Objective:To explore the high-risk factors affecting the severity of neonatal necrotizing enterocolitis (NEC).Methods:This study involved 153 NEC patients admitted to the Neonatology Department of the Children's Hospital of Soochow University from January 1, 2017, to December 30, 2023. Based on the severity of NEC determined by Bell's criteria, these patients were divided into two groups: mild group (Bell stage Ⅱ, n=70) and severe group (Bell stage Ⅲ, n=83). Clinical data including general conditions, clinical treatment and disease status before the onset of NEC, laboratory test results, and perinatal conditions of the mothers were retrospectively collected. Univariate analysis (rank-sum test and Chi-square test) and multivariate analysis (logistic regression analysis) were used to explore the risk factors affecting the severity of NEC. Results:The proportion of infants with gestational age<37 weeks or birth weight<1 500 g, the rate of antibiotic usage, sepsis or shock were higher in the severe group than in the mild group [91.6% (76/83) vs. 75.7% (53/70); 55.4% (46/83) vs. 34.3% (24/70); 85.5% (71/83) vs. 71.4% (50/70); 55.4% (46/83) vs. 17.1% (12/70); 30.1% (25/83) vs. 8.6% (6/70); with χ 2 values of 7.22, 6.84, 4.57, 23.64, and 10.91, respectively, all P<0.05]. Furthermore, the severe group had a late initiation of breastfeeding and longer durations of peripherally inserted central catheter (PICC) placement and parenteral nutrition [2.00 d (1.00-2.00 d) vs. 1.00 d (1.00-2.00 d); 0.00 d (0.00-18.00 d) vs. 0.00 d (0.00-7.50 d); 14.00 d (5.00-21.00 d) vs. 10.50 d (0.00-18.25 d), with Z values of -2.90, -1.98, and -2.09, respectively, all P<0.05]. (2) Within 48 h before the onset, the severe group had higher proportions of infants with decreased white blood cell count, decreased platelet count, electrolyte imbalance, and metabolic acidosis than the mild group [53.0% (44/83) vs. 14.3% (10/70); 49.4% (41/83) vs. 10.0% (7/70); 38.6% (32/83) vs. 14.3% (10/70); 37.3% (31/83) vs. 14.3% (10/70), with χ2 values of 24.94, 27.38, 11.23, and 10.30, respectively, all P<0.05]. Besides, the levels of procalcitonin and C-reactive protein were higher in the severe group than in the mild group [2.31 ng/ml (0.26-11.71 ng/ml) vs. 0.22 ng/ml (0.00-2.19 ng/ml); 58.50 mg/L (14.34-125.25 mg/L) vs. 8.20 mg/L (0.23-34.56 mg/L), with Z values of -3.88 and -5.02, respectively, both P<0.05]. (3) Multivariate logistic regression analysis showed that prolonged duration of PICC placement, decreased platelet count, electrolyte imbalance, metabolic acidosis, and concurrent sepsis were independent risk factors affecting the severity of NEC [ OR (95% CI) values were 1.104 (1.020-1.196), 5.364 (1.667-17.253), 4.047 (1.171-13.986), 4.333 (1.290-14.556), and 3.290 (1.005-10.774), respectively, with all P<0.05]. Conclusions:Prolonged duration of PICC placement, concurrent sepsis, decreased platelet count, electrolyte imbalance, and metabolic acidosis in NEC patients are more likely to lead to severe cases. In clinical practice, attention should be paid to relevant indicators, and abnormal changes should be identified and intervened in a timely manner to reduce the occurrence of severe NEC.

Pathogens, including bacteria, viruses, and fungi, can cause infections and inflammatory responses when invading the human body, posing life-threatening risks in severe cases. Pathogen culturing is considered the gold standard for diagnosing infections, but its time-consuming nature hampers early clinical diagnosis. Polymerase chain reaction offers high sensitivity and specificity but can result in false-negative outcomes. Nanopore sequencing, which features real-time sequencing while unwinding the DNA strands, allows for direct sequencing and immediate analysis. In viral detection, it rapidly obtains pathogen genomes and identifies genetic variations. Direct sequencing of the 16S ribosomal RNA in bacteria and the internal transcribed spacer sequences in fungi enables early diagnosis. It can also detect bacterial resistance, guiding clinical doctors in selecting appropriate antibiotics. Additionally, rapid pathogen detection can be achieved in vector-borne diseases and rare diseases. With advancements in technologies such as deep learning, nanopore sequencing technology is expected to become a powerful tool for early diagnosis of infectious pathogens.

Objective:To explore the high-risk factors affecting the severity of neonatal necrotizing enterocolitis (NEC).Methods:This study involved 153 NEC patients admitted to the Neonatology Department of the Children's Hospital of Soochow University from January 1, 2017, to December 30, 2023. Based on the severity of NEC determined by Bell's criteria, these patients were divided into two groups: mild group (Bell stage Ⅱ, n=70) and severe group (Bell stage Ⅲ, n=83). Clinical data including general conditions, clinical treatment and disease status before the onset of NEC, laboratory test results, and perinatal conditions of the mothers were retrospectively collected. Univariate analysis (rank-sum test and Chi-square test) and multivariate analysis (logistic regression analysis) were used to explore the risk factors affecting the severity of NEC. Results:The proportion of infants with gestational age<37 weeks or birth weight<1 500 g, the rate of antibiotic usage, sepsis or shock were higher in the severe group than in the mild group [91.6% (76/83) vs. 75.7% (53/70); 55.4% (46/83) vs. 34.3% (24/70); 85.5% (71/83) vs. 71.4% (50/70); 55.4% (46/83) vs. 17.1% (12/70); 30.1% (25/83) vs. 8.6% (6/70); with χ 2 values of 7.22, 6.84, 4.57, 23.64, and 10.91, respectively, all P<0.05]. Furthermore, the severe group had a late initiation of breastfeeding and longer durations of peripherally inserted central catheter (PICC) placement and parenteral nutrition [2.00 d (1.00-2.00 d) vs. 1.00 d (1.00-2.00 d); 0.00 d (0.00-18.00 d) vs. 0.00 d (0.00-7.50 d); 14.00 d (5.00-21.00 d) vs. 10.50 d (0.00-18.25 d), with Z values of -2.90, -1.98, and -2.09, respectively, all P<0.05]. (2) Within 48 h before the onset, the severe group had higher proportions of infants with decreased white blood cell count, decreased platelet count, electrolyte imbalance, and metabolic acidosis than the mild group [53.0% (44/83) vs. 14.3% (10/70); 49.4% (41/83) vs. 10.0% (7/70); 38.6% (32/83) vs. 14.3% (10/70); 37.3% (31/83) vs. 14.3% (10/70), with χ2 values of 24.94, 27.38, 11.23, and 10.30, respectively, all P<0.05]. Besides, the levels of procalcitonin and C-reactive protein were higher in the severe group than in the mild group [2.31 ng/ml (0.26-11.71 ng/ml) vs. 0.22 ng/ml (0.00-2.19 ng/ml); 58.50 mg/L (14.34-125.25 mg/L) vs. 8.20 mg/L (0.23-34.56 mg/L), with Z values of -3.88 and -5.02, respectively, both P<0.05]. (3) Multivariate logistic regression analysis showed that prolonged duration of PICC placement, decreased platelet count, electrolyte imbalance, metabolic acidosis, and concurrent sepsis were independent risk factors affecting the severity of NEC [ OR (95% CI) values were 1.104 (1.020-1.196), 5.364 (1.667-17.253), 4.047 (1.171-13.986), 4.333 (1.290-14.556), and 3.290 (1.005-10.774), respectively, with all P<0.05]. Conclusions:Prolonged duration of PICC placement, concurrent sepsis, decreased platelet count, electrolyte imbalance, and metabolic acidosis in NEC patients are more likely to lead to severe cases. In clinical practice, attention should be paid to relevant indicators, and abnormal changes should be identified and intervened in a timely manner to reduce the occurrence of severe NEC.

Pathogens, including bacteria, viruses, and fungi, can cause infections and inflammatory responses when invading the human body, posing life-threatening risks in severe cases. Pathogen culturing is considered the gold standard for diagnosing infections, but its time-consuming nature hampers early clinical diagnosis. Polymerase chain reaction offers high sensitivity and specificity but can result in false-negative outcomes. Nanopore sequencing, which features real-time sequencing while unwinding the DNA strands, allows for direct sequencing and immediate analysis. In viral detection, it rapidly obtains pathogen genomes and identifies genetic variations. Direct sequencing of the 16S ribosomal RNA in bacteria and the internal transcribed spacer sequences in fungi enables early diagnosis. It can also detect bacterial resistance, guiding clinical doctors in selecting appropriate antibiotics. Additionally, rapid pathogen detection can be achieved in vector-borne diseases and rare diseases. With advancements in technologies such as deep learning, nanopore sequencing technology is expected to become a powerful tool for early diagnosis of infectious pathogens.

Objective:To analysis the necessity of additional surgical intervention for non-curative endoscopic resection patients with early gastric cancer.Methods:A retrospective analysis was conducted on 73 patients with early gastric cancer who underwent additional surgical procedures after non-curative endoscopic resection at Chinese PLA General Hospital from July 2009 to May 2023. The main outcome measures included pathological classification, positive horizontal margins, positive vertical margins, invasion depth, vascular and lymphatic invasion, eCura grade, lymph node metastasis, and overall survival rate.Results:A total of 73 patients with early gastric cancer who were determined to have non-curative endoscopic resection underwent additional surgical procedures, including 58 males and 15 females with a mean age of 61 (53-67) years. In terms of the site of onset, 37 cases were located in the upper part of the stomach, 24 cases in the lower part, 11 cases in the middle part, and 1 case had multiple lesions. In terms of pathological classification, 43 cases were highly differentiated tubular adenocarcinoma, 16 cases were mucinous/signet ring cell carcinoma, 10 cases were poorly differentiated tubular adenocarcinoma, and 4 cases were high-grade intraepithelial neoplasia. In terms of morphological classification, 22 cases were type 0-Ⅱa, 43 cases were type 0-Ⅱb, and 8 cases were type 0-Ⅲ. In terms of invasion depth, 17 cases were mucosal cancer, 23 cases had submucosal invasion less than 500 μm, and 33 cases had submucosal invasion more than 500 μm. In terms of vascular and lymphatic invasion, 8 cases had lymphatic vessel invasion and 8 cases had venous invasion. Among the 73 patients, 4 were diagnosed as having eCura A, 5 as eCuraB, 4 as eCura C1, and 60 as eCura C2. Among the 60 patients diagnosed as having eCura C2, only 2 cases (3.3%) were found to have lymph node metastasis around the stomach based on postoperative pathological evaluation. Among the 73 endoscopic specimens, 7 patients had positive horizontal margins, 21 had positive vertical margins, and 2 had positive margins in both directions, totaling 30 patients with positive horizontal or vertical margins. According to postoperative pathological evaluation, 9 cases (30.0%) had residual tumors in the original site. Among the 73 patients, 5 were lost to follow-up and 4 died, resulting in an overall survival rate of 94.12% (64/68) and disease-specific survival rate of 98.53% (67/68). The follow-up time of patients was 61.37 (10-166) months.Conclusion:For early gastric cancer patients with eCura C2 following non-curative endoscopic resection, additional surgery is feasible. However, the proportion of patients with actual lymph node metastasis is relatively low.

Objective:To study the expression and significance of neutrophil extracellular traps (NETs) in neonatal sepsis.Methods:Prospective research were used in this study. Term infants with neonatal sepsis hospitalized for the first time in the Department of Neonatology, Children's Hospital of Soochow University from June 2020 to November 2020 were selected as the sepsis group. According to a ratio of about 1∶1, term infants with mild hyperbilirubinemia who were admitted in the same period, with gestational age difference less than 1 week from those in the sepsis group, and whose parents agreed to participate in the study were selected as the control group. On admission, clinical data as well as blood samples of the two groups were collected. Levels of NETs marker citrulline histone H3-DNA (CitH3-DNA) were detected by Enzyme-linked immunosorbent assay, and circulating cell-free DNA (cfDNA) was tested by the fluorescence microplate reader. General data, white blood cell (WBC), neutrophil count (NE), platelet (PLT), C- reactive protein (CRP), blood culture, CitH3-DNA and cfDNA were compared between the two groups. The diagnostic value of CITH3-DNA and cfDNA in neonatal septicemia was analyzed by the receiver operating characteristic (ROC) curve.Results:A total of 74 infants were included in the study, including 39 cases in the sepsis group and 35 cases in the control group. CitH3-DNA and cfDNA in the sepsis group were significantly higher than those in the control group [CitH3-DNA (optical density): 0.85±0.05 vs. 0.48±0.03, cfDNA (mg/L): 0.90±0.05 vs. 0.56±0.03] ( P<0.01). There was no significant correlation between CitH3-DNA and cfDNA. The level of CitH3-DNA had no correlation with gender, gestational age, age, birth weight, WBC, NE, PLT and CRP ( P>0.05). cfDNA was positively correlated with age and NE ( P<0.05), and negatively correlated with PLT ( P<0.05). Combined with CRP, the area under the ROC curve of CitH3-DNA+CRP, cfDNA+CRP, and CitH3-DNA+cfDNA+CRP were 0.947, 0.947 and 0.970 respectively, and the sensitivity to predict neonatal sepsis were 92.3%, 84.6% and 94.9% respectively, the specificity were 94.3%, 97.1% and 100% respectively, all higher than the predictive value of each index alone. Conclusions:The plasma NETs levels increase significantly in neonatal sepsis patients, especially CitH3-DNA with a strong specificity, and can be considered as a biomarker for early diagnosis of neonatal sepsis. NETs together with CRP, could drastically improve the predictive value of neonatal sepsis.

Objective:To explore the effect of amiodarone on warfarin′s time in therapeutic range (TTR), daily dose of warfarin, and the occurrence of over anticoagulation in patients treated with warfarin after heart valve surgery.Methods:Demographic information and clinical information of patients taking warfarin for heart valve surgery in the anticoagulation clinic in Fuwai Hospital of Chinese Academy of Medical Sciences from November 2019 to January 2021 were collected. The patients were divided into amiodarone group and control group according to whether they were treated with amiodarone. The percentage of TTR, stable daily dose of warfarin, and the proportion of times of INR>3 in patients in the 2 groups within 90 days of outpatient follow-up were retrospectively analyzed.Results:A total of 407 patients were included in the study. There were 35 patients in the amiodarone group, including 15 males and 20 females, with a median age of 56 (49, 64) years, in which 20 (57.1%) had concomitant atrial fibrillation (AF). There were 372 patients in the control group, including 227 males and 145 females, with a median age of 55 (48, 63) years, in which 105 (28.2%) with AF. Within 90 days of discharge, the difference of percentage of TTR between the amiodarone and control groups was not significant [57.6% (44.6%, 70.6%) vs. 67.3% (52.3%, 82.3%), P=0.061], but the stable daily dose of warfarin in patients in the amiodarone group was significantly lower than that in patients in the control group [2.25 (1.72, 2.78) mg vs. 3.38 (2.59, 4.18) mg, P<0.001]. The median proportion (range) of times of INR>3 in the 1-14 days, 15-90 days after discharge and the whole follow-up period in patients in the amiodarone group were higher than those in the control group[0 (0-0.3) vs. 0(0-0.3), P=0.016; 0.08(0-0.3) vs. 0(0-1.0), P=0.002; 0.06(0-0.85) vs. 0(0-0.22), P=0.001]. Conclusions:Amiodarone can significantly increase the risk of anticoagulation in patients treated with warfarin after heart valve surgery. The daily dose of warfarin needs to be reduced in order to achieve a higher TTR and maintain the stability of anticoagulation therapy.

Objective:To explore the effect of amiodarone on warfarin′s time in therapeutic range (TTR), daily dose of warfarin, and the occurrence of over anticoagulation in patients treated with warfarin after heart valve surgery.Methods:Demographic information and clinical information of patients taking warfarin for heart valve surgery in the anticoagulation clinic in Fuwai Hospital of Chinese Academy of Medical Sciences from November 2019 to January 2021 were collected. The patients were divided into amiodarone group and control group according to whether they were treated with amiodarone. The percentage of TTR, stable daily dose of warfarin, and the proportion of times of INR>3 in patients in the 2 groups within 90 days of outpatient follow-up were retrospectively analyzed.Results:A total of 407 patients were included in the study. There were 35 patients in the amiodarone group, including 15 males and 20 females, with a median age of 56 (49, 64) years, in which 20 (57.1%) had concomitant atrial fibrillation (AF). There were 372 patients in the control group, including 227 males and 145 females, with a median age of 55 (48, 63) years, in which 105 (28.2%) with AF. Within 90 days of discharge, the difference of percentage of TTR between the amiodarone and control groups was not significant [57.6% (44.6%, 70.6%) vs. 67.3% (52.3%, 82.3%), P=0.061], but the stable daily dose of warfarin in patients in the amiodarone group was significantly lower than that in patients in the control group [2.25 (1.72, 2.78) mg vs. 3.38 (2.59, 4.18) mg, P<0.001]. The median proportion (range) of times of INR>3 in the 1-14 days, 15-90 days after discharge and the whole follow-up period in patients in the amiodarone group were higher than those in the control group[0 (0-0.3) vs. 0(0-0.3), P=0.016; 0.08(0-0.3) vs. 0(0-1.0), P=0.002; 0.06(0-0.85) vs. 0(0-0.22), P=0.001]. Conclusions:Amiodarone can significantly increase the risk of anticoagulation in patients treated with warfarin after heart valve surgery. The daily dose of warfarin needs to be reduced in order to achieve a higher TTR and maintain the stability of anticoagulation therapy.

Objective:To investigate reflectance confocal microscopic features of childhood scabies, and to analyze clinical significance of reflectance confocal microscopy (RCM) in the diagnosis and treatment of childhood scabies.Methods:A retrospective analysis was performed in 77 children with confirmed scabies at Department of Dermatology, Tianjin Children′s Hospital from April 2018 to October 2019. These patients were divided into negative treatment history group (61 cases) and positive treatment history group (16 cases) . All the patients underwent RCM and microscopic examination of skin scrapings.Results:Among the 77 children with scabies, positive microscopic examination results were found in 33 (42.86%) , including 28 in the negative treatment history group and 5 in the positive treatment history group. Burrows, sarcoptid mites or their eggs and fecal pellets were observed in 56 cases (72.73%) by RCM, including 49 (80.33%) in the negative treatment history group and 7 in the positive treatment history group. RCM showed a significantly increased overall positive rate compared with microscopy of skin scrapings ( χ2=14.08, P<0.05) . In the negative treatment history group, RCM also showed a significantly increased positive rate compared with microscopy of skin scrapings ( χ2=15.53, P < 0.05) . Conclusion:RCM is of high clinical value to the diagnosis and treatment of childhood scabies.

Objective:To explore the pathogenic variants of a family with syndromic deafness by high-throughput sequencing.Methods:The family was from Puyang City, Henan Province, and had four members, including two with syndromic deafness. The proband and his sister had congenital deafness, and their parents had normal phenotypes. The clinical phenotype of the family was characterized using clinical examinations and pedigree analysis. The clinical examinations included imaging examination, audiometry (pure tone audiometry, acoustic immittance, brainstem auditory evoked potential, and otoacoustic emission), vestibular function test, and ophthalmic examination (visual acuity test, visual field test, fundus examination, visual evoked potential, and electroretinogram). Target exome sequencing of 129 known deafness genes and bioinformatics analysis were used to screen suspected pathogenic variants. Sanger sequencing and minigene assay were used to verify and functionally investigate the mutation detected, respectively. According to the standards and guidelines for interpreting genetic variants proposed by the American College of Medical Genetics and Genomics, the variants c.6049G>A and c.8699A>G were classified as pathogenic/likely pathogenic, and the variant c.9856C>G was classified as variants of uncertain significance.Results:The probands and his sister had severe sensorineural hearing loss with decreased binocular vision, night blindness, decreased peripheral visual field sensitivity and partial visual field defect, and normal vestibular function. Both of them had three CDH23 mutations, including CDH23 (NM_022124.5) c.6049G>A (p.Gly2017Ser),c.9856C>G (p.His3286Asp), and c.8699A>G (p. Asp2900Gly), The first two were inherited from the father, and the last one was from the mother. The missense variants c.9856C>G and c.8699A>G were not included in the gnomad database. The missense mutation c.6049G>A was located in the last position of exon 46 and was predicted to affect splicing by bioinformatics software. The minigene experiment showed that the mutation cause exon skipping of exon 46, resulting in an abnormal protein. Conclusions:Compound heterozygous variations of the CDH23 are the leading cause of USH1D in the family. This study confirms that the compound heterozygosity of splicing and missense variants of the CDH23 gene could lead to USH1D.