Renal involvement in myeloproliferative disorders (MPNs) is rare and presents unique challenges in terms of diagnosis and treatment. The exact pathogenesis of renal dysfunction in MPNs remains unclear. Most of these patients are elderly and have comorbid conditions that contribute to their renal dysfunction. Although symptomatic patients typically present with proteinuria, hypertension, anasarca, and hematuria, many patients remain asymptomatic with incidental detection of renal impairment. Early diagnosis using renal biopsy and prompt initiation of treatment with corticosteroids, cytoreductive drugs, and targeted agents are crucial for achieving a favorable outcome. We present a series of case vignettes describing our approach and management strategies in a spectrum of MPN patients (primary myelofibrosis, essential thrombocytosis, chronic myeloid leukemia, and pre-fibrotic myelofibrosis) with biopsy proven etiologies of renal dysfunction. Although extramedullary hematopoiesis was a common finding in all our cases, we discuss the various other mechanisms by which MPN can target the kidneys. Despite the widespread use of cytoreductive and targeted therapies, such situations require an individualized approach along with multidisciplinary effort.

Bufalin(BF)has a significant anti-tumor effect, but its clinical application is severely restricted by its high toxicity and poor water solubility. In this study, Scrophularia ningpoensis polysaccharide(SNP)and ursodeoxycholic acid(UDCA) were synthesized into an SNP-UDCA conjugate. BF was encapsulated to prepare BF/SNP-UDCA nanoparticles(NPs). The amphiphilic compound SNP-UDCA was synthesized via the one-step method, and its structure was characterized by Fourier-transform infrared spectroscopy(FT-IR)and proton nuclear magnetic resonance(~1H-NMR). The preparation process of BF/SNP-UDCA NPs was optimized through single-factor investigations. The encapsulation efficiency and drug-loading capacity of BF/SNP-UDCA NPs were determined by high-performance liquid chromatography(HPLC). The molecular form of BF/SNP-UDCA NPs was characterized by using a transmission electron microscope, X-ray diffraction(XRD), and differential scanning calorimeter(DSC). Additionally, the stability of BF/SNP-UDCA NPs was evaluated. The release behavior of BF/SNP-UDCA NPs at different pH values was determined by dialysis. The in vitro anti-tumor effect of BF/SNP-UDCA NPs was evaluated by MTT cytotoxicity assay, flow cytometry for apoptosis, and cellular uptake. The in vitro liver targeting was evaluated by measuring cellular uptake by laser confocal microscopy. The results demonstrated that the SNP-UDCA conjugate was successfully synthesized through an esterification reaction between SNP and UDCA. The preparation process of BF/SNP-UDCA NPs was as follows: the feed ratio of SNP-UDCA to BF was 2∶1, the ultrasonic time was 30 minutes, and the stirring time was two hours. The prepared BF/SNP-UDCA NPs were spherical in shape, with a particle size of(252.74±6.05)nm, an encapsulation efficiency of 65.00%±2.51%, and a drug-loading capacity of 6.80%±0.44%. The XRD and DSC results indicated that BF was encapsulated within the NPs and existed in a molecular or amorphous state. The short-term stability of BF/SNP-UDCA NPs and stability in DMEM medium are good, and their in vitro release behavior followed the first-order equation and was pH-dependent according to the in vitro experiment. Compared with BF, BF/SNP-UDCA NPs at the same concentration showed significantly stronger cytotoxicity and apoptotic effects on HepG2 cells(P<0.05, P<0.01). The uptake of coumarin 6(C6)/SNP-UDCA NPs in HepG2 cells was time-dependent and higher than that in HeLa cells at the same concentration of C6/SNP-UDCA NPs. Moreover, after treatment with SNP, the uptake of C6/SNP-UDCA NPs in HepG2 cells decreased. In conclusion, the preparation process of BF/SNP-UDCA NPs was simple and feasible. BF/SNP-UDCA NPs could enhance the targeting ability and inhibitory effect of BF on liver cancer cells. This study will provide a foundation for liver-targeting nanoformulations of BF.

Prostate cancer(PCa) is a common malignant tumor among elderly men, with high incidence and mortality rates worldwide, posing a serious threat to human health. Traditional treatments face limitations, highlighting the urgent need for novel therapeutic strategies. Recent studies on the regulatory mechanisms of micro ribonucleic acid(microRNA, miRNA) in tumor development has identified miRNA as new targets for PCa diagnosis and treatment. Traditional Chinese medicine(TCM), with its multi-mechanism, multi-target, and multi-pathway regulatory properties, shows promising potential in miRNA-based PCa therapy. This review summarized recent findings on miRNA' roles in PCa and research progress of TCM intervention and found that a variety of miRNA played important regulatory roles in cell differentiation, proliferation, apoptosis, invasion, metastasis, immune microenvironment, and drug resistance, and their potential as biomarkers for PCa diagnosis, prognosis, and therapy, indicating the potential to be a biomarker for the diagnosis, prognosis evaluation, and treatment of PCa. The review concluded that the active components of TCM(terpenoids, flavonoids, alkaloids, and others) and compounds(Yishen Tonglong Decoction, Shenhu Decoction, Zhoushi Qiling Decoction, Fuzheng Yiliu Decoction, and Qilan Formula) could regulate the expression of their downstream target genes by acting on specific miRNA and affect the above biological behaviors of PCa cells, thus playing a role in the treatment of PCa. This review aims to provide a theoretical basis for miRNA as potential biomarkers and therapeutic targets for PCa and suggest new avenues for further development of targeted therapy strategies against miRNA.

Colorectal cancer(CRC) is one of the most common malignant tumors worldwide, primarily originating from recurrent inflammatory bowel disease(IBD). Therefore, blocking the inflammation-cancer transformation in the colon has become a focus in the early prevention and treatment of CRC. The inflammation-cancer transformation in the colon involves multiple types of cells and complex pathological processes, including inflammatory responses and tumorigenesis. In this complex pathological process, immune cells(including non-specific and specific immune cells) and non-immune cells(such as tumor cells and fibroblasts) interact with each other, collectively promoting the progression of the disease. In traditional Chinese medicine(TCM), inflammation-cancer transformation in the colon belongs to the categories of dysentery and diarrhea, with the main pathogenesis being cold and heat in complexity. This paper first elaborates on the complex molecular mechanisms involved in the inflammation-cancer transformation process in the colon from the perspectives of inflammation, cancer, and their mutual influences. Subsequently, by comparing the pathogenic characteristics and clinical manifestations between inflammation-cancer transformation and the TCM pathogenesis of cold and heat in complexity, this paper explores the intrinsic connections between the two. Furthermore, based on the correlation between inflammation-cancer transformation in the colon and the TCM pathogenesis, this paper delves into the importance of the interaction between inflammation and cancer. Finally, it summarizes and discusses the clinical and basic research progress in the TCM intervention in the inflammation-cancer transformation process, providing a theoretical basis and treatment strategy for the treatment of CRC with integrated traditional Chinese and Western medicine.

The tumor microenvironment is a crucial factor in tumor occurrence and progression. The hypoxic microenvironment is widely present in tumor tissue and is a key endogenous factor accelerating tumor deterioration. The "blood stasis toxin" theory, as an emerging perspective in tumor research, is regarded as the unique "soil" in tumor progression from the perspective of traditional Chinese medicine(TCM) due to its dynamic evolution mechanism, which closely resembles the formation of the hypoxic microenvironment. Scientifically integrating TCM theories with the biological characteristics of tumors and exploring precise syndrome differentiation and treatment strategies are key to achieving comprehensive tumor prevention and control. This article focused on the hypoxic microenvironment of the tumor, elucidating its formation mechanisms and evolutionary processes and carefully analyzing the internal relationship between the "blood stasis toxin" theory and the hypoxic microenvironment. Additionally, it explored the interaction among blood stasis, toxic pathogens, and hypoxic environment and proposed micro-level prevention and treatment strategies targeting the hypoxic microenvironment based on the "blood stasis toxin" theory, aiming to provide TCM-based theoretical support and therapeutic approaches for precise regulation of the hypoxic microenvironment.

Cancer is one of the biggest causes of death in today's world. In the field of cancer treatment, the use of natural compounds has attracted the attention of researchers. A variety of nanoparticles, including zinc oxide nanoparticles, represent a widely utilized therapeutic approach today due to their exceptional biocompatibility and safety profile. In this study, ellagic acid, which is a natural polyphenolic compound, was used together with synthesized zinc oxide nanoparticles. The loading of ellagic acid in zinc oxide nanoparticles was confirmed by FT-IR and XRD methods. Examination of the viability of A549 cancer cells showed that the cytotoxicity of nano drug Ellagic acid-Zno nanoparticle (EAN) is more than that of ellagic acid alone. The percentage of reactive oxygen species (ROS) produced by EAN was higher than that of ellagic acid. Apoptosis was observed in the treated cells by acridine-orange-ethidium-bromide staining. Investigating the cell migration of EAN caused a decrease in cell migration. Based on the research, suggested that EAN can be used as multifunctional nanomedicine nanoparticles.

Coumestans are natural phytoestrogens with strong therapeutic potential for inhibiting hormone-induced cancers, such as breast, ovarian, and prostate malignancies. They regulate many signaling pathways, including the PI3K/AKT, MAPK, NF-κB, and JAK/STAT pathways. Challenges regarding the clinical application of coumestans include their poor bioavailability and distribution, rapid metabolic rate, low water solubility, and formulation. This review aims to provide a comprehensive overview of the anticancer mechanisms of a few important coumestan derivatives, namely coumestrol, wedelolactone, isofraxidin, and psoralidin. Methods for increasing the coumestan efficacy via synthetic biology, bioinformatics, and artificial intelligence are described in this review. To bridge the gap between bench to bedside, future directions should focus on emphasizing clinical validation and developing targeted delivery systems to understand the therapeutic potential of coumestans.

Hepatitis B virus (HBV), a lethal virus that results in the loss of two lives every minute, induces chronic and acute infections. Chronic infections may result in liver cirrhosis, which in turn may lead to hepatocellular carcinoma (HCC). Our study analysed 1,06,970 protein sequences of HBV genotypes (Gen A to H) from the HBV database (HBVdb) to construct position-specific scoring matrices. A total of 5,058 mutations were detected across all proteins, reflecting the notorious mutability of HBV. Among these, 2,658 significant mutations (sigmuts) with frequencies ranging between 10 and 80 were screened. Gen A presented the greatest number of sigmuts, whereas Gen H presented the least. Gen C, the most common HBV gene, featured 417 sigmuts, which we used for structural studies using DynaMut2 and molecular docking. We found that most core protein signatures significantly impact functions, including B-cell receptor binding and dimerisation. Interestingly, most sigmuts of the RNase H domain (694-843) of polymerase proteins promoted structural disorder, with possible impact on interactions with LINE-1 elements and progression to hepatocellular carcinoma. Intriguingly, despite the use of prominent nucleoside reverse transcriptase inhibitors (NRTIs) for over two decades, the drug-binding pockets of polymerase proteins have been found to be highly conserved. Nevertheless, since the long-term use of a few drugs as monotherapies has resulted in the development of drug resistance in recent years, we propose novel HBV targets for alternative therapeutic interventions.

BACKGROUND Disseminated peritoneal leiomyomatosis (DPL), or leiomyomatosis peritoneal disseminata, is a benign condition that presents with multiple lower abdominal peritoneal nodules consisting of smooth muscle cells, which can slowly increase in size. The risk of malignant transformation is 2% to 5%. The mechanisms underlying the pathogenesis and malignancy of DPL are unclear and can be associated with a variety of factors. This report describes a 59-year-old woman presenting with multiple abdominal masses and a diagnosis of DPL. CASE REPORT This report describes a 59-year-old female patient who experienced abdominal pain and difficulty defecating. Proctoscopy showed intestinal stenosis and inflammatory changes. She may have had renal dysfunction. The medical history showed that the patient had uterine fibroids in the past and had undergone hysterectomy surgery. We cannot confirm whether the patient received hormone therapy before admission. Based on the results of histopathology and immunohistochemistry, it was considered to be a DPL. The patient died 6 months after surgery. CONCLUSIONS DPL is a rare disease that is difficult to diagnose and traditionally considered a benign condition. This report emphasizes the importance of understanding the presentation and distribution of DPL, as it can mimic the deposition of malignant tumors. This case also emphasizes the importance of diagnosing benign tumors through histopathology. The mechanism of malignant transformation of DPL is currently unclear, and it is of great significance to combine multiple detection methods in clinical practice to determine its malignancy.

Polycystic liver disease (PLD) is a hereditary disorder characterized by the formation of fluid-filled cysts derived from cholangiocytes, leading to progressive disease and a significant reduction in patients' quality of life. Current treatments for PLD are inadequate, emphasizing the need for novel therapeutic strategies. The role of epigenetic regulation in PLD progression, particularly chromatin accessibility and histone modifications, remains underexplored. Traditional epigenetic profiling techniques, such as ChIP-seq and DNase-seq, require large numbers of cells, which are difficult to obtain from primary cholangiocytes. To address this, we optimized low-input ChIP-seq and ATAC-seq protocols for low numbers of primary cholangiocytes. These approaches allow for the analysis of histone modifications and chromatin accessibility with minimal cell input. Low-input ChIP-seq utilizes micrococcal nuclease (MNase) for DNA fragmentation, while ATAC-seq employs Tn5 transposase to capture open chromatin regions. These multi-omics techniques provide valuable insights into chromatin state dynamics during cholangiocyte fate transitions in PLD and other biliary diseases. Importantly, the optimized protocols are confidently applicable to other low-input primary cells, enabling the exploration of epigenetic mechanisms across various cellular contexts. This work presents a systematic approach for studying chromatin state alterations, contributing to the development of epigenetic-based therapeutic strategies for PLD and related diseases.