The coronavirus disease 2019 (COVID-19) pandemic continues worldwide. We report here two cases of chronic hepatitis B patients with acute respiratory syndrome coronavirus 2 infection treated with tenofovir disoproxil fumarate who demonstrated a favorable outcome. This report adds some evidence that concurrent HBV infection may not worsen COVID-19 infection and tenofovir disoproxil fumarate treatment may have partial positive effect on COVID-19 rapid recovery.

This study was performed to determine whether atrial fibrillation (AF) is related to the precise location of a coronary artery lesion.

A single-center retrospective study was conducted to compare data from clinical, laboratory, and instrumental examinations of 89 patients with AF (main group) who were admitted to the department between October 2015 and October 2019. One-hundred-and-sixty patients (comparison group) were selected according to balanced matching.

There were no statistically significant differences in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), troponin, or creatine kinase-myocardial band (CK-MB) between the two groups. However, the levels of homocysteine (17.0 ± 1.7 µmol/L vs. 13.7 ± 1.0 µmol/L, p = 0.001), uric acid (342.8 ± 16.7 µmol/L vs. 308.5 ± 15.1 µmol/L, p = 0.003) and creatinine (79.3 ± 4.7 µmol/L vs. 72.9 ± 3.1 µmol/L, p = 0.017) were higher in the AF group compared to the non-AF group. Moreover, the left atrium (LA) diameter (40.2 ± 1.4 mm vs. 33.5 ± 0.8 mm, p = 0.001) was larger in the AF group compared to the non-AF group. Patients with AF compared to those without AF had no significant differences in the degree or location of coronary artery lesions.

AF in patients was not associated with specific coronary artery lesions in the current study.

The recognition of transarterial chemoembolization (TACE) failure/refractoriness among Chinese clinicians remains unclear. Using an online survey conducted by the Chinese College of Interventionalists (CCI), the aim of this study was to explore the recognition of TACE failure/refractoriness and review TACE application for hepatocellular carcinoma (HCC) treatment in clinical practice.

From 27 August 2020 to 30 August 2020 during the CCI 2020 annual meeting, a survey with 34 questions was sent by email to 264 CCI clinicians in China with more than 10 years of experience using TACE for HCC treatment.

A total of 257 clinicians participated and responded to the survey. Most participants agreed that the concept of “TACE failure/refractoriness” has scientific and clinical significance (n=191, 74.3%). Nearly half of these participants chose TACE-based combination treatment as subsequent therapy after so-called TACE failure/refractoriness (n=88, 46.1%). None of the existing TACE failure/refractoriness definitions were widely accepted by the participants; thus, it is necessary to re-define this concept for the treatment of HCC in China (n=235, 91.4%). Most participants agreed that continuing TACE should be performed for patients with preserved liver function, presenting portal vein tumor thrombosis (n=242, 94.2%) or extrahepatic spread (n=253, 98.4%), after the previous TACE treatment to control intrahepatic lesion(s).

There is an obvious difference in the recognition of TACE failure/refractoriness among Chinese clinicians based on existing definitions. Further work should be carried out to re-define TACE failure/refractoriness.

In recent years, with a gradual increase of health awareness, society has become more concerned about the frequent occurrence of air pollution. As is known to all, fine particulate matter (particles less than 2.5 micrometers in diameter [PM2.5]) is the main cause of haze, which is suspended in the air and generated through a series of physical and chemical changes. Of note, different components and sources of PM2.5 cause different kinds of damage. Identification of the components and analysis of the sources have guiding significance for the prevention of PM2.5 damage. Indoor PM2.5 that is mainly from smoking and biomass combustion also has an adverse influence on human health. The prediction of indoor PM2.5 sedimentation and suspension is of great significance for maintaining good indoor air quality. Thus, the present review was conducted to provide a brief overview of new insights into the composition analysis, source analysis, indoor diffusion and deposition model, and the pathogenic mechanism of PM2.5, which have been explored with new technologies in recent years. This review will help to provide reference for PM2.5 related policy formulation.

The role of runt-related transcription factor 2 (RUNX2) in tumorigenesis and tumor progression in many cancers has been identified except for lung cancer. This study aimed to explore the expression level, functions and prognostic values of RUNX2 in lung cancer.

ONCOMINE was utilized to compare RUNX2 expression difference between cancers and normal tissue. GEPIA was used to further detect the expression pattern of RUNX2 between lung cancer and corresponding normal lung tissue. Then, the prognosis value of RUNX2 in lung cancer was evaluated through Kaplan-Meier Plots. The genomic alterations of RUNX2 neighbor genes were analyzed by cBioPortal, and GO enrichment was conducted to identify functional categories of RUNX2 and genes associated with RUNX2 alterations.

ONCOMINE and GEPIA revealed the upregulated expression level of RUNX2 in lung cancer compared to normal lung tissue. Higher RUNX2 level was associated with lower progression-free survival and overall survival in lung cancer patients. GO enrichment implicated that cell proliferation, invasion and metastasis-related genes as well as the functions of cell adhesion, cell migration, and cell proliferation were significantly associated with RUNX2 alterations.

Our findings indicated the value of RUNX2 as a novel prognostic biomarker and a potential therapeutic target for lung cancer.

Fibromyalgia is a complex disorder characterised by chronic pain, fatigue, sleep disturbance and cognitive dysfunction with limited benefit gained with current therapies. The mean global prevalence of 2.7% is estimated for this chronic condition. Pharmacological and non-pharmacological therapeutic approaches are often required as treatments of the challenges associated with fibromyalgia. Flupirtine, a non-opioid drug, exhibits effective analgesia in a range of acute and persistent pain conditions, and evidence as treatment of fibromyalgia is considered. Activation of Kv7 potassium channels and agonism at gamma-aminobutyric acid receptor A leading to indirect N-methyl-D-aspartate receptor antagonism is responsible for the analgesic effects of flupirtine and appears to be involved in other symptoms associated with fibromyalgia. Patients with fibromyalgia reported improved control of their symptoms without significant adverse effects in an observational audit in clinical practice. This article presents evidence that flupirtine, or related drugs, is a therapeutic option for the treatment of fibromyalgia. The pharmacology of flupirtine and mechanisms of action involved provide a spectrum of effects that would not only control the chronic pain characteristic of fibromyalgia but many of the other symptoms. Thus, further investigation of the efficacy of flupirtine or related drugs exhibiting a similar pharmacology as a treatment of fibromyalgia would be of interest.

The pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the most formidable challenge to humanity in this century. The research and development of COVID-19 vaccines, which are believed to be the most effective tools to control this pandemic, has been a topic of critical importance, not only in the field of biomedicine but also in the entire international community. Here, we introduce the concepts related to COVID-19 vaccines, including their development process, clinical trials, designs and types. On this basis, we further summarize the research, development, and application of vaccines in different regions of the world, and describe the vaccines according to their respective regions. Finally, we discuss existing and emerging challenges, strategies and prospects of in the development and application of COVID-19 vaccines.

Programmed cell death-1 (PD-1) plays an important role in downregulating T lymphocytes but the mechanisms are still poorly understood. This study aimed to explore the role of PD-1 in CD8+ T lymphocyte dysfunction in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).

Thirty patients with HBV-ACLF and 30 healthy controls (HCs) were recruited. The differences in the numbers and functions of CD8+ T lymphocytes, PD-1 and glucose transporter-1 (Glut1) expression from the peripheral blood of patients with HBV-ACLF and HCs were analyzed. In vitro, the CD8+ T lymphocytes from HCs were cultured (HC group) and the CD8+ T lymphocytes from ACLF patients were cultured with PD-L1-IgG (ACLF+PD-1 group) or IgG (ACLF group). The numbers and functions of CD8+ T lymphocytes, PD-1 expression, glycogen uptake capacity, and Glut1, hexokinase-2 (HK2), and pyruvate kinase (PKM2) expression were analyzed among the HC group, ACLF group and ACLF+ PD-1group.

The absolute numbers of CD8+ T lymphocytes in the peripheral blood from patients with HBV-ACLF were lower than in the HCs (p<0.001). The expression of PD-1 in peripheral blood CD8+ T lymphocytes was lower in HCs than in patients with HBV-ACLF (p=0.021). Compared with HCs, PD-1 expression was increased (p=0.021) and Glut1 expression was decreased (p=0.016) in CD8+ T lymphocytes from the HBV-ACLF group. In vitro, glycogen uptake and functions of ACLF CD8+ T lymphocytes were significantly lower than that in HCs (p=0.017; all p<0.001). When PD-1/PD-L1 was activated, the glycogen uptake rate and expression levels of Glut1, HK2, and PKM2 showed a decreasing trend (ACLF+PD-1 group compared to ACLF group , all p<0.05). The functions of CD8+ T lymphocytes in the ACLF+PD-1 group [using biomarkers of Ki67, CD69, IL-2, interferon-gamma, and tumor necrosis factor-alpha- were lower than in the ACLF group (all p<0.05).

CD8+ T lymphocyte dysfunction is observed in patients with HBV-ACLF. PD-1-induced T lymphocyte dysfunction might involve glycolysis inhibition.

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy. This study was designed to investigate the value of computed tomography (CT) spectral imaging in differentiating HCC from hepatic hemangioma (HH) and focal nodular hyperplasia (FNH).

This was a retrospective study of 51 patients who underwent spectral multiple-phase CT at 40–140 keV during the arterial phase (AP) and portal venous phase (PP). Slopes of the spectral curves, iodine density, water density derived from iodine- and water-based material decomposition images, iodine uptake ratio (IUR), normalized iodine concentration, and the ratio of iodine concentration in liver lesions between AP and PP were measured or calculated.

As energy level decreased, the CT values of HCC (n=31), HH (n=17), and FNH (n=7) increased in both AP and PP. There were significant differences in IUR in the AP, IUR in the PP, normalized iodine concentration in the AP, slope in the AP, and slope in the PP among HCC, HH, and FNH. The CT values in AP, IUR in the AP and PP, normalized iodine concentration in the AP, slope in the AP and PP had high sensitivity and specificity in differentiating HH and HCC from FNH. Quantitative CT spectral data had higher sensitivity and specificity than conventional qualitative CT image analysis during the combined phases.

Mean CT values at low energy (40–90 keV) and quantitative analysis of CT spectral data (IUR in the AP) could be helpful in the differentiation of HCC, HH, and FNH.

Hepatic sinusoidal obstruction syndrome (HSOS) is caused by toxic injury to sinusoidal endothelial cells in the liver. The intake of pyrrolizidine alkaloids (PAs) in some Chinese herbal remedies/plants remains the major etiology for HSOS in China. Recently, new diagnostic criteria for PA-induced HSOS (i.e. PA-HSOS) have been developed; however, the efficacy has not been clinically validated. This study aimed to assess the performance of the Nanjing criteria for PA-HSOS.

Data obtained from consecutive patients in multiple hospitals, which included 86 PA-HSOS patients and 327 patients with other liver diseases, were retrospectively analyzed. Then, the diagnostic performance of the Nanjing criteria and simplified Nanjing criteria were evaluated and validated. The study is registered in www.chictr.org.cn (ID: ChiCTR1900020784).

The Nanjing criteria have a sensitivity and specificity of 95.35% and 100%, respectively, while the simplified Nanjing criteria have a sensitivity and specificity of 96.51% and 96.33%, respectively, for the diagnosis of PA-HSOS. Notably, a proportion of patients with Budd-Chiari syndrome (11/49) was misdiagnosed as PA-HSOS on the basis of the simplified Nanjing criteria, and this was mainly due to the overlapping features in the enhanced computed tomography/magnetic resonance imaging examinations. Furthermore, most of these patients (10/11) had occlusion or thrombosis of the hepatic vein, and communicating vessels in the liver were found in 8/11 patients, which were absent in PA-HSOS patients.

The Nanjing criteria and simplified Nanjing criteria exhibit excellent performance in diagnosing PA-HSOS. Thus, both could be valuable diagnostic tools in clinical practice.

To investigate the usefulness of inflammation biomarkers to serve as a predictors of portal vein thrombosis (PVT) postoperatively (post) in patients with portal hypertension after splenectomy and periesophagogastric devascularization.

A total of 177 liver cirrhosis patients were recruited from January 2013 to December 2017. They were divided into a PVT group (n=71) and a non-PVT group (n=106), according to ultrasound examination findings at 7-day post. Inflammation biomarkers involving platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), red blood cell distribution width-to-platelet ratio(RPR), mean platelet volume-to-platelet ratio (MPR) preoperatively (pre) and at 1, 3, 7-days post were recorded.

The univariate logistic regression analysis indicated that PLR (pre) (odds ratio (OR)=3.963, 95% confidence interval (CI)=2.070–7.587, p<0.000), MLR (pre) (OR=2.760, 95% CI=1.386–5.497, p=0.004), PLR (post-day 7) (OR=3.345, 95% CI=1.767–6.332, p=0.000) were significantly associated with the presence of PVT. The multivariate logistic regression analysis results indicated that PLR (pre) (OR=3.037, 95% CI=1.463–6.305, p=0.003), MLR (pre) (OR=2.188, 95% CI=1.003–4.772, p=0.049), PLR(post-day 7) (OR=2.166, 95% CI=1.053–4.454, p=0.036) were independent factors for predicting PVT.

The PLR (pre), MLR (pre), and PLR (post-day 7) are predictors of portal vein thrombosis post in patients with portal hypertension after splenectomy and periesophagogastric devascularization.

Acute-on-chronic liver failure (ACLF) is a risk factor for fungal infection. Endogenous fungal endophthalmitis is a serious, sight-threatening disease. Common causes include immunocompromised state and intravenous drug use, permitting opportunistic pathogens to reach the eye through the blood stream. We report a case of Candida endophthalmitis in a 47 year-old woman who was admitted to our hospital with ACLF and poorly controlled diabetes. In addition, she was treated with glucocorticoids due to severe jaundice. After treatment for ACLF, the patient experienced fever with blurred vision in the left eye and was diagnosed with candidemia, endogenous Candida endophthalmitis in the left eye, and chorioretinitis in the right eye. Systemic and topical antifungal treatment was administered based on the positive Candida albicans test in intraocular fluid using second-generation sequencing. The patient underwent vitrectomy in the left eye and C. albicans was confirmed in vitreous cultures. Follow-up visit, at 6 weeks after the operation, showed only light perception in the left eye and stable visual acuity in the right eye. Physicians should be aware of endogenous fungal endophthalmitis in patients with ACLF, especially those with Candida infection, a history of glucocorticoid use, and diabetes. A dilated retinal examination should be performed by an ophthalmologist if ACLF patients develop fever and fungal infection.

The safety and efficacy of mesenchymal stem cells (MSCs) in the treatment of acute-on-chronic liver failure (ACLF) have been validated. However, the impact of the pathological ACLF microenvironment on MSCs is less well understood. This study was designed to explore the changes in the functional properties of MSCs exposed to ACLF serum.

MSCs were cultured in the presence of 10%, 30% and 50% serum concentrations from ACLF patients and healthy volunteers. Then, the cell morphology, phenotype, apoptosis and proliferation of MSCs were evaluated, including the immunosuppressive effects. Subsequently, mRNA sequencing analysis was used to identify the molecules and pathways involved in MSC functional changes in the context of ACLF.

In the presence of ACLF serum, MSC morphology significantly changed but phenotype did not. Besides, MSC proliferation activity was weakened, while the apoptosis rate was lightly increased. Most importantly, the immunosuppressive function of MSCs was enhanced in a low-concentration serum environment but transformed into a proinflammatory response in a high-concentration serum environment. RNA sequencing indicated that 10% serum concentration from ACLF patients mediated the PI3K-Akt pathway to enhance the anti-inflammatory effect of MSCs, while the 50% serum concentration from ACLF patients promoted the conversion of MSCs into a proinflammatory function by affecting the cell cycle.

The 50% ACLF serum concentration is more similar to the environment in the human body, which means that direct peripheral blood intravenous infusion of MSCs may reduce the effect of transplantation. Combining treatments of plasma exchange to reduce harmful substances in serum may promote MSCs to exert a stronger anti-inflammatory effect.

The therapeutic effect of tenofovir alafenamide fumarate (TAF), tenofovir disoproxil fumarate (TDF) and entecavir (ETV) on chronic hepatitis B (CHB) patients remains inconsistent. The aim of this study was to explore the differences in virological responses to TAF, TDF and ETV in patients with CHB.

Literature searches were conducted of the PubMed, EMBASE, and the Cochrane Library databases to identify randomized controlled trials and observational studies published up to July 21, 2020. Statistical comparisons of virological response between TDF, ETV, and TAF were carried out with pooled odds ratio (OR) values.

The virological response in TDF-treated CHB patients was notably superior to that of the ETV-treated CHB patients after 12-weeks [OR=1.12, 95% confidence interval (CI): 0.89–1.41], 24-weeks (OR=1.33, 95% CI: 1.11–1.61), 48-weeks (OR=1.62, 95% CI: 1.16–2.25), 72-weeks (OR=1.43, 95% CI: 0.78–2.62), and 96-weeks (OR=1.56, 95% CI: 0.87–2.81) treatment. No significant difference was observed for the virological responses in CHB patients after 48-weeks treatment with TAF or TDF. The virological response in TDF+ETV-treated CHB patients was superior to that of TDF-treated CHB patients after 24-weeks, 48-weeks (OR=1.54, 95% CI: 1.17–2.02), 96-weeks, and 144-weeks.

The virological response in TDF-treated CHB patients was superior to that in ETV-treated CHB patients, but there was no significant difference between TAF and TDF. In addition, the therapeutic effect of TDF+ETV was superior to TDF alone.

Hepatocellular carcinoma (HCC) ranks among the leading cancer-related causes of morbidity and mortality worldwide. Downstaging of HCC has prevailed as a key method to curative therapy for patients who present with unresectable HCC outside of the listing criteria for liver transplantation (LT). Even though LT paves the way to lifesaving curative therapy for HCC, perpetually severe organ shortage limits its broader application. Debate over the optimal protocol and assessment of response to downstaging treatment has fueled immense research activity and is pushing the boundaries of LT candidate selection criteria. The implicit obligation of refining downstaging protocol is to ensure the maximization of the transplant survival benefit by taking into account the waitlist life expectancy. In the following review, we critically discuss strategies to best optimize downstaging HCC to LT on the basis of existing literature.

We present a 52-year-old Iraqi female patient who presented with extensive bilateral pulmonary micronodules on a chest X-ray (CXR) after a recent month-long visit to Turkey. She had a history of sarcoidosis, diagnosed 2 years ago, and was initially treated with a tapering dose of prednisone and maintained on a high dose of inhaled budesonide. High resolution computed tomography of the chest showed the new development of pulmonary nodules in a miliary pattern. Infectious causes were excluded with bronchoalveolar lavage. Non-necrotizing granulomatous inflammation and a lymphocyte count of 29% were obtained from a transbronchial lung biopsy and the differential cell count of the bronchoalveolar lavage, respectively. The patient started a treatment regimen of methotrexate and prednisone. Her repeat CXR at a subsequent follow up session showed resolution of the pulmonary micronodules. The association between sarcoidosis and tuberculosis was discussed. Published cases of miliary pulmonary nodules were examined for association with tuberculosis. To date, there has been no definitive evidence of tuberculosis as a cause for sarcoidosis despite the reported association. This case report emphasizes that sarcoidosis patients with pulmonary miliary patterns may have underlying risk factors for tuberculosis, and calls for more investigations to be performed to further delineate the association.

Within a year of its emergence, coronavirus disease-2019 (COVID-19) has evolved into a pandemic. What has emerged during the past 1 year is that, apart from its potentially fatal respiratory presentation from which the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) derives its name, it presents with a myriad of gastrointestinal (GI) and liver manifestations. Expression of the angiotensin-converting enzyme-2 (ACE-2) receptor throughout the GI tract and liver, which is the receptor for the SARS-CoV-2, may be responsible for the GI and liver manifestations. Besides acting directly via the ACE-2 receptor, the virus triggers a potent immune response, which might have a role in pathogenesis. The virus leads to derangement in liver function tests in close to 50% of the patients. The impact of these derangements in patients with a normal underlying liver seems to be innocuous. Severe clinical presentations include acute decompensation and acute-on-chronic liver failure in a patient with chronic liver disease, leading to high mortality. Evolving data suggests that, contrary to intuition, liver transplant recipients and patients with autoimmune liver disease on immunosuppression do not have increased mortality. The exact mechanism underlying why immunosuppressed patients fare well as compared to other patients remains to be deciphered. With newer variants of COVID-19, which can spread faster than the original strain, the data on hepatic manifestations needs to be updated to keep a step ahead of the virus.