Hepatitis B virus (HBV) infection contributes to hepatocellular carcinoma (HCC) tumorigenesis, drug resistance, and recurrence, although the underlying molecular mechanisms remain unclear. Recent studies suggest that HBV infection may be associated with liver cancer stem cells (LCSCs), but the exact mechanisms are yet to be resolved. In this study, we aimed to analyze the role of HBV infection in regulating the stemness of HCCs, which is closely linked to drug resistance.

Sphere formation assay and real-time Polymerase Chain Reaction quantification were used to isolate and confirm liver cancer stem cells. The inhibitory concentration values of sorafenib and regorafenib were calculated and compared using the Cell Counting Kit-8 assay. HBV infection was used to assess the effect of HBV replication on LCSC markers. Co-immunoprecipitation assay was performed to detect the interaction between CD133 and SRC. Furthermore, we utilized the CRISPR-Cas9 system to knockout CD133 expression in HepG2.2.15 cells.

LCSCs derived from HCCs exhibited high expression of stem cell markers and demonstrated reduced sensitivity to sorafenib and regorafenib. HBV replication promoted both drug resistance and stemness in hepatoma cells and clinical samples. Overexpression of HBx protein in HepG2 cells upregulated the expression of CD133, EpCAM, and CD24, enhancing resistance to sorafenib and regorafenib. Knockout of CD133 expression using the CRISPR-Cas9 system significantly inhibited drug resistance to both sorafenib and regorafenib in HepG2.2.15 cells. Mechanistically, HBV replication promoted CD133 expression, which in turn interacted with the SRC/STAT3 signaling pathway.

Our data suggest that HBV replication enhances the stemness and drug resistance of HCC, providing a strong theoretical foundation for the development of targeted and efficient treatments for HBV-infected HCCs.

Recent studies have highlighted a link between amyotrophic lateral sclerosis (ALS) and gut microbiota. This prospective study aimed to evaluate the effects of electroacupuncture combined with Chinese herbal medicine on gut microbiota and metabolomics in ALS patients.

Ten ALS patients were randomly assigned to either a treatment group (electroacupuncture with Chinese herbal medicine, n = 6) or a control group (waiting treatment, n = 4). Healthy controls (age- and sex-matched, n = 10) were also included. Data were collected after 12 sessions of electroacupuncture and follow-ups at three and six months. ALS functional rating scale scores were documented pre- and post-treatment. Stool samples were collected at two time points (T0 and T4 weeks) and analyzed, and metabolomic profiles from urine samples were analyzed post-treatment. Heatmap correlation analysis was used to explore relationships between microbiota, metabolomics, and clinical outcomes.

Treatment with electroacupuncture reduced Eisenbergiella abundance in the treatment group. A significant positive correlation was found between Lachnospiraceae and ALS functional rating scale scores (P < 0.005 and P < 0.001, respectively). Differential expression of purine metabolism was observed in ALS patients (P = 0.0017).

Imbalances in the gut microbiome and metabolic disorders have been found among patients with ALS. These imbalances appear to be partially mitigated by treatment with electroacupuncture combined with Chinese herbal medicine. Our research suggests that Eisenbergiella might be a diagnostic biomarker and a potential therapeutic target for ALS.

Reprogramming of lipid metabolism has emerged as a significant characteristic of malignancy during tumor development. Research indicates a critical link between lipid metabolism and the tumor immune microenvironment. This relationship not only facilitates cancer progression by remodeling the tumor microenvironment but also influences the functionality of immune cells. Alterations in lipid metabolism regulate the function and status of immune cells within the microenvironment, impacting immune evasion and the therapeutic efficacy of tumors. Consequently, targeting lipid metabolism is a viable strategy for intervening in tumorigenesis and tumor development. This review examines the roles of key lipid molecules, such as fatty acids and cholesterol, within the tumor microenvironment, highlighting how aberrant lipid metabolism can alter immune cell function. By investigating the interactions between lipid metabolism and immune cells in this setting, the review offers novel insights into early diagnosis, screening, and immunotherapy of malignant tumors. Furthermore, lipid metabolic reprogramming may act as a biomarker for monitoring early immune escape from tumors and predicting therapeutic outcomes, thereby enhancing early diagnosis and personalized cancer treatment.

Surgical management of supratentorial spontaneous intracerebral hemorrhage (sICH) remains controversial. Craniotomy (CT) reduces mortality but offers limited functional benefits. Neuroendoscopic surgery (NE) has emerged as a viable alternative, providing improved outcomes. Recent randomized controlled trials (RCTs) strengthen ongoing comparisons between these approaches. This meta-analysis systematically evaluates the efficacy and safety of NE versus CT for supratentorial sICH.

RCTs comparing NE versus CT for supratentorial sICH were systematically identified through comprehensive searches of PubMed, Embase, Cochrane Library, and Web of Science databases. Evaluated outcomes included functional outcome (favorable or unfavorable), hematoma evacuation rate, mortality, intraoperative blood loss, operation time, rebleeding, infection (including pulmonary and intracranial), and total complications. Cochrane’s Risk of Bias-2 tool was employed to assess the risk of bias across the included studies.

Eight RCTs were included, comprising 1,354 patients. NE demonstrated a significant advantage in achieving a favorable functional outcome (risk ratio: 1.43; 95% confidence interval (CI) 1.22, 1.68; p < 0.001) and a notably higher hematoma evacuation rate (mean difference (MD): 7.60; 95% CI 3.59, 11.61; p < 0.001). Additionally, NE was associated with a marked reduction in intraoperative blood loss (MD: −152.95; 95% CI −261.68, −44.22; p = 0.006) and a substantial reduction in operative time (MD: −118.49; 95% CI −147.30, −89.67; p < 0.001). The incidences of unfavorable functional outcome and total complications, including pulmonary infection, were significantly lower in the NE group. However, NE did not lead to an improvement in the mortality rate, and there were no significant differences in the incidences of postoperative rebleeding or intracranial infection between the two groups.

These findings suggest that NE offers distinct advantages in terms of functional outcomes and surgical efficiency for patients with supratentorial sICH. Future studies should involve larger, higher-quality RCTs, and neuroendoscopic techniques should be continuously optimized.

Portal hypertension can cause serious complications such as upper gastrointestinal bleeding, primarily due to esophageal and gastric varices. The risk of mortality from variceal hemorrhage is significant, particularly when the hepatic venous pressure gradient exceeds 12 mmHg. Established treatments generally include endoscopic variceal band ligation and cyanoacrylate glue for gastric varices; however, challenges such as limited availability and a lack of technical expertise can hinder the use of glue, leading to preventable complications. This study investigates the efficacy of using a 50% glucose solution for injection sclerotherapy in cases of gastric varices. We present three unique patient cases. The first case involves a 21-year-old with persistent upper gastrointestinal bleeding and a portal vein thrombus, who experienced temporary relief after receiving injection sclerotherapy but tragically succumbed to significant bleeding later. The second case describes a 24-year-old who successfully managed his bleeding with the same treatment but was subsequently lost to follow-up. Lastly, a 72-year-old patient with recurrent painless hematemesis remained free of symptoms following injection sclerotherapy. Overall, while cyanoacrylate glue remains the preferred treatment, injection sclerotherapy with 50% dextrose shows promise as an effective alternative, particularly in settings where conventional treatments are not readily available, potentially reducing the risks associated with untreated variceal bleeding.

Protein disulfide isomerases (PDIs) are essential enzymes that facilitate the proper folding of proteins and maintain protein quality within the endoplasmic reticulum. Dysregulation of PDIs has been correlated with numerous disorders, including cancer and rheumatoid arthritis (RA). E64FC26 (EFC), a small molecule that inhibits a wide range of PDI family members, has shown promise as a therapeutic agent in oncology. However, its effects on RA have not yet been studied. This research investigates the efficacy of EFC as a potential treatment for RA.

To investigate EFC’s effects on RA fibroblast-like synoviocytes, several assays were employed, including Cell Counting Kit-8 for cell viability, EdU for cell proliferation, Transwell for migration and invasion, TUNEL for apoptosis, and in vitro tube formation assays for angiogenesis. Flow cytometry was used to assess apoptosis in detail. Cytokine production was analyzed using ELISA and real-time polymerase chain reaction. In vivo, a collagen-induced arthritis model was developed in DBA mice to evaluate EFC’s effects on inflammation, disease progression, and bone damage. RNA sequencing was utilized to identify the molecular pathways influenced by EFC treatment.

EFC exhibited significant anti-inflammatory effects on RA fibroblast-like synoviocytes, reducing cell proliferation, migration, invasion, angiogenic activity, and cytokine secretion, while simultaneously promoting apoptosis. In vivo experiments using the collagen-induced arthritis mouse model showed that EFC alleviated inflammation, slowed disease progression, and preserved joint and bone integrity. RNA sequencing data suggested that EFC acts through pathways associated with inflammation and apoptosis regulation.

The findings of this research underscore EFC’s therapeutic potential in managing RA. These results pave the way for the development of inhibitors targeting the PDI family as innovative treatments for RA.

Waist circumference (WC) is closely associated with metabolic diseases, including diabetes mellitus (DM), metabolic syndrome, and mortality. However, the correlation between WC and mortality varies across populations and has rarely been examined specifically in patients with DM. In this study, we explored the relationships between WC and both all-cause and cardiovascular mortalities among individuals with DM.

Participants from the National Health and Nutrition Examination Survey 2003–2018 included 3,151 women and 3,473 men with DM who had baseline WC measurements. Survival data were collected from enrollment until December 31, 2019. Cox proportional hazard models were adjusted for demographic features and other confounders. Restricted cubic spline curves and threshold effect analyses were performed separately for men and women. Sensitivity analyses were conducted to minimize reverse causality.

Among 6,624 participants with DM, 621 women and 871 men died during median follow-ups of 6.8 and 6.3 years, respectively. WC demonstrated a U-shaped association with all-cause and cardiovascular mortalities in women, and a J-shaped trend in men. The optimal WC thresholds for minimizing mortality risk were 107.0 cm for women and 89.0 cm for men. For women, adjusted hazard ratios for all-cause mortality were 0.97 (95% confidence interval (CI): 0.96–0.98, P < 0.001) for WC below 107.0 cm and 1.04 (95% CI: 1.02–1.05, P < 0.001) for WC above 107.0 cm. In men, the corresponding ratios were 0.94 (95% CI: 0.90–0.97, P < 0.001) for WC below 89.0 cm and 1.03 (95% CI: 1.02–1.05, P < 0.001) for WC above 89.0 cm.

WC showed a U-shaped association with all-cause and cardiovascular mortalities in women and a J-shaped association in men among U.S. adults with DM from the National Health and Nutrition Examination Survey. Further research is needed to explore the underlying mechanisms rather than promoting preconceived notions about an optimal WC.

Breast cancer is the most common cancer among women, with hormone receptors playing a crucial role, not only in cancer cell growth but also as primary targets in breast cancer treatment. This systematic literature review aimed to summarize the current evidence on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) discordance rates between primary and recurrent breast cancer. Additionally, it seeks to identify how discordance affects prognosis, metastasis, and the potential evidence of primary tumor heterogeneity.

The databases Web of Science, Scopus, MEDLINE, and PubMed were searched for publications of original research in English from 2013 to 2023. Studies with paired histopathology from primary and recurrent breast cancer that employed immunohistochemistry and fluorescence in situ hybridization were included. Ten studies were deemed eligible for inclusion.

Concordance between primary and recurrent breast cancer was high for ER (80%), PR (65%), and HER2 (85%). Average discordance rates were: ER 19%, PR 34%, and HER2 15%, with PR discordance consistently being the highest. Loss of ER and PR receptors was observed more frequently than gain, while the opposite trend was noted for HER2. Loss of ER and PR was associated with a worse prognosis. Discordance was also observed in cases of tumor metastasis.

Discordance in receptor expression between primary and recurrent breast cancer was common, highlighting the importance of re-biopsy in recurrent or metastatic breast cancer, if possible. Patients who lost hormone receptors experienced worse outcomes, suggesting the development of treatment-resistant tumor clones.

Autoimmune hepatitis (AIH) is a chronic, progressive inflammatory liver disease characterized by autoimmune-mediated hepatic injury. Currently, glucocorticoid drugs, primarily prednisone, with or without azathioprine, are commonly recommended as first-line therapeutic agents in treatment guidelines by many scientific associations. However, the primary objective of treatment is to achieve a complete biochemical response, which is defined as the normalization of both transaminases and immunoglobulin G levels within six to twelve months. Ideally, this should also be accompanied by histological remission. Nevertheless, corticosteroid therapy is associated with significant adverse effects, potentially resulting in treatment discontinuation. In this context, it has become evident that standard treatment is inadequate for a proportion of patients, leading to the emergence of other treatment options and lines. Novel immunomodulatory agents, a class of drugs that regulate the body’s immune functions, have been confirmed to possess properties that modulate immune balance and induce immune tolerance. In recent years, these agents have played an increasingly significant role in the clinical management of AIH. This article provided an in-depth review of recent advancements in the development of novel immunomodulators, including immune cell nucleic acid inhibitors, calmodulin phosphate inhibitors, mammalian target of rapamycin inhibitors, tumor necrosis factor-α inhibitors, interleukin-2, anti-CD20 monoclonal antibodies, and B cell-activating factor inhibitors, for the treatment of AIH.

The spatial heterogeneity of tumors has long been a subject of significant interest in oncology. Recent research has revealed that tumors and their microenvironments undergo dynamic changes over time, particularly in the form of periodic circadian rhythms. Disruptions to these rhythms have been recognized as a pivotal factor in the advancement of tumorigenesis. Such disruptions not only induce dysregulation of gene expression within tumor cells, influencing tumor growth, metabolism, the cell cycle, and vascular homeostasis but also facilitate metastasis. Furthermore, they mediate the remodeling of the tumor immune microenvironment, fostering the development of an immunosuppressive milieu. Additionally, the in vivo metabolism and therapeutic responsiveness of tumor treatments—including chemotherapy, targeted therapy, and immunotherapy—have been shown to be modulated by circadian rhythms. This suggests that time-specific drug administration may enhance treatment efficacy, offering novel insights for precision cancer therapy. In this review, we systematically update contemporary research on the impact of circadian rhythms on tumor biology, encompassing both tumor progression and the efficacy of drug therapies. Building upon these insights, we explore the potential for a synergistic approach that integrates the targeting of rhythmic genes with current tumor treatment modalities. We also discuss the feasibility of tailoring tumor therapy to the rhythmic alterations that define in vivo metabolism and the efficacy of specific therapeutic agents, highlighting the significance of rhythm-based strategies in the personalized treatment of tumors and the prevention of associated diseases.