Clinical phenotype and laboratory characteristics of 93 patients with congenital fibrinogen disorders from unrelated 36 families.

Background: Congenital fibrinogen disorders (CFDs) are rare bleeding disorders (RBDs) caused by mutations in 1 of the 3 fibrinogen genes (FGA, FGB, and FGG). Objectives: To investigate the clinical phenotype, laboratory features, diagnosis, treatment, and prognosis of CFDs. Methods: Clinical data of 93 subjects with CFDs identified from June 2018 to December 2023 were retrospectively analyzed. Results: Among the 93 patients, there were 46 males (49.5%) and 47 females (50.5%), with a median age of 23 years. Fifty-three of 93 (57%) subjects experienced bleeding, 3/93 (3.2%) experienced thrombosis, and 37/93 (39.8%) were asymptomatic. Females were more prone to experience bleeding (P < .0001). The 93 patients exhibited prolonged thrombin time, significantly decreased fibrinogen activity (Fg:C), and normal or decreased fibrinogen antigen. The 93 patients included 3 with hypofibrinogenemia, 16 with hypodysfibrinogenemia, and 74 with dysfibrinogenemia. Among the 53 patients with bleeding, bleeding episodes were identified in 3.8% (2/53), 20.8% (11/53), and 75.5% (40/53) patients with hypofibrinogenemia, hypodysfibrinogenemia, and dysfibrinogenemia, respectively. Genetic analysis was performed on 22 cases from 8 pedigrees, revealing 10 mutations, including 1 novel splice mutation. Twenty-eight (30.1%) subjects received replacement therapy to treat or prevent bleeding, consisting of 8 fresh frozen plasma transfusions, 3 packing and suture treatment, and 61 fibrinogen infusions. Conclusion: Most patients with CFDs have mild or no bleeding symptoms. Fg:C combined with fibrinogen antigen and pedigree investigation can improve the feasibility and accuracy of diagnosis of CFDs. The severity of bleeding symptoms was negatively correlated with Fg:C.

Human monkeypox virus: Epidemiologic review and research progress in diagnosis and treatment.

Monkeypox virus (MPXV) is responsible for causing a zoonotic disease called monkeypox (mpox), which sporadically infects humans in West and Central Africa. It first infected humans in 1970 and, along with the variola virus, belongs to the genus Orthopoxvirus in the poxvirus family. Since the World Health Organization declared the MPXV outbreak a "Public Health Emergency of International Concern" on July 23, 2022, the number of infected patients has increased dramatically. To control this epidemic and address this previously neglected disease, MPXV needs to be better understood and reevaluated. In this review, we cover recent research on MPXV, including its genomic and pathogenic characteristics, transmission, mutations and mechanisms, clinical characteristics, epidemiology, laboratory diagnosis, and treatment measures, as well as prevention of MPXV infection in light of the 2022 and 2023 global outbreaks. The 2022 MPXV outbreak has been primarily associated with close intimate contact, including sexual activity, with most cases diagnosed among men who have sex with men. The incubation period of MPXV infection usually lasts from 6 to 13 days, and symptoms include fever, muscle pains, headache, swollen lymph nodes, and a characteristic painful rash, including several stages, such as macules, papules, blisters, pustules, scabs, and scab shedding involving the genitals and anus. Polymerase chain reaction (PCR) is usually used to detect MPXV in skin lesion material. Treatment includes supportive care, antivirals, and intravenous vaccinia immune globulin. Smallpox vaccines have been designed with four givens emergency approval for use against MPXV infection.

Study on the epidemiological characteristics of enterovirus among pediatric patients in Hangzhou, China: A comparison between the pre-COVID-19, COVID-19 pandemic, and post-COVID-19 periods.

Nonpharmaceutical interventions (NPIs) for coronavirus disease 2019 (COVID-19) not only reduce the prevalence of this disease among children but also influence the transmission of other viruses. This retrospective study investigated the impact of NPIs on human enterovirus (HEV) infection in children diagnosed with hand, foot, and mouth disease (HFMD) or herpangina (HA) in Hangzhou, China. We collected and analyzed the laboratory results and clinical data of children diagnosed with HFMD or HA during the following periods: pre-COVID-19 (January 2019 to December 2019), the COVID-19 pandemic (January 2020 to December 2022), and post-COVID-19 (January to December 2023). A total of 41 742 specimens that met the inclusion criteria were obtained, of which 1998 (4.79%) tested positive for enterovirus. In comparison to those in the pre-COVID-19 period, which had 695 (5.63%) HEV-positive specimens, the numbers dramatically decreased to 69 (1.19%), 398 (5.12%), and 112 (1.58%) in 2020, 2021, and 2022, respectively, but significantly increased to 724 (8.27%) in 2023. Seasonal peaks of infections occurred in May, June, July, and August each year, with the total detection rate ranging from 2019 to 2023 being 9.41% in May, 22.47% in June, 28.23% in July, and 12.16% in August, respectively. The difference in the detection rates of HEV infection between males and females was statistically significant (p < 0.005), with 5.11% (1221/23 898) of males and 4.35% (777/17 844) of females testing positive, resulting in a male-to-female positive ratio of 1.57:1. Among the age groups, 11.25% (378/3360) of the children aged 3-5 years had the highest detection rate, which steadily decreased with increasing or decreasing age. The detection of HEV indicated that >95% of the viruses were other types than the previously commonly reported enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16). In conclusion, NPIs for COVID-19 may be effective at reducing the transmission of HEV. However, with the relaxation of NPIs, the detection rate of HEVs increased slowly to a certain extent. Active awareness and surveillance of the epidemiological characteristics of HEV are essential for preventing, controlling, and managing the development of HFMD and HA, as well as contributing to the development of a multivalent HFMD vaccine.

Competing Effects of Molecular Additives and Cross-Link Density on the Segmental Dynamics and Mechanical Properties of Cross-Linked Polymers.

The introduction of molecular additives into thermosets often results in changes in their dynamics and mechanical properties that can have significant ramifications for diverse applications of this broad class of materials such as coatings, high-performance composites, etc. Currently, there is limited fundamental understanding of how such additives influence glass formation in these materials, a problem of broader significance in glass-forming materials. To address this fundamental problem, here, we employ a simplified coarse-grained (CG) model of a polymer network as a model of thermoset materials and then introduce a polymer additive having the same inherent rigidity and polymer-polymer interaction strength as the cross-linked polymer matrix. This energetically "neutral" or "self-plasticizing" additive model gives rise to non-trivial changes in the dynamics of glass formation and provides an important theoretical reference point for the technologically more important case of interacting additives. Based on this rather idealized model, we systematically explore the combined effect of varying the additive mass percentage (m) and cross-link density (c) on the segmental relaxation dynamics and mechanical properties of a model thermoset material with additives. We find that increasing the additive mass percentage m progressively decreases both the glass-transition temperature Tg and the fragility of glass formation, a trend opposite to increasing c so that these thermoset variables clearly have a competing effect on glass formation in these model materials. Moreover, basic mechanical properties (i.e., bulk, shear, and tensile moduli) likewise exhibit a competitive variation with the increase of m and c, which are strongly correlated with the Debye-Waller parameter ⟨u2⟩, a measure of material stiffness at a molecular scale. Our findings prove beneficial in the development of structure-property relationships for the cross-linked polymers, which could help guide the design of such network materials with tailored physical properties.

Lupus anticoagulant-hypoprothrombinemia syndrome in children: Three case reports and systematic review of the literature.

OBJECTIVE: Children with lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) are characterized by prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT), lupus anticoagulant positivity and low prothrombin (factor II, FII) levels. Bleeding or thrombosis tendencies related to LAHPS in children can occur due to the development of anti-prothrombin antibodies that are usually linked to autoimmune or infectious diseases. METHODS: We report three pediatric cases of LAHPS and describe details on their clinical symptoms, laboratory characteristics, treatment. PubMed, Medline, and Web of Science searches were conducted on LAHPS in children between 1960 and 2023; articles in English were included. RESULTS: The coagulation profile revealed prolonged PT and APTT, with low prothrombin levels (19.4%, 21.0% and 12.9%, respectively) and positive lupus anticoagulant in 3 pediatric cases. Fifty-nine relevant articles reported 93 pediatric LAHPS cases (mean age: 9 years (0.8-17 years)); 63 females and 30 males, 87 patients presented with minor to severe bleeding diathesis, and 3 patients presented with thrombosis events. Among 48 patients ≥9 years old, 36 had SLE; among 45 patients <9 years, 29 had viral infection. When all patients were divided into two groups based on age, associated disease, and factor II level, Pearson's χ2 tests were performed, p =.00, and there was clinical significance between autoimmune and infectious disease in patients ≥9 years old and <9 years old, and in patients FII level ≤10% and >10%. LAHPS patients with autoimmune disease had a protracted course and needed prolonged treatment with immune-modulating therapy, while those patients with infectious disease resolved spontaneously or needed short-term immune-modulating therapy. CONCLUSION: LAHPS caused by autoimmune disease are common in patients ≥9 years old, especially SLE, and FII level ≤10% is often reported in patients caused by autoimmune disease, suggesting that children ≥9 years old diagnosed with LAHPS-related autoimmune disease should pay special attention to the FII level. While LAHPS caused by infectious disease is more frequently observed in patients <9 years, especially viral infection. Early diagnostic investigations are critical to differentiating LAHPS caused by autoimmune or infectious disease, as the prognosis, treatment and outcome are distinct.

The Epidemiological Features of the SARS-CoV-2 Omicron Subvariant BA.5 and Its Evasion of the Neutralizing Activity of Vaccination and Prior Infection.

From December 2021 to May 2022, the Omicron BA.1 and BA.2 subvariants successively became the most dominant strains in many countries around the world. Subsequently, Omicron subvariants have emerged, and Omicron has been classified into five main lineages, including BA.1, BA.2, BA.3, BA.4, BA.5, and some sublineages (BA.1.1, BA.2.12.1, BA.2.11, BA.2.75, BA.4.6, BA.5.1, and BA.5.2). The recent emergence of several Omicron subvariants has generated new concerns about further escape from immunity induced by prior infection and vaccination and the creation of new COVID-19 waves globally. In particular, BA.5 (first found in southern Africa, February 2022) displays a higher transmissibility than other Omicron subvariants and is replacing the previously circulating BA.1 and BA.2 in several countries.

Red Cell Distribution Width Is an Independent Risk Factor of Patients with Renal Function Damage in Type 1 Diabetes Mellitus of Children in China.

AIMS: The aim of this study is to investigate whether red cell distribution width (RDW) is associated with renal function damage in patients with type 1 diabetes mellitus (T1DM) of children in China. METHODS: We used urine albumin-creatinine ratio to define microalbuminuria (MAU). A total of 170 patients were recruited in the study including 88 patients with MAU and 82 patients without MAU. Clinical and laboratory data of two groups were compared. RESULTS: The present study demonstrated that the RDW values were significantly higher in patients with MAU than those without MAU. Multivariate logistic regression indicated that RDW was an independent risk factor for renal function damage in T1DM. The receiver operating characteristic curves were used to investigate the relationship between MAU and RDW, the area under the curve was 0.75. Using the cut-off point of 12.8, RDW predicts renal function damage in T1DM patients with a sensitivity of 75.8% and a specificity of 58.2%. CONCLUSION: In this study, we suggested that RDW could be used as an effective predictor of diabetic early renal function damage or diabetes-related complications.

Antitumor activity and underlying mechanism of Sargassum fusiforme polysaccharides in CNE-bearing mice.

This study was designed to investigate the antitumor effects of Sargassum fusiforme polysaccharides (SFPS) on nasopharyngeal carcinoma (NPC) and the underlying mechanism of its effect on splenic lymphocytes. As a result, SFPS significantly inhibited the growth of nasopharyngeal carcinoma CNE in vivo, and remarkably increased the serum cytokines and IgM levels in CNE-bearing mice. Meanwhile, SFPS stimulated the peritoneal macrophages to secrete the cytokines, exerted a stimulatory effect on splenic lymphocytes proliferation, and increased the expression of IgM from splenic lymphocytes. The pretreatment of splenic lymphocytes with special antibodies (anti-TLR4 and anti-TLR2) significantly suppressed the proliferation of splenic lymphocytes and blocked SFPS-induced IgM production. SB203580, a specific inhibitor of p38 MAPK, effectively suppressed SFPS-induced IgM secretion in splenic lymphocytes. Taken together, SFPS has antitumor and immunomodulatory activities in NPC, and its activity is mediated, at least in part, by TLR2/TLR4 receptors and p38 MAPK signaling pathway.

Antitumor effects of polysaccharide from Sargassum fusiforme against human hepatocellular carcinoma HepG2 cells.

Sargassum fusiforme (Harv.) Setchel, a kind of brown algae, has been applied as a therapeutic for thousands of years. This study was designed to investigate the antitumor effects of the polysaccharide (SFPS) from S. fusiform in liver cancer. The mice inoculated with HepG2 cells were orally administrated with SFPS at the doses of 100, 200 and 400 mg/kg body weight for 28 days. The products from peritoneal macrophages and serum in HepG2-bearing mice were measured. The effect of SFPS-induced cell apoptosis was measured by flow cytometry. Meanwhile, the expression levels of Bax and Bcl-2 were detected. Furthermore, the cytotoxicity of SFPS was evaluated by CCK-8 assay. Results showed that SFPS significantly inhibited growth of human HepG2 cell-transplanted tumor in nude mice, and remarkably increased serum TNF-α, IL-1, NO and IgM levels in HepG2-bearing mice. SFPS also promoted the cytokines (IL-1 and TNF-α) secreted by peritoneal macrophages in HepG2-bearing mice. SFPS exerted a stimulatory effect on apoptosis of HepG2 cells, increased the expression of Bax, and decreased the expression of Bcl-2. The results indicated that SFPS has anti-tumor and immunomodulatory activities at the high concentration, and it could be used as a potential chemopreventative and/or adjuvant chemotherapeutic agent in liver cancer.

A polysaccharide from Sargassum fusiforme protects against immunosuppression in cyclophosphamide-treated mice.

A water-soluble polysaccharide (SFPS) isolated from Sargassum fusiforme was purified by DEAE-52 cellulose anion-exchange and Sephadex G-200 gel filtration chromatography. The high performance gel permeation chromatography (HPGPC) analysis showed that the average molecular weight (Mw) of SFPS was 299 kDa. The SFPS was composed of D-fucose, L-xylose, D-mannose and D-galactose in a molar ratio of 5.9:1.0:2.3:2.2. The results showed that SFPS stimulated proliferation and the cytokines (IL-2, IL-6 and IFN-γ) secretion of splenic lymphocytes in cyclophosphamide-induced immunosuppressed mice. SFPS markedly increased the phagocytic rates and cytokines (IL-2, IL-6 and TNF-α) secretion of peritoneal macrophages. Administration of SFPS significantly raised spleen index. It could act as an efficacious adjacent immunopotentiating therapy or an alternative means in lessening chemotherapy-induced immunosuppression, and also can be utilized as immunostimulants for food and pharmaceutical industries.

Antitumor and immunomodulatory activity of polysaccharides from Sargassum fusiforme.

Sargassum fusiforme (Harv.) Setchel is an ingredient of Chinese herbal medicine that has been applied for thousands of years. This study was set up to evaluate the in vivo and in vitro anti-tumor potential of the polysaccharide (SFPS) from S. fusiforme and the immune response in tumor-bearing mice. SFPS was isolated by hot water extraction and ethanol precipitation. The mice inoculated with A549 cells were orally administrated with SFPS at the doses of 100 and 200mg/kg body weight for 28 days. The effects on the growth of tumor, serum TNF-α level, splenocyte proliferation, production of cytokines from peritoneal macrophages in A549-bearing mice were measured. Meanwhile, the cytotoxicity of SFPS on A549 cell line was also studied. Results showed that SFPS could not only significantly inhibit the growth of A549 lung adenocarcinoma in mice, but also remarkably promote IL-1 and TNF-α production from peritoneal macrophages, serum TNF-α level, and splenocytes proliferation in A549-bearing mice. The results indicate that SFPS has anti-tumor properties in vivo and in vitro, and improves the immune response in tumor-bearing mice. It could act as anti-tumor agent with immunomodulatory activity.