ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

Background and aim:Few studies have reported hepatitis B surface antigen(HBsAg)kinetics after nucleos(t)ide analog(NA)discontinuation in patients with noncirrhotic chronic hepatitis B(CHB).The study specifically investigated long-term HBsAg kinetics after NA discontinuation. Methods:Between January 2014 to January 2024,this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation treatment.Demographic,clinical,and laboratory data were collected and analyzed after NA discontinuation. Results:Ninety-six patients who finished 5 years of follow-up were included.HBsAg remained unde-tectable in 29 patients with end of treatment(EOT)HBsAg negativity.Among 67 patients with EOT HBsAg positivity,HBsAg seroclearance occurred in 12(17.9％)patients with an estimated annual inci-dence of HBsAg seroclearance of 3.6％.Patients with EOT HBsAg levels of ≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of＞1000 IU/mL(33.3％vs.5.4％).The pro-portion of patients with HBsAg ≤1000 IU/mL increased during follow-up.Logistic regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL.The optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/mL. Conclusions:Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg sero-clearance during 5 years of follow-up after NA discontinuation.A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of ≤1000 IU/mL during 5 years of follow-up after NA discontinuation.Close monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation.

Objective To compare the advantages of robot assisted and DSA guided PBC for the treatment of trigeminal neuralgia.Methods A retrospective clinical analysis was conducted on 85 patients(28 in robot group and 57 in DSA group)who underwent robot assisted and DSA guided PBC surgery in a same center from September 2021 to February 2024.The single puncture success rate,improvement rate of VAS score,clinical efficacy rate,incidence of complications,average surgical time and fluoroscopy time were compared between the two groups.Results There was no statistically significant difference between the two groups in terms of single puncture success rate(96.43% vs.84.21% ),VAS improvement rate[88.9% (77.78%,100.00% )vs.88.89% (55.56%,100.00% )],clinical effective rate(92.86% vs.94.74% ),and total incidence of complications(35.09% vs.42.11% )(P>0.05).The average surgical time was significantly higher in the robot group[38.50(35.00,48.00)min]than the DSA group[19.00(15.00,25.50)min],and the average fluoroscopy time in the robot group[13.00(12.00,15.75)s]was significantly lower than the DSA group[194.00(152.50,259.50)s].The difference in average surgical and fluoroscopy time between the two groups was statistically significant(P<0.05).Conclusion DSA guided surgery has more advantages in centers with a large number of patients and a pursuit of efficiency.The robot assisted surgical puncture process is safe and controllable and patient radiation exposure time is short,thereby having high clinical application and promotion value.

17q12 microdeletion syndrome is a rare genetic disease,commonly characterized by newly occurring mutations,which can cause abnormalities of the urinary and reproductive tract,diabetes mellitus,neurological and psychiatric disorders and mild deformities.This article reports a case of 17q12 microdeletion syndrome with CRYBB2 gene missense mutation,combined with menstrual abnormalities,multiple cysts in both kidneys,hypomagnesemia,hyperuricemia,small pancreatic morphology and low pancreatic enzyme levels.

Immune checkpoint inhibitor(ICI)associated diabetes mellitus(DM)a rare specific type of diabetes,usually developed after the treatment of programmed cell death protein 1(PD-1)inhibitor or programmed cell death ligand 1(PD-L1)inhibitor.We reported 4 cases of DM after ICI use.These patients had a subacute onset,6 to 17 months after the first use of the drug,with diabetic autoantibodies negative.Pancreas atrophy was observed in one of them.All of the patients received treatment of insulin.

Objective:To evaluate deep learning for differentiating invasion depth of colorectal adenomas under image enhanced endoscopy (IEE).Methods:A total of 13 246 IEE images from 3 714 lesions acquired from November 2016 to June 2021 were retrospectively collected in Renmin Hospital of Wuhan University, Shenzhen Hospital of Southern Medical University and the First Hospital of Yichang to construct a deep learning model to differentiate submucosal deep invasion and non-submucosal deep invasion lesions of colorectal adenomas. The performance of the deep learning model was validated in an independent test and an external test. The full test was used to compare the diagnostic performance between 5 endoscopists and the deep learning model. A total of 35 videos were collected from January to June 2021 in Renmin Hospital of Wuhan University to validate the diagnostic performance of the endoscopists with the assistance of deep learning model.Results:The accuracy and Youden index of the deep learning model in image test set were 93.08% (821/882) and 0.86, which were better than those of endoscopists [the highest were 91.72% (809/882) and 0.78]. In video test set, the accuracy and Youden index of the model were 97.14% (34/35) and 0.94. With the assistance of the model, the accuracy of endoscopists was significantly improved [the highest was 97.14% (34/35)].Conclusion:The deep learning model obtained in this study could identify submucosal lesions with deep invasion accurately for colorectal adenomas, and could improve the diagnostic accuracy of endoscopists.

Objective:To investigate the effect of ring finger protein 187 (RNF187) on cell pro-liferation, migration and invasion of hepatocellular carcinoma (HCC).Methods:Messenger RNA (mRNA) level of RNF187 in HCC was analyzed by bioinformatics. Huh7 cells transfected with small interfering RNA (siRNA) of negative control or target gene respectively were classified as non-transfection (NC) group and RNF187 knockdown group. After 24 hours of transfection, the above two groups dimethyl sulfoxide (DMSO) were used as NC+ DMSO group and RNF187 knockdown + DMSO group. 24 hours after transfection with siRNA of target gene, the cells dealt with bafliomycin A1 (BFA) were set as RNF187 knockdown + BFA group. The regulation of RNF187 on malignant biological behavior and autophagy level of HCC cells were explored by cell counting kit-8 (CCK8) proliferation assay, cell scratch assay, transwell assay and western blot.Results:Compared with normal liver tissue, the mRNA level of RNF187 was higher in HCC tissue ( P<0.05). Compared with NC group, the absorbance at 48 h and 72 h and the scratch healing rate at 12 h and 24 h of RNF187 knockdown group were all lower, the differences were statistically significant (all P<0.001). The number of transmembrane cells in RNF187 knockdown group (39.50±5.57) at 24 h was lower than that in NC group (128.25±17.35), the differences were statistically significant ( t=9.74, P<0.001). Compared with NC group, the relative expression of total LC3 and Beclin-1 in RNF187 knockdown group all increased, while the relative expression of phosphorylated mammalian target of rapamycin decreased, the difference were statistically significant (all P<0.05). Compared with RNF187 knockdown+ DMSO group, the autophagy flow level, the 48 h and 72 h absorbance, the scratch healing rate at 24 h in RNF187 knockdown + BFA group were higher, the differences were statistically significant (all P<0.001). The number of transmembrane cells in RNF187 knockdown + BFA group (119.00±2.65) was more than that in RNF187 knockdown + DMSO group (57.67±2.52), the differences were statistically significant ( t=29.09, P<0.001). Conclusion:RNF187 is highly expressed in HCC tissue and knockdown of RNF187 inhibits the malignant biological behavior of HCC by enhancing the level of autophagy.

Objective The objective of this study was to analyze the expression of ubiquitin -conjugating enzyme E2T (UBE2T)in primary liver cancer and its relationship with clinicopathological parameters and prognosis of patients with liver cancer. Methods The second generation sequencing data and clinical pathological data of UBE2T gene mRNA in normal liver tissues and liver cancer tissues were downloaded from the Cancer Genome Atlas(TCGA)database. The expression of UBE2T in cancer tissues and normal tissues was analyzed to elucidate the relationship between UBE2T at mRNA level and clinicopathological parameters of patients with liver cancer. Kaplan-Meier was used for prognostic analysis. The Cox proportional hazard regression model was performed for the multivariate analysis of the prognostic factors associated with HCC. Based on the results of gene set enrichment analysis(GSEA), UBE2T was involved in the possible regulating pathways of HCC development. Results The expression of UBE2T at mRNA level in hepatocarcinoma tissues was significantly higher than that in adjacent tissues(P<0. 01). The high expression of UBE2T was closely related to pathological grade,TNM staging,and vascular invasion(P<0. 01),suggesting a poor prognosis of patients with liver cancer. Multivariate Cox regression analysis showed that TNM staging,vascular invasion and UBE2T expression were independent risk factors affecting the prognosis of patients with liver cancer. Conclusion The high expression of UBE2T is significantly associated with the clinicopathological factors and prognosis of patients with liver cancer. It can be used as a potential marker for predicting the prognosis of liver cancer patients and a target for tumor therapy.

Objective To analyze the magnetic resonance imaging (MRI) of the spinal cord and clinical characteristics in patients with autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.Methods A total of 1 040 samples of cerebrospinal fluid (CSF) and sera collected in the Second Affiliated Hospital of Guangzhou Medical University from March 2013 to June 2018 were tested with tissue-and cell-based assays,and 42 patients were found positive for GFAP-IgG.The clinical data and MRI characteristics of the spinal cord of 19 patients who were positive for GFAP-IgG in CSF with autoimmune GFAP astrocytopathy and lesions in the spinal cord were retrospectively reviewed.Results There were 12 females and seven males among the 19 patients,with onset age of (44±17) years.The main manifestations of these patients included limb weakness (14/19),abnormal vision (5/19),headache (4/19),seizure (4/19),dementia (3/19),etc.On MRI of the spinal cord,five patients showed involvement in the cervical cord alone,eight showed involvement in the thoracic cord alone and six had both cervical and thoracic segment involvement.Fifteen patients had longitudinally extensive myelitic abnormalities (≥3 vertebral segments long).Seven enhancement patterns were encountered.Lesions were displayed in the spinal cord and brain in eight patients.Central gray matter involvement in the spinal cord was found in all the 19 patients.Conclusions Autoimmune GFAP astrocytopathy more frequently presents in females than in males.MRI of the spinal cord has complex presentations and longitudinally extensive myelitic abnormalities usually.Patients often show central gray matter involvement in the spinal cord.Myelitic abnormalities present more often in thoracic segment than in cervical segment.Abnormalities in lumbar segment are less encountered.