Current Progress of Ferroptosis Study in Hepatocellular Carcinoma.

Ferroptosis, an emerging type of programmed cell death, is initiated by iron-dependent and excessive ROS-mediated lipid peroxidation, which eventually leads to plasma membrane rupture and cell death. Many canonical signalling pathways and biological processes are involved in ferroptosis. Furthermore, cancer cells are more susceptible to ferroptosis due to the high load of ROS and unique metabolic characteristics, including iron requirements. Recent investigations have revealed that ferroptosis plays a crucial role in the progression of tumours, especially HCC. Specifically, the induction of ferroptosis can not only inhibit the growth of hepatoma cells, thereby reversing tumorigenesis, but also improves the efficacy of immunotherapy and enhances the antitumour immune response. Therefore, triggering ferroptosis has become a new therapeutic strategy for cancer therapy. In this review, we summarize the characteristics of ferroptosis based on its underlying mechanism and role in HCC and provide possible therapeutic applications.

Lipopolysaccharide promotes cancer cell migration and invasion through METTL3/PI3K/AKT signaling in human cholangiocarcinoma.

Purpose: As a major structural component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS) has been detected in the blood circulation and tissues in patients with chronic diseases and cancers, which plays a critical role in the tumor formation and progression. However, the biological role of LPS in human intrahepatic cholangiocarcinoma remains unclear. The aims of this study were to investigate the role of LPS in the malignant progression of intrahepatic cholangiocarcinoma. Methods: The cell migration and invasion capacities of cholangiocarcinoma cell lines were evaluated by Boyden chamber assays. Expression levels of the key molecules involved in the PI3K/AKT signaling and METTL3 were detected by qPCR and western blot. The molecular mechanism by which LPS promotes the malignant behaviors was investigated by using siRNAs, plasmids and small molecule inhibitors. Results: In vitro experiments showed that exogenous LPS treatment promoted cell migration and invasion capacities in both QBC939 and HUCCT1 cell lines, while did not affect cell proliferation and apoptosis. Mechanistically, exogenous LPS treatment had been proved to induce the increased expression of METTL3 and activate the downstream PI3K/AKTsignaling pathway. In addition, suppression of METTL3 expression reduced cell proliferation, migration and invasion capacities in both cell lines. Furthermore, inhibition of METTL3 expression or inhibition of PI3K/AKT signaling decreased LPS-induced cell migration and invasion capacities. Moreover, knockdown of METTL3 or inhibition of METTL3 significantly inhibited LPS-induced activation of the PI3K/AKT signaling. Conclusion: In general, these results suggest that the LPS-METTL3-PI3K/AKT signal axis promotes cell migration and invasion in ICC, which contributes to a reduced overall survival in patients with ICC. It may broaden the horizon of cancer therapy with potential therapeutic targets.

Infection pattern and immunological characteristics of Epstein-Barr virus latent infection in cervical squamous cell carcinoma.

Previous studies reported the association between Epstein-Barr virus (EBV) and cervical squamous cell carcinoma (CSCC), but its infection pattern and clinical significance unclear. This study aimed to comprehensively investigate the infection pattern, clinicopathology, outcomes, and immunology of this entity in central China. We evaluated a total of 104 untreated CSCC tumor tissue specimens using in situ hybridization for EBV-encoded small RNAs (EBERs), and by employing flowcytometry fluorescence hybridization for human papillomavirus (HPV) genotyping. The expression of EBV latency proteins and immune biomarkers was evaluated and quantified by immunohistochemistry. EBERs transcripts were detected in 21 (20.2%) cases overall (in malignant epithelial cells of 13 cases and in lymphocytes of 8 cases). EBV belonged to latency type I infection in CSCC. The high-risk (HR)-HPV was detected in all of EBV-positive CSCC, and the difference of detection rate of HR-HPV was significant when compared with EBV-negative CSCC (p = 0.001). The specific clinicopathology with increased frequency of advanced clinical stages, tumor-positive lymph nodes, neural invasion, and increased infiltration depth (all p value < 0.05) were observed in cases with EBV. However, EBV infection was found to have no impact on prognosis of patients with CSCC. Increased densities of forkhead box P3 (FoxP3)+-tumor infiltrating lymphocytes (TILs) (p = 0.005) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)+-TILs (p = 0.017) and higher expression of programmed cell death-1 (PD-1) (p = 0.002) and programmed cell death-1 ligand 1 (PD-L1) (p = 0.040) were associated with EBV latent infection in CSCC, and these immunological changes were more likely to be associated with the infection in lymphocytes rather than tumor cells. Moreover, in patients with HPV-positive CSCC, similar significant differences were still found. In conclusions, EBV-positive CSCC may have specific infection pattern and clinicopathology and can exhibit an immunosuppressive microenvironment dominated by Treg cells aggregation and immune checkpoint activation.

Pulmonary infection in patients with severe fever with thrombocytopenia syndrome: A multicentre observational study.

Co-infection in patients with severe fever with thrombocytopenia syndrome (SFTS) has been reported, posing a serious threat to survival and treatment. We aimed to systematically investigate the SFTS associated pulmonary infection, particularly invasive pulmonary fungal infection (IPFI). During April 2019 to October 2021, we conducted a multicentre observational study on adult hospitalized patients confirmed with SFTS from three tertiary hospital in central China. Demographic, clinical and laboratory data of patients were collected and re-assessed. A total of 443 patients (51.7% were male sex) were included for analysis with median age of 65-year-old. Among them, 190 (42.9%) patients met the criteria for pulmonary infection. Pulmonary infection was associated with shorter survival time (p < 0.0001 by log-rank test), and adjusted hazard ratio was 1.729 [95% confidence interval, 1.076-2.780] (p = 0.024). Age (odds ratio (OR) 1.040 [1.019-1.062], p < 0.001), time from onset to admission (OR 1.163 [1.070-1.264], p < 0.001), having severe status (OR 3.166 [2.020-4.962], p < 0.001) and symptoms of skin change (OR 2.361 [1.049-5.316], p < 0.001) at admission and receiving intravenous immunoglobin (OR 2.185 [1.337-3.569], p = 0.002) were independent risk factors for the occurrence of pulmonary infection. A total of 70 (15.8%) patients were defined as IPFI. Multivariate analysis showed that time from onset to admission (OR 1.117 [1.016-1.229], p = 0.022), severe status (OR 5.737 [3.054-10.779], p < 0.001), having smoking history (OR 3.178 [1.251-8.070], p = 0.015) and autoimmunity disease (OR 7.855 [1.632-37.796], p = 0.010), receiving intravenous immunoglobin (OR 3.270 [1.424-7.508], p = 0.005) were independent risk factors for the occurrence of IPFI. In SFTS patients with pulmonary infection, white blood count <2.09 × 109 per L (OR 11.064 [3.708-33.012], p < 0.001) and CD3+ CD4+ T cell count <104.0 per µL (OR 10.429 [3.395-32.038], p < 0.001) could independently predict IPFI. This study showed the high prevalence and poor outcomes of pulmonary infection and IPFI in patients with SFTS. These findings highlighted the need for active surveillance of fungal pathogens and early antifungal treatment in patients with SFTS.

Development and validation of a clinical risk score to predict the occurrence of critical illness in hospitalized patients with SFTS.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality. Early identification of patients who may advance to critical stages is crucial. This investigation aimed to establish models to predict SFTS before it reaches the critical illness stage. METHODS: Between January 2016 and September 2022, 278 cases have been included in this study. There were 87 demographic and systemic chosen variables. For selecting the predictive variables from the cohort, the LASSO was utilized, and for identifying independent predictors, multivariate logistic regression was performed. Based on these factors, a nomogram was established for critical illness. Concordance index values, decision curve analysis and the area under the curve (AUC) were also examined. RESULTS: Multivariate logistic regression demonstrated the most important differentiating factors as;> 65 years old (P < 0.001, OR 3.388, 95 % CI 1.767-6.696), elevated serum PT (P = 0.011, OR 6.641, 95 % CI 1.584-31.934), elevated serum TT (P = 0.005, OR 3.384, 95 % CI 1.503-8.491), and elevated serum bicarbonate (P = 0.014, OR 0.242, 95 % CI 0.070-0.707). The C-index of the nomogram was 0.812 (95 % CI: 0.754-0.869), representing good discrimination. The model also showed excellent calibration. The AUC of the nomogram established based on four factors, as mentioned earlier, was 0.806. Furthermore, the model had the excellent net benefit, as revealed by the decision curve analysis. CONCLUSION: An accurate risk score system built on manifestations noted in patients with SFTS upon admission to hospital, might be advantageous in managing SFTS.

First Study of Bacteremia Caused by Herbaspirillum huttiense in China: A Brief Research Report and Literature Review.

Bacteremia caused by Herbaspirillum huttiense (H. huttiense) is relatively rare in positive blood cultures. H. huttiense is an opportunistic bacterium in patients with cancer and cirrhosis and has also been described in immunocompromised hosts. In this study, H. huttiense was isolated from a patient with repeated chest tightness and chest pain. Smears were prepared, stained, and examined by microscopy. Single colonies were analyzed by Gram staining, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), 16S rRNA sequencing and Next-Generation Sequencing (NGS). Antibiotic sensitivity was assessed by agar dilution. Almost all publications on H. huttiense infections in the PubMed/ScienceDirect/EBSCO databases were reviewed and summarized. Blood sample culturing yielded white, gelatinous, and slightly raised colonies without hemolytic rings. The bacilli were found to be Gram-negative, and MS results showed 99.2% homology with H. huttiense. This was confirmed by 16S rRNA gene sequencing, phylogenetic tree analysis and NGS all of which were homologous with H. huttiense in GenBank. Antibiotic susceptibility tests were performed to determine the minimum inhibitory concentrations (MICs) of imipenem, meropenem, piperacillin-tazobactam, and levofloxacin. A comprehensive literature review revealed that H. huttiense was an emergent pathogen. After medical treatment, the patient's body temperature returned to normal. This is the first report of bacteremia caused by H. huttiense in China. The findings could improve the awareness and attention of the rare pathogenic microorganisms in China.

MicroRNA-146a promotes proliferation, migration, and invasion of HepG2 via regulating FLAP.

Abnormal expression of 5-Lipoxygenase Activating Protein (FLAP) has been detected in many tumor cells. MicroRNAs (miRNAs) negatively regulate gene expression post-transcriptionally by binding to the 3'-untranslated region (3'-UTR) of the target mRNA sequences and have been shown to be involved in various types of cancers. Herein, we aimed to demonstrate the expression of miR-146a and FLAP in human HCC tissues and liver cancer cell lines. We demonstrated that miR-146a expression is overexpressed, while FLAP protein and mRNA are suppressed in hepatocellular carcinoma tissues and HepG2 cells compared to para-carcinoma tissues and HL-7702 cells. Dual luciferase reporter gene assay showed that miR-146a-5p can directly target FLAP mRNA. Knockdown of miR-146a also resulted in increased FLAP expression of cancer cells. Additionally, miR-146a silencing or restoration of FLAP led to a reduction of HepG2 cell proliferation, cell cycle progression, migration, and invasion. This study showed that miR-146a has a stimulatory role in HepG2 cells and promotes HepG2 cell migration and invasion by targeting FLAP mRNA. Thus, miR-146a may be a tumor promoter and a potential therapeutic target for the treatment of HCC patients.

The AST/ALT Ratio (De Ritis Ratio) Represents an Unfavorable Prognosis in Patients in Early-Stage SFTS: An Observational Cohort Study.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS), a widely prevalent infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV) that carries with it a high mortality rate, has emerged to be a public health concern. This study aimed to investigate the epidemiological and clinical characteristics of patients infected with SFTSV, seeking novel prognostic risk factors for SFTS. METHODS: In this retrospective and cross-sectional study, confirmed SFTS patients from the First Affiliated Hospital of Anhui Medical University were enrolled from September 1, 2019, to December 12, 2020. Cases were analyzed for epidemiological, demographic, clinical, and laboratory data. Logistic regression models were used to assess the association between predictors and outcome variables. A generalized additive mixed model (GAMM) was conducted to analyze the trending shift of aspartate aminotransferase/alanine transaminase-ratio (AST/ALT-ratio) and platelet (PLT) in SFTS patients treated with ribavirin. p values ≤ 0.05 were considered statistically significant. RESULTS: Clinical and laboratory results of 107 hospitalized patients with SFTSV infection were retrospectively described. The mean age at onset of disease was 60.38 ± 11.29 years old and the ratio between male and female was 1:1.2. Fever and thrombocytopenia are hallmark features of SFTS. Furthermore, multiple cases also experienced neurological complications, gastrointestinal/skeletal muscle symptoms together with other non-specific clinical manifestations; laboratory dataset outcomes reported dysregulated levels for routine blood biomarkers, coagulation function, and biochemistry. Overall, 107 patients were segregated into two groups according to patient condition at the clinical endpoint (survivors/non-survivors). SFTS survivors had a higher level of PLT- counts, total protein (TP), and estimated glomerular filtration rate (eGFR), while levels of activated partial thromboplastin time (APTT), thrombin time (TT), D-dimer (D-D), fibrinogen degradation products (FDP), ALT, AST, AST/ALT-ratio, creatinine (Cr), creatine phosphokinase (CK) and procalcitonin (PCT) was higher in non-survivors. Results from univariate Cox regression revealed that elevated levels of FDP, TT, AST/ALT-ratio, PCT, as well as decreased eGFR level and presence of central nervous system symptoms (CNS), were significant predictors for SFTS prognostic, results from multivariate logistic regression analysis in three adjusted models showed AST/ALT-ratio and PCT were independent risk factors for the prognosis of SFTS patients. Kaplan-Meier survival analysis showed that SFTS patients with AST/ALT-ratio >2.683 were associated with a shorter futime (means survival time), therefore indicating an unfavorable prognosis. Treatment with ribavirin could increase PLT count while decreasing AST/ALT-ratio within SFTS patients. CONCLUSION: SFTS is an emerging infectious disease, possibly leading to multiple-organ injury; AST/ALT-ratio was an independent risk factor for the prognosis of SFTS patients. Further investigation should be performed in order to gain more knowledge on this disease and guide clinical management.

Dynamic regulation and functions of mRNA m6A modification.

N6-Methyladenosine (m6A), the most abundant internal modification associated with eukaryotic mRNAs, has emerged as a dynamic regulatory mechanism controlling the expression of genes involved in many physiological activities by affecting various steps of mRNA metabolism, including splicing, export, translation, and stability. Here, we review the general role of m6A, highlighting recent advances related to the three major types enzymes that determine the level of m6A modification (i.e., writers, erasers, and readers) and the regulatory mechanism by which m6A influences multiple stages of RNA metabolism. This review clarifies the close connection and interaction between m6A modification and nuclear gene expression, and provides key background information for further studies of its roles in numerous physiological and pathophysiological processes. Among them, perhaps the most eye-catching process is tumorigenesis. Clarifying the molecular mechanism of tumorigenesis, development and metastasis in various tissues of the human body is conducive to curbing out-of-control cell activities from the root and providing a new strategy for human beings to defeat tumors.

The Application of the CRISPR/Cas9 System in the Treatment of Hepatitis B Liver Cancer.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system was originally discovered in prokaryotes and functions as part of the adaptive immune system. The experimental research of many scholars, as well as scientific and technological advancements, has allowed prokaryote-derived CRISPR/Cas genome-editing systems to transform our ability to manipulate, detect, image, and annotate specific DNA and RNA sequences in the living cells of diverse species. Through modern genetic engineering editing technology and high-throughput gene sequencing, we can edit and splice covalently closed circular DNA to silence it, and correct the mutation and deletion of liver cancer genes to achieve precise in situ repair of defective genes and prohibit viral infection or replication. Such manipulations do not destroy the structure of the entire genome and facilitate the cure of diseases. In this review, we discussed the possibility that CRISPR/Cas could be used as a treatment for patients with liver cancer caused by hepatitis B virus infection, and reviewed the challenges incurred by this effective gene-editing technology.

Quantification of m6A RNA methylation modulators pattern was a potential biomarker for prognosis and associated with tumor immune microenvironment of pancreatic adenocarcinoma.

BACKGROUND: m6A is the most prevalent and abundant form of mRNA modifications and is closely related to tumor proliferation, differentiation, and tumorigenesis. In this study, we try to conduct an effective prediction model to investigated the function of m6A RNA methylation modulators in pancreatic adenocarcinoma and estimated the potential association between m6A RNA methylation modulators and tumor microenvironment infiltration for optimization of treatment. METHODS: Expression of 28 m6A RNA methylation modulators and clinical data of patients with pancreatic adenocarcinoma and normal samples were obtained from TCGA and GTEx database. Differences in the expression of 28 m6A RNA methylation modulators between tumour (n = 40) and healthy (n = 167) samples were compared by Wilcoxon test. LASSO Cox regression was used to select m6A RNA methylation modulators to analyze the relationship between expression and clinical characteristics by univariate and multivariate regression. A risk score prognosis model was conducted based on the expression of select m6A RNA methylation modulators. Bioinformatics analysis was used to explore the association between the m6Ascore and the composition of infiltrating immune cells between high and low m6Ascore group by CIBERSORT algorithm. Evaluation of m6Ascore for immunotherapy was analyzed via the IPS and three immunotherapy cohort. Besides, the biological signaling pathways of the m6A RNA methylation modulators were examined by gene set enrichment analysis (GSEA). RESULTS: Expression of 28 m6A RNA methylation modulators were upregulated in patients with PAAD except for MTEEL3. An m6Ascore prognosis model was established, including KIAA1429, IGF2BP2, IGF2BP3, METTL3, EIF3H and LRPPRC was used to predict the prognosis of patients with PAAD, the high risk score was an independent prognostic indicator for pancreatic adenocarcinoma, and a high risk score presented a lower overall survival. In addition, m6Ascore was related with the immune cell infiltration of PAAD. Patients with a high m6Ascore had lower infiltration of Tregs and CD8+T cells but a higher resting CD4+ T infiltration. Patients with a low m6Ascore displayed a low abundance of PD-1, CTLA-4 and TIGIT, however, the IPS showed no difference between the two groups. The m6Ascore applied in three immunotherapy cohort (GSE78220, TCGA-SKCM, and IMvigor210) did not exhibit a good prediction for estimating the patients' response to immunotherapy, so it may need more researches to figure out whether the m6A modulator prognosis model would benefit the prediction of pancreatic patients' response to immunotherapy. CONCLUSION: Modulators involved in m6A RNA methylation were associated with the development of pancreatic cancer. An m6Ascore based on the expression of IGF2BP2, IGF2BP3, KIAA1429, METTL3, EIF3H and LRPPRC is proposed as an indicator of TME status and is instrumental in predicting the prognosis of pancreatic cancer patients.

Epidemiological, Clinical and Laboratory Characteristics of Patients with Brucella Infection in Anhui Province, China.

BACKGROUND: Brucellosis is currently one of the most widespread zoonotic diseases caused by Brucella genus, and the Brucella melitensis is the major pathogen. The number of people infected with Brucella has gradually increased in Anhui Province. PURPOSE: To retrospectively evaluate the epidemiological, clinical, and laboratory data of brucellosis patients in Anhui Province. PATIENTS AND METHODS: A total of 109 brucellosis patients were admitted to the First Affiliated Hospital of Anhui Medical University from January 2012 to March 2021. Data from all patients were retrieved from the hospital's electronic medical system. The final results were grouped and compared according to the presence or absence of bacteremic brucellosis and three phases of brucellosis. RESULTS: The most common symptoms among all 109 brucellosis patients were fever (89.0%), followed by chills (52.3%), arthralgia (48.6%), and weight loss (30.3%), and laboratory results presented with anemia (65.1%), elevate of C-reactive protein (CRP) (91.7%), erythrocyte sedimentation rate (ESR) (86.2%), aspartate aminotransferase (AST) (40.4%), and lactate dehydrogenase (LDH) (43.1%). The percentage of fever (96.1%), arthralgia (58.8%), anorexia (35.3%), leukopenia (31.4%), and the AST (51.0%) were higher in bacteremic than nonbacteremic group. Additionally, the median level of LDH (332.0 mg/L, IQR, 209.0-553.0) was higher in bacteremic than nonbacteremic group. Nevertheless, the albumin (36.0 mg/L, IQR, 33.9-38.2) was lower in the bacteremic group. The percentage of fever (94.9%) and the median LDH level (316.0 U/L (IQR,218.0-517.5)) in the acute phase of brucellosis were higher than the percentage of fever (72.0%) and the median LDH level (209.0 U/L (IQR,162.0-276.0)) in the subacute phase of brucellosis. CONCLUSION: Brucellosis has become an important public health issue in Anhui Province. Brucellosis is a disease with diverse clinical manifestations. Our data showed that unexplained fever, arthralgia, and elevated AST and LDH should be considered as a diagnosis of bacteremia brucellosis for early treatment intervention.

Development of a SARS-CoV-2 rapid antibody detection kit and study on dynamic changes in antibodies in infected patients.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly to 185 regions and countries around the world with more than 2.8 million confirmed infections and 203,044 deaths. Respiratory diseases caused by SARS-CoV-2 are serious threats to human health. OBJECTIVES: To develop a rapid detection kit for new coronavirus antibodies and use it to study the dynamic changes in antibodies in clinically confirmed SARS-CoV-2-infected patients. METHODS: The SARS-CoV-2 IgM/IgG antibody test kit (colloidal gold method) was developed. Serum SARS-CoV-2 IgM and IgG antibodies were tested in SARS-CoV-2- and non-SARS-CoV-2-infected persons, respectively. RESULTS AND CONCLUSION: The sensitivities of the SARS-CoV-2 IgM/IgG antibody test kit (colloidal gold method) were 50%, 70%, 92.5% and 97.5% after 1-3 days, 4-6 days, 7-9 days and >9 days of admission, respectively, and the specificities of the IgM, IgG and IgM + IgG antibodies were all 100%. Using the SARS-CoV-2 IgM/IgG antibody test kit (colloidal gold method), the positive rates of SARS-CoV-2 IgM and IgG antibodies increased from 50% to 92.5% after 1-3 days, 4-6 days and 7-9 days of admission, which showed an increasing trend. The titers of the SARS-CoV-2 IgM and IgG antibodies in the positive specimens increased with the length of admission.

Efficacy of Artificial Intelligence-Assisted Psychotherapy in Patients With Anxiety Disorders: A Prospective, National Multicenter Randomized Controlled Trial Protocol.

BACKGROUND: Anxiety disorders have the highest prevalence of all psychiatric disorders in China. Medication and psychotherapy are two main treatment approaches for this group of disorders, and when used in combinations are significantly more beneficial than medication alone. The resources are insufficient. The availability of psychotherapy is low due to the limited resources. Artificial intelligence (AI)-assisted psychotherapy offers an opportunity to develop an efficient and standardized psychotherapy model and improve the availability of psychotherapy, which is key to improve the clinical efficacy of anxiety disorder treatments. OBJECTIVES: The present protocol aims to determine whether medication plus AI-assisted psychotherapy has greater efficacy than medication alone in the treatment of anxiety disorders. METHODS: We will recruit patients in eight hospitals in China. Seven hundred and eight patients with anxiety disorders will be randomly allocated on a 1:1 basis to either medication plus AI-assisted psychotherapy group, or medication alone group. We have built an AI psychotherapy robot named XIAO AN. In this study we will deliver psychotherapy to patients in the medication plus AI-assisted psychotherapy group. Patients will be assessed at baseline and at the end of week 2, 4, 8, and 12. Follow-up assessments will be conducted at 3 and 6 months posttreatment. The primary outcome is change of Hamilton Anxiety Rating Scale (HAMA) score from baseline the end of 12-week treatment. A secondary efficacy outcome will be improvement in treatment at an early stage (score reduction in HAMA ≥25% after 2 weeks of treatment). Other measurements include Hamilton Depression Scale, Clinical Global Impression, Treatment Emergent Symptom Scale, Social Disability Screening Schedule, Insomnia Severity Index and so on. Scales will be assessed by independent raters who are blind to treatment allocation and analyses will be conducted by a statistician who is also blind to treatment allocation. DISCUSSION: This will be the first multicentered randomized controlled single-blind trial in China to assess the efficacy of medication plus AI-assisted psychotherapy compared with medication alone for anxiety disorders. The study has the potential to address the limitations of the limited availability of psychotherapy, and to augment the efficacy of the treatment of anxiety disorders in China.

Characteristics of laboratory indexes in COVID-19 patients with non-severe symptoms in Hefei City, China: diagnostic value in organ injuries.

This study compared the laboratory indexes in 40 non-severe COVID-19 patients with those in 57 healthy controls. In the peripheral blood system of non-severe symptom COVID-19 patients, lymphocytes, eosinophils, basophils, total procollagen type 1 amino-terminal propeptide, osteocalcin N-terminal, thyroid-stimulating hormone, growth hormone, and insulin-like growth factor-binding protein 3 significantly decreased, and total protein, albumin, alanine transaminase, alkaline phosphatase, γ-glutamyl transferase, activated partial thromboplastin time, prothrombin time, fibrinogen, D-dimer, fibrinogen degradation products, human epididymal protein 4, serum ferritin, and C-reactive protein were elevated. SARS-CoV-2 infection can affect hematopoiesis, hemostasis, coagulation, fibrinolysis, bone metabolism, thyroid, parathyroid glands, the liver, and the reproductive system.

The genetic sequence, origin, and diagnosis of SARS-CoV-2.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new infectious disease that first emerged in Hubei province, China, in December 2019, which was found to be associated with a large seafood and animal market in Wuhan. Airway epithelial cells from infected patients were used to isolate a novel coronavirus, named the SARS-CoV-2, on January 12, 2020, which is the seventh member of the coronavirus family to infect humans. Phylogenetic analysis of full-length genome sequences obtained from infected patients showed that SARS-CoV-2 is similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and uses the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), as SARS-CoV. The possible person-to-person disease rapidly spread to many provinces in China as well as other countries. Without a therapeutic vaccine or specific antiviral drugs, early detection and isolation become essential against novel Coronavirus. In this review, we introduced current diagnostic methods and criteria for the SARS-CoV-2 in China and discuss the advantages and limitations of the current diagnostic methods, including chest imaging and laboratory detection.

Circulating tumor DNA/circulating tumor cells and the applicability in different causes induced hepatocellular carcinoma.

In 2015, liquid biopsy was rated one of the top 10 breakthrough technologies of the year by MIT Technology Review. Liquid biopsy is a type of in vitro diagnostic method involving a noninvasive blood test. It is also a breakthrough technology used to detect tumors and cancers and assist in therapeutic strategies. The most widely used markers are circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Primary carcinoma of the liver is a malignancy of hepatocytes or intrahepatic biliary epithelial cells. The most common type of liver cancer is hepatocellular carcinoma (HCC), the causes of which mainly include infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), alcohol abuse, aflatoxicosis, and nonalcoholic fatty liver disease/ nonalcoholic steatohepatitis. As there are few typical clinical characteristics during the early stage of the disease, early diagnosis of HCC is very challenging. However, CTCs and ctDNA carry tumor-specific information. Therefore, the detection and analysis of CTCs and ctDNA can provide evidence for the early diagnosis of HCC and guide treatment. Furthermore, several studies have indicated that different inducers of HCC cause different DNA mutations, and accordingly, detection of specific mutations in ctDNA will facilitate the determination of the HCC type and help physicians provide distinctive therapies.

Multiple roles of microRNA-146a in immune responses and hepatocellular carcinoma.

MicroRNAs (miRNAs/miRs), consisting of ~22 nucleotides of single-stranded RNA, participate in post-transcriptional gene regulation by binding to the 3'-untranslated region (UTR) of mRNAs, repressing their translation and promoting their degradation. Studies have shown that certain miRNAs play a key role in the control of various cellular activities, such as inhibiting inflammation, modulating cell differentiation and suppressing cancer growth. The role of miR-146a in the immune response and in the pathogenesis of hepatocellular carcinoma (HCC) has also been investigated. Although some studies have shown that increased miR-146a levels are associated with HCC, others have revealed that miR-146a suppresses cancer cell proliferation, invasion and metastasis. Toll-like receptor 4 (TLR4) signaling has an important role in regulating innate and adaptive immune responses. In addition, TLR4 is functionally expressed in HCC cells and promotes HCC cell proliferation, which can be regulated by miR-146a. The present review focuses on the recent progress in analyzing the multiple roles of miR-146a in mediating the TLR4 pathway and adaptive immune response. Finally, the function of miR-146a in the pathogenesis of HCC is also discussed.

Association between glycosylated hemoglobin A1c and bone biochemical markers in type 2 diabetic postmenopausal women: a cross-sectional study.

BACKGROUND: type 2 diabetes mellitus (T2DM) is a complicated disease that can affect bone health, but the change in bone biochemical markers caused by T2DM was controversial, so the aim of this study was to investigate whether there was a discrepancy in the levels of bone biochemical markers between postmenopausal women with T2DM and non-diabetic women and to explore the relationship between the level of glycosylated hemoglobin A1c (HbA1c) and bone biochemical markers in these subjects. METHODS: A total of 237 type 2 diabetic postmenopausal women visiting the First Affiliated Hospital of Anhui Medical University from January 2017 to October 2018 and 93 healthy postmenopausal women were retrospectively enrolled. The differences in the levels of bone biochemical markers between patients and controls were analyzed by one-way ANOVA or chi-square test. The relationship between HbA1c and bone biochemical markers was analyzed by multivariate regression, forest plot and fitted curve. RESULTS: Bone formation markers including N-MID osteocalcin and procollagen type 1 amino-terminal pro-peptide (PINP) were decreased in postmenopausal women with T2DM compared to controls (17.42 ± 9.50 vs 23.67 ± 7.58, p < 0.001; 48.47 ± 27.27 vs 65.86 ± 21.06, p < 0.001, respectively), but the bone resorption markers ß-crossLaps (ß-CTX) was no difference between the two groups (0.57 ± 0.28 vs 0.55 ± 0.21, p = 0.868). Multivariate regression showed that HbA1c was inversely associated with N-MID osteocalcin and PINP after adjusting for age, BMI, menopause's years, diabetic duration, TC, TG, HDL-c, LDL-c, creatinine, UA and eGFR. The adjusted coefficients for N-MID osteocalcin and PINP per 1% HbA1c decrease were - 0.71 (- 1.19, - 0.22) and - 1.79 (- 3.30, - 0.28), respectively. A segmentation effect was seen in the fitted curve between HbA1c and ß-CTX with an inflection point at 7.4% of HbA1c, the highest quartile of ß-CTX (> = 0.74 ng/ml) showed a significantly negative with HbA1c. No significant association was seen between HbA1c and other biochemical markers. CONCLUSIONS: Our study found that bone formation was inhibited in postmenopausal women with T2DM, but bone resorption was not affected, and poor glycemic control was related to lower levels of bone formation, may increase the risk of bone fracture in postmenopausal women with T2DM.