Binzhou Medical College Hospital

AIM: Whether Tai Chi (TC) is effective in the cardiac rehabilitation of patients with chronic heart failure (CHF) remains controversial. We performed a meta-analysis to examine the effects of TC on exercise capacity and quality of life (QoL) in CHF patients. METHODS AND RESULTS: PubMed and EMBASE databases were searched (up to May 2012) for relevant studies. Studies including participants with reduced left ventricular systolic function (ejection fraction ≤ 45%) were selected. Interventions considered were TC with or without comparisons (education or usual care). Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the I(2) test. Four randomized controlled trials (RCTs) (n = 242) met the inclusion criteria. TC significantly improved QoL (WMD -14.54 points; 95% CI -23.45 to -5.63). TC was not associated with a significant reduction in N-terminal pro brain natriuretic peptide (WMD -61.16 pg/mL; 95% CI -179.27 to 56.95), systolic blood pressure (WMD -1.06 mmHg; 95% CI -13.76 to 11.63), diastolic blood pressure (WMD -0.08 mmHg; 95% CI -3.88 to 3.73), improved 6 min walking distance (WMD 46.73 m; 95% CI -1.62 to 95.09), or peak oxygen uptake (WMD 0.19 mL/kg/min; 95% CI -0.74 to 1.13). CONCLUSIONS: TC may improve QoL in patients with CHF and could be considered for inclusion in cardiac rehabilitation programmes. However, there is currently a lack of evidence to support TC altering other important clinical outcomes. Further larger RCTs are urgently needed to investigate the effects of TC.

OBJECTIVE: The objective of this study was to analyze the clinical manifestation, course, evolution, image manifestation, and treatments of LGI1 limbic encephalitis (LE). PATIENTS AND METHODS: Studies confirmed that LE with the complex antibody of voltage-gated potassium channels is LGI1 LE. Since then, LE cases have been reported. In this study, 10 typical LE cases were searched in PubMed. These cases and one additional case, which we reported herein, were retrospectively analyzed. RESULTS: All the patients suffered from recent memory deterioration. The following cases were observed: eight with faciobrachial dystonic seizures (FBDS), six with different kinds of epileptic seizures (four complex partial seizures, one myoclonus seizure, and one generalized tonic-clonic seizure), four with FBDS and different kinds of epileptic seizures at the same time, five with mental disorders (one visual hallucination, one paranoia, one depression, one anxiety, and one dysphoria), five with hyponatremia, and two with sleep disorder. The brain MRI of nine patients revealed abnormalities in the mediotemporal lobe and the hippocampus. The LGI1 antibodies in the blood and/or cerebrospinal fluid (CSF) were positive. The content of the CSF protein of two patients increased slightly. The tumor marker of all the patients was normal, but capitate myxoma was detected in the combined pancreas duct of one patient. Gamma globulin and hormone treatments were administered to nine patients. Of these patients, six received a combination of antiepileptic drugs. The clinical symptoms of all the patients improved. CONCLUSION: LGI1 LE is an autoimmune encephalitis whose clinical manifestations are memory deterioration, FBDS, epileptic seizure, mental disorders, and hyponatremia. Brain MRI shows that this autoimmune disease mainly involves the mediotemporal lobe and the hippocampus. This condition can also be manifested with other autoimmune encephalitis cases but can be rarely associated with tumors. After patients with LGI1 LE receive gamma globulin and hormone treatments, their clinical prognosis is good.

Desmosomes, which are intercellular adhesive complexes, are essential for the maintenance of epithelial homeostasis. They are located at the cell membrane, where they act as anchors for intermediate filaments. Downregulation of desmosome proteins in various cancers promotes tumor progression. However, the role of desmosomes in carcinogenesis is still being elucidated. Recent studies revealed that desmosome family members play a crucial role in tumor suppression or tumor promotion. This review focuses on studies that provide insights into the role of desmosomes in carcinogenesis and address their molecular functions.

BACKGROUND: Donor-derived cell-free DNA (dd-cfDNA) is a potential noninvasive molecular marker of graft rejection after kidney transplant, whose diagnostic accuracy remains controversial. METHODS: We performed a systematic review and metaanalysis to evaluate the diagnostic accuracy of dd-cfDNA. Relevant literature was searched from online databases, and the data on the diagnostic accuracy of discriminating main rejection episodes (MRE) and antibody-mediated rejection (AMR) were merged, respectively. RESULTS: Nine studies were included in the metaanalysis, of which 6 were focused on the diagnostic accuracy of dd-cfDNA for MRE, whose pooled sensitivity, specificity, area under the receiver operating characteristics curve, diagnostic odds ratio, overall positive likelihood ratio, and negative likelihood ratio with 95% confidence intervals were 0.70 (0.57-0.81), 0.78 (0.70-0.84), 0.81 (0.77-0.84), 8.18 (5.11-13.09), 3.15 (2.47-4.02), and 0.39 (0.27-0.55), respectively. Five tests were focused on discriminating AMR, whose pooled indicators were 0.84 (0.75-0.90), 0.80 (0.74-0.84), 0.89 (0.86-0.91), 20.48 (10.76-38.99), 4.13(3.21-5.33), and 0.20(0.12-0.33), respectively. CONCLUSIONS: Donor-derived cell-free DNA can be a helpful marker for the diagnosis of AMR among those recipients suspected of renal dysfunction. Its diagnostic accuracy on the MRE remains uncertain, which requires further prospective, large-scale, multicenter, and common population research.

Ischemia-reperfusion (I/R)-mediated intestinal mucosal injury is usually induced by oxygen-derived toxic free radicals from the xanthine oxidase system after reperfusion, but the detailed molecular mechanisms underlying glutamine protection is still unclear. This study aims to elucidate whether glutamine prevents damage to the intestinal mucosa after I/R in rats and to investigate signaling by the Nrf2/ARE pathway induced by GLN in a rat model. Our results revealed that Glutamine pretreatment reduced jejunum injury and microvascular hyper-permeability induced by I/R. MDA level significantly increased while the SOD and GSH-Px levels decreased in the I/R group compared to the sham group and the GLN-I/R group. Both the mRNA and protein levels of the Nrf2 and HO-1 were significantly elevated by GLN pretreatment when compared to the I/R group. GLN treatment also elevated Bcl-2 levels, and accordingly suppressed apoptotic damage in the jejunum cells shown by decreased cleaved caspase-3 level. Mechanistic investigation revealed that GLN treatment augmented binding of Nrf2 onto Bcl2 gene promoter. These results indicate that glutamine has protective effects on I/R in vivo by activating the Nrf2/ARE signaling pathway to inhibit ROS production and reduce intestinal apoptosis.

Journal Article Association analysis of filaggrin gene mutations and atopic dermatitis in Northern China Get access L. Ma, L. Ma State Key Department of Dermatology, No. 1 Hospital of China Medical University, 155 North Nanjing Street, Shenyang 110001, ChinaDepartment of Dermatology, Binzhou Medical College Hospital, Binzhou, China Search for other works by this author on: Oxford Academic Google Scholar L. Zhang, L. Zhang State Key Department of Dermatology, No. 1 Hospital of China Medical University, 155 North Nanjing Street, Shenyang 110001, China Search for other works by this author on: Oxford Academic Google Scholar Z‐H. Di, Z‐H. Di Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, China Search for other works by this author on: Oxford Academic Google Scholar L‐P. Zhao, L‐P. Zhao Department of Dermatology, The General Hospital of Shenyang Military Command, Shenyang, China Search for other works by this author on: Oxford Academic Google Scholar Y‐N. Lu, Y‐N. Lu Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, China Search for other works by this author on: Oxford Academic Google Scholar J. Xu, J. Xu Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, China Search for other works by this author on: Oxford Academic Google Scholar H‐D. Chen, H‐D. Chen State Key Department of Dermatology, No. 1 Hospital of China Medical University, 155 North Nanjing Street, Shenyang 110001, China Search for other works by this author on: Oxford Academic Google Scholar X‐H. Gao X‐H. Gao State Key Department of Dermatology, No. 1 Hospital of China Medical University, 155 North Nanjing Street, Shenyang 110001, China Xing‐Hua Gao. E‐mail: gaobarry@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 1, 1 January 2010, Pages 225–227, https://doi.org/10.1111/j.1365-2133.2009.09539.x Published: 01 January 2010

BACKGROUND AND AIM: It remains challenging to determine the inflammatory activity in Crohn's disease (CD) for lack of specific laboratory markers. Recent studies suggest that serum omentin-1 is associated with inflammatory response. We aimed to assess the potential of serum omentin-1 as a marker of disease activity in CD patients. METHODS: Serum omentin-1 concentrations were determined by enzyme-linked immunosorbent assay (ELISA) in patients with CD (n = 240), functional gastrointestinal disorders (FGDs, n = 120), and healthy controls (HC, n = 60) and evaluated for correlation with disease activity. Expression of omentin-1 in colonic tissues from patients with CD was also analyzed by real-time PCR and Western blotting. Serum omentin-1 levels as an activity index were evaluated using a receiver operating characteristic (ROC) curve. RESULTS: Serum omentin-1 concentrations were significantly decreased in active CD patients compared with patients in remission, FGDs, and HC (all P < 0.001). Expression of omentin-1 was decreased at mRNA and protein levels in inflamed colonic tissues in active CD than that in noninflamed colonic tissues. Serum omentin-1 levels were negatively correlated with disease activity in CD, better than C-reactive protein (CRP). CONCLUSION: Our results indicate that serum and colonic omentin-1 expressions are decreased in active CD patients. The correlation of serum omentin-1 with disease activity in CD is superior to that of CRP. Serum omentin-1 is a potential marker for CD disease activity.

OBJECTIVE: To investigate the efficacy and effect on outcome of goal-directed therapy in patients with septic shock compared with conventional therapy. METHODS: Sixteen patients with septic shock were randomly assigned to receive goal-directed therapy, with central venous pressure (CVP) 8-12 mm Hg (1 mm Hg=0.133 kPa), mean arterial pressure (MAP) >or=65 mm Hg, venous oxygen saturation (SvO(2))>0.70 (superior vena cava saturation), and urine output >or=0.5 ml/min as therapeutic goals. Another 17 patients received conventional therapy as controls. The arterial oxygen saturation (SaO(2)), SvO(2), MAP, CVP, heart stroke volume cardiac index (CI), serum lactate, volume of fluid, amount of vasopressors, the numbers of organ injured and patients who needed continuity blood purification (CBP) and/or ventilation were recorded serially for 6-48 hours, and they were compared between the two groups. The mortality of the patients in two groups on 7 days and 14 days were also recorded. RESULTS: There were no significant differences between the groups with respect to base-line characteristics. During the interval from 24 to 48 hours, the patients assigned to goal-directed therapy had a significantly higher in SaO(2), SvO(2), MAP, CVP, CI (P<0.05 or P<0.01), a lower lactate concentration (P<0.01), significantly more fluid during 6-24 hours and less vasopressors (both P<0.01). Seven and 14 days in-hospital mortality were lower in goal-directed therapy group as compared with the control group(P<0.05). CONCLUSION: The efficacy of goal-directed therapy in patients with septic shock is significantly better than conventional therapy in ameliorating outcome of shock and can be easily used in intensive care unit (ICU).

Cardiovascular disease (CVD) remains the predominant cause of mortality and disability worldwide. Against this backdrop, finding effective drugs for the pharmacological treatment of CVD has become one of the most urgent and challenging issues in medical research. Garlic (Allium sativum L.) is one of the oldest plants and is world-renowned for its dietary and medicinal values. Allicin (diallyl thiosulfinate) is one of the primary natural active ingredients in garlic, which has been proven to have powerful cardioprotective effects and mediate various pathological processes related to CVD, such as inflammatory factor secretion, myocardial cell apoptosis, oxidative stress, and more. Therefore, allicin holds a promising application prospect in the treatment of CVD. This review summarized the biological functions of allicin and its potential mechanisms in CVD, including antioxidation, anti-inflammation, and anti-apoptosis effects. Reckoning with these, we delved into recent studies on allicin's cardioprotective effects concerning various CVDs, such as atherosclerosis, hypertension, myocardial infarction, arrhythmia, cardiac hypertrophy, heart failure, and cardiotoxicity. Further, considering the tremendous advancement in nanomedicine, nanotechnology-based drug delivery systems show promise in addressing limitations of allicin's clinical applications, including improving its solubility, stability, and bioavailability. Through this review, we hope to provide a reference for further research on allicin in cardioprotection and drug development.

BACKGROUND: The study was conducted to retrospectively evaluate the safety and effectiveness of computed tomography (CT)-guided percutaneous microwave ablation (MWA) for peripheral non-small cell lung cancer (NSCLC) in 11 patients with a single lung after pneumonectomy. METHODS: From May 2011 to March 2015, 11 single-lung patients (8 men and 3 women; mean age 60.3 years, range 46-71) with peripheral NSCLC underwent 12 sessions of MWA. Eleven tumors measuring 13-52 mm (mean 30.2 mm) were treated. Follow-up was performed via CT scan at 1, 3, 6, 12, 18, and 24 months after the procedure and annually thereafter. Clinical outcomes were evaluated and complications after MWA were summarized. RESULTS: At a median follow-up period of 20 months (range 6-38), four patients showed evidence of local recurrence at a rate of 36.4% (4/11). Median overall survival was 20 months. The overall survival rates at one, two, and three years after MWA were 88.7%, 63.6%, and 42.3%, respectively. Complications after MWA included pneumothorax (33.3%), hemoptysis (33.3%), intrapulmonary bleeding (25%), pleural effusion (16.7%), and pulmonary infection (8.3%). None of the patients died during the procedure or in the 30 days after MWA. CONCLUSION: CT-guided percutaneous MWA is safe and effective for the treatment of peripheral NSCLC in patients with a single lung after prior pneumonectomy.

INTRODUCTION: Up to present, EGF 61*A/G, TGF-β1 -509*T/C and TNF-α -308*A/G gene polymorphisms have been analysed in other cancer entities than hepatocellular carcinoma (HCC). We here investigated the frequency of these gene polymorphisms among HCC patients. MATERIALS AND METHODS: A total of 73 HCC patients and 117 cancer-free healthy people were recruited at the Surgical Department of Zhongshan Hospital. Genomic DNA was isolated from peripheral blood and gene polymorphisms were analyzed by PCR-RFLP. RESULTS: The distribution of EGF 61*G/G homozygotes among HCC patients was more frequent than that in the control group (24.7% vs 11.1%, OR=2.618, 95%CI=1.195-5.738). In parallel, the frequency of the "G" allele in the HCC patient group was also higher than that in the control group (45.9% vs 33.3%, OR= 1.696, 95%CI=1.110-2.592). No difference could be found for the TGF-β1-509 and TNF-α -308 genotypes. CONCLUSION: EGF 61*G/G genotype and G allele are significantly increased among patients with HCC. TGF-β1-509*T/C and TNF-α -308*A/G gene polymorphisms are not related to this cancer entity.

Athletes whose knees are subjected to sudden changes of direction and high jumps such as martial arts athletes, dancers, wrestlers and football players are at higher risk of injuring popliteomeniscal fascicles. Painful squatting and mechanical symptoms such as locking sensation are common. Current available treatments includes open or arthroscopic in repair. Arthroscopic repair with all-inside device can relieve symptoms and restore knee function. Six patients from two surgical centers with isolated popliteomeniscal fascicles tears were treated with arthroscopic all-inside repair. The surgical technique is thoroughly described. All patients showed consistent symptoms and MRI findings, as well as meniscal hypermobility during arthroscopic probing. Moreover, four out of six showed a chondral lesion of the lateral femoral condyle. All of them had their lateral meniscus sutured with one or more sutures. Symptoms were relieved and all but one were able to return to play at the pre-injury level. No postoperative complications were encountered. The diagnosis of the disruption of popliteomeniscal fascicles is challenging and often seen in athletes that play sports which involve repetitive twisting. However, patients’ complaints are consistent. Arthroscopic repair with an all-inside device showed to be a reliable and easy technique for addressing the condition, although some issues still need to be investigated, such as how much constraint the repair should provide. Arthroscopic all-inside repair of popliteomeniscal tears prove to be safe and effective in the short-term follow-up, allowing for sport activity resumption.

The aim of this study was to investigate whether calcitonin gene-related peptide (CGRP) administration could produce neuroprotective effects after brain ischemia reperfusion in rats. Brain ischemia reperfusion injury was induced by a 2-hour left middle cerebral artery occlusion (MCAO) using an intraluminal filament, followed by 46hours of reperfusion. CGRP (1 microg/ml) at the dose of 3 microg/kg, i.p., was administered at the beginning of reperfusion. Saline (3 ml/kg body weight) treated animals were used as control. Sham-operated animals were also used. Subsequently, 48 hours after MCAO, infarct volume, histological alterations, based fibroblast growth factor (bFGF) and aquaporin-4 (AQP4) expression were examined. The results showed that CGRP could significantly decrease infarct volume, improve brain tissue histological damage, promote bFGF expression and inhibit AQP4 expression after brain ischemia reperfusion injury. The results suggested that the neuroprotective effects of CGRP may be mediated by promoting bFGF expression and inhibiting AQP4 expression. The spatial and temporal distribution of molecules involved in the ischemic cascade by CGRP administration should be further studied.

Baitouweng Decotion (BD) is a famous traditional Chinese medicinal prescription, which is composed of Pulsatilla chinensis (bunge) regel, Coptis chinensis franch., Phellodendron chinense and Cortex Fraxini. In this study, a simple and sensitive high performance liquid chromatography coupled with ultraviolet detection method was established for the simultaneous determination of eight marker compounds including Esculin, Fraxin, Esculetin, Fraxetin, Columbamine, Coptisine, Palmatine Chloride and Berberine hydrochloride in BD, the single herbs and their negative controls. The chromatographic separation was performed using an Agilent Eclipse XDB-C18 column with a gradient elution system of acetonitrile and 0.1% phosphoric acid (contained 0.2% triethylamine) solution at a flow rate of 0.8 mL/min. The results demonstrated that the validated method was simple, reliable and successfully applied to evaluate the selected compounds in water extraction (BDW) and ethanol extraction (BDE) of BD, the single herbs and their negative control for quality control. Moreover, the experimental data showed that the contents of the major active components detected in BDE were significantly higher than those in the BDW, while the BDW had several peaks BDE without. The paper also suggested a method to extract Fraxin, Esculin, Fraxetin, Esculetin and Berberine from Baitouweng Decotion more effectively.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a high mortality rate and poor prognosis. miR-637 has been reported to regulate tumor progression and act as a prognosis biomarker of various cancers. Its functional role in NSCLC was investigated in this study. METHODS: The expression level of miR-637 in NSCLC tissues and adjacent normal tissues of 123 NSCLC patients was analyzed by qRT-PCR. The association between miR-637 and clinical pathological features in the prognosis of patients was analyzed. Cell transfection was performed to overexpress or knockdown miR-637 in H1299 and HCC827. The proliferation, migration, and invasion of H1299 and HCC827 were evaluated by CCK8 and Transwell assay. RESULTS: miR-637 expression was significantly decreased in NSCLC tissues and cell lines relative to normal tissues and cells. The survival rate of NSCLC patients with low miR-637 expression was lower than that of patients with high miR-637 expression. Additionally, miR-637 served as a tumor suppressor that inhibited cell proliferation, migration, and invasion of NSCLC. CONCLUSION: Downregulation of miR-637 in NSCLC was associated with TNM stage and poor prognosis of patients and served as a tumor suppressor in NSCLC. These results provide a potential strategy to control NSCLC.

Background and Purpose It is well known that microsatellite instability‐high (MSI‐H) is associated with 5‐fluorouracil (5‐FU) resistance in colorectal cancer. MSI‐H is the phenotype of DNA mismatch repair deficiency (MMR‐D), mainly occurring due to hypermethylation of MLH1 promoter CpG island. However, the mechanisms of MMR‐D/MSI‐H are unclear. We aim to investigate the pathway of MMR‐D/MSI‐H involved in 5‐FU resistance. Experimental Approach Human colorectal cancer specimens were diagnosed for MSI‐H by immunohistochemistry and western blotting. Proteome microarray interactome assay was performed to screen nuclear proteins interacting with ATG5. Nuclear ATG5 and ATG5‐Mis18α overexpression were analysed in ATG5 high colorectal cancer bearing mice. The methylation assay determined the hypermethylation of hMLH1 promoter CpG island in freshly isolated human colorectal cancer tissue samples and HT29 atg5 and SW480 atg5 cancer cells. Key Results In ATG5 high colorectal cancer patients, 5‐FU‐based therapy resulted in nuclear translocation of ATG5, leading to MSI‐H. Colorectal cancer in Atg5 Tg mice demonstrated 5‐FU resistance, compared to Atg5 +/− and WT mice. Proteome microarray assay identified Mis18α, a protein localized on the centromere and a source for methylation of the underlying chromatin, which responded to the translocated nuclear ATG5 leading to ATG5‐Mis18α conjugate overexpression. This resulted in MLH1 deficiency due to hypermethylation of hMLH1 promoter CpG island, while the deletion of nuclear Mis18α failed to induce ATG5‐Mis18α complex and MMR‐D/MSI‐H. Conclusions and Implications Nuclear ATG5 resulted in MMR‐D/MSI‐H through its interaction with Mis18α in ATG5 high colorectal cancer cells. We suggest that ATG5‐Mis18α or Mis18α may be a therapeutic target for treating colorectal cancer.

OBJECTIVE: The objective of the study is to evaluate levels of chemokine (C-C motif) ligand 18 (CCL18) in human glioma tissues and effects of CCL18 on U251 glioma cells. MATERIALS AND METHODS: By using the real-time reverse transcription polymerase chain reaction and immunochemically histological staining, we determined the mRNA and protein levels of CCL18 in tissues of 60 patients with World Health Organization (WHO) Grades II, III and IV glioma and the normal brain. Cultured U251 glioma cells were incubated with CCL18 and then subjected to transwell. The scratch wound-healing and cell count kit (CCK-8) assays were performed to detect the possible effects of CCL18 on the cell invasion, migration, and proliferation. RESULTS: In the tissues of the normal brain (n = 10), glioma Grade II (n = 26), III (n = 18), and IV (n = 16), CCL18 mRNA expression levels were 1.00 ± 0.09, 6.02 ± 1.26, 26.35 ± 3.98, and 112.21 ± 13.25 fold, respectively (P < 0.01); the percentage of CCL18-positive glioma cells was 0%, 58.8%, 70.0%, and 100% in the normal brain, glioma WHO Grade II, III, and IV, respectively (P < 0.01). Different concentrations of CCL18 (0, 5, and 10 ng/ml) enhanced the of U251 glioma cell invasion in 24 h transwell assays [from 43.5 ± 8.3 to 202.0 ± 18.5 and 279.7 ± 18.6 cells (P < 0.01)], increased the cell migration quantified by comparing the areas of the scratch (pixel) [at 12 h, 498.4 ± 75.3, 381.3 ± 21.4, and 347.7 ± 14.2; at 24 h, 299.5 ± 15.3, 284.6 ± 7.8, and 237.3 ± 20.6 (P < 0.05)], and significantly increased the cell growth in CCK-8 assay [from 1.000 ± 0.019-1.260 ± 0.094 and 2.070 ± 0.138 fold in CCL18, respectively (n = 20/each group) (P < 0.01)]. CONCLUSION: We have found that CCL18 is highly expressed in glioma tissues and enhances the invasion, migration, and proliferation of U251 glioma cells. Therefore, CCL18 may be a potential biomarker for detecting and grading human glioma.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is difficult to predict and carries high mortality. This study utilized radiomic techniques with clinical examinations to assess recurrence in HCC. PURPOSE: To develop a Cox nomogram to assess the risk of postoperative recurrence in HCC using radiomic features of three volumes of interest (VOIs) in preoperative dynamic contrast-enhanced MRI (DCE-MRI), along with clinical findings. STUDY TYPE: Retrospective. SUBJECTS: 249 patients with pathologically proven HCCs undergoing surgical resection at three institutions were selected. FIELD STRENGTH/SEQUENCE: Fat saturated T2-weighted, Fat saturated T1-weighted, and DCE-MRI performed at 1.5 T and 3.0 T. ASSESSMENT: Three VOIs were generated; the tumor VOI corresponds to the area from the tumor core to the outer perimeter of the tumor, the tumor +10 mm VOI represents the area from the tumor perimeter to 10 mm distal to the tumor in all directions, finally, the background liver parenchyma VOI represents the hepatic tissue outside the tumor. Three models were generated. The total radiomic model combined information from the three listed VOI's above. The clinical-radiological model combines physical examination findings with imaging characteristics such as tumor size, margin features, and metastasis. The combined radiomic model includes features from both models listed above and showed the highest reliability for assessing 24-month survival for HCC. STATISTICAL TESTS: The least absolute shrinkage and selection operator (LASSO) Cox regression, univariable, and multivariable Cox regression, Kmeans clustering, and Kaplan-Meier analysis. The discrimination performance of each model was quantified by the C-index. A P value <0.05 was considered statistically significant. RESULTS: The combined radiomic model, which included features from the radiomic VOI's and clinical imaging provided the highest performance (C-index: training cohort = 0.893, test cohort = 0.851, external cohort = 0.797) in assessing the survival of HCC. CONCLUSION: The combined radiomic model provides superior ability to discern the possibility of recurrence-free survival in HCC over the total radiomic and the clinical-radiological models. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Social anhedonia, a loss of interest and pleasure in social interactions, is a common symptom of major depression as well as other psychiatric disorders. Depression can occur at any age, but typically emerges in adolescence or early adulthood, which represents a sensitive period for social interaction that is vulnerable to stress. In this study, we evaluated social interaction reward using a conditioned place preference (CPP) paradigm in adolescent male and female mice. Adolescent mice of both sexes exhibited a preference for the social interaction-associated context. Chronic unpredictable stress (CUS) impaired the development of CPP for social interaction, mimicking social anhedonia in depressed adolescents. Conversely, administration of leptin, an adipocyte-derived hormone, enhanced social interaction-induced CPP in non-stressed control mice and reversed social anhedonia in CUS mice. By dissecting the motivational processes of social CPP into social approach and isolation avoidance components, we demonstrated that leptin treatment increased isolation aversion without overt social reward effect. Further mechanistic exploration revealed that leptin stimulated oxytocin gene transcription in the paraventricular nucleus of the hypothalamus, while oxytocin receptor blockade abolished the leptin-induced enhancement of socially-induced CPP. These results establish that chronic unpredictable stress can be used to study social anhedonia in adolescent mice and provide evidence that leptin modulates social motivation possibly via increasing oxytocin synthesis and oxytocin receptor activation.

Abstract Background Shen-Zhi-Ling oral liquid (SZL) is an herbal formula known for its efficacy of nourishing “heart and spleen”, and is used for the treatment and prevention of middle- and early-stage dementia. This study investigated the effects of SZL on amelioration of AD, and examined whether the underlying mechanisms from the perspective of neuroprotection are related to brain glucose metabolism. Methods Firstly, LC–MS/MS was used to analysis the SZL mainly enters the blood component. Then, the effects of SZL on cognitive and behavioral ability of APP/PS1 double transgenic mice and amyloid protein characteristic pathological changes were investigated by behavioral study and morphological observation. The effects of SZL on the ultrastructure of mitochondria, astrocytes, and micrangium related to cerebral glucose metabolism were observed using transmission electron microscopy. Then, micro-PET was also used to observe the effects of SZL on glucose uptake. Furthermore, the effects of SZL on insulin signaling pathway InR/PI3K/Akt and glucose transporters (GLUT1 and GLUT3) were observed by immunohistochemistry, Western-blot and RT-qPCR. Finally, the effects of SZL on brain glucose metabolism and key enzyme were observed. In vitro, the use of PI3K and/or GSK3β inhibitor to observe the effects of SZL drug-containing serum on GLUT1 and GLUT3. Results In vivo, SZL could significantly ameliorate cognitive deficits, retarded the pathological damage, including neuronal degeneration, Aβ peptide aggregation, and ultrastructural damage of hippocampal neurons, improve the glucose uptake, transporters and glucolysis. Beyond that, SZL regulates the insulin signal transduction pathway the insulin signal transduction pathway InR/PI3K/Akt. Furthermore, 15% SZL drug-containing serum increased Aβ 42 -induced insulin signal transduction-pathway related indicators and GLUT1 and GLUT3 expression in SH-SY5Y cells. The improvement of GLUT1 and GLUT3 in the downstream PI3K/Akt/GSK3β signaling pathway was reversed by the use of PI3K and/or GSK3β inhibitor. Conclusions In summary, our results demonstrated that improving glucose uptake, transport, and glycolysis in the brain may underlie the neuroprotective effects of SZL, and its potential molecular mechanism may be related to regulate the insulin signal transduction pathway.