Schistosomiasis is prevalent in 78 countries and territories worldwide, while the eastern and western parts of sub-Sahara Africa bear the highest disease burden due to schistosomiasis. Recently, climate change, international trade and travel, urbanization and war have increased the risk of cross-boundary importation and transmission of schistosomiasis, and schistosomiasis has increasingly become a public health concern in non-endemic countries and territories. Biomphalaria straminea, the intermediate host of Schistosoma mansoni, has colonized in southern China and its habitats continue to move northward. In addition, cross-boundary imported cases of schistosomiasis have been reported occasionally in China. However, the real number of cases may be underestimated greatly due to insufficient diagnostic capacity and weak awareness of case reporting for overseas imported schistosomiasis in healthcare facilities. It is necessary to establish a multi-party collaborative mechanism, improve corresponding systems and technical specifications, reinforce surveillance and early warning, and border management, enhance technical reserves and capability building, and improve the awareness of schistosomiasis prevention and healthcare-seeking among entry-exit personnel, in order to effectively address the threat of cross-boundary imported schistosomiasis.

ObjectiveThe human angiotensin converting enzyme2 （hACE2） transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus （Delta/Omicron） to angiotensin converting enzyme2 （ACE2）. Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group， SARS-CoV-2 infection group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1， with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice， detect the virus titer of the lung tissue of the mice， and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro， with median inhibitory concentration （IC₅₀） of 526.3 mg·L^-1 and 653.0 mg·L^-1， respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT， Omicron， and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died， while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1 could reduce the mortality of mice， significantly lower the virus titer in the lung tissue of mice （P<0.05）， and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However， its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.

ObjectiveTo observe the therapeutic effect of BD-77 by nebulized inhalation on animal models of various respiratory viral infections and investigate the mechanism of broad-spectrum antiviral action of BD-77 using proteomics. MethodThe influenza virus H1N1/FM1 experiment used ICR mice and divided them into a normal group， model group， Tamiflu group， and BD-77 groups of 75 and 37.5 g·L^-1 for inhalation of 20 min and 25 min. Human coronavirus 229E and OC43 experiment divided the BALB/c mice into a normal group， model group， chloroquine phosphate group， and BD-77 groups of 75， 37.5， 18.75， and 9.375 g·L^-1， with 10 mice in each group. Influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection-induced pneumonia models were used to detect mouse lung index， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the viral load in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect related inflammatory factors in lung tissue， and proteomics analysis was performed on the lung tissue of OC43-infected mice. ResultCompared with that in the normal group， the lung index of mice in each infection group was significantly increased （P<0.01）， and viral nucleic acid could be detected in the lung tissue of mice infected with human coronaviruses 229E and OC43. The levels of interleukin-6 （IL-6）， IL-10， and tumor necrosis factor-α （TNF-α） in the lung tissue of mice infected with human coronavirus 229E were all significantly increased （P<0.01）. BD-77 could significantly reduce the lung index of mice infected with influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 （P<0.05， P<0.01）， cut down the viral load in the lungs of mice infected with human coronaviruses 229E and OC43 （P<0.01）， and lower the contents of IL-6， IL-10， and TNF-α in the lung tissue of mice infected with human coronavirus 229E （P<0.01）. Proteomics analysis of the lung tissue of OC43-infected mice showed that BD-77 regulated the AMPK signaling pathway， TNF signaling pathway， NOD-like signaling pathway， IL-17 signaling pathway， Forkhead box protein O （FoxO） signaling pathway， transforming growth factor-β （TGF-β） signaling pathway， and other signaling pathways. ConclusionNebulized inhalation of BD-77 is effective in treating pneumonia caused by influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection in mice and may exert its antiviral effects by regulating the balance of cellular metabolism， enhancing the immune function of the host， and attenuating inflammatory responses.

Objective:To analyze the research status of scleral lenses by bibliometric method based on the relevant collection of scleral lenses in the Web of Science database.Methods:Using the scleral lens-related literature collected in the Web of Science Core Collection database in the past 10 years (January 2013 to December 2022) as the object of analysis, bibliometric method and CiteSpace tools were used to conduct visual analysis of the literature.A comprehensive analysis of the volume of literature published, the distribution of countries and institutions, the information of core authors, the distribution of journals, and keyword clustering was performed.Results:A total of 340 articles were retrieved, which were published in 54 journals, with an average of 6.3 articles per journal, involving 301 authors.Research in this area covered 35 countries or regions, and 256 research institutions were involved.Discipline development was mainly in the United States, India, Spain and Australia.The main focus was on scleral lens (scleral contact lens), ocular surface disease, corneal edema, miniature scleral lens, etc.In the past 10 years, the trend of research hot topics in scleral lenses had shifted from the initial study of combining scleral contact lenses with ocular surface diseases to the subsequent study of prosthetic replacement of the ocular surface ecosystem, and the exploration of corneal clearance and shape.From 2013 to 2021, the main focuses were ocular surface diseases, scleral contact lenses, and corneal edema.After 2021, research on ocular surface diseases and keratoplasty declined.From January 2013 to December 2022, emergent keywords related to scleral lens mainly included scleral contact lens, transplantation, anti-host disease, prosthetic device in the first stage, artificial replacement of ocular surface ecosystem and irregular cornea in the second stage, and the research on corneal gap and characteristic shape in the third stage.Optical coherence tomography and corneal topography were commonly used examinations for scleral lens research and fitting.Conclusions:At present, the scleral lens is mainly used for dry eye, corneal diseases, corneal ectasia, keratitis, and corneal transplantation, especially after penetrating keratoplasty and refractive errors.Prosthetic replacement of the ocular surface ecosystem, and the exploration of corneal clearance and shape are the research hotspots in scleral lenses.

Objective Explore differences in the cognitive abilities of socially different Labradors.Methods The dog mentality assessment(DMA)test created by the Swedish Working Dog Association was modified to employ 12 behavioral variables from five subtests of the DMA test,social contact,play Ⅰ,distance-play,ghosts and play Ⅱ,to assess sociability of the dogs.In accordance with the scoring criteria,49 labradors provided by the China Guide Dog Training Centre in Dalian were scored on the social behavioral variables and classified into high(n=15)and low(n=34)sociability groups by cluster analysis.A new system to test canine cognitive ability was developed using the dog cognitive development battery,which tests various domains of cognitive ability such as social cue use,unsolvable task,inhibitory control,cognitive flexibility,working memory,and multistep problem solving task.The dogs'behavioral performance and duration of the test were also recorded.Statistical analysis was performed to determine assess differences in the cognitive abilities of socially diverse dogs.Results Dogs in the high and low social subgroups differed significantly in behavioral variables of the unsolvable task,inhibitory control test,and multistep problem solving task.In the unsolvable task,dogs in the high social group looked at people for significantly longer than dogs in the low social grouping(P=0.008)and looked at people with significantly less latency time than dogs in the low social group(P=0.0001).In the inhibitory control,dogs in the high social group chose significantly more correctly than dogs in the low social group(P=0.034)and chose for significantly less time than dogs in the low social group(P=0.039).In the multistep problem solving task,for dogs in the high social group.successfully completed number of stakes was significantly higher than for dogs in the low social group(P=0.044).The percentage of operation pale time was significantly lower than for dogs in the low social group(P=0.05).The average latency time to solve the bone task was significantly higher than for dogs in the low social group(P=0.037).Moreover,the percentage of operation bone time was significantly lower than for dogs in the low social group(P=0.038).In tests involving a manipulable apparatus,dogs in the high social group spent more time looking at people than dogs in the low social group and less time manipulating the apparatus than dogs in the low subgroup,but no statistically significant differences were observed(P＞0.05).Conclusions Highly sociable labradors have a greater cognitive ability,they are more able to suppress impulses during tests,more able to complete the multistep problem solving task,and more inclined to change strategies to seek new cues from people rather than obsessing over manipulating the apparatus when they are unable to solve a problem.

Objective:To summarize the clinical characteristics of eosinophilic esophagitis (EoE) in children.Methods:Clinical data of children with EoE who were hospitalized in the Department of Gastroenterology, Beijing Children′s Hospital, Capital Medical University from January 1, 2017, to December 31, 2022, were retrospectively analyzed.Results:A total of 18 children with EoE were included in the study, including 13 males and 5 females, with the age of 11.96 (4.96, 12.81) years.Vomiting was more common in preschool children (4/5), while abdominal pain was the main symptom in school-age and adolescent children (11/13). There were 22.22% (4/18) of the children with EoE had an increased white blood cell count, and 33.33%(6/18) had an increased eosinophil count.Allergic history in the first-degree relatives was detected in 55.56%(10/18) of the children with EoE.Total immunoglobulin E (IgE) level was elevated in 68.75% (11/16) of the children.Food-specific IgE was positive in 66.67% (12/18) of the children with EoE.Milk, eggs, and wheat were the most common allergens.Esophageal mucosal hyperemia and erythema, rough, erosion, linear ulcers, annular changes, furrow or wrinkled paper changes, granular changes, polypoid or relaxation of the cardia were seen under endoscopy, whereas 27.78% (5/18) of the children showed normal esophageal mucosa.The histopathology showed chronic inflammation of the esophagus and increased eosinophil count.Three patients were lost of follow-up, and the remaining 15 were followed up for 6-24 months.All children with EoE were treated with the elimination diet.Nine children treated with glucocorticoids experienced clinical remission in a short period of time, involving 1 case with recurrence after withdrawal and being effectively treated by hormone therapy, and 2 cases of repeated digestive system symptoms or increased eosinophil count after withdrawal and being effectively relieved by the elimination diet.Conclusions:EoE is more common in elderly children and boys.Vomiting is the main symptom in pre-school aged children, whereas abdominal pain is the main symptom in school-aged children and adolescents.Increased peripheral white blood cell count and eosinophil count can be detected in some cases, and most of them are positive for food allergen tests.Gastrointestinal endoscopy and histopathology are important in the diagnosis of EoE.Elimination diet may be effective in some patients.Glucocorticoids are of great significance in the treatment of EoE, but a few children are steroid-dependent.

Objective:To analyze the difference and reliability of blood 17-hydroxyprogesterone (17-OHP), an indirect screening index for congenital adrenal hyperplasia (CAH), between preterm and full-term infants.Methods:In this retrospective cross-sectional study, a total of 210 285 newborns who underwent CAH screening at the Neonatal Screening Center of Shanghai Children′s Hospital from January 2019 to December 2022 were collected, including 14 312 premature infants and 195 973 full-term infants.The concentration of 17-OHP in dried blood spots on filter paper was determined by an automatic fluorescence analyzer.The distribution of 17-OHP levels in preterm and full-term infants and its statistical index were analyzed.The Kolmogorov-Smirnov test was used for normal distribution.The skewed distribution data was converted into approximately normal distribution using Box-Cox.Outliers were eliminated by the interquartile range method.The cumulative frequency distribution map was drawn by R language programming.The 99.5 th percentile value was used as the screening threshold and compared with the reference value given by the manufacturer or laboratory and with the reference change value (RCV). Results:According to the threshold provided by the laboratory, 26.76‰ of premature infants were tested positive in preliminary screening, and 4 were confirmed with an incidence of 1∶3 578, while 0.79‰ of full-term infants were tested positive in preliminary screening, and 11 were confirmed with an incidence of 1∶17 816.The thresholds for CAH screening established indirectly were 20.35 nmol/L in preterm infants and 10.78 nmol/L in full-term infants.The relative deviations between the indirect CAH screening thresholds and the manufacturer′s or laboratory′s CAH screening thresholds were higher than the RCV, respectively.According to the indirect CAH screening thresholds, the negative and positive coincidence rates of 65 samples in 13 batches from the Centers for Disease Control and Prevention interlaboratory quality assessment program in the United States reached 100%.A retrospective analysis of 210 285 neonates showed that 17-OHP concentration was higher than the screening threshold in all CAH-positive neonates.The application of this screening threshold reduced the false positive rate of preterm infants by 59.79%.Conclusions:It is feasible to establish the CAH screening thresholds for premature and full-term infants by an indirect method, which can improve the efficiency of screening and provide better diagnostic basis for clinical practice.

Objective:This study aims to evaluate the quality and explore the preliminary clinical applications of a domestically developed hepatitis D virus nucleic acid quantification reagent (abbreviated as"domestic HDV RNA reagent").Methods:The sensitivity and accuracy of the reagent were evaluated in accordance with the WHO HDV RNA international standard, employing the Bio-Rad CFX Opus 96 real-time fluorescence quantitative PCR analysis system. Serial dilutions of pseudo-viruses or cell culture-derived virus were used to determine the linear range of the domestic HDV RNA reagent. Specificity was assessed using positive samples of HAV, HBV, HCV infection, and HEV national reference materials. Precision was evaluated with samples at both high and low concentrations. In a comparative analysis, 30 HDV IgG positive samples were tested using both the domestic HDV RNA reagent and the RoboGene HDV RNA kit based on the ABI 7500 FAST DX system. The Pearson correlation coefficient (r) was used to examine the correlation between the two reagents.Results:The domestic HDV RNA reagent demonstrated a high sensitivity of up to 6 IU/ml, consistent with that of the comparator reagent. The calibration curve for WHO HDV RNA standards had a slope of -3.286, with an amplification efficiency of 101.6%. The linear detection range spanned from 10 to 10 8 IU/ml for eight HDV genotypes. The domestic HDV RNA reagent exhibited exceptional specificity, without cross-reactivity observed with HAV, HBV, HCV, or HEV. Accuracy assessments at five concentration levels met the required standards, with intra-assay precision coefficient of variation ( CV) ranging from 1.20% to 4.20%, and inter-assay precision CV from 1.20% to 7.90%. The detection results for HDV IgG positive samples were highly correlated with the comparator reagent ( r=0.984, P<0.001), achieving a diagnostic accuracy of 100% compared to sequencing results. Conclusion:In this study, the domestic HDV RNA reagent possesses excellent specificity, accuracy, precision, and a broad linear range, attaining a sensitivity level on par with international reagents of the same type.

Objective To investigate the feasibility of developing a grading diagnostic model for schistosomiasis-induced liver fibrosis based on B-mode ultrasonographic images and clinical laboratory indicators. Methods Ultrasound images and clinical laboratory testing data were captured from schistosomiasis patients admitted to the Second People’s Hospital of Duchang County, Jiangxi Province from 2018 to 2022. Patients with grade I schistosomiasis-induced liver fibrosis were enrolled in Group 1, and patients with grade II and III schistosomiasis-induced liver fibrosis were enrolled in Group 2. The machine learning binary classification tasks were created based on patients’radiomics and clinical laboratory data from 2018 to 2021 as the training set, and patients’radiomics and clinical laboratory data in 2022 as the validation set. The features of ultrasonographic images were labeled with the ITK-SNAP software, and the features of ultrasonographic images were extracted using the Python 3.7 package and PyRadiomics toolkit. The difference in the features of ultrasonographic images was compared between groups with t test or Mann-Whitney U test, and the key imaging features were selected with the least absolute shrinkage and selection operator (LASSO) regression algorithm. Four machine learning models were created using the Scikit-learn repository, including the support vector machine (SVM), random forest (RF), linear regression (LR) and extreme gradient boosting (XGBoost). The optimal machine learning model was screened with the receiver operating characteristic curve (ROC), and features with the greatest contributions to the differentiation features of ultrasound images in machine learning models with the SHapley Additive exPlanations (SHAP) method. Results The ultrasonographic imaging data and clinical laboratory testing data from 491 schistosomiasis patients from 2019 to 2022 were included in the study, and a total of 851 radiomics features and 54 clinical laboratory indicators were captured. Following statistical tests (t = −5.98 to 4.80, U = 6 550 to 20 994, all P values < 0.05) and screening of key features with LASSO regression, 44 features or indicators were included for the subsequent modeling. The areas under ROC curve (AUCs) were 0.763 and 0.611 for the training and validation sets of the SVM model based on clinical laboratory indicators, 0.951 and 0.892 for the training and validation sets of the SVM model based on radiomics, and 0.960 and 0.913 for the training and validation sets of the multimodal SVM model. The 10 greatest contributing features or indicators in machine learning models included 2 clinical laboratory indicators and 8 radiomics features. Conclusions The multimodal machine learning models created based on ultrasound-based radiomics and clinical laboratory indicators are feasible for intelligent identification of schistosomiasis-induced liver fibrosis, and are effective to improve the classification effect of one-class data models.

Objective:To explore the clinical, biochemical and genetic characteristics of three children with Isoleucine metabolic disorders due to variants of HSD17B10 and ACAT1 genes. Methods:Two children with 17β hydroxysteroid dehydrogenase 10 (HSD17B10) deficiency and a child with β-ketothiolase deficiency (BKD) diagnosed at Shanghai Children′s Hospital between 2014 and 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to blood acylcarnitine, urinary organic acid and genetic testing, and candidate variants were analyzed with bioinformatic tools.Results:The main symptoms of the three children had included epilepsy, developmental delay, hypotonia and acidosis. Their blood acylcarnitine methylcrotonyl carnitine (C5: 1), 3-hydroxyisovalerylcarnitine (C5-OH) and 3-hydroxybutylcarnitine (C4OH) were increased to various extents, and urine organic acids including methyl crotonylglycine and 2-methyl-3-hydroxybutyric acid were significantly increased. Child 1 and child 2 were respectively found to harbor a c. 347G>A (p.R116Q) variant and a c. 274G>A (p.A92T) variant of the HSD17B10 gene, and child 3 was found to harbor compound heterozygous variants of the ACAT1 gene, namely c. 547G>A (p.G183R) and a c. 331G>C (p.A111P). Among these, the c. 274G>A (p.A92T) and c. 331G>C (p.A111P) variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variant of unknown significance (PP3_Strong+ PM2_supporting) and likely pathogenic (PM3+ PM2_Supporting+ PP3_Moderate+ PP4). Conclusion:Both the HSD17B10 deficiency and BKD can lead to Isoleucine metabolism disorders, which may be difficult to distinguish clinically. Genetic testing can further confirm the diagnosis. Discoveries of the HSD17B10: c. 274G>A (p.A92T) variant and the ACAT1: c. 331G>C (p.A111P) variant have enriched the mutational spectrum of the two diseases.