The impact of nonalcoholic fatty liver disease (NAFLD) on the treatment outcome of chronic hepatitis B (CHB) is undefined and deserves an in-depth investigation.

Histologically-proven CHB receiving first-line antiviral regimens as initial therapy was enrolled and grouped by the concurrence of NAFLD, and followed up at six monthly intervals. Therapeutic response related data were recorded and compared at multiple time points. Kaplan-Meier and Cox regression analyses were utilized to estimate the impact of NAFLD on complete virological response (CVR).

We enrolled 267 patients (CHB: 164; CHB with NAFLD: 103) with comparable follow-up durations. They were also comparable in baseline HBV DNA levels and HBeAg positivity. Patients with concomitant NAFLD showed less significant decline in HBV DNA, qHBsAg, pgRNA, and liver enzyme levels over time; moreover, their cumulative incidences of CVR were significantly lower and that of low-level viremia (LLV) were significantly higher at 6, 12, 18, 24 months. First CVR of CHB was delayed with the presence NAFLD (11.0 vs. 7.0 months, p<0.001) and further prolonged with higher grade of liver steatosis (Grade 2–3 vs. 1: 13.0 vs. 9.0 months). On multivariate analysis, HBeAg positivity (HR: 0.650, p=0.036), grade of steatosis (G2 [HR: 0.447, p=0.004]; G3 [HR: 0.085, p=0.002]) and HBV DNA (log10 IU/mL) (HR: 0.687, p<0.001) were significantly associated with delayed CVR, whereas grade of necroinflammation (HR: 1. 758, p<0.001) accelerated the CVR.

In CHB patients receiving initial antiviral therapy, NAFLD was associated with higher levels of HBV DNA, pgRNA, and liver enzymes, and higher incidence of LLV and delayed CVR.

The study established and compared the efficacy of the clinicoradiological model, radiomics model and clinicoradiological-radiomics hybrid model in predicting the microvascular invasion (MVI) of hepatocellular carcinoma (HCC) using gadolinium ethoxybenzyl diethylene triaminepentaacetic acid (Gd-EOB-DTPA) enhanced MRI.

This was a study that enrolled 602 HCC patients from two institutions. Least absolute shrinkage and selection operator (Lasso) method was used to screen for the most important clinicoradiological and radiomics features that predict MVI pre-operatively. Three machine learning algorithms were used to establish the clinicoradiological, radiomics, and clinicoradiological-radiomics hybrid models. Area under the curve (AUC) of receiver operating characteristic (ROC) curves and Delong’s test were used to compare and quantify the predictive performance of the models.

The AUCs of the clinicoradiological model in training and validation cohorts were 0.793 and 0.701, respectively. The radiomics signature of arterial phase (AP) images alone achieved satisfying predictive efficacy for MVI, with AUCs of 0.671 and 0.643 in training and validation cohort, respectively. The combination of clinicoradiological factors and fusion radiomics signature of AP and VP images achieved AUCs of 0.824 and 0.801 in training and validation cohorts, 0.812 and 0.805 in prospective validation and external validation cohorts, respectively. The hybrid model provided the best prediction results. The results of the Delong test revealed that there were statistically significant differences among the clinicoradiological-radiomics hybrid model, clinicoradiological model, and radiomics model (p<0.05).

The combination of clinicoradiological factors and fusion radiomics signature of AP and VP images based on Gd-EOB-DTPA-enhanced MRI can effectively predict MVI.

Urachal carcinoma (UC) cases are rare but aggressive that pose significant diagnostic and therapeutic challenges. To summarize the diagnostic features of UC, we report our case findings.

Retrospectively analyzed the clinical features of patients with UC between 2010 and 2020 at our center. Patient demographics, clinical history, treatment, and follow-up information were obtained.

All 11 UC patients with a mean age of 54.2 years, including 8 men and 3 women. The initial symptom in 7 cases was painless gross hematuria, followed by urinary tract irritation and abdominal pain. Pathological findings revealed malignancies in all patients, including three mucinous UC, six moderate differentiated UC, one poorly differentiated UC, and one undifferentiated typed UC. Most of the patients underwent extended partial cystectomy. In addition, the majority of patients (82%) had a short duration of follow-up (2–36 months), and 18% of patients were lost to follow-up. As a result, the average postoperative follow-up time was 19.7 months and the 2-year survival rate was 54.5%.

The incidence of UC is concealed and patients often complain about hematuria and mucinuria. There is a lack of effective systemic treatment, and the prognosis of UC is poor.

Vagal stimulation under general anesthesia can lead to life-threatening bradycardia and cardiac arrest. Here we present two cases of cervical carcinoma and tongue carcinoma, developing intra-operative cardiac arrest due to severe vagal stimulation, treated and resuscitated as per Advanced Cardiac Life Support protocol followed by clinical evaluation along with 12 lead electrocardiogram, arterial blood gases and screening echocardiogram, and completion of surgery. Also, we stress that intra-operative cardiac arrest is a dreadful consequence of severe vagal bradycardia leading to asystole, which needs to be recognized early and treated promptly followed by thorough clinical assessment and a decision regarding whether to proceed or abandon the surgery. This kind of cardiac arrest due to severe vagal stimulation which is resuscitated with minimal intervention may not call for deferring the surgical procedure if the evaluation done clinically together with tools of electrocardiogram, arterial blood gases, and screening echocardiogram are within the normal range.

Severe alcoholic hepatitis (sAH) is defined by a modified discriminant function ≥32 or model for end-stage liver disease (MELD) >20. Patients with sAH are in an immunocompromised state attributed to cirrhosis-related immunoparesis and corticosteroid use. Individuals with sAH often develop severe infections that adversely impact short-term prognosis. Currently, the corticosteroid prednisolone is the only treatment with proven efficacy in sAH; however, the combination of corticosteroid treatment and altered host defense in sAH has been thought to increase the risk of acquiring of bacterial, opportunistic fungal, and viral infections. Newer studies have shown that corticosteroids do not increase occurrence of infections in those with sAH; unfortunately, the lack of response to corticosteroids may instead predispose to infection development. Prompt and appropriate antibiotic treatment is therefore essential to improving patient outcomes. This review highlights common infections and risk factors in patients with sAH. Additionally, current diagnostic, therapeutic, and prophylactic strategies in these patients are discussed.

Nonalcoholic fatty liver disease (NAFLD) is emerging globally, while no therapeutic medication has been approved as an effective treatment to date, lifestyle intervention through dietary modification and physical exercise plays a critical role in NAFLD management. In terms of dietary modification, Mediterranean diet is the most studied dietary pattern and is recommended in many guidelines, however, it may not be feasible and affordable for many patients. Recently, a ketogenic diet and intermittent fasting have gained public attention and have been studied in the role of weight management. This article reviews specifically whether these trendy dietary patterns have an effect on NAFLD outcomes regarding intrahepatic fat content, fibrosis, and liver enzymes, the scientific rationales behind these particular dietary patterns, as well as the safety concerns in some certain patient groups.

Antibody-dependent enhancement (ADE) is an inadequate response to reinfection or vaccination. ADE was described for influenza and dengue fever: patients already exposed are likely to develop a more severe infection when exposed to a virus of another type than the first. Vaccine antibodies also appear to be responsible for an increased risk of severe disease in a naive person. In COVID-19, ADE is likely with antibodies acquired following infection or vaccination. The aggravation of the disease by measles vaccination has been shown for the inactivated virus vaccines. Atypical measles was also described after the live attenuated vaccine (LAV). ADE mechanisms are the penetration into cells of virus-antibody complexes promoted by FcγR or complement receptors and by an imbalance between neutralizing and facilitating antibodies. The role of maternal antibodies in ADE has been suggested after influenza vaccination in piglets. Facilitation of virus entry into the cell by complement fixation and an imbalance between anti-hemagglutinin and anti-fusion protein antibody levels have been suggested as a mechanism for atypical measles after the inactivated vaccine. Antibodies induced by the current LAV can induce ADE in vitro by binding to FcγR and the same imbalance. A recent vaccination campaign during an outbreak and the comparative history of measles before and during the vaccine era may alert to a possible ADE by the current LAV: it could be caused in infants by maternal antibodies and in adults by waning vaccine immunity. Improvement of current LAV or the development of a new type of vaccine could eliminate this phenomenon.

Tabersonine (Tab), an indole alkaloid, is a traditional Chinese medicine that can be used as an anti-inflammatory agent and is mainly isolated from the medicinal plant Catharanthus roseus. This study aims to develop safer and more promising new treatments for arthritis.

We tested the biological activity of Tab against rheumatoid arthritis fibroblast-like synoviocytes (RA -FLS) and evaluated its effect on the progression of rheumatoid arthritis through animal experiments. The mechanism of Tab in rheumatoid arthritis (RA) was further clarified by network prediction and a series of molecular biology experiments.

The results showed that Tab inhibited the proliferation, migration, invasion and other biological functions of RA-FLS, effectively reducing the expression of inflammatory factors in RA-FLS and the number of vascular loops in 1730 cells in vitro. In vivo, Tab significantly reduced paw and joint swelling and inhibited inflammatory cytokine expression in collagen-induced arthritis model mice. Preliminary mechanistic studies showed that Tab inhibited the expression and activation of key molecules in the PI3K pathway, suggesting that Tab influences the progression of RA disease by inhibiting the PI3K-Akt signaling pathway.

In general, Tabersonine can be used as a new potential treatment for RA.

(Pro)renin receptor (PRR), a tissue-specific gene, exhibits hypertensive actions and plays an essential role in the pathogenesis of kidney injuries through the renin-angiotensin system (RAS) -dependent and -independent mechanisms. Saigo et al. recently demonstrated that PRR may be irrelevant to RAS but functions as a vacuolar H+-ATPase (V-ATPase) in renal tubules using transgenic mice overexpressing the tubular epithelial PRR gene. This may challenge the initial concept that PRR works as a receptor of (pro)renin/renin and the idea that PRR is directly involved in intracellular signaling. This mini-review comments on the report by Saigo et al. and provides several opinions on the roles of PRR. The investigator considers that PRR functions as a V-ATPase that controls the V-ATPase activity, whereas whether the link between PRR and RAS truly occurs in vivo still awaits future investigation.

In 2015, the Chinese Society of Hepatology and the Chinese Society of Gastroenterology issued a consensus statement on the diagnosis and management of cholestatic liver diseases. More clinical data on this topic have appeared during recent years. The Autoimmune Liver Disease Group of the Chinese Society of Hepatology organized an expert group to review recent evidence and provide an update to these previous guidelines. Herein, we provide 22 recommendations as a working reference for the management of cholestatic liver diseases by clinical practitioners.

Chronic obstructive pulmonary disease (COPD) dyspnea intensity is strongly correlated with respiratory drive, when assessed in relation to EMGdi activity expressed as a percentage of maximum (EMGdi%max). There is growing evidence that respiratory drive can be improved by exercise. The present systematic review investigates the effects and clinical significance of exercise interventions on respiratory drive in COPD patients.

With the application of PRISMA guidelines, Pubmed, PEDro, Science direct, and the Cochrane Central Register of Controlled Trials were searched from inception until 25 January 2022.

A total of 14 studies (n = 238) were identified, and 12 studies were included in the meta-analysis. The meta-analysis revealed that EMGdi%max was higher during intense exercise, when compared to at rest, with significant heterogeneity (I2 = 89%). However, EMGdi%max significantly decreased after eight weeks of inspiratory muscle training (IMT). Three studies that examined the acute exercise effects revealed that breathlessness is highly correlated to EMGdi%max during aerobic exercise. During constant work rate exercise, EMGdi%max initially increased, and subsequently reached a plateau, while during incremental exercises, this gradually increased without reaching a plateau. This was associated with low ventilatory and neuromuscular efficiency.

Intense (≥75% of peak work rate) exercise induces a higher EMGdi%max, when compared to at rest, in COPD patients, and is highly correlated to dyspnea intensity during exercise. Eight weeks of IMT can reduce the dyspnea intensity and improve exercise tolerance. Measuring EMGdi%max during exercise is a useful clinical approach. This is associated with dyspnea severity, and reduced ventilatory and neuromuscular efficiency, and is sensitive to exercise interventions.

Due to its invasiveness, heterogeneity and multiple-drug resistance, pancreatic ductal adenocarcinoma (PDAC) has been considered as a refractory malignant tumor. Although various studies have been conducted on the potential mechanisms that promote PDAC origination and metastasis, the research results and clinical translation to treat PDAC still need improvement. With the development of individualized medicine and the implementation of gene sequencing, it has been confirmed that myelocytomatosis oncogene (MYC) contributes to poor prognosis in cancer cases. Furthermore, the deregulation of MYC exists in a majority of pancreatic cancer types, and is crucial for tumor cell proliferation and migration. Several recent studies have revealed the specific mechanisms of MYC in affecting PDAC, and clarified suppression of MYC as a promising therapeutic strategy. This review focused on emerging novel therapeutic strategies based on the direct or indirect targeting of MYC to combat PDAC.

Previous studies have shown that a traditional Chinese herbal medicine, Yinyangdayu decoction, and repetitive transcranial magnetic stimulation (rTMS) are both effects treatment methods for depression. This study is designed to observe the combined clinical efficacy of Yinyangdayu decoction and rTMS with magnetic stimulation at the taichong point (LR03) in the treatment of depression.

Based on the real-world study, 204 patients with depressive disorder will be recruited and randomized into 3 groups (control group, treatment group 1, and treatment group 2). The control group will receive rTMS only (1 HZ, 1,800 pulses, 100% threshold). Treatment group 1 will receive rTMS + magnetic stimulation at LR03 (the left side, 1 HZ, 1,800 pulses, 100% threshold), and treatment group 2 will be given rTMS + Yinyangdayu decoction (200 mL, 2 times/day). The treatment course will last for 8 weeks, and relevant rating scales will be assessed at baseline, week 4, and week 8 to evaluate the efficacy.

This study might optimize the TCM comprehensive treatment scheme of depression, integrated with Western and traditional Chinese medicine.

Chinese Clinical Trial Registry, ChiCTR1900027443. Registered on 13 November 2019, www.chictr.org.cn

Naringenin is an anti-inflammatory flavonoid that has been studied in chronic liver disease. The mechanism specific to its antifibrosis activity needs further investigation This study was to focused on the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) pathway in hepatic stellate cells and clarified the antifibrosis mechanism of naringenin.

The relationship between the cGAS-stimulator of interferon genes (STING) pathway and liver fibrosis was analyzed using the Gene Expression Omnibus database. Histopathology, immunohistochemistry, fluorescence staining, Western blotting and polymerase chain reaction were performed to assess gene and protein expression levels associated with the cGAS pathway in clinical liver tissue samples and mouse livers. Molecular docking was performed to evaluate the relationship between naringenin and cGAS, and western blotting was performed to study the expression of inflammatory factors downstream of cGAS in vitro.

Clinical database analyses showed that the cGAS-STING pathway is involved in the occurrence of chronic liver disease. Naringenin ameliorated liver injury and liver fibrosis, decreased collagen deposition and cGAS expression, and inhibited inflammation in carbon tetrachloride (CCl4)-treated mice. Molecular docking found that cGAS may be a direct target of naringenin. Consistent with the in vivo results, we verified the inhibitory effect of naringenin on activated hepatic stellate cells (HSCs). By using the cGAS-specific agonist double-stranded (ds)DNA, we showed that naringenin attenuated the activation of cGAS and its inflammatory factors affected by dsDNA. We verified that naringenin inhibited the cGAS-STING pathway, thereby reducing the secretion of inflammatory factors by HSCs to ameliorate liver fibrosis.

Interrupting the cGAS-STING pathway helped reverse the fibrosis process. Naringenin has potential as an antihepatic fibrosis drug.

Acute-on-chronic liver failure (ACLF) is a clinical syndrome that develops in patients with chronic liver diseases following a precipitating event and associated with a high mortality rate due to systemic multiorgan failure. Establishing a suitable and stable animal model to precisely elucidate the molecular basis of ACLF pathogenesis is essential for the development of effective early diagnostic and treatment strategies. In this context, this article provides a concise and inclusive review of breakthroughs in ACLF animal model development.

The pandemic of Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), represents an unprecedented threat to health and the world economy. According to the scientific background and preliminary clinical trials, ozone therapy (OT) may help as complementary therapy in prophylaxis, treatment, and in the recovery of convalescents. During the COVID-19 pandemic, the number of registered clinical trials using OT on COVID-19 represented an increment of 36% compared to the total number of previously recorded clinical studies. At present, papers that report an intervention in COVID-19 patients total 25. Four trials have been done in prophylaxis, there are 3 manuscripts enrolled convalescents, and there is 1 meta-analysis. Manuscripts with outcomes, indexed in the MedLine database, represent 73%. The most widely used routes of administration for the intervention in COVID-19 patients are ozonated saline solution and major autohemotherapy. Preliminary results are encouraging, indicating that OT reduces inflammation indices, decreases the time of assisted respiration, decreases C-reactive protein, improves oxygen saturation, could decrease mortality, and makes polymerase chain reaction tests negative in shorter periods. When trained medical doctors follow the correct protocols and use certified devices, the improvements that have been reported allow the patients to recover more quickly. However, it is considered that larger clinical studies are needed.

Hepatitis B virus (HBV) biomarkers have been used for a better categorization of patients, even though the lack of simple algorithms and the impact of genotypes limit their application. Our aim was to assess the usefulness of noninvasive markers for the identification of HBV inactive carriers (ICs) in a single-point evaluation and to design a predictive model for their identification.

This retrospective-prospective study included 343 consecutive HBeAg-negative individuals. Clinical, analytical, and virological data were collected, and a liver biopsy was performed if needed. Subjects were classified at the end of follow-up as ICs, chronic hepatitis B and gray zone.A predictive model was constructed, and validated by 1000-bootstrap samples.

After 39 months of follow-up, 298 subjects were ICs, 36 were chronic hepatitis B CHB, and nine were gray zone. Eighty-nine (25.9%) individuals required a liver biopsy. Baseline HBV DNA hazard ratio (HR) 6.0, p<0.001), HBV core-related antigen (HBcrAg) (HR 6.5, p<0.001), and elastography (HR 4.6, p<0.001) were independently associated with the IC stage. The ACE score (HBV DNA, HBcrAg, elastography), obtained by bootstrapping, yielded an area under the receiver operating characteristics (AUROC) of 0.925 (95% CI: 0.880–0.970, p<0.001) for identification of ICs. The AUROC for genotype D was 0.95, 0.96 for A, 0.90 for E, and 0.88 for H/F. An ACE score of <1 had a positive predictive value of 99.5%, and a score ≤12 points had a diagnostic accuracy of 93.8%.

Low baseline HBV DNA, HBcrAg, and liver stiffness were independently associated with the IC phase. A score including those variables identified ICs at a single-point evaluation, and might be applied to implement less intensive follow-up strategies.

Three-dimensional (3D) printing has provided individuals in various industries with a tool to bring their creations to life. The medical field is no stranger to 3D printing, which has been utilized in various applications since its inception. The various additive technologies currently available to elucidate the differences between them will be discussed briefly. The current applications of 3D printing in medicine could be divided into applications in medical education, patient care, equipment modification or fabrication, and research. The various applications in these categories are described with examples of upcoming research and technology that may be available in the near future. Despite the benefits of 3D printing, challenges remain, and technology improvements are required before there will be more adoption in the medical field. The technology is growing rapidly and evolving, and more 3D printing applications will be seen in the future.