Objective Objective To analyze the potential spatial factors affecting the genetic differentiation of Oncomelania hupensis robertsoni in Yunnan Province. Methods A total of 13 administrative villages were selected from schistosomiasis-endemic areas of Yunnan Province as O. hupensis snail sampling sites. At least 200 snails were collected in each site, and the spatial variable data of each site were recorded, including longitude, latitude and altitude. Thirty active and Schistosoma japonicum uninfected O. hupensis snails were selected from each sampling site by means of the crawling method and the cercarial shedding method. Genomic DNA was extracted from O. hupensis snails. Following PCR amplification, purification of PCR amplification products and sequencing, the gene sequences of O. hupensis snail samples were spliced and edited using the DNAstar software and the NCBI database to yield the complete mitochondrial sequences of O. hupensis snails at each sampling site, and the mitochondrial genetic distance matrix of O. hupensis robertsoni was calculated at each sampling site. The geographical coordinates of each sampling site were marked using the software ArcGIS 10.2, and the straight-line geographical distance between each sampling site was calculated. The altitude difference, longitude difference and latitude difference between each sampling site were calculated using the Excel software, and the correlation between the mitochondrial genetic distance matrix of O. hupensis robertsoni and each spatial variable matrix was examined by using the Mantel test at 13 sampling sites in Yunnan Province. Results Among the 13 O. hupensis snail sampling sites in Yunnan Province, the largest mitochondrial genetic distance of O. hupensis robertsoni snail populations was seen between Anding Village, Nanjian Yi Autonomous County and Caizhuang Village, Midu County (26.244 2), and the largest geographical distance was seen between Dongyuan Village, Gucheng District and Cangling Village, Chuxiong County (272.64 km). The highest altitude difference was seen between Anding Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1 086.10 m), and the largest longitude difference was found between Qiandian Village, Eryuan County and Cangling Village, Chuxiong County (1.86°), while the largest latitude difference was measured between Leqiu Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1.81°). In addition, the mitochondrial genetic distance of O. hupensis robertsoni snail populations was positively correlated with altitude at 13 snail sampling sites in Yunnan Province (r = 0.542 8, P < 0.001), and showed no significant correlations with geographical distance (r = 0.093 4, P > 0.05), longitude (r = −0.199 5, P > 0.05) or latitude (r = 0.205 7, P > 0.05). Conclusion Altitude may be a potential spatial factor affecting the genetic differentiation of O. hupensis robertsoni in Yunnan Province.

BACKGROUND:The preparation of curved root canals is a difficult point in root canal treatment,and the main way used in clinical preparation for curved root canals is to gradually deepen the technique,but this technique is prone to lateral penetration when preparing curved root canals,resulting in treatment failure.In view of this situation,some scholars have proposed the use of touch activation technology to prepare,but there are few studies on the influence of this technology combined with different mechanical nickel-titanium instruments on the forming effect of curved root canals at home and abroad.OBJECTIVE:To observe the shaping effect of WaveOneGold,Trunatomy and M3-Pro mechanized nitinol device preparation root canal by using resin simulated root canal step-down technology and tactile controlled activation.METHODS:60 single-bending resin simulated root canals were divided into 6 groups(r=10)according to the random number table method according to the nitinol instrument used.The A1 group was prepared with step-down+WaveOneGold;the A2 group was prepared with step-down+Trunatomy,and the A3 group was prepared with step-down+M3-Pro.Tactile controlled activation+WaveOneGold was used for preparation in group B1;tactile controlled activation+Trunatomy was used for group B2,and tactile controlled activation+M3-Pro was used for preparation in group B3.After the preparation was completed,the pre-preparation and posterior root canal images are obtained using a dental surgical microscope.The root canal offset was analyzed before and after preparation.RESULTS AND CONCLUSION:(1)When WaveOneGold was used,the root canal deviation at 1,4,and 7 mm from the apex was smaller with the tactile controlled activation technique than with the step-down technique(P＜0.05);when Trunatomy was used,the root canal deviation at 6,8,and 10 mm from the apex was smaller with the tactile controlled activation technique than with the step-down technique(P＜0.05);when M3-Pro was used,the root canal deviation at 1,2,and 3 mm from the apex was smaller with the tactile controlled activation technique than with the step-down technique(P＜0.05).(2)When the step-down technique was used,the root canal deviation at 1,4,5,and 7 mm from the apex was smaller with the Trunatomy than with the other two files(P＜0.05),and the root canal deviation at 1,2,3,and 6 mm from the apex was larger with the M3-Pro machine-made nickel-titanium instrument than with the other two files(P＜0.05);when the tactile controlled activation technique was used,the root canal deviation at 2,5,6,8,and 9 mm from the apex after preparation with the Trunatomy file was smaller than that of the other two groups(P＜0.05),and the root canal deviation at 1,4,5,6,and 7 mm from the apex after preparation with the M3-Pro file was larger than that of the other two groups(P＜0.05).(3)The results showed that the three files could cause root canal deviation when preparing root canals.The three files combined with the tactile controlled activation technique could reduce the root canal deviation at some sites of the root canal.The root canal deviation at some sites of the Trunatomy file was less than that of the other two files.

BACKGROUND:The preparation of curved root canals is a difficult point in root canal treatment,and the main way used in clinical preparation for curved root canals is to gradually deepen the technique,but this technique is prone to lateral penetration when preparing curved root canals,resulting in treatment failure.In view of this situation,some scholars have proposed the use of touch activation technology to prepare,but there are few studies on the influence of this technology combined with different mechanical nickel-titanium instruments on the forming effect of curved root canals at home and abroad.OBJECTIVE:To observe the shaping effect of WaveOneGold,Trunatomy and M3-Pro mechanized nitinol device preparation root canal by using resin simulated root canal step-down technology and tactile controlled activation.METHODS:60 single-bending resin simulated root canals were divided into 6 groups(r=10)according to the random number table method according to the nitinol instrument used.The A1 group was prepared with step-down+WaveOneGold;the A2 group was prepared with step-down+Trunatomy,and the A3 group was prepared with step-down+M3-Pro.Tactile controlled activation+WaveOneGold was used for preparation in group B1;tactile controlled activation+Trunatomy was used for group B2,and tactile controlled activation+M3-Pro was used for preparation in group B3.After the preparation was completed,the pre-preparation and posterior root canal images are obtained using a dental surgical microscope.The root canal offset was analyzed before and after preparation.RESULTS AND CONCLUSION:(1)When WaveOneGold was used,the root canal deviation at 1,4,and 7 mm from the apex was smaller with the tactile controlled activation technique than with the step-down technique(P＜0.05);when Trunatomy was used,the root canal deviation at 6,8,and 10 mm from the apex was smaller with the tactile controlled activation technique than with the step-down technique(P＜0.05);when M3-Pro was used,the root canal deviation at 1,2,and 3 mm from the apex was smaller with the tactile controlled activation technique than with the step-down technique(P＜0.05).(2)When the step-down technique was used,the root canal deviation at 1,4,5,and 7 mm from the apex was smaller with the Trunatomy than with the other two files(P＜0.05),and the root canal deviation at 1,2,3,and 6 mm from the apex was larger with the M3-Pro machine-made nickel-titanium instrument than with the other two files(P＜0.05);when the tactile controlled activation technique was used,the root canal deviation at 2,5,6,8,and 9 mm from the apex after preparation with the Trunatomy file was smaller than that of the other two groups(P＜0.05),and the root canal deviation at 1,4,5,6,and 7 mm from the apex after preparation with the M3-Pro file was larger than that of the other two groups(P＜0.05).(3)The results showed that the three files could cause root canal deviation when preparing root canals.The three files combined with the tactile controlled activation technique could reduce the root canal deviation at some sites of the root canal.The root canal deviation at some sites of the Trunatomy file was less than that of the other two files.

ObjectiveTo explore the anti-eczema efficacy and mechanism of Mongolian medicine Cymbaria dahurica n-butanol extract. MethodsThe compounds of C. dahurica n-butanol extract were obtained by ultra-performance liquid chromatography-quadrupole-electrostatic field orbital trap high resolution mass spectrometry （UPLC-Q-Exactive MS） analysis and literature mining. GEO chip analysis and network pharmacology were employed to predict potential targets and pathways for the anti-eczema effect. Seventy-five mice were randomized into a normal group （10 mice） and a modeling group （65 mice）. The model was induced by 1% dinitrochlorobenzene （DNCB） for 3 days. The modeled mice were grouped as follows： Positive drug （hydrocortisone butyrate cream， 250 mg·kg^-1·d^-1） and low-， medium-， and high-dose （95.94， 191.88， and 383.76 mg·kg^-1·d^-1， respectively） C. dahurica n-butanol extract， with 13 mice in each group. From day 5 of the experiment， 0.5% DNCB was applied， once every other day， until day 22. At the same time， drugs were applied daily from day 5. The appearance damage of back skin of mice in each group was analyzed. The pathological changes of the back skin of mice in each group were observed by hematoxylin-eosin （HE） staining and toluidine blue （TB） staining. The levels of inflammatory factors ［histamine （HIS）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TFN-α）］， thymic stromal lymphopoietin （TSLP）， and immunoglobulin E （IgE） in the serum were determined by enzyme-linked immunosorbent assay （ELISA）. Metabolomics analysis was performed for the mouse skin. The HaCaT cell model of eczema was induced with TNF-α/interferon-γ （IFN-γ）. The secretion levels of IL-6， IL-8， thymus and activation-regulated chemokine （TARC/CCL17）， macrophage-derived chemokine （MDC）， and TSLP in the cell supernatant from each group were measured by ELISA， while the protein levels of phosphorylated （p）-Janus kinase 2 （JAK2）， JAK2， p-signal transducer and activator of transcription 3 （STAT3）， and STAT3 were assessed by Western blot. ResultsThrough UPLC-Q-Exactive MS and literature review， a total of 125 compounds of C. dahurica n-butanol extract were obtained. The Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis showed that the anti-eczema mechanism of C. dahurica n-butanol extract may be related to the Janus kinase/signal transducer and activator of transcription （JAK/STAT） pathway. The results of animal experiments showed that compared with the normal group， the modeling group exhibited redness， swelling， exudation， erosion， and scab formation on the back skin surface， and thickened dermis and epidermis with inflammatory cell infiltration. Compared with the modeling group， the positive drug and C. dahurica n-butanol alleviated the skin lesions （including redness， swelling， exudation， roughness， and keratosis and scab formation on the back）， reduced the thickness of dermis and epidermis， mitigated inflammatory cell infiltration， and restored the skin tissue structure. Compared with the normal group， the modeling group showed elevated levels of HIS， IL-4， IL-6， IL-8， TNF-α， TSLP， and IgE （P<0.05， P<0.01）， which were reversed in the positive drug group and C. dahurica n-butanol extract groups （P<0.05， P<0.01）. The results of metabolomics analysis showed that 12 differential metabolites might be the key substances for mitigating metabolic disorders of the skin and were closely related to the JAK/STAT signaling pathway. The cell experiement showed that compared with the normal group， the model group exhibited upregulated expression levels of IL-6， IL-8， MDC， TARC， TSLP， p-JAK2， p-STAT3， p-JAK2/JAK2， and p-STAT3/STAT3 in HaCaT cells （P<0.05， P<0.01）. Compared with the model group， C. dahurica n-butanol extract and dexamethasone downregulated the expression levles of these molecules （P<0.05， P<0.01）. ConclusionC. dahurica n-butanol extract may play an anti-eczema role by inhibiting the JAK2/STAT3 signaling pathway， reducing the inflammatory response， and correcting the metabolic disorder.

Objective: o analyze the epidemic characteristics of five sexually transmitted diseases (STDs), including syphilis, gonorrhea, condyloma acuminatum, genital herpes and genital Chlamydia trachomatis infection in Yangzhou City, Jiangsu Province from 2019 to 2023, so as to provide the reference for the prevention and control strategies of STDs. Methods: Data of the onset time and diagnostic types of STDs cases in Yangzhou City from 2019 to 2023 were collected from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. The temporal, regional and population characteristics of five types of STDs was analyzed using the descriptive epidemiological method. Results: A total of 10 895 cases of STDs were reported in Yangzhou City from 2019 to 2023, with an average annual reported incidence rate of 47.83/105. The average annual reported incidence rates of syphilis, gonorrhea, condyloma acuminatum, genital herpes and genital Chlamydia trachomatis infections were 41.11/105, 2.83/105, 2.59/105, 0.43/105 and 0.85/105, respectively. The reported incidence rate of STDs showed a decreasing trend from 2019 to 2023 (P<0.05), with an average annual growth rate of -3.44%. The reported incidence rates of syphilis and gonorrhea showed a decreasing trend (both P<0.05), with average annual growth rates of -4.26% and -6.47%, respectively. The reported incidence rate of genital Chlamydia trachomatis infection showed an increasing trend (P<0.05), with an average annual growth rate of 22.32%. Baoying County, Guangling District and Hanjiang District had the top three reported incidence rates of STDs, at 56.61/105, 55.61/105 and 46.50/105, respectively. The average annual reported incidence rate of STDs among males was higher than that among females (53.19/105 vs. 42.54/105, P<0.05). The STD cases were primarily people aged 50 years and above, with 6 641 cases accounting for 60.95%. The occupations of STD cases were mainly farmers, housekeepers and unemployed, with 4 670 and 3 273 cases accounting for 42.86% and 30.04%, respectively. Conclusions The overall reported incidence of STDs in Yangzhou City from 2019 to 2023 showed a downward trend, while the reported incidence of genital Chlamydia trachomatis infection showed an upward trend. The individuals aged 50 years and above, farmers, housekeepers and the unemployed were identified as high-risk groups for STDs.

Despite the remarkable clinical efficacy achieved by immune checkpoint blockade(ICB)and adoptive T cell therapy,the majority of patients with solid tumors still fail to achieve long-term responses to immunotherapy.One important reason is the complex metabolic patterns and inhibitory signals within the tumor microenvironment(TME),which induce metabolic reprogramming in immune cells and thereby impair their anti-tumor efficacy.This review summarizes the metabolic preferences of CD8+T cells across various differentiation states,explores the metabolic changes that occur during their interaction with tumor cells and the TME,and discusses how these metabolic changes affect differentiation,function,and stemness of CD8+T cells.Additionally,strategies that target metabolic molecules or pathways are highlighted to enhance the antitumor ability of CD8+T cells,thereby improving the efficacy of chimeric antigen receptor gene-modified T lymphocyte(CAR-T cell)immunotherapy and ICB therapy.

Objective To observe the value of prenatal ultrasound graded management of Sylvian fissure for diagnosing fetal lissencephaly.Methods Totally 39 fetuses with MRI diagnosed lissencephaly who underwent prenatal ultrasound examination were retrospectively enrolled and divided into non-graded management group(n=20)and graded management group(n=19)according to prenatal ultrasound examination before or after the application of prenatal ultrasound graded management of Sylvian fissure(i.e.prenatal ultrasound routine screening for fetal Sylvian fissure morphology).The diagnosis of prenatal ultrasound were compared and analyzed between groups,and the diagnostic value of graded management was evaluated.Results Among 20 fetuses in non-graded management group,prenatal ultrasound showed lissencephaly in 4 fetuses,but only other structural abnormalities in 16 fetuses.Then the latter were re-evaluated based on prenatal ultrasound graded management of Sylvian fissure,among which 4 fetuses could not be evaluated since not standard ultrasonic section,2 fetuses with severe hydrocephalus and Sylvian fissure could not be seen,while Sylvian fissure morphology did not match the corresponding gestational week in 4 fetuses,and type Ⅰ(no platform type)and type Ⅴ(Z-shaped)were noticed in 5 and 1 fetus,respectively.In graded management group,prenatal ultrasound indicated 15 fetuses with lissencephaly,including Sylvian fissure morphology did not match the corresponding gestational week in 6 fetuses,type Ⅰ(no platform type),type Ⅲ(linear type)and type Ⅴ(Z-shaped)were detected in 7,1 and 1 fetus,respectively,while no clear diagnosis was obtained in 4 fetuses.Prenatal ultrasound detection rate of fetal lissencephaly in graded management group(15/19,78.95％)was significantly higher than that in non-graded management group(4/20,20.00％)(P＜0.01).Conclusion Based on graded management of Sylvian fissure could improve the efficiency of prenatal ultrasound for diagnosing fetal lissencephaly.

Objective:To investigate the situation of computed tomography(CT)equipment and socio economic development of various grades and classifications of medical institutions in Jiangsu Province,and to analyze the interrelationship between them.Methods:From October 20,2023 to November 20,2023,a questionnaire survey was conducted on imported and domestic CT equipment of various grades and classifications of medical institutions in 13 prefecture-level cities in Jiangsu Province through online questionnaire survey of"questionnaire star".The gross domestic product(GDP)of each prefecture-level city in Jiangsu province was used as an indicator of measuring the level of socio-economic development in the region.The CT number,the row number of detector,quality of image,the total examination case number of daily average and the daily average case number of single machine examination of medical institutions of various grades and classifications of 13 prefecture-level cities were used to conduct correlation analysis with GDP values of various districts.Results:A total of 910 questionnaires were distributed,and 512 questionnaires were retrieved.There were 482 valid questionnaires in the 512 questionnaires,and the valid rate was 94.15,which involved to 482 various grade and classification institutions of 13 prefecture-level cities in Jiangsu province.The number of imported and domestic CT equipment in the 13 prefecture-level cities of Jiangsu Province positively correlated with the GDP of each city(r=0.882,0.880,P<0.001).The number of imported CT equipment with 64 rows and more than 64 rows,and with less than 64 rows,and the number of domestic CT equipment with 64 rows and more than 64 rows,and with less than 64 rows all positively correlated with the GDP of each city(r=0.880,0.881,0.736,0.897,P<0.05).The total number of daily average of examinations for imported and domestic CT equipment of 13 prefecture-level cities positively correlated with the GDP of each city(r=0.774,0.814,P<0.05).There were no significant difference in the image quality and the daily average case number of single machine examination between the domestic CT equipment and the imported CT equipment(P>0.05).Conclusion:The medical institutions of city with high level of economic development have more quantitative and more high-end CT equipment,and the quality of image of domestic CT equipment is equal to that of imported CT equipment regardless of the high and low level of economic development.

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

Objective:To identify and trace the origin of the Francisella tularensis subsp. novicida strain SJCS-979 isolated from the blood of a patient, so as to provide a reference for the traceability investigation of such infection events. Methods:Hot spring water samples that the patient had recently bathed in were collected to culture the causative agent, combined with the pathogenic characteristics and the patient′s activity before the bloodstream infection. The water samples were concentrated, acid-treated, and then the isolation of the causative agent was performed, following the method for Legionella detection in circulating cooling water. Suspected strains detected from the hot spring water were subjected to classical phenotypic identification, API ZYM and API NH strips tests, drug sensitivity testing, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) identification, and the obtained data were compared with those of strain SJCS-979 isolated from the patient′s blood. A phylogenetic tree was constructed based on genomic analysis to determine the taxonomic status of strain SJCS-979 and related strains. Epidemiological data of Francisella tularensis subsp. novicida were collected and analyzed by integrating the global genetic and genomic data on GenBank database. Core single nucleotide polymorphism(SNP) comparisons were obtained using Snippy 3.2 software, and then an evolutionary tree was built to determine its population structure based on BAPS analysis. Results:Strain CC-2, isolated from the hot spring water, shared the same biochemical and drug sensitivity phenotype, and had a nearly consistent mass spectrometric profile with strain SJCS-979 isolated from the blood of a patient. Genomic phylogenetic tree analysis based on 120 core protein sequences showed that strains SJCS-979 and CC-2 fell on the same branch with known Francisella tularensis subsp. novicida strains. Bayesian genotyping showed that the global Francisella tularensis subsp. novicida strains with genomic data could be divided into six different sequence clusters. Strains SJCS-979 and CC-2 were located in the same taxonomic group with only 4 SNP differences, indicating that they might be the same clone. Conclusions:This study reports a case of bacteremia caused by Francisella tularensis subsp. novicida, and natural hot spring water may be the environmental source of this infection event.