The relationship of exercise and cancer-related fatigue in patients with advanced liver cancer: a cross-sectional study.

There is increasing interest in understanding exercise as a potential treatment for cancer-related fatigue (CRF); however, rarely research has been conducted on more aggressive cancers with short survival, such as liver cancer. The purpose of this study was to provide educational ideas for insufficient exercise and provide clues for the design of effective and safe exercise intervention programs with high compliance in patients of advanced liver cancer in the future. Participants were recruited from a tertiary cancer hospital using convenience sampling. All participants were asked to complete self-report questionnaires that assessed their medical and demographic variables, exercise habits and CRF during their hospitalization in the interventional department. Spearman's correlation analysis and Nonparametric test was used to explore correlations between exercise subgroups and CRF. The Baron and Kenny's Approach was used to investigate the mediating effect of exercise index between P-EX and CRF. 207 out of 255 participants were enrolled in this study, with an average age of 55.4 years. The CRF score was 33 (28, 36), and 93.2% had insufficient exercise. Exercise frequency (≥ 3 Times/week) (Z = 4.34, p = 0.037) and maintaining exercise trend (Z = 15.85, p = 0.001) had a positive effect on CRF. P-EX had a great impact on exercise index and affecting CRF directly. Participants in the study showed serious fatigue and insufficient exercise. Exercise education can be initiated earlier, particularly those without regular exercise experience. Sustained light exercise, compliant with exercise habits and interests, three times a week may be a practical way to reduce the risk of CRF in advanced liver cancer.

Differential proteomic analysis of plasma-derived exosomes as diagnostic biomarkers for chronic HBV-related liver disease.

Hepatitis B virus (HBV) infection is still a major public health problem worldwide. We aimed to identify new, non-invasive biomarkers for the early diagnosis of chronic HBV-related diseases, reveal alterations in the progression of chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Here, exosomes were isolated and characterized through size exclusion chromatography and nanoparticle tracking analysis. Profiles of differentially expressed proteins (DEPs) were analyzed through liquid chromatography-tandem mass spectrometry (LC-MS/MS), Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. Results showed that the DEPs, including CO9, LBP, SVEP1, and VWF levels in extracellular vesicles (EVs) were significantly higher in CHB than in healthy controls (HCs). VWF expression levels in EVs were significantly lower in CHB than in those with LC. KV311 expression levels in EVs were significantly higher, whereas LBP levels were significantly lower in patients with CHB than in those with HCC. All biomarkers seemed to exhibit a high diagnostic capacity for HBV-related liver disease. Patients with HBV-induced chronic liver disease exhibit characteristic protein profiles in their EVs. Thus, serum exosomes may be used as novel, liquid biopsy biomarkers to provide useful clinical information for the diagnosis of HBV-related liver diseases at different stages.

Novel Compound Heterozygous PKLR Mutation Induced Pyruvate Kinase Deficiency With Persistent Pulmonary Hypertension in a Neonate: A Case Report.

Background: Pulmonary hypertension could be associated with pyruvate kinase deficiency (PKD). There are few reported cases of PPHN as the first clinical manifestation of PKD. Herein we report a rare case of PKD in which the patient exhibited persistent pulmonary hypertension in the neonate (PPHN), and genetic testing helped to rapidly identify an potential association. Case presentation: The patient was a newborn boy who suffered from severe dyspnea, extreme anemia, skin pallor, and hypoxemia. Repeated echocardiography indicated persistent severe pulmonary hypertension with a calculated pulmonary artery pressure of 75 mmHg, and right ventricular hypertrophy. The administration of nitric oxide significantly reduced the pulmonary artery pressure. Whole-exome sequencing revealed a compound heterozygous mutation consisting of c.707T > G and c.826_827insAGGAGCATGGGG. PolyPhen_2 and MutationTaster indicated that both the c.707T > G (probability 0.999) and c.826_827insAGGAGCATGGGG (probability 0.998) mutations were disease causing. PROVEAN protein batch analysis indicated that the associated p.L236R region was deleterious (score -4.71) and damaging (SIFT prediction 0.00), and this was also the case for p.G275_V276insEEHG (deleterious score -12.00, SIFT prediction 0.00). Substantial structural changes in the transport domain of the protein were predicted using SWISS-MODEL, and indicated that both mutations led to an unstable protein structure. Thus, a novel compound heterozygous mutation of PKLR-induced PKD with PPHN was diagnosed. Conclusion: The current study suggests that molecular genetic screening is useful for identifying PPHN, particularly in children with metabolic disorders. In patients exhibiting unexplained hyperbilirubinemia combined with severe pulmonary hypertension, PKD might be a potential possible alternative explanation. Genetic screening is helpful for identifying genetic causes of pulmonary hypertension, especially in patients with PPHN. This report expands the mutation spectrum of the PKLR gene, and contributes to the genotype-phenotype map of PKD.

Serum level of testosterone predicts disease severity of male COVID-19 patients and is related to T-cell immune modulation by transcriptome analysis.

BACKGROUND: Severe disease of COVID-19 and mortality occur more frequently in male patients than that in female patients may be related to testosterone level. However, the diagnostic value of changes in the level of testosterone in predicting severe disease of male COVID-19 patients has not been determined yet. METHODS: Sixty-one male COVID-19 patients admitted to the First Affiliated Hospital of Zhejiang University School of Medicine were enrolled. Serum samples at different stages of the patients after admission were collected and testosterone levels were detected to analyze the correlation between testosterone level and disease severity. Transcriptome analysis of PBMC was performed in 34 patients. RESULTS: Testosterone levels at admission in male non-ICU COVID-19 patients (3.7 nmol/L, IQR: 1.5 âˆ¼ 4.7) were significantly lower than those in male ICU COVID-19 patients (6.7 nmol/L, IQR: 4.2 âˆ¼ 8.7). Testosterone levels in the non-ICU group increased gradually during the progression of the disease, while those in the ICU group remained low. In addition, testosterone level of enrolled patients in the second week after onset was significantly correlated with the severity of pneumonia, and ROC curve showed that testosterone level in the second week after onset was highly effective in predicting the severity of COVID-19. Transcriptome studies have found that testosterone levels of COVID-19 patients were associated with immune response, including T cell activation and regulation of lymphocyte activation. In addition, CD28 and Inositol Polyphosphate-4-Phosphatase Type II B (INPP4B) were found positively correlated with testosterone. CONCLUSIONS: Serum testosterone is an independent risk factor for predicting the severity of COVID-19 in male patients, and the level of serum testosterone in the second week after onset is valuable for evaluating the severity of COVID-19. Testosterone level is associated with T cell immune activation. The monitoring of serum testosterone should be highlighted in clinical treatment and the related mechanism should be further studied.

Meta-analysis and systematic review of electronic bronchoscopy in refractory pneumonia.

BACKGROUND: A systematic review and meta-analysis were performed to explore the adoption value of electronic bronchoscopy (EBS) in the diagnosis and treatment of refractory pneumonia and to provide a theoretical basis for the clinical bronchoscopy treatment of patients. METHODS: Randomized controlled trials of treatment-resistant pneumonia searched on PubMed, Embase, and other websites before December 31, 2020 were collected. Literature was selected by inclusion and exclusion criteria. Bias risk was assessed using Cochrane intervention system Review manual 5.0.2 and Review Manager 5.3. RESULTS: A total of 6 articles meeting the requirements were included, comprising 796 participants. The results of meta-analysis showed that the clinical efficacy [odds ratio (OR) =3.8; 95% confidence interval (CI): 1.11-12.99; Z=2.13; P =0.03] and white blood cell counts [mean difference (MD) =0.55; 95% CI: -0.57 to 1.67; Z=0.96; P=0.34] of patients both increased. The mortality rate (OR =0.7; 95% CI: 0.3-1.63; Z=0.82; P=0.41), the incidence of infection (OR =0.84; 95% CI: 0.5-1.39; Z=0.69; P=0.49), ICU hospitalization days (OR =0.59; 95% CI: 0.36-0.98; Z=2.04; P=0.04), days of antibiotic use (OR =0.39; 95% CI: 0.18-0.84; Z=2.41; P=0.02), body temperature (MD =-0.2; 95% CI: -0.24 to 0.16; Z=9.5; P<0.0001), and the PaO2:FIO2 ratio (MD =-9.96; 95% CI: -13.31 to -6.61; Z=5.83; P<0.0001) of patients in the experimental group were lower than those of the control group. Differences in white blood cell count, mortality rate, and incidence of infection of patients in the experimental group were not statistically significant compared with those in the control group. DISCUSSION: EBS adopted in the diagnosis and treatment of refractory pneumonia can reduce the occurrence of postoperative adverse reactions, reduce the infection rate, and effectively improve the clinical symptoms. It is therefore suitable for the treatment of this disease.

Genome-wide screening identifies oncofetal lncRNA Ptn-dt promoting the proliferation of hepatocellular carcinoma cells by regulating the Ptn receptor.

Oncofetal genes are genes that express abundantly in both fetal and tumor tissues yet downregulated or undetected in adult tissues, and can be used as tumor markers for cancer diagnosis and treatment. Meanwhile, long noncoding RNAs (lncRNAs) are known to play crucial roles in the pathogenesis of hepatocellular carcinoma (HCC), including tumor growth, proliferation, metastasis, invasion, and recurrence. We performed a genome-wide screening using microarrays to detect the lncRNA expression profiles in fetal livers, adult livers, and liver cancer tissues from mice to identify oncofetal lncRNAs in HCC. From the microarray data analysis, we identified lncRNA Ptn-dt as a possible oncofetal gene. Both in vitro and in vivo experiments results confirmed that overexpression of Ptn-dt significantly promoted the proliferation of mouse HCC cells. RNA pulldown assay showed that Ptn-dt could interact with the HuR protein. Interestingly, miR-96 binds with HuR to maintain its stability as well. Overexpression of lncRNA Ptn-dt led to the downregulation of miR-96, which might be due to the interaction between Ptn-dt and HuR. Meanwhile, previous studies have reported that Ptn can promote tumor growth and vascular abnormalization via anaplastic lymphoma kinase (Alk) signaling. In our study, we found that overexpression of Ptn-dt could promote the expression of Alk through repressing miR-96 via interacting with HuR, thus enhancing the biologic function of Ptn. In summary, a new oncofetal lncRNA Ptn-dt is identified, and it can promote the proliferation of HCC cells by regulating the HuR/miR-96/Alk pathway and Ptn-Alk axis.

Porous Iron-Carboxylate Metal-Organic Framework: A Novel Bioplatform with Sustained Antibacterial Efficacy and Nontoxicity.

Sustained drug release plays a critical role in targeting the therapy of local diseases such as bacterial infections. In the present work, porous iron-carboxylate metal-organic framework [MOF-53(Fe)] nanoparticles (NPs) were designed to entrap the vancomycin (Van) drugs. This system exhibited excellent chemical stability under acidic conditions (pH 7.4, 6.5, and 5.5) and much higher drug-loading capability because of the high porosity and large surface area of MOF NPs. The results showed that the drug-loading ratio of Van could reach 20 wt % and that the antibacterial ratio of the MOF-53(Fe)/Van system against Staphylococcus aureus could reach up to 90%. In addition, this MOF-53(Fe)/Van system exhibited excellent biocompatibility because of its chemical stability and sustained release of iron ions. Hence, these porous MOF NPs are a promising bioplatform not only for local therapy of bacterial infections but also for other biomedical therapies for tissue regeneration.

Lumbar puncture-administered resveratrol inhibits STAT3 activation, enhancing autophagy and apoptosis in orthotopic rat glioblastomas.

Trans-resveratrol suppresses glioblastoma growth in vitro, but its effects on intracranial glioblastomas remain untested. Resveratrol crosses the blood-brain barrier, and lumbar puncture (LP) greatly increases its bioavailability in rat brains; therefore, we investigated the effectiveness of LP-administered resveratrol on orthotopic rat glioblastomas. Twenty-four tumor-bearing rats were separated into two groups: Group 1 receiving 100 µl saline containing 0.3% DMSO and Group 2 receiving 100 µl resveratrol (300 µM). Treatments started 3 days after transplantation in 2-day intervals until death. Intracranial drug availabilities, tumor sizes, average life spans and the impacts on STAT3 signaling, apoptosis and autophagy rates were evaluated. MRI imaging revealed that average tumor size in the LP group (495.8 ± 22.3 mm2) was smaller than the control groups (810.3 ± 56.4 mm2; P<0.05). The mean survival time in the LP group (22.2 ± 2.1 d) was longer than control animals (16.0 ± 1.8 d; P<0.05). LP resveratrol-treated glioblastomas showed less Cyclin D1 staining, enhanced autophagy with up-regulated LC3 and Beclin1 expression, and widely distributed apoptotic foci around tumor capillaries with suppressed STAT3 expression and nuclear translocation. In conclusion, LP-delivered resveratrol efficiently inhibited orthotopic rat glioblastoma growth by inactivating STAT3 signaling and enhancing autophagy and apoptosis.

Down-regulation of HDAC5 inhibits growth of human hepatocellular carcinoma by induction of apoptosis and cell cycle arrest.

Histone deacetylases (HDACs) play a critical role in the proliferation, differentiation, and apoptosis of cancer cells. An obstacle for the application of HDAC inhibitors as effective anti-cancer therapeutics is that our current knowledge on the contributions of different HDACs in various cancer types remains scarce. The present study reported that the mRNA and protein levels of HDAC5 were up-regulated in human hepatocellular carcinoma (HCC) tissues and cells as shown by quantitative real-time PCR and Western blot. MTT assay and BrdU incorporation assay showed that the down-regulation of HDAC5 inhibited cell proliferation in HepG2, Hep3B, and Huh7 cell lines. Data from in vivo xenograft tumorigenesis model also demonstrated the anti-proliferative effect of HDAC5 depletion on tumor cell growth. Furthermore, the suppression of HDAC5 promoted cell apoptosis and induced G1-phase cell cycle arrest in HCC cells. On the molecular level, we observed altered expression of apoptosis-related proteins such as p53, bax, bcl-2, cyto C, and caspase 3 in HDAC5-shRNA-transfected cells. Knockdown of HDAC5 led to a significant up-regulation of p21 and down-regulation of cyclin D1 and CDK2/4/6. We also found that the down-regulation of HDAC5 substantially increased p53 stability and promoted its nuclear localization and transcriptional activity. Our study suggested that knockdown of HDAC5 could inhibit cancer cell proliferation by the induction of cell cycle arrest and apoptosis; thus, suppression of HDAC5 may be a viable option for treating HCC patients.

[Sonographic features and diagnostic analysis of breast granulomatous diseases: a report of 32 cases].

OBJECTIVE: To evaluate the sonographic features of different pathological types of breast granulomatous diseases and analyze the feasibility of ultrasonic diagnosis. METHODS: A total of 32 patients with different pathological types of breast granulomatous diseases were recruited. Their clinical and sonographic findings were retrospectively reviewed. There were granulomatous mastitis (n = 12), breast xanthogranuloma (n = 5), lipogranuloma (n = 2), foreign body granuloma (n = 1) and nonspecific granulation hyperplasia (n = 12). RESULTS: Based on major sonographic appearances, they were divided into 4 patterns of tubular, mass, diffuse and cystic mass. In 12 patients with granulomatous mastitis and 12 patients with nonspecific granulation hyperplasia, the major sonographic appearance was of tubular pattern (n = 6, 5), followed by mass pattern (n = 4, 5) and diffuse pattern (n = 2, 2). Five patients with breast xanthogranuloma and 1 patient with foreign body granuloma all showed mass pattern. In 2 patients with lipogranuloma, one was of mass pattern and another cystic pattern. In patients with granulomatous mastitis and patients with nonspecific granulation hyperplasia, it showed a high diagnostic reliability of ultrasound. The ratio of inflammatory lesion as the first sonographic diagnosis was 10/12 and 8/12 respectively and ultrasonic BI-RADS 4b or above both only 1/12. However, the ratio of sonographic imaging in patients with xanthogranuloma and Lipogranuloma mimic breast cancer, in which ultrasonic score as breast imaging-reporting and data system (BI-RADS) 4b or above was 4/5 and 1/1 respectively. CONCLUSIONS: Ultrasound is valuable in evaluating the lesions in patients with granulomatous mastitis and nonspecific granulation hyperplasia. However a definite diagnosis is still dependent on histopathology.

N1-guanyl-1,7-diaminoheptane (GC7) enhances the therapeutic efficacy of doxorubicin by inhibiting activation of eukaryotic translation initiation factor 5A2 (eIF5A2) and preventing the epithelial-mesenchymal transition in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) cells undergo the epithelial-mesenchymal transition (EMT) during chemotherapy, which reduces the efficacy of doxorubicin-based chemotherapy. We investigated N1-guanyl-1,7-diaminoheptane (GC7) which inhibits eukaryotic translation initiation factor 5A2 (eIF5A2) activation; eIF5A2 is associated with chemoresistance. GC7 enhanced doxorubicin cytotoxicity in epithelial HCC cells (Huh7, Hep3B and HepG2) but had little effect in mesenchymal HCC cells (SNU387, SNU449). GC7 suppressed the doxorubicin-induced EMT in epithelial HCC cells; knockdown of eIF5A2 inhibited the doxorubicin-induced EMT and enhanced doxorubicin cytotoxicity. GC7 combination therapy may enhance the therapeutic efficacy of doxorubicin in HCC by inhibiting eIF5A2 activation and preventing the EMT.

Molecular cloning, characterization and expression of cDNA encoding translationally controlled tumor protein (TCTP) from Jatropha curcas L.

A cDNA encoding translationally controlled tumor protein (TCTP) of Jatropha curcas L., JcTCTP, was isolated from an endosperm cDNA library. JcTCTP consisted of a 5' untranslated region (UTR) of 526 bp, a 3' UTR of 377 bp and an open reading frame (ORF) of 507 bp, encoding a protein of 168 amino acid residues, which contained two signature sequences of TCTP family. Its deduced amino acid sequence was similar to the other known plants TCTPs in a range of 77.4-92.3%. Expression of JcTCTP was the highest in the stem, endosperm at embryo formation stage and embryo of J. curcas tissues, and the lowest in the endosperm at seminal leaf embryo stage and flower, demonstrating a pattern of temporal and spatial specific expression.

[Application of fetal echocardiography in detection of fetal arrhythmia and its clinical significance].

OBJECTIVE: To investigate application of fetal echocardiography in diagnosis of fetal arrhythmia and its clinical significance. METHODS: Fetal echocardiography was performed on 725 fetuses for evaluation of fetal heart structures and arrhythmias. Two-dimensional, M-mode, Color M-mode and pulsed Doppler echocardiography were used. RESULTS: Ninety fetuses were documented with fetal arrhythmia, the commonest fetal arrhythmia encountered in 72 cases extrasystole was (65 atrial extrasystoles, 7 ventricular extrasystoles), followed by bradycardia in 9 cases, tachycardia in 6 cases, 2:1 atrioventricular block in 2 cases, atrial flutter in 1 case. There were 4 fetuses with arrhythmias and structural heart diseases: 2 fetuses were found died in uterus within two-week follow-up (1 with single ventricle and pulmonary stenosis, 1 with cardiac rhabdomyoma, fetal echocardiographic findings were confirmed at autopsy), another 2 cases (1 with mitral atresia and 1 with atrioventricular canal defect, autopsy confirmed the fetal echocardiographic diagnoses) received termination of pregnancy later. One 38-week fetus with atrial flutter underwent cesarean section, neonatal ECG confirmed the arrhythmia, and Cedilanid D induced successful conversion. All the other 85 fetuses were with intermittent arrhythmia, normal heart structures, and had no fetal hydrops. After receiving routine treatment, all of them had term deliveries and follow-up monitoring showed normal neonatal heart rhythms (auscultation). CONCLUSIONS: Fetal echocardiography is the main diagnostic tool for prenatal evaluation of fetal arrhythmias. The outcomes of the vast majority of fetal arrhythmias are benign, especially for fetuses with extrasystoles. Their arrhythmias are always well tolerated and disappear during the perinatal period. Fetuses with intermittent arrhythmias without structural heart malformations, fetal hydrops or heart failure, can be followed up with routine prenatal care without the need for special intervention.