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 explore the therapeutic efficacy and prognostic factors of induction therapy for secondary central nervous system lymphoma(SCNSL).Methods:Clinical data of patients diagnosed with SCNSL from 2010 to 2021 at Guangdong Provincial People's Hospital were retrospectively collected.A retrospective cohort study was performed on all and grouped patients to analyze the efficacy and survival.Multivariate logistic regression analysis was used to explore the adverse prognostic factors.Results:Thirty-seven diffuse large B-cell lymphoma patients with secondary central involvement were included in the research.Their 2-year overall survival(OS)rate was 46.01％and median survival time was 18.1 months.The 2-year OS rates of HD-MTX group and TMZ group were 34.3％and 61％,median survival time were 8.7 and 38.3 months,and median progression-free survival time were 8.1 and 47 months,respectively.Multivariate logistic regression analysis showed that age,sex,IPI,Ann Arbor stage were correlated with patient survival time.The median survival time of patients with CD79B,KMT2D,CXCR4.ERBB2,TBL1XR1,BTG2,MYC,MYD88,and PIM1 mutations was 8.2 months,which was lower than the overall level.Conclusion:HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis,and early application of gene sequencing is beneficial for evaluating prognosis.

Objective:To investigate the effect of low expression of silencing information regulator-6 (SIRT-6) on inflammatory reaction and autophagy in monocytes.Methods:Human acute monocytic leukemia cell line THP-1 was transfected with si-SIRT6 to establish THP-1 cell line with low expressed SIRT-6. The cells were divided into control group, MUS group and MUS+ RAPA group. Cells in control group were cultured with medium added with PBS, cells in MUS Group were cultured with medium added with MUS, and cells in MUS+ RAPA Group were added with MUS and Rapamycin. Cells in each group were cultured for 48 hours. The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the supernatant of each group were detected by enzyme-linked immunosorbent assay (ELISA). The gene expression levels of autophagy-associated protein-5 (ATG-5), Beclin-1, lysosomal-associated membrane protein-1 (LAMP-1), microtubule-associated protein-1 light chain 3B (LC3B) and p62 in cells of each group were detected by Q-PCR. The protein expression levels of p62, ATG-5 and LC3B Ⅱ/LC3BⅠ in cells of each group. The one-way analysis of variance (ANOVA) was used for the measurement data in multi-groups, and the LSD- t test was used for the measurement data in both groups. Results:The gene and protein expression of SIRT-6 in THP-1 cells decreased significantly after si-SIRT6 transfection (Gene: 1.09±0.08 vs. 0.57±0.03, t=14.91, P<0.001; Protein: 0.21±0.04 vs. 0.12±0.03, t=4.41, P=0.070). The levels of IL-1β, IL-6, and TNF-α in the supernatant of si-SIRT6/si-SIRT6 NC-transfected THP-1 cells increased significantly by MUS ( P<0.05), and the levels of IL-1β, IL-6, and TNF-α in the supernatant of cells further increased by MUS ( P<0.05). The levels of IL-1β, IL-6 and TNF-α in the supernatant of si-SIRT6-transfected THP-1 cells increased significantly compared with those of si-SIRT6 NC-transfected THP-1 cells ( P<0.05). The gene expression of p62 in si-SIRT6/si-SIRT6 NC-transfected THP-1 cells significantly decreased by MUS ( P<0.05), the gene expression of ATG-5, Beclin-1, LAMP-1 and LC3B in si-SIRT6/si-SIRT6 NC-transfected THP-1 cells significantly increased by MUS ( P<0.05). The gene expression of p62 in si-SIRT6/si-SIRT6 NC-transfected THP-1 cells further decreased by RAPA ( P<0.05), the gene expression of ATG-5, Beclin-1, LAMP-1 and LC3B in si-SIRT6/si-SIRT6 NC-transfected THP-1 cells further increased by RAPA ( P<0.05). The gene expression level of p62 in si-SIRT6 transfected THP-1 cells significantly decreased than that in si-SIRT6 NC transfected THP-1 cells ( P<0.05), and the gene expression level of ATG-5, LC3B, Beclin-1 and LAMP-1 significantly increased than that in si-SIRT6 NC transfected THP-1 cells ( P<0.05). The protein expression of p62 in si-SIRT6/si-SIRT6 NC-transfected THP-1 cells significantly decreased by MUS ( P<0.05), the protein expression of ATG-5 and LC3B Ⅱ/LC3BⅠ protein in si-SIRT6/si-SIRT6 NC-transfected THP-1 cells significantly increased by MUS ( P<0.05). The protein expression of p62 in si-SIRT6/si-SIRT6 NC-transfected THP-1 cells further decreased by RAPA P<0.05), the protein expression of ATG-5 and LC3B Ⅱ/LC3BⅠ in si-SIRT6/si-SIRT6 NC-transfected THP-1 cells further increased by RAPA ( P<0.05). The protein expression level of p62 in si-SIRT6 transfected THP-1 cells significantly decreased than that in si-SIRT6 NC transfected THP-1 cells ( P<0.05), and the protein expression level of ATG-5 and LC3B Ⅱ/LC3BⅠ significantly increased than that in si-SIRT6 NC transfected THP-1 cells ( P<0.05). Conclusion:Low expression of SIRT-6 gene can promote inflammatory reaction and autophagy in monocytes, and Monosodium urate and autophagy agonist rapamycin can aggravate inflammatory reaction and autophagy.

ObjectiveTo investigate the value of reduced field-of-view DWI （r-FOV DWI） in quantitative assessment of axial spondyloarthritis. MethodsA total of 112 patients with chronic back pain or suspected axial spondyloarthritis receiving full field-of-view DWI （f-FOV DWI） and reduced field-of-view DWI （r-FOV DWI） from December 2019 to December 2021 were enrolled. Next， subjective image quality assessment （anatomical detail， artifacts， distortion， overall image quality） and objective image quality assessment including （signal to noise ratio and contrast to noise ratio） were conducted by two experienced radiologists. In addition， the Apparent Diffusion Coefficient （ADC） values of three groups （active group， inactive group， and control group） on the two DWI sequences were measured by the two radiologists， respectively. Finally， the consistency of measurement between the two researchers was evaluated and the differences in ADC values was compared. Results102 patients were included and were divided into three groups， including the active group （n=32）， inactive group （n=29）， and control group （n=41） according to ASAS diagnostic criteria. All subjective and objective image quality metrics were rated in favor of r-FOV DWI images compared with f-FOV DWI images ［overall image quality： DWI 4（3~4） vs. 3（3~3） and SNR： 6.58（5.05~10.38） vs. 4.46（2.37~10.04）， CNR： 2.04（-1.14~8.29） vs. 0.97（-8.19~7.12）；P＜0.05］. Inter-rater consistency of the two researchers were 0.60~0.74. According to the AUC curve， group inactive vs. control showed r-FOV DWI was better than f-FOV DWI. In other groups （lesion vs. control， active vs. inactive）， there were no differences between both sequences（P＜0.05）. ConclusionThe subjective image quality score and signal to noise ratio of r-FOV DWI were higher than those of f-FOV DWI， which could be used for quantitative assessment of axial spondyloarthritis.

Humans ; Mpox (monkeypox) ; China

OBJECTIVE: To investigate the significance of anti-histidyl tRNA synthetase (Jo-1) antibody in idiopathic inflammatory myopathies (IIM) and its diseases spectrum. METHODS: We enrolled all the patients who were tested positive for anti-Jo-1 antibody by immunoblotting in Peking University People's Hospital between 2016 and 2022. And the patients diagnosed with anti-synthetase antibody syndrome (ASS) with negative serum anti-Jo-1 antibody were enrolled as controls. We analyzed the basic information, clinical characteristics, and various inflammatory and immunological indicators of the patients at the onset of illness. RESULTS: A total of 165 patients with positive anti-Jo-1 antibody were enrolled in this study. Among them, 80.5% were diagnosed with connective tissue disease. And 57.6% (95/165) were diagnosed with IIM, including ASS (84/165, 50.9%), immune-mediated necrotizing myopathy (7/165, 4.2%) and dermatomyositis (4/165, 2.4%). There were 23.0% (38/165) diagnosed with other connective tissue disease, mainly including rheumatoid arthritis (11/165, 6.7%), undifferentiated connective tissue disease (5/165, 3.0%), interstitial pneumonia with autoimmune features (5/165, 3.0%), undifferentiated arthritis (4/165, 2.4%), Sjögren's syndrome (3/165, 1.8%), systemic lupus erythematosus (3/165, 1.8%), systemic vasculitis (3/165, 1.8%), and so on. Other cases included 3 (1.8%) malignant tumor patients, 4 (2.4%) infectious cases and so on. The diagnoses were not clear in 9.1% (15 /165) of the cohort. In the analysis of ASS subgroups, the group with positive serum anti-Jo-1 antibody had a younger age of onset than those with negative serum anti-Jo-1 antibody (49.9 years vs. 55.0 years, P=0.026). Clinical manifestations of arthritis (60.7% vs. 33.3%, P=0.002) and myalgia (47.1% vs. 22.2%, P=0.004) were more common in the ASS patients with positive anti-Jo-1 antibody. With the increase of anti-Jo-1 antibody titer, the incidence of the manifestations of arthritis, mechanic hands, Gottron sign and Raynaud phenomenon increased, and the proportion of abnormal creatine kinase and α-hydroxybutyric dehydrogenase index increased in the ASS patients. The incidence of myalgia and myasthenia were significantly more common in this cohort when anti-Jo-1 antibody-positive ASS patients were positive for one and more myositis specific antibodies/myositis associated autoantibodies (P < 0.05). CONCLUSION The disease spectrum in patients with positive serum anti-Jo-1 antibody includes a variety of diseases, mainly ASS. And anti-Jo-1 antibody can also be found in many connective tissue diseases, malignant tumor, infection and so on.
Humans ; Middle Aged ; Myalgia ; Myositis/epidemiology* ; Autoantibodies ; Connective Tissue Diseases ; Arthritis, Rheumatoid ; Neoplasms

Objective To explore the risk factors for intracranial infection in patients after neurosurgery,con-struct and validate a Nomogram prediction model.Methods Data of 978 patients who underwent neurosurgery in a hospital in Nanjing from January 1,2019 to December 31,2022 were retrospectively analyzed.Independent risk fac-tors were screened through logistic univariate and multivariate analyses.Modeling variables were screened through Lasso regression.A Nomogram model was constructed and internally validated by logistic regression.Effectiveness of the model was evaluated with receiver operating characteristic(ROC)curve,calibration curve and decision curve.Results Among 978 patients underwent neurosurgery,293 had postoperative intracranial infection,with an inci-dence of healthcare-associated infection of 29.96％.There was no significant difference in age,gender,proportion of coronary heart disease,cerebral infarction,diabetes and hypertension between the infected group and the non-in-fected group(all P＞0.05).Multivariate logistic analysis showed that postoperative intracranial hypertension,fe-ver,increased neutrophil percentage in blood routine examination,turbid cerebrospinal fluid,positive Pan's test,decreased glucose concentration,abnormal ratio of cerebrospinal fluid/serum glucose,positive microbial culture,absence of indwelling external ventricular drainage tubes,presence of indwelling lumbar cistern drainage tubes,use of immunosuppressive agents,and long duration of surgery were independent risk factors for postoperative intracra-nial infection in patients who underwent neurosurgery(all P＜0.05).Fifteen variables were screened out through Lasso regression.Fourteen variables were finally included for modeling after collinear screening,missing data impu-tation(random forest method)and checking pairwise interaction items.A Nomogram prediction model was con-structed,with the area under ROC curve,sensitivity,specificity,and accuracy of 0.885,0.578,0.896,and 0.704,respectively.Internal validation of the model was conducted.The modeling and validation groups presented similar effects.The calibration curve and decision curve also indicated that the model had good predictive efficacy.Conclusion The constructed Nomogram prediction model for postoperative intracranial infection after neurosurgery is scientific,and the prediction indicators are easy to obtain.The model presents with high stability,reliability,and application value,thus can provide reference for the assessment of postoperative intracranial infection after neuro-surgery.

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10^-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10^-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

Objective: To analyze the clinical and genetic characteristics of 33 children with congenital lipoid adrenal hyperplasia (CLAH) caused by StAR gene defects. Methods: The clinical, biochemical, genetic, and follow-up (until December 2021) data of 33 children diagnosed with CLAH from 2006 to 2021 were retrospectively analyzed in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Results: Of the 33 children with CLAH, 17 had a karyotype of 46, XX and 16 had a karyotype of 46, XY; 31 were female and 2 were male by social gender. Classic type and non-classic type were found in 30 and 3 children respectively. The age at diagnosis was 9.0 (3.0, 34.5) months. All the 30 cases with classic CLAH presented within the first year of life with skin hyperpigmentation (28 cases, 93%), vomiting and(or) diarrhea (19 cases, 63%), no increase in body weight (8 cases, 27%), elevated adrenocorticotropic hormone levels (21cases (70%)>275 pmol/L), decreased cortisol levels (47 (31,126) nmol/L), hyponatremia ((126±13) mmol/L), hyperkalemia ((5.7±1.1) mmol/L), and normal 17α-hydroxyprogesterone levels (30 cases, 100%). All these with classic CLAH exhibited female external genitalia. Three children with non-classic CLAH (including 2 cases of 46, XY and 1 case of 46, XX) also showed signs and symptoms of adrenal insufficiency, but 2 of them had an age of onset later than 1 year of age, including 1 case of 46, XY with male external genitalia and 1 case of 46, XX with female external genitalia. The other 46, XY patient with non-classic CLAH presented with adrenal insufficiency at 2 months of age, showing micropenis and hypospadias. In the 17 females with 46, XX, 4 older than 10 years of age showed spontaneous pubertal development. A total of 25 StAR gene pathogenic variants were identified in 33 patients, with p.Q258* (18/66, 27%), p.K236Tfs*47 (8/66, 12%) and p.Q77* (6/66, 9%) being the common variantion. Six novel variants were found, including c.358T>G, c.713_714del, c.125del, c.745-1G>A, c.179-2A>C, and exon 1 deletion. Conclusions: Patients with classic CLAH typically present with signs and symptoms of primary adrenal insufficiency in the early infancy period and female external genitalia. p.Q258*, p.K236Tfs*47 and p.Q77* are common variants in CLAH patients.
Adrenal Hyperplasia, Congenital/genetics* ; Adrenal Insufficiency ; Adrenocorticotropic Hormone ; Child, Preschool ; China ; Disorder of Sex Development, 46,XY ; Female ; Humans ; Hydrocortisone ; Hydroxyprogesterones ; Hyperplasia ; Infant ; Male ; Mutation ; Phosphoproteins/genetics* ; Retrospective Studies

OBJECTIVES: To study the clinical features of intestinal polyps and the risk factors for secondary intussusception in children. METHODS: A retrospective analysis was performed for the medical data of 2 669 children with intestinal polyps. According to the presence or absence of secondary intussusception, they were divided into two groups: intussusception (n=346) and non-intussusception (n=2 323). Related medical data were compared between the two groups. The multivariate logistic regression analysis was used to identify the risk factors for secondary intussusception. RESULTS: Among the children with intestinal polyps, 62.42% were preschool children, and the male/female ratio was 2.08∶1; 92.66% had hematochezia as disease onset, and 94.34% had left colonic polyps and rectal polyps. There were 346 cases of secondary intussusception, with an incidence rate of 12.96% (346/2 669). Large polyps (OR=1.644, P<0.001), multiple polyps (≥2) (OR=6.034, P<0.001), and lobulated polyps (OR=93.801, P<0.001) were the risk factors for secondary intussusception. CONCLUSIONS Intestinal polyps in children often occur in preschool age, mostly in boys, and most of the children have hematochezia as disease onset, with the predilection sites of the left colon and the rectum. Larger polyps, multiple polyps, and lobulated polyps may increase the risk of secondary intussusception, and endoscopic intervention is needed as early as possible to improve prognosis.
Child, Preschool ; Female ; Gastrointestinal Hemorrhage ; Humans ; Intestinal Polyps/complications* ; Intussusception/complications* ; Male ; Retrospective Studies ; Risk Factors