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 observe the clinical efficacy of pressing-kneading manipulation combined with herb-insulated moxibustion at Shuidao(ST28)for postpartum urinary retention after labor analgesia and its effect on bladder urination function. Methods:A total of 154 patients with postpartum urinary retention after labor analgesia were randomly divided into a Western medication group and a herb-insulated moxibustion group,with 77 cases in each group.In the Western medication group,neostigmine sulfate was injected into Zusanli(ST36).In the herb-insulated moxibustion group,after pressing-kneading manipulation at Shuidao(ST28),herb-insulated moxibustion was applied to Shuidao(ST28)with self-made Tong Quan San.Both groups were treated once,and the clinical efficacy was evaluated 5 h after treatment.The first urination time,first urination volume,average urinary flow rate,bladder residual urine volume,hospitalization days,and costs were recorded. Results:The total effective rate and markedly effective rate of the herb-insulated moxibustion group were higher than those of the Western medication group(P<0.05),the time to the first urination and residual urine volume in the bladder of the herb-insulated moxibustion group were shorter or smaller than those of the Western medication group(P<0.01),the first urination volume and average urine flow rate of the herb-insulated moxibustion group were larger than those of the Western medication group(P<0.01).There were no significant differences in the hospitalization days and costs between the two groups(P>0.05). Conclusion:Pressing-kneading manipulation combined with herb-insulated moxibustion at Shuidao(ST28)can effectively treat postpartum urinary retention after labor analgesia and improve bladder urination function.

This paper reports a case of recurrent peritoneal dialysis-associated peritonitis caused by Salmonella, as identified through metagenomic next-generation sequencing. This patient was treated regularly with peritoneal dialysis due to stage 5 chronic kidney disease. One month ago, she was hospitalized for peritoneal dialysis-associated peritonitis. The result of bacterial culture of the dialysate was Salmonella, and she was discharged after anti-infective treatment for 3 weeks. However, on the 12th day after discharge, the patient was readmitted to the hospital due to peritonitis.Both metagenomic next-generation sequencing and bacterial culture of the fluid confirmed the presence of Salmonella. After 3 weeks of intraperitoneal and intravenous anti-infection treatment, the patient underwent metagenomic next-generation sequencing to assess pathogen eradication before discharge.

Objective:To evaluate the predictive value of stress+ rest gated myocardial perfusion imaging (G-MPI) in assessing all-cause mortality risk in patients with familial hypercholesterolemia (FH).Methods:From June 2010 to March 2022, 72 patients (39 males, 33 females; age (21.1±12.3) years) who diagnosed with FH clinically and genetically and underwent stress+ rest G-MPI in Beijing Anzhen Hospital, Capital Medical University were retrospectively followed up. Image analysis was performed using the 17-segment 5-point method to obtain left ventricular myocardial perfusion and functional parameters. Patients were followed for all-cause mortality events, and predictors associated with the risk of all-cause mortality were analyzed using Cox regression. The efficiencies of predictors were evaluated by ROC curve analysis, and the Kaplan-Meier method and log-rank test were used to compare the differences in the incidence of all-cause mortality in different groups of patients with FH. Independent-sample t test or Mann-Whitney U test was used to analyze the data. Results:The follow-up time of 72 patients was 7(4, 10) years, and all-cause death occurred in 16(22.2%) patients during the follow-up period. There were statistically significant differences in total cholesterol (TC), low density lipoprotein cholesterol (LDLC), summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), stress end-systolic volume (SESV), stress ejection fraction (SEF), rest end-diastolic volume (REDV), rest end-systolic volume (RESV) and rest ejection fraction (REF) between the death group and the survival group ( t values: from -2.65 to 4.47, z values: from -3.43 to -1.98, all P<0.05). Cox regression analysis showed that SDS (hazard ratio ( HR)=1.337, 95% CI: 1.114-1.604, P=0.002), SESV ( HR=1.019, 95% CI: 1.008-1.030, P<0.001) and LDLC ( HR=1.355, 95% CI: 1.049-1.749, P=0.020) were independent predictors associated with the risk of all-cause mortality in patients with FH. The optimal cut-off value of SESV for predicting mortality in patients with FH determined by ROC curve analysis was 35.5 ml, with the AUC of 0.701 (95% CI: 0.517-0.885). The incidence of all-cause mortality in the group with SESV≥35.5 ml was significantly higher than that in the group with SESV<35.5 ml (28.6% vs 6.9%; χ2=5.15, P=0.023). Conclusion:Stress+ rest G-MPI is an important imaging method for all-cause mortality risk assessment in patients with FH, and SDS, SESV and LDLC are important factors in predicting mortality in patients with FH.

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 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.

Promoting the transformation of scientific and technological achievements in hospitals can significantly enhance the new productivity levels and innovation capabilities in China's biomedicine sector.However,specialized hospitals face several challenges due to their smaller scale and singular discipline layout.These include insufficient interdisciplinary collaboration,in-adequate funding and capacity to attract funds,a lack of awareness and motivation among hospital staff regarding achievement transformation,limited experience in transforming results,and difficulties in industrializing outcomes.To effectively improve the transformation of scientific and technological achievements,specialized hospitals can adopt strategies such as strengthening the in-tegration of industry,academia,research,and healthcare;increasing financial investment;enhancing theoretical training on a-chievement transformation;building a team of transformation professionals;and exploring diverse pathways for achievement trans-formation.

Objective To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for determination of tobramycin in human serum,and examine the utility of the method in a clinical pharmacokinetic study of tobramycin inhalation.Methods Serum samples were pretreated by solid phase extraction with tobramycin-D12 as internal standard.Chromatographic separation was performed on a TitankHilic(2.1 mm × 100 mm,3 μm)column.The mobile phase consisted of0.1％formic acid-acetonitrile and 0.1％formic acid aqueous solution at a flow rate of 0.4 mL/min.Electrospray ionization source and multiple reaction monitoring(MRM)scanning were used for monitoring the quantitative ion pairs with m/z 468.3→m/z 163.3(tobramycin)and m/z 480.6→m/z 166.2(tobramycin-D12).The established method was investigated in terms of selectivity,interaction,concomitant medication,standard curve and lower limit of quantitation,precision and accuracy,recovery,matrix effect,and stability of tobramycinin.Results The linear range of tobramycin was 0.050 0-10.0 mg/L(R2=0.999 5).The intra-and inter-batch precision was satisfactory(coefficient of variation[CV]≤3.6％).The accuracy ranged from-0.4％to 6.0％.The matrix effect factor(MF)in human serum samples(including hemolysis and lipemia)ranged from 92.2％to 94.9％(CV≤2.7％).The recovery of tobramycinin was 79.5％-81.9％in serum samples,while the recovery of internal standard was 78.9％.The analyte was stable in serum samples for 72 h at room temperature and for 274 days at-20℃/-70℃.The pharmacokinetic study of tobramycin inhalation in bronchiectasis patients showed that after continuous administration of tobramycin 300 mg twice a day to 3 patients,the mean Cmax of tobramycin was(0.72±0.61)mg/L on Day 1 and(0.76±0.73)mg/L on Day 28,respectively.The corresponding Tmax was(1.83±0.61)h and(1.50±0.50)h,respectively.Conclusions The UPLC-MS/MS method established in this study is sensitive,accurate and rapid.It is successfully applied to the clinical pharmacokinetic study of tobramycin inhalation.The method may be suitable for therapeutic drug monitoring of tobramycin in clinical practice.

Objective:To investigate the relationship between serum osteopontin (OPN), bone morphogenetic protein 2 (BMP2), retinol binding protein 4 (RBP4) and renal function and bone mineral density in patients with diabetes nephropathy (DN).Methods:A total of 120 patients with DN diagnosed in the Affiliated Hospital of Jining Medical University from January 2020 to December 2021 were selected as the DN group, 60 patients with simple diabetes as the type 2 diabetes mellitus (T2DM) group, and 60 subjects with normal glucose tolerance test as the control group. The serum OPN, BMP2, RBP4, low bone mineral density (LBMD), femoral neck bone density (FNBMD) and renal function indicators of the three groups were compared. According to the urinary albumin excretion rate (UAER) of DN patients, the patients were divided into microalbuminuria DN group (71 cases) and massive albuminuria DN group (49 cases), and stratified comparison was made. The simple linear correlation analysis was used to analyze the OPN of DN patients. BMP2, RBP4, renal function and bone mineral density.Results:The fasting blood glucose (FPG), glycated hemoglobin (HbA 1c), serum creatinine (Scr), UAER, and cystatin (CysC) levels of DN group patients were significantly higher than those of T2DM group and control group, and the differences were statistically significant (all P<0.05); The FPG and HbA 1c in the T2DM group were higher than those in the control group, and the differences were statistically significant (all P<0.05); The OPN and BMP2 of DN group patients were higher than those of T2DM group and control group, while the RBP4, LBMD, FNBMD of DN group were lower than those of T2DM group and control group, and the differences were statistically significant (all P<0.05); The OPN and BMP2 of the T2DM group were higher than those of the control group, while RBP4 was lower than that of the control group, and the differences were statistically significant (all P<0.05); The levels of FPG, HbA 1c, Scr, UAER, and CysC in patients with macroalbuminuria DN were significantly higher than those in patients with microalbuminuria DN, and the differences were statistically significant (all P<0.05); The OPN and BMP2 of patients in the large albuminuria DN group were higher than those in the microalbuminuria DN group, while the RBP4, LBMD, and FNBMD of patients in the large albuminuria DN group were lower than those in the microalbuminuria DN group, and the differences were statistically significant (all P<0.05). The OPN of DN group patients was positively correlated with Scr, UAER, and CysC (all P<0.05), while BMP2 was positively correlated with UAER and CysC (all P<0.05); The OPN and BMP2 of DN group patients were negatively correlated with LBMD and FNBMD (all P<0.05), while RBP4 was positively correlated with LBMD and FNBMD (all P<0.05). Conclusions:OPN, BMP2, RBP4 are closely related to the degree of renal function impairment and bone loss in DN patients, and can to some extent reflect the degree of bone metabolism and osteoporosis in T2DM patients.

Objective To observe the value of semi-quantitative parameters related to gated myocardial perfusion imaging(G-MPI)for predicting occurrence of major adverse cardiovascular events(MACE)in patients with chronic kidney disease(CKD).Methods Totally 148 CKD patients who underwent rest G-MPI(R-GMPI)(R-GMPI group,n=95)or stress/rest G-MPI(S/R-GMPI)(S/R-GMPI group,n=53)were retrospectively included.The patients were categorized into MACE subgroup and non-MACE subgroup according to MACE occurred or not during follow-up.Clinical data and G-MPI parameters were compared between subgroups,and independent predictors of MACE in CKD patients were obtained using multivariate Cox proportional hazards regression analysis.Receiver operating characteristic(ROC)curve was drawn,the area under the curve(AUC)was calculated to assess the efficacy of each independent predictor for predicting MACE.Among patients who underwent only R-GMPI,the optimal cut-off value of each parameter for predicting MACE was obtained by ROC curve analysis,and the risk of MACE was stratified,then Kaplan-Meier curves were drawn and compared with log-rank test.Results Among 95 patients who underwent only R-GMPI,compared with non-MACE subgroup,those in MACE subgroup had smaller body mass index(BMI)and higher proportion of previous myocardial infarction and hemodialysis,as well as higher R-GMPI left ventricle end-diastolic volume(R-LVEDV),left ventricle end-systolic volume(R-LVESV),sum rest score(R-SRS)but lower left ventricle ejection fraction(R-LVEF)(all P＜0.05),while R-SRS(HR=1.068,95％CI[1.027,1.110])and R-LVESV(HR=1.011,95％CI[1.005,1.017])were both independent predictors for MACE(both P＜0.05).Among 53 patients who underwent S/R-GMPI,compared with non-MACE subgroup,those in MACE subgroup had with higher blood creatinine and lower estimated glomerular filtration rate(eGFR),higher S-LVESV,R-LVEDV,sum stress score(SSS),SRS and sum difference score(SDS)(all P＜0.05),and SDS(HR=1.454,95％CI[1.063,1.989])was an independent predictor for MACE(P＜0.05).Among 95 CKD patients who underwent only R-GMPI,AUC of R-SRS and R-LVESV alone for predicting MACE was 0.659 and 0.694,respectively,and higher incidence of MACE was found in those w ith R-SRS ≥8 points,also in those with R-LVESV ≥91 ml(both P＜0.05).Conclusion G-MPI could be used to evaluate myocardial perfusion and function in CKD patients.For CKD patients just underwent only R-GMPI,R-SRS and R-LVESV were independent predictors for MACE,whereas SDS might be utilized to predict MACE in CKD patients who could undergo S/R-GMPI.