ZEB2 knockdown inhibits interleukin-1ß-induced cartilage degradation and inflammatory response through the Wnt/ß-catenin pathway in human chondrocytes.

OBJECTIVE: Osteoarthritis (OA) is a degenerative disease of the joints characterized by inflammation and cartilage degeneration. Zinc finger E-box binding homeobox 2 (ZEB2) contains various function domains that interact with multiple transcription factors involved in various cellular functions. However, the function of ZEB2 in OA has not been clearly illustrated. METHOD: Interleukin-1ß (IL-1ß) was used to establish an OA model in vitro. We quantified the ZEB2 expression in cartilage tissues from OA patients and IL-1ß-induced chondrocytes through reverse transcription-quantitative polymerase chain reaction and Western blot. We then used functional assays to explore the function of ZEB2 during OA progression. RESULTS: ZEB2 expression was increased in OA cartilage tissues and chondrocytes. The silencing of ZEB2 increased aggrecan and collagen II levels, and reduced the content of matrix metalloproteinase-3 (MMP-3), MMP-9, and MMP-13. ZEB2 knockdown inhibited the effects of IL-1ß on the production of nitric oxide and prostaglandin E2, and the expression of inducible nitric oxide synthase and cyclooxygenase-2. ZEB2 inhibition also suppressed the levels of IL-6 and tumour necrosis factor-α, and increased the IL-10 level in IL-1ß-treated cells. Mechanically, ZEB2 knockdown blocked the activation of the Wnt/ß-catenin pathway in chondrocytes. CONCLUSION: Knockdown of ZEB2 alleviated IL-1ß-induced cartilage degradation and the inflammatory response through the Wnt/ß-catenin pathway in chondrocytes.

[Multicenter evaluation of the diagnostic efficacy of jaundice color card for neonatal hyperbilirubinemia].

Objective: To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice. Methods: Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate's parents used the JCard to measure jaundice at the neonate's cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson's correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis. Results: Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) µmol/L, with a range of 23.7-717.0 µmol/L. The JCard level was (221.4±77.0) µmol/L and the TcB level was (252.5±76.0) µmol/L. Both the JCard and TcB values showed good correlation (r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2 µmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0 µmol/L. The TcB value of 205.2 µmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 µmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 µmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 µmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 µmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 µmol/L (both P<0.05). Conclusions: JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 µmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 µmol/L).

[Retrospective study of 70 cases with the head and neck non-parameningeal rhabdomyosarcoma].

Objective: To analyze the treatment outcomes and prognoses of children with head and neck non-parameningeal rhabdomyosarcoma (HNnPM RMS). Methods: A retrospective analysis was performed on the clinical data of children with HNnPM RMS admitted to Beijing Children's Hospital from September 2012 to September 2022. The clinical features, comprehensive treatment modes and prognoses of the patients were analyzed. The overall survival rate (OS) and event free survival rate (EFS) were calculated using the Kaplan-Meier method, and univariate analysis was performed using the Log-rank test. Results: A total of 70 children were included in this study, 38 males and 32 females, with a median age of 47 months (2-210 months). Pathological subtypes including the embryonal in 27 cases, the alveolar in 36 cases and the spindle cell and sclerosing in 7 cases. Thirty children (83.3%) with alveolar type were positive for FOXO1 gene fusion. All 70 children underwent chemotherapy, including 38 with neoadjuvant chemotherapy and 32 with adjuvant chemotherapy. Sixty of 70 children underwent surgery, of whom, 10 underwent two or more surgeries. There were 63 children underwent radiotherapy, including 54 with intensity-modulated radiation therapy, 4 with particle implantation and 5 with proton therapy. The median follow-up was 45 (5-113) months, the 5-year OS was 73.2%, and the 5-year EFS was 57.7%. Univariate analysis showed lymph node metastasis (χ2=5.022, P=0.025), distant metastasis (χ2=8.258, P=0.004), and high Intergroup Rhabdomyosarcoma Study (IRS) group (χ2=9.859, P=0.029) as risk factors for poor prognosis. Before June 2016, the 5-year OS based on BCH-RMS-2006 scheme was 63.6%, and after 2016, the 5-year OS based on CCCG-RMS-2016 scheme was 79.6%. Conclusion: Multidisciplinary combined standardized treatment can offer good treatment outcome and prognosis for children with HNnPM RMS. Local control is a key to the efficacy of comprehensive treatment.

Evidence from Mendelian randomization: increased risk of miscarriage in patients with asthma.

OBJECTIVE: Several observational studies have revealed a possible association between asthma and miscarriage. However, inferring causal relationships from observational studies may be fraught with problems like bias, reverse causation, and residual confounding. Therefore, to assess the possible causal effect of asthma on miscarriage, we performed a two-sample Mendelian randomization (MR) analysis. MATERIALS AND METHODS: Asthma (56,167 cases and 352,255 controls) and miscarriage (9,113 cases and 89,340 controls) data from two GWAS of European ancestry were evaluated. Single nucleotide polymorphisms (SNPs) were used as instrumental variables (IVs). The random effect inverse-variance weighted (IVW) Mendelian randomization approach was used as the primary method, and MR-Egger, weighted-median, and MR-PRESSO approaches were replenished as sensitivity analysis to test the robustness of the results. RESULTS: In total, 70 SNPs were obtained using the SNP criteria. Additionally, the MR study found substantial evidence of the causality between asthma and miscarriage [IVW, OR=1.092; 95% CI=1.017-1.174; p<0.05]. The sensitivity analysis demonstrated the reliability of the MR findings [horizontal pleiotropy (MR-Egger, intercept=-0.0002; Standard error of mean, se=0.006; p=0.975)]. CONCLUSIONS: Asthma is a causal risk factor for miscarriage in European populations, according to MR evidence. Our results emphasize the significance of asthma management in reducing the risk of miscarriage in individuals with asthma.

[Analysis of dynamic functional connectivity states and influencing factors of brain network in male patients with obstructive sleep apnea].

Objective: To analyze dynamic functional connectivity (dFNC) states and influencing factors of brain network in male patients with obstructive sleep apnea (OSA). Methods: A total of 111 male patients diagnosed with obstructive sleep apnea or presenting with simple snoring, who visited the Sleep Clinic at the Second Affiliated Hospital of Soochow University between August 2020 and December 2021, were prospectively selected for this study. General information was collected, and polysomnography (PSG) was performed. Based on the oxygen desaturation index (ODI), the participants were divided into three groups: primary snoring group (ODI<5 events/hour, n=34), mild to moderate OSA group (5 events/hour≤ODI<30 events/hour, n=43), and sever OSA group (ODI≥30 events/hour, n=34). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS). Resting-state functional magnetic resonance imaging (fMRI) data were collected and preprocessed. dFNC matrices were constructed using a sliding time window approach. The number of dFNC states was determined using k-means clustering analysis. Three parameters, namely, fractional time (FT), mean dwell time (MDT), and number of transitions (NT), were used to characterize the temporal properties of dFNC states. Differences in the temporal properties of dFNC states among the groups were compared. The correlations between temporal properties and PSG parameters, as well as MoCA and ESS scores, were further analyzed. Multiple stepwise linear regression analysis was performed to identify the influencing factors of the temporal properties of dFNC states. Results: The age of the patients was (40.2±8.6) years (range: 25-65 years). There were no significant differences in age, smoking history and alcohol history, and MoCA scores among the three groups (all P>0.05). Three dFNC states were extracted through k-means clustering analysis: state 1, characterized by strong connections within the visual and sensorimotor networks with a frequency of 31.7% (4 611/14 541); state 2, characterized by strong connections within the default mode network, attention network, and other cognitive networks, with the lowest frequency of 22.1% (3 213/14 541); state 3, characterized by weaker connections across the whole brain, with the highest frequency of 46.2% (6 717/14 541). The FT [0.28 (0.05, 0.35) vs 0.39 (0.26, 0.53)] and MDT [8.20 (4.35, 12.54) vs 11.68 (8.50, 16.69)] of state 2 in the sever OSA group were lower than those in the primary snoring group (both P<0.05), while there were no significant differences in the temporal properties of states 1 and 3 among the three groups (all P>0.05). The FT and MDT of state 2 were correlated with body mass index (BMI), apnea-hypopnea index (AHI), ODI, and minimum oxygen saturation (MinSaO2) (FT: r values were -0.218, -0.230, -0.249, 0.198, respectively; MDT: r values were 0.269, -0.253, -0.265, 0.209, respectively; all P<0.05). There were no significant correlations between the temporal properties and MoCA or ESS scores (all P>0.05). ODI was found to be an influencing factor for the temporal properties of state 2 (FT: ß=-0.225, 95%CI:-0.227 to -0.223; MDT: ß=-0.241, 95%CI:-0.289 to -0.195). Conclusions: Male patients with OSA exhibit alterations in specific temporal properties of brain network dynamic functional connectivity, which are associated with nocturnal oxygen parameters. This may be one of the mechanisms underlying brain functional damage in patients with OSA.

[Clinical analysis of 10 cases of multi-center tumor necrosis factor receptor-associated periodic syndrome].

Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.

[Impact of different diagnostic criteria for assessing mild micro-hepatic encephalopathy in liver cirrhosis: an analysis based on a prospective, multicenter, real-world study].

Objective: To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test. Methods: This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ (2) test. A kappa test was used to compare the consistency between groups. Results: After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea (Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences (P < 0.001). Conclusion: The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

[Clinical and genetic characteristics of children with dopa-responsive dystonia caused by tyrosine hydroxylase gene variations].

Objective: To explore the clinical and genetic characteristics of children with dopa-responsive dystonia (DRD) caused by tyrosine hydroxylase (TH) gene variations. Methods: Clinical data of 9 children with DRD caused by TH gene variations diagnosed in the Department of Children Rehabilitation, the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2022 were retrospectively collected and analyzed, including the general conditions, clinical manifestations, laboratory tests, gene variations and follow-up data. Results: Of the 9 children with DRD caused by TH gene variations, 3 were males and 6 were females. The age at diagnosis was 12.0 (8.0, 15.0) months. The initial symptoms of the 8 severe patients were motor delay or degression. Clinical symptoms of the severe patients included motor delay (8 cases), truncal hypotonia (8 cases), limb muscle hypotonia (7 cases), hypokinesia (6 cases), decreased facial expression (4 cases), tremor (3 cases), limb dystonia (3 cases), diurnal fluctuation (2 cases), ptosis (2 cases), limb muscle hypertonia (1 case) and drooling (1 case). The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included motor delay, truncal hypotonia, oculogyric crises, status dystonicus, hypokinesia, decreased facial expression, and decreased sleep. Eleven TH gene variants were found, including 5 missense variants, 3 splice site variants, 2 nonsense variants, and 1 insertion variant, as well as 2 novel variants (c.941C>A (p.T314K), c.316_317insCGT (p.F106delinsSF)). Nine patients were followed up for 40 (29, 43) months, and no one was lost to follow-up. Seven of the 8 severe patients were treated by levodopa and benserazide hydrochloride tablets and 1 severe patient was treated by levodopa tablets. All the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets. Although the weight of the patients increased and the drug dosage was not increased, the curative effect remained stable and there was no obvious adverse reaction. One severe patient developed dyskinesia in the early stage of treatment with levodopa and benserazide hydrochloride tablets and it disappeared after oral administration of benzhexol hydrochloride tablets. Until the last follow-up, motor development of 7 severe patients returned to normal and 1 severe patient still had motor delay due to receiving levodopa and benserazide hydrochloride tablets for only 2 months. The very severe patient was extremely sensitive to levodopa and benserazide hydrochloride tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed. Patients of the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets, and it takes a long time before full effects of treatment become established. Long-term effect is stable without increasing the drug dosage, and no obvious side effect is observed.

[Survey on the prevalence and related factors of thyroid disorders in different iodine intake regions in China in 2015-2017].

Objective: To observe the prevalence and related factors of thyroid diseases in different iodine intake areas from 2015 to 2017 after the implementation of national salt iodization policy in China for 20 years. Methods: A cross-sectional survey. Multi-stage stratified cluster random sampling was used to randomly select subjects meeting the inclusion criteria from 31 provinces, municipalities and autonomous regions in China from January 2015 to December 2017, and stratified by age and sex. The survey included questionnaire, physical examination and thyroid ultrasonography. At the same time, the concentrations of serum thyrotropin, thyroxine, thyroid peroxidase antibody (TPOAb), thyroid globulin antibody (TgAb) and urinary iodine were measured.To determine whether the patient has a certain thyroid disease according to the above results. Different iodine nutrition areas were defined according to urinary iodine concentration, and the influence of iodine nutrition status in different iodine intake areas on thyroid diseases was analyzed. Results: A total of 78 470 adults were included, including 39 893 in the area of moderate iodine, 28 779 in the area of adequate iodine, and 9 798 in the area of excessive iodine.In the above three regions, the prevalence of subclinical hyperthyroidism (hyperthyroidism) was 0.45% (95%CI: 0.39%-0.52%), 0.50%(95%CI: 0.35%-0.70%)and 0.27%(95%CI: 0.20%-0.35%), respectively, with statistical significance(χ²=6.92, P=0.003). The prevalence of subclinical hypothyroidism (hypothyroidism) was 11.36% (95%CI: 10.73%-12.02%), 13.57%(95%CI: 11.70%-15.69%) and 16.18%(95%CI: 12.41%-20.82%), respectively, with statistical significance(χ²=5.08, P=0.009). The prevalence rates of Graves' disease, TPOAb, goiter and thyroid nodule among the three regions were statistically significant (all P<0.05). There were no significant differences in the prevalence of clinical hyperthyroidism and clinical hypothyroidism and the positive rate of TgAb among the three regions (all P>0.05). Multivariate logistic regression model analysis showed that excess iodine was a risk factor for subclinical hypothyroidism (OR=1.24, 95%CI: 1.06-1.44), and a protective factor for thyroid nodules (OR=0.73, 95%CI: 0.57-0.94). Iodine overdose was a risk factor for subclinical hypothyroidism (OR=1.47, 95%CI: 1.08-2.01), while it was a protective factor for subclinical hyperthyroidism (OR=0.56, 95%CI: 0.41-0.77), and TPOAb positive (OR=0.93, 95%CI: 0.87-0.99), goiter (OR=0.33, 95%CI: 0.17-0.66) and thyroid nodule (OR=0.77, 95%CI: 0.61-0.97). Conclusions: There are significant differences in the prevalence of subclinical hyperthyroidism, subclinical hypothyroidism, positive TPOAb, thyroid nodule and goiter in different iodine intake regions. Different iodine intake levels have an effect on the incidence of thyroid diseases.

[Study on the distribution pattern of allergen sIgE in patients with respiratory allergic diseases in a hospital in Shanxi Province].

To explore the allergen sensitization status of patients with respiratory allergic diseases in Shanxi Province, and to provide a basis for the diagnosis, treatment and prevention of allergic diseases. It is a cross-sectional study, a total of 1 680 patients with allergic rhinitis and/or asthma diagnosed at the Department of Allergic Reaction of Shanxi Bethune Hospital from July 2021 to June 2023 who underwent allergen sIgE testing and/or skin prick test were retrospectively enrolled.There were 772 males and 908 females.The age range was 3 to 88 years. The median age was 35 years.There were 108 cases in the child group (≤12 years old), 102 cases in the adolescent group (13-17 years old), 819 cases in the youth group (18-40 years old), 498 cases in the middle-aged group (41-65 years old), and 153 cases in the elderly group (>65 years old). There were 333 cases in the allergic rhinitis group, 827 cases in the allergic asthma group, and 520 cases in the allergic rhinitis with asthma group. There were 1 254 urban patients and 426 rural patients.There were 253 cases in the northern Shanxi region, 1 195 cases in the central Shanxi region, and 232 cases in the southern Shanxi region. Statistical analyses were performed using the χ 2 test or Fisher's exact probability method to compare the differences in allergen sIgE positivity rates by sex, age, disease, living environment, and geography. The results showed that 1 027 patients (61.1%) were positive for at least one allergen sIgE, with Artemisia having the highest rate of positivity (603/1 680, 35.9%), followed by ragweed (302/1 680, 18.0%) and dust mite combinations (245/1 680, 14.6%). The number of individuals with single-allergen sIgE positivity was 357 (357/1 027, 34.8%), with the highest number of single-allergen sIgE positive results associated with Artemisia (114/357, 31.9%). The number of multiple-allergen sIgE positive results was 670 cases (670/1 027, 65.2%), with the highest number of patients having 2 allergen sIgE positive results (243/670, 36.3%). The overall positivity rate for allergen sIgE was significantly higher among males than among females (65.7% vs. 57.3%, χ2=12.405, P<0.001). Overall positivity for inhalant allergen sIgE was higher in the child and adolescent groups (88.0% vs. 88.2% vs. 59.8% vs. 40.2% vs. 19.0%, χ2=223.372, P<0.001), and food allergen sIgE positivity was highest in the child group (54.6% vs. 36.3% vs. 26.0% vs. 18.9% vs. 21.6%,χ2=66.383,P<0.001). The sIgE positivity rate of inhalant allergens was significantly higher in the allergic rhinitis group and the allergic rhinitis with asthma group than in the allergic asthma group, except for cockroaches and molds (P<0.05). The overall positive rate of allergen sIgE was significantly higher among urban patients than among rural patients (66.2% vs. 46.2%, χ2=53.230, P<0.001). The difference in the overall positive rate of allergen sIgE among patients from different regions was not statistically significant (56.1% vs. 62.0% vs. 62.1%, χ2=3.140, P=0.208). The sIgE positivity of dust mite combinations was significantly higher in the central Shanxi region and the southern Shanxi region than in the northern Shanxi region (15.5% vs. 18.1% vs. 7.1%,χ2=14.411, P=0.001). In conclusion, artemisia was the most important sensitizer for respiratory allergic diseases in Shanxi Province. The types of allergens and positivity rates were different for different sexes, ages, diseases, living environments, and regions. Therefore, patients with allergic diseases should be tested for allergens to help with the diagnosis, treatment and prevention of allergic diseases.

[Feasibility of ultrasound radiomics-based models for classification of hepatic echinococcosis].

OBJECTIVE: To investigate the feasibility of establishment of ultrasound radiomics-based models for classification of hepatic echinococcosis, so as to provide insights into precision ultrasound diagnosis of hepatic echinococcosis. METHODS: The ultrasonographic images were retrospectively collected from 200 patients with hepatic echinococcosis in Shiqu County, Ganzi Tibetan Autonomous Prefecture, Sichuan Province in October 2014, and the regions of interest were plotted in ultrasonographic images of hepatic echinococcosis lesions. The ultrasound radiomics features of hepatic echinococcosis were extracted with 25 methods, and screened using pre-selection and the least absolute shrinkage and selection operator. Then, all ultrasonographic images were randomly assigned into the training and independent test sets according to the type of lesions at a ratio of 7:3. Machine learning models for classification of hepatic echinococcosis were created based on two classifiers, including kernel logistic regression (KLR) and medium Gaussian support vector machine (MGSVM). The receiver operating characteristic (ROC) curves were plotted, and the sensitivity, specificity and areas under the curves (AUC) of the created machine learning models for classification of hepatic echinococcosis were calculated. RESULTS: A total of 5 005 ultrasound radiomics features were extracted from 200 patients with hepatic echinococcosis using 25 methods, and 36 optimal radiomics features were screened through feature selection, based on which two machine learning models were created, including KLR and MGSVM. ROC curve analysis showed that MGS-VM presented a higher efficacy for hepatic echinococcosis classification than KLR in the training set, with a sensitivity of 0.82, a specificity of 0.78 and AUC of 0.88, while KLR presented a higher efficacy for hepatic echinococcosis classification than MGSVM in the independent test set, with a sensitivity of 0.82, a specificity of 0.72 and AUC of 0.86, respectively. CONCLUSIONS: Ultrasound radiomics-based machine learning models are feasible for hepatic echinococcosis classification.

[Preclinical study of T cell receptor specifically reactive with KRAS G12V mutation in the treatment of malignant tumors].

OBJECTIVE: KRAS gene is one of the most common mutations of proto-oncogenes in human tumors, G12V is one of the most common mutation types for KRAS. It's challenging to chemically acquire the targeted drug for this mutation. Recent studies reported that this mutation peptides can form a neoepitope for T cell recognition. Our study aims to clone the T cell receptor (TCR) which specifically recognizes the neoepitope for KRAS G12V mutation and constructs TCR engineered T cells (TCR-T), and to investigate if TCR-Ts have strong antitumor response ability. METHODS: In this study, tumor infiltrating lymphocytes were obtained from one colorectal cancer patient carrying KRAS G12V mutation. Tumor-reactive TCR was obtained by single-cell RT-5' rapid-amplification of cDNA ends PCR analysis and introduced into peripheral blood lymphocytes to generate TCR-Ts. RESULTS: We obtained a high-affinity TCR sequence that specifically recognized the HLA-A*11:01-restricted KRAS G12V8-16 epitope: KVA11-01. KVA11-01 TCR-T could significantly kill various tumor cells such as PANC-1, SW480 and HeLa (overexpressing HLA-A*11:01 and KRAS G12V), and secreting high levels of interferon-γ (IFN-γ). Non-specific killing experiments suggested KVA11-01 specifically recognized tumor cells expressing both mutant KRAS G12V and HLA-A*11:01. In vivo assay, tumor inhibition experiments demonstrated that infusion of approximately 1E7 KVA11-01 TCR-T could significantly inhibit the growth of subcuta-neously transplanted tumors of PANC-1 and HeLa (overexpressing HLA-A*11:01 and KRAS G12V) cells in nude mice. No destruction of the morphologies of the liver, spleen and brain were observed. We also found that KVA11-01 TCR-T could significantly infiltrate into tumor tissue and had a better homing ability. CONCLUSION: KVA11-01 TCR-T cells can effectively target a variety of malignant tumor cells carrying KRAS G12V mutation through in vitro and in vivo assay. KVA11-01 TCR-T cells have excellent biological activity, high specificity of target antigen and homing ability into solid tumor tissue. KVA11-01 TCR-T is expected to be an effective treatment for patients with KRAS G12V mutant solid malignancies.

Deep Underground Laboratory Measurement of

The ^{13}C(α,n)^{16}O reaction is the main neutron source for the slow-neutron-capture process in asymptotic giant branch stars and for the intermediate process. Direct measurements at astrophysical energies in above-ground laboratories are hindered by the extremely small cross sections and vast cosmic-ray-induced background. We performed the first consistent direct measurement in the range of E_{c.m.}=0.24 to 1.9 MeV using the accelerators at the China Jinping Underground Laboratory and Sichuan University. Our measurement covers almost the entire intermediate process Gamow window in which the large uncertainty of the previous experiments has been reduced from 60% down to 15%, eliminates the large systematic uncertainty in the extrapolation arising from the inconsistency of existing datasets, and provides a more reliable reaction rate for the studies of the slow-neutron-capture and intermediate processes along with the first direct determination of the alpha strength for the near-threshold state.

[International multi-center evaluation of a rapid antigen test based on gold immunochromatographic assay for detection of severe acute respiratory syndrome coronavirus 2].

Objective: The gold immunochromatographic assay for detection of SARS-CoV-2 antigen was evaluated by international multi-center clinical trial. Methods: A total of 1 855 clinical parallel samples with valid test results (for nucleic acid and antigen tests, respectively) were collected from nine countries, including Germany, the United Kingdom, Ukraine, France, India, Thailand, Malaysia, the United States of America and Brazil, with sampling period from January 3 to September 22, 2021. These samples were detected by SARS-CoV-2 antigen test kit (colloidal gold immunochromatography assay) and nucleic acid detection kit (real-time fluorescent quantitative reverse transcription polymerase chain reaction). Positive coincidence rates [(number of antigen-positive cases/nucleic acid-positive cases)×100%], negative coincidence rates [(number of antigen-negative cases/nucleic acid-negative cases)×100%], total coincidence rates [(number of cases with consistent results for both antigen and nucleic acid detection/number of total cases) ×100%], as well as Kappa values were calculated. The differences of the above indictors among different countries were evaluated by the coefficient of variation. The detection rates of the antigen test for samples with different cycle threshold values (Ct values) for the nucleic acid detection, different characteristics and different mutant strains were analyzed. Results: For all samples, the positive, negative, and total coincidence rate between the antigen test and nucleic acid assay was 90.8% (569/627), 99.7% (1 224/1 228) and 96.7% (1 793/1 855), respectively, and the consistency coefficient Kappa value was 0.924. Among these countries, the coefficient of variation for positive coincidence rates (except for Malaysia with a lot of samples with Ct value>30), negative coincidence rates (except for France without negative samples) and total coincidence rates (except for France) was 6%,<1%, and 6%, respectively. When Ct values were less than 25, the detection rates of antigen test were 83.3%-100% for each countries (the coefficient of variation was 6%); the total detection rate and the coefficient of variation was 93.4% (428/458) and 5%, respectively, for asymptomatic infected persons and cases within 7 days post onset of symptoms; the total detection rate for various SARS-CoV-2 mutant strains was 97.5% (119/122); and it showed negative results for samples from cases infected with other viruses, including influenza A virus subtype H1N1, influenza B virus, respiratory syncytial virus subgroups A and B, coxsackievirus 16, human metapneumovirus, parainfluenza virus types 1 and 4, Epstein-Barr virus and adenovirus. Conclusion: The SARS-CoV-2 antigen test kit showed excellent authenticity, and there were few differences for its indictors among nine countries, therefore it can meet the needs of large-scale early screening of SARS-CoV-2 infection.

[Advances in studies on schistosome-host interactions mediated by extracellular vesicles].

Extracellular vesicles (EVs) are minute particles secreted by the cells of living organisms, which can encapsulate various bioactive molecules for long-distance transport to present biological functions. With the recent studies on parasite-host interactions, EVs, as a carrier for long-distance transport of worm-derived molecules, have been paid much attention during the across-species regulation of hosts. During schistosome infections, adult worms and eggs have been found to mediate hosts via secretion of EVs. This review presents the advances in the studies on schistosome-host interactions mediated by EVs.

[Changes of serum lipid profiles and the correlation analysis in clinic-pathological features of pancreatic cancer patients].

Objective: To examine the characteristics of blood lipid profile and the correlation with clinic-pathological features of pancreatic cancer patients. Methods: The clinical and pathological data of 265 pancreatic cancer patients who received radical surgical treatment at Department of General Surgery,Qilu Hospital,Shandong University from January 2013 to September 2020 were collected and analyzed retrospectively. Among the 265 pancreatic cancer patients,there were 170 males and 95 females,with age of (61.0±9.6)years(range:28 to 86 years). General information,lipid indicators and clinic-pathological information were collected from electronic medical record system,and follow-up information gained by telephone. According to level of serum lipid in pancreatic cancer patients,265 patients were divided into dyslipidemia group(n=115) and normal lipid group(n=150). Pearson χ2,Student's t tests, variance analysis or univariate Logistic regression was used to analyze the correlation between dyslipidemia and clinico-pathological characteristics of pancreatic cancer,respectively. Kaplan-Meier survival curve was used to assessed the influence of dyslipidemia on prognosis of pancreatic cancer patients. Results: In 265 pancreatic cancer patients,115(43.4%)of them had dyslipidemias,and the most common form was increase of triglyceride(TG)(72.2%). In pancreatic cancer with dyslipidemias group,patients with body mass index ≥25 kg/m2 had higher proportion than normal lipid group(36.1%(26/72) vs. 21.2%(21/99),χ²=4.643,P=0.031); The proportion of carcinoma located at head of pancreas(83.5%(96/115) vs. 40.7%(61/150),χ²=49.412,P<0.01), staging of T1/T2(79.1%(91/115) vs. 60.7%(91/150),χ²=10.316,P<0.01) and lymphatic metastasis(36.5%(42/115) vs. 22.7%(34/150),χ²=6.007,P<0.01) were higher. In patients of pancreatic cancer, dyslipidemias were closely associated with tumor location(OR=10.529,P<0.01)and body mass index(OR=3.671,P=0.008). Serum lipid profile results showed that TG,total cholesterol and high-density lipoprotein(HDL) disorders were associated with tumor location(P<0.05). TG disorder had association with body mass index(P<0.05), and HDL disorder had association with tumor stage(P<0.05). Moreover, the result of survival analysis showed that dyslipidemia was not a factor to impact the prognosis of pancreatic cancer patients underwent surgery(P>0.05). Conclusions: In pancreatic cancer patients,TG disorder was the most common type of dyslipidemia. Dyslipidemia has closely association with clinicopathologic features,including tumor location,body mass index,tumor stage. However,dyslipidemia had little effect on prognosis of pancreatic cancer patients.

[Clinical characteristics and prognostic analyses of cervical neuroblastoma].

Objective: To determine the characteristics of cervical neuroblastoma and the effect of resection extent on survival and outcomes. Methods: We performed a retrospective review of 32 children with cervical neuroblastoma treated at Beijing Children's Hospital between April 2013 and August 2020. Data were collected from the medical record. The individualized therapy was designed based on staging and risk group. Based on the extent of resection, patients were divided into incomplete and complete resection groups. Event free and overall survival rates were compared between two groups using the Kaplan-Meier method. Results: The ages of patients ranged from 1 month to 81 months, with a median age of 11 months, including 7 males and 15 females. Twenty-nine patients (90.6%) presented with cervical painless mass. The average diameter of the primary tumors was (5.12±1.43) cm. Tumors were located in the parapharyngeal space in 25 cases (78.1%) and in the root of the neck in 7 cases (21.9%). None had MYCN amplification. According to International Neuroblastoma Staging System (INSS), 15 patients (46.9%) were identified as stage 1, 11 patients (34.3%) as stage 2B, 3 patients (9.4%) as stage 3 and 3 patients (9.4%) as stage 4. There were 12 patients (37.5%) at low risk, 17 patients (53.1%) at intermediate risk and 3 patients at high risk according to Children's Oncology Group (COG) risk classification system. All patients underwent tumor resection. Postoperatively Horner's syndrome occurred in 13 patients (40.6%), pneumonia in 9 patients (28.1%), pharyngeal dysfunction in 8 patients (25.0%) and transient hoarseness in 4 patients (12.5%). At a median follow-up of 36.5 months, the overall survival rate was 96.4%, with no significant difference between incomplete and complete resection groups (100.0% vs. 96.3%, χ2=0.19, P=0.667); the event free survival rate was 78.1%, with a significant difference between the two groups (40.0% vs. 85.2%, χ²=6.71, P=0.010). Conclusions: Primary cervical neuroblastoma has a young onset age, mostly in low and medium risk groups, and represents favorable lesions with good outcomes after multidisciplinary therapy. Less aggressive surgery with preservation of important structures is recommended. Complete resection should not be attempted if it would compromise vital structures.

Assembly of Ultralong Hydroxyapatite Nanowires into Enamel-like Materials.

To develop dental restorative materials with enamel-like structures, ultralong hydroxyapatite (HA) nanowires were synthesized by a hydrothermal method, followed by functionalization with 3-methacryloxypropyltrimethoxysilane (KH-570). The mixture of HA nanowires, KH-570, and light initiator was stirred and centrifuged. The precipitate was vacuum filtered to remove excessive KH-570 and then pressured under cold isostatic pressing (10 MPa × 24 h). Finally, the block was polymerized by lighting. Scanning electron microscopy and transmission electron microscopy showed that HA nanowires with aspect ratios >1,000 were assembled into enamel rod-like microstructures and evenly dispersed in the polymerized KH-570 silane matrix to form enamel-like structures. Thermogravimetric analysis demonstrated that the content of HA nanowires reached 72 wt% in the composite. The enamel-like composite showed a similar hardness, frictional property, and acid-etching property to those of enamel and a comparable or even better diametral tensile strength and compressive strength than some commercial composite resins in mechanical tests in vitro. In addition, the enamel-like composite had good cytocompatibility. Such enamel-like composites may have the potential to be used in biomimetic tooth restorations in the future.