Objective:To predict pre-treatment clinical parameters that are associated with poor response and prognosis to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC) and to use second-line treatment drugs in the early stages to delay the progression of the disease so that patients can benefit from early-stage treatment.Methods:Patients diagnosed with PBC at the Second Affiliated Hospital of Kunming Medical University from 2013 to 2022 were collected. Two hundred fifty-seven cases were screened in accordance with the inclusion and exclusion criteria. The response and prognosis conditions one year after treatment were followed up in outpatient and inpatient departments, as well as through telephone calls. Statistical analyses were performed using t-tests, Mann-Whitney U test, χ2 test, Fisher's exact test, and logistic regression analysis according to different data. Results:A total of 257 PBC cases were included, with 223 females (86.80%) and 34 males (13.20%). Univariate and multivariate binary logistic regression analyses showed that baseline high albumin levels [odds ratio ( OR): 0.882, 95% confidence interval ( CI): 0.805～0.967, P=0.008] were a protective factor for PBC patients' response to UDCA treatment after adjusting for different confounding factors, while baseline high alkaline phosphatase ( OR: 1.012, 95% CI: 1.008～1.016, P<0.001) and baseline high neutrophil/lymphocyte ratio (NLR) level ( OR: 1.462, 95% CI:1.079～1.981, P=0.014) were risk factors for a poor response to UDCA. Trend analysis showed that the baseline NLR quantile was positively correlated with the risk of poor response to UDCA ( OR: 5.512, 95% CI: 1.040～29.216, P=0.045) in patients with PBC. Cox proportional hazards regression analysis identified that age [hazard ratio ( HR): 1.050, 95% CI: 1.019～1.082] and NLR value ( HR:1.089, 95% CI:1.021～1.161) were independent influencing risk factors for all-cause mortality in PBC patients ( P<0.05). Conclusion:Baseline high albumin levels are protective factors against a poor biochemical response to UDCA, while baseline high alkaline phosphatase levels and high NLR are risk factors for a poor biochemical response to UDCA in patients with PBC. Additionally, baseline high NLR values are positively correlated with poor biochemical response to UDCA treatment.

Eight new diterpenoids, Isodons A-H (1-8), comprising seco-abietane and abietane-type structures, together with 13 known analogues (9-21), were isolated from Isodon lophanthoides (Buch.-Ham. ex D. Don) Hara. The compounds (+)-3/(-)-3, (+)-4/(-)-4, and (+)-5/(-)-5 were identified as three enantiomeric pairs. The planar structures and absolute configurations of 1-8 were determined through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D & 2D nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) calculations, and X-ray diffraction crystallography. A cholesterol 7α-hydroxylase (Cyp7a1) luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1, (+)-4, 6, 7, 12-14, and 16. Additionally, compound 6 demonstrated anti-cholestatic effects through the farnesoid X receptor (FXR)-associated signaling pathways in vitro and in vivo. These findings suggest potential applications for I. Lophanthoides in pharmaceutical development.
Abietanes/pharmacology* ; Molecular Structure ; Animals ; Isodon/chemistry* ; Humans ; Diterpenes/pharmacology* ; Plant Extracts/chemistry*

Objective:To explore the spatial correlation between gray matter volume (GMV) changes and neurotransmitter receptors/transporters in patients with first-episode schizophrenia (FES) .Methods:Fifty-four FES patients(FES group) and fifty-nine healthy controls (HC group) were selected from June 2014 to May 2020 in the Psychiatry Department of Renmin Hospital of Wuhan University. Structural magnetic resonance imaging (sMRI) was conducted on all subjects. Differences of GMV were compared across 400 cortical regions and 32 subcortical regions. Based on the positron emission tomography(PET) data from Neuromaps, which provides the density of 19 different neurotransmitter receptors and transporters, Spearman correlation analysis was performed to evaluate the spatial correlation between GMV changes and neurotransmitter systems.Results:Compared to the HC group, FES group exhibited significant GMV reductions in widespread cortical (90/400) and subcortical (6/32) regions (all FDR-corrected P<0.05). The effect size of GMV reduction (Cohen’s d) showed significant positive correlations with the density of 5-hydroxytryptamine 1a(5HT1a) ( r=0.400, Pspin=0.002), γ-aminobutyric acid type A receptor(GABA A)( r=0.307, Pspin=0.002), and metabotropic glutamate receptor 5(mGluR5) ( r=0.275, Pspin=0.020) receptors (all FDR-corrected P<0.05). Conclusion:GMV reductions in a wide range of brain regions existed in patients with FES. There are significant correlations between 5HT1a, GABA A and mGluR5 receptors and gray matter reduction in patients with FES. The disorder of these neurotransmitter receptors may be the potential neurobiological mechanism of gray matter structural abnormalities in the early stage of schizophrenia.

Objective:To establish a risk prediction model based on least absolute shrinkage and selection operator (LASSO) regression for procalcitonin (PCT), milk fat globule-epidermal growth factor 8 (MFG-E8) and CXC chemokine ligand 9 (CXCL9) in elderly patients with liver cancer after transcatheter arterial chemoembolization (TACE) .Methods:A total of 150 elderly patients with liver cancer who underwent TACE treatment in Shishi City Hospital, Fujian Province and 910th Hospital of the Chinese People's Liberation Army Joint Logistic Support Force from August 2020 to August 2023 were selected as the study subjects. Patients with infection after TACE were included in the infected group and those without infection were included in the non-infected group according to whether the patients had infection during the postoperative hospitalization. The baseline data of patients were collected and compared. LASSO regression was used to screen the factors that may affect the infection after TACE in elderly patients with liver cancer and binary logistic regression analysis was performed. According to the results of regression analysis, a nomogram model was constructed based on the regression analysis results and the nomogram was internally validated using Bootstrap and receiver operator characteristic (ROC) curves.Results:There were 18 cases of infection in 150 elderly patients with liver cancer after TACE, with an incidence of 12.00%. There were statistically significant differences in focal rupture and bleeding ( χ2=5.92, P=0.015), ascites ( χ2=6.70, P=0.010), skin or mucosal damage ( χ2=6.67, P=0.010) between the infected group ( n=18) and the non-infected group ( n=132). The levels of serum PCT [ (1.17±0.32 ) μg/L vs. (0.91±0.14) μg/L], MFG-E8 [ (194.29±45.85) pg/ml vs. (158.76±28.63) pg/ml] and CXCL9 [ (948.49±52.38) pg/ml vs. (886.05±50.07) pg/ml] were higher than those in the non-infected group, with statistically significant differences ( t=4.13, P<0.001; t=4.55, P<0.001; t=4.94, P<0.001). Four factors related to infection after TACE intervention in patients with liver cancer were finally selected by LASSO regression model, skin or mucosal damage, PCT, MFG-E8, CXCL9 levels. Binary logistic regression analysis showed that skin or mucosal damage ( OR=13.48, 95% CI: 1.29-140.47, P=0.030), high levels of serum PCT ( OR=1.13, 95% CI: 1.05-1.22, P=0.001), MFG-E8 ( OR=1.04, 95% CI: 1.01-1.07, P=0.003), CXCL9 ( OR=1.05, 95% CI: 1.02-1.08, P=0.001) were risk factors for infection after TACE in elderly patients with liver cancer. Based on skin or mucosa damage, PCT, MFG-E8 and CXCL9, a nomogram prediction model for postoperative infection in elderly patients with liver cancer after TACE intervention was established. Calibration curve showed that the C-index of postoperative infection predicted by the nomogram model in elderly patients with liver cancer after TACE intervention was 0.939, indicating the model had good discrimination. ROC curve analysis showed that the area under the curve (AUC) predicted by the nomogram model for infection after TACE intervention in elderly patients with liver cancer was 0.960 (95% CI: 0.926-0.995, P<0.001), which had certain predictive value. The specificity, sensitivity and Youden index were 0.864, 0.944 and 0.808, respectively. Conclusions:Skin or mucosal damage, high levels of serum PCT, CXCL9 and MFG-E8 are closely related to postoperative infection in elderly patients with liver cancer after TACE, and the prediction model constructed based on this has better predictive performance for postoperative infection.

Objectives:This study aims to investigate the expression changes of transient receptor potential vanilloid type 1 (TRPV1) channel and inflammatory factors in the peripheral blood of patients with schizophrenia, and to evaluate their potential value for diagnostic prediction.Methods:This cross-sectional study was conducted at Renmin Hospital of Wuhan University from September 2023 to June 2024. A total of 35 patients with schizophrenia (patient group) from the outpatient/inpatient departments and 35 age-and sex-matched healthy individuals (control group) were recruited. Psychiatric symptoms and cognitive function were evaluated using the Positive and Negative Syndrome Scale (PANSS) and the Brief Assessment of Cognition in Schizophrenia (BACS), respectively. The between-group comparisons of the total scores of these two instruments were calculated using independent samples t-tests. Fasting peripheral blood samples were collected from all participants. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated for subsequent analysis. TRPV1 protein expression was quantified by Western blotting, while inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), and interleukin-10 (IL-10), were measured using enzyme-linked immunosorbent assay (ELISA). The between-group differences in TRPV1 and inflammatory cytokines were analyzed using the analysis of covariance (ANCOVA), controlling for age and sex. Pearson correlation analysis was employed to examine relationships between continuous variables, controlling for years of education, age, and sex. The diagnostic performance of TRPV1 and inflammatory cytokines for schizophrenia was assessed using receiver operating characteristic (ROC) curve analysis. Results:Significant between-group differences were observed in BACS total and subscale scores ( t=2.57-9.72, all P<0.01). Compared with the control group, the patient group exhibits significantly decreased expression of TRPV1, IL-4, and IL-10 ( t=6.78, 2.75, 2.53, all P<0.01), increased expression of TNF-α, IL-2, and IL-6 ( t=4.08, 2.64, 2.63, all P<0.01), and an increased IL-6/IL-10 ratio ( t=3.18, P<0.01). Correlation analyses revealed that in the patient group, the TRPV1 expression level was negatively correlated with levels of TNF-α and IL-6, and positively correlated with levels of IL-4 and IL-10 ( r=-0.589, -0.234, 0.341, 0.293, all P<0.05). In the patient group, the TRPV1 expression level was negatively correlated with the negative symptom score of PANSS ( r=-0.299, P<0.05), and the IL-6 level was positively correlated with the negative symptom score, the general pathology score, and the total score of PANSS ( r=0.387, 0.356, 0.321, all P<0.05). The TRPV1 level was positively correlated with the total score of BACS in both the control group and the patient group ( r=0.144, 0.828, all P<0.01). The IL-6/IL-10 ratio was positively correlated with the total score of PANSS and negatively correlated with the total score of BACS in the patient group ( r=0.623, -0.333, all P<0.05). The area under the ROC curve for the combination of TRPV1 level and IL-6/IL-10 ratio was 0.98 (95% confidence interval=0.96 to 1.00). Conclusions:Patients with schizophrenia exhibit reduced expression levels of TRPV1 along with an imbalanced inflammatory response. The combined assessment of TRPV1 level and IL-6/IL-10 ratio has demonstrated a high predictive and diagnostic value for schizophrenia.