With the development of gene editing technology, its application in tumor diagnosis is becoming increasingly widespread. The CRISPR/Cas system is an important gene editing tool that can significantly improve the early detection rate and precision diagnosis level, enabling high-throughput and high-sensitivity detection of tumors. This article focuses on CRISPR/Cas system for detecting various tumor-related targets and elaborates on its applications in tumor diagnosis from five aspects: (1) detection of tumor-derived exosomes: by recognizing the surface proteins or nucleic acids of exosomes secreted by tumor cells into blood or other samples through adaptors, the CRISPR system is activated, achieving non-invasive liquid biopsy of tumors; (2) detection of circulating tumor DNA tumor cells disseminate DNA into the circulatory system to trigger nucleic acid reactions involving gene editing enzymes, enabling the monitoring of tumor dynamic states; (3) detection of circulating tumor cells (CTCs): by using aptamers to recognize surface proteins of tumor cells or directly detecting tumor-related nucleic acids, the integrated CRISPR system allows for the detection of circulating tumor cells even in trace amounts, achieving precise diagnosis; (4) detection of tumor markers: high sensitivity is achieved through the coupling of various tumor marker aptamers and gene editing systems; (5) detection and identification of tumor microenvironments: by activating gene editing enzyme activity through differential factors in the tumor tissue microenvironment and triggering nucleic acid reactions, the diagnosis and dynamic monitoring of tumors can be achieved. The progress and bottlenecks of the CRISPR/Cas system in tumor diagnosis in the future are also discussed.

The application of antifibrotic drugs to treat patients with chronic liver diseases who are receiving antiviral therapies for hepatocellular carcinoma (HCC) has not been established. Here, we aimed to assess the impact of the Traditional Chinese Medicine Fuzheng Huayu (FZHY) on the occurrence of HCC in patients with hepatitis B virus-related compensated cirrhosis receiving the antiviral drug entecavir (ETV).

A multicenter retrospective cohort study was performed. Compensated liver cirrhosis patients were divided into the ETV+FZHY group or the ETV group according to treatment. The cumulative incidence of HCC was analyzed using Kaplan-Meier and log-rank tests. Propensity score matching was used for confounding factors. Stratified analysis and Cox regression were used to determine the effects of FZHY on the occurrence of HCC and liver function decompensation.

Out of 910 chronic hepatitis B patients, 458 were in the ETV+FZHY group and 452 were in the ETV group. After propensity score matching, the 5-year cumulative incidence of HCC was 9.8% in the ETV+FZHY group and 21.8% in the ETV group (p<0.01). The adjusted hazard ratio for HCC was 0.216 (0.108, 0.432) when FZHY treatment was >36 months. Age, diabetes, alanine aminotransferase, γ-glutamyl transpeptidase, albumin, hepatitis B e-antigen, and fibrosis 4 score were associated with the occurrence of HCC. FZHY decreased the risk of HCC in patients aged >45 years with a hepatitis B virus DNA level of ≥2,000 IU/l.

Adjunctive FZHY treatment reduced HCC occurrence in patients with hepatitis B virus cirrhosis who were treated with ETV, possibly due to the antifibrotic properties of FZHY.

Huaier (Trametes robiniophila Murr) is a traditional Chinese medicine with a clinical application history of over 1,000 years. Its chemical components mainly include polysaccharides, sterols, and alkaloids. Huaier has been shown to demonstrate potent antitumor effects in a variety of cancer types, including breast cancer, colorectal cancer, gastric cancer, liver cancer, lung cancer, and others. In recent years, multiple in-vitro experiments have confirmed the good antitumor effect of Huaier and its mechanism of action, such as inhibiting proliferation, inducing apoptosis and oxidative stress, interfering with cell cycle arrest, inhibiting tumor metastasis and angiogenesis, inducing autophagy, and regulating immune function. In addition, multiple in-vivo studies and clinical trials have demonstrated the multidimensional antitumor potential of Huaier, such as slowing tumor progression, reversing drug resistance, improving chemotherapy drug sensitivity, and extending the survival time of cancer patients. In this article, the extraction methods of Huaier and its properties for the treatment of many cancers are reviewed. Moreover, the current molecular mechanisms of Huaier are summarized, revealing that it has great potential as an anticancer drug and providing strong theoretical support for related research. Furthermore, this review also provides suggestions for further research on the anticancer effects of Huaier, hoping to offer fresh perspectives for researchers in the realm of anticancer medicine.

This review explores the convergence of traditional wisdom and modern science in the realm of herbal medicines, focusing on the safety, efficacy, and bioactivity of these natural remedies in contemporary healthcare. The rich history of herbal medicines, deeply embedded in cultural traditions, is witnessing a resurgence as the quest for holistic and personalized healthcare gains momentum. Herbal medicine, a time-honored practice passed down through generations, is experiencing renewed interest amid the growing acknowledgment of its potential benefits. This review delves into the safety profiles of herbal remedies, subjecting them to rigorous scientific scrutiny. Additionally, it investigates the efficacy of herbal interventions, aiming to bridge the gap between historical anecdotes and empirical research. The complex bioactivity of herbal compounds, often containing numerous active ingredients, is a focal point, unraveling the mechanisms through which these natural substances interact with the human body. In a world where the synthesis of traditional wisdom and modern science holds promise for advancing healthcare, this review contributes to the ongoing dialogue. By critically examining the safety, efficacy, and bioactivity of herbal remedies, it aims to illuminate the evolving landscape of herbal medicine. The goal is to integrate the best of both worlds to enhance global well-being, acknowledging the potential of herbal medicine as a valuable complement to modern healthcare practices.

Partial hepatectomy is a first-line treatment for hepatocellular carcinoma. Within 2 weeks following partial hepatectomy, specific molecular pathways are activated to promote liver regeneration. Nevertheless, residual microtumors may also exploit these pathways to reappear and metastasize. Therapeutically targeting molecules that are differentially regulated between normal cells and malignancies, such as fibrinogen-like protein 1 (FGL1), appears to be an effective approach. The potential functions of FGL1 in both regenerative and malignant cells are discussed within the ambit of this review. While FGL1 is normally elevated in regenerative hepatocytes, it is normally downregulated in malignant cells. Hepatectomy does indeed upregulate FGL1 by increasing the release of transcription factors that promote FGL1, including HNF-1α and STAT3, and inflammatory effectors, such as TGF-β and IL6. This, in turn, stimulates certain proliferative pathways, including EGFR/Src/ERK. Hepatectomy alters the phase transition of highly differentiated hepatocytes from G0 to G1, thereby transforming susceptible cells into cancerous ones. Activation of the PI3K/Akt/mTOR pathway by FGL1 allele loss on chromosome 8, a tumor suppressor area, may also cause hepatocellular carcinoma. Interestingly, FGL1 is specifically expressed in the liver via HNF-1α histone acetylase activity, which triggers lipid metabolic reprogramming in malignancies. FGL1 might also be involved in other carcinogenesis processes such as hypoxia, epithelial-mesenchymal transition, immunosuppression, and sorafenib-mediated drug resistance. This study highlights a research gap in these disciplines and the necessity for additional research on FGL1 function in the described processes.

Cancer treatment has been revolutionized in the last 10 years. Previously, highly toxic chemotherapy regimens that attack both healthy cells and cancer cells as well as induce significant side effects were used. Nowadays, a more targeted approach is employed. Cancer cells are being treated at the molecular level. Patients with carcinoma of unknown primary who previously only had “broad spectrum” combination therapy as a treatment option can now have their cancer’s genome sequenced with next-generation sequencing in a matter of hours and be offered a more targeted approach. Here, we report a case of a patient with metastatic cancer of an unknown primary origin who was progressing on multiple lines of treatment. Next-generation sequencing showed that the patient had a high tumor mutational burden; therefore, he was able to access immunotherapy through a compassionate access scheme, which resulted in a near complete and sustained clinical and radiological response.

With the highest incidence rate and death rate among malignant tumors, lung cancer is the most prevalent malignant tumor worldwide. Tumor-node-metastasis (TNM) staging provides a basis for clinical therapy and prognosis while the fundamental principle of traditional Chinese medicine (TCM) is the syndrome differentiation and treatment. This study offers an objective foundation for the distinction and classification of TCM syndromes by methodically assessing the relationship between TNM staging indicators and the various types of the syndrome in lung cancer.

To find pertinent material, we searched a number of databases, including CNKI, PubMed, VIP, and Wanfang. Literature on the relationship between TCM syndrome categories and TNM staging indexes of lung cancer published from the database’s inception until May 2023 was gathered. The meta-analysis was carried out using Rev Man 5.4.

In the end, seven pieces of literature totaling 264 patients were included. Lung cancer is mainly characterized by phlegm dampness syndrome, Qi Yin deficiency syndrome, Yin deficiency internal heat syndrome, and Qi stagnation and blood stasis syndrome. In stage I and II, phlegm dampness syndrome > Yin deficiency internal heat syndrome (p < 0.5), phlegm dampness syndrome > Qi Yin deficiency syndrome (p < 0.5), phlegm dampness syndrome > Qi stagnation and blood stasis syndrome (p < 0.5). In stages III and IV, Qi Yin deficiency syndrome > Qi stagnation and blood stasis syndrome > Yin deficiency internal heat syndrome > phlegm dampness syndrome (p < 0.5).

Phlegm dampness syndrome is the main syndrome in stages I and II of lung cancer, while Qi and Yin deficiency syndromes are the main syndromes in stages III and IV of lung cancer.

Impairment in the cerebral glymphatic system may be one of the primary etiologic reasons for insomnia. Traditional Chinese medicine (TCM) physiotherapy is helpful for treating insomnia patients, with few side effects; however, its influence on glymphatic system function has not yet been examined. The DTI-ALPS (diffusion tensor image analysis along the perivascular space) technique and structural brain network graph theory analysis are the only current methods that can show the glymphatic system’s function and the operating efficiency of the neurofibrillary network in a noninvasive and quantitative manner, but their utility has yet to be proven. We employed DTI-ALPS and structural brain network small-worldness to examine changes in the glymphatic system’s function and the network’s working efficiency before and after TCM meridian sinew treatment in a 35-year-old female with chronic insomnia. The ALPS index and small-worldness, the Insomnia Severity Index, and the Pittsburgh Sleep Quality Index were collected at various time intervals following therapy. The results showed that the patient’s glymphatic system functioning, neurofibrillary network arrangement status, and insomnia symptoms improved during the therapy period. Additionally, her glymphatic system functioning and network status had stabilized and her quality of sleep had improved one month after the treatment ended. Thus, TCM physiotherapy can improve insomnia symptoms, and this report suggests that the corresponding mechanism of action may be achieved by repairing the glymphatic system’s function and optimizing the state of neurofibrillary network arrangement, providing a new perspective for the study of the TCM therapeutic mechanism of insomnia.

Three-dimensional power Doppler (3DPD) ultrasound has been used for assessing adnexal masses, and in this study, we aimed to perform a meta-analysis to evaluate its role in the differential diagnosis of adnexal masses.

A search for primary studies assessing the diagnostic performance of 3DPD in discriminating benign from malignant masses carried out between January 1990 and May 2023 was performed in Medline (PubMed), Scopus, and Web of Science databases with study quality evaluated using QUADAS-2.

We identified 404 citations. Ultimately, 18 studies comprising 2,975 women were included, and the mean prevalence of malignant lesions was 37%. In most cases, the quality of studies was moderate. Overall, pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 3DPD vascular tree assessment for studies including any type of mass were 77% (95% confidence interval [CI] = 52%–91%), 80% (95% CI = 37%–97%), 3.9 (95% CI = 0.7–20.9), and 0.29 (95% CI = 0.10–0.81), respectively. Heterogeneity was high for both sensitivity and specificity. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 3DPD vascular tree assessment for studies including only “complex” or “suspicious” adnexal masses were 90% (95% CI = 82%–94%), 88% (95% CI = 74%–95%), 7.3 (95% CI = 3.2–16.4), and 0.12 (95% CI = 0.06–0.22), respectively. Heterogeneity was moderate for both sensitivity and specificity. We could not perform quantitative synthesis for studies estimating 3D vascular indexes.

The diagnostic performance of 3DPD for discriminating benign from malignant adnexal masses is good, and there is great heterogeneity in diagnostic criteria when using this technique.

Oncology patients undergoing cancer treatment and experiencing episodes of fever are known to be at increased risk for invasive bacterial infection, including bloodstream infection. This study aimed to identify the incidence of bacteremia along with the bloodstream isolates for immunocompromised oncology patients referred to the emergency department (ED) due to fever.

Oncology patients with fever were referred to the ED according to a protocol previously reported. Virtually all children had central venous access devices (CVAD) that underwent sterile access according to Hematology-Oncology (Hem-Onc) and ED protocol. Antibiotics were administered to all patients once CVAD were accessed and laboratory studies, including blood culture, were obtained. Data collected included patient demographic features, complete blood count profiles, proportions receiving antibiotics within 60 minutes of ED arrival and subsequent blood culture results.

Of 1,088 consecutively referred Hem-Onc patients, 439 were eligible for inclusion. The overall blood culture positive rate was 5.7%. Fifty-six percent of patients with positive blood cultures had an absolute neutrophil count greater than 500 µL at the time of ED presentation. Gram-positive organisms comprised 64% of isolates while gram-negative organisms accounted for 36% of the total isolates.

Immunocompromised oncology patients presenting to the ED with fever are susceptible to bloodstream infection caused by an array of gram-positive and gram-negative organisms. Bloodstream infection during episodes of fever includes many patients without severe neutropenia at presentation and with bloodstream isolates not typically associated with catheter-related bloodstream infection alone, highlighting the diversity and variability within this patient population.

Coptis teeta Wall. (C. teeta) is a herb that goes by the name “Mishmi Tita”, and holds significant value as a medicinal plant for treating various health conditions. This endangered plant, listed in the Red Data Book, is commonly found in India, Nepal, Bhutan and China. The present review aims to comprehensively summarize the traditional, pharmaceutical, and phytochemical aspects of C. teeta, providing a foundation for researchers to explore this endangered plant, and take bold steps to conserve, cultivate, and promote awareness among local people. A thorough literature search was conducted on PubMed, Google Scholar, Research Gate, SciFinder, and the ISI Web of Knowledge, using the following terms: “Coptis teeta”, “Coptis teeta Wall.”, “Mishmi tita”, “Rhizoma coptidis”, “Chinese medicine from Coptis teeta”, and “Traditional uses of Coptis teeta”. A comprehensive examination of 69 articles published between 1982 and 2023 was conducted to explore the properties and traditional applications of C. teeta. It was found that this plant and its active compounds exhibit a range of effects, such as fighting against microbes, alleviating diarrhoea, lowering blood pressure, regulating heart rhythm, reducing inflammation, improving mood, treating trachoma, managing diabetes, providing pain relief, and countering reactions. A total of 27 compounds were identified in different parts of this plant, according to the surveyed literature. These have been traditionally utilized to address ailments, including conditions, eye disorders, skin issues, gastrointestinal troubles like constipation and jaundice, and urinary disorders. Furthermore, these have shown potential in cancer treatment and mitigating inflammation. C. teeta boasts diverse traditional uses and promising pharmacological activities due to its rich chemical composition. Berberine is the main constituent, and various communities utilize it for various ailments. While endangered, C. teeta offers exciting medicinal potential, warranting further research and sustainable conservation efforts. Cultivating the plant and raising public awareness are crucial steps towards its preservation.

The global burden of colorectal cancer (CRC) is a pressing concern, with a substantial impact on public health. Despite advancements in understanding the molecular mechanisms of CRC development, challenges remain in translating this knowledge into effective clinical interventions. Key genetic mutations, notably in the adenomatous polyposis coli (APC) and Kirsten rat sarcoma virus (KRAS) genes, are central to CRC initiation and progression. Current CRC treatments include surgery and chemotherapy, often combined with targeted agents. However, resistance and heterogeneity within CRC patients limit the effectiveness of these therapies. Promisingly, research has focused on targeting APC and KRAS mutations for therapy. Small molecules inhibiting the Wnt pathway and antibodies targeting specific components are under investigation. Targeting KRAS itself is challenging due to its conserved structure, but disrupting its membrane interactions and subcellular localization are potential therapeutic strategies. To address the limitations of single-drug therapy, combination approaches are gaining traction. Combination therapy not only minimizes off-target effects but also tackles drug resistance and diverse genetic alterations within tumors. The intricate interplay of mutations and pathways in CRC necessitates multifaceted therapeutic strategies. Although progress has been made in understanding CRC genetics and developing targeted therapies, there is still work to be done to translate these insights into effective clinical treatments for CRC patients. This review provides crucial information for novel combination treatments for CRC.

Prostate cancer (PC) is the second leading cause of death among American men, with most patients receiving androgen deprivation therapy and eventually developing resistance to treatment. The 5-year survival rate from 2015–2020 for men with distant disease was 33%, demonstrating the need for more optimal treatment regimens for patients with distant or metastatic PC. Pharmacogenomic (PGx) testing, a component of precision medicine, focuses on the way a patient’s genome affects drug metabolism. Combining PGx testing with current genetic testing provides an innovative and personalized approach to treating PC while both reducing adverse events and optimizing treatment dosages to fit the patient’s genetic make-up. This review paper describes how clinicians can use PGx testing in combination with genetic testing for PC patients.

High-grade endometrial stromal sarcoma (HGESS) is a rare sarcoma with aggressive biological behavior. Here we reported a case of molecularly confirmed ZC3H7B-BCOR HGESS in an extrauterine location, with morphologic and immunohistochemical findings resembling a gastrointestinal stromal tumor. The patient, a 51-year-old woman, presented with extensive pelvic and abdominal masses. Histologically, the tumor displayed fascicles of spindle cells with myxoid stroma and abundant mitosis. Immunohistochemical staining revealed that the tumor cells were diffusely positive for cluster of differentiation 117 (CD117) and discovered on gastrointestinal stromal tumor 1 (DOG1). Gastrointestinal stromal tumor was initially diagnosed, and DNA sequencing was performed for targeted therapy. Unexpectedly, no mutations in KIT proto-oncogene, receptor tyrosine kinase (CKIT) or platelet-derived growth factor receptor, alpha polypeptide (PDGFRA) were identified, but amplification of murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) was found. Further, ZC3H7B-BCOR fusion was detected via RNA sequencing. Additional immunostaining showed that CD10 was diffusely positive, the estrogen receptor was negative, and the progesterone receptor was weakly positive. ZC3H7B-BCOR HGESS was definitively diagnosed. In conclusion, the coexpression of CD117 and DOG1 may present a potential diagnostic pitfall in the evaluation of pelvic/abdominal masses, which should be paid great attention to.

Olaparib is a selective poly (ADP-ribose) polymerase inhibitor. However, its clinical application is hindered by low solubility and undesired pharmacokinetic profiles (e.g., relatively short circulation). Therefore, the present study aims to exploit polymeric micelles as a safe solubilizer and nanocarrier of olaparib, in order to improve its solubility and pharmacokinetics.

Poly (ε-caprolactone)-co-poly (benzyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate), i.e., benzyl-functionalized trimethylene carbonate)-b-poly (ethylene glycol) (P(CL-co-TMC-Bz)-PEG), was synthesized by ring-opening polymerization, and used to prepare the π-π-stacked polymeric micelles for olaparib encapsulation. A series of olaparib-loaded micelles with different polymer concentrations and wt% loadings were prepared using different methods to investigate the effect of formulation variables on the size of polymeric micelles and drug loadings. In addition, the in vitro release of olaparib from the micelles, and the cytotoxicity of micellar olaparib formulations on the SKOV3 tumor cell line were evaluated by UV spectrophotometry and CCK-8 assay, respectively. Finally, the blood circulation kinetics and side effects of the incorporated olaparib in the micelles and free olaparib were investigated in SD rats using ultra-high performance liquid chromatography analysis and H&E staining, respectively.

It was found that P(CL11-co-TMC-Bz5)-PEG micelles served as a safe and excellent solubilizer for olaparib, and that the solubilization capacity was easily tailored by adjusting the polymer concentration. In addition, when loaded in micelles, olaparib exhibited a sustained release behavior in vitro, and obvious cytotoxicity on SKOV3 cells. The in vivo studies revealed that olaparib incorporated in P(CL11-co-TMC-Bz5)-PEG polymeric micelles exhibited prolonged circulation (t1/2 = 2.00 hours), when compared to free olaparib (t1/2 ≤ 0.25 hours), and excellent safety. However, in terms of taking advantage of the EPR effect of the micelle delivery system to achieve the targeted olaparib delivery, the circulation time of olaparib in the micelles remained rather short.

Improvements, such as chemical crosslinking and drug conjugation, are required to improve the retention of olaparib-loaded polymeric micelles in blood circulation, and benefit from the use of micelles as a targeted delivery system.

Eurotium cristatum (E. cristatum), commonly known as “golden flower”, is the dominant strain in the microbial fermentation process of Fu brick tea. E. cristatum has favorable biological characteristics, including enzyme production, antimicrobial properties, immune regulation, antitumor properties, fat reduction capabilities, and weight loss benefits. With its probiotic characteristics, E. cristatum can be combined with different varieties of tea substrates to make a variety of fermented teas. More importantly, in the process of tea fermentation, E. cristatum can secrete a variety of extracellular enzymes, including some hydrolytic enzymes and oxidoreductases. They metabolize and transform various chemical components in tea through a series of reactions such as oxidation, degradation, and condensation, which significantly affect the quality of tea. In this review, by summarizing its basic functional characteristics as well as its application in fermented tea, an in-depth analysis of the key problems existing in the fermentation application of E. cristatum is described and some beneficial suggestions are presented in order to provide a rich theoretical basis for the development and utilization of E. cristatum to a greater extent.

China accounts for nearly half of liver cancer deaths globally. A better understanding of the current liver cancer mortality will be helpful to establishing priorities for intervention and to decreasing the disease burden of liver cancer. The study aimed to explore and predict the mortality burden of liver cancer in China.

Data were extracted from the Disease Surveillance Point system of the Chinese Center for Disease Control and Prevention from 2008 to 2020. Crude and age-standardized liver cancer mortality rates were reported by sex, urban or rural residence, and region. Trends in liver cancer mortality rates from 2008 to 2020 were estimated as average annual percentage change (AAPC). The changing trend of live cancer mortality in the future is also predicted.

In 2020, the crude mortality of liver cancer was 25.57/100,000, and males and people lived in rural areas had higher age-standardized liver cancer mortality rates than females and people lived in people in urban areas. Crude mortality and age-standardized mortality rates in southwest provinces (Guangxi, Sichuan, Tibet) and in a northeast province (Heilongjiang) were higher than that in other provinces, and age-specific mortality rates increased with age. From 2008 to 2020, liver cancer mortality rates decreased, but people under 50 years of age had a higher AAPC than those over 50 years of age, possibly because of the adoption of hepatitis B virus vaccination in newborns and children. Furthermore, the mortality of liver cancer in 2021–2030 is predicted to have a downward trend.

Liver cancer mortality rates declined in China from 2008 to 2020. Future interventions to control liver cancer mortality need to focus on people of male sex, older age, and living in rural areas or less developed provinces.

Obesity is a global health burden and is closely associated with severe chronic co-morbidities, which remain the leading causes of death. Significant progress has been made in the treatment of hypertension, diabetes, and hyperlipidemia over the last half-century. However, advancements in the management of obesity have been slow, with some medications exhibiting inadequate efficacy and dangerous side effects. Improved understanding of the gut-brain axis has inspired the pursuit of novel medications aiming to provide sustainable and safe weight loss. Current evidence-based practices for obesity management involve multi-modal approaches, including lifestyle modification, mechanical gastric restriction, modulation in the secretion of multiple gut hormones, alteration in the composition and secretion of bile acids, and alterations of the gut microbiome. Each physician is responsible for recognizing obesity as a disease and assisting patients in appropriate management based on strong evidence and a good safety profile, aligned with the patient’s goals. Through this review, we aim to inform the readers of recent approaches for managing obesity and comparing their beneficial effects and efficacy on obesity and its long-term co-morbidities.

The clinical introduction of hepcidin25 (Hep25) has led to a more detailed understanding of its relationship with ferroportin (FP) and divalent metal transporter1 in primary iron overload syndromes (PIOSs). In 2012, we proposed a classification of PIOSs based on the Hep25/FP system, which consists of prehepatic aceruloplasminemia, hepatic hemochromatosis (HC), and posthepatic FP disease (FP-D). However, in consideration of accumulated evidence on PIOSs, we aimed to renew the classification.

We reviewed the 2012 classification and retrospectively renewed it according to new information on PIOSs.

Iron-loading anemia was included in PIOSs as a prehepatic form because of the newly discovered erythroferrone-induced suppression of Hep25, and the state of traditional FP-D was remodeled as the BIOIRON proposal. The key molecules responsible for prehepatic PIOSs are low transferrin saturation in aceruloplasminemia and increased erythroferrone production by erythroblasts in iron-loading anemia. Hepatic PIOSs comprise four genotypes of HC, in each of which the synthesis of Hep25 is inappropriately reduced in the liver. Hepatic Hep25 synthesis is adequate in posthepatic PIOSs; however, two mutant FP molecules may resist Hep25 differently, resulting in SLC40A1-HC and FP-D, respectively. PIOS phenotypes are diagnosed using laboratory tests, including circulating Hep25, followed by suitable treatments. Direct sequencing of the candidate genes may be outsourced to gene centers when needed. Laboratory kits for the prevalent mutations, such as C282Y, may be the first choice for a genetic analysis of HC in Caucasians.

The revised classification may be useful worldwide.