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Introducción. En Colombia, solo un 24 % de los pacientes en lista recibieron un trasplante renal, la mayoría de donante cadavérico. Para la asignación de órganos se considera el HLA A-B-DR, pero la evidencia reciente sugiere que el HLA A-B no está asociado con los desenlaces del trasplante. El objetivo de este estudio fue evaluar la relevancia del HLA A-B-DR en la sobrevida del injerto de los receptores de trasplante renal. Métodos. Estudio de cohorte retrospectivo que incluyó pacientes trasplantados renales con donante cadavérico en Colombiana de Trasplantes, desde 2008 a 2023. Se aplicó un propensity score matching (PSM) para ajustar las covariables en grupos de comparación por compatibilidad y se evaluó la relación del HLA A-B-DR con la sobrevida del injerto renal por medio de la prueba de log rank y la regresión de Cox. Resultados. Se identificaron 1337 pacientes transplantados renales, de los cuales fueron mujeres un 38,7 %, con mediana de edad de 47 años y de índice de masa corporal de 23,8 kg/m2. Tras ajustar por PSM las covariables para los grupos de comparación, la compatibilidad del HLA A-B no se relacionó significativamente con la pérdida del injerto, con HR de 0,99 (IC95% 0,71-1,37) para HLA A y 0,75 (IC95% 0,55-1,02) para HLA B. Solo la compatibilidad por HLA DR fue significativa para pérdida del injerto con un HR de 0,67 (IC95% 0,46-0,98). Conclusión. Este estudio sugiere que la compatibilidad del HLA A-B no influye significativamente en la pérdida del injerto, mientras que la compatibilidad del HLA DR sí mejora la sobrevida del injerto en trasplante renal con donante cadavérico
Introduction. In Colombia, only 24% of patients on the waiting list received a renal transplant, most of them from cadaveric donors. HLA A-B-DR is considered for organ allocation, but recent evidence suggests that HLA A-B is not associated with transplant outcomes. The objective of this study was to evaluate the relevance of HLA A-B-DR on graft survival in kidney transplant recipients. Methods. Retrospective cohort study that included kidney transplant recipients with a cadaveric donor in Colombiana de Trasplantes from 2008 to 2023. A propensity score matching (PSM) was applied to adjust the covariates in comparison groups for compatibility, and the relationship of HLA A-B-DR with kidney graft survival was evaluated using the log rank test and Cox regression. Results. A total of 1337 kidney transplant patients were identified; of those, 38.7% were female, with median age of 47 years, and BMI 23.8 kg/m2. After adjusting the covariates with PSM for the comparison groups, HLA A-B matching was not significantly related to graft loss, with HR of 0.99 (95% CI 0.71-1.37) and 0.75 (95% CI 0.55-1.02), respectively. Only HLA DR matching was significant for graft loss with an HR of 0.67 (95% CI 0.46-0.98). Conclusions. This study suggests that HLA A-B matching does not significantly influence graft loss, whereas HLA DR matching does improve graft survival in renal transplantation with a cadaveric donor.
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Humains , Transplantation rénale , Rejet du greffon , Antigènes HLA , Analyse de survie , Transplantation d'organe , Score de propensionRésumé
Primary biliary cholangitis （PBC） is a liver autoimmune disease with a strong genetic tendency characterized by the degeneration and necrosis of bile duct epithelial cells， and it is often observed in middle-aged and elderly women. With the continuous development of genome-wide association studies， the genetic susceptibility of PBC has attracted more and more attention. This article elaborates on the research advances in the genetic susceptibility genes closely associated with PBC， in order to provide effective targets for the treatment of PBC.
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ABSTRACT Introduction: To date, 340 antigen-organized 43 blood group systems are recognized, being ABO, Rh, Kell, Duffy, Kidd, MNS and Diego the most clinically relevant. The aim of this study was to assess the distribution of alleles and genotypes of the blood group systems Rh, Kell, Duffy, Kidd, MNS and Diego in 810 blood donors registered in the hemotherapy unit in northwest Rio Grande do Sul, Brazil Methods: We evaluated the genetic variability of blood groups Rh (c.676G>C and c.307C>T), Kell (c.578C>T), Kidd (c.838A>G), Duffy (c.125A>G and c.l-67T>C), Diego (c.2561C>T) and MNS (c.143T>C) in 810 volunteer blood donors of Rio Grande do Sul, southern Brazil. The genetic profiling was performed through allelic discrimination assays using hydrolysis probes (TaqMan®) real-time PCR system. Results: The most frequent blood group genotypes found in our study population were: RHC*Cc (51.5%), RHC*ee (70.1%), FY*A/FY*B (49.3%), GATA -67T/T (93.5%), KEL*2/KEL*2 (93.4%), Jk*A/JK*B (53.2%) and DI*02/DI*02 (95.4%). Some statistical differences were observed on comparing the population of this study with populations from other states in Brazil, mainly with population of Minas Gerais, Bahia and Paraná, which showed some differences from the population of Porto Alegre, which was more similar to those of Santa Catarina and São Paulo Conclusion: The frequency of red blood cell polymorphisms in our study is different from that of blood donors in other regions of Brazil. The results showed the importance of extended genotyping in adequate blood screening and the existence of rare genotypes in Brazilian regular blood donors
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Introduction. The existing methods for Paracoccidioides spp. antigen production are problematic in terms of standardization, specificity, stability, repeatability, and reproducibility. Objective. To optimize the methodology for Paracoccidioides spp. antigen production and evaluate its applicability in paracoccidioidomycosis immunodiagnosis. Materials and methods. The antigens were obtained from Paracoccidioides lutzii isolates (01, 66, and 8334), Paracoccidioides brasiliensis sensu stricto (113), and Paracoccidioides restripiensis (B-339). These fungi were grown at 36 °C ± 1 °C, on modified Fava-Netto agar, according to Freitas et al. (2018). Paracoccidioides lutzii antigens were obtained after 5, 10, and 20 days of culture, whereas P. brasiliensis and P. restripiensis antigens were obtained after 10 days. Antigens were evaluated in natura, 10 and 20 times concentrated. Antigenic capacity was evaluated using a double immunodiffusion assay against serum samples from patients with paracoccidioidomycosis, histoplasmosis, and aspergillosis, and random blood donors. Results. Cross-reactivity between Paracoccidioides spp. antigens was observed when P. brasiliensis, P. restrepiensis antigens, and P. lutzii antigens were evaluated with the polyclonal antibodies against P. lutzii and P. brasiliensis, respectively. No cross-reactivity was obtained for polyclonal antibodies against Histoplasma capsulatum, Aspergillus fumigatus, and random blood donors. The proposed protocol allowed stable, repeatable, and reproducible genus-specific antigen production at a low cost and in a short cultivation time. Conclusion. The proposed protocol allowed us to obtain genus-specific antigens that can be developed and reproduced in all laboratories in Brazil and South America, where paracoccidioidomycosis is a neglected disease, contributing to an early diagnosis, especially in endemic regions, regardless of the species.
Introducción. Los métodos existentes para la producción de los antígenos de Paracoccidioides spp. son problemáticos en su estandarización, especificidad, estabilidad, repetibilidad y reproducibilidad. Objetivo. Optimizar la metodología para la producción de antígenos de Paracoccidioides spp. y evaluar su aplicabilidad en el inmunodiagnóstico de la paracoccidioidomicosis. Materiales y métodos. Los antígenos se obtuvieron de aislamientos de P. lutzii (01, 66 y 8334), P. brasiliensis sensu stricto (113) y P. restripiensis (B-339). Estos hongos se cultivaron a 36 °C ± 1 °C en agar Fava-Netto modificado, según Freitas et al. (2018). Los antígenos de P. lutzii se obtuvieron a los 5, 10 y 20 días de cultivo y los antígenos de P. brasiliensis y P. restripiensis se obtuvieron a los 10 días. Los antígenos se evaluaron in natura, concentrados 10 y 20 veces. La capacidad antigénica se evaluó mediante un ensayo de inmunodifusión doble con muestras de suero de pacientes con paracoccidioidomicosis, histoplasmosis, aspergilosis y donantes de sangre aleatorios. Resultados. Se observó reacción cruzada con Paracoccidioides spp. cuando se evaluaron los antígenos de P. brasiliensis, P. restrepiensis y P. lutzii frente a los anticuerpos policlonales contra P. lutzii y P. brasiliensis, respectivamente. No hubo reactividad cruzada con los anticuerpos policlonales contra Histoplasma capsulatum y Aspergillus fumigatus, ni contra los donantes de sangre aleatorios. El protocolo propuesto permitió la producción estable, repetible y reproducible de antígenos dirigidos de un género específico (Paracoccidiodes) en un tiempo corto de cultivo y a un menor costo. Conclusión. El protocolo propuesto permitió obtener antígenos específicos de un género, que pueden ser desarrollados y reproducidos en todos los laboratorios de Antígenos de Paracoccidioides spp.: protocolo rápido Brasil y Surámerica donde la paracoccidioidomicosis es una enfermedad endémica y desatendida. Estos antígenos pueden contribuir al diagnóstico precoz de la infección, independientemente de la especie.
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Paracoccidioides , Antigènes , Blastomycose sud-américaine , Tests immunologiquesRésumé
ABSTRACT Introduction: The Glanzmann Thrombasthenia (GT) and Bernard-Soulier Syndrome (BSS) are rare hereditary disorders of platelet function. Their treatment often requires platelet transfusion, which can lead to the development of alloantibodies. Objective: In this study, we aim to develop a strategy for alloantibody detection and to describe the frequency of alloimmunization in a patient population from a single center in southeastern Brazil. Methods: Samples from patients with GT or BSS were tested using the Platelet Immunofluorescence Test (PIFT). If a positive result was obtained, a confirmatory step using the Monoclonal Antibody Immobilization of Platelet Antigens (MAIPA) and Luminex bead-based platelet assay (PAKLx) was executed. Main results: Among 11 patients with GT, we detected the presence of alloantibodies in 5 using PIFT, with confirmation through MAIPA and PAKLx in 2 (1 anti-HLA and 1 anti-HPA), resulting in a frequency of 18.1%. Among 4 patients with BSS, PIFT was positive in 3, with confirmation by MAIPA and PAKLx in 1 (anti-HLA), showing a frequency of 25%. The two patients with anti-HLA antibodies exhibited a panel reactive antibody (PRA-HLA) testing greater than 97%. Conclusion: Our study highlights the importance of identifying platelet alloimmunization in this patient population. The proposed algorithm for platelet alloantibodies detection allows resource optimization.
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ABSTRACT Introduction: Data on the prevalence of clinically significant antigens (Rh, Kell, Kidd, Duffy, MNSs, Lewis, P and Lutheran) among the Indian donor population is sparse. Objective: This prospective study was aimed at determining the prevalence of 21 clinically significant antigens for the first time in the South Indian donor population. Method: A total of 672 regular O group blood donors were enrolled for Rh (C, c, E, e) and Kell (K) antigens typing. Of these, 188 donors were typed for other clinically significant antigens (k, Kpa, Kpb, Jka, Jkb, Fya, Fyb, M, N, S, s, P1, Lea, Leb, Lua and Lub). Results: Antigen frequencies were expressed in percentages. In our study, R1R1 and rr were the most common phenotypes among D+ and D− donors, respectively. Among the Rh antigens, the e antigen was expressed by 97.5% and 100% of D+ and D− donors, respectively. The K antigen was found in only 0.15% of donors. In the Duffy and Kidd blood group system, Fy (a+b+) and Jk (a+b+) were the most frequent phenotypes, respectively. In the MNSs blood group system, M+N+ and S−s+ were the most common phenotypes reported. The Le (a−b+) was found to be the phenotype with the highest prevalence in the Lewis blood group system. The Lu (a−b+) was the only phenotype found in the Lutheran blood group system. Conclusion: Knowledge regarding the prevalence of antigens in a given population is essential in developing cost-effective in-house panels and a rare donor registry comprising donors typed negative for a high-frequency antigen or a combination of common multiple antigens.
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Background: Chronic viral hepatitis is a major global public health problem, an important cause of morbidity and mortality. We conducted this study to evaluate the behavioral risk factors of HBV infection and its association with HBsAg positivity among residents of Kaza sub-division of district Lahaul & Spiti in Himachal Pradesh. Material & Methods: The study was carried out by the Gastroenterology, Community Medicine, and Microbiology Department at Indira Gandhi Medical College Shimla at Kaza, a subdivision of Lahaul & Spiti. The cluster sampling technique was used to get the desired sample size of 4000. Forty clusters were chosen using a probability proportionate to size sampling method, and 100 research participants were added to each cluster using a simple random sampling method. The data was gathered using a pre-tested interview plan. A blood sample of 5ml from each study participant was obtained, and its HBsAg content was examined. Results: In our study, 2.7% of the interviewed respondents’ parents were positive for hepatitis B and 3.7% reported one positive family member. Injectable drug use was reported by 1.6 (68/4231). Among these users 8.8% (6/68) shared needles with other IDUs in last 12 months and 35.3% (24/68) used a common container to draw up drug solution. Sexual intercourse was reported to be experienced by 15.5 (655/4231) and 12.2% either did not disclose or were children. Out of those who ever experienced sexual/penetrative intercourse 38.3% (251/655) had reported it with someone else other than a spouse. Majority of these had two partners other than a spouse (30.3%; 76/251). Around 30% (195/655) reported of using a condom in their last intercourse. Body piercings or a tattoo from someone who doesn’t sterilize his or her equipment, including local treatment from lamas, was prevalent among 16.3% of the population (689/4231). Acupuncture was taken as a remedy for any medical condition by 9% of participants. Regression analysis also revealed that one infected family member emerged as an independent factor associated with HBsAg positive test after adjusting for confounders. Conclusion: Our study provided much important information concerning hepatitis B risk factors in this tribal group. Health education about behavioral risk factors among this tribal population should be the main intervention that might help limit the spread of these blood-borne infections.
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ABSTRACT Objective This study verified the replication efficiency of the Rocio virus in a primary culture of mouse neural cells. Methods Mixed primary cultures (neurons/glia) obtained from the brains of newborn isogenic BALB/c mice were inoculated with Rocio virus on the 7 th day of culture, and the development of cytopathogenic effects was monitored. The infection was confirmed via immunocytochemistry (anti-ROCV), while viral replication was quantified in infected primary cultures. The titration method used depended on the infection period. Results Rocio virus efficiently infected primary cultured neural cells, with the highest viral titer causing cytopathic changes was observed at 2 days post infection. The virus-infected primary culture survived for up to 7 days post infection, and viral load quantitation showed viral replication kinetics compatible with the cell death kinetics of cultures. Conclusion The findings of this study suggest that mouse neural cell primary cultures support Rocio virus replication and could be used as an alternative system for studying Flavivirus infection in the central nervous system.
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SUMMARY OBJECTIVE: In this study, we aimed to determine and compare hepatitis B surface antigen level, anti-hepatitis B surface, and anti-hepatitis C virus positivity in Turkish pregnant women and Syrian refugee pregnant women residing in Turkey. METHODS: The study was conducted on Syrian refugee pregnant women aged 15-45 years and Turkish pregnant women who applied to state hospital's gynecology and obstetrics outpatient clinics between April 30, 2012, and April 30, 2022. In our study, 136,376 pregnant women (104,629 Turkish and 31,747 Syrian) tested for hepatitis B surface antigen, 72,035 pregnant women (53,070 Turkish and 18,965 Syrian) tested for anti-hepatitis B surface, and 120,611 pregnant women (92,514 Turkish and 28,097 Syrian) tested for anti-hepatitis C virus were included. The patients were divided into six groups for hepatitis B surface antigen, anti-hepatitis B surface, and anti-hepatitis C virus results based on their age: <20 years, 20-24 years, 25-29 years, 30-34 years, 35-39 years, and >40 years. For each age group, the results of Syrian refugee pregnant women and Turkish pregnant women were compared. RESULTS: Hepatitis B surface antigen positivity and anti-hepatitis B surface positivity were significantly higher in Turkish pregnant women compared to Syrian refugee pregnant women. Anti-hepatitis C virus positivity was significantly higher in Syrian refugee pregnant women compared to Turkish pregnant women. CONCLUSION: Based on the available data, we think that hepatitis B surface antigen, anti-hepatitis B surface, and anti-hepatitis C virus tests should be done routinely for pregnant women. Raising awareness among Syrian refugees about the hepatitis B virus vaccine as well as encouraging them to be vaccinated may reduce the negative impact of migration.
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SUMMARY OBJECTIVE: Fetal vascular malperfusion is associated with poor perinatal outcomes in women with preeclampsia and gestational diabetes mellitus. The aim of this study was to determine the association between fetal vascular malperfusion score and syncytiotrophoblast basement membrane thickness and clinicopathological variables, such as developing preeclampsia in women with gestational diabetes mellitus. METHODS: This retrospective cohort study included 65 pregnant participants (34 with gestational diabetes mellitus and 31 controls) between January 2019 and January 2022. Gestational diabetes mellitus was diagnosed as ≥2 of 4 elevated values on a 3-h, 100-g oral glucose tolerance test. The fetal vascular malperfusion score was evaluated by endothelial CD34 positivity in the villous stroma of the placenta. The association between fetal vascular malperfusion score and syncytiotrophoblast basement membrane thickness with clinicopathological variables in women with gestational diabetes mellitus was evaluated. RESULTS: It was revealed that the gestational diabetes mellitus group had greater fetal vascular malperfusion scores than the control group (gestational diabetes mellitus group fetal vascular malperfusion score: 34.2±9.1 and control group fetal vascular malperfusion score: 26.5±8.7, respectively, p=0.0009). Syncytiotrophoblast basement membrane thickness was correlated with the development of preeclampsia, trophoblast proliferation, and fetal vascular malperfusions (0.3952, p=0.0129; 0.3487, p=0.0211; and 0.4331, p=0.0082, respectively). On the contrary, fetal vascular malperfusions were correlated with the development of preeclampsia, villous edema, and trophoblast proliferation (0.3154, p=0.0343; 0.2922, p=0.4123; and 0.3142, p=0.0355, respectively). CONCLUSION: The gestational diabetes mellitus group displayed significantly higher fetal vascular malperfusion scores and thickening of the syncytiotrophoblast basement membrane than the control group. There is a correlation between developing preeclampsia and the fetal vascular malperfusion scores and the syncytiotrophoblast basement membrane thickness.
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Objective To investigate the ability of combined baseline serum markers, i.e., HBV DNA, HBV RNA, HBsAg, and HBcrAg, to predict HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) treated by nucleos(t)ide analogues. Methods A retrospective analysis was performed for 83 HBeAg-positive patients selected as subjects from the prospective CHB follow-up cohort established by Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, from June 2007 to July 2008, and the baseline serum levels of HBV DNA, HBV RNA, HBsAg, and HBcrAg were analyzed. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman method was used for correlation analysis. A Cox regression model was established to calculate HBeAg seroconversion prediction score, and the time-dependent receiver operating characteristic curve was used to evaluate the ability of combined markers in predicting HBeAg seroconversion. The Kaplan-Meier method was used to calculate cumulative seroconversion rate in each group, and the Log-rank test was used for comparison between groups. Results For the 83 HBeAg-positive patients, the median follow-up time was 108 months, and 44.58%(37/83) of these patients achieved HBeAg seroconversion. Compared with the non-seroconversion group, the HBeAg seroconversion group had significantly lower baseline serum levels of HBV DNA [6.23(1.99-9.28) log 10 IU/mL vs 7.69(2.05-8.96) log 10 IU/mL, Z =-2.345, P =0.019] and HBV RNA [4.81(1.40-7.53) log 10 copies/mL vs 6.22(2.00-8.49) log 10 copies/mL, Z =-1.702, P =0.010], and there were no significant differences in the levels of HBsAg and HBcrAg between the two groups ( P > 0.05). The Cox regression equation constructed based on the above serum markers showed a median score of 0.95(range 0.37-3.45) for predicting HBeAg seroconversion. In the total population, the combined score was negatively correlated with HBsAg, HBV DNA, HBV RNA, and HBcrAg ( r =-0.697, -0.787, -0.990, and -0.819, all P < 0.001). Based on the median prediction score, the patients were divided into high HBeAg seroconversion group and low HBeAg seroconversion group; as for the prediction of HBeAg seroconversion rate at 36, 60, and 84 months, the high HBeAg seroconversion group had a seroconversion rate of 43.90%, 51.20%, and 63.10%, respectively, while the low HBeAg seroconversion group had a seroconversion rate of 9.60%, 17.00%, and 19.8%, respectively, and there was a significant difference between the two groups ( χ 2 =11.6, P < 0.001). Conclusion The combined prediction score based on baseline serum HBV markers can predict HBeAg seroconversion in CHB patients treated by nucleos(t)ide analogues.
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@#Objective To analyze the evolutionary characteristics of GZ19 strain of G Ⅱ.4 norovirus(NoV) in China,and clarify its ability and mode of binding to receptors of histo-blood group antigens(HBGAs).Methods According to the sequence of ORF2 region in GZ19 strain,the evolutionary tree was constructed and the amino acid sequences at HBGA binding sites(HBSs) and key blocking epitopes were analyzed.P particles were expressed by prokaryotic expression system and purified.The obtained protein was identified by SDS-PAGE and indirect ELISA,and analyzed for the receptor binding characteristics of P particles by saliva binding and oligosaccharide binding assays.Results The GZ19 strain belonged to G Ⅱ.4Sydney [P31] lineage,of which the amino acid sequences of receptor binding sites and blocking epitopes were relatively conservative.It showed high homology with other G Ⅱ.4 Sydney [P31] strains in recent five years,while significant difference from G Ⅱ.4 Sydney 2012 original strain and G Ⅱ.4 Sydney [P16] strains.P particles only combined with A,B,O,AB secretory saliva and H-di oligosaccharide.Conclusion GZ19 strain represented the current evolutionary direction of G Ⅱ.4Sydney [P31] NoV.The successful expression of P particles and analysis of the binding characteristics with HBGA receptors laid a foundation of the research of epidemic evolution dynamics and vaccine development of G Ⅱ.4 NoVs in China.
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Objective:To investigate the correlation of CD8 positive tumor-infiltrating lymphocytes (CD8 + TIL) density and programmed-death receptor ligand 1 (PD-L1) expression in rectal cancer with clinicopathological characteristics and prognosis of patients after neoadjuvant chemoradiotherapy. Methods:The clinicopathological data of 166 patients with locally advanced rectal cancer (LARC) who received neoadjuvant therapy before surgery in the Beijing Chao-Yang Hospital, Capital Medical University from January 2015 to December 2018 were retrospectively analyzed. CD8 + TIL density and PD-L1 expression were detected by using immunohistochemistry. The correlation of CD8 + TIL density and PD-L1 expression with clinicopathological characteristics of patients after neoadjuvant chemoradiotherapy was analyzed. Kaplan-Meier method was used to analyze the disease-free survival (DFS) and Cox regression risk model was used to make univariate and multivariate analysis of the influencing factors for DFS. Results:Among 166 LARC patients, 81 cases (48.8%) had high density of CD8 + TIL, 85 cases (51.2%) had low density of CD8 + TIL; 63 cases (38.0%) had PD-L1 expression, and 103 cases (62.0%) had non-expression of CD8 + TIL. The expression rate of PD-L1 in CD8 + TIL high density group was higher than that in CD8 + TIL low density group [50.6% (41/81) vs. 25.9%(22/85), χ2 = 10.78, P < 0.001]. According to the density of CD8 + TIL and PD-L1 expression, immunophenotype was divided among 4 groups; the 3-year DFS rate of the CD8 + TIL high density /PD-L1 expression group was 87.1%, which was higher than that of the other groups (CD8 + TIL low density /PD-L1 expression group was 72.8%, CD8 + TIL high density /PD-L1 non-expression group was 67.0%, CD8 + TIL low density /PD-L1 non-expression group was 64.3%), and the difference was statistically significant ( P < 0.05). Univariate analysis showed that tumor differentiation degree, TNM stage, CD8 + TIL density, PD-L1 expression and CD8 + TIL density /PD-L1 expression were correlated with the DFS of patients (all P < 0.05). Multivariate analysis results showed that CD8 + TIL high density /PD-L1 expression was an independent protective factor for DFS ( HR = 0.049, 95% CI 0.005-0.497, P = 0.011), while TNM stage 3 was an independent risk factor for DFS ( HR = 2.752,95% CI 1.300-5.825, P = 0.008). Conclusions:In LARC after neoadjuvant therapy, CD8 + TIL density is positively correlated with the expression of PD-L1, and the high density of CD8 + TIL/PD-L1 expression is an independent influencing factor for good prognosis, suggesting that these patients may benefit from the immunotherapy.
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Objective:To explore clinical value of nucleic acid detection for hepatitis B virus (HBV) screening in hospitalized patients.Methods:This cross-sectional study collected and analyzed plasma samples from patients admitted to 10 domestic medical institutions from July 2021 to December 2021. Serological immunoassay and nucleic acid screening were used to simultaneously detect hepatitis B markers such as hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B e Antigen (HBeAg), hepatitis B e antibody (HBeAb), hepatitis B core antibody (HBcAb),and HBV DNA. Statistical analysis was performed on the serology, nucleic acid test results and clinical information of the patients.Results:Of the 8 655 collected samples, HBsAg was positive in 216 (2.50%) samples,HBV DNA was positive in 238 (2.75%) samples ( P>0.05); 210 (2.43%) samples were positive for both HBsAg and HBV DNA, 28 (0.32%) were HBsAg negative and HBV DNA positive, 6 cases (0.07%) were HBsAg positive and HBV DNA negative. Conclusion:These results indicate that the HBV DNA testing is equally effective as hepatitis B virus serological detection for hepatitis B virus screening in hospitalized patients.
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Objective:To investigate whether endoplasmic reticulum aminopeptidase 1 ( ERAP1) is a susceptible gene for pre-eclampsia (PE) and the possible mechanism in the pathogenesis. Methods:This retrospective study included 990 PE patients (case group) and 1 240 healthy pregnant women (control group) in six prefecture-level tertiary hospitals in Shandong Province, including the Affiliated Hospital of Qingdao University and Zaozhuang Maternal and Child Health Hospital, from September 2018 to April 2021. Peripheral blood were collected for DNA extraction. Single-nucleotide polymorphisms in the ERAP1 gene (rs30187, rs27044, and rs469783 loci) were analyzed by Taqman probe polymerase chain reaction (PCR). Two missense mutant plasmids, rs30187(c.1583A>G) and rs27044(c.2188C>G), were constructed by point mutation induction based on wild-type plasmids. Six groups (knock-down control, knock-down, over-expression control, over-expression, variant 1 and 2 groups) were set up in this study. After transfecting Htr8 cells with different transfection molecules, the expression of ERAP1 at mRNA and protein levels were detected. Besides, the effects of different transfections on cell function were detected using Transwell migration assay, Transwell invasion assay, cell scratch assay, and CCK-8 assay. Statistical analysis was performed using two independent samples t-test, rank sum test, and Chi-square test. Results:(1) There were significant differences in the genetic distribution of rs30187 (Genotype: χ2=29.25, Allele: χ2=4.68) and rs469783 (Genotype: χ2=7.01, Allele: χ2=6.45) as well as the genotype distribution of rs27044 ( χ2=28.95) between the case group and the control group (all P<0.05). Statistical analysis of the genetic model revealed that rs30187 and rs27044, both recessive models, were statistically different between the two groups with a higher frequency of CC genotypes in the case group ( χ2=20.82 and 19.97, both P<0.05), but a lower frequency in CC dominant gene pattern for rs469783 ( χ2=5.82, P=0.016). (2) Compared with the knock-down control group, the knock-down group showed significantly inhibited expression of ERAP1 (mRNA: 0.5±0.1 vs 1.0±0.0, t=7.49; protein: 0.4±0.1 vs 0.7±0.1, t=2.81; both P<0.05), reduced cell migration rate after 48 h of scratching [(16.5%±1.8%) vs (23.8%±2.4%), t=3.33, P=0.031] and decreased number of cells crossing Transwell chambers after 24 h of culture (423.7±21.3 vs 499.0±24.6, t=3.29, P=0.031). Compared with the over-expression group, variant 1 group and variant 2 group showed significantly inhibited expression of ERAP1 at mRNA (both P<0.001) and protein ( P=0.003 and 0.006) levels after transfection, decreased number of cells crossing Transwell chambers ( P=0.001 and 0.032) and down-regulated cell migration rate after 48 h of scratching [variant 1: P=0.004; variant 2: (21.1±4.6)% vs (28.3±1.1)%, t=2.10, P=0.099]. ERAP1 expression at both mRNA ( P<0.001) and protein ( P=0.008) levels, as well as cell proliferation ( P<0.001) and invasion ability ( P<0.001), were all enhanced in the over-expression group than those in the over-expression control group. Moreover, the migration rate of cells after 48 h of scratching ( P=0.002) and the number of cells crossing Transwell chambers after 24 h of culture ( P=0.001) were also increased. Conclusions:The rs30187, rs27044, and rs46978 on ERAP1 gene were all associated with PE susceptibility, with more carriers of the CC genotype in PE patients at rs30187 and rs27044 loci and more carriers of the CC genotype in healthy gravida at rs469783 locus. ERAP1 may be involved in the pathogenesis of PE by affecting the migratory and invasive ability of trophoblast cells.
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This article reported the prenatal diagnosis of a fetus with ZTTK syndrome. A pregnant woman underwent preimplantation genetic diagnosis because her partner carried a balanced chromosomal translocation. Chromosomal karyotype analysis and copy number variation sequencing (CNV-seq) performed on amniocytes collected at 18 + weeks of gestation revealed no abnormalities. Ultrasonography performed at 23 +5 and 26 +3 weeks of gestation revealed severe fetal growth restriction, cerebellar dysplasia, poorly visualized sacrum and coccyx, and spina bifida. MRI of the fetal brain showed that the bilateral cerebellar hemispheres of the fetus were small and the cisterna magna was large at 23 +6 weeks of gestation. Whole exome sequencing in the pedigree identified a heterozygous variant c.2092delG (p.Glu698fs*4) in the exon 3 of the fetal SON gene, which was not inherited from the parents and proved to be a de novo mutation. Mutations in the locus are pathogenic, causing ZTTK syndrome. After genetic counseling, the pregnant woman and her family chose to terminate the pregnancy.
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Objective:To develop the anti-CD30 monoclonal antibody 64Cu-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-CD30 and visualize CD30 expression in lymphoma non-invasively. Methods:The CD30 expression levels of 5 cell lines (Karpas299, Raji, Daudi, Ramos, and U266) were assessed by Western blot. Cell lines with high and low CD30 expression were selected for flow cytometry to evaluate the specific binding affinity of anti-CD30 monoclonal antibody. Thirteen NSG mice were used to established CD30 positive and negative subcutaneous xenograft models. 64Cu-NOTA-CD30 was obtained and 64Cu-NOTA-immunoglobulin (Ig)G was used as the control. ImmunoPET imaging was performed 2, 24, and 48 h after the injection of 64Cu-NOTA-CD30 or 64Cu-NOTA-IgG. Finally, the biodistribution studies were conducted. Repeated-measures analysis of variance and Bonferroni test were conducted for comparison. Results:Karpas299 showed the highest CD30 expression, while Raji showed the lowest. Flow cytometry showed specific binding affinity of the anti-CD30 monoclonal antibody to the Karpas299 cell line. The radiochemical purities of the probes were both higher than 95%. In microPET, the 64Cu-NOTA-CD30 uptake of Karpas299 xenograft tumors increased over time, with (11.46±0.58), (17.60±1.16) and (19.46±0.99) percentage activity of injection dose per gram of tissue (%ID/g) at 2, 24 and 48 h respectively. The contrast to normal tissue was good at 48 h, with the tumor/heart (blood) ratio of 2.20±0.22. The uptake of 64Cu-NOTA-CD30 in Karpas299 tumor at 48 h after injection was significantly higher than that in Raji tumor ((6.10±1.03) %ID/g) and 64Cu-NOTA-IgG in Karpas299 tumor ((5.12±0.89) %ID/g; F=290.99, t values: 19.65 and 22.25, all P<0.001). The uptake of 64Cu-NOTA-CD30 and the control probe in the heart and liver decreased over time in all groups. Ex vivo biodistribution at 48 h was mainly consistent with the results of microPET in vivo. Conclusions:64Cu-NOTA-CD30 is able to visualize the expression level and distribution of CD30 non-invasively. It is promising to be applied for screening the beneficial groups and evaluating efficacy for CD30-targeted immunotherapy.
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Objective:To analyze the effects of apatinib on quality of life and immune function in older adult patients with advanced non-small cell lung cancer.Methods:A total of 187 older adult patients with advanced non-small cell lung cancer admitted to Taizhou Cancer Hospital from January 2017 to January 2021 were included in this study. They were divided into the control group ( n = 93) and the observation group ( n = 94). The control group was treated with carboplatin combined with pemetrexed and the observation group was treated with apatinib based on carboplatin and pemetrexed. Sign and symptoms remission was compared between the observation and control groups. The levels of tumor markers, immune function, and quality of life score were compared between the two groups before and after treatment. Results:Total remission rate in the observation group was significantly higher than that in the control group (88.30% vs. 69.89%, χ2 = 9.59, P < 0.05). After treatment, carbohydrate antigen 125, carbohydrate antigen 50, and carcinoembryonic antigen in the observation group were (16.25 ± 5.47) μg/L, (15.23 ± 3.27) μg/L and (5.91 ± 2.66) mg/L, respectively, which were significantly lower than (21.49 ± 6.61) μg/L, (19.11 ± 3.48) μg/L and (10.14 ± 2.73) mg/L in the control group ( t = 5.91, 7.86, 10.73, all P < 0.05). The percentage of CD3 + and CD4 + cells, and the ratio of CD4 +/CD8 + cells in the observation group were (69.34 ± 8.85)%, (38.15 ± 6.52)%, (1.40 ± 0.33), respectively, which were significantly higher than (64.51 ± 8.74)%, (33.55 ± 6.33)%, (1.23 ± 0.25) in the control group ( t = -3.75, -5.36, -3.97, all P < 0.05). Quality of life score was increased in each group ( P < 0.001). The amplitude of increase in quality of life score was greater in the observation group compared with the control group ( P < 0.001). Conclusion:Apatinib can effectively reduce the level of tumor markers and improve immune function in older adult patients with advanced non-small cell lung cancer and improve quality of life.
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Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.
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Objective:To explore the efficacy and safety of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 8 patients with relapsed/refractory B-ALL treated with blinatumomab in Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from September 2020 to December 2021 were retrospectively analyzed, and their clinical characteristics, overall survival, lymphocyte subsets, cytokines, tandem transplantation and adverse reactions were analyzed.Results:The median follow-up time of 8 patients was 143 d (range: 41-534 d). Five of the 8 patients were alive; among them, 4 of 6 patients assessed to be in minimal residual disease (MRD)-negative complete remission (CR) and 1 of 2 patients assessed to be in non-remission at the time of belintuzumab discontinuation were alive. The median duration of treatment with belintuzumab was 28 d (10-56 d), and it was 23 d (10-56 d) for patients with MRD-positive at baseline and 28 d (25-31 d) for the 4 non-remission patients. Six patients achieved MRD-negative CR after treatment, of which 4 were assessed as MRD-positive at baseline and 2 were assessed as non-remission at baseline. All 4 patients with MRD-positive CR achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Philadelphia chromosome-positive (Ph +) ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph + ALL and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation and had persistent MRD-negative CR. Two of the 4 non-remission patients achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Ph + ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation, and the 2 patients had persistent MRD-negative CR. Leukocyte counts and neutrophils decreased in both MRD-positive CR and non-remission patients after receiving belintumomab. The proportion and absolute number of CD3 + T and CD3 + CD8 + T lymphocytes in patients with MRD-positive CR were higher than those in patients without remission, and both decreased after drug administration. Median interleukin-6 (46.23, 1.42 pg/ml), interleukin-8 (17.85, 2.10 pg/ml), interleukin-10 (7.43, 1.49 pg/ml) and interferon-γ (11.82, 0.39 pg/ml) levels were elevated in MRD-positive CR and non-remission patients at week 3 of treatment. Grade 1 cytokine release syndrome occurred in 1 case with clinical manifestations of fever, which improved after drug suspension. Three cases developed infections, 2 of which were pulmonary and 1 of which was upper respiratory tract infection. No immune effector cell-associated neurotoxic syndrome was observed. Conclusions:Belintumomab is effective for MRD clearance in relapsed/refractory B-ALL with manageable adverse reactions, providing an effective therapeutic option for bridging hematopoietic stem cell transplantation to prolong the survival of patients.