Objective:To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. Methods:The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). Results:Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a " cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. Conclusion:The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.

Objective:To explore the relationship between Epstein-Barr virus (EBV) infection, hepatitis B virus (HBV) reactivation and clinical features and prognosis in HBV-infected non-Hodgkin lymphoma (NHL) patients and influencing factors of HBV reactivation.Methods:A retrospective cohort study was conducted. A total of 80 NHL patients with hepatitis B surface antigen (HBsAg) positive (which was defined as HBV positive) who were admitted to the Second People's Hospital of Lianyungang and Jiangsu Province Hospital from December 2012 to October 2022 were selected. All patients were divided into EBV-positive group and EBV-negative group according to EBV DNA results, and further grouped into the HBV reactivation group and the non-reactivation group according to whether HBV were reactivated after chemotherapy. The clinical characteristics of patients among groups were compared. Multivariate logistic regression model was used to analyze the factors influencing HBV reactivation. The Kaplan-Meier method was used to evaluate the progression-free survival (PFS) and overall survival (OS) of patients, and the log-rank test was used for inter-group comparison.Results:Among NHL patients with HBV positive, 27 cases (33.8%) were EBV-positive and 29 cases (36.3%) were HBV reactivation. Compared with the EBV-negative group, the proportion of patients with Ann Arbor stage Ⅲ-Ⅳ [92.6% (25/27) vs. 66.0% (35/53)], elevated β 2-microglobulin level [88.9% (24/27) vs. 62.3% (33/53)], bone marrow involvement [40.7% (11/27) vs. 15.1% (8/53)], and HBV reactivation [51.9% (14/27) vs. 28.3% (15/53)] was higher in the EBV-positive group, and the differences were statistically significant (all P<0.05). There were no statistically significant differences in the composition of patients stratified by age, gender, pathological type, B symptom, lactate dehydrogenase level, international prognostic index score, number of extranodal involvements, liver involvement, hepatitis outbreak, prophylactic anti-HBV therapy, hepatitis B surface antibody (HBsAb), rituximab therapy, and the last chemotherapy effects between the 2 groups (all P > 0.05). Compared with the HBV non-reactivation group, the proportion of patients undergoing hepatitis outbreak [48.3% (14/29) vs. 17.6% (9/51)], not receiving prophylactic anti-HBV therapy [65.5% (19/29) vs. 39.2% (20/51)], HBsAb negative [79.3% (23/29) vs. 21.6% (11/51)], EBV positive [48.3% (14/29) vs. 25.5% (13/51)], receiving rituximab [82.8% (24/29) vs. 60.8% (31/51)] was higher in the HBV reactivation group, and the differenves were statistically significant (all P < 0.05); while there were no statistically significant differences in the composition of patients stratified by the other clinical characteristics between the 2 groups (all P > 0.05). Multivariate logistic regression analysis showed that EBV-positivity was an independent risk factor for HBV reactivation after chemotherapy in NHL patients with HBsAg positive ( OR = 7.073, 95% CI: 1.613-31.010, P = 0.009), while HBsAb positive ( OR = 0.038, 95% CI: 0.008-0.186, P < 0.001) and preventive anti-HBV therapy ( OR = 0.172, 95% CI: 0.039-0.756, P = 0.020) were independent protective factors. The last follow-up was in December 2023 and the median follow-up time was 36.5 months. There were no statistically significant differences in PFS and OS between the EBV-positive group and the EBV-negative group, HBV reactivation group and the non-reactivation group (all P > 0.05). Conclusions:Among HBV-infected NHL patients, those with concurrent EBV infection have a more advanced clinical stage and are very prone to bone marrow invasion, and they also show a higher probability of HBV reactivation; HBV reactivation may be related to whether receiving preventive anti-HBV therapy and rituximab therapy. EBV infection may increase the risk of HBV reactivation in NHL patients; EBV infection and HBV reactivation may not be relevant to the prognosis of patients.

Acute T-lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy, and in recent years, with the advancement of combined chemotherapy and hematopoietic stem cell transplantation, the prognosis of T-ALL has improved significantly, but for patients with primary drug resistance or relapsed/refractory disease the prognosis is still poor. The plant homeodomain finger 6 (PHF6) is a tumor suppressor protein, it plays a pivotal role in T cell differentiation, epigenetic regulation and oncogenic pathway synergy, and its mutations and deletions are commonly associated with the development of T-lymphocytic leukemia. However, the underlying mechanism of PHF6 in the pathogenesis of T-ALL remains unclear. This article reviews the structure, function and mechanism of action of PHF6 in T-ALL, the important coexisting genes associated with the progression of T-ALL, and the research progress in targeted therapy.

Objective:To design and evaluate a cell membrane vaccine strategy based on dendritic cell membrane microbubbles(DCM@MBs),and to explore its potential application in tumor immunotherapy,especially the immune-specific killing of tumor cells through the activation of T cells.Methods:At first,tumor cell membrane proteins were extracted and dendritic cells(DCs)were acti-vated to confirm that tumor antigens could effectively stimulate the maturation of immature DCs.Mature DC membranes were then mixed with lipids to prepare DCM@MBs,which were characterized for morphology,size,and protein composition by confocal laser scanning microscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis.Finally,in vitro co-culture experiments were con-ducted to assess the effect of DCM@MBs on the activation of T cells and their ability for specific killing of tumor cells.Results:In the in vitro DC activation experiment,after stimulation with tumor cell membrane proteins,the 25 μg/mL group had a significant increase in the expression level of MHC class Ⅱ molecule(25.167%±1.203%)on the surface of immature DCs compared with the control group(P<0.001),and DCM@MBs presented with microbubbles encapsulated by red cell membranes,with uniform dispersion and a size of 1-5 μm.In the in vitro co-culture experiment,the amount of breast cancer cells(9.893±0.341)%.Conclusion:The DCM@MBs strategy proposed in this study shows significant potential in tu-mor immunotherapy and can effectively activate T cells and specifically kill and eliminate tumor cells,which provides new ideas for tu-mor immunotherapy.

OBJECTIVE: To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. METHODS: The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). RESULTS: Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a "cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. CONCLUSION The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.
Humans ; Male ; Female ; Child, Preschool ; Infant ; Child ; Olivopontocerebellar Atrophies/genetics* ; Arginine-tRNA Ligase/genetics* ; Mutation ; Cerebellar Diseases

Objective:To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. Methods:The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). Results:Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a " cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. Conclusion:The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.

Objective:To investigate the effects of compound Duzhong Jiangu Granules on joint function and gut microbiota in patients with Kashin-Beck disease.Methods:A single group pre- and post-experimental design was conducted, the patients with Kashin-Beck disease were selected as the subjects in Xunyi County, Xianyang City, Shaanxi Province; and treated with oral administration of compound Duzhong Jiangu Granules (12 g/bag, 1 bag/time, 3 times/day) for a period of 1 month. The improvement of joint function was evaluated using the joint dysfunction index scoring method before and after treatment. Morning stool samples of patients were collected and the changes in gut microbiota were analyzed before and after treatment using 16S rDNA sequencing technology.Results:A total of 87 patients with Kashin-Beck disease were included, including 44 males and 43 females; the age was (60.38 ± 7.12) years old, and the body mass index was (23.67 ± 3.59) kg/m 2. The comprehensive scores of joint dysfunction index for patients with Kashin-Beck disease before and after treatment were (7.27 ± 2.05) and (5.86 ± 2.01) points, respectively, and the difference was statistically significant ( t = 5.88, P < 0.001). The sequencing results of gut microbiota showed that there were statistically significant differences in the alpha diversity (chao1, observed species index) and beta diversity of gut microbiota in patients with Kashin-Beck disease before and after treatment ( Z = - 5.08, - 5.03, R = 0.09, P < 0.001). In the distribution of gut microbiota, Firmicutes was the dominant phylum, with relative abundances of 50.21% and 52.09% before and after treatment, respectively; the Bifidobacterium was the dominant bacterial genus, with relative abundances of 16.83% and 18.81% before and after treatment, respectively. At the genus level, a total of 17 gut microbiota genera were screened out, among which the relative abundances of Hafnia-Obesumbacterium, Gammaproteobacteria_unclassified, Acinetobacter, Pantoea, Leuconostoc, and Akkermanisia were significantly higher than before treatment ( Z = - 2.40, - 2.24, - 2.06, - 3.59, - 2.24, - 2.11, P < 0.05). The relative abundances of Dubosiella, Selenomonas, Anaeroplasma, Lachnospiraceae_ NK4A136_group, Rikenella, Prevotella, Megasphaera, Lactobacillus, Prevotella-9, Phascolarctobacterium, and Desulfovibrio were significantly lower than before treatment ( Z = - 9.38, - 2.61, - 2.18, - 8.43, - 2.45, - 2.46, - 2.49, - 7.29, - 2.29, - 2.55, - 2.08, P < 0.05). Conclusions:Compound Duzhong Jiangu Granules can effectively improve the joint function of patients with Kashin-Beck disease, and alter the diversity and richness of the gut microbiota community. It may reduce clinical symptoms in patients by regulating the structure of gut microbiota.

Objective:To investigate clinical characteristics and high-risk factors of prognosis of twin-to-twin transfusion syndrome(TTTS) combined with necrotizing enterocolitis(NEC).Methods:The clinical data of 102 children with TTTS admitted to the NICU at the Third Affiliated Hospital of Zhengzhou University from January 2017 to January 2020 were collected.Fifty-one pairs(102 cases)of twins without TTTS who were hospitalized at the same time and in the same gestational age were selected as the control group, and the relevant case data were collected and compared.The clinical data of 14 children with NEC in TTTS group were analyzed retrospectively.Results:(1)The average gestational age of TTTS group was(32.24±2.12)weeks, and that was (32.47±1.84) weeks in control group, with no statistical significance( P>0.05). The average birth weight of TTTS group was(1 547.63±523.80)g, which was lower than that of control group(1 658.71±454.13)g( P<0.05). There were 14 children in TTTS group with NEC, with an incidence of 13.7%(14/102), and seven children in the control group with NEC, with an incidence of 6.9%(7/102)( P<0.05). The proportion of very low birth weight infants, NEC occurrence within 2 weeks and mortality in TTTS group were higher than those in control group( P<0.05). (2)Compared with the non-NEC group, the NEC group of TTTS children had lower birth weight, the incidence of intrauterine distress and severe postnatal asphyxia, and the rate of sepsis were significantly higher than those in non-NEC group( P<0.05). (3)Among TTTS children, NEC was diagnosed in ten donors(71.4%) and four recipients(28.6%), with statistically significant difference between two groups( P<0.05). (4)The early clinical symptoms of TTTS complicated with NEC were mainly bloody stools, abdominal distension, poor response, apnea, and vomiting. Conclusion:TTTS is one of the risk factors for NEC, which the occurrence time of TTTS combined with NEC is not completely consistent with the classic NEC, which is more likely to occur within 2 weeks after birth.Children with TTTS complicated with NEC mostly occur in donor infants, and fetal distress in utero, severe asphyxia and sepsis are the high risk factors.The early clinical symptoms of TTTS combined with NEC are not significantly different from those of common NEC, mainly including bloody stools, abdominal diste, poor response, apnea, and vomiting.Vigilance should be raised when similar digestive symptoms appear in children.

Pressure injury is a common problem faced by global health care institutions, which seriously threatens the lives and health of patients. The treatment and care of pressure injuries need people in multiple professional fields to work together. This article interprets the assessment and planning part of the clinical practice guideline for the third edition of " Assessment and Management of Pressure Injuries for the Interprofessional Team" developed by the Registered Nurses' Association of Ontario, Canada. This article aims at helping the interprofessional team conduct accurate, comprehensive, and full-process assessments of patients with pressure injuries, formulate a reasonable diagnosis and treatment plan, and providing a basis for the implementation of correct treatment measures, so as to promote the improvement and healing of pressure injuries.

Objective To study the clinical manifestations, risk factors, treatment and prognosis of carbapenem-resistant klebsiella pneumoniae (CRKP) sepsis in premature infants. Method A retrospective analysis was done for the premature infants diagnosed with klebsiella pneumoniae sepsis and admitted to the neonatal wards of the Hospital from April 2015 to March 2018. According to the results of drug sensitive test, the infants was assigned to CRKP group and non-CRKP group. The perinatal factors, clinical manifestations, treatment, and prognosis of the two groups were analyzed. Furthermore, high risk factors for CRKP group were analyzed. Result A total of 39 premature infants with KP sepsis were included in our study. There were 23 cases in the CRKP group and 16 cases in the non-CPAP group. In CPKP group, the gestational age was (29.5 ± 0.6) weeks, the birth weight was (1177 ± 272) g. In non-CRKP group, the gestational age was (30.0 ± 0.5) weeks, the birth weight was (1387 ± 220) g. Univariate Logistic regression analysis showed that low birth weight was a risk factor for CRKP sepsis in premature infants (OR=1.203, 95％CI 1.068～1.355, P=0.002). The proportion of that required combination treatment with antibiotics and the incidence of intracranial hemorrhage after infection in the CPKP group were both higher than that in the non-CRKP group (P<0.05). The proportion and duration of antibiotics used in the first week before the onset of infection in infants with CRKP sepsis and combined antibiotic treatment were significantly higher than those in infants with CPKP sepsis and single antibiotic treatment. The use of antibiotics in the first week before the onset of infection was an independent risk factor for the combined drug treatment of premature infants with CRKP sepsis (OR=10.500, 95％CI 1.015～108.577, P=0.049). In the CRKP group, the improvement rate was 87.0％(20/23), 2 cases were withdrew, and 1 case deceased. In the non-CPKP group, the improvement rate was 87.5％(14/16), and 2 deceased. Conclusion The lower the birth weight, the greater the risk of infection with CRKP sepsis. The proportion of need combination treatment with antibiotics is high in infants with CRKP sepsis. The use of antibiotics in the first week before the onset of infection is a risk factor for combined antibiotic treatment in premature infants with CRKP sepsis .