BACKGROUND: PANoptosis has the features of pyroptosis, apoptosis, and necroptosis. Numerous studies have confirmed the diverse roles of various types of cell death in acute liver failure (ALF), but limited attention has been given to the crosstalk among them. In this study, we aimed to explore the role of PANoptosis in ALF and uncover new targets for its prevention or treatment. METHODS: Three ALF-related datasets (GSE14668, GSE62029, and GSE74000) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). Hub genes were identified through intersecting DEGs, genes obtained from weighted gene co-expression network analysis (WGCNA), and genes related to PANoptosis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein‍‒‍protein interaction (PPI) analyses and gene set enrichment analysis (GSEA) were performed to determine functional roles. Verification was performed using an ALF mouse model. RESULTS: Our results showed that expression of seven hub genes (B-cell lymphoma-2-modifying factor (BMF), B-cell lymphoma-2-interacting protein 3-like (BNIP3L), Caspase-1 (CASP1), receptor-interacting protein kinase 3 (RIPK3), uveal autoantigen with coiled-coil domains and ankyrin repeats protein (UACA), uncoordinated-5 homolog B receptor (UNC5B), and Z-DNA-binding protein 1 (ZBP1)) was up-regulated in liver samples of patients. However, in the ALF mouse model, the expression of BNIP3L, RIPK3, phosphorylated RIPK3 (P-RIPK3), UACA, and cleaved caspase-1 was up-regulated, while the expression of CASP1 and UNC5B was down-regulated. The expression of ZBP1 and BMF increased only during the development of ALF, and there was no significant change in the end stage. Immunofluorescence of mouse liver tissue showed that macrophages expressed all seven markers. Western blot results showed that pyroptosis, apoptosis, and necroptosis were always involved in lipopolysaccharide (LPS)/ d-galactosamine (d-gal)‍-induced ALF mice. The ALF cell model showed that bone marrow-derived macrophages (BMDMs) form PANoptosomes after LPS stimulation. CONCLUSIONS: Our results suggest that PANoptosis of macrophages promotes the development of ALF. The seven new ALF biomarkers identified and validated in this study may contribute to further investigation of diagnostic markers or novel therapeutic targets of ALF.
Animals ; Liver Failure, Acute/genetics* ; Computational Biology ; Mice ; Pyroptosis/genetics* ; Humans ; Protein Interaction Maps ; Apoptosis/genetics* ; Necroptosis/genetics* ; Gene Regulatory Networks ; Gene Ontology ; Gene Expression Profiling ; Disease Models, Animal

Objective: To compare the effectiveness of blonanserin and olanzapine in the treatment of first-episode schizophrenia, so as to provide the basis for the medication choice for the treatment of first-episode schizophrenia. Methods: A total of 98 patients with first-episode schizophrenia admitted to the Second People's Hospital of Taizhou City were selected and randomly divided into the olanzapine group and the blonanserin group for a treatment period of two months. The Positive and Negative Syndrome Scale (PANSS), Pittsburgh Sleep Quality Index (PSQI), MATRICS Consensus Cognitive Battery (MCCB) were used to investigate the improvement of symptoms, sleep quality and cognitive function before and after treatment, respectively, and the level of prolactin was detected. The generalized estimation equation was used to compare the differences between the two groups. The adverse reactions of the two groups were recorded and the safety of medication was evaluated. Results: Forty-nine patients each group were included, with 29 males and a mean age of (37.22±7.17) years in the olanzapine group, and 27 males and a mean age of (37.54±7.31) years in the blonanserin group. There were no significant differences in gender, age, disease course and educational duration between the two groups (all P>0.05). The scores of positive symptom, negative symptom, general psychopathology and overall PANSS in the two groups after treatment were decreased compared with those before (all P<0.05). However, there was no significant difference between the two groups, and no interaction between the drugs and treatment duration (all P>0.05). The MCCB score of the blonanserin group was higher than that of the olanzapine group, while the PSQI score and the prolactin level of the blonanserin group were lower than that of the olanzapine group, and there was an interaction between the drugs and treatment duration (all P<0.05). The incidence of adverse reactions in the blonanserin group was 6.12%, which was lower than that in the olanzapine group of 20.41% (P<0.05). Conclusion Either blonanserin or olanzapine can improve psychotic symptoms inpatients with first-episode schizophrenia, while blonanserin is more effective than olanzapine in improving sleep quality, cognitive function and reducing prolactin level, and has higher safety.

Objective To establish a nomogram for predicting the risk of post-hepatectomy complications (PHC) in hepatic echinococcosis by analyzing the risk factors for PHC in two types of hepatic echinococcosis, and to investigate its value in clinical practice. Methods A retrospective analysis was performed for the clinical data of 263 patients with two types of hepatic echinococcosis who underwent hepatectomy in Qinghai University Affiliated Hospital from January 2015 to August 2020, and among these patients, 93 were enrolled as PHC group and 170 were enrolled as control group. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the independent samples t -test was used for comparison of normally distributed continuous data between two groups; the chi-square test and the Fisher's exact test were used for comparison of categorical data between two groups. Univariate and multivariate logistic regression analyses were used to screen out independent risk factors for PHC, and a nomogram risk prediction model was established based on the weight of each independent risk factor. The Bootstrap resampling method was used for internal verification of the model; the receiver operating characteristic (ROC) curve was plotted to evaluate the discriminatory ability of the model; calibration curve and the Hosmer-Lemeshow test were used to evaluate the consistency of the model; decision curve analysis (DCA) was performed to verify the clinical effectiveness of the model. Results Albumin-bilirubin (ALBI) score (odds ratio [ OR ]=3.694, 95% confidence interval [ CI ]: 1.860-7.336, P < 0.05), time of operation ( OR =2.848, 95%CI: 1.384-5.859, P < 0.05), intraoperative blood loss ( OR =4.832, 95%CI: 2.384-9.793, P < 0.05), and hydatid diameter ( OR =3.073, 95%CI: 1.528-6.177, P < 0.05) were independent risk factors for PHC in two types of hepatic echinococcosis. A nomogram risk prediction model was established based on the weight of the above four independent risk factors, and the model had an area under the ROC curve of 0.877 (95% CI : 0.831-0.923). The model had a consistency index of 0.871 after internal verification using the Bootstrap resampling method, suggesting that the model had good discriminatory ability. The fitting of the observed value and the actual value of the calibration curve and the Hosmer-Lemeshow test ( P =0.905) showed that the predicted value of the nomogram risk prediction model had good consistency with the actual observed value. When the threshold probability was 35.6%, DCA showed a net clinical benefit of 22%, and the model had good clinical applicability within the threshold probability ranging from 8% to 89%. Conclusion ALBI score, time of operation, intraoperative blood loss, and hydatid diameter are independent risk factors for PHC in patients with two types of hepatic echinococcosis, and the nomogram risk prediction model established based on these factors has good accuracy, consistency, and clinical practicability.

Objective To study the clinical effect of aripiprazole combined with lithium carbonate in the treatment of acute mania .Methods 72 patients with acute mania were selected in this research .According to the order of admission,the patients with odd numbers were selected as the control group (n=36),and the patients with even numbers were selected as the observation group (n=36).The control group was treated with clozapine combined with lithium carbonate ,the observation group was treated by aripiprazole combined with lithium carbonate .The safety and efficacy of the treatment were evaluated by BRMS score , effective rate , incidence rate of adverse reaction etc .Results After treatment for 1 week,2 weeks,the BRMS scores of the observation group were (21.23 ±2.22)points and (20.02 ±2.12)points,which were significantly lower than those of the control group (t=4.0390,4.0025,all P<0.05).After treatment for 4 and 8 weeks,the BRMS scores of the two groups were similar .The effective rate of the observation group was 94.44%,which of the control group was 91.67%,the difference was not statistically signifi-cant (P>0.05).The incidence rate of adverse reactions of the observation group was 19.44%,which was significantly lower than 41.67% of the control group,the difference was statistically significant (χ2 =11.6446,P<0.05) .Conclusion Aripiprazole combined with lithium carbonate has similar effect with clozapine combined with lithium carbonate in the treatment of acute mania ,but the combination therapy of aripiprazole and lithium carbonate can effec -tively alleviate the symptoms of the disease ,and with less adverse reaction ,high safety,which can be promoted and applicated in clinical .

Objective To explore the alteration of brain pain functional areas in patients with functional dyspepsia (FD) irritable bowel syndrome (IBS) overlap by rectal balloon volume stimulation and magnetic resonance imaging (MRI) and the differences with IBS alone patients and healthy individuals were compared.Methods A total of 11 IBS alone patients,16 IBS overlapped with FD patients (IBS-FD) and 10 healthy controls were recruited.Sensory thresholds and visual analogue scale (VAS) were recorded during the rectal balloon air injection process. The changes of brain activated areas were analyzed by functional MRI (fMRI) when the rectum was stimulated at the volume of 50,100 and 150 ml.The data were analyzed by least significant difference (LSD) test.Results Under rectal volumetric stimulation,the sensory thresholds of IBS-FD group and IBS alone group were (53.14 ± 16.05) ml and (59.20 ± 20.55) ml and the difference was not statistically significant (LSD test,P＞0.05).There was no significant difference in VAS score between IBS alone group and IBS-FD group (LSD test,P＞0.05).Rectal stimulated under different volume,the results of fMRI indicated the activation of anterior cingulated cortex, dorsolateral prefrontal cortex,postporietal cortex,thalamus and insular cortex in both IBS alone group and IBS-FD group.And there was no significant difference in activated areas and intensity between IBS alone group and IBS-FD group (LSD test,P＞0.05).Conclusions There was no significant difference in activations of brain areas between IBS alone and IBS-FD patients under rectal volumetric stimulation. Under rectal volumetric stimulation,although symptoms overlapped,there was no evidence of the overlap of braingut axis and visceral hypersensitivity between IBS alone and IBS-FD.

Objective To analyze the role of multislice spiral CT in the diagnosis of biliary com-plications following liver transplantation. Methods Forty-four patients with biliary complications re-ceived tri-phase contrast-enhancement CT examination and cholangiography (CP) within one week af-ter the CT scanning. Using the results of CP as the standard, we investigated the efficacy of multislice spiral CT for each kind of biliary complication. All the analyses for bile duct were based on the images on the late portal venous phase and the reconstruction of images performed with multiplan reformat,Results CP depicted biliary strictures involved in extrahepatic bile duct in 23 cases (including the common bile duct and common hepatic duct), left or right hepatic duct in 24 and intrahepatic bile duct in 27. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the CT examination were 91.3%, 83. 3% , 87. 8%, 87. 5% and 88. 2% for biliary stricture in extrahe-patic bile duct, 83. 3% , 88. 2%, 85. 4%, 90. 9% and 78. 9% for biliary stricture in left or right he-patic duct, 74.1%, 92.7%, 80.5%, 95.2% and 65.0%, for biliary stricture in intrahepatic bile duct, respectively. CT detected intrahepatic biloma in 4 cases and abscess in 2 but CP only detected biloma in 2 cases. The other 4 cases did not detected by CP because of severe biliary strictures which filled with biliary sludge. CP confirmed anastomotic bile leak in 3 cases. In these cases, CT only de-picted the fluid collection in hepatic hilum and abdominal cavity, none of the exact leak site could be detected. CP detected biliary sludge or stones in 33 cases. However, the sensitivity, specificity, accu-racy, positive predictive value and negative predictive value of the CT examination for biliary sludge or stones were 72.7%,100.0%,78.1%,100.0%and 47.6%,respectively.Meanwhile,in 1 patient with diffuse intrahepatic biliary strictures,active biliary bleeding was correctly detected by CT exami-nation and confirmed by hepatic arteriography.Conclusion Tri-phase contrast-enhancement CT exam-ination can be used as a general method for biliary complications after liver transplantation.Besides its benefits in biliary complications,it is of great value for depicting complications involved in hepatic pa-renchyma and acute biliary bleeding in the same examination.