To investigate the changes in peripheral blood immune cells before and after the onset of septic shock in patients with malignant tumors, and to analyze the relationship between these immune cells and patient prognosis.

ObjectiveTo investigate the role of interleukin （IL）-17A in acute inhalational pneumonia induced by the highly drug-resistant and hypervirulent Staphylococcus aureus strain USA300-R in mice. MethodsAn acute inhalational pneumonia model was established in mice using an aerosolized pulmonary delivery technique. RNA sequencing （RNA-seq） and enzyme-linked immunosorbent assay （ELISA） were employed to examine the expression dynamics of Il17a mRNA and IL-17A protein， respectively， in the lungs of infected mice. Il17a knockout （Il17a^-/-） mice were generated using CRISPR/Cas9 gene editing technology. The survival rate， body weight， bacterial load in lung tissue， and histopathological changes were compared between Il17a^-/- and wild-type （WT） mice following inhalational infection with USA300-R. Results12 hours after USA300-R infection， compared to pre-infection， the expression level of Il17a mRNA in lung tissue and the level of IL-17A protein in bronchoalveolar lavage fluid （BALF） increased by approximately 50-fold （P<0.01） and 6-fold （P<0.001）， respectively. Compared to WT mice， Il17a^-/- mice exhibited approximately 10-fold higher bacterial loads in lung tissue at both 12 and 24 hours post-infection （P<0.001， P<0.05）. However， they showed significantly attenuated lung histopathological injury， reduced alveolar wall thickening， markedly decreased neutrophil infiltration， and an approximately 50% improvement in survival rate （P<0.05）. ConclusionIn acute Staphylococcus aureus USA300-R inhalational pneumonia， IL-17A contributes to bacterial clearance by recruiting neutrophils； however， excessive neutrophil infiltration exacerbates pulmonary inflammation and injury， reduces survival rates， and represents a potential therapeutic target.

ObjectiveTo investigate the difference in the risk of cardiovascular diseases between patients with different subtypes of non-alcoholic fatty liver disease （NAFLD） from the perspective of metabolism， since cardiovascular events induced by metabolic disorders are the leading cause of death in NAFLD. MethodsThe cluster sampling method was used to conduct a multicenter cross-sectional study among three representative hospitals in Pudong New Area of Shanghai， China. A total of 37 122 sets of physical examination data from July 2022 to June 2023 were collected and stratified according to body mass index （BMI）. The chi-square test was used for comparison of continuous data between groups， and a multivariable Logistic regression analysis was used to investigate the association between NAFLD subtypes and cardiometabolic risk factors. ResultsA total of 9 372 cases of NAFLD were detected， with a detection rate of 25.25%， and more than 97% of these patients were diagnosed with metabolic associated fatty liver disease （MAFLD）. The subgroup analysis showed that the detection rates of lean， overweight， and obese NAFLD were 7.72%， 33.99%， and 63.56%， respectively. Compared with the patients with lean or overweight NAFLD， the patients with obese NAFLD showed a significantly higher proportion of patients with abnormalities in blood pressure， blood glucose， triglyceride （TG）， high-density lipoprotein （HDL） or uric acid （all P<0.001）. Among related risk factors， lean NAFLD was associated with the increase in total cholesterol （TC）（P<0.05）， while overweight NAFLD and obese NAFLD were not associated with TC abnormalities （P>0.05）； obese NAFLD was not associated with TG abnormalities， while lean NAFLD and overweight NAFLD were associated with TG abnormalities （both P<0.05）； all types of NAFLD were associated with the abnormalities of waist-hip ratio， blood pressure， blood glucose， low-density lipoprotein， HDL， and uric acid （all P<0.05）. ConclusionThe detection rates of different subtypes of NAFLD in Shanghai Pudong are close to those reported in China and globally， and the epidemiologic data of NAFLD can be used analogously for MAFLD. There are certain differences in the distribution and association of cardiometabolic risk factors between different subtypes of NAFLD， and targeted interventions should be formulated based on the metabolic characteristics of each type of NAFLD.

To summarize the clinical experience of Professor LIU Jinmin in treatment for epilepsy. It is believed that main pathogenesis of epilepsy is yangming failure to close and vital activity loss control， so a therapeutic approach focused on restoring the closure of yangming and regaining vital activity was proposed for the treatment of epilepsy. For excess syndrome， the treatment focuses on draining excess and descending qi， promoting purgation and restoring spirit. When yangming dryness-heat predominates， the approach involves unblock the bowels and regulating the spirit， descending qi and reducing fire， with modified Chengqi Decoction （承气汤） as prescription； when yangming phlegm-fire predominates， the treatment focuses on clearing heat and resolving phlegm， calming mind and suppressing fright， with modified Qingxin Wendan Decoction （清心温胆汤） as prescription； when yangming blood stasis predominates， the approach involves breaking up blood stasis and promoting purgation， eliminating stasis and awakening the mind， with Taoren Chengqi Decoction （桃核承气汤） as prescription. For deficiency syndrome， the treatment emphasizes tonifying deficiency and raising qi， strengthening the stomach and nourishing the spirit. When center qi deficiency and sinking of clear qi of the nutrients from food， the approach involves replenishing and uplifting qi while nourishing vital activity， with modified Liujunzi Decoction （六君子汤） as prescription； when yin deficiency and fluid consumption， the treatment focuses on nourishing stomach and tonifying yin， promoting fluid production and calming the spirit， with modified Maimendong Decoction （麦门冬汤） combined with Yiwei Decoction （益胃汤） as prescriptions. In clinical situations of deficiency-excess complex， it is essential to distinguish the primary condition from the secondary， applying both supplementing and draining methods flexibly to achieve optimal treatment.

AIM: To investigate the predictive value of serum histone deacetylase 1(HDAC1)and endothelial nitric oxide synthase(eNOS)for infectious endophthalmitis after cataract surgery.METHODS: A total of 362 cataract patients(362 eyes)admitted to our hospital from January 2020 to January 2023 were selected as the research objects. According to the occurrence of postoperative infectious endophthalmitis, they were divided into infection group(15 cases, 15 eyes)and non-infection group(347 cases, 347 eyes). Enzyme linked immunosorbent assay(ELISA)was applied to detect the levels of serum HDAC1 and eNOS in all subjects, and the levels of serum HDAC1 and eNOS in both groups were compared; the influencing factors of infectious endophthalmitis were analyzed by multivariate Logistic regression; the receiver operative curve(ROC)was applied to analyze the predictive value of serum HDAC1 and eNOS levels for postoperative infectious endophthalmitis in cataract patients.RESULTS: The levels of serum HDAC1 and eNOS in the infected group were obviously higher than those in the uninfected group(all P<0.01). Surgical time, vitreous overflow, HDAC1, and eNOS were all risk factors for postoperative infectious endophthalmitis(all P<0.05). ROC results showed that the AUC of HDAC1 and eNOS in predicting postoperative infectious endophthalmitis in cataract patients was 0.878 and 0.877, respectively, with sensitivity of 88.7% and 87.7%, specificity of 70.4% and 7.8%, respectively, while the AUC of the two combination in predicting postoperative infectious endophthalmitis in cataract patients was 0.978, with a sensitivity of 86.7% and a specificity of 85.3%.CONCLUSION:The serum levels of HDAC1 and eNOS in patients with infectious endophthalmitis after cataract surgery are obviously increased, and the combined detection of serum HDAC1 and eNOS can improve the predictive efficacy of infectious endophthalmitis in cataract patients after surgery. Both can provide reference for clinical diagnosis and treatment.

AIM: To investigate the predictive value of serum histone deacetylase 1(HDAC1)and endothelial nitric oxide synthase(eNOS)for infectious endophthalmitis after cataract surgery.METHODS: A total of 362 cataract patients(362 eyes)admitted to our hospital from January 2020 to January 2023 were selected as the research objects. According to the occurrence of postoperative infectious endophthalmitis, they were divided into infection group(15 cases, 15 eyes)and non-infection group(347 cases, 347 eyes). Enzyme linked immunosorbent assay(ELISA)was applied to detect the levels of serum HDAC1 and eNOS in all subjects, and the levels of serum HDAC1 and eNOS in both groups were compared; the influencing factors of infectious endophthalmitis were analyzed by multivariate Logistic regression; the receiver operative curve(ROC)was applied to analyze the predictive value of serum HDAC1 and eNOS levels for postoperative infectious endophthalmitis in cataract patients.RESULTS: The levels of serum HDAC1 and eNOS in the infected group were obviously higher than those in the uninfected group(all P<0.01). Surgical time, vitreous overflow, HDAC1, and eNOS were all risk factors for postoperative infectious endophthalmitis(all P<0.05). ROC results showed that the AUC of HDAC1 and eNOS in predicting postoperative infectious endophthalmitis in cataract patients was 0.878 and 0.877, respectively, with sensitivity of 88.7% and 87.7%, specificity of 70.4% and 7.8%, respectively, while the AUC of the two combination in predicting postoperative infectious endophthalmitis in cataract patients was 0.978, with a sensitivity of 86.7% and a specificity of 85.3%.CONCLUSION:The serum levels of HDAC1 and eNOS in patients with infectious endophthalmitis after cataract surgery are obviously increased, and the combined detection of serum HDAC1 and eNOS can improve the predictive efficacy of infectious endophthalmitis in cataract patients after surgery. Both can provide reference for clinical diagnosis and treatment.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Oral-facial-digital syndrome type Ⅰ(OFDSⅠ). METHODS: A child with OFDSⅠ who received treatment at the Women and Children's Hospital Affiliated to Ningbo University in March 2023 was selected as the study subject. A retrospective research method was used to collect the clinical data of the child. Peripheral venous blood samples were collected from the child, her parents and sister. Genomic DNA was extracted, and whole exome sequencing (WES) was performed. Candidate variants were validated using Sanger sequencing for familial verification. According to the Standards and Guidelines for the Interpretation of Sequence Variants developed by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the "ACMG Guidelines"), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Ningbo University Affiliated Women and Children's Hospital (Ethic No.: EC 2024-063). RESULTS: The child was a prematurely born female with deformities of the oral cavity, fingers, and toes. She was admitted to the Neonatal Department of the Hospital where she was born due to shortness of breath 15 minutes after birth. The WES results indicated that the child has harbored a heterozygous c.710dup (p.Y238Vfs*2) frameshifting variant of the OFD1 gene. Sanger sequencing confirmed that neither of the child's parents nor her sister had carried the same variant. According to the ACMG guidelines, the variant was rated as pathogenic (PVS1+PS4_Moderate+PM2-Supporting+PM6_Supporting+PP4). CONCLUSION Children with OFDSⅠ have clinical features such as oral, finger, and toe deformities. The c.710dup (p.Y238Vfs*2) variant of the OFD1 gene probably underlay the OFDSⅠ in this child. Above result has enriched the mutational spectrum of the OFD1 gene.
Humans ; Female ; Orofaciodigital Syndromes/genetics* ; Exome Sequencing ; Retrospective Studies ; Mutation ; Child ; Proteins

OBJECTIVE: To explore the genetic characteristics and pathogenesis for a child with mosaicism trisomy 21 and Congenital leukemia (CL). METHODS: A child who was admitted to Ningbo Women and Children's Hospital in March 2023 was selected as the study subject. A retrospective analysis was carried out on the clinical data, laboratory test results, immunophenotyping, and genetic characteristics of the child. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: EC2024-063). RESULTS: Whole genome sequencing (WGS) revealed that the child has mosaicism trisomy of chromosome 21, with a ratio of approximately 74%. In addition, copy number variations involving multiple OMIM genes that could explain his clinical phenotype were detected and rated as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). No pathogenic variant was detected with the GATA1 gene. Blood immune typing of the child conformed to the immunophenotype of acute myeloid leukemia. CONCLUSION For children with trisomy 21, even in the absence of GATA1 gene variants, the occurrence of CL should be monitored, and early diagnosis and treatment are of great significance for improving the prognosis.
Child, Preschool ; Humans ; DNA Copy Number Variations/genetics* ; Down Syndrome/genetics* ; GATA1 Transcription Factor/genetics* ; Leukemia/congenital* ; Mosaicism ; Mutation ; Retrospective Studies ; Whole Genome Sequencing

Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease primarily affecting the joints of the limbs. As the disease progresses, it can involve multiple organ systems. Interstitial lung disease (ILD) is the most common pulmonary manifestation of RA. Reported animal models of RA-ILD include adjuvant-induced arthritis (AA), collagen-induced arthritis (CIA), and transgenic mouse arthritis. However, the establishment criteria and evaluation methods for these models lack uniform standards, and they fail to fully replicate the clinicopathological characteristics of RA-ILD. This limitation significantly hinders research into the pathogenesis and development of therapeutic drugs for RA-ILD. Objective: The aim of the study was to review literature in China and abroad on RA-ILD animal models, analyze current research progress, identify existing issues, and propose research recommendations. Methods: Literature searches were conducted using the English keywords “rheumatoid arthritis, interstitial lung disease, model” and the Chinese keywords “(rheumatoid arthritis), (interstitial lung disease), (model)” or “(rheumatoid arthritis), (lung interstitial lesions), (model).” The search was performed in PubMed, Web of Science, CNKI, Wanfang Data, and VIP (China Science and Technology Journal Database) for articles published before November 2024. A total of 41 articles were included. Results and conclusions: The CIA model and the CIA model combined with bleomycin are commonly used due to their similarities to the histopathology and disease manifestations of human RA-ILD. Additionally, these models have appropriate cost and modeling duration, along with a high success rate, making them preferable choices. Transgenic animal models exhibit pathological features similar to the nonspecific interstitial pneumonia subtype of human RA-ILD and are useful for studying the genetic effects on RA-ILD. However, they have drawbacks such as high economic costs, long modeling durations, and a low success rate in some cases. The AA model is easy to establish, requires a short modeling period, and has low experimental costs. However, it lacks the chronic pathological development characteristic of human RA and exhibits a degree of self-limitation in lesion progression. Among other models, the comprehensive HLA-DQ8 transgenic mouse model can be used to study the combined effects of genetic and environmental factors on RA-ILD. The collagen autoantibody-induced arthritis model combined with bleomycin has a short modeling period, but it does not align well with the disease course of RA-ILD. These established animal models provide valuable insights into the pathogenesis of RA-ILD, the identification of novel biomarkers, and the development of new therapeutic approaches. Future research should focus on identifying an animal model that better replicates the physiological and pathological changes of clinical RA-ILD while being more convenient, cost-effective, and comprehensive in reflecting disease progression.

Objective:To develop an artificial intelligence (AI)-based automatic scoring model for magnetic resonance imaging-detected extramural vascular invasion (AI-mrEMVI) and evaluate its performance and prognostic value in patients with rectal cancer.Methods:In this multicenter retrospective cohort study, a total of 2 501 rectal cancer patients from seven centers between November 2012 and December 2020 were included and divided into completely independent training ( n=1 830) and validation ( n=671) cohorts. A nnUNet-based AI-mrEMVI scoring model was constructed. Manual mrEMVI scores assigned by two radiologists served as the reference standard for accessing the accuracy of the AI-mrEMVI scoring. Kaplan-Meier survival analysis and Cox regression were used to evaluate the prognostic stratification ability of the AI-mrEMVI scores. The concordance index (C-index) was calculated to evaluate prognostic performance. Results:In the validation cohort, the manual mrEMVI scores were 0-2 in 425 patients (63.3%), 3 in 89 (13.4%), and 4 in 157 (23.4%). The AI-mrEMVI model identified 0-2 in 375 patients (55.9%), 3 in 95 (14.2%), and 4 in 201 (30.0%), with an overall accuracy of 81.1% (544/671, 95% CI 77.9%-84.0%). The 3-year disease-free survival (DFS) rates for patients with AI-mrEMVI scores of 0-2, 3, and 4 were 85.2%, 70.0%, and 58.2%, respectively, and the 5-year overall survival (OS) rates were 87.2%, 81.6%, and 62.6%, respectively (DFS: χ2=48.74, P<0.001; OS: χ2=30.04, P<0.001). Multivariable Cox regression showed that for DFS, AI-mrEMVI scores of 3 and 4 were associated with hazard ratios ( HR) of 1.75 (95% CI 1.11-2.77, P=0.016) and 2.65 (95% CI 1.86-3.78, P<0.001), respectively. For OS, an AI-mrEMVI score of 4 was associated with an HR of 2.56 (95% CI 1.62-4.03, P<0.001). The C-index values of the AI-mrEMVI scoring model for predicting DFS and OS were 0.647 (95% CI 0.608-0.686) and 0.650 (95% CI 0.598-0.702), respectively. Conclusion:The proposed AI-mrEMVI automatic scoring model demonstrated high diagnostic accuracy and performed favorably in predicting DFS and OS prognostic risk in patients with rectal cancer.