Hereditary hemochromatosis caused by a C282Y/H63D mutation in the HFE gene: A case report.

Hereditary hemochromatosis (HH) is a disease characterized by disordered iron metabolism. It often involves mutations of the HFE gene, which encodes the homeostatic iron regulator protein (HFE), as well as mutations affecting hepcidin antimicrobial peptide, hemojuvelin, or transferrin receptor 2. Historically, HH has been observed primarily in European and European diaspora populations, while classical HH is rare in Asian populations, including in China. In this article, we report a rare case of HH in a Chinese man that could be attributed to a heterozygous C282Y/H63D HFE mutation. Based on clinical examination, liver biopsy, and genetic testing results, the patient was diagnosed with HH. Clinical signs and symptoms and serum iron-related test results were recorded for a period of two years after the patient began treatment. Over this observation period, the patient was subjected to 25 phlebotomies (accounting for a total blood loss of 10.2 L). His serum ferritin levels decreased from 1550 µg/L to 454 µg/L, his serum iron concentration decreased from 40 µmol/L to 24.6 µmol/L, and his transferrin saturation decreased from 97.5% to 55.1%. Early diagnosis is essential for patients with HH to obtain good outcomes. Regular phlebotomy after diagnosis can improve HH symptoms and delay HH disease progression.

Increased antibody titers but induced T cell AICD and apoptosis response in COVID-19 convalescents by inactivated vaccine booster.

It is urgently needed to evaluate the necessity and benefits of booster vaccination against the coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) Omicron to facilitate clinical decision-making for 2019 coronavirus disease (COVID-19) convalescents. We conducted a multicenter, prospective clinical trial (registration number: ChiCTR2100045810) in the first patients with COVID-19 from 28 January 2020 to 20 February 2020 to assess the long-term durability of neutralizing antibodies against live Omicron BA.5 and further assess the efficiency and safety of CoronaVac in the convalescent group. A total of 96 COVID-19 convalescents were enrolled in this study. Neutralizing antibody titers in convalescents were significantly reduced in 9-10 months. A dose-refreshing vaccination in 28 convalescents with an antibody titer below 96 significantly induced neutralizing antibodies against live Omicron by 4.84-fold. Meanwhile, the abundance of naive T cells increased dramatically, and TEMRA and TEM cells gradually decreased after vaccination. Activation-induced cell death and apoptosis-related genes were significantly elevated after vaccination in all T-cell subtypes. One-dose booster vaccination was effective in inducing a robust antibody response against SARS-CoV-2 Omicron in COVID-19 convalescents with low antibody titers. However, vaccine-mediated T-cell consumption and regeneration patterns may be detrimental to the antiviral response.IMPORTANCEThe globally dominant coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) Omicron variant raises the possibility of repeat infections among 2019 coronavirus disease (COVID-19) convalescents with low neutralizing antibody titers. The importance of this multicenter study lies in its evaluation of the long-term durability of neutralizing antibodies in COVID-19 convalescents and the efficacy of a booster vaccination against the live Omicron. The findings suggest that a one-dose booster vaccination is effective in inducing a robust antibody response against SARS-CoV-2 Omicron in convalescents with low antibody titers. However, the study also highlights the potential detrimental effects on the antiviral response due to vaccine-mediated T-cell consumption and regeneration patterns. These results are crucial for facilitating clinical decision-making for COVID-19 convalescents and informing public health policies regarding booster vaccinations.

Case report: Successful immunomodulators combined with electromagnetic field therapy in a patient with methazolamide-induced Steven Johnson syndrome/toxic epidermal necrolysis overlap.

Methazolamide is used to treat patients with glaucoma. However, as a sulfonamide derivative, methazolamide shares the same adverse reaction profile as other sulfa-based medications. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare delayed-type hypersensitivity cutaneous reactions with high morbidity and mortality. Here, we report a severe SJS/TEN overlap syndrome in an 85-year-old Chinese male patient who received methazolamide 25 mg twice daily for his left eye glaucoma. The causal relationship between SJS/TEN and methazolamide was categorized as "highly likely" on the algorithm for assessing drug causality for epidermal necrolysis. In addition to the treatments with methylprednisolone and immunoglobulin, we used a special electromagnetic spectrum therapeutic apparatus to provide skin wound care. The patient had a thoroughly satisfying recovery. This is the first case report to use electromagnetic field therapy in a patient with SJS/TEN. We share our experience here and suggest that electromagnetic field therapy can provide advanced skin wound care and facilitate the recovery of SJS/TEN.

Exosomes Derived from Baicalin-Pretreated Mesenchymal Stem Cells Alleviate Hepatocyte Ferroptosis after Acute Liver Injury via the Keap1-NRF2 Pathway.

Acute liver injury (ALI) is characterized as a severe metabolic dysfunction caused by extensive damage to liver cells. Ferroptosis is a type of cell death dependent on iron and oxidative stress, which differs from classical cell death, such as apoptosis and necrosis. Ferroptosis has unique morphological features, which mainly include mitochondrial dissolution and mitochondrial outline reduction. Furthermore, the intracellular accumulation of lipid peroxides directly affects the occurrence of ferroptosis. Baicalin, the main compound isolated from Scutellaria baicalensis, has anti-inflammatory and antioxidative effects. Recently, exosomes derived from preconditioned mesenchymal stem cells (MSCs) have shown great potential in the treatment of various diseases including ALI. This study investigates the ability of exosomes derived from baicalin-pretreated MSCs (Ba-Exo) to promote liver function recovery in mice with ALI compared with those without pretreatment. Through in vivo and in vitro experiments, this study demonstrates for the first time that Ba-Exo greatly attenuates D-galactosamine and lipopolysaccharide (D-GaIN/LPS)-induced liver damage and inhibits reactive oxygen species (ROS) production and lipid peroxide-induced ferroptosis. Moreover, P62 was significantly upregulated in Ba-Exo, whereas its downregulation in Ba-Exo counteracted the beneficial effect of Ba-Exo. P62 regulates hepatocyte ferroptosis by activating the Keap1-NRF2 pathway. The beneficial effect of Ba-Exo in inhibiting ferroptosis was also attenuated after the NRF2 pathway was inhibited. Therefore, baicalin pretreatment is an effective and promising approach to optimize the therapeutic efficacy of MSC-derived exosomes in ALI.

Clinical and pathological investigation of patients with severe COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), has become a pandemic. This study addresses the clinical and immunopathological characteristics of severe COVID-19. METHODS: Sixty-nine patients with COVID-19 were classified into severe and nonsevere groups to analyze their clinical and laboratory characteristics. A panel of blood cytokines was quantified over time. Biopsy specimens from 2 deceased cases were obtained for immunopathological, ultrastructural, and in situ hybridization examinations. RESULTS: Circulating cytokines, including IL-8, IL-6, TNF-α, IP10, MCP1, and RANTES, were significantly elevated in patients with severe COVID-19. Dynamic IL-6 and IL-8 were associated with disease progression. SARS-CoV-2 was demonstrated to infect type II and type I pneumocytes and endothelial cells, leading to severe lung damage through cell pyroptosis and apoptosis. In severe cases, lymphopenia, neutrophilia, depletion of CD4+ and CD8+ T lymphocytes, and massive macrophage and neutrophil infiltrates were observed in both blood and lung tissues. CONCLUSIONS: A panel of circulating cytokines could be used to predict disease deterioration and inform clinical interventions. Severe pulmonary damage was predominantly attributed to both cytopathy caused by SARS-CoV-2 and immunopathologic damage. Strategies that prohibit pulmonary recruitment and overactivation of inflammatory cells by suppressing cytokine storm might improve the outcomes of patients with severe COVID-19.

SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19.

Background & Aims: Liver enzyme abnormalities are common in patients with coronavirus disease 2019 (COVID-19). Whether or not severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to liver damage per se remains unknown. Herein, we reported the clinical characteristics and liver pathological manifestations of COVID-19 patients with liver enzyme abnormalities. Methods: We analyzed 156 patients diagnosed with COVID-19 from 2 designated centers in China and compared clinical features between patients with or without elevated aminotransferases. Postmortem liver biopsies were obtained from 2 cases who had elevated aminotransferases. We investigated the patterns of liver impairment by electron microscopy, immunohistochemistry, TUNEL assay and pathological studies. Results: Sixty-four out of 156 (41.0%) patients with COVID-19 had elevated aminotransferases. The median levels of alanine aminotransferase were 50 U/L vs. 19 U/L, respectively, aspartate aminotransferase were 45.5 U/L vs. 24 U/L, respectively in abnormal and normal aminotransferase groups. Liver enzyme abnormalities were associated with disease severity, as well as a series of laboratory tests including higher alveolar-arterial oxygen partial pressure difference, higher gamma-glutamyltransferase, lower albumin, decreased CD4+ T cells and B lymphocytes. Ultrastructural examination identified typical coronavirus particles, characterized by spike structures, in the cytoplasm of hepatocytes in 2 COVID-19 cases. SARS-CoV-2-infected hepatocytes displayed conspicuous mitochondrial swelling, endoplasmic reticulum dilatation and glycogen granule decrease. Histologically, massive hepatic apoptosis and some binuclear hepatocytes were observed. Taken together, both ultrastructural and histological evidence indicated a typical lesion of viral infection. Immunohistochemical results showed scarce CD4+ and CD8+ lymphocytes. No obvious eosinophil infiltration, cholestasis, fibrin deposition, granuloma, massive central necrosis, or interface hepatitis were observed. Conclusions: SARS-CoV-2 infection in the liver directly contributes to hepatic impairment in patients with COVID-19. Hence, a surveillance of viral clearance in liver and long-term outcome of COVID-19 is required. Lay summary: Liver enzyme abnormalities are common in patients with coronavirus disease 2019 (COVID-19). We reported the clinical characteristics and liver pathological manifestations of COVID-19 patients with elevated liver enzymes. Our findings suggested that SARS-CoV-2 infection of the liver is a crucial factor contributing to hepatic impairment in patients with COVID-19.

Transfusion-transmitted virus co-infection in other types of hepatitis and its genotypes.

OBJECTIVE: To identify the influence of transfusion transmitted virus (TTV) co-infection in other virus infected patients and its genotypes. METHODS: A conservative sequence of ORF1 in the TTV genome was selected as primers and TTV DNA was measured in students and other hepatitis patients by using microplate nucleic acid hybridization and ELISA. The results were statistically analyzed. Nucleotide sequence of divergence>50% was used as color probe for distinguishing TTV genotypes I or II. RESULTS: TTV DNA was detected in the sera from 2 (3.3%) of 60 students, 2 (14.3%) of 14 patients with non A-non E hepatitis, 6 (12%) of 50 patients with chronic hepatitis B, and 4 (16%) of 25 patients with liver cirrhosis, respectively. Statistical difference was observed between the patient group and the student group (P<0.05), but no significant difference in age, gender, serum ALT levels and TBiL between TTV DNA positive and negative patients (P>0.05). TTV genotype type I was by far the most frequent viral genotype (66.7%), followed by type II (25%), and mixed infection (8.3%). CONCLUSIONS: These results suggest that the routes of TTV infection may be similar to those of HBV and HCV, and concurrent infection with HBV, HCV are common. TTV co-infection could not affect the clinical features of patients with liver diseases and the pathological process. TTV is not a main causative factor for patients with non A-non E hepatitis. Further study is needed to clarify the role of TTV in patients with non A-non E hepatitis.