T lymphocytes play a pivotal role in resolving hepatitis B virus infection. This study aimed to investigate the dynamics of peripheral blood T lymphocyte subsets during peginterferon alpha (peg-IFN-α) therapy and their association with hepatitis B surface antigen (HBsAg) clearance in inactive HBsAg carriers (IHCs).

This prospective observational study enrolled 197 IHCs treated with peg-IFNα-2a/2b for 48 weeks and followed for 24 weeks (treatment group), and 221 IHCs who were regularly monitored for 72 weeks without treatment (IHC control group). Peripheral blood T lymphocyte subsets were evaluated using flow cytometry at baseline, and at 12, 24, 48, and 72 weeks in both groups. At 72 weeks, IHCs in the treatment group were categorized into an HBsAg clearance group and an HBsAg persistence group. Differences in T lymphocyte subsets among these groups were compared, and correlations between T lymphocyte subsets and HBsAg clearance were analyzed.

At 72 weeks, intention-to-treat analysis showed significantly higher HBsAg clearance (46.7%) and seroconversion rates (34.5%) in the treatment group compared to the IHC control group (HBsAg clearance rate of 1.4%, seroconversion rate of 0.9%; both p < 0.001). The median absolute counts of CD3+, CD4+, and CD8+ cells significantly decreased at 12, 24, and 48 weeks in both the HBsAg clearance and persistence groups, returning to baseline at 72 weeks (all p < 0.001). IHCs with HBsAg clearance had higher median percentages of CD3+ CD8+ cells and lower median percentages of CD3+ CD4+ cells and CD4+/CD8+ ratios at 12, 24, and 48 weeks compared to the HBsAg persistence and IHC control groups (all p < 0.001). Baseline HBsAg levels (below 2.0 log10 IU/mL) and hepatitis B virus DNA levels (below 20 IU/mL), alanine aminotransferase elevation at 12 weeks (greater than 2×upper limit of normal), and CD4+/CD8+ ratios (less than 1.5 at 12 weeks and below 1.4 at 24 weeks) were predictive of HBsAg clearance.

Peripheral blood CD4+/CD8+ ratios at 12 and 24 weeks may serve as predictive markers for HBsAg clearance in IHCs treated with peg-IFN-α.

Artificial intelligence (AI) is profoundly transforming the paradigm of solid tumor drug development. By integrating multi-omics data, spatial transcriptomics, and advanced computational models, AI has significantly accelerated the discovery and validation of new targets, compressing the traditional ten-year research and development cycle to two to three years. Generative AI platforms have optimized small molecule inhibitors, biologics, and messenger RNA vaccines, achieving breakthroughs in overcoming tumor heterogeneity, improving efficacy, and predicting drug resistance. However, clinical translation still faces challenges such as data bias, algorithm transparency, and the validation gap between models and real-world human experience. This review aims to systematically elaborate on the transformative role of AI in solid tumor drug development and to promote interdisciplinary cooperation as well as the construction of ethical frameworks to enable the full realization of precision oncology.

Escalating antimicrobial resistance is a global threat, emphasizing the need to explore alternative treatment options. Hence, we aimed to explore the in-vitro activity of ceftazidime-avibactam (CAZ-AVI) in clinical isolates of carbapenem-resistant gram-negative bacteria.

This was an observational, cross-sectional study conducted at the Microbiology Department of Indus Hospital, Karachi, Pakistan, from January 2023 to October 2024. Carbapenem-resistant gram-negative rods isolated from clinical specimens received from the outpatient, emergency, and inpatient departments were included. Consecutive, non-probability sampling was employed for the collection of isolates. Identification of the organisms was confirmed using API® ID strips, and antimicrobial susceptibility for carbapenems and CAZ-AVI was determined via the Kirby-Bauer disc diffusion method.

A total of 158 bacterial isolates were characterized as carbapenem-resistant. Of these, 92 (58%) were Enterobacterales, and 66 (42%) were Pseudomonas aeruginosa. CAZ-AVI was susceptible in 17 (11%) of the isolates, of which four (24%) were Klebsiella spp. and Escherichia coli each, and nine (52%) were P. aeruginosa. CAZ-AVI-susceptible strains were predominant among patients aged 26–50 years (n = 6; 35%), most of whom were females (n = 10; 59%) and inpatients (n = 8; 47%). Clinical samples from patients with urinary tract infections grew the most CAZ-AVI-susceptible strains (n = 9; 53%).

Our study demonstrated low CAZ-AVI susceptibility in our carbapenem-resistant gram-negative bacterial strains. Understanding regional antimicrobial patterns in multidrug-resistant bacteria is crucial for the effective use of CAZ-AVI, along with the strict implementation of strategies for controlling antimicrobial resistance.

Pituitary tumors are common intracranial neoplasms that can cause significant morbidity due to hormonal dysregulation and compression of surrounding structures. Despite advancements in surgical techniques, challenges persist in treating large, invasive, or recurrent tumors, where complete resection is often difficult. The molecular and genetic mechanisms underlying pituitary tumorigenesis are not yet fully understood, limiting the development of targeted therapies. This review provides a comprehensive overview of recent advancements in neuroendoscopic treatment of pituitary tumors, with a focus on pathogenesis, technological innovations, clinical outcomes, and future directions. We highlight the potential of neuroendoscopic surgery to improve patient outcomes while addressing persistent challenges, such as the steep learning curve and limitations in instrument maneuverability. Future research should prioritize enhancing instrument design, developing 3D and augmented reality visualization systems, and improving training programs to further advance neuroendoscopic techniques.

Cholesterol synthesis and gallstone formation are promoted by trimethylamine-N-oxide (TMAO), a derivative of trimethylamine, which is a metabolite of gut microbiota. However, the underlying mechanisms of TMAO-induced lithogenesis remain incompletely understood. This study aimed to explore the specific molecular mechanisms through which TMAO promotes gallstone formation.

Enzyme-linked immunosorbent assays were used to compare serum concentrations of TMAO, apolipoprotein A4 (APOA4), and proprotein convertase subtilisin/kexin type 9 (PCSK9) between patients with cholelithiasis and normal controls. A murine model of TMAO-induced cholelithiasis was employed, incorporating assays of gallstone weight and bile cholesterol content, along with RNA sequencing of murine hepatic tissue. A TMAO-induced AML12 hepatocyte line was constructed and transfected with targeted small interfering RNAs and overexpression plasmids. In vivo and in vitro experiments were performed to determine the expression and regulation of genes related to cholesterol metabolism.

Serum TMAO and PCSK9 levels were elevated, whereas APOA4 levels were reduced in patients with cholelithiasis. Furthermore, our murine model demonstrated that TMAO upregulated hepatic expression of PCSK9, 3-hydroxy-3-methylglutaryl-CoA reductase, and ATP-binding cassette sub-family G member 5/8, while reducing APOA4 expression, thereby modulating cholesterol metabolism and promoting lithogenesis. PCSK9 and APOA4 were identified as key regulatory genes in the cholesterol metabolic pathway. PCSK9 knockdown increased APOA4 expression, while APOA4 overexpression led to reduced PCSK9 expression.

TMAO upregulated hepatic PCSK9 expression and reduced APOA4 expression, initiating a feedback loop that dysregulated cholesterol metabolism and promoted lithogenesis.

Endometrial cancer (EC) is one of the most prevalent malignancies of the female reproductive system and ranks among the three primary types of gynecological cancers. Recent trends indicate a rising incidence of EC in younger patients, highlighting the urgent need for effective early screening strategies. This review examines the challenges associated with early diagnosis and screening, including ambiguous methodologies (e.g., transvaginal ultrasound: sensitivity 80–90%, specificity 60–70%), undefined target populations, and the absence of efficient, cost-effective, minimally invasive solutions (e.g., cytology sensitivity ≤50% in community settings). The article provides an overview of the current landscape and emerging innovations in universal EC screening, highlighting advancements in early detection and diagnosis, such as DNA methylation panels (sensitivity 89–94%, specificity 91–97% in phase II trials) and vibrational spectroscopy (sensitivity 92%, specificity 88% in pilot studies). Additionally, future directions for implementing effective screening strategies are explored, emphasizing the potential of high-accuracy biomarkers and scalable technologies to reduce mortality and healthcare costs.

Traditional Chinese medicine (TCM) is widely used in cancer care in China as an integral part of treatment. This study aimed to understand the motivations of cancer patients in China for adopting TCM in their treatment and to examine their communication with oncologists. Gaining insights into these factors can enhance culturally sensitive, patient-centered oncology care.

A consecutive sample of 287 outpatients with cancer was recruited. Sociodemographic and clinical data, TCM usage, primary reasons for adopting TCM, and communication about TCM with oncologists were collected. Descriptive statistics, binary logistic regression, and thematic analysis were used to analyze the data.

Patients’ primary reasons for choosing TCM fell into five main categories: (1) belief in the benefits of TCM itself, (2) recommendations from others (family, friends, or oncologists), (3) belief in the benefits of combining TCM with Western medicine (WM), (4) previous positive experiences with TCM, and (5) dissatisfaction with or intolerance to WM. Among the 103 patients who consulted external TCM providers, 65% disclosed this to their oncologists. A longer time since diagnosis was associated with a higher likelihood of disclosure, while employed patients were less likely to inform their oncologists. Oncologists’ responses varied, with 55% neither approving nor disapproving of external TCM prescriptions.

The primary reasons for TCM use were perceived benefits and recommendations from oncologists and family members. However, communication about TCM with oncologists remains inconsistent. Enhancing patient-provider communication through education and fostering the integration of TCM and WM can improve holistic cancer care.

Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) deletions are frequently identified in patients with biliary tract cancer; however, standard treatment options for this genetic alteration are lacking. Here, we present the case of a 64-year-old woman diagnosed with intrahepatic cholangiocarcinoma and hilar lymph node metastasis who underwent radical surgery. Postoperative pathology confirmed moderately differentiated adenocarcinoma. The tumor recurred during the second cycle of adjuvant chemotherapy following surgery, and the metastatic sites included the cranial region, right lung, and right adrenal gland. Genetic analysis revealed a CDKN2A/2B deletion, indicating palbociclib sensitivity. Subsequently, the patient received palbociclib plus lenvatinib as systemic therapy, along with stereotactic radiotherapy for the intracranial lesion. Notably, the right pulmonary metastasis significantly regressed after 12 months of treatment, with the complete disappearance of the intracranial tumor. However, the disease progressed at 32.2 months, with significant enlargement of the right adrenal gland metastasis and new metastasis in the right lung. The progression-free survival and overall survival were 32.2 months and 34.4 months, respectively. In conclusion, our case demonstrates that palbociclib plus lenvatinib is a promising chemotherapy-free second-line treatment for intrahepatic cholangiocarcinoma with a CDKN2A/2B deletion.

Acetaminophen (APAP) is one of the most commonly used analgesic and antipyretic medications and is generally considered safe at therapeutic doses. However, overdose remains a leading cause of acute liver failure, primarily characterized by centrilobular (zone 3) hepatic necrosis, oxidative stress, mitochondrial dysfunction, and sterile inflammation. The hepatotoxic effects of APAP are localized to the centrilobular region, where cytochrome P450 2E1 is highly expressed. Cytochrome P450 2E1 catalyzes the conversion of APAP to a toxic metabolite, N-acetyl-p-benzoquinone imine. During overdose, the liver’s detoxification capacity is overwhelmed and excess N-acetyl-p-benzoquinone imine binds to cellular proteins, initiating oxidative stress and mitochondrial injury that culminate in hepatocyte death. A central component of APAP-induced hepatotoxicity is the activation of innate immune responses, particularly via inflammasome pathways. Inflammasomes are cytosolic multiprotein complexes that detect cellular damage and trigger inflammation. Among these, the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome plays a significant role in APAP-induced liver injury. Upon activation, the NLRP3 inflammasome promotes autocatalytic cleavage of procaspase-1 into its active form, caspase-1, which subsequently processes the pro-inflammatory cytokines pro-interleukin-1β and pro-interleukin-18 into their mature forms. These cytokines recruit additional immune cells and amplify liver inflammation, exacerbating tissue injury. Thus, the NLRP3 inflammasome serves as a key mechanistic link between the initial toxic insult and the ensuing inflammatory response in APAP hepatotoxicity. This review aimed to explore the molecular mechanisms underlying APAP-induced liver injury, particularly inflammasome activation, and evaluate the current and emerging therapeutic strategies.

Mitochondria are highly dynamic organelles that adapt to cellular stress and metabolic demands through processes such as fission, fusion, mitophagy, and transport, all of which are vital for maintaining cellular signaling and metabolic homeostasis. Fission facilitates mitochondrial division and biogenesis, while fusion enhances mitochondrial fitness and metabolic flexibility by mitigating damage. Together, these processes play a critical role in regulating cellular stress responses and apoptosis. Dysregulation of mitochondrial dynamics has been linked to impaired development and cancer progression, including breast cancer metastasis. A comprehensive understanding of mitochondrial dynamics in breast cancer progression is essential for advancing precision medicine. This review delves into the intricate molecular mechanisms governing mitochondrial biogenesis, fission, fusion, and mitophagy, with a particular focus on the role of mitophagy in maintaining mitochondrial homeostasis and its connection to metastasis progression. Furthermore, it discusses potential therapeutic strategies targeting mitochondrial dynamics and highlights the critical steps necessary to translate these approaches into clinical trials.