Genomics-Microbiome Based Assessment of Bidirectional Causality Between Gut Microbiota and Psoriasis.

Background: Traditional observational studies have found a possible risk association of the gut microbiota for psoriasis. Meanwhile, psoriasis may also affect the changes in the gut microbiota. However, the available evidence does not demonstrate a reciprocal relationship between the gut microbiota and psoriasis. This limits our understanding on the role of the gut microbiota in the mechanisms of psoriasis. Methods: To address this question we used Mendelian randomization, a novel epidemiological approach, and acquired the largest current gut microbiota GWAS data from the MiBioGen consortium as well as psoriasis GWAS data from the FinnGen consortium, and performed two-sample bidirectional MR analyses using a multiple MR analysis approach. Finally, the robustness of the results was assessed by sensitivity analysis. Results: Our results indicate that five bacterial genera are causally related to psoriasis and psoriasis is causally related to four bacterial genera. Conclusion: These results suggest a bidirectional causal influence of psoriasis on the gut microbiota. Our results somewhat challenge the causal inferences of previous observational studies. We found that the specific bacterial genera with a risk effect on psoriasis were different from those found to characterize psoriasis in previous observational studies, and that these psoriasis-characterizing genera were inversely associated with psoriasis.

Point-Based Learnable Query Generator for Human-Object Interaction Detection.

Transformer-based and interaction point-based methods have demonstrated promising performance and potential in human-object interaction detection. However, due to differences in structure and properties, direct integration of these two types of models is not feasible. Recent Transformer-based methods divide the decoder into two branches: an instance decoder for human-object pair detection and a classification decoder for interaction recognition. While the attention mechanism within the Transformer enhances the connection between localization and classification, this paper focuses on further improving HOI detection performance by increasing the intrinsic correlation between instance and action features. To address these challenges, this paper proposes a novel Transformer-based HOI Detection framework. In the proposed method, the decoder contains three parts: learnable query generator, instance decoder, and interaction classifier. The learnable query generator aims to build an effective query to guide the instance decoder and interaction classifier to learn more accurate instance and interaction features. These features are then applied to update the query generator for the next layer. Especially, inspired by the interaction point-based HOI and object detection methods, this paper introduces the prior bounding boxes, keypoints detection and spatial relation feature to build the novel learnable query generator. Finally, the proposed method is verified on HICO-DET and V-COCO datasets. The experimental results show that the proposed method has the better performance compared with the state-of-the-art methods.

Hepatic inflammatory myofibroblastic tumor: A case report.

BACKGROUND: Hepatic inflammatory myofibroblastic tumor (HIMT) is a rare type of hepatic tumor. It is always misdiagnosed and mistreated because it is primarily found with no obvious specific manifestation, and its imaging findings are diverse. CASE SUMMARY: Here, we report a case of HIMT that was initially diagnosed as liver malignancy but was confirmed as HIMT by histopathology after hepatectomy. Mostly, HIMTs are infiltrated with plasma cells and stain positively for anaplastic lymphoma kinase on immunohistochemistry as well as for some other kinases. CONCLUSION: HIMT can be treated with single nonsteroidal anti-inflammatory drugs and without surgery when it is diagnosed accurately. Because the etiology of HIMT is unknown and the diagnosis is difficult, the pathogenesis and clinical process need to be further studied.

A Chinese scoring system for predicting successful retrograde collateral traverse in patients with chronic total coronary occlusion.

BACKGROUND: Retrograde approach technique has been challenging in percutaneous coronary interventional treatment of chronic total occlusion (CTO) coronary disease. The present study endeavors to determine a novel Chinese scoring system for predicting successful collateral channels traverse via retrograde approach. METHODS: The demographic characteristics and angiographic characteristics of 309 CTO patient were analyzed by univariable and multivariable analysis for selecting potential predictors. And the nomogram was used to establish the scoring system. Then it was evaluated by the internal and external validation. RESULTS: The predictors of Age, Connections between collateral channels and recipient vessels, and Channel Tortuosity (ACT) were identified with univariable and multivariable analysis and employed to the ACT score system. With acceptable calibrations, the area under curve of the scoring system and the external validation were 0.826 and 0.816 respectively. Based on score, the predictors were divided into three risk categories and it showed a consistent prediction power in the validation cohort. CONCLUSIONS: The novel Chinese ACT score is a reliable tool for predicting successful retrograde collateral traverse.

Successful Treatment of Psoriasis Combined with Bullous Pemphigoid with Dupilumab: A Case Report.

Psoriasis is an immune-mediated chronic inflammatory disease that can be combined with complications such as diabetes, cardiovascular disease, obesity, and kidney disease. The comorbidity of psoriasis with autoimmune bullous diseases (AIBD) has been reported previously in several cases, the most frequent of which is bullous pemphigoid (BP). The underlying mechanisms of psoriasis with BP are not clear and there are no uniform treatment criteria. Based on previous case reports, the coexistence of psoriasis and BP may be related to inflammatory activity, medications, phototherapy, and infection. We report a case of a psoriasis patient who developed BP after taking Chinese herbal compounds and was successfully treated with dupilumab, which is the first reported case of applying dupilumab to treat psoriasis with BP comorbidities.

Retinal honeycomb appearance and its role in patients with X-linked retinoschisis.

BACKGROUND: To investigate the clinical characteristics of retinal honeycomb appearance in a large cohort of patients with X-linked retinoschisis (XLRS) and to determine whether it is associated with complications like retinal detachment (RD) and vitreous hemorrhage (VH). METHODS: A retrospective observational case series. A chart review of medical records, wide-field fundus imaging, and optical coherence tomography (OCT) was performed on 78 patients (153 eyes) diagnosed with XLRS at Beijing Tongren eye center between Dec 2017 and Feb 2022. The chi-square test or Fisher exact test was performed on the 2 × 2 cross-tabulations of honeycomb appearance and other peripheral retinal findings and complications. RESULTS: Thirty-eight patients (48.7%), and 60 eyes (39.2%) had a honeycomb appearance of different areas on the fundus. The supratemporal quadrant was the most commonly affected (45 eyes, 75.0%), followed by the infratemporal (23 eyes, 38.3%), the infranasal (10 eyes,16.7%), and supranasal (9 eyes,15.0%). The appearance was significantly associated with peripheral retinoschisis, inner retinal layer break, outer retinal layer break, RD, and rhegmatogenous retinal detachment (RRD) (p < 0.01, p = 0.032, p < 0.01, p = 0.008, p < 0.01, respectively). All the eyes complicated with RRD had the appearance. None of the eyes without the appearance had RRD. CONCLUSIONS: The data suggest that the honeycomb appearance is not uncommon in patients with XLRS and is more likely to be accompanied by an RRD, and inner and outer layer breaks, thus should be treated with caution and close observation.

Treatment of severely calcified coronary artery disease by intravascular lithotripsy primary outcomes and 180-day follow-up from the Chinese SOLSTICE Trial.

OBJECTIVE: To assess the safety and effectiveness of intravascular lithotripsy (IVL) treatment for de novo coronary lesion involving severely calcified vessels in a Chinese population. METHODS: The Clinical Trial of the ShOckwave Coronary IVL System Used to Treat CalcIfied Coronary ArtEries (SOLSTICE) was a prospective, single-arm, multicentre trial. According to the inclusion criteria, patients with severely calcified lesions were enrolled in the study. IVL was used to perform calcium modification prior to stent implantation. The primary safety endpoint was freedom from major adverse cardiac events (MACEs) at 30 days. The primary effectiveness endpoint was procedural success, defined as successful stent delivery with residual stenosis < 50% by core lab assessment without in-hospital MACEs. The morphological changes of calcium modification were assessed by optical coherence tomography (OCT) before and after IVL treatment. RESULTS: Patients (n = 20) were enrolled at three sites in China. Severe calcification by core lab assessment was present in all lesions, with a mean calcium angle and thickness of 300 ± 51° and 0.99 ± 0.12 mm (by OCT), respectively. The 30-day MACE rate was 5%. Both primary safety and effectiveness endpoints were achieved in 95% of patients. The final in-stent diameter stenosis was 13.1% ± 5.7% with no patient had a residual stenosis < 50% after stenting. No serious angiographic complications (severe dissection grade D or worse, perforation, abrupt closure, slow flow/no-reflow) observed at any time during the procedure. OCT imaging demonstrated visible multiplane calcium fracture in 80% of lesions with a mean stent expansion of 95.62% ± 13.33% at the site of maximum calcification and minimum stent area (MSA) of 5.34 ± 1.64 mm2. CONCLUSIONS: The initial coronary IVL experience for Chinese operators resulted in high procedural success and low angiographic complications consistent with prior IVL studies, reflecting the relative ease of use of IVL technology.

A high triglyceride-glucose index associated with adverse cardiovascular events in patients with type 2 diabetes mellitus and chronic total occlusion after percutaneous coronary intervention.

Triglyceride-glucose index (TyG index) is a reliable surrogate marker of insulin resistance, associated with morbidity and prognosis of cardiovascular disease. However, its predictive value for cardiovascular events in patients with type 2 diabetes mellitus (T2DM) and chronic total occlusion (CTO) after percutaneous coronary intervention (PCI) has not been studied. Here, we retrospectively enrolled 681 patients with T2DM and CTO after PCI. Patients were divided into two groups based on a median TyG index of 9.02. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The primary observational end point was the composite of overall death, nonfatal myocardial infarction, and unplanned revascularization. The Multivariate Cox hazards regression analysis showed that the TyG index was significantly correlated with the primary end point (hazard ratio = 1.699, 95% confidence interval 1.254-2.303, p = 0.001). The addition of TyG to a baseline risk model had an incremental effect on the predictive value for the primary end point (area under the curve: TyG index vs baseline model, 0.693 vs 0.663, comparison p = 0.040; integrated discrimination improvement = 0.049, p = 0.020). The TyG index might be a predictor of adverse cardiovascular events. Moreover, adding the TyG index into a baseline risk model had a cumulative effect on the predictive potential for the primary end point.

[Diagnosis Significance of the Levels of Cytokines IL-6, IL-10 and CXCL-13 in Cerebrospinal Fluid for Central Nervous System Infiltration of Lymphoma].

OBJECTIVE: To evaluate the diagnostic value of the expression levels of cytokines interleukin-6(IL-6), interleukin-10 (IL-10) and chemokine （C-X-C motif） ligand-13 (CXCL-13) in cerebrospinal fluid (CSF) for central nervous system infiltration of lymphoma. METHODS: Forty patients diagnosed as lymphoma or acute lymphoblastic leukemia in General Hospital of Northern Theater Command from July 2020 to July 2021 were collected and recorded their CSF indexes, including pressure, protein, Pandy test, nucleated cell count, glucose and chlorine content in CSF. The levels of cytokines IL-6, IL-10 and CXCL-13 were detected by Enzyme-linked immunosorbent assay. RESULTS: The patients were divided into CNSI (central nervous system infiltration) group and non-CNSI group, the average levels of IL-6, IL-10, CXCL-13 and IL-10/IL-6 ratio in CNSI group were higher than those in non-CNS group, but the difference of IL-10/IL-6 ratio between the two groups was statistically significant (P<0.05). Then the patients were divided into protein elevated(n=14) group and protein normal group(n=26), the levels of IL-6 ï¼» (5.78±2.69) pg/ mlï¼½ and CXCL-13 ï¼»(0.83±0.59) pg/mlï¼½ in protein elevated group were significantly higher than those in the protein normal group ï¼»IL-6: (2.41±1.16) pg/ml; CXCL-13: (0.38±0.18) pg/mlï¼½ (P<0.05). Further analysis of the expression levels of the cytokines in non-CNSI group (n=32), IL-6, IL-10, CXCL-13 level and IL-10/IL-6 ratio in the protein elevated group (n=12) were higher than those in the protein normal group (n=20), but the difference was not statistically significant. CONCLUSION: The levels of IL-6, IL-10 and CXCL-13 in CSF of lymphoma patients with CNS infiltration were higher than those in non-CNS infiltration group, and those in patients with protein elevated group are higher than those in the protein normal group.

Serum glycated albumin is associated with in-stent restenosis in patients with acute coronary syndrome after percutaneous coronary intervention with drug-eluting stents: An observational study.

Background: Previous studies have confirmed the predicted value of serum glycated albumin (GA) in atherosclerotic cardiovascular disease. However, the relationship between GA and the development of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation has not been verified in patients with acute coronary syndrome (ACS). Materials and methods: In this study, 797 patients diagnosed with ACS who underwent re-coronary angiography more than 6 months after the first successful DES-based percutaneous coronary intervention (PCI) were eventually included. Patients were categorized into two groups based on the median GA levels of 14.94%. Moreover, multivariate logistic regression analysis models and the net reclassification improvement and integrated differentiation improvement risk models were constructed to assess the relationship between the GA and DES-ISR in patients with ACS. Results: The GA was significantly associated with an increased risk of DES-ISR, upon adjusting for confounding factors (as nominal variate: OR 1.868, 95% CI 1.191-2.932, P = 0.007; as continuous variate: OR 1.109, 95% CI 1.040-1.183, P = 0.002). The addition of GA to a baseline risk model had an incremental effect on the predictive value for DES-ISR (AUC: GA vs. baseline model, 0.714 vs. 0.692, comparison P = 0.017; category-free net reclassification improvement (NRI) 0.080, P = 0.035; integrated discrimination improvement (IDI) 0.023, P < 0.001). Conclusion: GA level was significantly associated with a high risk of DES-ISR in patients with ACS treated with PCI. Moreover, the addition of the GA to a baseline risk model has an incremental effect on the predictive potential for DES-ISR.

[Methods for the evaluation of intestinal mucosal permeability].

The intestinal mucosal barrier (IMB), which consists of mechanical barrier, chemical barrier, biological barrier and immune barrier, plays an important role in the maintenance of intestinal epithelium integrity and defense against invasion of bacteria, endotoxins and foreign antigens. Impaired IMB, characterized by increased intestinal mucosal permeability (IMP) and decreased transmembrane resistance (TR), has been implicated in the pathogenesis of various digestive, urinary, circulatory, neurological and metabolic dysfunctions. Electrophysiological recording of TR in the ex vivo intestinal tissues or cultured epithelial cell monolayers, or biochemical quantification of transepithelial movement of orally-administered molecular probes or specific endogenous protein molecules has frequently been used in the evaluation of IMB. In this paper, the composition and function of IMB will be summarized, with emphasis on the evaluation methods of IMP.

[Fibroblast growth factor 21 plays a protective role in cardiovascular diseases by inducing autophagy].

Fibroblast growth factor 21 (FGF21) is a growth factor with endocrine function in the fibroblast growth factor family. Previous reports have shown that FGF21 is involved in the regulation of energy metabolism and plays a protective role in cardiovascular diseases such as coronary heart disease, diabetes, non-alcoholic fatty liver disease and so on. Recent studies have found that FGF21 can induce autophagy in a variety of tissues and organs, and autophagy is involved in many pathological processes of cardiovascular diseases, including vascular calcification, atherosclerosis, and myocardial ischemia-reperfusion injury. Therefore, FGF21 may play a protective role in a variety of cardiovascular diseases by regulating autophagy. This article reviews the research progress on the protective role of FGF21 in cardiovascular diseases by inducing autophagy.

Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect.

BACKGROUND: Sepsis involves life-threatening organ dysfunction and is caused by a dysregulated host response to infection. No specific therapies against sepsis have been reported. Celastrol (Cel) is a natural anti-inflammatory compound that shows potential against systemic inflammatory diseases. This study aimed to investigate the pharmacological activity and molecular mechanism of Cel in models of endotoxemia and sepsis. METHODS: We evaluated the anti-inflammatory efficacy of Cel against endotoxemia and sepsis in mice and macrophage cultures treated with lipopolysaccharide (LPS). We screened for potential protein targets of Cel using activity-based protein profiling (ABPP). Potential targets were validated using biophysical methods such as cellular thermal shift assays (CETSA) and surface plasmon resonance (SPR). Residues involved in Cel binding to target proteins were identified through point mutagenesis, and the functional effects of such binding were explored through gene knockdown. RESULTS: Cel protected mice from lethal endotoxemia and improved their survival with sepsis, and it significantly decreased the levels of pro-inflammatory cytokines in mice and macrophages treated with LPS (P < 0.05). Cel bound to Cys424 of pyruvate kinase M2 (PKM2), inhibiting the enzyme and thereby suppressing aerobic glycolysis (Warburg effect). Cel also bound to Cys106 in high mobility group box 1 (HMGB1) protein, reducing the secretion of inflammatory cytokine interleukin (IL)-1ß. Cel bound to the Cys residues in lactate dehydrogenase A (LDHA). CONCLUSION: Cel inhibits inflammation and the Warburg effect in sepsis via targeting PKM2 and HMGB1 protein.

Timing theory continuous nursing, resistance training: Rehabilitation and mental health of caregivers and stroke patients with traumatic fractures.

BACKGROUND: Stroke is the leading cause of adult lifelong disability worldwide. A stroke is an acute cerebrovascular disease with a variety of causes and corresponding clinical symptoms. Around 75% of surviving stroke patients experience impaired nerve function, and some suffer from traumatic fractures, which can lead to special care needs. AIM: To determine the effect of timing theory continuous care, with resistance training, on the rehabilitation and mental health of caregivers and stroke patients with traumatic fractures. METHODS: Between January 2017 to March 2021, we selected 100 hospital admissions with post-stroke hemiplegia complicated with a traumatic fracture. Two participant groups were created: (1) Control group: given resistance training; and (2) Observation group: given timing theory continuous care combined with resistance training. The degree of satisfaction and differences in bone and phosphorus metabolism indexes between the two groups were compared. The self-perceived burden scale (SPBS) and caregiver burden questionnaire were used to evaluate the psychological health of patients and caregivers. The Harris hip function score, ability of daily living (ADL) scale, and global quality of life questionnaire (GQOL-74) were used to evaluate hip function, ability of daily living, and quality of life. RESULTS: Data were collected prior to and after intervention. Alkaline phosphatase (ALP), osteocalcin, and vitamin D3 in the observation group and control group increased after intervention (P < 0.05), and carboxy-terminal peptide of type I collagen ß Special sequence (ß-CTX) decreased (P < 0.05). ALP and osteocalcin in the observation group were higher than in the control group (P < 0.05). There was no significant difference in ß-CTX and vitamin D3 between the two groups (P > 0.05). The SPBS score of the observation group was lower and the ADL score was higher than the control group. The burden score was lower and the Harris hip function and GQOL-74 scores were higher than that of the control group (P < 0.05). The observation group's satisfaction rating was 94.00%, which was higher than the rating from the control group (P < 0.05). CONCLUSION: Timing theory continuous nursing with resistance training can reduce hip dysfunction in stroke patients with a traumatic fracture and enhance quality of life and mental health of patients and caregivers.

Admission high-sensitivity C-reactive protein levels improve the Grace risk score prediction on in-hospital outcomes in acute myocardial infarction patients.

BACKGROUND: Acute myocardial infarction (AMI) is the main cause of death and disability in cardiovascular and cerebrovascular diseases. Both the Global Registry of Acute Coronary Events (Grace) score and high-sensitivity C-reactive protein (hs-CRP) were associated with prognosis in patients with AMI. However, whether the addition of the hs-CRP to Grace risk score could improve the predictive power of Grace risk score on the prognosis of patients with AMI is unclear. HYPOTHESIS: We hypothesized that the inclusion of hs-CRP in the Grace risk score could improve the ability to correctly distinguish the occurrence of in-hospital outcomes. METHODS: We retrospectively enrolled 1804 patients with AMI in the final analysis. Patients were divided into four groups by hs-CRP quartiles. The relation between hs-CRP and Grace risk score was analyzed by Spearman rank correlation. Logistic regression was used to identify independent risk factors. The predictive value of hs-CRP add to Grace risk score was evaluated by C-statistic, net reclassification improvement (NRI), integrated differentiation improvement (IDI), calibration plot, and decision curve analysis. RESULTS: The hs-CRP and Grace risk score had a significantly positive correlation (r = .191, p < .001). hs-CRP combined with Grace risk score could improve the ability of Grace risk score alone to correctly redistinguish the occurrence of in-hospital outcome (C-statistic = 0.819, p < .001; NRI = 0.05956, p = .007; IDI = 0.0757, p < .001). CONCLUSION: Admission hs-CRP level was a significant independent risk factor for in-hospital outcomes in patients with AMI. The inclusion of hs-CRP in the Grace risk score could improve the ability to correctly distinguish the occurrence of in-hospital outcomes.

Clinical Characteristics of Pediatric Coats' Disease With Retinal Cyst Using Wide-Angle Fluorescein Angiography.

Purpose: To assess the demographic and treatment features of pediatric patients of Coats' disease with retinal cyst using wide-angle FA. Design: A retrospective, hospital based, cross-sectional study. Participants: Pediatric patients of Coats' disease underwent wide-angle FA. Methods: A retrospective review of pediatric patients of Coats' disease who underwent wide-angle FA at a single center from January 2015 to July 2020. Demographic and treatment features were compared between patients with or without retinal cyst. Main Outcome Measures: Demographic and treatment outcomes. Results: There were 123 pediatric Coats' patients in our study, and 18.70% (23/123) of the patients developed complications with retinal cyst, 73.9% (17/23) of the retinal cysts were located in the inferior-temporal quadrant and 82.6% (19/23) of the retinal cysts were located in the peripheral retina anterior to the vortex veins. Compared with patients without retinal cyst, patients with retinal cyst had more clock-hours of telangiectasia on FA (7.32 vs. 5.41, p = 0.031), and may need more total treatments (7.47 vs. 3.53, p = 0.023) including laser photocoagulation (4.08 vs. 2.31, p = 0.019) or intravitreal anti-VEGF (3.13 vs. 2.23, p = 0.039), and also required a longer time for telangiectasia resolution (22.33 vs. 18.53 months, p = 0.043). Conclusion: Pediatric patients with Coats' disease complicated by retinal cyst presented with more clock-hours of telangiectasia on FA and needed more total treatments and longer time for telangiectasia resolution.

Reduced acetylcholine and elevated muscarinic receptor 2 in duodenal mucosa contribute to the impairment of mucus secretion in 6-hydroxydopamine-induced Parkinson's disease rats.

Patients with Parkinson's disease (PD) have a higher incidence rate of duodenal ulcers. The mucus barrier provides the first line of defense for duodenal mucosal protection. However, it is unknown whether duodenal mucus secretion is affected in PD. In the present study, we used the rats microinjected 6-hydroxydopamine (6-OHDA) into the bilateral substantia nigra to investigate duodenal mucus secretion and potential therapeutic targets in duodenal ulcer in PD. Alcian blue-periodic acid-Schiff, transmission electron microscopy, immunofluorescence, duodenal mucosal incubation, and enzyme-linked immunosorbent assays were used. The 6-OHDA rats exhibited mucin accumulation and retention in duodenal goblet cells. Mucin granules were unable to fuse with the apical membranes of goblet cells, and the exocytosis ratio of goblet cells was significantly reduced. Moreover, decreased acetylcholine and increased muscarinic receptor 2 (M2R) levels were detected in the duodenal mucosa of 6-OHDA rats. Bilateral vagotomy rats were also characterized by defective duodenal mucus secretion and decreased acetylcholine with increased M2R levels in the duodenal mucosa. Application of the cholinomimetic drug carbachol or blocking M2R with methoctramine significantly promoted mucus secretion by goblet cells and increased MUC2 content in duodenal mucosa-incubated solutions from 6-OHDA and vagotomy rats. We conclude that the reduced acetylcholine and increased M2R contribute to the impaired duodenal mucus secretion of 6-OHDA rats. The study provides new insights into the mechanism of duodenal mucus secretion and potential therapeutic targets for the treatment of duodenal ulcers in PD patients.

Pericardial Tamponade Caused by Rotational Atherectomy Ablation Grinding Through a Barrier Stent Protruding From the Diagonal Artery: A Case Report.

Rotational atherectomy (RA) has been described in case reports to be effective in ablating under-expanded stents. We present a case of calcified bifurcation lesion percutaneous coronary intervention (PCI), in which the branch stent protruding into main branch blocked the balloon getting through, and the following RA led to pericardial tamponade. The first stent was deployed from the proximal of left anterior descending artery (LAD) to the proximal of diagonal for an 80-year-old man who suffered from non-ST-elevation myocardial infarction to make a Culotte dual stent PCI. The operator failed to make balloon get through the struts protruding into LAD lumen anyway. After RA drill through the LAD lumen, it showed an excellent angiographic outcome. Stent deployment in LAD was successful, but pericardial tamponade occurred in a short time. After pericardiocentesis was performed under fluoroscopic guidance, the patient was uneventful. After 1 year, the follow-up coronary computed tomography (CT) angiography showed no in-stent restenosis, stent fracture or disrupted struts protruding outside of the vessel's outline of LAD and the first diagonal (D1). This case shows stents' RA could be dangerous in grinding across the stents' lateral hole in an unsymmetrical lumen. Although RA could be a useful remedy in the situation of under-expansion of implanted stents, the debulking should be performed for longitudinal stent ablation and cautiously performed for bifurcation lesion in which the protruding stents from side branch were unsymmetrically blocking the path.

Pancreatic acinar cells utilize tyrosine to synthesize L-dihydroxyphenylalanine.

The pancreatic ß cells can synthesize dopamine by taking L-dihydroxyphenylalanine, but whether pancreatic acinar cells synthesize dopamine has not been confirmed. By means of immunofluorescence, the tyrosine hydroxylase -immunoreactivity and aromatic amino acid decarboxylase (AADC)- immunoreactivity were respectively observed in pancreatic acinar cells and islet ß cells. Treatment with L-dihydroxyphenylalanine, not tyrosine, caused the production of dopamine in the incubation of INS-1 cells (rat islet ß cell line) and primary isolated islets, which was blocked by AADC inhibitor NSD-1015. However, only L-dihydroxyphenylalanine, but not dopamine, was detected when AR42J cells (rat pancreatic acinar cell line) were treated with tyrosine, which was blocked by tyrosine hydroxylase inhibitor AMPT. Dopamine was detected in the coculture of INS-1 cells with AR42J cells after treatment with tyrosine. In an in vivo study, pancreatic juice contained high levels of L-dihydroxyphenylalanine and dopamine. Both L-dihydroxyphenylalanine and dopamine accompanied with pancreatic enzymes and insulin in the pancreatic juice were all significantly increased after intraperitoneal injection of bethanechol chloride and their increases were all blocked by atropine. Inhibiting TH with AMPT blocked bethanechol chloride-induced increases in L-dihydroxyphenylalanine and dopamine, while inhibiting AADC with NSD-1015 only blocked the dopamine increase. Bilateral subdiaphragmatic vagotomy of rats leads to significant decreases of L-dihydroxyphenylalanine and dopamine in pancreatic juice. These results suggested that pancreatic acinar cells could utilize tyrosine to synthesize L-dihydroxyphenylalanine, not dopamine. Islet ß cells only used L-dihydroxyphenylalanine, not tyrosine, to synthesize dopamine. Both L-dihydroxyphenylalanine and dopamine were respectively released into the pancreatic duct, which was regulated by the vagal cholinergic pathway. The present study provides important evidences for the source of L-dihydroxyphenylalanine and dopamine in the pancreas.

Combination of molecularly targeted therapies and immune checkpoint inhibitors in the new era of unresectable hepatocellular carcinoma treatment.

Multikinase inhibitors (MKIs) have been the only first-line treatment for advanced hepatocellular carcinoma (HCC) for more than a decade, until the approval of immune checkpoint inhibitors (ICIs). Moreover, the combination regimen of atezolizumab (anti-programmed cell death protein ligand 1 antibody) plus bevacizumab (anti-vascular endothelial growth factor monoclonal antibody) has recently been demonstrated to have superior efficacy when compared with sorafenib monotherapy. The remarkable efficacy has made this combination therapy the new standard treatment for advanced HCC. In addition to MKIs, many other molecularly targeted therapies are under investigation, some of which have shown promising results. Therefore, in the era of immuno-oncology, there is a significant rationale for testing the combinations of molecularly targeted therapies and ICIs. Indeed, numerous preclinical and clinical studies have shown the synergic antitumor efficacy of such combinations. In this review, we aim to summarize the current knowledge on the combination of molecularly targeted therapies and immune checkpoint therapies for HCC from both preclinical and clinical perspectives.