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Four previously unreported phenylpropanoid glycosides (1-4), together with four known analogues (5-8), were isolated from the leaves of Illicium dunnianum. The structures of these new compounds were elucidated based on spectroscopic analysis (HR-ESI-MS, NMR, IR, UV) and chemical methods. In addition, the neuroprotective activities of all the isolates were evaluated by measuring their cell viability in H2O2-induced OLN-93 cell injury model.
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Boron-doped graphdiyne (B-GDY) material exhibits an excellent performance in electrocatalysis, ion transport, and energy storage. However, accurately identifying the structures of B-GDY in experiments remains a challenge, hindering further selection of suitable structures with the most ideal performance for various practical applications. In the present work, we employed density functional theory (DFT) to simulate the X-ray photoelectron spectra (XPS) and near-edge X-ray absorption fine-structure (NEXAFS) spectra of pristine graphdiyne (GDY) and six representative single boron-doped graphdiynes at the B and C K-edges to establish the structure-spectroscopy relationship. A notable disparity in the C 1s ionization potentials (IPs) between substituted and adsorbed structures is observed upon doping with a boron atom. By analyzing the C and B 1s NEXAFS spectra on energy positions, spectral widths, spectral intensities, and different spectral profiles, we found that the six single boron-doped graphdiyne configurations can be sensitively identified. Moreover, this study provides a reliable theoretical reference for distinguishing different single boron-doped graphdiyne structures, enabling accurate selection of B-GDY structures for diverse practical applications.
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BACKGROUND: Congenital heart disease (CHD) is the predominant birth defect. This study aimed to explore the association between maternal cardiovascular health (CVH) and the CHD risk in offspring. METHODS: We used the prospective data from the Fujian Birth Cohort Study, collected from March 2019 to December 2022 on pregnant women within 14 weeks of gestation. Overall maternal CVH was assessed by seven CVH metrics (including physical activity, smoking, sleep duration, body mass index, blood pressure, total cholesterol, and fasting plasma glucose), with each metric classified as ideal, intermediate or poor with specific points. Participants were further allocated into high, moderate and low CVH categories based on the cumulative CVH score. The association with offspring CHD was determined with log-binominal regression models. RESULTS: A total of 19810 participants aged 29.7 (SD: 3.9) years were included, with 7846 (39.6%) classified as having high CVH, 10949 (55.3%) as having moderate CVH, and 1015 (5.1%) as having low CVH. The average offspring CHD rate was 2.52%, with rates of 2.35%, 2.52% and 3.84% across the high, moderate and low CVH categories, respectively (P = 0.02). Adjusted relative risks (RRs) of having offspring CHD were 0.64 (95% CI: 0.45-0.90, P = 0.001) for high CVH and 0.67 (95% CI: 0.48-0.93, P = 0.02) for moderate CVH compared to low CVH. For individual metrics, only ideal total cholesterol was significantly associated with lower offspring CHD (RR: 0.73, 95% CI: 0.59-0.83, P = 0.002). CONCLUSIONS: Pregnant women of high or moderate CVH categories in early pregnancy had reduced risks of CHD in offspring, compared to those of low CVH. It is important to monitor and improve CVH during pre-pregnancy counseling and early prenatal care.
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Cardiopatías Congénitas , Humanos , Femenino , Embarazo , Cardiopatías Congénitas/epidemiología , Adulto , Estudios Prospectivos , China/epidemiología , Factores de Riesgo , Cohorte de Nacimiento , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Salud Materna/estadística & datos numéricos , Complicaciones Cardiovasculares del Embarazo/epidemiologíaAsunto(s)
Neoplasias Cerebelosas , Ángulo Pontocerebeloso , Tumores Fibrosos Solitarios , Humanos , Tumores Fibrosos Solitarios/cirugía , Tumores Fibrosos Solitarios/patología , Tumores Fibrosos Solitarios/diagnóstico por imagen , Ángulo Pontocerebeloso/patología , Ángulo Pontocerebeloso/diagnóstico por imagen , Neoplasias Cerebelosas/patología , Neoplasias Cerebelosas/diagnóstico por imagen , Neoplasias Cerebelosas/cirugía , Masculino , Femenino , Persona de Mediana Edad , Imagen por Resonancia MagnéticaRESUMEN
OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.
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Empiema , Hidrocefalia , Meningitis Neumocócica , Efusión Subdural , Lactante , Femenino , Masculino , Humanos , Niño , Recién Nacido , Adolescente , Meningitis Neumocócica/tratamiento farmacológico , Meningitis Neumocócica/epidemiología , Meropenem , Vancomicina , Levofloxacino , Linezolid , Moxifloxacino , Estudios Retrospectivos , Rifampin , Streptococcus pneumoniae , CloranfenicolRESUMEN
BACKGROUND: Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology. METHODS: The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing. RESULTS: Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before. CONCLUSION: Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.
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Disostosis Mandibulofacial , Infecciones del Sistema Respiratorio , Femenino , Humanos , China , Pérdida Auditiva Conductiva , Disostosis Mandibulofacial/genética , Proteínas Nucleares/genética , Fosfoproteínas/genética , Estudios RetrospectivosRESUMEN
The emergence of SARS-CoV-2 presents a significant global public health dilemma. Vaccination has long been recognized as the most effective means of preventing the spread of infectious diseases. DNA vaccines have attracted attention due to their safety profile, cost-effectiveness, and ease of production. This study aims to assess the efficacy of plasmid-encoding GM-CSF (pGM-CSF) as an adjuvant to augment the specific humoral and cellular immune response elicited by DNA vaccines based on the receptor-binding domain (RBD) antigen. Compared to the use of plasmid-encoded RBD (pRBD) alone, mice that were immunized with a combination of pRBD and pGM-CSF exhibited significantly elevated levels of RBD-specific antibody titers in serum, BALF, and nasal wash. Furthermore, these mice generated more potent neutralization antibodies against both the wild-type and Omicron pseudovirus, as well as the ancestral virus. In addition, pGM-CSF enhanced pRBD-induced CD4+ and CD8+ T cell responses and promoted central memory T cells storage in the spleen. At the same time, tissue-resident memory T (Trm) cells in the lung also increased significantly, and higher levels of specific responses were maintained 60 days post the final immunization. pGM-CSF may play an adjuvant role by promoting antigen expression, immune cells recruitment and GC B cell responses. In conclusion, pGM-CSF may be an effective adjuvant candidate for the DNA vaccines against SARS-CoV-2.
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COVID-19 , Vacunas de ADN , Humanos , Animales , Ratones , Factor Estimulante de Colonias de Granulocitos y Macrófagos , SARS-CoV-2 , Vacunas contra la COVID-19 , COVID-19/prevención & control , Adyuvantes Inmunológicos/farmacología , Adyuvantes Farmacéuticos , Vacunación , ADN , Anticuerpos Antivirales , Anticuerpos NeutralizantesRESUMEN
Cationic nanostructures have emerged as an adjuvant and antigen delivery system that enhances dendritic cell maturation, ROS generation, and antigen uptake and then promotes antigen-specific immune responses. In recent years, retinoic acid (RA) has received increasing attention due to its effect in activating the mucosal immune response; however, in order to use RA as a mucosal adjuvant, it is necessary to solve the problem of its dissolution, loading, and delivery. Here, we describe a cationic nanoemulsion-encapsulated retinoic acid (CNE-RA) delivery system composed of the cationic lipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOTAP), retinoic acid, squalene as the oil phase, polysorbate 80 as surfactant, and sorbitan trioleate 85 as co-surfactant. Its physical and chemical properties were characterized using dynamic light scattering and a spectrophotometer. Immunization of mice with the mixture of antigen (ovalbumin, OVA) and CNE-RA significantly elevated the levels of anti-OVA secretory immunoglobulin A (sIgA) in vaginal lavage fluid and the small intestinal lavage fluid of mice compared with OVA alone. This protocol describes a detailed method for the preparation, characterization, and evaluation of the adjuvant effect of CNE-RA.
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Adyuvantes Inmunológicos , Inmunización , Femenino , Animales , Ratones , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/química , Membrana Mucosa , Vacunación , Antígenos , Inmunidad Mucosa , Tensoactivos/farmacología , Ovalbúmina , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis. METHODS: A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed. RESULTS: OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study. CONCLUSIONS: Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.
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Diagnóstico Prenatal , Humanos , Femenino , Embarazo , Estudios Prospectivos , Diagnóstico Prenatal/métodos , Adulto , Cariotipificación , Mapeo Cromosómico , Líquido Amniótico/química , Líquido Amniótico/citologíaRESUMEN
N-Acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) therapies have received approval for treating both orphan and prevalent diseases. To improve in vivo efficacy and streamline the chemical synthesis process for efficient and cost-effective manufacturing, we conducted this study to identify better designs of GalNAc-siRNA conjugates for therapeutic development. Here, we present data on redesigned GalNAc-based ligands conjugated with siRNAs against angiopoietin-like 3 (ANGPTL3) and lipoprotein (a) (Lp(a)), two target molecules with the potential to address large unmet medical needs in atherosclerotic cardiovascular diseases. By attaching a novel pyran-derived scaffold to serial monovalent GalNAc units before solid-phase oligonucleotide synthesis, we achieved increased GalNAc-siRNA production efficiency with fewer synthesis steps compared to the standard triantennary GalNAc construct L96. The improved GalNAc-siRNA conjugates demonstrated equivalent or superior in vivo efficacy compared to triantennary GalNAc-conjugated siRNAs.
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Enfermedades Cardiovasculares , Hepatocitos , Humanos , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/química , Análisis Costo-Beneficio , ARN Bicatenario , Acetilgalactosamina/química , Proteína 3 Similar a la AngiopoyetinaRESUMEN
BACKGROUND: Non-liquefied multiple liver abscesses (NMLA) can induce sepsis, septic shock, sepsis-associated kidney injury (SA-AKI), and multiple organ failure. The inability to perform ultrasound-guided puncture and drainage to eradicate the primary disease may allow for the persistence of bacterial endotoxins and endogenous cytokines, exacerbating organ damage, and potentially causing immunosuppression and T-cell exhaustion. Therefore, the search for additional effective treatments that complement antibiotic therapy is of great importance. CASE SUMMARY: A 45-year-old critically ill female patient presented to our hospital's intensive care unit with intermittent vomiting, diarrhea, and decreased urine output. The patient exhibited a temperature of 37.8 °C. Based on the results of liver ultrasonography, laboratory tests, fever, and oliguria, the patient was diagnosed with NMLA, sepsis, SA-AKI, and immunosuppression. We administered antibiotic therapy, entire care, continuous renal replacement therapy (CRRT) with an M100 hemofilter, and hemoperfusion (HP) with an HA380 hemofilter. The aforementioned treatment resulted in a substantial reduction in disease severity scores and a decrease in the extent of infection and inflammatory factors. In addition, the treatment stimulated the expansion of the cluster of differentiation 8+ (CD8+) T-cells and led to the complete recovery of renal function. The patient was discharged from the hospital. During the follow-up period of 28 d, she recovered successfully. CONCLUSION: Based on the entire therapeutic regimen, the early combination of CRRT and HP therapy may control sepsis caused by NMLA and help control infections, reduce inflammatory responses, and improve CD8+ T-cell immune function.
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The fruits of Alpinia oxyphylla have been used for centuries in China as both edible resources and traditional Chinese medicine. In order to identify structurally interesting and bioactive constituents from the fruits of A. oxyphylla, bioassay-guided fractionation and purification of the crude extracts were performed, which led to the isolation of 38 sesquiterpenoids, including six previously undescribed eremophilane sesquiterpenoids (1-6), six new cadinane sesquiterpenoids (23-24, 26-29), and 26 known analogues (7-22, 25 and 31-38). The structures of these compounds were elucidated by comprehensive spectroscopic data analysis, single crystal X-ray diffraction, quantum chemistry calculations (13C-NMR and ECD), and Mo2(OAc)4 reaction. Several of the isolated compounds (8, 13, 17, 18, 30, 31 and 35) showed moderate to strong inhibition of the secretion of cytokines (NO, TNF-α and IL-6) in LPS-stimulated BV-2 cells. Furthermore, western blot, immunofluorescence, and real-time PCR assays indicated that 18 could down-regulate the mRNA levels of TNF-α, IL-6, COX-2, and iNOS and the protein expression of COX-2 and iNOS. Meanwhile, 18 was able to partially inhibit the phosphorylation of ERK1/2, JNK, and p38. Thus, the discovery of structurally diverse anti-inflammatory sesquiterpenoids from the fruits of A. oxyphylla in this study could benefit the further development and utilization of this plant.
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Alpinia , Sesquiterpenos , Frutas/química , Alpinia/química , Factor de Necrosis Tumoral alfa/genética , Ciclooxigenasa 2/genética , Interleucina-6/genética , Sesquiterpenos Policíclicos , Sesquiterpenos/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/análisisRESUMEN
Eradication of methicillin-resistant Staphylococcus aureus (MRSA) is challenging due to multi-drug resistance of strains and biofilm formation, the latter of which is an important barrier to the penetration of antibiotics and host defences. As such, there is an urgent need to discover and develop novel agents to fight MRSA-associated infection. In this study, HL-J6, a novel indolylbenzoquinone compound, was shown to inhibit S. aureus strains, with a minimum inhibitory concentration against MRSA252 of 2 µg/mL. Moreover, HL-J6 exhibited potent antibiofilm activity in vitro and was able to kill bacteria in biofilm. In the mouse models of wound infection, HL-J6 treatment reduced the MRSA load significantly and inhibited biofilm formation on the wounds. The potent targets of its antibiofilm activity were explored by real-time reverse transcriptase polymerase chain rection, which indicated that HL-J6 downregulated the transcription levels of sarA, atlAE and icaADBC. Moreover, Western blot results showed that HL-J6 reduced the secretion level of α-toxin, a major virulence factor. These findings indicate that HL-J6 is a promising lead compound for the development of novel drugs against MRSA biofilm infections.
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Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Animales , Ratones , Staphylococcus aureus , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Biopelículas , Pruebas de Sensibilidad MicrobianaAsunto(s)
Anestesiólogos , Agotamiento Profesional , COVID-19 , Humanos , Agotamiento Profesional/epidemiología , Agotamiento Profesional/psicología , Agotamiento Psicológico , COVID-19/epidemiología , COVID-19/psicología , Pueblos del Este de Asia/psicología , Pandemias , Anestesiólogos/psicología , Anestesiólogos/estadística & datos numéricos , China/epidemiologíaRESUMEN
One undescribed benzofuran derivative (illiciumphenolicacid A, 1) and one new phenolic glycoside (illiciumphenolicacid B, 2), together with six known compounds (3-8) were isolated from the leaves of Illicium dunnianum Tutcher. Their structures were elucidated by detailed spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR). In addition, we determined the α-glucosidase inhibitory activity of the isolates in vitro using spectrophotometric methods. Compared with the positive control acarbose (IC50 306.2 ± 4.1 µM), compounds 1-8 were shown to be moderate potential α-glucosidase inhibitory activity with IC50 values in the range 380-655 µM.
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Endotoxin-induced acute kidney injury (AKI) is commonly observed in clinical practice. Renal tubular epithelial cell (RTEC) pyroptosis is one of the main factors leading to the development of endotoxin-induced AKI. Mitochondrial dysfunction can lead to pyroptosis. However, the biological pathways involved in the potential lipopolysaccharide (LPS)-induced pyroptosis of RTECs, notably those associated with mitochondrial dysfunction, are poorly understood. Previous studies have demonstrated that heme oxygenase (HO)-1 confers cell protection via the induction of PTEN-induced putative kinase 1 (PINK1) expression through PTEN to regulate mitochondrial fusion/fission during endotoxin-induced AKI in vivo. Therefore, the present study investigated the role of HO-1/PINK1 in maintaining mitochondrial function and inhibiting the pyroptosis of RTECs exposed to LPS. Primary cultures of RTECs were obtained from wild-type (WT) and PINK1-knockout (PINK1KO) rats. An in vitro model of endotoxin-associated RTEC injury was established following treatment of the cells with LPS. The WT RTECs were divided into the control, LPS, Znpp + LPS and Hemin + LPS groups, and the PINK1KO RTECs were divided into the control, LPS and Hemin + LPS groups. RTECs were exposed to LPS for 6 h to assess cell viability, inflammation, pyroptosis and mitochondrial function. In the LPS-treated RTECs, the mRNA and protein expression levels of HO-1 and PINK1 were upregulated. Cell viability, adenosine triphosphate (ATP) levels and the mitochondrial oxygen consumption rate were decreased, whereas the inflammatory response, pyroptosis and mitochondrial reactive oxygen species (ROS) levels were increased. The cell inflammatory response and the induction of pyroptosis were inhibited, whereas the levels of mitochondrial ROS were decreased. In addition, the cell viability and ATP levels were increased in the WT RTECs following the upregulation of HO-1 expression. These effects were reversed by the downregulation of HO-1 expression. However, no statistically significant differences were noted between the LPS and the Hemin + LPS groups in the PINK1KO RTECs. Collectively, the findings of the present study indicate that HO-1 inhibits inflammation and regulates mitochondrial function by inhibiting the pyroptosis of LPS-exposed RTECs via PINK1.
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Helicobacter pylori (H. pylori) colonizes the stomach epithelium of half the world's population and is responsible for various digestive diseases and even stomach cancer. Vaccine-mediated protection against H. pylori infection depends primarily on the specific mucosal and T-cell responses. In this study, the synthetic lipopeptide vaccines, Hp4 (Pam2 Cys modified UreB T-cell epitope) and Hp10 (Pam2 Cys modified CagA T/B cell combined epitope), not only induce the bone marrow derived dendritic cells (BMDCs) maturation by activating a variety of pattern-recognition receptors (PRRs) such as Toll-like receptor (TLR), Nod-like receptor (NLR), and retinoic acid-inducing gene (RIG) I-like receptor (RLR), and but also stimulate BMDCs to secret cytokines that have the potential to modulate T-cell activation and differentiation. Although intranasal immunization with Hp4 or Hp10 elicits robust epitope-specific T-cell responses in mice, only Hp10 confers protection against H. pylori infection, possibly due to the fact that Hp10 also induces substantial specific sIgA response at mucosal sites. Interestingly, Hp4 elevates the protective response against H. pylori infection of Hp10 when administrated in combination, characterized by better protective effect and enhanced specific T-cell and mucosal antibody responses. The results suggest that synthetic lipopeptide vaccines based on the epitopes derived from the protective antigens are promising candidates for protection against H. pylori infection.
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Infecciones por Helicobacter , Helicobacter pylori , Animales , Ratones , Helicobacter pylori/genética , Infecciones por Helicobacter/prevención & control , Lipopéptidos/farmacología , Vacunas Bacterianas , Adyuvantes Inmunológicos , Epítopos de Linfocito T , Vacunas Sintéticas , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: Newborn screening (NBS) is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases. The development of next-generation sequencing (NGS) technology provides new opportunities to expand current newborn screening methodologies. METHODS: We designed a a newborn genetic screening (NBGS) panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS. With this panel, a large-scale, multicenter, prospective multidisease analysis was conducted on dried blood spot (DBS) profiles from 21,442 neonates nationwide. RESULTS: We presented the positive detection rate and carrier frequency of diseases and related variants in different regions; and 168 (0.78%) positive cases were detected. Glucose-6-Phosphate Dehydrogenase deficiency (G6PDD) and phenylketonuria (PKU) had higher prevalence rates, which were significantly different in different regions. The positive detection of G6PD variants was quite common in south China, whereas PAH variants were most commonly identified in north China. In addition, NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants, which were normal in conventional NBS, but were confirmed later as abnormal in repeated biochemical testing after recall. Eighty percent of high-frequency gene carriers and 60% of high-frequency variant carriers had obvious regional differences. On the premise that there was no significant difference in birth weight and gestational age, the biochemical indicators of SLC22A5 c.1400C > G and ACADSB c.1165A > G carriers were significantly different from those of non-carriers. CONCLUSIONS: We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS methods. Our data also showed that the prevalence of diseases has significant regional characteristics, which provides a theoretical basis for screening diseases in different regions.
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Tamizaje Neonatal , Fenilcetonurias , Humanos , Recién Nacido , Tamizaje Neonatal/métodos , Estudios Prospectivos , Pruebas Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Proteínas de Transporte de Membrana Mitocondrial/genética , Miembro 5 de la Familia 22 de Transportadores de Solutos/genéticaRESUMEN
OBJECTIVE: Olecranon osteotomy and paratricipital approaches were widely used in the treatment of type C distal humerus fracture but some disadvantages exist, so a combined medial and lateral approach was designed. The objective of this study was to investigate and compare the clinical outcomes of combined medial and lateral approach with the paratricipital approach in open reduction and internal fixation of type C distal humerus fractures. METHODS: From May 2018 to April 2020, 37 patients with type C distal humerus fracture who accepted open reduction and internal fixation in our hospital were enrolled in this study. All cases were randomly divided into two groups according to the surgical approach: combined medial and lateral approach group (19 cases), paratricipital approach group (18 cases). All of the patients received open reduction and double vertical plates fixation. The operation and follow-up indexes, including operation time, blood loss, incision length, triceps muscle strength, flexion-extension arc of elbow and forearm rotation arc, were recorded and compared. Caja score was used to assess the quality of fractures reduction. Mayo Elbow Performance Score (MEPS) was used to evaluate the elbow function in the follow-up. Complications such as incision infection, ulnar nerve injury, degenerative osteoarthritis, and heterotopic ossification were analyzed. RESULTS: The differences in age, gender, and AO classification of fractures between two groups were not statistically significant (p > 0.05). The sum of medial and lateral incision length of combined approach group was longer than the midline incision of paratricipital approach group (15.4 ± 0.8 vs. 14.6 ± 0.8, p < 0.05), but there was no significant difference in operation time (103.5 ± 10.2 vs. 106.0 ± 8.8, p > 0.05), blood loss (71.3 ± 24.5 vs. 72.8 ± 24.6, p > 0.05), and Caja score (16.05 ± 5.67 vs. 15.56 ± 5.66, p > 0.05). During the follow-up, the MEPS of combined approach group was higher than that of paratricipital approach group at 3 months postoperatively (80.5 ± 5.7 vs. 68.9 ± 8.1, p < 0.05), but there was no significant difference in MEPS at 6 months postoperatively (83.9 ± 6.6 vs. 79.7 ± 7.0, p > 0.05) and at the last follow-up (86.8 ± 7.1 vs. 86.9 ± 7.7, p > 0.05) between the two groups. There was no significant difference in triceps muscle strength (p > 0.05), flexion-extension arc (126.8 ± 5.3 vs. 128.9 ± 6.0, p > 0.05), and forearm rotation arc (163.2 ± 5.3 vs. 163.6 ± 4.8, p > 0.05) at the last follow-up. Although the incidence of complication of combined approach group (15.8%) was lower than that of paratricipital approach group (22.2%), the difference was not statistically significant (p > 0.05). CONCLUSIONS: The combined medial and lateral approach was an effective and safe way of open reduction and internal fixation for type C distal humerus fractures. Compared with the paratricipital approach, the combined medial and lateral approach could restore the elbow function more quickly postoperatively, and the long-term results were comparable.