[Objective] To conduct serological identification and molecular mechanism study on a ambiguous ABO blood group. [Methods] Standard serological techniques were used for the forward and reverse typing of ABO blood type. ABO gene coding and regulatory regions were analyzed by PCR after DNA extraction. Monoclonal sequencing was used to detect the haplotypes of the DNA sequence, and bioinformatics analysis was applied to predict the possible translation outcomes of the mutated DNA sequence. [Results] The sample’s red blood cells showed mixed field agglutination with anti-A, and the serum agglutinated with B cells, exhibiting serological characteristics of subtype A. Direct sequencing and monoclonal sequencing analysis of the ABO gene confirmed one allele as O02, the other had a c.27delC mutation compared with A102, which could cause the translation sequence to terminate prematurely at the 19th amino acids. Analysis and prediction suggested that the mutation might affect the function of the transferase through mechanisms such as shifting the initiation codon, altering the reading frame and affecting the splice sites. [Conclusion] This case is a rare A subtype caused by the c.27delC variation, and the impact on the glycosyltransferase may involve multiple mechanisms, which require further research and exploration.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective To analyze the effects of agatroban combined with mitochondrial transplantation on endothelial function and hemorheology in mice with cerebral ischemia-reperfusion injury.Methods 50 SPF grade Kunming mice,with 10 as the normal group,38 mices were successfully modeled and divided into a model group of 9,a mitochondrial transplantation group of 9,an Agatroban group of 10,and a combination group of 10.The mitochondrial transplantation group was given exogenous mitochondrial extract,the agatroban group was given agatroban,the combined group was given agatroban combined with mitochondrial transplantation,and the blank group and model group were injected with normal saline.Observation of changes in cerebral infarction volume,pathological morphology of brain tissue,endothelial function,hemorheology,and relative expression of apoptosis related proteins in mice after 7 days of intervention.Results Compared with normal group,cerebral infarction volume ratio,ET-1,whole blood viscosity,plasma viscosity,Caspase-3 and Bax protein expression levels were increased in model group,mitochondrial transplantation group,agatroban group and combined group,while NO level and Bcl-2 protein expression levels were decreased(P<0.05).Compared with the model group,the cerebral infarction volume ratio,ET-1,whole blood viscosity,plasma viscosity,Caspase-3 and Bax protein expressions in the mitochondrial transplantation group,agatroban group and combined group were decreased,and the combined group was lower than the mitochondrial transplantation group and agatroban group,and the NO level and Bcl-2 protein expression were increased.The combined group was higher than that of mitochondrial transplantation group and agatriban group(P<0.05).Conclusion In mice with cerebral ischemia-reperfusion injury,endothelial function injury was improved,hemorheology was regulated,and brain injury was alleviated after agatroban combined with mitochondrial transplantation.

Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorders (PTLD) are one of the most severe complications after hematopoietic stem cell transplantation (HSCT). This study includes 31 cases of aplastic anemia (AA) patients who developed PTLD after haploidentical transplantation, summarizing their clinical characteristics and categorizing them into either rituximab monotherapy group or combination therapy group based on whether their condition improved by 1 log after a single dose of rituximab. The incidence of PTLD after HSCT in children with AA was 10.16%, and the incidence of PTLD in patients with age >10 years was significantly increased ( χ2=11.336, P=0.010). Of the 31 patients, 27 were clinically diagnosed and 4 were pathologically confirmed. Finally, 15 patients were classified into the rituximab treatment group and 15 patients into the combination treatment groups. Finally three patients died, and the 2-year overall survival rate was (89.7±5.6) %. Standard pre-treatment protocols and EBV reactivation are risk factors affecting the prognosis of PTLD. There was no statistically significant difference in the impact of the two treatment schemes on prognosis.

OBJECTIVE: To identify the pathogenesis in two patients of restrictive cardiomyopathy (RCM) using high-throughput sequencing. METHODS: Peripheral blood samples from the two patients and their parents were collected and genomic DNAs were extracted to conduct targeted next generation sequencing or whole exome sequencing. Bioinformation analysis was performed to identify the pathogenic variants in genes associated with cardiomyopathy, which were further validated by Sanger sequencing. RESULTS: By high throughput sequencing, we detected a de novo heterozygous variant c.549+1G>T in TNNI3 gene in patient 1. The variant has not been reported previously and was predicted to be pathogenic in line with American College of Medical Genetics and Genomics (ACMG) guidelines (PVS1+PS2+PM2). Another heterozygous variant c.433C>T (p.Arg145Trp) in TNNI3 gene was identified in patient 2 and his father. The variant had been reported as pathogenic variant in Clinvar and HGMD databases; based on ACMG guidelines, the variant was predicted to be likely pathogenic (PS3+PM1+PP3). CONCLUSION TNNI3 variants may be the causative gene responsible for restrictive cardiomyopathy in the two patients. High throughput sequencing results provide bases for the diagnosis of restrictive cardiomyopathy.
Cardiomyopathy, Restrictive/genetics* ; Child ; Genomics ; Heterozygote ; Humans ; Mutation ; Whole Exome Sequencing

Metabolic regulation has been proven to play a critical role in T cell antitumor immunity. However, cholesterol metabolism as a key component of this regulation remains largely unexplored. Herein, we found that the low-density lipoprotein receptor (LDLR), which has been previously identified as a transporter for cholesterol, plays a pivotal role in regulating CD8

Objective:To investigate the reoperation and perioperative management of residual cyst wall with perineal intractable sinus after resection of presacral cyst tumors.Methods:The clinical data of 29 patients with residual cyst wall and perineal intractable sinus after resection of presacral cyst tumors in Affiliated Cancer Hospital of Zhengzhou University from January 2014 to August 2019 were reviewed, including the characteristics of the residual cyst wall with perineal intractable sinus after resection of presacral cyst tumors, surgical method, and perioperative management.Results:Twenty-nine patients with residual cyst wall and perineal intractable sinus after resection of presacral cyst tumors, including 9 cases of epidermoid cysts, 7 cases of dermoid cysts, 10 cases of mature teratomas and 3 cases of malignant cysts (including malignant transformation of caudate cyst and teratoma); The 29 patients underwent posterior approaches for cyst resection in other hospital before, of whom 1 patient underwent posterior combined with transabdominal approach. All of thes patients underwent resection of residual presacral cyst wall and perineal intractable sinus in our hospital, of whom 25 patients underwent a transperineal approach through an arc-shaped incision anterior to the apex of the coccyx, and the other 4 patients underwent transperineal arc-shaped incision combined with transabdominal approach. All of the patients were cured without serious complications occurring, postoperative pathological and the magnetic resonance imaging diagnosis showed that the residual cyst wall and perineal intractable sinus were all completely removed.Conclusion:Appropriate surgical approache and perioperative treatment for the patients with residual cyst wall and perineal intractable sinus are very important to promote the resection of residual cyst wall and the healing of perineal intractable sinus.

Objective:To investigate the reoperation and perioperative management of residual cyst wall with perineal intractable sinus after resection of presacral cyst tumors.Methods:The clinical data of 29 patients with residual cyst wall and perineal intractable sinus after resection of presacral cyst tumors in Affiliated Cancer Hospital of Zhengzhou University from January 2014 to August 2019 were reviewed, including the characteristics of the residual cyst wall with perineal intractable sinus after resection of presacral cyst tumors, surgical method, and perioperative management.Results:Twenty-nine patients with residual cyst wall and perineal intractable sinus after resection of presacral cyst tumors, including 9 cases of epidermoid cysts, 7 cases of dermoid cysts, 10 cases of mature teratomas and 3 cases of malignant cysts (including malignant transformation of caudate cyst and teratoma); The 29 patients underwent posterior approaches for cyst resection in other hospital before, of whom 1 patient underwent posterior combined with transabdominal approach. All of thes patients underwent resection of residual presacral cyst wall and perineal intractable sinus in our hospital, of whom 25 patients underwent a transperineal approach through an arc-shaped incision anterior to the apex of the coccyx, and the other 4 patients underwent transperineal arc-shaped incision combined with transabdominal approach. All of the patients were cured without serious complications occurring, postoperative pathological and the magnetic resonance imaging diagnosis showed that the residual cyst wall and perineal intractable sinus were all completely removed.Conclusion:Appropriate surgical approache and perioperative treatment for the patients with residual cyst wall and perineal intractable sinus are very important to promote the resection of residual cyst wall and the healing of perineal intractable sinus.

Objective To explore the feasibility and potential application value of establishing the neonatal pig models of islet transplantation under the renal capsule. Methods Nine wild-type neonatal Duroc pigs were selected, including 1 animal as the control (p6307), 6 as islet transplant donors and 2 as islet transplant recipients (p6210, p6207). After islet isolation and differentiation in vitro, islet transplantation under the renal capsule of the pig was performed. Immunosuppressive therapy of tacrolimus (Tac) combined with sirolimus was given after operation. Postoperative body weight, blood glucose and serum creatinine levels of the recipients were monitored. The p6210 recipient neonatal pig was sacrificed at postoperative 4 weeks, while the p6207 recipient and the control neonatal pig were sacrificed at postoperative 8 weeks. The islet grafts under the renal capsule were collected for pathological staining and insulin immunofluorescent staining. Results After islet transplantation under the renal capsule of the pigs, the growth rate of body weight of the recipients was significantly slower than that of the control neonatal pig, accompanied with intermittent symptoms, such as anorexia and diarrhea, etc. However, the blood glucose and serum creatinine levels of the recipients did not significantly differ from preoperative levels and those of the control neonatal pig. Evident islet mass was observed under the renal capsule of the p6210 recipient. Pathological staining and insulin immunofluorescent staining confirmed that the islet mass had the function of secreting insulin, whereas no obvious islet mass could be seen under the renal capsule of the p6207 recipient. Pathological staining detected no evident islet mass, suggesting the possibility of islet transplantation failure caused by rejection in the p6207 recipient. Conclusions The establishment of neonatal pig models of islet transplantation under the renal capsule is a feasible technique, which provides preliminary evidence for the establishment of composite islet-kidney donor graft in pig models for xenotransplantation in the treatment of end-stage diabetic nephropathy.