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 types and distribution of pathogenic variants for neonatal genetic diseases in Huzhou, Zhejiang Province.Methods:One thousand neonates (48 ~ 42 h after birth) born to Huzhou region were selected as the study subjects. Dry blood spot samples were collected from the newborns, and targeted capture high-throughput sequencing was carried out for pathogenic genes underlying 542 inherited diseases. Candidate variants were verified by Sanger sequencing.Results:Among the 1 000 newborns, the male to female ratio was 1.02 : 1.00. No pathogenic variants were detected in 253 cases, whilst 747 cases were found to carry at least one pathogenic variant, which yielded a carrier rate of 74.7%. The most frequently involved pathogenic gene was FLG, followed by GJB2, UGT1A1, USH2A and DUOX2. The variants were classified as homozygous, compound heterozygous, and hemizygous variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), 213 neonates were verified to have carried pathogenic and/or likely pathogenic variants, with a positive rate of 21.3%. The most commonly involved genes had included UGT1A1, FLG, GJB2, MEFV and G6PD. Conclusion:Newborn screening based on high-throughput sequencing technology can expand the scope of screening and improve the positive predictive value. Genetic counseling based on the results can improve the patients′ medical care and reduce neonatal mortality and childhood morbidity, while provide assistance to family members′ health management and reproductive decisions.

Objective:To investigate the clinical efficacy of neuroendoscopic hematoma removal versus soft channel drainage in the treatment of chronic subdural hematoma. Methods:The clinical data of 102 patients with chronic subdural hematoma who received treatment in Jincheng People's Hospital from May 2018 to May 2020 were retrospectively analyzed. They were divided into the neuroendoscopy group ( n = 50) and the soft channel group ( n = 52) according to different surgical methods. Perioperative indexes, hematoma clearance rate, China Stroke Scale score, the activity of daily living score, and oxidative stress indexes were compared between the two groups. All patients were followed up for 3 months. The incidence of complications during the follow-up period was calculated. Results:The retention time of the drainage tube in the neuroendoscopy group was shorter than that in the soft channel group [(2.45 ± 0.63) days vs. (3.30 ± 0.78) days, t = 6.06, P < 0.001]. The length of hospital stay in the neuroendoscopy group was shorter than that in the soft channel group [(7.14 ± 1.65) days vs. (9.07 ± 2.11) days, t = 5.15, P < 0.001]. The hematoma clearance rate at postoperative 7 days in the neuroendoscopy group was higher than that in the soft channel group [(93.45 ± 5.50)% vs. (81.86 ± 7.24)%, χ2 = 9.12, P < 0.001]. There were no significant differences in operation time and intraoperative blood loss between the two groups (both P > 0.05). At postoperative 30 days, the China Stroke Scale score in the neuroendoscopy group was lower than that in the soft channel group [(12.74 ± 2.23) points vs. (18.67 ± 2.45) points, t = 12.79, P < 0.001]. The activity of daily life score in the neuroendoscopy group was significantly higher than that in the soft channel group [(77.69 ± 7.11) points vs. (91.35 ± 7.25) points, t = 9.60, P < 0.001]. At postoperative 7 days, glutathione peroxidase level in the neuroendoscopy group was significantly lower than that in the soft channel group [(130.75 ± 13.66) U/L vs. (148.60 ± 14.64) U/L, t = 6.37, P < 0.001]. Malondialdehyde level in the neuroendoscopy group was significantly lower than that in the soft channel group [(5.11 ± 0.65) nmol/L vs. (6.19 ± 0.74) nmol/L, t = 7.83, P < 0.001]. Superoxide dismutase level in the neuroendoscopy group was significantly higher than that in the soft channel group [(275.60 ± 22.33) U/L vs. (254.60 ± 18.55) U/L, t = 5.15, P < 0.001]. There was no significant difference in the incidence of complications between the two groups ( P > 0.05). Conclusion:Compared with soft channel drainage, neuroendoscopic hematoma removal can obtain better short-term curative effects and less oxidative stress response in the treatment of chronic subdural hematoma. Neuroendoscopic hematoma removal does not increase the incidence of postoperative complications and is highly safe.

Medical homogenization in multi-campus hospital plays an essential role in leveraging the advantages of public hospitals, promoting the expansion of high-quality medical resources and balancing regional layout. The Second Affiliated Hospital Zhejiang University School of Medicine deeply used digital intelligence technology to build a new integrated mobile health service system consisting of internet hospital and 5G intelligent applications, which empowered medical efficiency in multi-campus hospital. This system broke the limitations of inconsistent medical resources, unbalanced discipline layout, and insufficient information connectivity in the construction of multi-campus hospitals, and achieved remarkable results in practice. It could provide reference for the multi-campus construction of other large public hospitals.

OBJECTIVE: To detect pathogenic variant in a child featuring Usher syndrome type II. METHODS: Peripheral blood samples of the child and his parents were collected for the analysis of variants of hearing impairment-related genes. The findings were verified in 100 individuals with normal hearing. RESULTS: The child was found to harbor compound heterozygous variants of the USH2A gene, namely c.8224-1G>C in intron 41 and c.5678C>G(p.Ser1893X) in exon 28, which were inherited respectively from his mother and father. Based on the American College of Medical Genetics and Genomics standards and guidelines, both c.8224-1G>C and c.5678C>G(p.Ser1893X) variants of USH2A gene were predicted to be pathogenic(PVS1+PM2+PM3). CONCLUSION The compound heterozygous variants c.8224-1G>C and c.5678C>G of the USH2A gene probably underlay the disease in this child. Above finding has enriched the spectrum of USH2A gene variants.
Child ; Exons ; Extracellular Matrix Proteins/genetics* ; Family ; Humans ; Introns ; United States ; Usher Syndromes/genetics*

OBJECTIVE: To provide genetic testing and prenatal diagnosis for a woman with Sheldon-Hall syndrome. METHODS: The woman was subjected to targeted capture and next-generation sequencing for variant of genes associated with skeletal disorders. And the result was verified in her parents and fetus. RESULTS: The woman was found to harbor a c.188G>A variant of the TNNT3 gene, which was also found in her affected mother and the fetus. Her grandmother and grandmother's brother had similar manifestations, which was in line with an autosomal dominant inheritance. The same variant was not found in her father. CONCLUSION The c.188G>A variant of the TNNT3 gene probably underlay the distal joint contracture in this pedigree, based on which prenatal diagnosis was attained.

Objective To investigate the candidate profile and pass rate of the 2016 pilot qualification examination for registered dietitians in Shanghai,and attempt to inform the improvement of the examination.Methods An analysis was conducted on the profiles of all the 193 qualified candidates in the signing-up system of the 2016 pilot examination.Questionnaire surveys were carried out to collect feedback from the candidates on the enrollment requirements of the examination.The pass rates were compared between subgroups divided by age,gender,education,major,workplace (as employee or intern),working years and academic rank.Results 81.3％ of the candidates were aged between 20 and 29.Females accounted for 80.3％.The candidates had all received bachelor's degree,75.6％ from full-time undergraduate programs and 96.4％ from programs of nutrition.78.3％ of the candidates rated the enrollment requirements of the examination as "reasonable" or "relatively reasonable".The overall pass rate of the examination was 38.3％.The pass rate of the examinees working or doing internship in hospitals (45％) was significantly higher than that of others (24.5％) (P=0.012).Conclusions The overall pass rate is reasonable.Examinees working or doing internship in hospitals had a higher pass rate than those working in other places.The majority of the candidates had bachelor's degree of nutrition,which is in accordance with the requirement of similar exams in other parts of the world.

A rapid and sensitive method of loop-mediated isothermal amplification(LAMP) was established to detect Pseudomonas aeruginosa(P.aeruginosa).Three pairs of LAMP primers(inner,outer and ring primers) were designed according to the gbca gene of P.aeruginosa.Since adding hydroxy naphthol blue(HNB) to the reaction system, a positive reaction was indicated by a colorchange before and after the reaction,and was verified by agarose gellectrophoresis.Both LAMP and PCR were applied to detect clinical specimens, the sensitivity and specificity of the detection method were evaluated,and were compared with those of conventional PCR.A LAMP method for detecting P.aeruginosa was successfully established.The LAMP method showed specificity for P.aeruginosa without other bacteria amplification.The established LAMP method in this study enables rapid,sensitive and specific detection of P.aeruginosa,and can be applied for grass roots and small scale laboratories as well as field surveillance.

OBJECTIVETo investigate the value of C-reactive protein (CRP) on transplantation day in predicting early post-transplant infections and outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSWe retrospectively analyzed the clinical data of 78 recipients undergoing allo-HSCT. The clinical reference value of CRP on transplantation day was determined, and its sensitivity and specificity for diagnosing bacteremia was analyzed using receiver-operating characteristic curve (ROC). The incidence of transplant-related complications, overall survival, and relapse rate of the patients were analyzed with respect to the CRP level.

RESULTSThe clinical reference value of CRP for diagnosing bacteremia was 23.3 mg/L (AUC=0.735 [95% CI: 0.623-0.848], P=0.001), which had a diagnostic sensitivity and specificity of 0.793 and 0.592, respectively. Compared with the patients with low CRP levels, the patients with high CRP levels tended to have delayed neutrophil reconstitution and platelet engraftment by 0.71 days (P=0.237) and 4.09 days (P=0.048), respectively, and had a significantly higher incidence of bacteremia (17.1% vs 53.5%, P=0.001) and CMV viremia (37.1% vs 72.1%, P=0.003) within 100 days following the transplantation; the incidences of EBV viremia, pulmonary invasive fungal infection, or acute graft versus host disease (aGVHD) showed no significant difference between the two groups (41.9% vs 22.9%, P=0.094; 14.0% vs 5.7%, P=0.285; 51.2% vs 45.7, P=0.656, respectively). During the follow-up for a median of 318 (7-773) days in high-CRP group and for 299 (78-747) days in low-CRP group, the high-CRP group showed a significantly lower 2-year overall survival than the low-CRP group (42.5% vs 78.4%, P=0.022), and tended to have a higher 2-year cumulative relapse rate (52.3% vs 19.8%, P=0.235). Logistic multivariate analysis identified a high CRP level on transplantation day as the independent risk factor for post-transplant bacteremia within 100 days (OR=5.090 [95% CI: 1.115 -23.229], P=0.036).

CONCLUSIONA high CRP level on transplantation day can be indicative of a high risk of early post-transplant bacteremia and CMV viremia and also a poor prognosis following allo-HSCT.

Bacteremia ; diagnosis ; C-Reactive Protein ; chemistry ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Mycoses ; Prognosis ; Recurrence ; Retrospective Studies ; Risk Factors ; Sensitivity and Specificity ; Viremia ; diagnosis