OBJECTIVES: To evaluate the clinical value of next-generation sequencing (NGS) in neonatal disease screening, particularly its advantages when combined with tandem mass spectrometry (MS/MS). METHODS: A prospective study was conducted involving blood samples from 1 999 neonates born at the Shenzhen Guangming District People's Hospital, between May and August 2021. All samples were initially screened using MS/MS and fluorescence immunoassay, followed by NGS to detect high-frequency variation sites in 135 related pathogenic genes. Suspected positive variants were validated using Sanger sequencing or multiplex ligation-dependent probe amplification in family studies. RESULTS: No confirmed positive cases were found in the MS/MS analysis of the 1 999 neonates. Genetic screening identified 58 positive cases (2.90%), 732 carriers of pathogenic genes (36.62%), and 1 209 negative cases (60.48%). One case of neonatal intrahepatic cholestasis was diagnosed (0.05%, 1/1 999). Fluorescence immunoassay identified 39 cases of glucose-6-phosphate dehydrogenase (G6PD) deficiency (1.95%, 39/1 999), while genetic screening identified 43 cases of G6PD deficiency (2.15%, 43/1 999). The fluorescence immunoassay also detected 6 cases of hyperthyrotropinemia (0.30%, 6/1 999), all of whom carried DUOX2 gene variants. The top ten pathogenic gene carrier rates were G6PD (12.8%), DUOX2 (8.7%), HBB (8.2%), ATP7B (6.6%), GJB2 (5.7%), SLC26A4 (5.6%), PAH (5.6%), ACADSB (4.6%), SLC25A13 (4.2%), and SLC22A5 (4.1%). CONCLUSIONS NGS can serve as an effective complement to MS/MS, significantly improving the detection rate of inherited metabolic disorders in neonates. When combined with family validation, it enables precise diagnosis, particularly demonstrating complementary advantages in screening for monogenic diseases such as G6PD deficiency.
Humans ; Infant, Newborn ; High-Throughput Nucleotide Sequencing/methods* ; Neonatal Screening/methods* ; Tandem Mass Spectrometry ; Prospective Studies ; Female ; Male ; Infant, Newborn, Diseases/diagnosis* ; Genetic Testing

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

Objective:To investigate the relationship between ultrasonic shear wave elastic imaging, blood flow quantitative parameters and expression levels of GATA binding protein 3 (GATA3) and CD34 in breast cancer tissues.Methods:Ultrasound shear wave elastic imaging and blood flow parameter examination were performed with Resona R9 full-digital high-end color Doppler ultrasound diagnostic instrument of Shenzhen Mindray Biomedical Electronics Co., LTD., and maximum elasticity values (Emax), mean elasticity (Emean), minimum elasticity (Emin), pulsatility index (PI), and resistance index (RI) were recorded. The expression levels of GATA3 and CD34 in breast cancer tissues and adjacent tissues were detected by immunohistochemistry.Results:Compared with adjacent normal tissues, the proportion of low expression of GATA3 in breast cancer tissues was significantly increased, the difference was statistically significant ( χ2=9.673, P=0.002), and the proportion of high expression of CD34 was significantly increased, the difference was statistically significant ( χ2=37.104, P<0.001). The Emax, Emin, PI and RI in breast cancer patients with high GATA3 expression were significantly lower than those with low GATA3 expression, and the difference was statistically significant ( t was 4.136, 4.005, 5.387 and 4.103, respectively, P<0.05). The Emax, Emean, Emin, PI and RI of breast cancer patients with high expression of CD34 were significantly higher than those with low expression, with statistical significance ( t was 4.553, 4.037, 5.491, 3.894 and 5.273, respectively, P<0.05). Multivariate binary Logistic regression analysis showed that Emax, PI and RI were independent risk factors for low expression of GATA3 in breast cancer tissues, and the difference was statistically significant ( P<0.05). Emax, Emean, PI and RI were independent risk factors for high expression of CD34 in breast cancer tissues. The difference was statistically significant ( P<0.05). The sensitivity and specificity of ultrasound shear wave elastography combined with blood flow quantitative parameters were 78.7% and 81.7% for evaluating the low expression of GATA3 in breast cancer tissue, and 81.5% and 76.6% for evaluating the high expression of CD34 in breast cancer tissue, respectively. Conclusion:Ultrasonic shear wave elastic imaging and blood flow quantitative parameters are related to the expression levels of GATA3 and CD34 in breast cancer tissue, and have certain evaluation value.

Objective:To analyze the iodine nutrition status of children aged 8 to 10 years in Zhejiang Province from 2016 to 2021.Methods:A multi-stage stratified sampling method was used to select non-residential children aged 8 to 10 years from 90 counties in Zhejiang Province. A total of 114 103 children were included in the study from 2016 to 2021. Direct titration method and arsenic-cerium catalytic spectrophotometry were used to detect salt iodine content and urinary iodine level, respectively, to evaluate the iodine nutritional status of children. Ultrasound was used to detect thyroid volume and analyze the current prevalence of goiter in school-age children.Results:The age of 114 103 children was (9.04 ± 0.81) years old, with 50.0% of (57 083) boys. The median of iodine content M ( Q1, Q3) in children's household salt was 23.00 (19.80, 25.20) mg/kg, including 17 242 non-iodized salt, 6 173 unqualified iodized salt, and 90 688 qualified iodized salt. The coverage rate of iodized salt was 84.89%, and the coverage rate of qualified iodized salt was 79.48%. The proportion of non-iodized salt increased from 11.85% in 2016 to 16.04% in 2021 ( χ 2trend=111.427, P<0.001). The median of urinary iodine concentration M ( Q1, Q3) in children was 182.50 (121.00, 261.00) μg/L, among which the proportions of iodine deficiency, iodine suitability, iodine over suitability, and iodine excess were 17.25% (19 686 cases), 39.21% (44 745 cases), 26.85% (30 638 cases), and 16.68% (19 034 cases), respectively. The median of urinary iodine concentration in children in inland areas [ M ( Q1, Q3): 190.90 (128.80, 269.00) μg/L] was significantly higher than that in children in coastal areas [ M ( Q1, Q3): 173.00 (113.00, 250.30) μg/L] ( P<0.001). From 2016 to 2021, a total of 39 134 ultrasound examinations were conducted, and 1 229 cases of thyroid enlargement were detected. The goiter rate was 3.14% (95% CI: 2.97%-3.32%). The incidence of goiter in children in coastal areas [3.45% (95% CI: 3.19%-3.72%), 641/18 604] was higher than that in children in inland areas [2.86% (95% CI: 2.64%-3.10%), 588/20 530] ( P=0.001). Conclusion:From 2016 to 2021, the iodine nutrition level of children aged 8-10 years in Zhejiang Province is generally suitable, and the rate of goiter in children meets the limit of iodine deficiency disease elimination standards.

Newborn screening (NBS) plays a significant role in reducing the risk of birth defects. NBS in China began in the early 1980s. Under the protection of laws and regulations and the leadership of the national health administration, approved screening centers in public hospitals took the responsibility for publicity, screening, diagnosis, treatment, follow-up and management of birth defects. As of 2022, 31 provinces (autonomous regions and municipalities directly under the central government) have carried out NBS for phenylketonuria, congenital hypothyroidism, and hearing loss, 23 provinces have carried out screening for glucose-6-phosphate dehydrogenase (with a screening rate of 89.24%), and 24 provinces have carried out screening for congenital adrenal cortical hyperplasia (91.45% screening rate). Over the past four decades, screening techniques have evolved from bacterial inhibition, fluorescence analysis, and tandem mass spectrometry for the detection of biochemical markers to genetic testing, which has greatly contributed to the expansion of the types of diseases screened for. The combined use of metabolomics and genomics is currently being explored. Effective management and rigorous quality control of NBS are prerequisites for improving the quality and ensuring the accuracy of screening. The Quality Management System for Newborn Screening System Network (QMS-NBS), established by the National Center for Clinical Laboratories, covers all screening centers and related blood collection agencies. The operation of the QMS-NBS allows the quality and performance of screening to be transparent and measurable, ensuring the quality and efficiency of screening. This article provides an overview of the history of NBS, especially the evolution of policies for the NBS in China, the construction of screening institutions, the number of newborns screened, the incidence rates of screened diseases, the changes in screening technology, the expansion of new diseases screened for, and the quality control of NBS. Overall, the progress in NBS in China has not only benefited from the development and standardization at the technological level, but also benefited from the construction of policies, regulations and ethics.
Infant, Newborn ; Humans ; Neonatal Screening ; Phenylketonurias ; Genetic Testing ; Congenital Hypothyroidism ; China

OBJECTIVES: Major depressive disorder (MDD) patients with anhedonia tend to have a poor prognosis. The underlying imaging basis for anhedonia in MDD remains largely unknown. The relationship between nodal properties and anhedonia in MDD patients need to be further investigated. Herein, this study aims to explore differences of cerebral functional node characteristics in MDD patients with severe anhedonia (MDD-SA) and MDD patients with mild anhedonia (MDD-MA) before and after the antidepressant treatment. METHODS: Ninety participants with current MDD were recruited in this study. 24-Item Hamilton Depression Scale (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess the severity of depression and anhedonia at baseline and the end of 6-months treatment. The MDD patients who scored above the 25th percentile on the SHAPS were assigned to an MDD-SA group (n=19), while those who scored below the 25th percentile were assigned to an MDD-MA group (n=18). All patients in the 2 groups received antidepressant treatment. Functional magnetic resonance imaging (fMRI) images of all the patients were collected at baseline and the end of 6-months treatment. Graph theory was applied to analyze the patients' cerebral functional nodal characteristics, which were measured by efficiency (e_i) and degree (k_i). RESULTS: Repeated measures 2-factor ANCOVA showed significant main effects on group on the e_i and k_i values of left superior frontal gyrus (LSFG) (P=0.003 and P=0.008, respectively), and on the e_i and k_i values of left medial orbital-frontal gyrus (LMOFG) (P=0.004 and P=0.008, respectively). Compared with the MDD-MA group, the significantly higher e_i and k_i values of the LSFG (P=0.015 and P=0.021, respectively), and the significantly higher e_i and k_i values of the LMOFG (P=0.015 and P=0.037, respectively) were observed in the MDD-SA group at baseline. Meanwhile, higher SHAPS scores could result in higher e_i and k_i values of LSFG (P=0.019 and P=0.026, respectively), and higher e_i value of LMOFG (P=0.040) at baseline; higher SHAPS scores could result in higher e_i values of LSFG (P=0.049) at the end of 6-months treatment. The multiple linear regression analysis revealed that sex were negatively correlated with the e_i and k_i values of LSFG (r= -0.014, P=0.004; r=-1.153, P=0.001, respectively). The onset age of MDD was negatively correlated with the k_i value of LSFG (r=-0.420, P=0.034) at the end of 6-months treatment. We also found that SHAPS scores at baseline were positively correlated with the HAMD-24 scores (r=0.387, P=0.022) at the end of 6-months treatment. CONCLUSIONS There are obvious differences in nodal properties between the MDD-SA and the MDD-MA patients, such as the high e_i of LSFG in the MDD-SA patients, which may be associated with the severity of anhedonia. These nodal properties could be potential biomarkers for the prognosis of MDD. The increased e_i and k_i values in the LSFG of MDD-SA patients may underlie a compensatory mechanism or protective mechanism. The mechanism may be an important component of the pathological mechanism of MDD-SA. The poor prognosis in the MDD-SA patients suggests that anhedonia may predict a worse prognosis in MDD patients. Sex and onset age of MDD may affect the nodal properties of LSFG at baseline and the end of 6-months treatment.
Anhedonia ; Antidepressive Agents/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Humans ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging ; Prefrontal Cortex

Squamous cell carcinoma (SCC) of the renal pelvis is extremely rare and hardly to be diagnosed due to its lack of specificity in clinical manifestations and traditional imaging features. We reported a case with history of multiple operations for double kidney stones, who was admitted to our hospital twice due to "right kidney ureteral stones, left kidney complex stones, chronic renal insufficiency and urinary tract infection" . During this period, a total of 6 surgeries were performed. In the first 19-day hospitalization, right transurethral ureteroscopic lithotripsy and right percutaneous nephroscope lithotripsy(PCNL)were performed respectively. And 20 days later, the patient was admitted to hospital again for management of left complex kidney stones, and the left side PCNL was performed for 4 times within 27 days. During the two hospitalizations, no tumor was reported during the three times of contrast-enhanced CT examination of the urinary system. The patient continued to have fever after the 4th time of left PCNL, with failure of anti-infection treatment. Then, the of the left renal pelvis was considered clinically, and left nephrectomy was suggested after communication with the patient and his family members. Postoperative pathology confirmed renal pelvis SCC. After surgery, the patient’s temperature was back to normal and then discharged. The patient died 3 months after discharging due to the systemic metastasis.

Objective To investigate the biodistribution of 18F-Alfatide II in patients with breast diseases and to compare its uptake with 18F-fluorodeoxyglucose(FDG)uptake.Methods A total of 44 female patients(age:(50.7±8.0)years)with clinically suspected breast cancer from December 2015 to May 2017 were prospectively enrolled and underwent 18 F-Alfatide II and 18F-FDG PET/CT prior to treatment.By drawing regions of interest in normal organs and breast lesions,differences between 18F-Alfatide II uptake and l8F-FDG uptake were evaluated in all patients.Paired t test,two-sample t test and Wilcoxon rank sum test were used for data analysis.Results There were 53 breast lesions confirmed by histopathology in 44 patients.Among them,42 lesions were malignant and the others were benign.The uptake of 18F-Alfatide II was very low in the brain,vocal cords,lungs,blood pool and muscle.But the renal cortex and bladder had high 18F-Alfatide II accumulation.Different levels of 18F-Alfatide II uptake were found in other normal organs including normal breast tissue.There were differences(t values:2.04-41.65,all P<0.05)between 18F-Alfatide II and 18F-FDG maximum standardized uptake value(SUVmax)and mean standardized uptake value(SUVmean)in many normal organs except for the choroid plexus,salivary glands,liver,colon and normal breast tissue.The uptake of 18F-Alfatide II was significantly lower than 18F-FDG in breast cancer lesions(SUVmax:3.77±1.78 vs 7.37±4.48,SUVmean:2.25±0.98 vs 4.54±2,82;t values:4.89,4.82,both P< 0.05),but it was still higher in benign breast lesions(SUVmax:2.37±1.62,SUVmean:1.50±0.92;t val-ues:2.35,2.29,both P<0.05).Also,target/non-target(T/NT)of 18F-Alfatide II in breast cancer lesions was higher than that in benign breast lesions(5.32±3.08 vs 2.60±2.37;t = 2.72,P<0.05).Condusion The biodistribution of 18F-Alfatide II in patients is favorable and 18F-Alfatide II can be clinically used for breast cancer imaging.

This paper summarizes the factors affecting schistosomiasis transmission in the middle and lower reaches of the Yangtze River before and after the completion of the Three Gorges Dam and analyzes schistosomiasis prevalence trends to provide a basis for the application of the Three Gorges project methodologies in other areas.The Three Gorges Dam has demonstrated a positive effect on schistosomiasis control.Hubei,Hunan,Jiangxi,Anhui,and Jiangsu in the middle and lower reaches of the Yangtze River are currently regions with a high prevalence of schistosomiasis.These five provinces contained 97.62％ of known snail areas and 93.66％ of calculated schistosomiasis cases with 90.07％ of counties (cities,districts) not yet meeting the criteria for schistosomiasis transmission interruption by the end of 2016.After the Three Gorges Dam was built,the prevalence of schistosomiasis in the middle and lower reaches of the Yangtze River decreased.By the end of 2016,the estimated number of cases decreased by 92.75％ and the snail habitat areas decreased by 6.56％ compared to 2004.No acute schistosomiasis cases have occurred for two consecutive years since 2015.

Objective To compare the clinical value of early enteral nutrition and parenteral nutrition therapy in postoperative patients of cholangiocarcinoma.Methods 56 cases of cholangiocarcinoma patients were randomly divided into early enteral nutrition group (EPN group) and parenteral nutrition group (PN group).All patients received nutritional support on the basis of metabolic support.Leukocyte count and neutrophil percentage decrease rate,total bilirubin decrease rate and hepatase (valley-C conversion) were counted at 3 and 7 days after operation.The decrease rate of aminase and glutamic oxaloacetic transaminase,recovery time of intestinal function (anal exhaust and defecation),incidence rate of surgical site infection (abdominal cavity and wound),hospitalization time after operation,incidence rate of bile leakage and hospitalization cost were compared between the two groups.Results The recovery time of intestinal function [(51.2 ±4.4) h],the decrease rate of leukocyte count (0.438 7 ±0.191 5) and neutrophil ratio (0.179 5 ± 0.046 1),the decrease rate of bilirubin (0.502 5 ± 0.153 5),alanine aminotransferase (ALT) (0.688 1 ±0.113 3),aspartate aminotransferase (AST) (0.617 0 ± 0.178 8) and hospitalization expenses [(87 852.37 ±9 127.04)yuan] in EPN group were better than those in PN group [(72.0 ± 12.9)h,0.090 5 ±0.120 3,0.083 4 ±0.036 8,0.201 5 ±0.077 8,0.251 6 ±0.419 0,0.230 9 ± 0.437,(109 036.69 ± 7 949.71) yuan,P ＜ 0.05].However,the incidence of abdominal distension (42.31％) was higher than that of PN group (13.33％,P ＜ 0.05).The incidence of bile leakage (7.69％) was not significantly different from that of PN group (13.33％,P ＞0.05).Conclusions Early enteral nutrition has obvious advantages in postoperative recovery of patients with cholangiocarcinoma.