Objective:To analyze the difference and reliability of blood 17-hydroxyprogesterone (17-OHP), an indirect screening index for congenital adrenal hyperplasia (CAH), between preterm and full-term infants.Methods:In this retrospective cross-sectional study, a total of 210 285 newborns who underwent CAH screening at the Neonatal Screening Center of Shanghai Children′s Hospital from January 2019 to December 2022 were collected, including 14 312 premature infants and 195 973 full-term infants.The concentration of 17-OHP in dried blood spots on filter paper was determined by an automatic fluorescence analyzer.The distribution of 17-OHP levels in preterm and full-term infants and its statistical index were analyzed.The Kolmogorov-Smirnov test was used for normal distribution.The skewed distribution data was converted into approximately normal distribution using Box-Cox.Outliers were eliminated by the interquartile range method.The cumulative frequency distribution map was drawn by R language programming.The 99.5 th percentile value was used as the screening threshold and compared with the reference value given by the manufacturer or laboratory and with the reference change value (RCV). Results:According to the threshold provided by the laboratory, 26.76‰ of premature infants were tested positive in preliminary screening, and 4 were confirmed with an incidence of 1∶3 578, while 0.79‰ of full-term infants were tested positive in preliminary screening, and 11 were confirmed with an incidence of 1∶17 816.The thresholds for CAH screening established indirectly were 20.35 nmol/L in preterm infants and 10.78 nmol/L in full-term infants.The relative deviations between the indirect CAH screening thresholds and the manufacturer′s or laboratory′s CAH screening thresholds were higher than the RCV, respectively.According to the indirect CAH screening thresholds, the negative and positive coincidence rates of 65 samples in 13 batches from the Centers for Disease Control and Prevention interlaboratory quality assessment program in the United States reached 100%.A retrospective analysis of 210 285 neonates showed that 17-OHP concentration was higher than the screening threshold in all CAH-positive neonates.The application of this screening threshold reduced the false positive rate of preterm infants by 59.79%.Conclusions:It is feasible to establish the CAH screening thresholds for premature and full-term infants by an indirect method, which can improve the efficiency of screening and provide better diagnostic basis for clinical practice.

Objective: To investigate the resistance to rifampicin and isoniazid and the changing trends among patients with pulmonary tuberculosis in Luohu District, Shenzhen City, Guangdong Province from 2012 to 2022, so as to provide insights into improving drug-resistant pulmonary tuberculosis control and prevention strategies. Methods: Basic information, treatment classification and drug resistance data of patients with pulmonary tuberculosis and positive pathogenic detection in Luohu District from 2012 to 2022 were collected through the Tuberculosis Surveillance System of Chinese Disease Prevention and Control Information System, and resistance rates of rifampicin and isoniazid and the changing trends were analyzed. Results: A total of 2 126 patients with pulmonary tuberculosis were collected and had a median age of 34 (interquartile range, 25) years, including 1 334 males (62.75%) and 792 females (37.25%). There were 302 patients with drug-resistance in Luohu District from 2012 to 2022, with a resistance rate of 14.21%. Among them, 60 patients were monoresistant to rifampicin (2.82%), 113 patients were monoresistant to isoniazid (5.32%), and 129 patients were multidrug resistant (6.07%). The rate of rifampicin monoresistance showed a downward trend from 2012 to 2022, while the rate of multidrug resistance showed an upward trend (both P<0.05). There was no significant tendency in the rate of isoniazid monoresistance (P>0.05). The rate of multidrug resistance among patients without Shenzhen residence was higher than that among patients with Shenzhen residence; the rates of rifampicin resistance and multidrug resistance among retreated patients were higher than those among treatment-naïve patients (all P<0.05). Conclusions The rate of rifampicin monoresistance appeared a downward trend and the rate of multidrug resistance appeared an upward trend among patients with pulmonary tuberculosis in Luohu District from 2012 to 2022. Attention should be given to non-Shenzhen residence and retreated patients.

[Objective]Childhood trauma(CT)is considered one of the major risk factors for developing major depres-sive disorder(MDD)in adulthood.However,the neural basis of MDD patients with CT(CT-MDD)remains poorly under-stood.Therefore,the objective of our study is to explore the resting-state global brain functional connectivity(FC)in CT-MDD.[Methods]A total of 34 CT-MDD and 34 healthy controls performed resting-state fMRI.Whole-brain voxel-level degree centrality(DC)analysis was performed,and the brain regions with significant differences between the two groups were selected as region of interest(ROI)for further estimating the global brain FC.Subsequently,correlation analysis was performed between DC values,FC values in abnormal brain areas and clinical characteristics.[Results]The CT-MDD group showed increased DC value of the right middle frontal gyrus(MFG)compared with the healthy controls.Seed-based FC revealed that the CT-MDD group showed increased connections between the left precuneus and the right MFG or the right medial prefrontal cortex,relative to healthy controls(threshold at P<0.05).Additionally,the DC value of the right MFG was correlated with the severity of CT.[Conclusion]Our results show the increased FC between the left precuneus and the ROI(right MFG)as well as the right medial prefrontal cortex,which are two important brain regions within the de-fault mode network(DMN),and might suggest increased synchronism between the cognitive executive networks and DMN in CT-MDD.These findings may provide insights into the pathophysiological mechanisms underlying CT-MDD.

Objective:To explore the clinical, biochemical and genetic characteristics of three children with Isoleucine metabolic disorders due to variants of HSD17B10 and ACAT1 genes. Methods:Two children with 17β hydroxysteroid dehydrogenase 10 (HSD17B10) deficiency and a child with β-ketothiolase deficiency (BKD) diagnosed at Shanghai Children′s Hospital between 2014 and 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to blood acylcarnitine, urinary organic acid and genetic testing, and candidate variants were analyzed with bioinformatic tools.Results:The main symptoms of the three children had included epilepsy, developmental delay, hypotonia and acidosis. Their blood acylcarnitine methylcrotonyl carnitine (C5: 1), 3-hydroxyisovalerylcarnitine (C5-OH) and 3-hydroxybutylcarnitine (C4OH) were increased to various extents, and urine organic acids including methyl crotonylglycine and 2-methyl-3-hydroxybutyric acid were significantly increased. Child 1 and child 2 were respectively found to harbor a c. 347G>A (p.R116Q) variant and a c. 274G>A (p.A92T) variant of the HSD17B10 gene, and child 3 was found to harbor compound heterozygous variants of the ACAT1 gene, namely c. 547G>A (p.G183R) and a c. 331G>C (p.A111P). Among these, the c. 274G>A (p.A92T) and c. 331G>C (p.A111P) variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variant of unknown significance (PP3_Strong+ PM2_supporting) and likely pathogenic (PM3+ PM2_Supporting+ PP3_Moderate+ PP4). Conclusion:Both the HSD17B10 deficiency and BKD can lead to Isoleucine metabolism disorders, which may be difficult to distinguish clinically. Genetic testing can further confirm the diagnosis. Discoveries of the HSD17B10: c. 274G>A (p.A92T) variant and the ACAT1: c. 331G>C (p.A111P) variant have enriched the mutational spectrum of the two diseases.

Objective:To compare the feasibility and efficacy of translocator protein (TSPO) molecular probes N, N-diethyl-2-(2-(4- 18F-fluorophenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-FDPA) and 18F-(R)-( N-sec-butyl)-3-fluoromethyl- N-methyl-4-phenylquinoline-2-carboxamide (LW223) for the detection of abdominal vulnerable atherosclerotic plaques (VAP) in rabbit models. Methods:Nine healthy New Zealand white rabbits were divided into group A (control group, n=3), group B (VAP group, n=3) and group C (VAP treatment group, n=3) using completely randomized design. Animals were injected with 18F-FDPA and 18F-LW223 at the end of 12, 16 and 24 weeks. PET/CT and CT angiography (CTA) was performed 40-50 min post injection. All rabbits were sacrificed at the end of 24 weeks after imaging studies. All abdominal aortas were collected for pathological and immunofluorescence examination. Repeated measures analysis of variance (Bonferroni test) and paired t-test were used to analyze the data. Results:Target-to-background ratio (TBR; abdominal aortic lesion/left ventricular blood pool) values of 18F-FDPA in 3 groups at the end of 12, 16 and 24 weeks were significantly different ( F values: 68.09-144.88, all P<0.001). At the end of 12 weeks, there was no increased uptake of 18F-FDPA in the abdominal aorta region in 3 groups. The local 18F-FDPA uptake of the abdominal aorta in group B was significantly higher than the uptake in group C and that in group A at the end of 16 and 24 weeks( P<0.05 or P<0.001), and there were significant differences between group C and group A, with higher uptake in group C (both P<0.01). In 3 groups, there was no significant 18F-LW223 uptake in the abdominal aorta region at 3 time points of PET/CTA imaging. At the end of 12, 16 and 24 weeks, TBR values of 18F-FDPA and 18F-LW223 in 3 groups exhibited statistical differences ( t values: 2.88-36.79, all P<0.05). HE, immunofluorescent CD68 and TSPO staining showed more macrophage infiltration in group B than group C. Conclusion:18F-FDPA can be used to detect VAP in rabbits′ abdominal arteries at early time compared to 18F-LW223, and to evaluate the changes in the stability of vulnerable plaque after lipid-lowering drug intervention.

Objective:To investigate the diagnostic value of fluorescence quantitative method and G6PD/6PGD ratio method in glucose-6-phosphate dehydrogenase (G6PD) deficiency and the type of gene mutation.Methods:A total of 1 201 patients (711 males and 490 females) with suspected G6PD deficiency in Shanghai Children′s Hospital were collected from June 2018 to March 2021. Fluorescence quantification method, G6PD/6PGD ratio method and multicolor melting curve were used to detects enzyme activity, ratio and gene mutation type. Comparison of each index and evaluation of its diagnostic efficiency were performed.Results:Among 1 201 suspicious samples, 163 cases (135 males and 28 females) were finally diagnosed. 156 cases were diagnosed by fluorescence quantitative method with a detection rate of 95.71%, and 140 cases were diagnosed by G6PD/6PGD ratio method with a detection rate of 85.89%. enzymatic activity of G6PD and ratio of G6PD/6PGD in male were significantly lower than female, and the differences were statistically significant ( U=642.5, 734.5, P<0.001). 112 cases received G6PD gene mutation detection and 92 cases were diagnosed, 74 were hemizygous mutations, 1 were homozygous mutations, 15 were heterozygous mutations, and 2 were compound heterozygous mutations. Among 15 cases of heterozygous mutations, 11 cases were diagnosed by fluorescence quantitative method, the diagnosed rate was 73.33%, 4 cases were diagnosed by G6PD/6PGD ratio method, and the diagnosed rate was 26.67%. A total of 7 mutation sites were detected and the proportions were c.1388G>A (32.22%), c.1376G>T (30.00%), c.871G>A (13.33%), c.1024C>T (11.11%). c.95A>G (7.78%), c.487G>A (4.44%), c.392G>T (1.11%). The enzymatic activities of c.1376G>T and c.1024C>T, c.487G>A were statistically significant ( P<0.001,0.015); the G6PD/6PGD ratios of c.1024C>T and c.1388G>A, c.1376G>T were statistically significant ( P=0.017,0.002,0.011,0.013). Fluorescence quantitative method had sensitivity of 100%, specificity of 95.65%, and the area under the curve (AUC) is 0.972. The sensitivity of the G6PD/6PGD ratio method was 100%, the specificity was 94.57%, and the AUC was 0.979. The sensitivity of fluorescence quantitative method combined with G6PD/6PGD ratio was 96.7%, the specificity was 100%, and the AUC was 0.992. Conclusions:Compared with fluorescence quantification, the G6PD/6PGD ratio method might not be able to diagnose female heterozygotes effectively; The panel of G6PD fluorescence quantification and G6PD/6PGD ratio was helpful to reduce the missed diagnosis. Combined with gene mutation analysis, it could improve the diagnosis rate of G6PD deficiency in the children.

Objective:To observe the repairing effect of ozone water injection in the articular cavity for the treatment of knee osteoarthritis (KOA) on articular cartilage and to explore its repair mechanism.Methods:48 rats were randomly divided into fourgroups, the normal, model, normal saline and ozone water group, each group had 12 rats. The rats were injectied into the joint cavity with papain to establish a KOA model other than the normal group. After confirming the success of the model, the ozone water group and normal saline group was treated with ozone water and normal saline injection into the joint cavity once a week for a total of 3 treatments, the normal group and the model group are all raised routinely. Before and after the treatment, the ratknee joint behavioral score MG score was conducted; after the treatment articular cartilage surface gross score, hematoxylin and eosin (HE) staining and modified Mankin score of articular cartilage pathological changes was measured, and Western blot and Rt-PCR to measure the level of protein and mRNA expression of NF-κB p65, IKKβ and IκBα in articular cartilage tissues.Results:Compared with before the treatment, the rat knee joint behavioral score of the ozone water group was significantly lower (all P<0.05); after the treatment, the gross articular cartilage surface score and the modified Mankin score of the ozone water group were significantly reduced compared with the model and normal saline group (all P<0.05); Compared with the model and normal saline group, the protein and mRNA expression levels of NF-κB p65 and IKKβ in the ozone water group are significantly lower (all P<0.05), and the levels of IκBα are significantly higher (all P<0.05). Conclusion:Ozone water injection in the articular cavity can effectively repair damaged articular cartilage. The repair mechanism may be achieved by inhibiting the activation of NF-κB signaling pathway.

[Objective]To investigate the micro-structural alterations within whole brain white matter(WM) in cough syrup abuse addiction patients containing codeine,and to explore the correlation between aberrant WH and abuse time of cough medicine abuse patients.[Methods]Thirty cough syrup abuse addiction patients containing codeine and 30 controls participated in the study. Structural changes in FA and(mean diffusivity)MD were examined in cough syrup abuse addiction patients containing codeine which derived from DTI tractography. Pearson correlation analysis was performed to compare the mean FA value and duration of cough syrup abuse addiction in patients.[Results]Cough syrup abuse addiction patients containing codeine had lower FA value in bilateral anterior limb of internal capsule(ALIC)and higher MD in the bilateral hippocampus and insula,right anterior cingulate cortex(ACC)and superior temporal gyrus,compared to the controls. Cough syrup abuse addiction group also had positive correlation between mean FAvalues and duration of cough syrup abuse addiction in patients.[Conclusion]Micro-structural alterations within whole brain white matter(WM)are found in cough syrup abuse addiction patients containing codeine. This disturbance progresses as duration increases of cough syrup abuse addiction in patients.

Objective: To explore the relationship between glycemic control and visceral adiposity index (VAI) among type 2 diabetes mellitus (T2DM) patients.Methods: A community-based epidemiological field study for patients with T2DM aged ≥ 40 years was conducted in China.Every participant underwent physical examinations, biochemical tests of fasting glucose, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and so on, and a questionnaire, including anthropometric characteristics, lifestyle, disease history, family history, and medication use.Those participants with HbA1c ≥7.0% were classified as the poorly controlled in our analysis of relationship between glycemic control and VAI.Anthropometric characteristics, lifestyle, and biochemical indexes of the participants were compared among the groups of different VAI levels.Logistic models were applied in multiple analysis adjusting for possible confounders.Results: A total of 1 607 patients with T2DM were recruited in our analysis with a mean age of (59.4±8.1) years and an average T2DM duration of (7.0±6.4) years.Among them, 78.3% were on hypoglycemic therapy.The cutoff points of quartiles of VAI were calculated for the males and females, respectively.According to the ascending order of the quartiles of VAI, the participants were divided into four groups, i.e.Q1, Q2, Q3, and Q4.The poor glycemic control rate for these groups were 60.6%, 65.7%, 70.1%, and 71.0%, respectively (Trend χ2=12.20, P<0.001).After adjustment for age, gender, systolic blood pressure (SBP), diastolic blood pressure (DBP), LDL-C, smoking, cardio-cerebral vascular disease (CVD) history, hypoglycemic therapy, T2DM duration, and family history of diabetes, the Logistic regression models showed that the glycemic control rate was significantly associated with VAI levels among the patients with T2DM.Compared with the participants in group Q1, the ORs of poor glycemic control for those in groups Q2, Q3, and Q4 were 1.239 (95%CI 0.918 to 1.672), 1.513 (95%CI 1.117 to 2.050), and 1.535 (95%CI 1.128to 2.088), respectively (trend P=0.003).With each quartile increase in VAI, the OR of poor glycemic control was 1.162 (95%CI 1.054 to 1.282).Conclusion: The glycemic control among the patients with T2DM is significantly associated with VAI.High level of VAI is an indicator of poor glycemic control.

Objective To investigate w hether the iterative reconstruction (iDose 4 ) technique improves imaging quality of the low-radiation-dose w hole brain CT perfusion (CTP). Methods Thirty-five consecutive patients w ith clinical y suspected ischemic stroke w ere col ected. Bril iance 256 iCT w as used to perform low-radiation-dose w hole brain CTP, and the filtered back projection (FBP) and iDose 4 algorithm w ere used to conduct image reconstruction. The noise and signal to noise ratio of the 2 kinds of reconstruction algorithms, as w el as the imaging quality of each parameter map w ere compared. Results The effective dose of the w hole brain CTP w as 2.2 mSv. Compared w ith FBP, the noise of each region of interest in the iDose4 Tmax map was decreased significantly ( P<0.05) and the signal to noise ratio was increased significantly (P<0.05). The imaging quality scores (median, interquartile range) reconstructed by FPB group w ere significantly low er than by iDose 4 for cerebral blood flow (CBF) map ( 5.00 [3.00-6.00]vs. 6.00 [5.00-6.00]; Z= -2.784, P=0.005), cerebral blood volume (CBV) map ( 6.00 [5.00-6.00] vs. 6.00 [6.00-7.00]; Z= -3.674, P<0.001), and mean transit time (MTT) map (4.00 [3.00-5.00] vs. 5.00 [4.00-6.00]; Z=3.394, P=0.001). The proportions of the poor quality in CBF map ( 34.3%vs. 11.4%;χ2 =7.036, P=0.030), CBV map (11.4%vs.2.9%; χ2 =7.485, P=0.024 ) and MTT map (28.6%vs.11.4%;χ2 =5.318, P=0.070) reconstructed by FBP w ere significantly higher than by iDose 4 . Conclusions The iDose4 technique may improve imaging quality of low er-radiation-dose CTP.