Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

Corticotomy is a clinical procedure to accelerate orthodontic tooth movement characterized by the regional acceleratory phenomenon (RAP). Despite its therapeutic effects, the surgical risk and unclear mechanism hamper the clinical application. Numerous evidences support macrophages as the key immune cells during bone remodeling. Our study discovered that the monocyte-derived macrophages primarily exhibited a pro-inflammatory phenotype that dominated bone remodeling in corticotomy by CX3CR1^CreERT2; R26^GFP lineage tracing system. Fluorescence staining, flow cytometry analysis, and western blot determined the significantly enhanced expression of binding immunoglobulin protein (BiP) and emphasized the activation of sensor activating transcription factor 6 (ATF6) in macrophages. Then, we verified that macrophage specific ATF6 deletion (ATF6^f/f; CX3CR1^CreERT2 mice) decreased the proportion of pro-inflammatory macrophages and therefore blocked the acceleration effect of corticotomy. In contrast, macrophage ATF6 overexpression exaggerated the acceleration of orthodontic tooth movement. In vitro experiments also proved that higher proportion of pro-inflammatory macrophages was positively correlated with higher expression of ATF6. At the mechanism level, RNA-seq and CUT&Tag analysis demonstrated that ATF6 modulated the macrophage-orchestrated inflammation through interacting with Tnfα promotor and augmenting its transcription. Additionally, molecular docking simulation and dual-luciferase reporter system indicated the possible binding sites outside of the traditional endoplasmic reticulum-stress response element (ERSE). Taken together, ATF6 may aggravate orthodontic bone remodeling by promoting Tnfα transcription in macrophages, suggesting that ATF6 may represent a promising therapeutic target for non-invasive accelerated orthodontics.
Animals ; Mice ; Macrophages/metabolism* ; Tumor Necrosis Factor-alpha/genetics* ; Tooth Movement Techniques/methods* ; Activating Transcription Factor 6/metabolism* ; Bone Remodeling ; Flow Cytometry ; Blotting, Western

This study introduced a time-delay exposure system independent of the mobile digital radiography equipment. The system consisted of lithium battery, delay control circuit, micro electric motor and related auxiliary facilities. When the starting time was reached through the delay circuit, the motor pushed out the rod to squeeze the exposure button and completed the exposure. The accessories used in this system were easy to purchase and cheap. At the same time, the technology was mature and had good compatibility. The exposure success rate was high and the exposure effect was satisfactory. This time-delay exposure system had good practicability and popularization value.
Radiographic Image Enhancement ; Technology ; Electric Power Supplies

Objective:To investigate the brain characteristics of chronic schizophrenia by voxel-mirrored homotopic connectivity (VMHC).Methods:Forty seven patients with chronic schizophrenia from Tianjin Anding Hospital and 31 healthy controls from nearby communities were included in the study. The MRI data of the subjects were collected by Siemens Skyra 3.0 T MRI.Positive and negative symptoms scale (PANSS) was used to assess the illness severity of patients with chronic schizophrenia.SPM12 was used to process the collected MRI data. DPARSF was used to calculate the VMHC values of subjects in the two groups. The independent sample t test based on SPM12 was used to compare the VMHC values of the two groups. The significant brain regions in VMHC were regarded as regions of interest (ROI), and VBM8 was used to further analyze the gray matter volume of the ROI of the two groups. Results:Compared with healthy controls, the patients with chronic schizophrenia demonstrated decreased VMHC mainly located in lingual gyrus(voxel=208, T=4.98), occipital middle occipital gyrus(voxel=156, T=3.75) and postcentral gyrus(voxel=237, T=4.36) (FDR correction, q=0.05). Compared with healthy controls, the gray matter volumes in bilateral lingual gyrus(left(0.0034±0.0008), (0.0028±0.0013), t=-2.141, P=0.037; right(0.0025±0.0006), (0.0020±0.0011), t=2.268, P=0.028) and postcentral gyrus((0.0432±0.0051), (0.0372±0.0162), t=-2.070, P=0.045) increased, but non-significant change in postcentral gyrus of the patients with chronic schizophrenia. Conclusion:The abnormal VMHC mainly locate in lingual gyrus, middle occipital gyrus and postcentral gyrus in patients with chronic schizophrenia.

Objective:To investigate the magnetic resonance imaging (MRI) features of Cryptococcus infection in central nervous system patients with acquired immune deficiency syndrome (AIDS).Methods:The retrospective study on magnetic resonance imaging (MRI) and clinical data of cryptococcal meningitis (CM) was carried out between July 2011 and March 2017.These patients had not received anti-retroviral treatment.Patients with other specific or suspicious diseases in the central nervous system were not included in the analysis.Results:A total of 39 patients were included in the analysis,with CD4 cell counts of 13.0×106/L [(0-205)×106/L],and 94.9％ (37/39) of patients with CD4 cell count ＜100×106/L.Of the 39 patients,26 patients showed abnormal MRI signals in the brain,which were most frequently involved in the basal ganglia (20/26,76.9％).The basal ganglia lesions showed dilated VirchowRobin space (VRS)/gelatinous spseudocysts (18/20,90％).Postcontrast T 1-weighted MRI revealed no significant enhancement (3/5,60％) and mild enhancement (2/5,40％).The incidence of cerebral cryptococcal granuloma were 35％ (7/20).Nineteen of 26 patients with lesions outside the basal ganglia,of which 13 patients also complicated with basal ganglia lesions.Postcontrast T1-weighted MRI revealed no significant enhancement.The incidence of cryptococcal granuloma and meningeal thickening were 15.7％ (3/19) and 26.3％ (5/19),respectively.Postcontrast T1-weighted MRI meningeal thickening revealed enhancement (5/5,100％).Conclusion:The incidence of brain MRI abnormality in AIDS complicated with central nervous system Cryptococcus infection may not be low,and the lesions are mostly located in the basal ganglia.It most frequently displays the dilated VRS/gelatinous spseudocysts.It can also be showed cryptococcal granuloma.Postcontrast T1-weighted MRI often reveals no enhancement or mild enhancement.

Objective To studying the MR findings and pathology of peripheral small intrahepatic cholangiocarcinoma and improving the understanding of peripheral small cholangiocarcinoma with no-bile duct dilatation. Methods A retrospective analysis of 12 patients with intrahepatic peripheral cholangiocarcinoma which were confirmed by surgery and pathology, all patients were examined by abdominal MRI without and with contrast. Correlation was made with gross pathology and surgical pathological specimen. Results On T1WI, there were 4 cases of complex low signal intensity and 8 cases of low signal intensity. On T2WI, there were 8 cases of high signal intensity and 4 cases of complex high signal intensity. Enhanced MRI showed: marked nidus enhancement on arterial phase in 1 case, and the pathological diagnosis was poorly differentiated adenocarcinoma. Inhomogeneous enhancement or annular enhancement were seen in 10 cases on arterial phase, 3 of these cases showed thin annular enhancement on arterial phase, low signalintensity on portal venous phase and isointensity on delayed phase. One case showed delayed enhancement. Thick circular enhancement correlated with pathological changes of survival of tumor cells, center areas correlated with fibrous connective tissue, and a small amount of necrotic tissue. Island-like enhancement or inhomogeneous enhancement were seen in 3 cases. Corresponding pathological changes consisted of tumor tissue and a small amount of fibrous connective tissue, as well as somenecrotic tissue. In 1 case, no enhancement was seen on all three phases and pathological changes showed cystic changes, hemorrhage, necrosis, with survival tumor cells seen between cyst and normal liver tissue. Conclusions MRI scanning of peripheral small cholangiocarcinoma lacked characteristic features, but dynamic contrast-enhanced MR had certain specific findings. Due to different pathology, the fibrous tissue, necrotic tissue and survival tumor tissue components were exhibited different imaging findings.

Objective To evaluate the feasibility,technique and preliminary clinical results of the intraoperative three-dimensional (3-D) computer navigation system assisted free vascularized fibular grafting for the treatment of osteonecrosis of the femoral head.Methods From October 2010 to April 2013,14 patients (18 hips) with osteonecrosis of the femoral head were treated by free vascularized fibular graft transfer,assisted by intraoperative3-D computer navigation system.Of 18 hips,8 were classified as stage Ⅱ ;6 as stage Ⅲ,4 as stage Ⅳ according to Steinberg system.The entire procedures were visualized and guided by the 3-D navigation system,including location of optimal entry point,exploration of the field,excision of the necrotic bone tissues,and the fibular grafting transfer with vessel anastomosis.The follow-up records included the results of X-ray,the Harris score of the hip,and the complications.Results Operations of all 14 patients (18 hips) were smooth and successful with patent vessel and umcompromised grafts evidenced by ECT scan at day 7 postoperatively.Postoperative X-ray confirmed the complete eradication of necrotic focuses with surrounding calcified bone and the accurate positioning of fibular grafts.The mean follow-up period was 23.6 months (8-29 months).Harris scores significantly improved from 57.5 ± 14.5 before operations to 87.5 ±2.5 after,with 6 hips' scores classified as Excellent,and 11 as Good.X-ray obtained more than 1 year after operation suggested improvement was achieved in 15 hips.Conclusion Intraoperative 3-D computer navigation system has multiple merits in assisting free vascularized fibular grafting for the treatment of osteonecrosis of the femoral head,including clear anatomic structure,better accuracy,less damage,and reliable functional recovery,which imply it is a highly applicable approach.