Objective:To establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.

Objective:To establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.

Objective:To summarize the clinical and genetic characteristics of early-onset spinocerebellar ataxia type 5 (SCA5) caused by SPTBN2 gene mutation. Methods:The clinical and genetic data of a child with early-onset SCA5 diagnosed in the Department of Children′s Rehabilitation, Women and Children′s Hospital Affiliated to Qingdao University in February 2022 were retrospectively analyzed. The literatures related to early-onset SCA5 in major databases at home and abroad were retrieved and summarized.Results:The patient, a 4 years and 1 month old girl, was admitted to hospital because of "unable to stand independently at 2 years and 3 months", primarily presented with developmental delay, ataxia, hypotonia, and tendon hyperreflexia during infancy. Progressive cerebellar atrophy was observed on brain magnetic resonance imaging. A de novo heterozygous mutation of the SPTBN2 c.793G>C(p.Asp265His) was identified in the patient. Following hospitalization, the child received comprehensive rehabilitation therapy encompassing physical, occupational, language, educational interventions as well as bicycle ergometer training and transcranial magnetic stimulation. The patient was followed-up for more than 1 year to 4 years and 1 month old, whose motor function, cognitive abilities, and language skills were improved to some extent. A total of 13 English articles and 1 Chinese article were retrieved from the databases. A total of 20 early-onset SCA5 patients have been reported, with onset ages all within 12 months. Infants exhibited decreased muscle tone and delayed motor milestones, with the main clinical manifestations of ataxia, generalized developmental delay, and cerebellar atrophy. The previously reported cases involved 11 mutation sites in the SPTBN2 gene, and the main types of mutations were de novo missense mutations. The mutation site in this case has not been reported in the previous literature. Conclusions:Early-onset SCA5 is a rare autosomal dominant disorder caused by heterozygous mutations in the SPTBN2 gene. The main clinical manifestations include ataxia from infancy, developmental retardation and cerebellar atrophy. Early rehabilitation intervention can improve the degree of the dysfunction.

Objective:To explore the clinical characteristics of cardiotoxicity due to 5-hydroxytryptamine 3 receptor (5-HT 3) antagonists. Methods:Relevant databases at home and abroad (up to June 20, 2023) were searched and case literature of cardiotoxicity induced by 5-HT 3 receptor antagonist were collected. Relevant information of patients, medication status (drug name, usage and dosage, indication, combined drugs), occurrence of cardiotoxicity, evaluation of the association between 5-HT 3 receptor antagonists and cardiotoxicity, intervention measures and outcomes were extracted and analyzed descriptively and statistically. Results:A total of 23 case reports, 22 in English and 1 in Chinese, were enrolled in the analysis. There were 26 patients, 6 males and 20 females, and the age ranged from 8 to 60 years, with an average of 40 years. The reasons for drug use were perioperative antiemesis in 19 patients, chemotherapy antiemesis in 2 patients, and other reasons in 5 patients. Ondansetron was used in 19 patients, dolasetron in 4 patients, granisetron, tropisetron and palonosetron in 1 patient each. Except for 1 patient with overdose by self-medication, the dosage in 25 patients was within the recommended range in labels. A total of 50 case time of cardiotoxicity occurred in 26 patients, mainly including tachycardia (12 cases), electrocardiogram (ECC) changes (11 cases), bradycardia (9 cases), cardiac arrest (1 case), and myocardial infarction (1 case), etc. Twenty-one patients experienced cardiotoxicity after initial medication, of which 8 occurred immediately after the initial medication, 5 patients occurred after ≥2 times of medication. After the occurrence of cardiotoxicity, 26 patients stopped 5-HT 3 receptor antagonists successively, of which 24 stopped the drug immediately and received symptomatic treatments, 1 stopped the drug after 8 days of medication without other intervention, and 1 stopped the drug and received symptomatic treatment after the symptoms aggravated. After drug withdrawal and/or symptomatic treatments, the mentioned symptoms disappeared and ECC returned to normal in 25 patients. Of them, 22 patients had a recovery time of ≤48 hours, while the other 3 patients had their ECG returned to normal at 1 week, 2 weeks, and 2 months, respectively; one patient died due to ineffective treatment for ventricular fibrillation. Conclusions:The cardiotoxicity induced by 5-HT 3 receptor antagonists mostly occurs after the initial medication, and mainly manifests as tachycardia, bradycardia, ECG changes, etc. Most patients have a good prognosis after timely drug withdrawal and symptomatic treatments, and in severe cases, it can lead to death.

Objective:To explore the clinical characteristics of cardiotoxicity due to 5-hydroxytryptamine 3 receptor (5-HT 3) antagonists. Methods:Relevant databases at home and abroad (up to June 20, 2023) were searched and case literature of cardiotoxicity induced by 5-HT 3 receptor antagonist were collected. Relevant information of patients, medication status (drug name, usage and dosage, indication, combined drugs), occurrence of cardiotoxicity, evaluation of the association between 5-HT 3 receptor antagonists and cardiotoxicity, intervention measures and outcomes were extracted and analyzed descriptively and statistically. Results:A total of 23 case reports, 22 in English and 1 in Chinese, were enrolled in the analysis. There were 26 patients, 6 males and 20 females, and the age ranged from 8 to 60 years, with an average of 40 years. The reasons for drug use were perioperative antiemesis in 19 patients, chemotherapy antiemesis in 2 patients, and other reasons in 5 patients. Ondansetron was used in 19 patients, dolasetron in 4 patients, granisetron, tropisetron and palonosetron in 1 patient each. Except for 1 patient with overdose by self-medication, the dosage in 25 patients was within the recommended range in labels. A total of 50 case time of cardiotoxicity occurred in 26 patients, mainly including tachycardia (12 cases), electrocardiogram (ECC) changes (11 cases), bradycardia (9 cases), cardiac arrest (1 case), and myocardial infarction (1 case), etc. Twenty-one patients experienced cardiotoxicity after initial medication, of which 8 occurred immediately after the initial medication, 5 patients occurred after ≥2 times of medication. After the occurrence of cardiotoxicity, 26 patients stopped 5-HT 3 receptor antagonists successively, of which 24 stopped the drug immediately and received symptomatic treatments, 1 stopped the drug after 8 days of medication without other intervention, and 1 stopped the drug and received symptomatic treatment after the symptoms aggravated. After drug withdrawal and/or symptomatic treatments, the mentioned symptoms disappeared and ECC returned to normal in 25 patients. Of them, 22 patients had a recovery time of ≤48 hours, while the other 3 patients had their ECG returned to normal at 1 week, 2 weeks, and 2 months, respectively; one patient died due to ineffective treatment for ventricular fibrillation. Conclusions:The cardiotoxicity induced by 5-HT 3 receptor antagonists mostly occurs after the initial medication, and mainly manifests as tachycardia, bradycardia, ECG changes, etc. Most patients have a good prognosis after timely drug withdrawal and symptomatic treatments, and in severe cases, it can lead to death.

Objective:To investigate the molecular etiology of Perrault syndrome by analyzing the clinical phenotype and pathogenic gene variants of 2 male patients with bilateral severe sensorineural deafness.Methods:Two male patients with Perrault syndrome characterized by severe sensonrineual deafness adimitted to the First Affiliated Hospital of Zhengzhou University between February 2021 and March 2022 were selected, and the clinical phenotype and pathogenic gene variants of them and their family members were summarized. The whole exome sequencing technology was used to screen the pathogenic variants of the probands, and the candidate variants were determined by combining with clinical phenotype. The probands and their family members were verified by the Sanger sequencing method.Results:The whole exome sequencing results showed that the proband of family 1 had a compound heterozygous variants of the LARS2 (NM_015340.4) gene c.1565C>A (p.Thr522Asn) and c.1079T>C (p.Ile360Thr). The reported pathogenic variant c.1565C>A came from the mother, and the novel variant c.1079T>C came from the father. The second proband harbored compound heterozygous variants of HARS2 gene (NM_012208.4) c.1273C>T (p.Arg425Trp) and c.1403G>C (p.Gly468Ala), with the former from the proband′s mother, the latter from the father. The c.1273C>T was novel and c.1403G>C was the reported pathogenic variant. All above variants were respectively classified as pathogenic, uncertain significance, uncertain significance and likely pathogenic based on the ACMG guidelines. Conclusion:This study expands the mutational spectrum of LARS2 and HARS2 genes, which highlights that genetic testing plays an important role in the early diagnosis of syndromic deafness.

Objective:To screen the causative genes of five families with branchio-oto-renal syndrome (BORS) or branchio-oto syndrome(BOS) and to analyze the phenotypic characteristics and clinical management strategies of patients.Methods:Five families with BORS/BOR from December 2018 to September 2021 were recruited, information of patients, including family history and medical history, was collected, and genealogies were drawn. The examinations concerning audiology, nephrology, and radiology were performed on the affected individuals. Peripheral blood was obtained for DNA extraction, then next-generation sequencing technology was used to screen candidate variants associated with BORS/BOS. Based on patient′s clinical results, the appropriate interventions were recommended and implemented.Results:Eight individuals were diagnosed with BOS or BORS. Of the eight patients, all had hearing loss, preauricular pits and ear malformations, and only four presented with branchial cleft fistulae or cysts. Except for two patients(5-I-2, 5-II-2) who did not undergo renal examination, the remaining six lacked renal abnormalities. Genetic analysis identified four likely pathogenic or pathogenic EYA1 variants (c.1715G>T, c.1140+1G>A, c.639G>C, c.1475+1G>C; NM_000503.6), and c.1715G>T was first reported in this study. Middle ear ossicular reconstruction was performed in 1-II-2,2-I-2 and 3-II-2, but did not yield the expected results; then hearing aids and cochlear implantation were recommended and achieved satisfactory results. Conclusions:Next-generation sequencing technology facilitates the diagnosis and genetic counseling of BORS/BOS. Hearing loss, preauricular pits, ear malformations and branchial cleft fistulae or cysts are the most common manifestations of patients in this study. Middle ear surgeries for improving hearing loss may have some limitations in BORS/BOS patients, and hearing aids and cochlear implantation can contribute to hearing gains.

Objective To analyze the correlation between intestinal flora changes and neonatal necrotizing enterocolitis (NEC)through 16S rRNA metagenomic sequencing and bacterial culture. Methods From September 2018 to March 2019, 10 NEC cases and 6 controls were randomly selected in the neonatal ICU ward of Nanjing maternal and child health care hospital to analyze the 16S rRNA metagenomic diversity of the for intestinal flora. The fecal samples and corresponding environmental samples were corrected from 51 cases of NEC children and their case controls to isolate and culture Clostridium. Results The dispersion of samples within the case group was smaller than that of the control group, and the sample diversity was higher than that of the control group. In the isolation and culture of Clostridium, the overall detection rate of Clostridium in the case group was 43.14% (22/51), and the detection rate of Clostridium butyricum was the highest (19.61%, 10/51). There was a statistical difference between the two groups (χ²=5.85, P=0.015 58). All Clostridium strains did not carry the A, B and E type neurotoxin genes. Conclusion: Increased intestinal flora diversity, intestinal flora abundance and changes in the abundance of Clostridium may be closely related to the intestinal environment of children with NEC; Clostridium, especially Clostridium butyricum, may be related to the occurrence of NEC.

OBJECTIVETo explore the impact of electroacupuncture (EA) on the protein expression of adenosine receptors in the heart of the rats with myocardial ischemia (MI).

METHODSThirty healthy male SD rats were divided randomly into a control group (=6), a model group (=12) and an EA group (=12). We ligated the left anterior descending artery (LAD) for MI model in the model group and EA group, and exposed the heart after opening the chest without ligation in the control group. EA, 2 Hz /15 Hz and 1.5-2 mA, was applied at bilateral"Neiguan"(PC 6) in the EA group for 20 min, once a day for continuous 5 days. No intervention except grabbing and fixation was used in the control group and model group. We applied 2% TTC staining to observe the infarct size of myocardium, colorimetry to analyze serum lactic dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CK-MB), radio-immunity assessment to detect cardiac troponin T (cTnT), Western blot to evaluate the adenosine A1 receptor (A1AR), A2aAR, A2bAR and A3AR.

RESULTSAfter treatment, myocardial infarction of (27.56±3.24)% was obvious in the model group; the myocardial infarction in the EA group was (21.04±3.61)%, with statistical significance (<0.05). The expressions of serum LDH, CK, CK-MB and cTnT levels in the model group increased compared with those in the control group (all<0.01), and the expressions of LDH, CK, CK-MB and cTnT levels in the EA group decreased compared with those in the model group (<0.05，<0.01). The A1AR expression in the model group was not different from that in the control group (>0.05), and A2aAR、A2bAR、A3AR expressions decreased (<0.05,<0.01). A2aAR and A2bAR expressions in the EA group increased compared with those in the model group (both<0.01), and there was no statistical significance between A1AR and A3AR expressions (both>0.05). .

CONCLUSIONEA may achieve cardioprotective effect by regulating the expressions of A2aAR and A2bAR in myocardial tissue, which induce the corresponding signal cascade for reducing myocardial infarction area.

Objective To investigate the characters of cortical thickness and mean curvature for the patients with the first episode schizophrenia and explore the relationship with clinical symptoms.Method Eighty-six patients with first episode schizophrenia and 49 healthy controls were recruited.The structure data of T1 image was processed using FreeSurfer automatic package and obtained cortical thickness and mean curvature.These brain morphological indicators were compared between patients and healthy controls.For the patient group,Pearson correlation between cortical thickness,mean curvature and clinical symptoms was calculated.Results Compared with controls,the cortical thickness of bilateral central sulcus (left:(1.897±0.102) mm vs.(1.814±0.108) mm;right:(1.871 ±0.119) mm vs.(1.784±0.108) mm) was thicker in patient group (F=24.24,18.59;both P＜0.00 067);while the bilateral superior segment of the circular sulcus of the insula (left:(2.495±0.122) mm vs.(2.591±0.138) mm;right:(2.602±0.133) mm vs.(2.710±0.131) mm) and left anterior transverse collateral sulcus ((2.599±0.250) mm vs.(2.782±0.238) mm) were thinner in patient group (F=16.75,22.61,18.86,both P＜0.00 067).Patients with schizophrenia showed significant (F=14.52,13.08,both P＜0.000 67) higher mean curvature than healthy control only in post central gyrus ((0.166±0.026) mm-1 vs.(0.150±0.011) mm-1) and inferior temporal gyrus ((0.186±0.016) mm-1 vs.(0.177±0.011) mm-1) of the left brain;while in the right brain,patient group showed significant (F=14.20,14.42,12.75,15.02,14.80,12.16,13.74,16.70,12.77,all P＜0.000 67)higher mean curvature than healthy control in the middle frontal gyrus,frontal polar transverse gyrus and sulcus,lateral orbital sulcus,anterior cingulate cortex,the middle of the occipital-temporal sulcus and lingual sulcus,superior segment of the circular sulcus of the insula,cuneus,precuneus and superior occipital gyrus.The cortical thickness of left anterior transverse collateral sulcus showed positive correlation with PANSS total score (r=0.322,P＜0.01).The mean curvature of right anterior cingulate cortex showed negative correlation with PANSS negative scale (r=-0.262,P＜0.05).The mean curvature of right superior segment of the circular sulcus of the insula had a positive correlation with PANSS positive scale (r=0.240,P＜0.05).Tbe mean curvature of right collateral sulcus and lingual sulcus showed negative correlation with PANSS total score (r=-0.260,P＜0.05).Conclusions Cortical thickness and mean curvature displayed abnormally in multi regions of the first episode schizophrenia compared with healthy control.Besides that,some of the abnormal brain morphological indicators correlated with the clinical symptoms severity.