ObjectiveTo investigate the liver histopathological features of HBeAg-negative patients in the indeterminate phase of low-viral-load chronic hepatitis B virus （HBV） infection. MethodsA total of 271 patients with low-viral-load HBeAg-negative chronic HBV infection who underwent liver biopsy in Department of Infectious Diseases， Affiliated Hospital of Yan’an University， from September 2013 to June 2021 were enrolled as subjects， and the degree of liver injury was compared between patients based on age， sex， presence or absence of the family history of hepatitis B， HBsAg， and alanine aminotransferase （ALT） level. The chi-square test was used for comparison of categorical data between two groups. ResultsAmong the 271 patients with HBeAg-negative chronic HBV infection， 86 patients （31.73%） grade≥A2 liver inflammatory activity， 72 （26.57%） had a liver fibrosis stage of ive， and 112 （41.33%） had moderate or severe liver histological injury. The proportion of patients with grade≥A2 liver inflammatory activity in the patients with ALT>20 U/L was significantly higher than that in the patients with ALT≤20 U/L （χ²=3.938， P=0.047）. There were no significant differences in the proportion of patients with grade≥A2 liver inflammatory activity between the patients with different ages， sexes， family history of hepatitis B， HBsAg levels （all P>0.05），there were no significant differences in the proportion of patients with a liver fibrosis stage of ≥F2 between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels （all P>0.05）， and the stratified analysis of patients aged≤30 years and patients without the family history of hepatitis B showed no statistical significance between groups （all P>0.05）. There was no significant difference in the degree of liver histological injury between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels （all P>0.05）. ConclusionSignificant liver injury is observed in more than 40% of the patients with low-viral-load HBeAg-negative chronic HBV infection， and there is no significant difference in the degree of liver histological injury between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels. Even for the patients aged≤30 years who deny the family history of hepatitis B， there is still a considerable proportion of patients with liver injury， which should be taken seriously by clinicians.

Objective:To analyze the prenatal characteristics and pregnancy outcomes of fetuses with 17q12 microdeletion or microduplication.Methods:From January 2018 to December 2022, 14 fetuses diagnosed with 17q12 microdeletion and three with 17q12 microduplication by chromosomal microarray analysis folloning invasive prenatal diagnostic techniques at Nanjing Maternity and Child Health Care Hospital were retrospectively enrolled in this study. Relevant articles up to February 1, 2023, were retrieved from PubMed, Embase, China National Knowledge Infrastructure, Wanfang database, and Yiigle with the terms "17q12 microdeletion", "17q12 microduplication", "prenatal diagnosis", and "pregnancy outcome". Eighty-four 17q12 microdeletion cases and fourteen 17q12 microduplication cases were retrieved. Prenatal ultrasound features and pregnancy outcomes of those fetuses were analyzed and summarized.Results:In this study, ninety-eight 17q12 microdeletion cases and seventeen 17q12 microduplication cases were analyzed. (1) 17q12 microdeletion: The prenatal ultrasound showed all the 17q12 microdeletion cases had renal abnormalities (100.0%, 98/98), and renal hyperechogenicity was detected in 81.6% (80/98) of them; pedigree analysis suggested that 74.2% (49/66) mutations were de novo; 64.1% (41/64) of pregnant women chose to terminate the pregnancy and 35.9%(23/64) chose to continue pregnancy; eight out of 12 live births who were followed up had different degrees of abnormalities and four were normal during the follow-up period. (2) 17q12 microduplication: Among the 17 fetuses, 10 had upper gastrointestinal obstruction; pedigree analysis suggested that four were de novo mutations (4/13); nine out of 14 pregnant women with reported pregnancy outcomes chose to terminate the pregnancy, and five continued the pregnancy to delivery; follow up of the live births found that four neonates were normal and one had a good prognosis after surgery. Conclusions:Fetuses with 17q12 microdeletion often show renal hyperechogenicity in ultrasound images, and most mutations were de novo with poor prognosis. 17q12 microduplication in fetuses is often characterized by upper gastrointestinal obstruction, and most inherited from their parents.

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8⁺ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

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 genetic basis for a fetus with increased risk for Down syndrome and cardiac anomalies discovered by prenatal ultrasonography.Methods:A pregnant woman presented at the Women and Children′s Hospital of Ningbo University on August 21, 2023 were selected as the study subject. Clinical data were retrospectively analyzed. Maternal peripheral blood sample was collected for non-invasive prenatal testing (NIPT) based on fetal free DNA. Amniotic fluid sample was collected for G-banded chromosomal karyotyping analysis. Trio-whole exome sequencing (WES) was also carried out on the amniotic fluid sample and peripheral blood samples from the couple. Copy number variation (CNV) identified by the WES was validated by real-time fluorescent quantitative PCR (qPCR). Chromosomal karyotyping was also carried out for the couple. This study has been approved by the Medical Ethics Committee of Women and Children′s Hospital of Ningbo University (No. EC2020-048).Results:Ultrasound examination at 22 + 6 gestational weeks had indicated intrauterine growth retardation (IUGR). The fetus was also found to have ventricular septal defect, overriding aorta and pulmonary stenosis. NIPT indicated a low risk for aneuploidy of chromosomes 13, 18 and 21. G-banding analysis revealed that the fetus had a karyotype of 45, XY, -2[5]/46, XY, r(2)(p25q37)[55]. WES has identified a deletion of approximately 1 614.28 kb in the 2p25.3 region, namely seq[hg38]del(2)(p25.3p25.3)chr2: g.10500_1624775del. The same deletion was found in neither parent, suggesting a de novo origin. qPCR results confirmed the expression of target genes in the fetal sample to be significantly reduced, whilst no similar anomaly was found in either parent. Conclusion:The mosaicism ring chromosome 2 probably underlay the IUGR and cardiovascular malformations in this fetus.

Objective This study aimed to investigate the protective effect and mechanism of carvacrol hydrogel on the alveolar bone in rats with periodontitis.Methods A thermosensitive hydrogel supported by carvacrol was pre-pared using poloxamer and hydroxypropyl methyl cellulose as matrix.SD rats were randomly divided into blank group,periodontitis group,blank hydrogel group,and low-,medium-,and high-dose hydrogel groups.The periodonti-tis symptoms and the CT structure of the alveolar bone were observed.The changes in liver,spleen,kidney,and peri-odontal tissues were observed.The related indexes of bone metabolism in serum were detected.The expression of os-teoprotegerin(OPG)and nuclear transcription factor-κB(NF-κB)pathway proteins was determined by Western blot.The levels of inflammatory factors were assessed by quantitative reverse transcription polymerase chain reaction(qRT-PCR).Results Carvacrol hydrogel had good slow release,biocompatibility,and cell adhesion.The periodontitis of rats in the carvacrol hydrogel group was significantly alleviated,the expression of OPG protein in gingival tissue was significantly increased(P<0.01),and the levels of receptor activator of NF-κB ligand(RANKL),receptor activator of NF-κB(RANK),NF-κB protein,and inflammatory factors were significantly decreased(P<0.01).Conclusion Car-vacrol hydrogel can regulate the OPG and NF-κB pathways,reduce alveolar bone absorption,and improve periodontal inflammation.

Objective:To investigate the association between sleep status and the risk for coronary heart disease in adults in Suzhou.Methods:Using the baseline and follow up information of 53 269 local residents aged 30-79 years in China Kadoorie Biobank conducted in Wuzhong District, Suzhou, 51 929 subjects were included in this study after excluding those reporting coronary heart disease, stroke and cancer at the baseline survey. A Cox proportional hazards regression model was used to analyze the association of healthy sleep score (0-3 points) and sleep factors (snoring, insomnia, long sleep duration and nap) with the risk for coronary heart disease.Results:The median follow-up time was 11.12 years, and 1 304 individuals were diagnosed with coronary heart disease during the follow-up. After adjusting for potential confounders, occasional snoring ( HR=1.20, 95% CI: 1.04-1.38), usual snoring ( HR=1.17, 95% CI: 1.02-1.33), insomnia disorder ( HR=1.41, 95% CI: 1.12-1.78), daytime dysfunction ( HR=1.56, 95% CI: 1.20-2.03) and perennial nap ( HR=1.37, 95% CI: 1.19-1.59) were associated with increased risk of coronary heart disease. Compared with those with sleep score of 0 - 1 (low sleep quality), the people with sleep score of 3 had reduced risk of coronary heart disease by 26% ( HR=0.74, 95% CI: 0.63-0.87). Stratified analysis showed that the association of healthy sleep score 3 with risk of coronary heart disease was stronger in low physically active individuals (interaction P<0.05). Conclusions:Snoring, insomnia disorders, daytime dysfunction, and perennial napping were all associated with increased risk for coronary heart disease, and keep healthy sleep mode might reduce the risk for coronary heart disease in adults.

Objective:To understand the prevalence, blood pressure control, and influencing factors of hypertension in residents aged 35-75 years in Jiangsu Province, and provide data support and basis for hypertension prevention and treatment.Methods:A stratified cluster sampling method was adopted to conduct community population surveys in 22 districts and counties in 12 prefectures in Jiangsu from 2021 to 2022. A total of 123 531 permanent residents aged 35-75 years were included in the study. The questionnaire survey collected the information about the demographic characteristics, disease history, lifestyle, and control of hypertension of study subjects. Statistical software SPSS 23.0 was used for χ2 test and multivariate logistic regression analysis, and Joinpoint 4.9.1.0 software was used to evaluate the trend of age change. Results:The standardized prevalence of hypertension in study subjects was 46.60%, the prevalence was higher in men than in women, and in rural residents than in urban residents, and the standardized blood pressure control rate was 11.24%, and it was lower in men than in women and in rural residents than in urban residents. The hypertension prevalence and control rates showed increasing trends with age (both P<0.001). The multivariate analysis results showed that being man, older age, being rural resident, higher frequency of alcohol consumption, marital status of being separated and widowed, overweight and obese, abdominal obesity and stroke, diabetes mellitus and dyslipidaemic diseases histories, and family history of hypertension were risk factors for hypertension, and being man, being rural resident, living north area, higher frequency of alcohol consumption, and obesity were risk factors for blood pressure control. Conclusions:The prevalence of hypertension in residents aged 35-75 years in Jiangsu was high, and the rate of blood pressure control was low. It is suggested to take integrated intervention measures, especially in in rural residents and people with low levels of education to reduce the disease burden of the patients.

Objective:To analyze the comorbidity status and influencing factors of hypertension, diabetes, and dyslipidemia among middle-aged and elderly in Jiangsu Province and to provide support for "co-management of the three diseases".Methods:Data originated from the Comprehensive Prevention and Control Project of Cardiovascular and Cerebrovascular Diseases baseline survey in Jiangsu Province. Questionnaire interviews, physical examinations, and laboratory tests were conducted on 136 433 permanent residents aged ≥35 years who participated in the survey from 2021 to 2023. A multinomial logit model was established using SPSS 23.0 to analyze the influencing factors of the three comorbidities.Results:The comorbidity rate of hypertension, diabetes, and dyslipidemia among middle-aged and older adults in Jiangsu Province was 7.3%. Hypertension combined with dyslipidemia was the main comorbidity pattern, and patients with diabetes accounted for the largest proportion. Multinomial logistic regression analysis showed that the risk of being two types of the three comorbidities was higher in male, aging, urban residents, and those with high/technical secondary school, higher frequency of cigarette smoking and alcohol drinking, and longer daily sedentary time; the risk was lower in those with higher the level of physical activity and longer daily sleep time. Among the three types of comorbidities, males with aging, high/technical secondary school, regular smoking/quitting, higher frequency of alcohol drinking, and longer daily sedentary time had higher risk; those with an annual family income of 30 000-99 999 RMB, higher level of physical activity, and the daily sleep time of 7 hours had the lower risk (all P<0.05). Conclusions:The prevention and control of the three comorbidities among middle-aged and older adults in Jiangsu Province still needs strengthening. High-risk groups for the three diseases and comorbidities, such as males, low-income , and high/technical secondary school should be focused on. Middle-aged and older adults are suggested to increase daily physical activity, reduce daily static time, reasonably arrange sleep duration, and quit smoking and drinking as early as possible to maintain a healthy weight.

Objective:To investigate the clinical characteristics and prognostic factors of extracranial malignant rhabdoid tumors (eMRTs) in children.Methods:In this retrospective case series study, a retrospective analysis was conducted on clinical data of 21 eMRT patients admitted to Children′s Hospital of Nanjing Medical University from April 2018 to January 2023 and followed up until October 30, 2023.Patients were grouped according to their gender, age, tumor origin site, clinical staging, initial lactate dehydrogenase (LDH) level, extent of tumor resection, chemotherapy regimen, and radiotherapy.The Kaplan-Meier method was used to calculate the 2-year progression-free survival rate (PFS) and overall survival rate (OS) of the patients, and the Cox regression model was used to analyze the prognostic factors.Results:Among the 21 patients with eMRTs, there were 7 males and 14 females, with the age of onset of 24 (3-138) months.Immunohistochemistry showed that all tumor tissues of the patients did not secrete integrase interactor 1 (INI-1).Among them, 13 cases originated from the kidney, and 8 cases originated from extrarenal non-central sites.At the time of diagnosis, there were 4 cases in clinical stages Ⅰ-Ⅱ, 17 cases in stage Ⅲ-Ⅳ.Thirteen patients underwent complete tumor resection surgery, 7 underwent partial resection, and 1 only underwent biopsy.Among the 13 cases of renal rhabdoid tumors, 8 cases were treated with the AVDC (Epirubicin, Vincristine, Actinomycin D, Cyclophosphamide)/ICE (Ifosfamide, Carboplatin, Etoposide) regimen, and 5 cases were treated with the protocol for nephroblastoma; among the 8 cases of extrarenal non-central rhabdoid tumors, 5 cases were treated with the AVDC/ICE regimen, and 3 cases were treated with the commonly used protocol for soft tissue sarcoma.Thirteen patients received radiotherapy.One patient received consolidation therapy with autologous stem cell transplantation following chemotherapy and radiotherapy.As of October 2023, there were 14 survivors and 7 deaths.The overall 2-year PFS and OS were 56%(95% CI: 35.7%-88.5%) and 62%(95% CI: 43.2%-89.4%), respectively.Among the patients who received the AVDC/ICE alternating chemotherapy regimen, the 2-year PFS and OS were 73%(95% CI: 47.0%-100.0%) and 79% (95% CI: 56.4%-100.0%), respectively.Univariate Cox regression analysis showed that complete tumor resection, the AVDC/ICE alternating chemotherapy, and radiotherapy were associated with a better prognosis in children (all P≤0.05).Multivariate Cox regression analysis showed that whether to receive radiotherapy was an independent risk factor affecting the overall survival in children. Conclusions:eMRTs are more common in infants and young children, with high malignancy and invasiveness.There is currently no standard treatment.Complete tumor resection combined with the AVDC/ICE alternating chemotherapy and radiotherapy may improve the prognosis of children with eMRTs.