (TI =2.91 ),indo methacin (TI =1 .67),5-flu-orouracil (TI =8.31 ),methotrexate (TI =1 .31 ),showed various levels of teratogenic effects,and the corresponding TI′s were calculated.Methi mazole appeared more obvious skeletal deformities;indo m-ethacin toxicity is mainly reflected in abnormal heart,blood circulation and other endpoints;5-FU at lower doses that result in higher mortality rates,but also took place over the lacking of pig mentation;aceta min-ophen for the heart,liver and other target organ toxicity,pericardial cyst;methotrexate appears signifi-cant so mites,skeletal deformity.Since the IT′s for ascorbic acid,isoniazid,penicillin G,saccharin can-not be calculated,these compounds are considered to show negative results,indicating that the data fro m the nine compounds in zebrafish test are consistent with traditional animal experiments and clinical information,the sensitivity of 100% and specificity of 100%.CONCLUSION Though validation test,it has been de monstrated that the established zebrafish embryos develop mental toxicity evaluation method can be applied to early screening of drug toxicity.

Expressions and clinical significance of EGFR,CTEN and E-cad in non-small cell lung cancer / 西安交通大学学报(医学版)

Objective To explore the expressions and clinical significance of epidermal growth factor receptor (EGFR),COOH-terminus tensin-like molecule (CTEN)and epithelial cadherin (E-cad)in non-small cell lung cancer (NSCLC).Methods The expressions of EGFR,CTEN and E-cad in 36 cases of normal lung tissue and 82 cases of NSCLC tissues were observed with immunohistochemical SP method and their correlation with NSCLC invasion,metastasis and prognosis was analyzed.Results The positive rate of EGFR,CTEN and E-cad was 58.5% (48/82),69.5% (57/82)and 28.1% (23/82)in 82 cases of lung cancer,while 13.9% (5/36),0.0% (0/36)and 100% (36/36)in normal tissues;the differences were all significant (P<0.05).EGFR,CTEN and E-cad expressions in NSCLC tissues were significantly correlated with tumor differentiation,TNM stage and lymph node metastasis (P<0 .0 5 ).The expressions of EGFR and CTEN were correlated with each other in NSCLC (r=0 .5 3 0 , P<0.001),while the expressions of EGFR and CTEN were correlated with that of E-cad (r=0.499,P<0.001;r=0.333,P=0.001 ).Multivariate Cox regression analysis showed that CTEN expression in NSCLC was an independent prognostic factor (P<0.05 ).Conclusion EGFR,CTEN and E-cad may play a role in the development,invasion and metastasis of NSCLC and have some significance in predicting the prognosis of NSCLC.

Spatial-temporal analysis on the distribution of infected snail at the village level in Anhui province, 2006-2012 / 中华流行病学杂志

Objective The characteristics of spatial-temporal distribution on infected snails were analyzed at the village level in Anhui province,2006-2012.Methods Data on the distribution of infected snails from 2006 to 2012 in Anhui province was collected.Spatial database was established by ArcGIS 9.3.Retrospective spatial-temporal cluster analysis was done by SaTScan 9.1.1 at the village level.Results Eight areas with increased risk and distributed along the upstream to downstream of Yangtze and connecting branch rivers,were found having infected snails,from 2006 through 2012,including one area in 2006,five in 2006-2008,one in 2007-2009 and one in 2009-2011,respectively.Proportion on the number of areas with infected snails decreased from 6.2％ in 2006 to 0.5％ in 2012.Conclusion The spatial-temporal distribution of infected snail was not random but there appeared significant clusters.The trend seemed to be declining in Anhui province,between 2006 and 2012.Areas being detected as smails positive were important for the schistosomiasis control program to be carried out in Anhui province.