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Endocervical adenocarcinoma (ECA) is reported increasingly often in young women, and this aggressive disease lacks effective methods of targeted therapy. Since mismatch repair deficiency (dMMR) is an important biomarker for predicting response to immune checkpoint inhibitors, it is important to investigate the clinicopathological features and immune microenvironment of dMMR ECAs. We assessed 617 ECAs from representative tissue microarray sections, gathered clinicopathologic information, reviewed histological characteristics, and performed immunohistochemical staining for MMR, programmed cell death 1 (PD-L1), and other immune markers. Of 617 ECA samples, 20 (3.2%) cases had dMMR. Among them, loss of MMR-related proteins expression was observed in 17/562 (3.0%) human papilloma virus-associated (HPVA) adenocarcinoma and 3/55 (5.5%) non-HPV-associated (NHPVA) adenocarcinoma. In NHPVA cohort, dMMR status was observed in 3 (3/14, 15.0%) patients with clear cells. dMMR ECAs had a higher tendency to have a family history of cancer, larger tumor size, p16 negative, HPV E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) negative, and lower ki-67 index. Among the morphological variables evaluated, poor differentiation, necrosis, stromal tumor-infiltrating lymphocytes, peritumoral lymphocytes, and lymphoid follicles were easily recognized in the dMMR ECAs. In addition, dMMR ECAs had higher CD3+, CD8+, CD38+, CD68+ and PD-1+ immune cells. A relatively high prevalence of PD-L1 expression was observed in dMMR ECAs. dMMR ECAs were significantly more likely to present with a tumor-infiltrating lymphocytes -high/PD-L1-positive status. In conclusion, dMMR ECAs have some specific morphological features and a critical impact on the immune microenvironment, which may provide insights into improving responses to immunotherapy-included comprehensive treatment for ECAs in the future.
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Neoadjuvant chemotherapy (NACT) is a viable therapeutic option for women diagnosed locally advanced cervical cancer (LACC). However, the factors influencing pathological response are still controversial. We collected pair specimens of 185 LACC patients before and after receiving NACT and conducted histological evaluation. 8 fresh tissues pre-treatment were selected from the entire cohort to conducted immune gene expression profiling. A novel pathological grading system was established by comprehensively assessing the percentages of viable tumor, inflammatory stroma, fibrotic stroma, and necrosis in the tumor bed. Then, 185 patients were categorized into either the good pathological response (GPR) group or the poor pathological response (PPR) group post-NACT, with 134 patients (72.4%, 134/185) achieving GPR. Increasing tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating lymphocytes volume (TILV) pre-treatment were correlated with GPR, with TILV emerging as an independent predictive factor for GPR. Additionally, CIBERSORT analysis revealed noteworthy differences in the expression of immune makers between cPR and non-cPR group. Furthermore, a significantly heightened density of CD8 + T cells and a reduced density of FOXP3 + T cells were observed in GPR than PPR. Importantly, patients exhibiting GPR or inflammatory type demonstrated improved overall survival and disease-free survival. Notably, stromal type was an independent prognostic factor in multivariate analysis. Our study indicates the elevated TILV in pre-treatment specimens may predict a favorable response to NACT, while identifying stromal type in post-treatment specimens as an independent prognostic factor. Moreover, we proposed this pathological grading system in NACT patients, which may offer a more comprehensive understanding of treatment response and prognosis.
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Linfocitos Infiltrantes de Tumor , Terapia Neoadyuvante , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Persona de Mediana Edad , Linfocitos Infiltrantes de Tumor/inmunología , Adulto , Resultado del Tratamiento , Anciano , Supervivencia sin EnfermedadRESUMEN
Objective: To analyze the clinical characteristics and prognostic impacts of SARS-CoV-2 Omicron infection among cancer inpatients during the December 2022 - February 2023 surge, in order to provide scientific evidence for clinical treatment and prevention and control measures. Methods: A retrospective analysis was conducted on the clinical features, prognosis, and vaccination status of cancer in-patients infected with the Omicron variant during the COVID-19 pandemic of December 2022 - February 2023. Results: A total of 137 cancer inpatients were included in the study, with a median age of 61 years, and 75 patients (54.74%) were male. The main symptoms were cough (69 cases, 50.36%), expectoration (60 cases, 43.80%), and fever (53 cases, 39.69%). Chest CT examination revealed bilateral pneumonia in 47 cases (34.31%, 47/137) and pleural effusion in 24 cases (17.52%, 24/137). Among the cancer patients, 116 cases (84.67%, 116/137) had solid tumors, and 21 cases (15.33%, 21/137) had hematologic malignancies, with the main types being breast cancer (25 cases, 18.25%) and lung cancer (24 cases, 17.52%). Among the cancer patients, 46 cases (33.58%) were asymptomatic, 81 cases (59.12%) had mild disease, 10 cases (7.30%) had severe infection, and 8 cases (5.84%) died. A total of 91 patients (66.42%) had been vaccinated, with 58 patients (42.34%) receiving three doses. Multivariate analysis showed that cerebral infarction and hypoproteinemia were risk factors for death from COVID-19 infection. Conclusion: Cancer patients infected with SARS-CoV-2 Omicron typically exhibit mild disease manifestations, but some cancer patients infected with the Omicron variant might progress to severe illness, and even death, necessitating close monitoring and attention during the early stages of infection. Additionally, the presence of cerebral infarction and hypoproteinemia significantly increases the risk of death.
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Largemouth bass (Micropterus salmoides) has emerged as a significant economic fish species, with a rise in Aeromonas veronii infections in farming. However, research on adjuvants for vaccines against A. veronii in largemouth bass remains scarce. In present study, recombinant largemouth bass IL-1ß (LbIL-1ß) was expressed to explore its adjuvant effect on the A. veronii inactivated vaccine. Following vaccination with recombinant LbIL-1ß (rLbIL-1ß) and the inactivated A. veronii, higher serum SOD levels and lysozyme activities were observed in largemouth bass from inactivated A. veronii + rLbIL-1ß vaccinated group. Furthermore, it was discovered that rLbIL-1ß was able to boost the serum-specific antibody levels induced by the inactivated A. veronii. The qRT-PCR analysis revealed that rLbIL-1ß also enhanced the expression of IgM, CD4, and MHC II in largemouth bass triggered by the inactivated A. veronii. After challenged with live A. veronii, the outcomes demonstrated that the relative percentage survival (RPS) for largemouth bass resulting from the inactivated A. veronii in combination with rLbIL-1ß was 76.67 %, surpassing the RPS of 60 % in the inactivated A. veronii group. Collectively, these findings indicate that rLbIL-1ß enhances the protective effect of the A. veronii inactivated vaccine on largemouth bass, showcasing potential as an adjuvant for further development.
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Adyuvantes Inmunológicos , Aeromonas veronii , Vacunas Bacterianas , Lubina , Enfermedades de los Peces , Interleucina-1beta , Vacunas de Productos Inactivados , Animales , Aeromonas veronii/inmunología , Vacunas Bacterianas/inmunología , Lubina/inmunología , Lubina/microbiología , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/prevención & control , Enfermedades de los Peces/microbiología , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Gramnegativas/veterinaria , Infecciones por Bacterias Gramnegativas/prevención & control , Vacunación , Vacunas de Productos Inactivados/inmunologíaRESUMEN
Objective: To investigate the clinical characteristics and risk factors of patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. Methods: A retrospective analysis of general clinical data was conducted on patients with SARS-CoV-2 omicron infection complicated with hypertension, coronary heart disease, and heart failure admitted to one hospital in Guangdong Province from December 1, 2022, to February 28, 2023. Clinical symptoms, laboratory tests, imaging examinations, treatment, and clinical outcomes were collected. Multivariate logistic regression analysis was used to analyze the risk factors for mortality in patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. ROC curves were drawn to evaluate the predictive value of CRP, D-dimer, and CK-MB in predicting the risk of death. Results: A total of 364 confirmed cases were included, divided into the asymptomatic group, mild to moderate group, and severe to critically ill group based on the symptoms of COVID-19. There were 216 males (59.34%) and 148 females (40.66%), with a median age of 75 years. The differences between the three groups in terms of sex and age were statistically significant (p < 0.05). The top three underlying diseases were hypertension (288 cases, 79.12%), coronary heart disease (100 cases, 27.47%), and diabetes (84 cases, 23.08%). The differences in unvaccinated and triple-vaccinated patients among the three groups were statistically significant (p < 0.05). The common respiratory symptoms were cough in 237 cases (65.11%) and sputum production in 199 cases (54.67%). In terms of laboratory tests, there were statistically significant differences in neutrophils, lymphocytes, red blood cells, C-reactive protein, D-dimer, aspartate aminotransferase, and creatinine among the three groups (p < 0.05). In imaging examinations, there were statistically significant differences among the three groups in terms of unilateral pulmonary inflammation, bilateral pulmonary inflammation, and bilateral pleural effusion (p < 0.05). There were statistically significant differences among the three groups in terms of antibiotic treatment, steroid treatment, oxygen therapy, nasal cannula oxygen inhalation therapy, non-invasive ventilation, and tracheal intubation ventilation (p < 0.05). Regarding clinical outcomes, there were statistically significant differences among the three groups in terms of mortality (p < 0.05). Multivariate logistic regression analysis showed that CRP (OR = 1.012, 95% CI = 1.004-1.019) and D-dimer (OR = 1.117, 95% CI = 1.021-1.224) were independent risk factors for patient mortality. The predictive value of CRP, D-dimer, and CK-MB for the risk of death was assessed. D-dimer had the highest sensitivity (95.8%) in predicting patient mortality risk, while CRP had the highest specificity (84.4%). Conclusion: For patients with COVID-19 and concomitant cardiovascular diseases without contraindications, early administration of COVID-19 vaccines and booster shots can effectively reduce the mortality rate of severe cases. Monitoring biomarkers such as CRP, D-dimer, and CK-MB and promptly providing appropriate care can help mitigate the risk of mortality in patients.
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BACKGROUND: Vessels encapsulating tumor clusters (VETC) is a newly described vascular pattern that is distinct from microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). Despite its importance, the current pathological diagnosis report does not include information on VETC and hepatic plates (HP). We aimed to evaluate the prognostic value of integrating VETC and HP (VETC-HP model) in the assessment of HCC. METHODS: A total of 1255 HCC patients who underwent radical surgery were classified into training (879 patients) and validation (376 patients) cohorts. Additionally, 37 patients treated with lenvatinib were studied, included 31 patients in high-risk group and 6 patients in low-risk group. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to establish a prognostic model for the training set. Harrell's concordance index (C-index), time-dependent receiver operating characteristics curve (tdROC), and decision curve analysis were utilized to evaluate our model's performance by comparing it to traditional tumor node metastasis (TNM) staging for individualized prognosis. RESULTS: A prognostic model, VETC-HP model, based on risk scores for overall survival (OS) was established. The VETC-HP model demonstrated robust performance, with area under the curve (AUC) values of 0.832 and 0.780 for predicting 3- and 5-year OS in the training cohort, and 0.805 and 0.750 in the validation cohort, respectively. The model showed superior prediction accuracy and discrimination power compared to TNM staging, with C-index values of 0.753 and 0.672 for OS and disease-free survival (DFS) in the training cohort, and 0.728 and 0.615 in the validation cohort, respectively, compared to 0.626 and 0.573 for TNM staging in the training cohort, and 0.629 and 0.511 in the validation cohort. Thus, VETC-HP model had higher C-index than TNM stage system(p < 0.01).Furthermore, in the high-risk group, lenvatinib alone appeared to offer less clinical benefit but better disease-free survival time. CONCLUSIONS: The VETC-HP model enhances DFS and OS prediction in HCC compared to traditional TNM staging systems. This model enables personalized temporal survival estimation, potentially improving clinical decision-making in surveillance management and treatment strategies.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Curva ROC , Anciano , Análisis de Supervivencia , Estimación de Kaplan-Meier , Reproducibilidad de los Resultados , Quinolinas/uso terapéutico , Compuestos de FenilureaRESUMEN
Viperin, also known as radical S-Adenosyl methionine domain containing 2 (RSAD2), is an IFN stimulated protein that plays crucial roles in innate immunity. Here, we identified a viperin gene from the koi carp (Cyprinus carpio) (kVip). The ORF of kVip is 1047 bp in length, encoding a polypeptide of 348 amino acids with neither signal peptide nor transmembrane protein. The predicted molecular weight is 40.37 kDa and the isoelectric point is 7.7. Multiple sequence alignment indicated that putative kVip contains a radical SAM superfamily domain and a conserved C-terminal region. kVip was highly expressed in the skin and spleen of healthy koi carps, and significantly stimulated in both natural and artificial CEV-infected koi carps. In vitro immune stimulation analysis showed that both extracellular and intracellular poly (I: C) or poly (dA: dT) caused a significant increase in kVip expression of spleen cells. Furthermore, intraperitoneal injection of recombinant kVip (rkVip) not only reduced the CEV load in the gills, but also improved the survival of koi carps following CEV challenge. Additionally, rkVip administration effectively regulated inflammatory and anti-inflammatory cytokines (IL-6, IL-1ß, TNF-α, IL-10) and interferon-related molecules (cGAS, STING, MyD88, IFN-γ, IFN-α, IRF3 and IRF9). Collectively, kVip effectively responded to CEV infection and exerted antiviral function against CEV partially by regulation of inflammatory and interferon responses.
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Carpas , Enfermedades de los Peces , Infecciones por Poxviridae , Poxviridae , Animales , Carpas/genética , Edema , Interferones , Antivirales/farmacologíaRESUMEN
G protein-coupled receptors (GPCRs) are expressed in a variety of cell types and tissues, and activation of GPCRs is involved in enormous metabolic pathways, including nutrient synthesis, transportation, storage or insulin sensitivity, etc. This review intends to summarize the regulation of metabolic homeostasis and mechanisms by a series of GPCRs, such as GPR91, GPR55, GPR119, GPR109a, GPR142, GPR40, GPR41, GPR43 and GPR120. With deep understanding of GPCR's structure and signaling pathways, it is attempting to uncover the role of GPCRs in major metabolic diseases, including metabolic syndrome, diabetes, dyslipidemia and nonalcoholic steatohepatitis, for which the global prevalence has risen during last two decades. An extensive list of agonists and antagonists with their chemical structures in a nature of small molecular compounds for above-mentioned GPCRs is provided as pharmacologic candidates, and their preliminary data of preclinical studies are discussed. Moreover, their beneficial effects in correcting abnormalities of metabolic syndrome, diabetes and dyslipidemia are summarized when clinical trials have been undertaken. Thus, accumulating data suggest that these agonists or antagonists might become as new pharmacotherapeutic candidates for the treatment of metabolic diseases.
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Enfermedades Metabólicas , Receptores Acoplados a Proteínas G , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Animales , Enfermedades Metabólicas/tratamiento farmacológico , Enfermedades Metabólicas/metabolismo , Desarrollo de Medicamentos , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Plutella xylostella (Linnaeus) is a destructive pest of cruciferous crops due to its strong reproductive capacity and extensive resistance to pesticides. Seminal fluid proteins (SFPs) are the main effective factors that determine the reproductive physiology and behaviour of both sexes. Although an increasing number of SFPs have been identified, the effects of astacins in SFPs on agricultural pests have not yet been reported. Here, we elucidated the mechanisms by which Sast1 (seminal astacin 1) regulates the fertility of Plutella xylostella (L.). RESULTS: PxSast1 was specifically expressed in the testis and accesssory gland. CRISPR/Cas9-induced PxSast1 knockout successfully constructed two homozygous mutant strains. Sast1 impaired the fertility of P. xylostella by separately regulating the reproductive capacity of males and females. Loss of PxSast1, on the one hand, significantly decreased the ability of males to mate and fertilize, mainly manifested as shortened mating duration, reduced mating competitiveness and decreased eupyrene sperm production; on the other hand, it significantly inhibited the expression of chorion genes in females, resulting in oogenesis deficits. Simultaneously, for mated females, the differentially expressed genes in signalling pathways related to oogenesis and chorion formation were significantly enriched after PxSast1 knockout. CONCLUSION: These analyses of the functions of PxSast1 as the regulator of spermatogenesis and oogenesis establish its importance in the fertility process of P. xylostella, as well as its potential as a promising target for genetic regulation-based pest control. © 2024 Society of Chemical Industry.
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Proteínas de Insectos , Mariposas Nocturnas , Animales , Femenino , Masculino , Fertilidad , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Mariposas Nocturnas/genética , Mariposas Nocturnas/crecimiento & desarrollo , Proteínas de Plasma Seminal/genética , Proteínas de Plasma Seminal/metabolismoRESUMEN
Background: Periaortic fat is associated with coronary disease. Thus, it was hypothesized that the inflammation associated with acute aortic dissection (AAD) spreads to pericoronary adipose tissue (PCAT) via thoracic periaortic fat. Pericoronary adipose tissue attenuation (PCATa) serves as a marker for inflammation of perivascular adipose tissue (PVAT). This study sought to examine PCATa in individuals diagnosed with AAD. Methods: Consecutive patients with chest pain from May 2020 to September 2022 were prospectively enrolled in this study and underwent coronary computed tomography angiography (CCTA) and/or aorta computed tomography angiography (CTA). Based on the results of the CTA, the patients were divided into the following two groups: (I) the AAD group; and (II) the non-AAD group. PCATa of the right coronary angiography (RCA), left anterior descending (LAD), and left circumflex (LCx) was quantified for each patient using semi-automated software. The PCATa values were compared between the AAD and non-AAD patients according to the atherosclerosis of the coronary arteries. Similarly, the PCATa values of the AAD patients were compared between the preoperative and postoperative steady states. Results: A total of 136 patients (42 female, 94 male; mean age: 63.3±11.9 years) were divided into the two groups according to the presence of aortic dissection on CTA. The RCAPCATa, LADPCATa, and LCxPCATa values were significantly higher in the AAD subjects than the non-AAD subjects, regardless of the presence or absence of atherosclerosis in the coronary arteries [-85.1±9.3 vs. -92.9±10.0 Hounsfield unit (HU); -83.2±7.4 vs. -89.9±9.1 HU; -77.5±8.4 vs. -85.6±7.9 HU, all P<0.001). The preoperative RCAPCATa, LADPCATa, and LCxPCATa values were higher in the AAD patients than the postoperative steady-state patients (-82.9±8.7 vs. -97.6±8.8 HU; -79.8±7.6 vs. -92.8±6.8 HU; -74.6±7.1 vs. -87.7±6.9 HU, all P<0.001). According to the multivariable logistic regression analysis, high RCAPCATa and LADPCATa values were associated with AAD regardless of the degree of stenosis [odds ratio (OR) =0.014; 95% confidence interval (CI): 0.001-0.177; P=0.001 and OR =0.010; 95% CI: 0.001-0.189; P=0.002]. Conclusions: PCATa on computed tomography was increased in patients with AAD regardless of the presence or absence of coronary artery disease (CAD). This suggests that vascular inflammation is present in AAD independent of CAD. Further research should be conducted to investigate the potential of this imaging biomarker to predict AAD and monitor patients' responses to therapies for AAD.
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BACKGROUND: In the majority of clinical environments, the treponema pallidum particle agglutination (TPPA) test is known for its higher specificity compared to the rapid plasma reagin (RPR) test and is commonly employed for the diagnosis of syphilis, but their use for serological monitoring after syphilis therapy is controversial. OBJECTIVES: We aim to evaluate whether the TPPA titers is suitable for monitoring syphilis treatment efficacy. METHODS: At first, 232 patients with primary syphilis were recruited. Serological testing was performed at baseline (initial visit) and at 6 months (±1 month) after benzathine penicillin G (BPG) treatment. Second, New Zealand white male rabbits were infected with Treponema pallidum (T. pallidum) to evaluate the changes in TPPA titers after BPG therapy. Finally, we compared the TPPA titers in the culture supernatant of rabbit splenocytes stimulated with T. pallidum with or without BPG. RESULTS: After 6 months of treatment, 150 (64.7%) of 232 primary syphilis patients achieved serological cure, and 82 (35.3%) had adverse outcomes. Among 110 patients with TPPA titers decreased by more than fourfold, 109 of them were serological cure patients (≥4-fold decrease in RPR titers) (P ï¼ 0.0001). In the rabbit model of syphilis, the TPPA titers was significantly decreased in the treatment subgroup (P = 0.016) and remained constant (±2-fold) or increased (≥4-fold) in the nontreatment subgroup. In addition, T. pallidum resulted in a positive TPPA titers in the culture supernatant of splenocytes (median titers was 1: 80), while BPG could directly reduce the TPPA titers in the culture supernatant (median titers was 1: 40) (P = 0.032). CONCLUSIONS: A 4-fold or greater decrease in TPPA titers may indicate effective treatment in primary syphilis. Combining TPPA titers with RPR titers results may potentially aid in the early diagnosis of syphilis.
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Sífilis , Humanos , Masculino , Animales , Conejos , Sífilis/diagnóstico , Sífilis/tratamiento farmacológico , Treponema pallidum , Penicilina G Benzatina/uso terapéutico , Serodiagnóstico de la Sífilis , Resultado del Tratamiento , AglutinaciónRESUMEN
BACKGROUND: Acute myelitis (AM) can lead to sudden sensory, motor and autonomic nervous dysfunction, which negatively affects their daily activities and quality of life, so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease. AIM: To investigate the effect of ganglioside (GM) combined with methylprednisolone sodium succinate (MPSS) on the curative effect and neurological function of patients with AM. METHODS: First, we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality, with 52 patients receiving gamma globulin (GG) + MPSS and 56 patients receiving GM + MPSS, assigned to the control group (Con) and observation group (Obs), respectively. The therapeutic effect, neurological function (sensory and motor function scores), adverse events (AEs), recovery (time to sphincter function recovery, time to limb muscle strength recovery above grade 2, and time to ambulation), inflammatory factors (IFs) [interleukin (IL)-6, C-reactive protein (CRP), and tumor necrosis factor (TNF)-α] and other data of the two groups were collected for evaluation and comparison. RESULTS: The Obs had: (1) A significantly higher response rate of treatment than the Con; (2) Higher scores of sensory and motor functions after treatment that were higher than the baseline (before treatment) and higher than the Con levels; (3) Lower incidence rates of skin rash, gastrointestinal discomfort, dyslipidemia, osteoporosis and other AEs; (4) Faster posttreatment recovery of sphincter function, limb muscle strength and ambulation; and (5) Markedly lower posttreatment IL-6, CRP and TNF-α levels than the baseline and the Con levels. CONCLUSION: From the above, it can be seen that GM + MPSS is highly effective in treating AM, with a favorable safety profile comparable to that of GG + MPSS. It can significantly improve patients' neurological function, speed up their recovery and inhibit serum IFs.
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Objective: The objective of this study was to analyze the clinical characteristics of pregnant women infected with the COVID-19 omicron variant and their neonates during the outbreak in Guangdong province, China. Methods: The clinical data of pregnant women infected with the COVID-19 omicron variant and their neonates were retrospectively collected from two hospitals in Guangdong province. Information recorded included age of mother, date of birth, sex, weight at birth, mode of delivery, gestational age, feeding mode, Apgar score, signs, medical records, underlying comorbidities and laboratory results. The presence of SARS-CoV-2 viral RNA was tested using an real-time PCR assay. Results: Seventy-nine pregnant women infected with COVID-19 omicron variant and their 68 neonates were included in this study. The vast majority (86.1%) of pregnant women was in their third trimester of pregnancy, and only 11 cases (15%) were in the first or second trimester. Of 79 pregnant women, 39 cases were asymptomatic at the time of infection, and 40 mothers presented with mild manifestations of COVID-19. The most common symptoms were fever (92.5%, 37/40) and cough (57.5%, 21/40). All of pregnant women did not receive chest computed tomography (CT) scan or X-ray. No pregnant woman developed severe pneumonia. A total of 68 neonates (3 set of twins) from 65 mothers with COVID-19 were reviewed. Among women who delivered, 34 cases underwent cesarean section, 31 cases underwent vaginal delivery. According to the timing of birth, there were 10 (14.7%) preterm neonates. Two babies were born dead (intrauterine fetal death after 22 weeks of gestation). Of the live babies born (66 cases) from mothers with COVID-19, 9 newborns were lower weight, and one preterm case was born with respiratory distress and intubated, he recovered and developed normally. SARS-CoV-2 nucleic acid testing was conducted on 41 neonates daily after birth, with only one neonate testing positive for SARS-CoV-2 infection on the third day after birth. The infected neonate exhibited typical fever and acute respiratory tract syndrome but ultimately had a good prognosis, recovering after 5 days of treatment. Conclusion: Although preliminary data suggests the risk of severe maternal and fetal complications from Omicron variant infection during pregnancy is lower than previous variants and Delta variant. Our study, which was conducted on a limited population sample, indicates that there is a possibility of severe complications, such as stillbirth, occurring in some fetal cases. These findings emphasize the need for continued attention from obstetricians.
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Hydrogen energy from solar water-splitting is known as an ideal method with which to address the energy crisis and global environmental pollution. Herein, the first-principles calculations are carried out to study the photocatalytic water-splitting performance of single-layer GaInSe3 under biaxial strains from -2% to +2%. Calculations reveal that single-layer GaInSe3 under various biaxial strains has electronic bandgaps ranging from 1.11 to 1.28 eV under biaxial strain from -2% to +2%, as well as a completely separated valence band maximum and conduction band minimum. Meanwhile, the appropriate band edges for water-splitting and visible optical absorption up to ~3 × 105 cm-1 are obtained under biaxial strains from -2% to 0%. More impressively, the solar conversion efficiency of single-layer GaInSe3 under biaxial strains from -2% to 0% reaches over 30%. The OER of unstrained single-layer GaInSe3 can proceed without co-catalysts. These demonstrate that single-layer GaInSe3 is a viable material for solar water-splitting.
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Rumination is closely linked to the onset and maintenance of major depressive disorder (MDD). Prior neuroimaging studies have identified the association between self-reported rumination trait and the functional coupling among a network of brain regions using resting-state functional magnetic resonance imaging (MRI). However, little is known about the underlying neural circuitry mechanism during active rumination in MDD. Degree centrality (DC) is a simple metric to denote network integration, which is critical for higher-order psychological processes such as rumination. During an MRI scan, individuals with MDD (N = 45) and healthy controls (HC, N = 46) completed a rumination state task. We examined the interaction effect between the group (MDD vs. HC) and condition (rumination vs. distraction) on vertex-wise DC. We further characterized the identified brain region's functional involvement with Neurosynth and BrainMap. Network-wise seed-based functional connectivity (FC) analysis was also conducted for the identified region of interest. Finally, exploratory correlation analysis was conducted between the identified region of interest's network FCs and self-reported in-scanner affect levels. We found that a left superior frontal gyrus (SFG) region, generally overlapped with the frontal eye field, showed a significant interaction effect. Further analysis revealed its involvement with executive functions. FCs between this region, the frontoparietal, and the dorsal attention network (DAN) also showed significant interaction effects. Furthermore, its FC to DAN during distraction showed a marginally significant negative association with in-scanner affect level at the baseline. Our results implicated an essential role of the left SFG in the rumination's underlying neural circuitry mechanism in MDD and provided novel evidence for the conceptualization of rumination in terms of impaired executive control.
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Trastorno Depresivo Mayor , Humanos , Encéfalo/diagnóstico por imagen , Corteza Prefrontal , Función Ejecutiva , Lóbulo Frontal , Imagen por Resonancia Magnética , Mapeo EncefálicoRESUMEN
OBJECTIVE: To investigate the clinical characteristics and risk factors of acute leukemia complicated with multi-drug resistant bacterial septicemia in children. METHODS: The clinical data of children with acute leukemia complicated with septicemia admitted to the Affiliated Hospital of Guangdong Medical University from January 2013 to May 2021 were retrospectively analyzed. Their flora composition and drug resistance were also analyzed. The children were divided into multi-drug resistant bacteria (MDRB) group and non-multi-drug resistant bacteria (non-MDRB) group according to the drug sensitivity results, and the differences in clinical data between the two group were compared. RESULTS: A total of 108 children had drug sensitivity results, 47 cases in the MDRB group, including 26 strians of Gram-positive bacteria (G+), the most common multi-drug resistant G+ bacteria were coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, and the most common multi-drug resistant Gram-negative bacteria G- bacteria were Escherichia coli and Klebsiella pneumoniae subspecies pneumoniae. Compared with non-MDRB group, children in MDRB group had higher C-reactive protein (CRP) level and mortality rate (P <0.001, P =0.009), lower initial empirical anti-infection efficiency (P <0.001), and were more likely to have septic shock (P =0.003). Logistic analysis showed that the risk factors of acute leukemia complicated with MDRB septicemia in children were previous MDRB infection (OR =6.763, 95% CI: 1.141-40.092, P =0.035), duration of agranulocytosis before infection≥7 days (OR =3.071, 95% CI: 1.139-8.282, P =0.027), and previous use of antimicrobial drugs within 90 days before infection (OR =7.675, 95% CI: 1.581-37.261, P =0.011). CONCLUSIONS: The clinical features of acute leukemia complicated with MDRB septicemia in children include a heavy inflammatory response, significantly elevated CRP, susceptibility to secondary septic shock, low efficiency of initial empirical anti-infective therapy, and high mortality rate. Previous MDRB infection, duration of agranulocytosis before infection≥7 days, and previous use of antimicrobial drugs within 90 days before infection are risk factors of acute leukemia complicated with MDRB septicemia in children.
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Agranulocitosis , Antiinfecciosos , Leucemia Mieloide Aguda , Sepsis , Choque Séptico , Humanos , Niño , Estudios Retrospectivos , Factores de Riesgo , Bacterias , Leucemia Mieloide Aguda/complicaciones , Enfermedad Aguda , Escherichia coliRESUMEN
The sap flow of trees is complex and difficult to express with multivariate linear or empirical models. A simple and feasible method on the basis of understanding sap flow variation to simulate its variation with environmental factors is of special importance for quantitatively analyzing forest ecohydrological processes and regional water demand. In this study, with one of the shelter forest species Euonymus bungeanus in the east sandy land of Yellow River in Ningxia as the research object, we continuously measured the trunk sap flow velocity by thermal diffusion sap flow meter, and analyzed the effects of environmental factors on stem sap flow. We used the particle swarm optimization (PSO) and sparrow search algorithm (SSA) optimized neural network model to predict sap flow velocity of E. bungeanus. Results showed that the main environmental factors influencing sap flow were solar radiation, vapor pressure deficit, air temperature, and relative humidity, with the influencing importance of 32.5%, 25.3%, 22.0% and 16.1%, respectively. The response process between sap flow and environmental factors presented a hysteresis loop relationship. The optimized BP, Elman and ELM neural network models improved the comprehensive evaluation index (GPI) by 1.5%, 30.0% and 5.3%, respectively. Compared with the PSO-Elman and SSA-ELM optimization models, the SSA-BP optimization model had the best prediction results with an improvement of 1.0% and 23.2% in GPI, respectively. Therefore, the prediction results of the BP neural network model based on the sparrow search algorithm could be used as an optimal model for predicting instantaneous sap flow velocity of E. bungeanus.
Asunto(s)
Euonymus , Redes Neurales de la Computación , Simulación por Computador , Algoritmos , BosquesRESUMEN
Syphilis has resurged in many countries, which has called attention to vaccine development. Based on the immunization-based rabbit model of infection with the Nichols strain, this study explored the protective immune response of a controversial syphilis vaccine candidate, TprK, and found that immunization with full-length rTprK was effective in attenuating lesion development and accelerating lesion resolution, which could reduce the probability of the pathogen spreading to distant tissue sites to prevent the progression of the disease to some extent. Furthermore, the results revealed that immunization with rTprK not only rapidly induced a strong Th1-like cellular response but also elicited a humoral immune response to produce opsonic antibodies to enhance macrophage-mediated opsonophagocytosis. Although complete protection against infection was not achieved, the study provided a comprehensive and in-depth exploration of the immunogenicity of TprK and highlighted the importance of TprK as a promising syphilis vaccine component.
RESUMEN
Treponema pallidum (Tp) has a well-known ability to evade the immune system and can cause neurosyphilis by invading the central nervous system (CNS). Microglia are resident macrophages of the CNS that are essential for host defense against pathogens, this study aims to investigate the interaction between Tp and microglia and the potential mechanism. Here, we found that Tp can exert significant toxic effects on microglia in vivo in Tg (mpeg1: EGFP) transgenic zebrafish embryos. Single-cell RNA sequencing results showed that Tp downregulated autophagy-related genes in human HMC3 microglial cells, which is negatively associated with apoptotic gene expression. Biochemical and cell biology assays further established that Tp inhibits microglial autophagy by interfering with the autophagosome-lysosome fusion process. Transcription factor EB (TFEB) is a master regulator of lysosome biogenesis, Tp activates the mechanistic target of rapamycin complex 1 (mTORC1) signaling to inhibit the nuclear translocation of TFEB, leading to decreased lysosomal biogenesis and accumulated autophagosome. Importantly, the inhibition of autophagosome formation reversed Tp-induced apoptosis and promoted microglial clearance of Tp. Taken together, these findings show that Tp blocks autophagic flux by inhibiting TFEB-mediated lysosomal biosynthesis in human microglia. Autophagosome accumulation was demonstrated to be a key mechanism underlying the effects of Tp in promoting apoptosis and preventing itself from clearing by human microglia. This study offers novel perspectives on the potential mechanism of immune evasion employed by Tp within CNS. The results not only establish the pivotal role of autophagy dysregulation in the detrimental effects of Tp on microglial cells but also bear considerable implications for the development of therapeutic strategies against Tp, specifically involving mTORC1 inhibitors and autophagosome formation inhibitors, in the context of neurosyphilis patients.
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Microglía , Neurosífilis , Humanos , Animales , Treponema pallidum/genética , Pez Cebra , Autofagia , ApoptosisRESUMEN
Lonicera ligustrina is a folk medicinal herb in China and India with highly potential medicinal value. Here, we reported the complete chloroplast (cp) genome of L. ligustrina (GenBank accession number: ON968694). The cp genome was 155,330 bp long, with a large single-copy region (LSC) of 88,855 bp and a small single-copy region (SSC) of 18,647 bp separated by a pair of inverted repeats (IRs) of 23,914 bp. We also reconstructed the phylogeny of Lonicera using maximum likelihood (ML) method, including our data and previously reported cp genomes of related taxa. The current study indicated that L. ligustrina is sister with the Nintooa clade of subgen. Lonicera.