This paper aims to establish a multidimensional evaluation model integrating appearance chromaticity, chemical fingerprints, and biological efficacy to scientifically quantify the processing intensity of wine-processed Angelicae Sinensis Radix and identify its processing-related quality marker(Q-marker). A colorimeter was used to digitally characterize the color evolution rule of Angelicae Sinensis Radix under different wine-processing temperatures(80, 120, and 160 ℃). High-performance liquid chromatography(HPLC) fingerprints combined with partial least squares discriminant analysis(PLS-DA) were used to analyze the variation rule of ferulic acid, phthalides, 5-hydroxymethylfurfural(5-HMF), and other components. Meanwhile, the phenol-sulfuric acid method was used to monitor the dynamic changes in polysaccharide content. A phenylhydrazine-induced zebrafish hemolytic anemia model was further introduced, and erythrocyte regeneration, heart rate, and hemodynamic parameters were taken as evaluation indices. The pharmacodynamic differences among Angelicae Sinensis Radix slices, wine-processed Angelicae Sinensis Radix decoctions, and their crude polysaccharide fractions. The suitable wine-processing condition was determined as stir-frying at 120 ℃ for 12-15 min. Under this condition, the powder of the prepared slices appeared deep yellow(L~*=69, a~*=5.5); the polysaccharide content of the prepared slices was significantly enriched compared with that of the raw material, reaching a maximum of 11.34%; an equilibrium was achieved between ferulic acid retention and 5-HMF formation. PLS-DA identified 5-HMF, ferulic acid, coniferyl ferulate, ligustilide, characteristic peak a, and other key differential markers. Pharmacodynamic evaluation of Zebrafish shows that the blood-enriching and blood-activating effects of wine-processed Angelicae Sinensis Radix were significantly stronger than those of Angelicae Sinensis Radix slices. Among them, the crude polysaccharides of wine-processed Angelicae Sinensis Radix contributed most to erythrocyte recovery and microcirculation improvement, showing significantly stronger effects than the water extract. This study established a multidimensional correlation evaluation model based on "appearance color-chemical components-biological efficacy" and suggested that polysaccharide dissolution enhancement during processing is a core mechanism underlying the efficacy enhancement of wine processing. Based on this correlation analysis, a system integrating "macromolecule + small molecule" and Q-marker for wine-processed Angelicae Sinensis Radix was successfully predicted and established, covering ferulic acid, 5-HMF, ligustilide, and Angelicae Sinensis Radix polysaccharides. This study not only realizes the scientific quantification of processing intensity, but also provides an objective basis for improving quality control standards for wine-processed Angelicae Sinensis Radix.

Toxic and adverse reactions associated with molecularly targeted anti-tumor drugs are highly prevalent and seriously affect the patients' quality of life. Drawing upon TCM meridian-collateral theory, this paper elucidated the essentials of TCM pathogenesis of toxic and adverse reactions associated with molecularly targeted anti-tumor drugs. It postulated a core pathological theory defined as " drug pathogens invade the meridians, resulting in disharmony of Qi and blood". The toxic and adverse reactions of molecularly targeted anti-tumor drugs are not isolated or disordered local injuries but display a well-defined and intrinsically interconnected pattern. Their dynamic progression follows a sequential transmission pattern of " skin and pores-collaterals-meridians-Zang-fu organs ". Pathologically, this manifests as an evolutionary process of wind-heat accumulation in the skin, heat-toxin congestion in the collaterals, Qi stagnation and blood stasis in the meridians, and imbalance of Yin and Yang, which is highly consistent with the pathogen transmission theory described in Miraculous Pivot: Treatise on Contralateral Puncture(Lingshu: Miuci Lun). Toxic and adverse reactions of different classes of molecularly targeted anti-tumor drugs also exhibit distinct affinity for meridians and collaterals. For example, anti-angiogenic drugs primarily affect the Shaoyin meridian system and are prone to inducing hand-foot syndrome, hypertension, and hypothyroidism. Epidermal growth factor receptor tyrosine kinase inhibitors predominantly involve the Yangming and Taiyang meridian systems, commonly leading to cutaneous rash, diarrhea, and interstitial pneumonia. Human epidermal growth factor receptor-2 inhibitors preferentially affect the heart and spleen meridian systems, with cardiac toxicity and anemia being the most frequently observed manifestations. Meridian-collateral theory offers a novel perspective for understanding the TCM pathogenesis of toxic and adverse reactions associated with molecularly targeted anti-tumor drugs, providing a theoretical basis for the clinical implementation of early intervention, meridian-based syndrome differentiation, and stage-specific treatment.

Anemia is a prevalent pathological characteristic observed in a variety of hematologic disorders, predominantly resulting from impaired red blood cell production or increased erythrocyte degradation. DOCK2, a pivotal guanine nucleotide exchange factor within the DOCK protein family, is uniquely expressed within the hematopoietic system. Previous research has established that the absence of Dock2 significantly disrupts the development and function of several immune cell subsets, including T cells, B cells, NK cells, and granulocytes. However, the role of DOCK2 in erythroid development and associated biological processes remains undefined. This study aimed to investigate the biological function and molecular mechanism of DOCK2 in erythropoiesis. We generated both global and hematopoietic-specific Dock2 knockout mouse models. Results from routine blood analyses and flow cytometry consistently revealed pronounced anemic characteristics in Dock2-deficient mice. Subsequent phenotypic evaluations preliminarily ruled out excessive erythrocyte apoptosis and exacerbated hemolysis as primary contributors to the observed anemia. The developmental defect was attributed to the aberrant differentiation of bone marrow hematopoietic stem and progenitor cells (HSPCs, Lin-Sca-1+c-Kit+). Subsequent bone marrow transplantation and in vitro colony formation assays demonstrated that the deletion of Dock2 led to a compensatory increase in the number of hematopoietic stem cells, while significantly impairing their intrinsic capacity for erythroid differentiation. Integrative transcriptomic and proteomic analyses further demonstrated significant downregulation of Pepd and Prkcd in Dock2-deficient mice, yet it remains unclear whether reduced Pepd and Prkcd expression regulates erythropoiesis. Further functional experiments are necessary to validate this hypothesis in future research. In conclusion, our study identifies DOCK2 as a critical regulator for maintaining normal erythroid differentiation in hematopoietic stem cells. The absence of Dock2 disrupts hematopoietic lineage commitment, resulting in a developmental arrest of the erythroid lineage and the onset of anemia. This research advances our understanding of the regulatory mechanisms underlying erythropoiesis and the pathogenesis of anemia. Additionally, it underscores the potential of DOCK2 as a promising therapeutic target for clinical anemic conditions.

Snakes of the genus Bothrops cause most snakebites in Peru. Among its complications, intracranial hemorrhage is infrequent, but potentially lethal. We describe two cases of hemoventricle after bites by juvenile specimens (<50 cm) in Loreto. The first case corresponds to a 58-year-old male with untreated arterial hypertension, who received antivenom in fractionated doses due to shortage. On the fourth day, he presented sudden headache and loss of consciousness; tomography revealed hemorrhage in the fourth ventricle. The second case corresponds to a five-year-old child who received traditional medicine and whose first dose of antivenom was administered after four days of the bite, following a prolonged fluvial transfer. He presented severe anemia, altered sensorium, and hemorrhage in the left lateral ventricle. Both patients required intensive care, additional antivenom, and supportive measures, and were discharged without neurological deficit. These cases illustrate that delayed or insufficient access to antivenom in the Amazon can be associated with hemorrhagic complications of the central nervous system.

We present a case of a woman who underwent a successful bone marrow transplant for beta-thalassemia major and later gave birth to a child who is compound heterozygous with HBB c.93-21G>A and HBB c.316-106C>G mutations to illustrate the critical gaps in reproductive risk assessment and genetic counseling. The prevalence of consanguinity, socioeconomic challenges, and the lack of a cohesive genetics health system in a thalassemia-endemic country all contribute to poor implementation of genetic care. Strengthening the education of healthcare practitioners, implementing centralized medical record systems, and expanding access to genetic services are becoming increasingly fundamental for improving genetic health care delivery across the Middle East and North Africa region.

We report a case of recurrent type A thymoma accompanied by pure red cell aplasia (PRCA) and agranulocytosis. Following local recurrence after thymoma resection, the patient gradually developed anemia and leukopenia as the lesion progressed; bone marrow examination showed marked suppression of erythropoiesis and reduced granulopoiesis. Taken together with the peripheral blood findings, these results suggested thymoma-associated immune-mediated hematopoietic injury. Following multidisciplinary evaluation, the patient underwent thoracoscopic resection of the recurrent lesion, and pathological examination confirmed type A thymoma with negative surgical margins. Postoperative follow-up showed gradual recovery of erythropoiesis and achievement of transfusion independence, whereas agranulocytosis persisted; only after regular cyclosporine A treatment and increased drug exposure did the white blood cell and neutrophil counts gradually rise. Based on this case and previous studies, thymoma resection may reduce immune attack on the bone marrow and create conditions favorable for hematopoietic recovery by removing the source of continued generation and export of abnormal T cells; however, abnormal T cells that have already entered the peripheral blood or bone marrow and continue to survive may perpetuate immune-mediated injury. Therefore, blood counts should be monitored serially after surgery, and standardized adjunctive immunosuppressive therapy should be instituted when necessary. During treatment, close attention should also be paid to medication adherence, therapeutic drug concentrations, and monitoring of hepatic and renal function to balance efficacy and safety.

A middle-aged man presented with myalgia, fever, hematemesis, and melena. He was found to have acute kidney injury, acute coronary syndrome, thrombocytopenia, and Coombs-negative hemolytic anemia, raising concern for thrombotic microangiopathy (TMA). While awaiting confirmatory testing, empirical plasma exchange was initiated. Initially, minimal red blood cell fragmentation was observed, which later progressed to florid fragmentation. Despite supportive care, his clinical status deteriorated requiring hemodialysis. The presence of TMA, along with ADAMTS13 metalloprotease activity above the diagnostic threshold, worsening kidney function, and negative stool Shiga toxin testing suggested complement-mediated TMA (C-TMA). Stool PCR testing revealed rotavirus. Eculizumab was initiated, resulting in rapid normalization of hematological parameters and eventual renal recovery. Genetic testing identified a heterozygous PLG c.1735G > A (p.Gly579Arg) variant classified as a variant of uncertain significance (VUS). The importance of serial review of peripheral blood smears and the diagnostic challenge of differentiating TTP, STEC-HUS, and C-TMA are the key learning points.