Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To investigate the influencing factors of pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC), and to compare the clinical prognosis of ESCC patients with and without pCR after NCRT (40 Gy/ 20F).Methods:Among patients enrolled in a prospective clinical study, 87 ESCC patients treated with NCRT followed by surgery in Tianjin Medical University Cancer Institute & Hospital between June 2015 and October 2019 were selected. They were divided into the pCR ( n=35) and non-pCR groups ( n=52). Clinicopathological characteristics were retrospectively analyzed and subsequent follow-up was performed. Clinical prognosis and influencing factors were compared between two groups by using Kaplan-Meier and Cox regression analyses. Results:After NCRT, 40% of the ESCC patients could achieve pCR. Univariate analysis showed that patients in the pCR group had a disease-free survival (DFS) of 39.3 months and an overall survival (OS) of 64.0 months. In comparison, patients in the non-pCR group had a DFS of only 14.1 months and an OS of only 25.2 months. The differences were statistically significant (DFS: P<0.01, OS: P<0.05). Multivariate analysis revealed that whether pCR or not after NCRT, age, number of primary lesions, evaluation results after NCRT and postoperative pathological outcomes were important prognostic factors. The differences were statistically significant between two groups (all P<0.05). Conclusion:pCR after NCRT is significantly correlated with long-time survival of patients with ESCC, and pCR after NCRT has an important value in predicting clinical prognosis for long-term survival of ESCC patients.

Objective:To analyse the core genes and mechanisms of brain injury induced by isoflurane using the bioinformatics analysis.Methods:The GSE358 and GSE359 isoflurane anesthesia data set were downloaded from the GEO database. Debatch processing, screening of differentially expressed genes (DEGs), construction and analysis of protein-protein interaction network, and functional enrichment analysis were performed. The gene expression heat map was plotted, and the diseases most related to the core genes were found by Comparative Toxicogenomics Database analysis.Results:A total of 500 DEGs were identified. According to the results of Gene Ontology analysis, they were mainly enriched in the response to foreign stimuli, the response to hypoxia, the apoptotic process, and the inflammatory response in the Biological Process analysis. In Cellular Component analysis, they were mainly enriched in the cytoplasm, extracellular space, and neuronal projections. In Molecular Function analysis, they focused on protein binding and sequence specific DNA binding in transcriptional regulatory regions. In Kyoto Encyclopedia of Genes and Genomes analysis, they were mainly enriched in phosphatidylinositol 3-kinase/protein kinase B signaling pathway, neuroactive ligand-receptor interaction, Toll-like receptor (TLR) signaling pathway, apoptosis and cAMP signaling pathway. Six core genes (interferon gamma [IFN-γ], TLR4, nuclear factor kappa B inhibitor alpha [NFKBIA], interleukins-1α [IL-1α], proto-oncogene fos[Fos]), CCAAT enhancer binding protein β [CEBPB]) were obtained by protein-protein interaction network. Comparative Toxicogenomics Database analysis revealed that core genes (IFN-γ, IL-1α, Fos) were associated with neurological disorders, brain injury, hyperalgesia, drug-related side effects and adverse reactions, neurodegeneration, etc. The inference score could reflect the degree of association between the gene and the disease, among which IFN-γ, IL-1α and Fos had higher inference scores in brain damage.Conclusions:IFN-γ, IL-1α, Fos, TLR4, NFKBIA and CEBPB are six core genes associated with isoflurane-induced brain injury, and these genes may play important roles in immune and inflammatory responses.

OBJECTIVE: To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier. METHODS: Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age, gender, and vaccination profile. Live virus-neutralizing antibodies against five SARS-CoV-2 variants, including WT, Gamma, Beta, Delta, and Omicron BA.1, and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed. RESULTS: The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection, but mainly increased the antibody level against the WT strain, and the antibody against the Omicron strain was the lowest. The neutralizing antibody level decreased rapidly 6 months after infection. The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months. CONCLUSION Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1. Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza. Thus, T-lymphocytes may play an important role in recovery.
Humans ; Antibodies, Neutralizing ; Prospective Studies ; SARS-CoV-2 ; Breakthrough Infections ; COVID-19 Vaccines ; COVID-19 ; T-Lymphocytes ; China/epidemiology* ; Antibodies, Viral

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.

Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML (n=10), MDS-AML (n=6), CMML-AML (n=1), and MDS (n=14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of Ⅰ/Ⅱ grade (48.4%) and one case of Ⅲ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and Ⅲ/Ⅳ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.
Male ; Female ; Humans ; Decitabine ; Myelodysplastic Syndromes/therapy* ; Leukemia, Myeloid, Acute/complications* ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Recurrence ; Chronic Disease ; Graft vs Host Disease/etiology* ; Transplantation Conditioning/adverse effects* ; Bronchiolitis Obliterans Syndrome ; Retrospective Studies

Objective: To evaluate the efficacy and safety of HLA-haploidentical hematopoietic stem cell transplantation (allo-HSCT) for hepatitis-related aplastic anemia (HRAA) patients. Methods: Retrospective analysis was performed on hepatitis-associated aplastic anemia patients who received haplo-HSCT at our center between January 2012 and June 2022. October 30, 2022 was the final date of follow-up. Results: This study included 28 HRAA patients receiving allo-HSCT, including 18 males (64.3% ) and 10 females (35.7% ), with a median age of 25.5 (9-44) years. About 17 cases of severe aplastic anemia (SAA), 10 cases of very severe aplastic anemia (VSAA), and 1 case of transfusion-dependent aplastic anemia (TD-NSAA) were identified. Among 28 patients, 15 patients received haplo-HSCT, and 13 received MSD-HSCT. The 2-year overall survival (OS) rate, the 2-year failure-free survival (FFS) rate, the 2-year transplant-related mortality (TRM) rate, the 100-day grade Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) cumulative incidence rate, and the 2-year chronic graft-versus-host disease (cGVHD) cumulative incidence rate were 81.4%, 81.4% (95% CI 10.5% -20.6% ), 14.6% (95% CI 5.7% -34.3% ), 25.0% (95% CI 12.8% -45.4% ), and 4.2% (95% CI 0.6% -25.4% ), respectively. After transplantation, all patients had no significant liver function damage. Compared with the MSD-HSCT group, only the incidence of cytomegaloviremia was significantly higher in the haplo-HSCT group [60.0% (95% CI 35.2% -84.8% ) vs 7.7% (95% CI 0-22.2% ), P=0.004]. No statistically significant difference in the Epstein-Barr virus was found in the 2-year OS, 2-year FFS, 2-year TRM, and 100-day grade Ⅱ-Ⅳ aGVHD cumulative incidence rates and 2-year cGVHD cumulative incidence rate. Conclusion: Allo-HSCT is safe and effective for HRAA, and haplo-HSCT can be used as a safe and effective alternative for newly diagnosed HRAA patients who cannot obtain HLA-matched sibling donors.
Male ; Female ; Humans ; Adult ; Treatment Outcome ; Anemia, Aplastic/therapy* ; Retrospective Studies ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Hepatitis/etiology* ; Bronchiolitis Obliterans Syndrome ; Transplantation Conditioning

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors