Developing risk models and subtypes of autophagy-associated LncRNAs for enhanced prognostic prediction and precision in therapeutic approaches for liver cancer patients.

Background: Limited research has been conducted on the influence of autophagy-associated long non-coding RNAs (ARLncRNAs) on the prognosis of hepatocellular carcinoma (HCC). Methods: We analyzed 371 HCC samples from TCGA, identifying expression networks of ARLncRNAs using autophagy-related genes. Screening for prognostically relevant ARLncRNAs involved univariate Cox regression, Lasso regression, and multivariate Cox regression. A Nomogram was further employed to assess the reliability of Riskscore, calculated from the signatures of screened ARLncRNAs, in predicting outcomes. Additionally, we compared drug sensitivities in patient groups with differing risk levels and investigated potential biological pathways through enrichment analysis, using consensus clustering to identify subgroups related to ARLncRNAs. Results: The screening process identified 27 ARLncRNAs, with 13 being associated with HCC prognosis. Consequently, a set of signatures comprising 8 ARLncRNAs was successfully constructed as independent prognostic factors for HCC. Patients in the high-risk group showed very poor prognoses in most clinical categories. The Riskscore was closely related to immune cell scores, such as macrophages, and the DEGs between different groups were implicated in metabolism, cell cycle, and mitotic processes. Notably, high-risk group patients demonstrated a significantly lower IC50 for Paclitaxel, suggesting that Paclitaxel could be an ideal treatment for those at elevated risk for HCC. We further identified C2 as the Paclitaxel subtype, where patients exhibited higher Riskscores, reduced survival rates, and more severe clinical progression. Conclusion: The 8 signatures based on ARLncRNAs present novel targets for prognostic prediction in HCC. The drug candidate Paclitaxel may effectively treat HCC by impacting ARLncRNAs expression. With the identification of ARLncRNAs-related isoforms, these results provide valuable insights for clinical exploration of autophagy mechanisms in HCC pathogenesis and offer potential avenues for precision medicine.

Association between body roundness index and non-alcoholic fatty liver disease detected by Fibroscan in America.

BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) and obesity is worldwide on the rise. Body roundness index (BRI), as a newly developed anthropometric indicator, has been recently reported to identify obesity. However, it is still unclear whether BRI is associated with the prevalence of NAFLD. METHODS: Data were from the National Health and Nutrition Examination Survey (NHANES) 2017-2018. NAFLD was diagnosed based on hepatic steatosis defined by CAP values ≥274 dB/m. Multivariable logistic regression analysis was performed to detect the association between BRI and the odds of NAFLD. Subgroup analysis stratified by age, gender, BMI, and race was further conducted. To explore the potential ability of BRI in predicting NAFLD, the area under the curve (AUC) of BRI was calculated by receiver operating characteristic (ROC) analysis. RESULTS: Among the 4467 study participants, 1718 (38.5%) were diagnosed with NAFLD. Compared to the non-NAFLD group, participants with NAFLD had a higher level of BRI. The positive associations between BRI and NAFLD were detected in all three models (mode 1: OR = 1.71, 95% CI: 1.65-1.78, p < 0.0001; mode 2: OR = 1.78, 95% CI: 1.71-1.86, p < 0.0001; mode3: OR = 1.23, 95% CI: 1.11-1.35, p < 0.0001). The positive association steadily existed in different subgroups after stratified by age, gender, and BMI. Moreover, the non-linear association between BRI and NAFLD was detected, presenting inverted U-shaped curves. Furthermore, BRI had a high predictive value (AUC = 0.807) in identifying NAFLD. CONCLUSIONS: BRI was positively associated with the prevalence of NAFLD among individuals in America, regardless of age, gender, and BMI. Besides, BRI presented a high ability for identifying NAFLD.

Association of serum uric acid-to-high-density lipoprotein cholesterol ratio with non-alcoholic fatty liver disease in American adults: a population-based analysis.

Objective: Non-invasive disease indicators are currently limited and need further research due to the increased non-alcoholic fatty liver disease (NAFLD) prevalence worldwide. The serum uric acid-to-high-density lipoprotein cholesterol ratio (UHR) has been recognized as a novel inflammatory and metabolic marker. Herein, we explored the correlation between UHR and the risk of NAFLD in-depth. Methods: A total of 3,766 participants were included in our survey, and the National Health and Nutrition Examination Survey (NHANES) 2017-2018 cycle provided the cross-sectional study population. Weighted multivariable logistic regression and multivariate linear regression analyses were performed to assess the association between the UHR and the odds of NAFLD and liver steatosis and fibrosis severity, respectively. Moreover, we explored the non-linear relationship between the UHR and NAFLD by the generalized additive model. Results: NAFLD probabilities were statistically demonstrated to be positively correlated with the UHR (OR = 1.331 per SD increase, 95% CI: 1.100, 1.611). The positive connection of the UHR with NAFLD risk persisted significantly in female subjects but not in male subjects in subgroup analyses stratified by gender. The non-linear relationship analysis demonstrated that a UHR between ~20 and 30% suggested a saturation effect of NAFLD risk. Furthermore, a dramatically positive correlation was found between the UHR and hepatic steatosis severity but not fibrosis. Finally, the receiver operating characteristic analysis suggested that UHR had a better predictive value for NAFLD than either serum uric acid (sUA) or high-density lipoprotein cholesterol (HDL) alone [UHR (area under curve): 0.6910; 95% CI: 0.6737-0.7083; P < 0.0001]. Conclusion: Our investigation revealed that the elevated UHR level was independently related to an increased NAFLD risk and the severity of liver steatosis in American individuals. The correlation differed according to sex. This non-invasive indicator may enhance the capacity to predict the onset of NAFLD and may uncover alternative therapeutic interventional targets.

Relative bradycardia presented as a clinical feature of Brucella melitensis infection: A case report.

Brucellosis, caused by Brucella species, is an infectious disease transmitted through contact with infected animals or their secretions. The clinical disease is characterized by fever and headache. Relative bradycardia is an inappropriate response of heart rate to body temperature, in which the heart rate does not increase proportionally despite a high fever. In this report, we document one case of Brucella melitensis infection demonstrating relative bradycardia. To our knowledge, this is the first report of relative bradycardia in a patient with brucellosis.

Changes of serum P62 and Beclin 1 in patients with pulmonary embolism during treatment and their predictive value for efficacy.

OBJECTIVE: This study was designed to analyze the changes of serum P62 and Beclin 1 in patients with acute pulmonary embolism (APE) during treatment and their predictive value for efficacy. METHODS: In this retrospective study, 84 patients diagnosed as APE in Ningbo First Hospital from January 2020 to January 2022 were enrolled and assigned to a patient group, and 40 healthy individuals who underwent physical examination in Ningbo First Hospital during the same time period were assigned to a control group. Serum P62 and Beclin 1 expressions were compared between the two groups, and receiver operating characteristic (ROC) curves were drawn to analyze the diagnostic value of serum P62 and Beclin 1. The changes of serum P62 and Beclin 1 before and after treatment were evaluated. The correlations of P62 and Beclin 1 levels with the efficacy in patients were analyzed, and corresponding ROC curves were drawn. Additionally, the expressions of serum P62 and Beclin 1 in patients with different disease degrees were determined, and their expressions in relapsed patients were compared before treatment. RESULTS: The patient group showed significantly lower level of serum P62 but higher level of Beclin 1 than the control group (P<0.05). The areas of under the curves (AUCs) of P62 and Beclin 1 in diagnosing APE were 0.888 and 0.795 respectively. After treatment, patients showed significantly increased P62 expression (P<0.05) and significantly decreased Beclin 1 expression (P<0.01). The P62 expression increased with the relief of patient's disease, with a positive correlation with the patient's disease condition, while the Beclin 1 expression decreased with the relief of patient's disease, with a negative correlation with the patient's disease condition (P<0.05). In addition, the improved group showed significantly higher serum P62 expression (P<0.05) and significantly lower serum Beclin 1 expression than the non-improved group (P<0.05), and the AUCs of P62 and Beclin 1 in predicting the efficacy in patients with APE were 0.801 and 0.675, respectively. The relapsed group showed significantly lower serum P62 expression (P<0.05) and significantly higher Beclin 1 expression than the non-relapsed group (P<0.05), and the AUCs of P62 and Beclin 1 in predicting the recurrence of APE were 0.815 and 0.769, respectively. CONCLUSION: In patients with APE, serum P62 decreased, but serum Beclin 1 increased. So, both indictors can be applied for diagnosis, efficacy prediction and recurrence prediction of APE.

Clinical features and predictors for patients with severe SARS-CoV-2 pneumonia at the start of the pandemic: a retrospective multicenter cohort study.

BACKGROUND: This study was performed to investigate clinical features of patients with severe SARS-CoV-2 pneumonia and identify risk factors for converting to severe cases in those who had mild to moderate diseases at the start of the pandemic in China. METHODS: In this retrospective, multicenter cohort study, patients with mild to moderate SARS-CoV-2 pneumonia were included. Demographic data, symptoms, laboratory values, and clinical outcomes were collected. Data were compared between non-severe and severe patients. RESULTS: 58 patients were included in the final analysis. Compared with non-severe cases, severe patients with SARS-CoV-2 pneumonia had a longer: time to clinical recovery (12·9 ± 4·4 vs 8·3 ± 4·7; P = 0·0011), duration of viral shedding (15·7 ± 6·7 vs 11·8 ± 5·0; P = 0·0183), and hospital stay (20·7 ± 1·2 vs 14·4 ± 4·3; P = 0·0211). Multivariate logistic regression indicated that lymphocyte count was significantly associated with the rate of converting to severe cases (odds ratio 1·28, 95%CI 1·06-1·54, per 0·1 ×  109/L reduced; P = 0·007), while using of low-to-moderate doses of systematic corticosteroids was associated with reduced likelihood of converting to a severe case (odds ratio 0·14, 95%CI 0·02-0·80; P = 0·0275). CONCLUSIONS: The low peripheral blood lymphocyte count was an independent risk factor for SARS-CoV-2 pneumonia patients converting to severe cases. However, this study was carried out right after the start of the pandemic with small sample size. Further prospective studies are warranted to confirm these findings. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000029839 . Registered 15 February 2020 - Retrospectively registered.

Case Report: Metagenomic Next-Generation Sequencing in Diagnosis of Disseminated Tuberculosis of an Immunocompetent Patient.

Disseminated tuberculosis (TB) is a rare disease and mainly occurs in immunodeficient patients. It is marked by hematogenous or lymphatic dissemination of Mycobacterium tuberculosis, causing tuberculous infection involving any organ system. Here, we report a case of disseminated TB involving lung, liver, spine, mediastinum, and prostate in an immunocompetent man. The present patient found a hepatic mass without any symptom during health examination. In the next 2 years, further examinations revealed multiple lesions in the lung, mediastinum, spine, and prostate. Imaging examinations, such as contrast-enhanced abdominal CT, F-18 FDG-PET/CT, and radionuclide bone scan, suggested the diagnosis of malignancy or metastatic tumor. Furthermore, histopathological results of the biopsies of the hepatic mass, mediastinal mass, and prostatic mass demonstrated granulomatous inflammation. Therefore, metagenomic next-generation sequencing (mNGS) was utilized to confirm the diagnosis. Mycobacterium tuberculosis complex was simultaneously detected in the spinal surgical resection specimens and bronchoalveolar lavage fluid (BALF), indicating the diagnosis of disseminated TB. mNGS is an emerging molecular diagnostic technology, and its application in disseminated TB has been rarely reported. We highlight that disseminated TB should be considered even in an immunocompetent patient, and mNGS can be performed when the diagnosis is difficult.

Differential diagnosis of coronavirus disease 2019 pneumonia or influenza A pneumonia by clinical characteristics and laboratory findings.

BACKGROUND: Pneumonia caused by the 2019 novel Coronavirus (COVID-2019) shares overlapping signs and symptoms, laboratory findings, imaging features with influenza A pneumonia. We aimed to identify their clinical characteristics to help early diagnosis. METHODS: We retrospectively retrieved data for laboratory-confirmed patients admitted with COVID-19-induced or influenza A-induced pneumonia from electronic medical records in Ningbo First Hospital, China. We recorded patients' epidemiological and clinical features, as well as radiologic and laboratory findings. RESULTS: The median age of influenza A cohort was higher and it exhibited higher temperature and higher proportion of pleural effusion. COVID-19 cohort exhibited higher proportions of fatigue, diarrhea and ground-glass opacity and higher levels of lymphocyte percentage, absolute lymphocyte count, red-cell count, hemoglobin and albumin and presented lower levels of monocytes, c-reactive protein, aspartate aminotransferase, alkaline phosphatase, serum creatinine. Multivariate logistic regression analyses showed that fatigue, ground-glass opacity, and higher level of albumin were independent risk factors for COVID-19 pneumonia, while older age, higher temperature, and higher level of monocyte count were independent risk factors for influenza A pneumonia. CONCLUSIONS: In terms of COVID-19 pneumonia and influenza A pneumonia, fatigue, ground-glass opacity, and higher level of albumin tend to be helpful for diagnosis of COVID-19 pneumonia, while older age, higher temperature, and higher level of monocyte count tend to be helpful for the diagnosis of influenza A pneumonia.

First case of bloodstream infection of Trichosporon loubieri in a patient with B-cell lymphocytic leukemia in China.

Trichosporon loubieri is an opportunistic pathogenic fungus that could causes invasive infections for human, which rarely been reported. In the present study, we reported a case of bloodstream infection from a patient with Ph-positive B-cell acute lymphocytic leukemia (B-ALL) due to Trichosporon loubieri. Trichosporon loubieri was identified by Internal Transcribed Spacer (ITS) gene sequencing. The patient was treated by intravenous voriconazole (VCZ) and amphotericin B (AmB) according to antifungal susceptibility testing and he was still alive so far. To the best of our knowledge, this is the fourth report of human bloodstream infection due to Trichosporon loubieri and the first survival case of its kind in an immunocompromised patient.

QTc prolongation during antiviral therapy in two COVID-19 patients.

WHAT IS KNOWN AND OBJECTIVE: Acquired long QT syndrome secondary to drug-induced QT prolongation and torsades de pointes has been reported for antiviral drugs. However, no studies have reported an association between corrected QT (QTc) prolongation and antiviral therapy in patients with novel coronavirus disease (COVID-19). CASE DESCRIPTION: We present two cases from our institution in which patients with COVID-19 experienced QTc prolongation during treatment with antiviral therapy. Lopinavir/ritonavir, together with gender and drug-drug interactions, may have contributed to the induction of QTc prolongation in those patients. WHAT IS NEW AND CONCLUSION: Co-administration of QT-prolonging medications and drugs interfering with the metabolism of those medications must be considered in patients with COVID-19. Careful analysis of electrocardiograms for QTc duration should be performed at baseline and during antiviral therapy to identify individuals at high risk of arrhythmias.

Long noncoding RNA MALAT1 promotes high glucose-induced inflammation and apoptosis of vascular endothelial cells by regulating miR-361-3p/SOCS3 axis.

Vascular complications are the important pathophysiologic manifestations of patients with diabetes mellitus (DM) and many long non-coding RNAs (LncRNAs) are involved in this process. In this study, we aimed to investigate the relationships among LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), microRNA-361-3p (miR-361-3p), and suppressor of cytokine signaling 3 (SOCS3) in high glucose (HG)-induced human umbilical vein endothelial cell (HUVEC) injury and its underlying mechanism. We found that HG treatment significantly promotes MALAT1 and SOCS3 expressions, but inhibits miR-361-3p expression in HUVECs. Furthermore, through bioinformatics analysis and dual luciferase assay, we found that MALAT1 directly sponges miR-361-3p to counteract its suppression on SOCS3 expression. Moreover, knockdown of MALAT1 evidently inhibits HG-induced inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 expressions in HUVECs (and HUVEC apoptosis) by regulating the miR-361-3p/SOCS3 axis. In conclusion, our results indicate that knockdown of MALAT1 inhibits HG-induced vascular endothelial injury through regulating miR-361-3p/SOCS3 axis, suggesting that inhibition of MALAT1 as a potential target for endothelial injury therapy for DM.

Combining interferon-γ release assays with lymphocyte enumeration for diagnosis of Mycobacterium tuberculosis infection.

OBJECTIVE: To investigate the possibility of combining tuberculosis (TB)-interferon (IFN)-γ release assays (IGRAs) with lymphocyte enumeration for diagnosis of Mycobacterium tuberculosis infection. METHODS: We performed a retrospective study of 166 TB patients [68 patients with pulmonary tuberculosis TB (PTB) and 98 patients with extra-pulmonary TB (EPTB)] diagnosed in our hospital between January 2016 and May 2018 along with 377 non-TB patients. The diagnostic performance of the TB-IGRA was evaluated using receiver operating characteristic (ROC) curves. Youden's index was used to determine the optimal cut-off threshold. RESULTS: IFN-γ release in patients with PTB and EPTB were dramatically higher compared with non-TB patients (203.58±18.00 pg/mL, 201.83±14.56 pg/mL and 32.12±4.36 pg/mL, respectively). IFN-γ release was positively correlated with lymphocyte counts and percentages in patients with PTB (r = 0.252 and r = 0.278, respectively) and EPTB (r = 0.229 and r = 0.298, respectively). No correlation was observed in non-TB patients. The area under the ROC curve for TB-IGRA was 0.884. When the optimal cut-off value for IFN-γ (14 pg/mL, Youden's index 0.661) was applied, the sensitivity was 88.6% and the specificity was 77.5%. CONCLUSIONS: Combining TB-IGRA with lymphocyte enumeration was effective for diagnosis of early-stage Mycobacterium tuberculosis infection.

Dynamic change process of target genes by RT-PCR testing of SARS-Cov-2 during the course of a Coronavirus Disease 2019 patient.

We report the dynamic change process of target genes by RT-PCR testing of SARS-Cov-2 during the course of a COVID-19 patient: from successive negative results to successive single positive nucleocapsid gene, to two positive target genes (orf1ab and nucleocapsid) by RT-PCR testing of SARS-Cov-2, and describe the diagnosis, clinical course, and management of the case. In this case, negative results of RT-PCR testing was not excluded to diagnose a suspected COVID-19 patient, clinical signs and symptoms, other laboratory findings, and chest CT images should be taken into account for the absence of enough positive evidence. This case highlights the importance of successive sampling and testing SARS-Cov-2 by RT-PCR as well as the increased value of single positive target gene from pending to positive in two specimens to diagnose laboratory-confirmed COVID-19.

Curcumin attenuates lipopolysaccharide/d-galactosamine-induced acute liver injury by activating Nrf2 nuclear translocation and inhibiting NF-kB activation.

Curcumin, a polyphenol in curry spice isolated from the rhizome of turmeric, has been reported to possess versatile biological properties including anti-inflammatory, anti-oxidant, antifibrotic, and anticancer activities. In this study, the hepatoprotective effect of curcumin was investigated in lipopolysaccharide (LPS)/d-galactosamine (d-GalN)-induced acute liver injury (ALI) in rats. Experimental ALI was induced with an intraperitoneal (ip) injection of sterile 0.9% sodium chloride (NaCl) solution containing 8µg LPS and 800mg/kg d-GalN. Curcumin was administered once daily starting three days prior to LPS/d-GalN treatment. Results indicated that curcumin could attenuate hepatic pathological damage, decrease serum ALT and AST levels, and reduce malondialdehyde (MDA) content in experimental ALI rats. Moreover, higher dosages of curcumin pretreatment inhibited NF-κB activation and reduced serum TNF-α and liver TNF-α levels induced by LPS/d-GalN ip injection. Furthermore, we found that curcumin up-regulated the expression of nuclear Nrf2 and Nrf2-dependent antioxidant defense genes including heme oxygenase-1 (HO-1), glutamate-cysteine ligase (GCLC), NAD(P)H dehydrogenase, and quinone (NQO-1) in a dose-dependent manner. Our results showed that curcumin protected experimental animals against LPS/d-GalN-induced ALI through activation of Nrf2 nuclear translocation and inhibition of NF-κB activation.

Paeoniflorin inhibits pulmonary artery smooth muscle cells proliferation via upregulating A2B adenosine receptor in rat.

Paeoniflorin (PF), which is the main active ingredient in the root of Paeonia Radix, has many pharmacological effects. Here, we investigated the effect of PF on rat pulmonary artery smooth muscle cells (PASMCs) under hypoxic conditions and explored the mechanisms of the effects. The anti-proliferative effect of PF increased in a dose dependent manner. At the highest dose (20 µmol/L), the anti-proliferative effect of PF peaked at 24 h after administration. However, the selective A2B adenosine receptor (A2BAR) antagonist MRS1754 abolished it. PF increased A2BAR mRNA levels from 0.0763±0.0067 of ß-actin mRNA levels (hypoxia group) to 0.1190±0.0139 (P<0.05) measured by Real Time Reverse Transcription-Polymerase Chain Reaction. A2BAR protein expression measured by Western Blot was also increased. PF inhibited the proliferation of PASMCs by blocking cell cycle progression in the S phase. These data indicated that activation of A2BAR might be involved in the anti-proliferative effect of PF on PASMCs under hypoxic conditions. The results suggested that a new mechanism of PF could be relevant to the management of clinical hypoxic pulmonary hypertension.