Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

OBJECTIVE To get the current situation of healthcare associated infection(HAI)and implement targe-ted management through analyzing the trends of HAI incidence rate,the distribution of clinical departments,the sites of HAI and the composition of pathogens in a children's hospital in a five-year period.METHODS Data on HAI cases were collected from all inpatients in Children's Hospital of Soochow University from 2019 to 2023 through the real-time monitoring system of XINGLIN Healthcare acquired Infection Surveillance;Cochran-Armit-age test was used to check for the significant changes of distribution of HAI cases.RESULTS A total of 383,376 hospitalized patients were monitored from 2019 to 2023,of which HAI occurred on 6670 cases and 7209 case-times with an incidence rate of 1.74%and an incidence case rate of 1.88%.The top five departments of HAI inci-dence rates were cardiac,neonatal,surgical and pediatric intensive care unit and department of hematology.HAI mainly occurred in blood and alimentary system,upper and lower respiratory tract.A total of 2668 strains of path-ogenic bacteria were isolated,of which 1346 strains were gram-negative bacteria,1140 strains were gram-positive bacteria and 182 strains were fungi.The top three gram-negative bacteria were Klebsiella pneumoniae,Escherich-ia coli and Pseudomonas aeruginosa;the top three gram-negative pathogens were Streptococcus,Staphylococcus aureus and Staphylococcus epidermidis;and the top three fungi were Candida albicans,Candida parapsilosis and Candida tropicalis.CONCLUSIONS The HAI incidence rate of this hospital steadily declines in the past five years,however the same changes are not observed in the departments with high incidence of HAI.Attention should be paid to the raising bloodstream infections and detection rate of S.epidermidis.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

OBJECTIVE To get the current situation of healthcare associated infection(HAI)and implement targe-ted management through analyzing the trends of HAI incidence rate,the distribution of clinical departments,the sites of HAI and the composition of pathogens in a children's hospital in a five-year period.METHODS Data on HAI cases were collected from all inpatients in Children's Hospital of Soochow University from 2019 to 2023 through the real-time monitoring system of XINGLIN Healthcare acquired Infection Surveillance;Cochran-Armit-age test was used to check for the significant changes of distribution of HAI cases.RESULTS A total of 383,376 hospitalized patients were monitored from 2019 to 2023,of which HAI occurred on 6670 cases and 7209 case-times with an incidence rate of 1.74%and an incidence case rate of 1.88%.The top five departments of HAI inci-dence rates were cardiac,neonatal,surgical and pediatric intensive care unit and department of hematology.HAI mainly occurred in blood and alimentary system,upper and lower respiratory tract.A total of 2668 strains of path-ogenic bacteria were isolated,of which 1346 strains were gram-negative bacteria,1140 strains were gram-positive bacteria and 182 strains were fungi.The top three gram-negative bacteria were Klebsiella pneumoniae,Escherich-ia coli and Pseudomonas aeruginosa;the top three gram-negative pathogens were Streptococcus,Staphylococcus aureus and Staphylococcus epidermidis;and the top three fungi were Candida albicans,Candida parapsilosis and Candida tropicalis.CONCLUSIONS The HAI incidence rate of this hospital steadily declines in the past five years,however the same changes are not observed in the departments with high incidence of HAI.Attention should be paid to the raising bloodstream infections and detection rate of S.epidermidis.

Background: Twenty-four-hour urinary free cortisol (UFC) measurement is the initial diagnostic test for Cushing’s syndrome (CS). We compared UFC determination by both direct and extraction immunoassays using Abbott Architect, Siemens Atellica Solution, and Beckman DxI800 with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the value of 24-hr UFC measured by six methods for diagnosing CS. Methods: Residual 24-hr urine samples of 94 CS and 246 non-CS patients were collected.A laboratory-developed LC-MS/MS method was used as reference. UFC was measured by direct assays (D) using Abbott, Siemens, and Beckman platforms and by extraction assays (E) using Siemens and Beckman platforms. Method was compared using Passing–Bablok regression and Bland–Altman plot analyses. Cut-off values for the six assays and corresponding sensitivities and specificities were calculated by ROC analysis. Results: Abbott-D, Beckman-E, Siemens-E, and Siemens-D showed strong correlations with LC-MS/MS (Spearman coefficient r = 0.965, 0.922, 0.922, and 0.897, respectively), while Beckman-D showed weaker correlation (r = 0.755). All immunoassays showed proportionally positive bias. The areas under the curve were 0.975 for Abbott-D, 0.972 for LCMS/MS, 0.966 for Siemens-E, 0.948 for Siemens-D, 0.955 for Beckman-E, and 0.877 for Beckman-D. The cut-off values varied significantly (154.8–1,321.5 nmol/24 hrs). Assay sensitivity and specificity ranged from 76.1% to 93.2% and from 93.0% to 97.1%, respectively. Conclusions Commercially available immunoassays for measuring UFC show different levels of analytical consistency compared to LC-MS/MS. Abbott-D, Siemens-E, and Beckman-E have high diagnostic accuracy for CS.

Background: Thyroid diseases are highly prevalent worldwide, but their diagnosis remains a challenge. We established reference intervals (RIs) for thyroid-associated hormones and evaluated the prevalence of thyroid diseases in China. Methods: After excluding outliers based on the results of ultrasound screening, thyroid antibody tests, and the Tukey method, the medical records of 20,303 euthyroid adults, who visited the Department of Health Care at Peking Union Medical College Hospital from January 2014 to December 2018, were analyzed. Thyroid-associated hormones were measured by the Siemens Advia Centaur XP analyzer. The RIs for thyroid-associated hormones were calculated according to the CLSI C28-A3 guidelines, and were compared with the RIs provided by Siemens. The prevalence of thyroid diseases over the five years was evaluated and compared using the chi-square test. Results: The RIs for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3) were 0.71–4.92 mIU/L, 12.2–20.1 pmol/L, 3.9–6.0 pmol/L, 65.6–135.1 nmol/L, and 1.2–2.2 nmol/L, respectively. The RIs of all hormones except TT4 differed significantly between males and females. The RIs of TSH increased with increasing age. The prevalence of overt hypothyroidism, overt hyperthyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism was 0.5% and 0.8%, 0.2% and 0.6%, 3.8% and 6.1%, and 3.3% and 4.7% in males and females, respectively, which differed from those provided by Siemens. Conclusions Sex-specific RIs were established for thyroid-associated hormones, and the prevalence of thyroid diseases was determined in the Chinese population.

Objective To investigate whether there are differences in the detection of biochemical items such as electrolytes , total protein and urea between arterial plasma and venous plasma .Methods Self paired design was used to compare and study the biochemical results of different samples .70 samples ( 36 samples from male patients and 34 from female patients ) that were performed with both arterial blood gas analysis and biochemical item test of venous blood in Clinical Laboratory of Peking Union Medical College Hospital during the period from June to September of 2017 were collected.18 biochemical items like electrolytes in arterial blood and venous blood were synchronously detected by automatic biochemical analyzer.Statistic analyses were carried out by SPSS 18.00.Whether the deviation was of clinic significance was determined by National Health Standards ( WS/T 403-2012 ) and the total error admitted by Royal Society of Pathology of Australia .Regression analysis of Passing-Bablok was performed by MedCalc software . The difference between the results of different samples was investigated by drawing Bland -Altman diagram.Results The results of Ca, Cl, K, Na, P, TP, ALB, ALT, AST, LDH, Glu, Cr, Urea, TG, CHO, UA, CHE, TBA in the samples of arterial blood plasma were 2.46(2.25-2.56) mmol/L,(105.68 ±7.29)mmol/L, 3.81(3.54-4.03) mmol/L, 140.45(137.08-144.20) mmol/L, 0.97(0.77-1.11) mmol/L,(60.39 ±9.40)g/L,(31.23 ±6.81)g/L, 17.4(11.95 -30.05)U/L, 20.85(14.9 -34.03) U/L, 210.1(163.15-342.60) U/L, 7.58(5.95-10.04) mmol/L, 76.35(51.05-110.7) μmol/L, 6.94(3.98-11.08) mmol/L, 1.15(0.84-1.89) mmol/L, 3.31(2.73-4.35) mmol/L, 271.55(187.78-423.30) μmol/L,(4.71 ±2.17)KU/L, 2.19(1.09 -4.19) μmol/L,respectively, and 2.24(2.05-2.35) mmol/L,(103.98 ±7.32)mmol/L, 3.84(3.58 -4.19) mmol/L, 139.30(136.08 -142.33) mmol/L, 0.99(0.78-1.14) mmol/L,(60.37 ±9.67) g/L,(32.62 ±6.89) g/L, 17.6(12.75-31.2) U/L, 20.6(15.28-36.6) U/L, 233.95(176.48-363.75) U/L, 7.55(5.62-9.52) mmol/L, 77.15 (56.08-111.98) μmol/L, 6.94(3.97 -10.53) mmol/L, 1.13(0.83 -1.93) mmol/L, 3.23(2.71-4.37) mmol/L, 273.4(187.30-401.55) μmol/L,(4.74 ±2.21) KU/L, 2.29(1.02 -4.23) μmol/L respectively in the samples of venous blood plasma .The difference of results of TP、Glu、Cr、TG、CHE、TBA between two types of samples were of no statistic significance ( the values of t or Z were 0.121,-0.054,-0.269,-0.480,-1.730 and -1.843 respectively, P>0.05), among these items the difference of Glu was of notable clinical significance (>1/2 TE percentage:50％).The difference of results of Ca , Cl, K, Na, P, ALB, ALT, AST, LDH, Urea, CHO, UA between two types of samples were of statistic significance (the values of t or Z were -7.115,6.794,-2.119,-4.996,-3.483,-8.839,-2.419,-2.742,-3.833,-5.010,-2.060 and -2.467 respectively, P<0.05), among these items the difference of Urea, CHO, UA, Na, P and ALT was of no notable clinical significance ( >total TE percentage: 0％, 2.86％, 0％, 2.9％, 4.3％, 1.43％ respectively), while the difference of Ca, Cl, K, ALB, AST and LDH was of clinical significance (>total TE percentage:90％, 10％, 14.3％, 32.9％, 10.00％, 32.9％respectively).Conclusions The differences in the detected data of some biochemical items between venous plasma and arterial plasma demonstrated clinical significance .When detecting those biochemical items , clinicians should pay attention to the selection of arterial blood sample .It should be considered to establish a reference interval for related biochemical items of arterial blood when necessary .