Cortisol, the body’s primary glucocorticoid, is central to maintaining homeostasis through its regulation of metabolism, immunity, cardiovascular tone, and neurobehavioral functions. However, chronic dysregulation of the hypothalamic–pituitary–adrenal axis, whether from persistent psychological stress, lifestyle imbalance, or circadian disruption, contributes to diverse metabolic, psychiatric, and inflammatory disorders. This comprehensive review aims to explore cortisol physiology, mechanisms of dysregulation, and emerging strategies for restoring hormonal balance through integrative management. Conventional approaches such as pharmacotherapy and surgical interventions remain essential for severe endocrine disorders like Cushing’s syndrome and Addison’s disease; however, they inadequately address chronic, stress-related dysfunction. Nutritional modulation, sleep optimization, moderate physical activity, and mind-body therapies, including yoga, meditation, and mindfulness-based stress reduction, demonstrate measurable reductions in cortisol and inflammatory cytokines. Adaptogenic botanicals such as Withania somnifera, Ocimum tenuiflorum, Rhodiola rosea, and Panax ginseng exhibit robust evidence for normalizing cortisol and enhancing resilience through hypothalamic–pituitary–adrenal axis modulation. Complementary modalities such as acupuncture, naturopathy, and homeopathy show potential in improving autonomic and neuroendocrine balance. By synthesizing biomedical, nutritional, psychological, and traditional perspectives, this review proposes an integrated model of cortisol management that harmonizes physiology and behavior. Such multidimensional frameworks offer promising, evidence-based pathways for mitigating stress-related diseases and promoting holistic well-being.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become one of the leading causes of chronic liver diseases in China, imposing a substantial and growing burden on the healthcare system. Considering the large number of individuals affected by MAFLD and the gap in disease management capacity at the primary care level, standardized guidance tailored to primary healthcare settings is urgently needed. In response, the Chronic Disease Management Branch of the China Medical Biotechnology Association convened a multidisciplinary working group incorporating hepatologists, general practitioners, and other specialists to initiate the first China national Guidelines for Diagnosis and Management of Metabolic Dysfunction-associated Fatty Liver Disease in Primary Care (2025). These guidelines provide recommendations and suggestions covering screening, risk assessment, diagnosis, treatment, referral pathways, and follow-up tailored for primary care institutions, thereby improving the long-term outcomes for the population with MAFLD and comprehensively strengthening the role of primary healthcare in chronic liver disease management.

Congenital portosystemic shunts (CPSS) are rare vascular anomalies characterized by abnormal communication between the portal and systemic venous systems, resulting in partial or complete diversion of portal blood away from the liver. These shunts can give rise to a broad spectrum of clinical manifestations, including hyperammonemia (with or without encephalopathy), hepatopulmonary syndrome, and portopulmonary hypertension. Notably, these complications often occur in the absence of portal hypertension. Advances in diagnostic imaging, particularly Doppler ultrasound, computed tomographic angiography, and magnetic resonance imaging, have enhanced the early detection and classification of CPSS. Treatment approaches vary depending on shunt type and clinical severity and may include interventional closure via embolization or surgical ligation. Most persistent or symptomatic shunts require immediate intervention. Recent studies have also identified potential genetic and embryological mechanisms contributing to CPSS development, offering new insights into their pathogenesis. This review aims to summarize current knowledge on the epidemiology, pathophysiology, clinical presentation, diagnostic evaluation, and management of CPSS, and to highlight their consideration in patients with hepatic encephalopathy or unexplained liver disease.

Dubin-Johnson syndrome (DJS) and Rotor syndrome (RS) are rare, autosomal recessive disorders that result in chronic, predominantly conjugated hyperbilirubinemia without cholestasis or hepatocellular injury. Although both conditions are benign and non-progressive, they reflect distinct molecular defects in hepatocellular transport pathways. DJS arises from mutations in the ABCC2 gene encoding the canalicular transporter multidrug resistance–associated protein 2, leading to impaired biliary excretion of conjugated bilirubin and organic anions. In contrast, RS results from combined deficiencies of the sinusoidal transporters OATP1B1 and OATP1B3, encoded by SLCO1B1 and SLCO1B3 genes, respectively, which mediate hepatic reuptake of conjugated bilirubin from the sinusoidal blood. These defects explain the characteristic biochemical and clinical distinctions between the syndromes, including the black hepatic pigmentation and markedly elevated urinary coproporphyrin I fraction in DJS, and the absence of pigmentation with moderate coproporphyrin I predominance in RS. Recent studies have expanded the understanding of how these transporters influence not only bilirubin handling but also the hepatic disposition of various drugs and endogenous metabolites. Recognition of DJS and RS is essential to prevent misdiagnosis of cholestatic or hepatocellular disease, avoid unnecessary investigations, and anticipate altered pharmacokinetics in affected individuals. This review synthesizes current evidence from molecular, biochemical, and clinical studies to highlight how these syndromes illuminate broader principles of hepatic transporter physiology and its relevance to inherited and acquired disorders of bilirubin metabolism.

Despite rapid advances in computational biology and regulatory reforms encouraging the reduction of animal use, a clear synthesis of how artificial intelligence (AI)-driven polypharmacology can function as a scientific and ethical bridge between traditional in vivo pharmacology and human-relevant drug development remains lacking. The shift from cage-based experimentation to code-based predictive modeling presents both opportunities and unresolved challenges in biological interpretation, regulatory acceptance, and pharmacology education. Therefore, this review aims to critically examine the transition toward AI-enabled, human-centric drug discovery within the framework of the 3R principles (Replacement, Reduction, and Refinement). Specifically, it explores (i) the global regulatory and ethical drivers accelerating non-animal methodologies, (ii) the scientific and educational gaps emerging from reduced dependence on animal models, and (iii) the role of AI and deep learning in reconstructing biological complexity through multi-omics integration and predictive toxicity modeling. By analyzing emerging AI platforms and computational strategies, this review highlights how AI-driven polypharmacology may offer a scalable, ethical, and precision-oriented framework for future pharmacological research.

Primary liver cancer is one of the most common malignant tumors in China, which seriously threatens people’s lives and health. In recent years, with the advancement of basic and clinical research, the diagnosis and treatment methods for primary liver cancer have been continually enriched. Traditional Chinese medicine (TCM) has played an important role in the diagnosis and treatment of primary liver cancer, but there is no unified standard for differentiation and treatment, and efficacy evaluation. In order to further standardize the TCM diagnosis and treatment of primary liver cancer, according to the requirements of TCM standardization and related technical guidance documents, the drafting team compiled this guideline through literature research, expert interviews, questionnaire surveys, consensus meetings, etc., for reference by clinicians. This guideline is approved and issued by the China Association of Chinese Medicine, standard number: T/CACM 1575-2024.

Precision medicine represents a paradigm shift in healthcare, emphasizing individualized approaches to disease prevention, diagnosis, and treatment based on a patient’s genetic, proteomic, and immunologic profile. In the field of oncology, this paradigm has gained traction, particularly with the integration of immunotherapeutic modalities. Among the most promising advancements are therapeutic cancer vaccines, which harness the body’s immune system to fight tumors more effectively. However, clinical translation remains limited by biological, manufacturing, regulatory, and evidentiary barriers. This mini-review highlights recent developments in therapeutic vaccine engineering, discusses key barriers to clinical translation, and summarizes selected findings from contemporary human clinical studies of personalized cancer vaccines. Particular attention is also given to biomarker-guided patient selection and the investigation of therapeutic cancer vaccines in adjuvant or minimal-residual-disease settings to reduce postoperative recurrence. Current evidence is promising but remains largely early-stage and does not yet establish broad clinical benefit.

The association between chronic inflammation and cancer has reshaped our understanding of tumorigenesis and cancer therapy. Inflammatory responses can both promote and suppress cancer, depending on the context and timing. Key molecular players, such as nuclear factor kappa-light-chain-enhancer of activated B cells, interleukin-6, signal transducer and activator of transcription 3, and a variety of immune cell types, including tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, orchestrate an environment conducive to tumor survival, angiogenesis, metastasis, and immune evasion. In recent years, immunotherapy, particularly immune checkpoint inhibitors, has revolutionized cancer treatment. However, its success varies across tumor types and patients, underscoring the need to understand the tumor microenvironment and inflammatory context. This review examines the mechanistic underpinnings of inflammation-driven cancer, discusses translational research efforts targeting inflammatory pathways, and explores clinical applications, including the integration of immunotherapy with anti-inflammatory agents and biomarkers for personalized treatment. Future directions in the field include the application of artificial intelligence, microbiome research, single-cell technologies, and gene editing tools to further tailor therapies and overcome resistance mechanisms.

Bone marrow metastasis (BMM) from non-hematolymphoid malignancies with resultant cytopenia(s) can mimic primary hematolymphoid disorders. This study aimed to investigate the clinical and pathological characteristics of BMM from non-hematopoietic tumors.

We conducted a retrospective cohort study of patients diagnosed with BMM by non-hematolymphoid malignancies at our institution over the past 10 years. Demographic and clinical characteristics, histopathological findings of bone marrow, types of metastatic tumors, and prognosis were analyzed.

A total of 54 cases were included. The four most common malignancies with BMM, regardless of gender, were prostatic adenocarcinoma (29.6%), breast carcinoma (25.9%), colorectal adenocarcinoma (5.5%), and lung carcinoma (5.5%). The main clinical and laboratory manifestations were anemia (90.7%), reticulocytosis (80.5%), thrombocytopenia (73.9%), bone pain (55.5%), disseminated intravascular coagulation (39.6%), leukoerythroblastosis (35.3%), and leukopenia (24%). The vast majority (96.3%) of metastatic tumors were identified by morphology alone; however, in approximately 2.7% of cases, immunohistochemistry was required due to subtle morphologic features. In 29.6% (16/54) of patients, BMM was identified prior to or concurrently with other metastatic sites. The median time interval between the initial diagnosis of non-hematolymphoid malignancies and BMM was 29 months. Although patients who received anti-tumor treatment after BMM diagnosis demonstrated longer overall survival (P < 0.01), no significant differences were observed between those treated with immunotherapy versus chemotherapy and/or radiotherapy (P = 0.145).

Prostate and breast carcinomas are the most common malignancies associated with BMM, with anemia, reticulocytosis, and thrombocytopenia being the most frequent clinical manifestations. While our data show that receipt of anti-neoplastic treatments, regardless of regimen, was associated with improved overall survival after BMM, no significant survival differences were observed when prostate and breast carcinomas were compared with other types of BMM.

Colorectal cancer (CRC), like all other cancers, results from genetic and epigenetic alterations of the genome. The mechanisms leading to epigenetic alterations include DNA methylation, histone modifications, and small non-coding RNAs. As shown in many studies, some histone modifications such as acetylation, methylation, and phosphorylation are reported to be altered in CRC. Since these epigenetic alterations are reversible, they can be targeted as a strategy for CRC treatment. Numerous studies demonstrate the effects of molecules (both natural and synthetic) as inhibitors of enzymes responsible for histone acetylation, methylation, and phosphorylation in CRC cell lines. Some of these molecules have reached clinical trial stages. Vorinostat and belinostat, as histone deacetylase inhibitors; pinometostat and ribavirin, as histone methyltransferase inhibitors; and staurosporine and barasertib, which target histone phosphorylation, are among the promising epigenetic modifiers targeting histone alterations. Some of these modifiers can be used alone or in combination with other anticancer drugs or radiotherapy to increase efficacy. This review aims to identify molecules that target enzymes responsible for altering acetylation, methylation, and phosphorylation of histones in CRC.