Objective: To explore the feasibility of constructing a lung cancer early-warning risk model based on facial image features, providing novel insights into the early screening of lung cancer. Methods: This study included patients with pulmonary nodules diagnosed at the Physical Examination Center of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 1, 2019 to December 31, 2024, as well as patients with lung cancer diagnosed in the Oncology Departments of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine and Longhua Hospital during the same period. The facial image information of patients with pulmonary nodules and lung cancer was collected using the TFDA-1 tongue and facial diagnosis instrument, and the facial diagnosis features were extracted from it by deep learning technology. Statistical analysis was conducted on the objective facial diagnosis characteristics of the two groups of participants to explore the differences in their facial image characteristics, and the least absolute shrinkage and selection operator (LASSO) regression was used to screen the characteristic variables. Based on the screened feature variables, four machine learning methods: random forest, logistic regression, support vector machine (SVM), and gradient boosting decision tree (GBDT) were used to establish lung cancer classification models independently. Meanwhile, the model performance was evaluated by indicators such as sensitivity, specificity, F1 score, precision, accuracy, the area under the receiver operating characteristic (ROC) curve (AUC), and the area under the precision-recall curve (AP). Results: A total of 1 275 patients with pulmonary nodules and 1 623 patients with lung cancer were included in this study. After propensity score matching (PSM) to adjust for gender and age, 535 patients were finally included in the pulmonary nodule group and the lung cancer group, respectively. There were significant differences in multiple color space metrics (such as R, G, B, V, L, a, b, Cr, H, Y, and Cb) and texture metrics [such as gray-levcl co-occurrence matrix (GLCM)-contrast (CON) and GLCM-inverse different moment (IDM)] between the two groups of individuals with pulmonary nodules and lung cancer (P < 0.05). To construct a classification model, LASSO regression was used to select 63 key features from the initial 136 facial features. Based on this feature set, the SVM model demonstrated the best performance after 10-fold stratified cross-validation. The model achieved an average AUC of 0.8729 and average accuracy of 0.799 0 on the internal test set. Further validation on an independent test set confirmed the model’s robust performance (AUC = 0.823 3, accuracy = 0.729 0), indicating its good generalization ability. Feature importance analysis demonstrated that color space indicators and the whole/lip Cr components (including color-B-0, wholecolor-Cr, and lipcolor-Cr) were the core factors in the model’s classification decisions, while texture indicators [GLCM-angular second moment (ASM)_2, GLCM-IDM_1, GLCM-CON_1, GLCM-entropy (ENT)_2] played an important auxiliary role. Conclusion The facial image features of patients with lung cancer and pulmonary nodules show significant differences in color and texture characteristics in multiple areas. The various models constructed based on facial image features all demonstrate good performance, indicating that facial image features can serve as potential biomarkers for lung cancer risk prediction, providing a non-invasive and feasible new approach for early lung cancer screening.

BACKGROUND: Neuroticism has been associated with numerous health outcomes. However, most research has focused on a single specific disorder and has produced controversial results, particularly regarding mortality risk. Here, we aimed to examine the association of neuroticism with morbidity and mortality and to elucidate how neuroticism affects trajectories from a healthy state, to one or more neuroticism-related disorders, and subsequent mortality risk. METHODS: We included 483,916 participants from the UK Biobank at baseline (2006-2010). Neuroticism was measured using the Eysenck Personality Questionnaire. Three clusters were constructed, including worry, depressed affect, and sensitivity to environmental stress and adversity (SESA). Cox proportional hazards regression and multistate models were used. Linear regression was used to examine the association between neuroticism and immune parameters and neuroimaging measures. RESULTS: High neuroticism was associated with 37 non-overlapping diseases, including increased risk of infectious, cardiometabolic, neuropsychiatric, digestive, and respiratory diseases, and decreased risk of cancer. After adjustment for sociodemographic variables, physical measures, healthy behaviors, and baseline diagnoses, moderate-to-high neuroticism was associated with a decreased risk of all-cause mortality. In multistate models, high neuroticism was associated with an increased risk of transitions from a healthy state to a first neuroticism-related disease (hazard ratio [HR] [95% confidence interval (CI)] = 1.09 [1.05-1.13], P  <0.001) and subsequent transitions to multimorbidity (1.08 [1.02-1.14], P  = 0.005), but was associated with a decreased risk of transitions from multimorbidity to death (0.90 [0.84-0.97], P for trend = 0.006). The leading neuroticism cluster showing a detrimental role in the health-illness transition was depressed affect, which correlated with higher amygdala volume and lower insula volume. The protective effect of neuroticism against mortality was mainly contributed by the SESA cluster, which, unlike the other two clusters, did not affect the balance between innate and adaptive immunity. CONCLUSION This study provides new insights into the differential role of neuroticism in health outcomes and into new perspectives for establishing mortality prevention programs for patients with multimorbidity.
Humans ; Neuroticism/physiology* ; Male ; Female ; Middle Aged ; Aged ; Proportional Hazards Models ; Surveys and Questionnaires ; Adult ; Risk Factors

[This corrects the article DOI: 10.1016/j.apsb.2021.07.004.].

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Abstract Traditional Chinese medicine (TCM) auscultation has a long history, and with advancements in equipment and analytical methods, the quantitative analysis of auscultation parameters has determined. However, the complexity and diversity of auscultation, along with variations in devices, analytical methods, and applications, bring challenges to its standardization and deeper application. This review presents the advancements in auscultation equipment and systems, auscultation characteristic parameters, and their application in the diagnosis of pulmonary diseases and syndromes over the past 10 years, while also exploring the progress and challenges of current digital research of auscultation. This review also proposes the establishment of standardized protocols for the collection and analysis of auscultation data, the incorporation of advanced artificial intelligence (AI) auscultation analysis methods, and an exploration of the diagnostic utility of auscultatory features in pulmonary diseases and syndromes, so as to provide more precise decision support for intelligent diagnosis of pulmonary diseases and syndromes

Objective:To explore the clinical features, histopathological morphology, and differential diagnosis of lymphoepithelioma-like carcinoma with abnormal expression of follicular dendritic cell markers.Methods:From 2020 to 2021, 4 cases of lymphoepithelioma-like carcinoma with abnormal expression of follicular dendritic cell markers diagnosed in Fujian Cancer Hospital (2 cases) and the Second Affiliated Hospital of Fujian Medical University (2 cases) were collected. Different ancillary procedures such as HE, special stains, immunohistochemistry, and in situ hybridization techniques were used to assess the histopathological features and immunophenotypes. The clinical data were collected and literature was reviewed.Results:All 4 cases of lymphoepithelioma-like carcinoma with abnormal expression of follicular dendritic cell markers were male. They were 32, 45, 67 and 39 years old, respectively. The main clinical manifestations were bloody phlegm, abdominal pain, fatigue and anorexia. The clinical stages at diagnosis were stage Ⅳ (3 cases) and stage Ⅱ (1 case). Cases 2 and 3 had two pathological examinations at different sites, with a total of six pathological examinations. The histomorphology showed singly scattered or nests of tumor cells in a background of abundant small lymphocytes. The tumor cells were enlarged and pleomorphic, some appeared polygonal with inconspicuous cell borders, and they were arranged in a syncytial pattern. There were megakaryocytes, multinucleated tumor cells, and a few spindle-shaped cells seen. Atypical mitosis was commonly noted. By immunohistochemistry, the tumor cells were positive for CKpan(5/6), CK8/18(4/4), CAM5.2(2/5), CK-H(0/4), CK-L(3/4), EMA(4/5), CK5/6(3/6), p63(1/6), p40(1/6), E-cadherin (4/6), SSTR2(6/6), PD-L1(5/5), LCA(0/6), vimentin(5/6), CD2 (6/6), CD23(6/6), CD35(5/6), CXCL-13(4/5) and D2-40(1/5). The Ki-67 proliferative index was 60%-95%. In situ hybridization for EBER were all positive (6/6). Special stain for reticulin showed positive staining surrounding nests of tumor cells.Conclusions:The expression of follicular dendritic cell markers in lymphoepithelioma-like carcinoma is very rare, which may be related to EBV infection. Occasionally, it can overlap with follicular dendritic cell sarcoma by morphology and immunophenotype, which can lead to misdiagnosis. Only by combining clinical information, morphological characteristics and immunophenotype can an appropriate diagnosis be made.

This article summarizes current research and real-world evidence on the combined use of 5-aminosalicylates acid (5-ASA) with biologic agents in ulcerative colitis (UC) patients undergoing step-up therapy. Furthermore, it explores the potential value of whether combination therapy or not in different clinical scenarios. The findings provide insights for personalized UC treatment strategies and suggest directions for future research.

AIM:This study aims to investigate the regulatory effects of caffeic acid phenethyl ester(CAPE)on metabotropic glutamate receptor 5(mGluR5)and tyrosine kinase Fyn,and to explore its role in alleviating neuroinflam-mation and pathological features of Alzheimer disease(AD).METHODS:In vitro,the murine neuroblastoma N2a cell line was treated with amyloid β-protein 42 oligomers(Aβ42Os;10 nmol/L to 10 μmol/L)for 24 h.Cell viability was as-sessed by MTT assay.Western blot analyzed mGluR5 expression and Fyn phosphorylation(Tyr416).Pharmacological modulators(CHPG/MPEP)were used to evaluate mGluR5-mediated inflammatory cytokine regulation(qPCR)and Fyn ac-tivation.In vivo,wild-type(WT)and 5×FAD mice(WT,WT+CAPE,5×FAD and 5×FAD+CAPE)were analyzed for AD-related proteins,neuroinflammation(ELISA),glial activation(GFAP/Iba-1 immunofluorescence),and β-amyloid deposi-tion(thioflavin S).RESULTS:(1)Treatment with 1 μmol/L Aβ42Os increased mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01)without affecting N2a cell viability.Intracerebral Aβ42Os injection similarly up-regulated hip-pocampal mGluR5 and Fyn(P<0.01).(2)MPEP reduced mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01),while suppressing tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)mRNA levels(P<0.01).(3)CAPE decreased mGluR5-Fyn activation in N2a cells,neurons,and 5×FAD mice(P<0.01).(4)CAPE-treated 5×FAD mice exhibited reduced neuroinflammation markers(GFAP,Iba-1,TNF-α,IL-1β,and IL-6),Aβ plaques,and p-APP levels(P<0.01).CONCLUSION:Treatment with CAPE inhibits Aβ42Os-induced mGluR5-Fyn signaling activation,thereby attenuating neuroinflammation and the pathology associated with AD.

Objective:To measure the distance between the fetal bladder neck and the rectal end using prenatal MRI and analyze the developmental patterns of this distance and the gender differences in the second and third trimesters of pregnancy.Methods:This retrospective cohort study involved fetuses born at Guangzhou Women and Children's Medical Center, Guangzhou Medical University after regular prenatal examinations from January 2019 to December 2022 and confirmed to have typical anorectal structures after birth. These fetuses had undergone prenatal MRI examinations for reasons other than abdominal issues. The morphology of the fetuses' colons, rectums, and bladders was observed, and the vertical distance between the bladder neck and the rectal end was measured on sagittal T1weighted imaging. Differences in the distance between male and female fetuses were analyzed. The fetuses were divided into five groups based on their gestational age at the time of MRI examination (23-24 weeks, >24-26 weeks, >26-28 weeks, >28- 30 weeks, and >30-32 weeks), and the changes in the distance with gestational age were analyzed. Statistical analysis was performed using t-test, Kruskal-Wallis test, and Spearman correlation analysis. Pairwise comparisons among multiple groups were conducted using the Bonferroni method. Results:(1) A total of 142 fetuses were included in this study, all of which were singletons, with 73 males (51.4%) and 69 females (48.6%). The gestational age at the MRI examination was 28 weeks (26-30 weeks). (2) All fetuses had meconium filling the entire rectum and colon, with the rectal end located 0.570-2.610 cm below the bladder neck. (3) The distance between the bladder neck and the rectal end was shorter in male fetuses than in female fetuses [(1.140±0.261) vs. (1.519±0.405) cm, t=－6.58, P<0.001]. (4) In female fetuses, four pairs of groups showed statistically significant differences in the distance (23-24 weeks group vs. >26-28 weeks, >28- 30 weeks, and >30-32 weeks groups, and >24-26 weeks group vs. >30-32 weeks group). However, only two groups of male fetuses (23-24 weeks group vs. >28-30 weeks group) had statistically significant differences in the distance (all P<0.005). (5) The distance was moderately correlated with gestational age in male fetuses ( r=0.42, P<0.001), but they were strongly correlated in female fetuses ( r=0.66, P<0.001). Conclusions:The distance between the bladder neck and the rectal end in fetuses shows certain developmental patterns and gender differences in pregnancy's second and third trimesters. The correlation between the value and gestational age is stronger in female fetuses.

Purpose To explore the clinicopathological features,diagnosis and differential diagnosis of mantle cell lymphoma(MCL)with aberrant expression of CD10.Methods 14 cases of MCL with aberrant expression of CD10 were analyzed using hematoxylin-eosin,immunohistochemical stains,in situ hybridization,and fluorescence in situ hy-bridization(FISH)techniques to observe the histological morphology,immunophenotype,and molecular genetic char-acteristics.The relevant literatures were reviewed.Results There were 11 males and 3 females,with a male-to-fe-male ratio of 11∶3.The age ranged from 49 to 80 years,with an average age of 64.4 years and a median age of 64 years.10 cases occurred in lymph nodes,1 case in the nasopharynx,1 case in the right colon,1 case in the right eye-lid,and 1 case in the right testis.According to the Ann Arbor staging system,8 cases were classified as stage Ⅳ and 5 cases as stage Ⅲ,and 1 case with undetermined staging.Histologically,there was diffuse effacement of the normal architecture by tumor cells infiltration.Transparent degenerate small blood vessels and scattered individual epithelial-like tissue cells could be observed in the background.Among them,8 cases(8/14,57.14％)were composed of uni-form small to medium-sized lymphocytes with slightly irregular nuclei,unevenly dispersed chromatin,inconspicuous nucleoli,and scant cytoplasm,along with observable mitotic figures.In 3 cases(3/14,21.43％),the tumor cells were large and markedly pleomorphic,with round or irregular nuclei,prominent nucleoli,frequent mitotic figures,and abundant pale cytoplasm.Tumor cells in 3 cases(3/14,21.43％)were resembling lymphoblasts,characterized by round nuclei,fine chromatin,inconspicuous nucleoli,frequent mitotic figures,and scant cytoplasm.Immunophenotyp-ically,CD21 staining showed residual follicular dendritic meshworks.The tumor cells were diffusely and strongly posi-tive for CD20(14/14),PAX5(7/7),CD5(14/14),Cyclin D1(14/14),SOX11(11/11),and BCL2(13/13),partially positive for BCL6(8/14,57.14％)and MUM1(6/9,66.67％),but negative for CD3(14/14)and CD23(14/14).Among 14 cases,10 cases were diffusely and strongly positive for CD10(10/14,71.43％),and 4 cases were partially positive for CD10(4/14,28.57％).The percentage of Ki67 index ranged from 10％to 90％.All cases were negative for EBER(8/8).FISH analysis was performed in 9 cases,among which 7 cases showed CCND1 gene rearrangement,another 2 cases failed to detect due to insufficient tissue samples.Bone marrow biopsy was performed in 13 cases,revealing involvement in 8 cases(8/13,61.54％)and no involvement in 5 cases(5/13,38.46％).Con-clusion MCL with aberrant expression of CD10 is very rare,which commonly exhibits a diffuse growth pattern and blastoid and pleomorphic variants.It often has a high Ki67 proliferation index and poorer prognosis,and should be dis-tinguished from other subtypes of CD1O-positive B-cell lymphomas.