Incomplete immune reconstitution is characterized by chronic immune activation and systemic inflammation, which are not fully reversed by antiretroviral therapy. Dihydroartemisinin (DHA) has demonstrated anti-inflammatory and immunosuppressive properties, which may benefit individuals with incomplete immune reconstitution. This study aimed to investigate the biological mechanisms underlying incomplete immune reconstitution and evaluate the therapeutic potential of DHA in modulating immune activation in immunological non-responders (INRs). This study aimed to investigate the biological mechanisms underlying incomplete immune reconstitution and evaluate the therapeutic potential of DHA in modulating immune activation in immunological non-responders (INRs).

RNA sequencing data (GSE106792) was retrieved from the Gene Expression Omnibus database. R software and Bioconductor packages were used to identify differentially expressed genes (DEGs) among INRs, immune responders (IRs), and healthy controls (HCs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, along with protein-protein interaction (PPI) network construction, were performed. Potential DHA-binding proteins were predicted using the STITCH server and molecular docking studies. Validation experiments were conducted on peripheral blood mononuclear cells from 18 INRs. Cells were treated with varying concentrations of DHA, and CD4+ and CD8+ T cell activation markers (CD38 and HLA-DR) were measured via flow cytometry.

Enrichment and PPI network analysis identified 119, 56, and 189 DEGs in the INR vs. HC, INR vs. IR, and IR vs. HC comparisons, respectively. Enrichment and PPI analyses showed that DEGs were mainly involved in immune response pathways. DHA was predicted to interact with multiple target proteins, indicating anti-inflammatory effects. In vitro, DHA significantly reduced the frequency of CD38− HLA-DR+ CD4+ T cells and CD38+ HLA-DR+ CD8+ T cells at 1,000 µM and 500 µM compared to the control.

This study provides insights into the biological mechanisms underlying incomplete immune reconstitution and supports DHA’s potential as a therapeutic agent. DHA effectively inhibits T cell activation in INRs, presenting a novel and promising treatment strategy.

Breast cancer is one of the leading causes of mortality among women worldwide. Tumor necrosis factor α-induced protein 3-interacting protein 1 (TNIP1) is a ubiquitin-binding protein that is widely expressed, but its function in breast cancer cells remains unknown. This study aimed to elucidate the molecular mechanism of TNIP1 regulation in the proliferation and apoptosis of breast cancer cells.

A colony formation assay was conducted on MCF-7 and T47D cells stably transfected with TNIP1/cyclin G1 (CCNG1) short hairpin RNAs. Quantitative polymerase chain reaction was performed to assess the relative abundances of TNIP1, CCNG1, and cyclin D1 (CCND1) messenger RNAs. Immunoprecipitation and immunoblotting were used to detect the expression of TNIP1, CCNG1, CCND1, and related proteins. A dual-luciferase reporter assay was employed to explore the molecular mechanism of TNIP1 in signal transduction. Caspase activity in MCF-7 and T47D cells transfected with TNIP1 short hairpin RNAs was measured using the Caspase-Glo 3/7 assay.

Ablation of TNIP1 induced growth arrest in breast cancer cells. TNIP1 directly interacted with CCNG1, and TNIP1 knockdown increased the ubiquitination of CCNG1. CCNG1 knockdown also induced growth arrest in MCF-7 and T47D cells. Furthermore, TNIP1 knockdown activated the NF-κB pathway and induced apoptosis in these cells.

TNIP1 regulates the proliferation and apoptosis of breast cancer cells, suggesting that TNIP1 may serve as a potential biomarker for breast cancer.

Liquid biopsy (LB) represents a promising strategy for the early diagnosis and treatment of lung cancer. However, relying solely on single-biomarker immunohistochemistry for predictive purposes has shown limited efficacy, often leading to suboptimal responses in certain patients. LB provides a complementary or alternative approach to immunohistochemistry by aiding in the identification of patients better suited for immunotherapy, thereby improving treatment precision. This review highlights key LB targets, including circulating tumor cells, exosomes, and small protein molecules, and explores the predictive and prognostic value of LB in immunotherapy for lung cancer and other tumors. These biomarkers play complex and multifaceted roles in liquid biopsies. Consequently, researchers have developed numerous targeted detection methods to study and identify key factors among multiple biomarkers in lung cancer and other tumor diseases. In addition, the limitations and future directions of LB are examined, aiming to advance its clinical application and support the development of personalized and precise immunotherapy. The integration of LB with artificial intelligence holds significant clinical potential for guiding immunotherapy and advancing precision medicine in lung cancer and other tumors.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by distinct histological subtypes and a poor prognosis. Among these, the micropapillary pattern, typically observed focally, has been associated with worse outcomes in various cancers. This study aimed to evaluate the prognostic significance of the micropapillary pattern in PDAC, focusing on its percentage within the tumor and its impact on overall survival.

A retrospective analysis was conducted on 71 patients with surgically resected PDAC. Micropapillary patterns were categorized based on their percentage within the tumor (≥20%) and compared to non-micropapillary cases. Demographic, clinical, and histological data, including tumor nodule metastasis stage, tumor grade, peripancreatic fat tissue invasion, and resection margin status, were analyzed. Survival data were assessed using Kaplan-Meier and Cox proportional hazards models. A p-value < 0.05 was considered statistically significant.

The cohort included 28 female and 43 male patients, with a mean age of 63.25 years. Of the 71 cases, 23.9% (n = 17) exhibited a micropapillary pattern. The median overall survival for the micropapillary group was eight months, compared to 18 months for the non-micropapillary group (p = 0.017). Multivariate analysis revealed that the micropapillary group had an increased risk of mortality (hazard ratio = 1.892, p = 0.042), independent of tumor nodule metastasis stage.

Our findings indicate that the micropapillary pattern, even when present in as little as 20% of the tumor, serves as an independent prognostic factor for decreased survival in PDAC. Incorporating the percentage of the micropapillary pattern into pathology reports could provide valuable insights into the tumor’s biological behavior, potentially enhancing patient management strategies.

Gastrointestinal endoscopy has revolutionized the entire practice of gastroenterology worldwide, including Nigeria. Endoscopy was introduced in Nigeria more than four decades ago, and it has been a story of varying successes and challenges. This study explored the various experiences of endoscopists, the challenges they face, and the efforts put in place to maintain the practice in Nigeria.

This cross-sectional survey was conducted from October to December 2023 among endoscopists practicing in Nigeria. It involved a 30-part self-administered online questionnaire that inquired about individual experiences in endoscopy practice. These included qualifications, competency, facility settings, challenges faced, and innovations employed to address them. At the end of the survey, responses were analyzed using descriptive statistics, Chi-square, and likelihood ratios at the 0.05 level of significance.

A total of 41 respondents participated in the survey from 19 states across the six geopolitical zones of Nigeria, with a mean age ± standard deviation of 43 ± 7 years. Male respondents made up 80.5%, with Nigerian-trained gastroenterologists via the residency program constituting the predominant population, and an average endoscopy experience of five to nine years (39.02%). Most of the respondents work in public institutions (73.17%), with 43.9% working in at least two centers. There was an average of five endoscopists and three to seven endoscopy centers per state. Most centers perform 11–12 upper and four to five lower GI endoscopies per week, respectively, with a predominance of diagnostic procedures. The most common endoscopic intervention was variceal band ligation. The most common challenge faced was the high cost of procedures, accessories, and maintenance of endoscopes.

Endoscopy practice cuts across all the zones and most states of the federation. Both diagnostic and therapeutic procedures are available in most centers. However, the practice is faced with a myriad of challenges, mainly poor financing and inadequate training, among others. As a result, some innovations were locally developed to ease the practice and prevent it from collapsing.

Human papillomavirus (HPV) infection is the primary cause of cervical, anogenital, and oropharyngeal cancers in the United States. These cancers are preventable through HPV vaccination. Research is critically needed to identify effective strategies for promoting HPV vaccination among high-risk groups. This study develops a risk prediction model to identify patients who are unlikely to complete HPV vaccination, with the goal of using the model to direct resources and increase vaccination rates.

We assessed vaccination status along with patient, provider, and clinic characteristics that predict vaccination completion. We then developed a predictive model to assess the likelihood of completing HPV vaccination, which can be used to target interventions based on patient needs. We used a retrospective cohort from a large integrated delivery system in Oregon. Using logistic regression with data available in the electronic health record, we created a risk model to determine the likelihood of vaccination completion among patients aged 11–17 years.

In a cohort of 61,788 patients, 40,570 (65.7%) had received at least one dose of the HPV vaccine. The full model included 17 demographic, clinical, provider, and community characteristics, achieving a bootstrap-corrected C-statistic of 0.67 with adequate calibration. The reduced model, which retained five demographic and clinical characteristics (age, language, race, ethnicity, and prior vaccinations), had a bootstrap-corrected C-statistic of 0.65 and adequate calibration.

Our findings suggest that a risk prediction model can guide the implementation of targeted interventions and the intensity of those interventions based on the likelihood of vaccination completion.

Neglected tropical diseases (NTDs) encompass a range of infectious diseases prevalent in tropical and subtropical regions, often overlooked despite their substantial health impacts and high mortality rates. Current treatments for NTDs frequently cause severe side effects due to the pharmacokinetic properties of drugs, which can be harmful even at therapeutic doses. There is a pressing need for innovative diagnostic and therapeutic strategies to mitigate these side effects and improve diagnostic capabilities, as many NTDs lack adequate diagnostic tools. Nanotechnology presents a promising avenue to address these challenges. Nanomaterials possess unique characteristics that enable dual functionality in disease diagnosis and treatment. When conjugated with drugs, nanomaterials can enhance the efficacy of treatments for parasitic diseases while reducing the toxicity associated with conventional medications. Nanomaterial-drug conjugates also serve as efficient carriers, improving drug delivery systems for existing NTD treatments and minimizing adverse effects. This study explores recent advancements in conjugating nanomaterials with drugs for the treatment and diagnosis of NTDs. A comprehensive review of primary database sources reveals significant gaps in current research, underscoring the vast potential for developing novel therapeutic and diagnostic tools. These innovations could revolutionize the management of NTDs, ushering in more effective and safer treatment modalities in the future.

Chronic liver disease (CLD) is a major global health challenge, characterized by chronic inflammation that can progress to liver fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. Early identification of biomarkers is crucial for effective intervention. Traditional Chinese medicine (TCM) has shown potential in improving CLD symptoms and protecting the liver, although its mechanisms remain unclear. Metabolomics, the comprehensive study of metabolites, offers a promising approach to understanding CLD pathogenesis and identifying biomarkers. Notably, metabolomics aligns with TCM’s holistic approach and may help reveal its therapeutic mechanisms. This review summarizes key metabolites associated with CLD diagnosis and progression and discusses how TCM may modulate metabolic pathways to alleviate CLD symptoms. These insights could lead to improved diagnostic and therapeutic strategies for CLD.

This study investigates the potential of methyl eugenol (ME), a compound found in the essential oils of various plants, to inhibit oxidative stress and its impact on diseases associated with this process. ME has been shown to possess antioxidant properties and antiproliferative activity in several cancers. It also demonstrates neuroprotective potential in conditions such as Alzheimer’s disease and ischemic brain injury. The mechanism of action involves the activation of the nuclear factor erythroid 2-related factor 2, which facilitates the transcription of antioxidant genes and modulation of pathways such as AMP-activated protein kinase/glycogen synthase kinase 3 beta, thereby reducing the production of reactive oxygen species and pro-inflammatory cytokines. However, research has identified potential toxicological risks associated with ME, including hepatotoxicity and changes in the gut microbiota. These findings highlight the need for caution when considering prolonged exposure to this compound.

Hermansky-Pudlak syndrome (HPS) is a rare, autosomal recessive disorder predominantly affecting individuals of Puerto Rican descent. It is characterized by oculocutaneous albinism, platelet storage pool deficiency, and lysosomal ceroid accumulation in tissues. Lysosomal dysfunction has been shown to be associated with pulmonary fibrosis and granulomatous colitis in HPS patients, accounting for a significant portion of morbidity and mortality in this population. Clinical and endoscopic gastrointestinal manifestations in HPS patients are similar to those of active Crohn’s disease, including abdominal pain, bleeding, fissures, fistulas, and perianal involvement. Histology reveals granulomatous colitis that can be difficult to distinguish from Crohn’s disease. Identifying distinct morphologic features from Crohn’s disease is crucial for the diagnosis of HPS. Here, we present a case of a 27-year-old male with a history of HPS and refractory granulomatous colitis with severe perianal disease, who underwent total proctocolectomy and perianal excision. The unique, distinguishing morphologic features from Crohn’s disease in this case are: 1) grossly diffuse ulceration in the ano-rectum and cecum, 2) ulcerative and granulomatous inflammation predominantly involving the mucosa and submucosa of the colon, and 3) accumulation of ceroid pigment in the histiocytes of the lamina propria throughout the entire gastrointestinal tract. Immunohistochemical stains for CD3 and FoxP3-positive T cells in the granulomatous colitis were further analyzed. Thus, we fully document the extent of disease involvement and morphologic features in this patient and extensively discuss the similarities and differences between HPS and Crohn’s disease.

Wilms tumor is the most common kidney tumor in children aged 0-14 years. MicroRNAs are small, noncoding RNAs linked to the development of malignant tumors. Several studies have shown the association between single nucleotide polymorphism in miR-27a and cancer risk. This study aimed to explore the potential impact of the miR-27a rs895819 T>C polymorphism on Wilms tumor susceptibility.

The rs895819 T>C polymorphism was genotyped using the TaqMan method in 145 patients with Wilms tumors and 531 controls. Logistic regression models were used to assess the association between this polymorphism and Wilms tumor risk. A stratified analysis was also performed based on age, sex, and clinical stage.

The rs895819 T>C polymorphism showed genotypic distribution consistent with Hardy-Weinberg equilibrium (P = 0.749). The differences were not statistically significant. The miR-27a rs895819 T>C polymorphism was not significantly associated with Wilms tumor susceptibility, and the stratified analysis did not yield any significant differences.

Our study provides evidence of a lack of association between the miR-27a rs895819 T>C polymorphism and Wilms tumor susceptibility. Further validation through larger sample sizes and additional genetic polymorphisms is warranted.

Hepatic biliary adenofibroma is an exceedingly rare biliary neoplasm that primarily affects adults. It typically presents as a solitary mass composed of low-grade microcystic and tubuloglandular bile duct structures, which are lined by low columnar to cuboidal non-mucin-producing biliary epithelium and supported by abundant fibrous stroma. Histologically, it resembles the Von Meyenburg complex but is much larger in size and often shows cytologic atypia. Although considered benign, emerging case studies and analyses suggest that biliary adenofibroma may serve as a precursor lesion to intrahepatic cholangiocarcinoma. However, its extreme rarity, coupled with an incompletely understood histogenesis, perpetuates diagnostic uncertainty and may lead to misclassification with other similar entities. This review consolidates the current understanding of the histopathological and molecular characteristics of biliary adenofibroma, highlights its differential diagnosis, explores its potential progression to cholangiocarcinoma, and discusses unresolved questions while proposing future research directions.

Colorectal cancer (CRC) is the second most commonly diagnosed cancer in China. Early detection and diagnosis of CRC are essential for improving survival rates. However, socioeconomic factors such as regional disparities, economic conditions, and varying levels of awareness impact the uptake of screening programs. Recently, rapid advancements in non-invasive tests, including high-quality fecal immunochemical tests and the emergence of stool and blood biomarkers for CRC, have facilitated improvements in early detection and diagnosis. Additionally, image-enhanced endoscopy, a group of advanced imaging technologies, has been developed to assist in the early identification of colorectal lesions, including narrow band imaging and linked-color imaging. The emergence of artificial intelligence also offers promising opportunities to improve early diagnosis and treatment of CRC. This review mainly introduces screening technologies and the current status of CRC screening in China, provides an overview of CRC early detection and diagnosis, and discusses the limitations and future prospects.