Plasma cell neoplasms are well-known for having diverse morphological and phenotype presentations and less commonly unusual immunophenotypical profiles. Such unexpected immunophenotypical variability could lead to inaccurate impressions upon initial assessment, thus delaying an accurate diagnosis. Here, the authors report seven plasma cell neoplasm cases with unusual morphology, immunophenotype, or unusual anatomic locations from the archives of Montefiore Medical Center Hematopathology department to highlight key considerations involved in diagnosing plasma cell neoplasms.

The authors reviewed the 2015 to 2022 electronic medical records at Montefiore Medical Center and identified seven plasma cell neoplasm cases with unusual immunophenotypes as well as anatomic localization. Clinical information including demographics, patient history, clinical presentation, and treatment was retrieved along with pertinent laboratory data. Cell morphology and immunohistochemistry were evaluated from formalin-fixed, paraffin-embedded biopsy specimens stained with hematoxylin and eosin (H&E). Morphologic features and immunophenotype determined by flow cytometry and immunohistochemistry were reviewed, along with molecular and cytogenetic studies.

The analysis of the cases underscores the diagnostic complexity associated with the diverse array of morphological and immunophenotypic features of plasma cell neoplasms and offers insight into overcoming diagnostic challenges while avoiding potential pitfalls.

Awareness of the spectrum of morphological and immunophenotypic variability in plasma cell neoplasms is key to avoiding misdiagnosing variants and delaying clinical workup. Correlation with clinical and laboratory findings and evaluation by immunostaining to confirm plasma cell origin is necessary to reach a correct diagnosis.

The liver is the largest glandular organ in the body and has a unique distribution of cells and biomolecules. However, the treatment outcome of end-stage liver disease is extremely poor. Single-cell sequencing is a new advanced and powerful technique for identifying rare cell populations and biomolecules by analyzing the characteristics of gene expression between individual cells. These cells and biomolecules might be used as potential targets for immunotherapy of liver diseases and contribute to the development of precise individualized treatment. Compared to whole-tissue RNA sequencing, single-cell RNA sequencing (scRNA-seq) or other single-cell histological techniques have solved the problem of cell population heterogeneity and characterize molecular changes associated with liver diseases with higher accuracy and resolution. In this review, we comprehensively summarized single-cell approaches including transcriptomic, spatial transcriptomic, immunomic, proteomic, epigenomic, and multiomic technologies, and described their application in liver physiology and pathology. We also discussed advanced techniques and recent studies in the field of single-cell; our review might provide new insights into the pathophysiological mechanisms of the liver to achieve precise and individualized treatment of liver diseases.

Liposomes are a potential drug delivery system involving encapsulation into a phospholipid-based vesicular carrier system. In comparison with conventional delivery systems, liposomes may be advantageous due to site-specific targeting, controlled release patterns, enhanced stability, and reduced associated toxicity, among other processes. Several researchers in the last decade have attempted to develop simple or modified forms of liposomes for the effective delivery of various types of therapeutic agents. This review is focused on a discussion about some of the recent literature on the medical application of liposomes. An account of the mode of action of different types of liposomes as a supporting basis for their superior therapeutic efficiency was provided. The application of liposomes in the delivery of anticancer, anti-bacterial, and anti-fungal drugs, among others, was discussed. Along with this discussion, liposomal carriers for the management of diseases related to the respiratory and nervous system were included along with a special emphasis on the outcomes of current literature. The information gathered through this review will be useful in furnishing ideas about the current status of research studies conducted on the formulation and development of liposomal carriers.

Functional bowel disorders (FBDs) afflict millions of people worldwide. The pathogenesis of FBDs remains unclear and there are no effective treatments currently available. The intestinal microbiota is deemed a critical etiological factor in FBDs, and microbiota-targeted treatment strategies have promising therapeutic value. However, no comprehensive scientometric analyses related to FBDs and the intestinal microbiota have been performed. This study aimed to employ scientometrics to thoroughly analyze the knowledge base and the viable frontier between the intestinal microbiota and FBDs research fields.

Scientometrics was used to analyze the global research trends and hotspots in the overlapping fields of FBDs and the intestinal microbiota. The Web of Science database was selected as the research tool, and documents written in English and published from database inception to June 26th, 2023, were investigated.

There was a growth in publications from 2007 to 2022, with a total of 2,924 articles identified. China (n = 685, 23.43%) made the greatest contribution, followed by the United States (n = 672, 22.98%) and United Kingdom (n = 276, 9.44%). Co-citation analysis of references reflected the knowledge base in the past 16 years, including updating the understanding of FBDs, unveiling the relationship between the intestinal microbiota and FBDs, and preliminary research on the effects of microbiota-targeted treatment on FBDs.

By utilizing scientometrics, we identified three main research frontiers including microbiome-metabolites-mechanisms in FBDs, microbiota-related biomarkers for FBDs, and mechanism of microbiota-targeted treatments towards FBDs for precise medicine. These findings could provide valuable guidance for future research.

Major depressive disorder (MDD) continues to be a prevalent disease worldwide. While selective serotonin reuptake inhibitors and other medications continue to be prescribed, further research has been conducted toward other treatment modalities. Within the past decade, ketamine, an N-methyl-d-aspartate receptor antagonist, has been extensively studied as a new treatment for MDD. Recent studies show that ketamine at subanesthetic doses provides antidepressant effects. An extensive overview of the latest statistics of MDD and treatment plans are emphasized, with a review of current medications and their subsequent side effects. However, an important factor to consider with ketamine is dissociation, and given ketamine’s psychotomimetic side effects, it must be reviewed further. Despite such side effects of hallucinations and depersonalization, studies have shown administration achieves rapid and lasting antidepressant effects. The synergistic effects of ketamine are also analyzed with recent studies to summarize the effects of different treatment modalities. A summary of the latest research studies of ketamine as a possible treatment for MDD is provided. By focusing on the evolution of ketamine as a treatment for MDD, physicians can now utilize newer techniques for depression, with better short-term and long-term outcomes for the patients.

Our aim was to determine the immune efficacy of a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) booster vaccination in cirrhotic patients who had received the primary series.

We performed a longitudinal assessment in 48 patients with cirrhosis, 57 patients with chronic hepatitis B (CHB) and 68 healthy controls (HCs) to continuously track the dynamics of SARS-CoV-2 specific antibodies and memory B cells after receiving the primary series and booster dose at different times. A pseudovirus neutralization assay was used to determine neutralization against Omicron subvariants BA.2.12.1, BA.4 and BA.5 from serum samples collected from three cohorts.

Serum anti-receptor-binding domain (RBD) immunoglobulin (Ig)G and neutralizing antibody (NAb) levels in cirrhotic patients were elevated within 15–45 days after completing the primary series before rapidly declining and reaching a valley at around 165–195 days. After receiving the booster dose, both antibody levels were significantly increased to levels comparable to patients with CHB and HCs. Subgroup analysis showed that booster vaccination induced weaker antibody responses in patients with decompensated cirrhosis than in those with compensated cirrhosis. The SARS-CoV-2 memory B-cell response in cirrhotic patients was durable during follow-up regardless of the hepatic fibro-cirrhosis grade. However, compared with the primary series, the booster dose did not result in an evident improvement of neutralization activity against the Omicron subvariants BA.2.12.1 and BA.4, and was followed by a significant decrease in the titer against BA.5.

A booster dose elicited a robust and durable humoral response to the wild-type strain in cirrhotic patients but not the Omicron subvariants. Repeated vaccination of inactivated SARS-CoV-2 vaccine may not benefit cirrhotic patients in neutralization against newly circulating strains.

Direct evidence on the outcomes of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with normal alanine transaminase after long-term antiviral treatment is lacking.

HBeAg-negative patients with normal ALT and positive HBV DNA (≥20 IU/mL) were retrospectively enrolled. The endpoints included virological response (HBV DNA<100 IU/mL), changes in aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 index (FIB-4), and the incidence of liver nodules, cirrhosis, and hepatocellular carcinoma (HCC).

This cohort (n=194) was divided into three subgroups, untreated (n=67), treatment-continued (n=87), and treatment-discontinued patients (n=40), with a median follow-up of 54 months. The treatment-continued group achieved 100% (95% CI: 94.7–100) virological response, and significantly reduced APRI and FIB-4 scores (both p<0.001). The risk of liver nodules and cirrhosis in that group was reduced by 76% (HR: 0.24, 95% CI: 0.11–0.54, p<0.001) and 89% (HR: 0.11, 95% CI: 0.14–0.91, p=0.041) vs. the untreated group and by 77% (HR: 0.23, 95% CI: 0.10–0.49, p<0.001) and 95% (HR: 0.05, 95% CI: 0.01–0.44, p=0.006) vs. the treatment-discontinued group. For patients with HBV DNA≥2,000 IU/mL, adherence to treatment lowered the risks of liver cirrhosis by 92% (95% CI: 0.01–0.67) and 93% (95% CI: 0.01–0.53) vs. the untreated and treatment-discontinued patients, respectively. No patient adhering to treatment developed HCC, but one in each of the remaining groups did.

Continuous nucleos(t)ide analog (NA) treatment has a satisfactory effectiveness and helps to lower the risk of liver cirrhosis in HBeAg-negative CHB patients with normal alanine transaminase, especially in those with HBV DNA≥2,000 IU/mL.

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global population. About 20% have a normal body mass index (BMI) and a variant known as lean NAFLD. Unlike typical NAFLD cases associated with obesity and diabetes, lean NAFLD causes liver disease by mechanisms not related to excess weight or insulin resistance. Genetic disorders are among the major factors in developing lean NAFLD, and genome-wide association studies have identified several genes associated with the condition. This review aims to increase awareness by describing the genetic markers linked to NAFLD and the defects involved in developing lean NAFLD.

Development of fibrosis in chronic liver disease requires activation of hepatic stellate cells (HSCs) and leads to a poor outcome. Artesunate (Art) is an ester derivative of artemisinin that can induce ferroptosis in HSCs, and activated transcriptional factor 3 (ATF3) is an ATF/CREB transcription factor that is induced in response to stress. In this study, we examined the role of the Rho-associated protein kinase 1 (ROCK1)/ATF3 axis in Art-induced ferroptosis in HSCs.

HSC activation and ferroptosis were studied in vitro by western blotting, polymerase chain reaction, immunofluorescence, and other assays. ATF3 electrophoretic mobility and ROCK1 protein stability were assayed by western blotting. Immunoprecipitation was used to detect the interaction of ROCK1 and ATF3, as well as ATF3 phosphorylation. A ubiquitination assay was used to verify ROCK1 degradation. Atf3-interfering and Rock1-overexpressing mice were constructed to validate the anti-hepatic fibrosis activity of Art in vivo.

Art induced ferroptosis in HSCs following glutathione-dependent antioxidant system inactivation resulting from nuclear accumulation of unphosphorylated ATF3 mediated by ROCK1-ubiquitination in vitro. Art also decreased carbon tetrachloride-induced liver fibrosis in mice, which was reversed by interfering with Atf3 or overexpressing Rock1.

The ROCK1/ATF3 axis was involved in liver fibrosis and regulation of ferroptosis, which provides an experimental basis for further study of Art for the treatment of liver fibrosis.

Coronavirus disease (COVID-19) exhibits a range of clinical symptoms, including viral pneumonia, which can progress to acute respiratory distress syndrome, substantial alveolar destruction, and even multi-organ failure in severe cases. Disease pathology is greatly influenced by the host immune response. Several studies reported the perturbation of T-cell responses in COVID-19 patients. Activation and differentiation of CD4+ T cells into various subsets depend on the expression of lineage-specific transcription factors and overall cytokine milieu. Hence, a thorough evaluation of T helper cell lineage-specific transcription factors and pro-inflammatory cytokines can provide crucial insight into COVID-19 pathogenesis and may aid in developing strategies to prevent disease severity. Here, we performed a cross-sectional study to delineate the dysfunctional T helper cell subset immune response associated with COVID-19 disease severity.

We assessed T helper cell responses in SARS-CoV-2 infected individuals who presented with either asymptomatic, mild, or severe disease. mRNA profiling of lineage specific transcription factors and associated cytokines was done using real-time qPCR. Cytokine profiling was done using ELISA.

mRNA levels of FOXP-3 were significantly decreased in patients with severe COVID-19. No significant difference was observed for T-bet and GATA-3 among all of the groups. Bcl-6, the transcription factor for Tfh cell subsets, showed an increased trend in its association with disease progression. Furthermore, mRNA levels of IL-21 were significantly increased with disease severity. We also observed a significant increase in the concentration of pro-inflammatory cytokines IL-6 and IL-1β in patients with severe COVID-19.

These findings provide new insight into COVID-19 disease pathology and may aid in developing effective strategies to manage/control disease severity.

Semisolid oral preparations (Avaleha) are used in Ayurvedic therapeutics. The problems with these preparations include a bitter taste and the use of a sugar base. Here, we aimed to modify the semisolid Vasavaleha (VA) preparation to an oral solution (syrup) and to observe the efficacy of the VA syrup on patients with bronchial asthma.

VA syrup was prepared by dissolving the water-soluble extracts of Adhatoda vasica leaves and Piper longum fruits in purified water; sorbitol solution and honey were used as sweeteners. Organoleptic tests as well as pH, specific gravity, and viscosity measurements were performed. Liquid chromatography-mass spectrometry analysis of the VA syrup was carried out using an Agilent UHPLC-MS/Q-TOF (6545) system coupled with a Dual AJS ESI source. An open-label clinical trial of the VA syrup was performed on 13 patients with bronchial asthma at a dose of 10 mL (oral, twice a day) for 30 days.

The prepared VA syrup was brown in color and sweet in taste. The pH, specific gravity, and viscosity of the prepared VA syrup were 7.52, 1.10, and 1.922, respectively. Piperine, piperdardine, vasicine, vasicol, vasicinol, and vasicinone were determined to be the major phytochemical compounds. This preparation significantly improved all clinical symptoms of asthma and lung function test results in patients with bronchial asthma. It had mucolytic, bronchodilator, and anti-allergic properties. It had no adverse effects at the indicated dose.

The oral solution (syrup) might be an effective alternative for Ayurvedic semisolid preparations. The VA syrup may be taken as an alternative for VA as it was found to be an effective formulation for the management of bronchial asthma.

Increasing utilization of extended criteria donor leads to an increasing rate of early allograft failure after liver transplantation. However, consensus of definition of early allograft failure is lacking.

A retrospective, multicenter study was performed to validate the Liver Graft Assessment Following Transplantation (L-GrAFT) risk model in a Chinese cohort of 942 adult patients undergoing primary liver transplantation at three Chinese centers. L-GrAFT (L-GrAFT7 and L-GrAFT10) was compared with existing models: the Early Allograft Failure Simplified Estimation (EASE) score, the model of early allograft function (MEAF), and the Early Allograft Dysfunction (EAD) model. Univariate and multivariate logistic regression were used to find risk factors of L-GrAFT high-risk group.

L-GrAFT7 had an area under the curve of 0.85 in predicting 90-day graft survival, significantly superior to MEAF [area under the curve (AUC=0.78, p=0.044)] and EAD (AUC=0.78, p=0.006), while there was no statistical significance between the predicting abilities of L-GrAFT7 and EASE (AUC=0.84, p>0.05). Furthermore, L-GrAFT7 maintains good predicting ability in the subgroup of high-donor risk index (DRI) cases (AUC=0.83 vs. MEAF, p=0.007 vs. EAD, p=0.014) and recipients of donors after cardiac death (AUC=0.92 vs. EAD, p<0.001). Through multivariate analysis, pretransplant bilirubin level, units of packed red blood cells, and the DRI score were selected as independent risk factors of a L-GrAFT7 high-risk group.

The accuracy of L-GrAFT7 in predicting early allograft failure was validated in a Chinese multicenter cohort, indicating that it has the potential to become an accurate endpoint of clinical practice and transitional study of machine perfusion.

Asiaticoside reduces inflammatory reactions and oxidative stress, the primary causes of photoaging. The authors speculated that asiaticoside might contain therapeutic potential for photoaging.

Network pharmacology and molecular docking were used to explore the mechanisms of asiaticoside in treating photoaging. After achieving the targets of asiaticoside using PharmMapper, SwissTargetPrediction, CTD and BATMAN databases, as well as, targets of photoaging using GeneCards database, the co-targets interaction network was formed and a network of asiaticoside, photoaging, and common targets were constructed by Cytoscape. Next, the common targets were analyzed using GO and KEGG enrichment.

The analysis highlighted 202 core targets of asiaticoside were involved in the pathogenesis of photoaging. KEGG indicated asiaticoside performed an anti-photoaging effect through inflammation- and apoptosis-related signalling pathways, especially the PI3K-AKT and NF-κB pathways. Furthermore, the anti-photoaging effect of asiaticoside was verified by human dermal fibroblasts with UVA irradiation in vitro.

Asiaticoside may alleviate UVA-induced cell proliferation inhibition, reverse the abnormal gene expressions involved in the PI3K-AKT and NF-κB pathways, and have a high affinity with those core targets.

To facilitate the achieving of the goal of “eliminating viral hepatitis as a major public health threat by 2030” set by the World Health Organization, the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases (both are branches of the Chinese Medical Association) organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China (version 2022). With the support of available evidence, this revision of the guidelines focuses on active prevention, large scale testing, and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B related disease burden.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is often diagnosed when affected individuals die with respiratory failure. Currently, there are few bibliometrics studies on ALS.

In this study, a comprehensive literature search using the PubMed, WangFang, China National Knowledge Infrastructure, and Chinese Science and Technology Periodical databases was conducted. The Core Collection database for scientific output related to ALS from 1990 to 2022 was also searched. The retrieved dataset was analyzed using.

Bibliometrix. A total of 12,450 articles published since 1990 were retrieved, and 243 articles were included in this study. Thirty-two countries contributed to ALS research, among which Italy had the dominant position with the highest number of publications. In addition, keyword co-occurrence was analyzed. As the three indirect subjects of this article, the sources, affiliations, as well as authors of the study were included in the analysis.

In recent years, ALS research has made some progress in terms of elucidating the mechanism of the disease and providing clinical treatment, but the results are concentrated in the United States and European countries. For more complicated research results, critical analysis must be performed.

Insulin resistance and hyperinsulinemia in type 2 diabetes mellitus induced dyslipidemia. This study aims to investigate the abrogative role of Terminalia catappa (T. catappa) leaf aqueous extract (TCLAE) on diabetes-induced dyslipidaemia in type 2 diabetic rats.

Diabetic rats were induced by fat-rich feed for eight weeks and intraperitoneal streptozotocin (STZ, 30 mg/kg) injection, while glibenclamide (10 mg/kg) and TCLAE-graded doses were orally administered for four weeks. Then, the biomarkers for diabetes, liver function, lipid profile, cardiovascular indices, and liver histology were measured, in addition to the hepatic expression of some lipid metabolic genes.

TCLAE reduced the diabetes-induced fasting blood glucose, weight loss, plasma insulin, alanine transaminase, bilirubin, cholesterol (CHOL), triglyceride (TRIG), low-density lipoprotein-CHOL and low-density lipoprotein-TRIG. TCLAE also decreased the abnormal cardiovascular indices. TCALE significantly enhanced the high-density lipoprotein-CHOL, the expression of peroxisome proliferator-activated receptor alpha (PPAR-α), PPAR delta (PPAR-δ), and carnitine palmitoyltransferase 1a, and decreased the hepatic expression of C-reactive protein of type 2 diabetic rats.

TCLAE alleviates diabetes-induced dyslipidaemia in type 2 diabetic rats by ameliorating the altered expression of lipid metabolic genes.

Thymic epithelial neoplasms, comprised of thymoma, thymic carcinoma, and others, account for less than 1% of human tumors. Fine needle aspiration (FNA) is performed to diagnose thymic lesions due to its minimal invasiveness. Since classification of thymic epithelial neoplasms usually requires thorough histologic examination of the entire lesion, it is necessary to understand the information FNA can provide as well as its limitations. The advantage of FNA lies in its comparable diagnostic accuracy and minimal invasiveness, but it is almost impossible to subtype thymomas with this technique owing to its sampling issues. This review summarizes the cytologic features of thymoma and thymic carcinoma as well as the potential diagnostic pitfalls associated with FNA.