Objective:To investigate the clinical value of targeted sequencing panel in the detection of genetic variation in neonates in neonatal intensive care unit (NICU).Methods:All neonates (≤28 d of age) admitted in the NICU (case group) and 200 full-term healthy neonates born with no obvious phenotypic abnormalities of Huzhou Maternity and Child Health Care Hospital were enrolled in this prospective study from November 2022 to January 2023. Based on a list of preventable and treatable rare diseases as well as newly screened diseases in China, a targeted sequencing panel suitable for Chinese newborns was designed to target the pathogenic genes and mutation sites associated with 601 genes and 542 diseases. Dried blood spot specimens were prepared and analyzed by the targeted sequencing panel. Pathogenic sites detected by the panel sequencing were verified using Sanger sequencing. The genetic testing results were analyzed according to the clinical features of the neonates. According to the number of primary clinical diagnosis index (including premature infants, neonatal hyperbilirubinemia, hemorrhagic diseases, neonatal infections, ventricular septal defect/patent ductus arteriosus, and others), these patients were divided into four groups with 1, 2, 3, and ≥4 diagnosis index, respectively. Chi-square test and linear correlation Chi-square test were used for statistical analysis. Results:There were 173 patients in the case group and 30.6% (53/173) of them carried pathogenic variants, including 52 positive for pathogenic genes and one with chromosome copy number variant. The positive rate of pathogenic genes was significantly higher in the case group than in the control group [30.1% (52/173) vs. 15.0% (30/200), χ 2=12.26, P<0.001]. Fourteen pathogenic genes were detected in the case group, including FLG, UGT1A1, G6PD, MYH7, AR, ABCC2, ACADS, CYP21A2, GJB2, MEFV, PAH, PKHD1, SCN4A, and HBA. In the case group, the detection rate of pathogenic variants in jaundiced neonates was higher than that in non-jaundiced neonates [35.2% (44/125) vs. 18.8% (9/48), χ 2=4.42, P=0.036]. However, there were no statistically significant differences in the detection rates of pathogenic variants between male and female infants, infants born to mothers of advanced maternal age or not, infants born to mothers with or without gestational diabetes mellitus, premature and term infants, or infants with or without hemorrhagic disorders, neonatal infections, or ventricular septal defects/patent ductus arteriosus in the case group (all P>0.05). The detection rate of pathogenic variants showed a linear increase in infants with 1, 2, 3, and ≥4 diagnosis index [21.1% (8/38), 25.4% (15/59), 38.2% (13/34), and 40.5% (17/42); linear correlation χ 2=4.84, P=0.028]. In the case group, seven genes with a high detection rate of genetic variation (including positive pathogenic genes and carriers) were UGT1A1 [had the highest detection rate, 24.9% (43/173)], GJB2, FLG, DUOX2, ABCA4, G6PD, and MUT. Seven loci with higher mutation frequency were c.211G>A(p.Gly71Arg), c.1091C>T(p.Pro364Leu), c.-41_-40dupTA, and c.686C>A(p.Pro229Gln) in the UGT1A1 gene, c.109G>A(p.Val37Ile) in the GJB2 gene, and c.12064A>T(p.Lys4022Ter) and c.3321del(p.Gly1109GlufsTer13) in the FLG gene. Conclusion:This panel sequencing can provide effective genetic testing for neonates in NICU, especially in children with complex clinical diagnosis.

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) to verify a fetus with partial 18p deletion signaled by non-invasive prenatal testing. METHODS: G-banding chromosomal karyotyping analysis was carried out on amniotic fluid sample of the fetus and peripheral blood samples from the parents. Amniotic DNA was also subjected to CMA analysis. The fetus was also subjected to systematic ultrasound scan. RESULTS: The fetus was found to have a karyotype of 46,XX,18p+. CMA has revealed a 5 Mb deletion at 18p11.32-p11.31, a 2.9 Mb duplication at 18p11.31-p11.23, and a 2.5 Mb duplication at 18p11.23-p11.22. No chromosomal aberration or microdeletion/microduplication was detected in either parent. CONCLUSION Non-invasive prenatal testing and CMA are both sensitive for the detection of chromosomal microdeletions and microduplications. CMA can help with clarification of genotype-phenotype correlation and facilitate prenatal diagnosis and genetic counseling for the family.
Chromosome Deletion ; Chromosomes ; Female ; Fetus ; Humans ; Karyotyping ; Pregnancy ; Prenatal Diagnosis

AIM: To study chronopharmacokinetics of helicid and its metabolites. METHODS: An HPLC-MS method for simultaneous determination of helicid and its three phase I metabolites were established and validated. At 8:00, 14:00 and 0:00, the rats were given helicid 50 mg/kg by gavage, respectively. Blood samples were collected from ophthalmic venous plexus. Then plasma concentration was measured. Pharmacokinetic behaviors of the original drug and its metabolites after administration at different time points were calculated and compared. RESULTS: This established HPLC-MS/MS method was successfully applied to simultaneous determination of helicid and its three metabolites in rat plasma after intragastric administration. Using AUC

In the COVID-19 epidemic prevention and control work, not only the safety management of in-hospital organ transplantation is facing severe challenges, but also a large number of patients at home after transplantation are in immunosuppressive state, and professional protection management is urgently needed. Since the outbreak of the epidemic, Shulan(Hangzhou)hospital fully identified the risks of transplant patients, established a special team, and formulated and implemented the control management plan for organ transplant patients based on the crisis leadership model. The control management plan has achieved staged results.From January 15 to March 2, 2020, 29 liver transplants and 31 kidney transplants were performed in our hospital. The remote health education of 1 002 patients after liver and kidney transplantation was completed. The goal of " zero infection" was achieved, and the protection management quality indicators were ideal.

In order to conduct surface monitoring of the three-dimensional spine morphology of the human body in daily life, a spine morphology measuring method using "single camera, multi-view" to construct stereo vision is proposed. The images of the back of the human body with landmarks of spinous process are captured from multiple angles by moving a single camera, and based on the "Zhang Zhengyou calibration method" and the triangulation principle of binocular stereo vision, the spatial conversion matrices corresponding to each other between all images and the 3D coordinates of the landmarks are calculated. Then the spine evaluation angle used to evaluate the spine morphology is further calculated. The tests' results showed that the spine evaluation angle error of this method is within ±3°, and the correlation between the results and the X-ray film Cobb angles is 0.871. The visual detection algorithm used in this paper is non-radioactive, and because only one camera is used in the measurement process and there is no need to pre-set the camera's shooting pose, the operation is simple. The research results of this article can be used in a mobile phone-based intelligent detection system, which will be suitable for the group survey of scoliosis in communities, schools, families and other occasions, as well as for the long-term follow-up of confirmed patients. This will provide a reference for doctors to diagnose the condition, predict the development trend of the condition, and formulate treatment plans.
Algorithms ; Calibration ; Humans ; Imaging, Three-Dimensional ; Scoliosis/diagnostic imaging* ; Spine/diagnostic imaging* ; Technology

Objective To study curative efficacy of aluminum phosphate gel combined with omeprazole in treatment of peptic ulcer and its effects on Gas, TGF-αlevels.Methods 80 patients of peptic ulcer who received therapy from April 2015 to April 2016 in our hospital were selected as research objects.According to random number table, those patients were divided into the observation group and the control group, 49 patients in each group.the control group was treated with omeprazole, while the observation group was treated with aluminum phosphate gel combined on the basis of control group.Then Transforming growth factor, adverse reaction and curative effect were compared.Results After treatment, the serum levels of Gas and TGF-αin both groups were improved (P<0.05); Two weeks after treatment,the level of GAS in the observation group were lower than those in the control group(P<0.05), TGF-αlevel was higher than that in control group(P<0.05); The total incidence of adverse reactions in the observation group was lower than that in the control group(P<0.05); The total effective rate in the observation group was higher than that in the control group(P<0.05). Conclusion Combined use of aluminum phosphate gel and omeprazole in the treatment of peptic ulcer can effectively improve the patient-related serum markers, improve the quality of ulcer healing, significant efficacy, high safety and low incidence of adverse reactions.

Objective To investigate the correlation of plasma brain natriuretic peptide (BNP) level with serum albumin, serum total bilirubin and thrombin time in patients with liver cirrhosis.Methods RandomLy selected from January 2014 to June 2016 to our hospital diagnosis and hospitalization of 200 cases of cirrhosis patients, according to the standard of Child-Pugh classification provided by Chinese Medical Hepatology Division in 2006, 48 cases were Child A group, 96 cases were Child B group and 56 cases were Child C group.The plasma BNP, serum albumin, serum total bilirubin, prothrombin time and QTc interval of electrocardiogram were analyzed in the clinical data of each group of patients and the correlation between plasma BNP and their correlation.Results The levels of plasma BNP in Child A, B and C groups were higher than those in B group and B group.The correlation between plasma BNP and Child's grade showed a positive correlation, and the results of each group were statistically different (P<0.05).The plasma BNP level was negatively correlated with ALB ( P<0.05 ) .The level of plasma BNP was positively correlated with ALB ( P <0.05 ) .The correlation between plasma BNP and PTIL was correlated with TBIL.The correlation between plasma BNP and TBIL was significantly correlated with TBIL ( P <0.05), The higher the plasma BNP, the regression analysis showed that plasma BNP and TBIL were positively correlated, the difference was statistically significant (P<0.05).The correlation between plasma BNP level and QTc was analyzed.The QTc interval of plasma BNP level was higher than that of the control group ( P<0.01 ) , and the difference was statistically significant ( P <0.01 ) .Conclusion The plasma BNP level in patients with liver function is closely related to ALB, TBIL, PT, QTc interval, and has the value of evaluating and predicting liver function.

OBJECTIVE: To study the mechanism of tumor necrosis factor( TNF)-α and its receptor( TNFR) signal transduction pathways in regulating cell apoptosis of alveolar macrophage( AM) in coal workers' pneumoconiosis( CWP).METHODS: Twenty-four coal workers with pneumoconiosis at stage Ⅰ were selected as CWP group and four observation subjects exposed to coal were chosen as observation group by using simple random sampling method. The bronchoalveolar lavage fluids of whole-lung lavage of two groups were collected. AMs were separated and purified. Then they were divided into 6 groups: a control group,a superoxide dismutase( SOD) group,a TNF/TNFR group,an anti-TNF-α antibody group,a Caspase-8 suppression group and a nuclear factor-κB( NF-κB) suppression group. The AMs of 6 groups with corresponding treatment were cultivated. After 24 hours,the cells were harvested and proteins extracted. The relative expression of TNF-α,TNFR1,TNFR2,Caspase-8,Caspase-3,NF-κB P50 and NF-κB P65 protein was detected by Western blotting. RESULTS: The protein relative expression of TNF-α,TNFR2,Caspase-8,Caspase-3,NF-κB P50 and NF-κB P65 in CWP group was significantly higher than those in the observation group( P < 0. 05). The protein relative expression of TNF-α,TNFR1,Caspase-8,Caspase-3 and NF-κB P50 in the TNF/TNFR group and the anti-TNF-αantibody group was lower than that of the control group( P < 0. 05). The above indexes in the anti-TNF-α antibody group were lower than that of the NF-κB suppression group( P < 0. 05). The protein relative expression of TNFR1,Caspase-8and Caspase-3 in the TNF/TNFR group was higher than that of the SOD group and the Caspase-8 suppression group( P <0. 05). The protein relative expression of TNFR1,Caspase-8 and NF-κB P50 in the TNF/TNFR group was lower than that of the NF-κB suppression group( P < 0. 05). Among the CWP patients,the relative expression of TNFR2 and NF-κB P65 in the TNF/TNFR group was lower than that of the control group( P < 0. 05),and higher than that of the SOD group( P <0. 05). CONCLUSION: AM apoptosis mediated by TNF-α/TNFR/NF-κB signal transduction pathway plays an important role in the occurrence and development of CWP. The TNF-α/TNFR/NF-κB signal transduction pathways inhibited or blocked at different stages can affect the expression of proteins related to AM apoptosis.

Objective To evaluate the curative effect of laparoscopic myomectomy combined with preoperative gonadotropin releasing hormone agonists (GnRH-a) in treating myoma patients with uterus volume large than 12 weeks of pregnancy size. Methods 46 patients with uterine volume over 12 gestational weeks from August 2009 to August 2016 were selected as research objects. Leuprolide was injected subcutaneously for three to six times, and then laparoscopic myomectomy was performed one month later. The changes of volumes in uterus and myoma before and after medication were observed as well as the changes of hemoglobin. And postoperative recurrence of uterus myoma was followed up. Results The average volume of the uterus in the 46 patients, detected by B ultrasound, before GnRH-a treatment was (705.47 ± 282.37) cm3, and the average volume of the uterus after GnRH-a treatment was (331.95 ± 84.53) cm3, which was shortened by 59.35%, with significant difference (P < 0.05). The volume of uterus myoma was (237.59 ± 138.46) cm3 before GnRH-a treatment and (81.59 ± 46.44) cm3 after GnRH-a treatment, shortened by 65.66%, with significant difference (P < 0.05). The hemoglobin value was (97.80 ± 20.19) g/L before GnRH-a and (119.63 ± 12.06) g/L after GnRH-a treatment, with significant difference (P < 0.05). Follow-up for 3 weeks to 5 years, the surgeries were accomplished successfully, and no case was transferred to laparotomy. Conclusion Preoperative GnRH-a could shorten volume of uterus myoma, increase hemoglobin value and ensure performance of laparoscopic myomectomy for myoma patients with uterus volume large than 12 weeks of pregnancy size.