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Compared with conventional therapies, photoimmunotherapy offers precise targeted cancer treatment with minimal damage to healthy tissues and reduced side effects, but its efficacy may be limited by shallow light penetration and the potential for tumor resistance. Here, an acceptor-donor-acceptor (A-D-A)-structured nanoaggregate is developed with dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), triggered by single near-infrared (NIR) light. Benefiting from strong intramolecular charge transfer (ICT), the A-D-A-structured nanoaggregates exhibit broad absorption extending to the NIR region and effectively suppressed fluorescence, which enables deep penetration and efficient photothermal conversion (η = 67.94%). A suitable HOMO-LUMO distribution facilitates sufficient intersystem crossing (ISC) to convert ground-state oxygen (3O2) to singlet oxygen (1O2) and superoxide anions (·O2 -), and catalyze hydroxyl radical (·OH) generation. The enhanced ICT and ISC effects endow the A-D-A structured nanoaggregates with efficient PTT and PDT for cervical cancer, inducing efficient immunogenic cell death. In combination with clinical aluminum adjuvant gel, a novel photoimmunotherapy strategy for cervical cancer is developed and demonstrated to significantly inhibit primary and metastatic tumors in orthotopic and intraperitoneal metastasis cervical cancer animal models. The noninvasive therapy strategy offers new insights for clinical early-stage and advanced cervical cancer treatment.
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OBJECTIVE: NeoBase 2 Non-derivatized MSMS assay kit (NeoBase 2 kit) was used for newborn screening, the performance of the NeoBase 2 kit should be validated before its implementation in clinical diagnostic laboratories. METHODS: Leftover dried blood spot samples, quality control materials in the NeoBase 2 kit, and proficiency testing materials received from the NSQAP were used. Precision, accuracy, LOD, LLOQ, recovery, and stability were carried out to verify the performance of the Waters ACQUITY TQD MS/MS system with the NeoBase 2 kit for newborn screening. Cutoffs were determined and analytes requiring different cutoffs in preterm neonates were investigated. RESULTS: Within-run and between-run precisions ranged from 3.95% to 14.41%. The accuracy and stability were within 15%. All analytes demonstrated acceptable LOD, LLOQ, and recoveries. Cutoffs for term and preterm neonates were established. CONCLUSIONS: The performance of the NeoBase 2 kit is acceptable and can be implemented in clinical diagnostic laboratories.
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OBJECTIVE: This study was aimed to investigate the serotypes, antibiotic susceptibilities, and multi-locus sequence type (MLST) profiles of group B Streptococcus (GBS) in the Beijing area. METHODS: Lower vaginal and rectal swabs were obtained from pregnant women of 35-37 gestational weeks (GWs) who attended the Beijing Obstetrics and Gynecology Hospital. All GBS isolates were identified with Gram staining, catalase reaction assays, and CAMP tests, followed by antibiotic susceptibility testing, serotype identification, multilocus sequence typing and erythromycin resistance gene analysis (ermB and mefE). RESULTS: From July 2020 to June 2022, 311 (5.17%) of 6012 pregnant women that were screened for GBS colonization were detected positive. Of the eight serotypes identified (III, Ia, Ib, IV, II, VIII, V, and NT), serotypes III (43.09%), Ia (34.08%) and Ib (17.04%) were the predominant species. In the antimicrobial susceptibility experiments, the resistant rates measured for erythromycin, clindamycin, levofloxacin, and tetracycline were 76.21%, 63.99%, 50.80%, and 81.03%, respectively, and 7.6% of GBS isolates showed inducible clindamycin in resistance (D-test phenotype). Meanwhile, the multilocus sequence typing analysis showed that sequence type 19 (ST19) (30.34%) and ST10 (18.62%) were the dominant sequence types. Among the 237 erythromycin-resistant isolates, 176 harbored ermB (128, 54.00%) or mefE (48, 20.30%) gene alone. CONCLUSION: The infection rates, serotypes or MSLT distribution, and antimicrobial resistance of GBS in Beijing area were investigated, which may be applied in analyses of the epidemiological characteristics of GBS. This contributes to the basic knowledge required for successful GBS vaccine development suited for disease prevention and treatment in China, as well as the implementation of effective clinical antimicrobials.
Subject(s)
Anti-Bacterial Agents , Streptococcal Infections , Female , Humans , Pregnancy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Serogroup , Pregnant Women , Clindamycin/pharmacology , Clindamycin/therapeutic use , Streptococcal Infections/drug therapy , Streptococcal Infections/epidemiology , Multilocus Sequence Typing , Drug Resistance, Bacterial/genetics , Erythromycin/pharmacology , Streptococcus agalactiae/genetics , China/epidemiology , Microbial Sensitivity TestsABSTRACT
Objectives: In this study, we aimed to establish the trimester-specific RIs of renal function tests (RFTs) in singleton pregnant women and investigate the associations between adverse perinatal outcomes and abnormal renal function laboratory results. Methods: The results of RFTs and the associated medical records were retrieved from 16489 singleton pregnant women who underwent first- and third-trimester prenatal screening and gave a live birth at out institute between August 2018 and December 2019. The RFTs were performed on the automated immunochemistry platform ARCHITECT ci16200 (Abbott Laboratories Ltd, Abbott Park, Illinois, US) in the clinical laboratory of our institute. The nonparametric 2.5th-97.5th percentile intervals and the indirect Hoffmann methods were used to define the trimester-specific RIs. The associations between abnormal RFTs and adverse pregnancy outcomes was assessed statistically by logistic regression. Results: There was no significant difference between the direct observational and the indirect Hoffmann methods in establishing RIs of RFTs. Compared with RFTs in the first trimester, the concentrations of serum BUN and Crea were slightly decreased (p < 0.001), and the serum UA and Cys C levels were significantly elevated in the third trimester (p < 0.001). In the logistic regression analysis, high concentrations of UA, Crea, and Cys C in late pregnancy were associated with an increased risk of postpartum hemorrhage. Meanwhile, early pregnancy UA was associated with a modestly increased risk of GDM, GH, and PE. Conclusion: It is necessary to establish trimester-specific RIs for RFTs, in order to appropriately interpret laboratory results and to identify women with high risks of developing various adverse outcomes.
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BACKGROUND: As folates are essential for embryonic development and growth, it is necessary to accurately determine the levels of folates in plasma and red blood cells (RBCs) for clinical intervention. The aims of this study were to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantitation of folates in plasma and RBCs and to examine the association between plasma and RBC folate concentrations and gestational diabetes mellitus (GDM), gestational hypertension (GH) and preeclampsia (PE). METHODS: With the in-house developed LC-MS/MS, a retrospective cross-sectional study was conducted. The healthy pregnant women of first- (n = 147), second- (n = 84) and third-trimester (n = 141) or the women diagnosed with GDM (n = 84), GH (n = 58) or PE (n = 23), that were aged between 22 and 46 years old and registered at our institute, were subjected for measurement of folic acid (FA) and 5-methyltetrahydrofolate (5-MTHF), followed by appropriate statistical association analysis. RESULTS: The assay for simultaneous quantitation of FA and 5-MTHF in plasma and RBCs was linear, stable, with imprecision less than 15% and recoveries within ±10%. The lower limits of quantification for FA and 5-MTHF measurement in whole blood were 0.57 and 1.09 nmol/L, and in plasma were 0.5 and 1 nmol/L, respectively. In the association analysis, the patients with lower RBC folate level (<906 nmol/L) presented higher risks of PE development (OR 4.861 [95% CI 1.411-16.505]) by logistic regression and restricted cubic spline (RCS) regression in a nonlinear fashion. In addition, higher level of plasma folates in pregnancy was significantly associated with GH risk but may be protective for the development of GDM. CONCLUSIONS: The in-house developed LC-MS/MS method for folates and metabolites in plasma or RBC showed satisfactory analytical performance for clinical application. Further, the levels of folates and metabolites were diversely associated with GDM, GH and PE development.
Subject(s)
Pre-Eclampsia , Tandem Mass Spectrometry , Female , Humans , Pregnancy , Young Adult , Adult , Middle Aged , Chromatography, Liquid , Tandem Mass Spectrometry/methods , Retrospective Studies , Cross-Sectional Studies , Folic Acid/analysis , Erythrocytes/chemistryABSTRACT
BACKGROUND: Elevated homocysteine (Hcy) level during pregnancy is positively associated with various gestational-specific diseases. However, there is no uniform standard for the reference interval (RI) of Hcy in pregnancy. METHODS: From January 2017 to January 2019, 14,530 singleton pregnant women registered at our institute were included for the establishment of trimester-specific RIs of Hcy with both the nonparametric approach and the indirect Hoffmann method, followed by pregnancy outcome association analysis conducted with logistic regression. RESULTS: The serum Hcy level in the nonpregnant group was significantly higher than that of pregnant women. A relatively decreased Hcy concentration was observed in the second trimester when compared with that of the first or third trimester. The direct RIs of Hcy in the first or third, and second trimesters were 4.6 to 8.0 mmol/L (merged) and 4.0 to 6.4 mmol/L, respectively, which showed no significant difference compared with the RI derived from the indirect Hoffmann method. In the subsequent risk analysis, the first trimester Hcy was found to be negatively associated with GDM development; whereas the third trimester Hcy conferred increased risk of postpartum hemorrhage after delivery. CONCLUSION: Having established trimester-specific RIs, our study sheds light on the complicated roles of Hcy in pregnancy-related complications.
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We present a case of a 76-year-old patient with recurrent cervical cancer who underwent first-line treatment with penpulimab combined with anlotinib. The patient was diagnosed with poorly differentiated stage III C1r cervical squamous cell carcinoma and received standard cisplatin-sensitized chemoradiotherapy, subsequently achieving a good treatment effect of complete response. Recurrence occurred nearly 14 months after treatment, with multiple metastases including in the brain and lung. Oral anlotinib was less effective, but the treatment of penpulimab combined with anlotinib showed an obvious curative effect. It has been maintained for more than 17 months, and as of April 2023 the patient is still maintaining her response. Our case suggests that penpulimab combined with anlotinib has promising efficacy in the treatment of elderly patients with recurrent cervical cancer.
A 76-year-old female patient was diagnosed with cervical cancer. She received a type of treatment called chemoradiotherapy, which helped her get better. However, after 14 months of treatment, the cancer came back and spread to other parts of the body including the brain and lungs. She was given a medicine called anlotinib, which did not work very well. Then she received two medications at the same time, penpulimab and anlotinib, which worked better. Her cancer went away completely and has stayed this way for 17 months. This case shows that the combination of penpulimab and anlotinib can help treat older people with cervical cancer that comes back.
Subject(s)
Quinolines , Uterine Cervical Neoplasms , Humans , Female , Aged , Uterine Cervical Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Indoles/therapeutic use , Quinolines/therapeutic useABSTRACT
BACKGROUND: The purpose of this study was to evaluate the effect of single-incision plus one port laparoscopic surgery (SILS + 1) for myomectomy. METHODS: We retrospectively analyzed data from patients who underwent laparoendoscopic single-site myomectomy (LESS-M group, n = 40) and SILS + 1 (SILS + 1-M group, n = 40) for myomectomy at our hospital from October 2018 through December 2020. The patients' baseline demographic information and clinical data were compared between the two groups. RESULTS: The results showed that no significant difference in basic characteristics or between the number, size, and location of uterine myomas between the two groups (p < 0.05). However, the surgery was more difficult and the total operating time was significantly longer in the LESS-M group compared to the SILS + 1-M group (83.5 ± 14.2 vs. 108.2 ± 18.1 min, p = 0.001). Moreover, the estimated intraoperative blood loss (113.4 ± 46.5 vs. 211.4 ± 60.3 ml, p = 0.001) and changes in hemoglobin level (13.1 ± 7.6 vs. 18.2 ± 6.0, p = 0.001) were significantly lower in the SILS + 1-M group compared to the LESS-M group. In addition, no serious intraoperative or postoperative complications occurred after surgery in either group. The clinical outcomes in the SILS + 1-M group were associated with a significant reduction in total surgical time compared to the LESS-M group (p < 0.05). CONCLUSION: SILS + 1 for myomectomy is popular in clinics, with a satisfactory clinical effect.
Subject(s)
Laparoscopy , Surgical Wound , Uterine Myomectomy , Uterine Neoplasms , Female , Humans , Uterine Myomectomy/adverse effects , Retrospective Studies , Uterine Neoplasms/surgery , Treatment Outcome , Laparoscopy/adverse effects , Laparoscopy/methods , Surgical Wound/surgery , Operative TimeABSTRACT
OBJECTIVES: Physiological changes during pregnancy can affect the results of renal function tests (RFTs). In this population-based cohort study, we aimed to establish trimester-specific reference intervals (RIs) of RFTs in singleton and twin pregnancies and systematically investigate the relationship between RFTs and adverse pregnancy outcomes. METHODS: The laboratory results of the first- and third-trimester RFTs, including blood urea nitrogen (BUN), serum uric acid (UA), creatinine (Crea) and cystatin C (Cys C), and the relevant medical records, were retrieved from 29,328 singleton and 840 twin pregnant women who underwent antenatal examinations from November 20, 2017 to January 31, 2021. The trimester-specific RIs of RFTs were estimated with both of the direct observational and the indirect Hoffmann methods. The associations between RTFs and pregnancy complications as well as perinatal outcomes were assessed by logistic regression analysis. RESULTS: Maternal RFTs showed no significant difference between the direct RIs established with healthy pregnant women and the calculated RIs derived from the Hoffmann method. In addition, elevated levels of RFTs were associated with increased risks of developing various pregnancy complications and adverse perinatal outcomes. Notably, elevated third-trimester RFTs posed strong risks of preterm birth (PTB) and fetal growth restriction (FGR). CONCLUSIONS: We established the trimester-specific RIs of RFTs in both singleton and twin pregnancies. Our risk analysis findings underscored the importance of RFTs in identifying women at high risks of developing adverse complications or outcomes during pregnancy.
Subject(s)
Pregnancy Complications , Premature Birth , Pregnancy , Female , Infant, Newborn , Humans , Cohort Studies , Uric Acid , Pregnancy Complications/diagnosis , Kidney/physiologyABSTRACT
BACKGROUND: During pregnancy, complex physiological changes take place in the hemostatic system, resulting in a hypercoagulable state. With the established trimester-specific reference intervals (RIs) of the coagulation tests, we investigated the associations between disturbance of hemostasis and adverse pregnant outcomes in a population-based cohort study. METHODS: The first- and third-trimester coagulation tests results were retrieved from 29,328 singleton and 840 twin pregnant women for regular antenatal check-ups from November 30th, 2017 to January 31st, 2021. The trimester-specific RIs for fibrinogen (FIB), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), d-dimer (DD) were estimated using both the direct observational and the indirect Hoffmann methods. The associations between the coagulation tests and the risks of developing pregnancy complications as well as adverse perinatal outcomes were assessed using the logistic regression analysis. RESULTS: Increased FIB, DD and decreased PT, APTT and TT were observed as the gestational age increases in the singleton pregnancy. An enhanced procoagulant state, marked by significant elevation of FIB, DD and reduction of PT, APTT and TT, was observed in the twin pregnancy. The subjects with anormal PT, APTT, TT, DD, tend to have increased risks of developing peri- and postpartum complications such as preterm birth, fetal growth restriction. CONCLUSIONS: The incidence of adverse perinatal outcomes was remarkably associated with the maternal increased levels of FIB, PT, TT, APTT and DD in the third trimester, which may be applied in early identification of women at high risk of adverse outcomes due to coagulopathy.
Subject(s)
Hemostatics , Pregnancy Complications , Premature Birth , Female , Infant, Newborn , Pregnancy , Humans , Pregnancy, Twin , Cohort Studies , Blood Coagulation Tests , FibrinogenABSTRACT
OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance of the following hemostatic markers in hypertensive disorder of pregnancy (HDP): tissue-type plasminogen activator and inhibitor-1 complex (tPAI-C), thrombomodulin, thrombin-antithrombin complex, plasmin inhibitor-plasmin complex, D-dimer, and fibrinogen degradation products. METHODS: A total of 311 individuals diagnosed with HDP and 187 healthy controls (HC) of matched gestational age were admitted, including 175 subjects with gestational hypertension, 94 with mild preeclampsia, and 42 with severe preeclampsia. RESULTS: Compared with those of the HC group, the plasma concentrations of all the hemostatic markers continuously increased with the clinical severity of the hypertensive disorder, regardless of their statistical significance. In the receiver operating characteristic analysis, tPAI-C displayed the best discrimination performance. CONCLUSION: The tPAI-C level was consistently and significantly elevated across the different HDP groups when compared with the HC group, suggesting aggravated fibrinolysis disorder increasing with the severity of the HDP.
Subject(s)
Hemostatics , Hypertension , Pre-Eclampsia , Pregnancy , Female , Humans , Fibrinolysis , Hemostatics/pharmacology , Retrospective Studies , Case-Control Studies , Fibrin Fibrinogen Degradation Products/metabolism , Fibrin Fibrinogen Degradation Products/pharmacologyABSTRACT
Background: Reliable biomarkers are needed to improve preeclampsia (PE) prediction accuracy. With the investigational tool of peptidomics, we aimed to identify and validate potential serum peptide biomarkers in cohorts suspected for PE development in middle or late pregnancy. Methods: Totally 195 serum samples were prospectively collected from pregnant women with PE-related syndromes who were followed up for PE development until delivery. Serum peptidomic analysis was performed in the discovery cohort of 115 samples using matrix-assisted laser desorption ionization-time of flight coupled with Linear Trap Quadropole Orbitrap mass spectrometry. The candidate biomarkers were further validated using an in-house developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method in an independent validation cohort of 80 serum samples. Results: We identified 8 peptides that were differentially expressed and originated from fibrinogen alpha chain (FGA), inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and complement component 3. In the subsequent LC-MS/MS quantitation analysis, the levels of the three peptides (FGA-1033.4, ITIH4-2026.9, ITIH4-2051.1) exhibited a significant difference between the PE-positive and PE-negative groups. Further, the three-peptide panel yielded an area under the ROC curve (AUC) of 0.985 [95% confidence interval (CI) 0.965-1.000] and 0.923 (95% CI 0.845-1.000) in the discovery and validation cohorts respectively, with negative predictive values of 98.1-98.8% and positive predictive values of 73.1-85.3% that were much improved when compared with that of soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio. Conclusions: We have discovered and validated a novel three-peptide biomarker panel predictive for the occurrence PE in pregnant women.
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Objective: The incidence of cervical cancer is increasing year by year, which seriously threatens the health of female patients. This study is aimed at investigating the association of sentinel lymph node biopsy (SLNB) with clinicopathological features in cervical cancer patients. Methods: Patients diagnosed with cervical cancer in our hospital from February 1, 2019, to June 30, 2021, were selected as the research subjects. Statistical analysis was performed on the SLN examination of patients with cervical cancer with different pathological characteristics and the correlation between the positive rate of SLN detection and the pathological characteristics of cervical cancer. Results: A total of 59 patients with cervical cancer were included in this study, the SLNB detection rate was 94.92%, 15 patients had lymph node metastasis, and the metastasis rate was 25.42% confirmed by histopathology. Thirteen of them had SLN metastases, and the other 2 had non-SLN metastases. The sensitivity of SLNB was 86.67%, and the false negative rate was 13.33%. Statistical analysis results showed that there was no significant difference in the positive rate of SLN among cervical cancer patients with different FIGO stages, pathological types, degree of differentiation, depth of invasion, and tumor size. In addition, the results of Pearson's correlation analysis showed that the positive rate of SLN was not significantly correlated with the FIGO stage, pathological type, degree of differentiation, depth of invasion, and tumor size of cervical cancer. Conclusion: SLNB has a high sensitivity, safety, and feasibility in the diagnosis and evaluation of lymph node metastasis in cervical cancer. There is no significant correlation between SLNB and the clinicopathological features of cervical cancer.
Subject(s)
Sentinel Lymph Node Biopsy , Uterine Cervical Neoplasms , Female , Humans , Lymphatic Metastasis , Sentinel Lymph Node Biopsy/methods , Uterine Cervical Neoplasms/pathologyABSTRACT
Background: The role of excess androgen in ovarian reserve remains unclear in patients with polycystic ovary syndrome (PCOS). Our study highlights the associations of serum androgen levels and ovarian reserve markers in PCOS and non-PCOS women. Methods: Totally 584 menstrual abnormalities women of 20-45 years were retrospectively evaluated at the Beijing Obstetrics and Gynecology Hospital between January 2021 to October 2021. The enrolled patients were classified into two groups: the PCOS group (n=288) and the non-PCOS group (n=296) based on the Rotterdam consensus for PCOS diagnosis. The serum androgens, including testosterone (T), free testosterone (FT, calculated), bioavailable testosterone (Bio-T, calculated), androstenedione (A2), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS) were assessed with an in-house developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The associations between the serum androgens and the hormone markers commonly used for evaluating ovarian reserve function, such as anti-mullerian hormone (AMH) and the ratio of luteinizing hormone (LH)/follicle stimulating hormone (FSH) were explored. Results: The serum T, FT, Bio-T, A2, DHT, DHEA, DHEAS, AMH and LH/FSH of the PCOS group were 51.7 ± 23.2 ng/dL/mL, 8.5 ± 5.0 pg/mL, 210.1 ± 127.7 pg/mL, 1.9 ± 0.8 ng/mL, 0.2 ± 0.1 ng/mL, 6.4 ± 4.2 ng/mL, 2431.0 ± 1030.7 ng/mL, 6.7 ± 3.8 ng/mL, and 1.8 ± 1.4 respectively, which were significantly higher than those in the non-PCOS group (p<0.05). In the group of PCOS patients, T and A2 levels were positively associated with AMH in both multivariate linear regression analysis and Pearson's correlation analysis. Similar but weaker associations were observed in the non-PCOS patients. In the PCOS patients with hyperandrogenemia (HA), the AMH level was significantly higher in the subjects with T increased than in the subjects with non-T androgen(s) increased (A2, DHT, DHEA or DHEAS). Conclusions: The serum androgen levels are positively associated with ovarian reserve markers in both of the PCOS and the non-PCOS patients in our study. In the PCOS group, the highest AMH level was observed in the subjects with the T elevation subgroup, suggesting that T is more closely related with the increase of AMH when compared with other androgens investigated.
Subject(s)
Ovarian Reserve , Polycystic Ovary Syndrome , Androgens , Anti-Mullerian Hormone , Biomarkers , Chromatography, Liquid , Dehydroepiandrosterone , Female , Follicle Stimulating Hormone , Humans , Luteinizing Hormone , Pregnancy , Retrospective Studies , Tandem Mass Spectrometry , TestosteroneABSTRACT
BACKGROUND: Prediction of delivery is important for assessing due dates, providing adequate prenatal care, and suggesting appropriate interventions in preterm and post-term pregnancies. Recent metabolomic findings suggested that the temporal abundance information of metabolome can be used to predict delivery timing with high accuracy in a cohort of healthy women. However, a targeted and quantitative assay is required to further validate the clinical performance and utility of this group of metabolomic candidates in delivery prediction with a larger and independent cohort. METHOD: LC-MS/MS quantitative assays were applied to determine the plasma concentrations of four steroid metabolites, including oestriol-16-glucuronide (E3-16-Gluc), 17-alpha-hydroxyprogesterone (17-OHP), tetrahydrodeoxycorticosterone (THDOC), and androstane-3,17-diol (A-3,17-Diol) in asymptomatic women of singleton pregnancies (≥30th gestational weeks). Subsequent statistical analysis was conducted to assess the performance of the above candidates in delivery prediction. RESULT: Using LC-MS/MS, four steroids were separated and quantified in 5.5 min. The coefficients of variation (CVs) of the four analytes at the lower limit of quantification ranged from 7.9% to 14.6%, with the R2 values greater than 0.990 in the calibration curves. Of the 585 recruited pregnant women who ended up with spontaneous delivery, 17.1% and 82.9% of the subjects delivered within and after 7 days since plasma collection, respectively. In the receiver operator curve analysis, the gestational age-adjusted area under the curve of the combined measurements of E3-16-Gluc and 17-OHP was 0.69 (95% CI: 0.60-0.76), with the sensitivity of 87.0% (95% CI: 78.8%-92.9%) and specificity of 60.2% (95% CI: 55.7%-64.6%). Moreover, the positive and the negative predictive values were 28.3%-34.0% and 93.1%-97.4% respectively for this combined panel. CONCLUSION: We performed analytical and clinical validation of a quantitation LC-MS/MS panel for the four steroids in the plasma of pregnant women. The steroid metabolites panel of E3-16-Gluc and 17-OHP was potentially useful for predicting delivery within one week in asymptomatic women of singleton pregnancies. Key messagesA quantitative LC-MS/MS assay for determining the plasma levels of 17-OHP, THDOC, A-3,17-Diol and E3-16-Gluc was developed and validated, in order to evaluate their predictive performance in asymptomatic delivery of singleton pregnancy. The levels of E3-16-Gluc and 17-OHP were found to be significantly elevated at the time of sampling in women that delivered within one week and their combinational testing may be potentially useful in delivery prediction.
Subject(s)
Pregnant Women , Tandem Mass Spectrometry , Chromatography, Liquid/methods , Female , Gestational Age , Humans , Infant, Newborn , Pregnancy , Steroids , Tandem Mass Spectrometry/methodsABSTRACT
BACKGROUND: Herlyn-Werner-Wunderlich (HWW) syndrome is a rare congenital Mullerian duct anomaly disease that is characterized by a triad of symptoms, didelphys uterus, blind hemivagina, and ipsilateral renal agenesis. Herein, we reported a case from China. CASE PRESENTATION: An 11-year-old patient presented to our hospital with lower abdominal pain and frequent urination. Computed tomography and magnetic resonance imaging revealed hematocolpos, uterine hemorrhage, didelphys uterus, and renal agenesis on the right side. Thus, the patient was diagnosed with HWW syndrome. Laparoscopic combined with transvaginal surgery to remove the vaginal septum, the symptoms of the lesion disappeared after the blood was discharged. CONCLUSION: Abnormal urination and other symptoms should be carefully examined in adolescent girls with abdominal pain not menarche, since they may be related to reproductive organ development disorders and other diseases. We recommend laparoscopy combined with transvaginal surgery to remove the oblique septum in HWW syndrome, which is rarely reported.
Subject(s)
Abnormalities, Multiple , Laparoscopy , Urogenital Abnormalities , Female , Adolescent , Humans , Child , Vagina/surgery , Vagina/abnormalities , Uterus/diagnostic imaging , Uterus/surgery , Uterus/abnormalities , Kidney/abnormalities , Urogenital Abnormalities/diagnostic imaging , Urogenital Abnormalities/surgery , Urogenital Abnormalities/complications , Abnormalities, Multiple/surgery , Laparoscopy/adverse effects , Abdominal Pain/etiologyABSTRACT
Background: Phenylalanine-restricted diets have been the basis of therapy for phenylketonuria; however, little is known how this treatment effects homeostasis of other amino acids. This study aimed to assess blood amino acid alterations in phenylketonuric neonates before and after treatment to identify any residual amino acid alterations with phenylalanine restriction in these treated children. Methods: Concentrations of 11 amino acids were measured using liquid chromatography-tandem mass spectrometry performed on dried blood spots. Results: Elevated blood phenylalanine, arginine, citrulline, valine, methionine concentrations and decreased tyrosine, proline concentrations were observed in phenylketonuria neonates relative to controls, of which phenylalanine, arginine, methionine, tyrosine, and proline levels could be either partially or completely restored with dietary intervention, whereas citrulline and valine were not restored and remained higher. Conclusions: Blood amino acid homeostasis is disrupted in phenylketonuria. Although dietary intervention adjusts amino acid homeostasis in the direction of a healthy equilibrium, complete restoration is not achieved.
Subject(s)
Phenylalanine , Phenylketonurias , Arginine , Benchmarking , Child , Child, Preschool , Citrulline , Diet , Humans , Infant, Newborn , Methionine , Phenylketonurias/metabolism , Proline , Tyrosine , ValineABSTRACT
BACKGROUND: Lysophosphatidylcholine (LPC) plays pivotal roles in several physiological processes and their disturbances are closely associated with various disorders. In this study, we described the development and validation of a reliable and simple flow injection analysis-tandem mass spectrometry (FIA-MS/MS)-based method using dried blood spots (DBS) for quantification of four individual LPC (C20:0, C22:0, C24:0, and C26:0). METHODS: Lysophosphatidylcholines were extracted from 3.2 mm DBS with 85% methanol containing 60 ng/ml internal standard using a rapid (30 min) and simple procedure. The analytes and the internal standard were directly measured by triple quadrupole tandem mass spectrometry in multiple reactions monitoring mode via positive electrospray ionization. RESULTS: Method validation results showed good linearity ranging from 50 to 2000 ng/ml for each LPC. Intra- and inter-day precision and accuracy were within the acceptable limits at four quality control levels. Recovery was from 70.5% to 107.0%, and all analytes in DBS were stable under assay conditions (24 h at room temperature and 72 h in autosampler). The validated method was successfully applied to assessment of C20:0-C26:0LPCs in 1900 Chinese neonates. C26:0-LPC levels in this study were consistent with previously published values. CONCLUSION: We propose a simple FIA-MS/MS method for analyzing C20:0-C26:0LPCs in DBS, which can be used for first-tier screening.
Subject(s)
Dried Blood Spot Testing/methods , Flow Injection Analysis/methods , Lysophosphatidylcholines/blood , Neonatal Screening/methods , Tandem Mass Spectrometry/methods , Humans , Infant, Newborn , Linear Models , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
BACKGROUND: Disturbances in maternal lipid metabolism may increase the risk of developing pregnancy complications and adverse perinatal outcomes. However, there is no consensus as to what constitutes normal serum lipid ranges during pregnancy. Our study was aimed to establish trimester-specific serum lipid reference intervals (RIs) and investigate the associations between maternal dyslipidaemia and adverse outcomes in a population-based study. METHODS: The first- and third-trimester lipid profiles were derived from 16,489 singlet pregnant women for regular antenatal check-ups between 2017 and 2019. The serum samples were assayed for total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) in the institutional clinical laboratory. The trimester-specific lipid RIs were estimated with both of the direct observational and the indirect Hoffmann methods. The associations between maternal lipid profiling and pregnancy complications and perinatal outcomes were assessed statistically. RESULTS: Serum levels of TC, TG, LDL-C and HDL-C were all increased significantly in the third trimester of pregnancy. There was no significant difference between the observed RIs established with healthy pregnant women and the calculated RIs derived from the Hoffmann method. A trend towards increased risks of gestational complications and adverse perinatal outcomes was observed in the subjects with elevated levels of TC, TG, and LDL-C or decreased level of HDL-C. CONCLUSIONS: In pregnancy, increased serum levels of TC, TG and LDL-C, and a decreased level of HDL-C posed higher risks of developing pregnancy complications and adverse perinatal outcomes.Key messagesIt is necessary to establish trimester-specific reference intervals for serum lipids including TC, TG, LDL-C and HDL-C that were found significantly increased as the gestational age went up. More importantly, around the upper reference limits of TC, TG and LDL-C (or the lower reference limit of HDL-C), the higher the serum lipid levels were (or the lower the HDL-C level was), the higher risks of developing pregnancy complications and adverse perinatal outcomes were observed.
Subject(s)
Lipids/blood , Pregnancy Complications/epidemiology , Pregnancy Trimesters/blood , Pregnancy/blood , Adult , Child, Preschool , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL , Female , Gestational Age , Humans , Laboratories, Clinical , Pregnancy Complications/blood , Prospective Studies , Reference Values , Triglycerides/bloodABSTRACT
BACKGROUND: Preeclampsia (PE) prediction has been shown to improve the maternal and fetal outcomes in pregnancy. We aimed to evaluate the PE prediction values of a series of serum biomarkers. METHODS: The singleton pregnant women (20-36 gestational weeks) with PE-related clinical and/or laboratory presentations were recruited and had the blood drawn at their first visits. The following markers were tested with the collected serum samples: soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), thrombomodulin (TM), tissue plasminogen activator inhibitor complex (tPAI-C), complement factors C1q, B, H, glycosylated fibronectin (GlyFn), pregnancy-associated plasma protein-A2 (PAPP-A2), blood urea nitrogen (BUN), creatinine (Cre), uric acid (UA), and cystatin C (Cysc). RESULTS: Of the 196 recruited subjects, 25% (n = 49) developed preeclampsia before delivery, and 75% remained preeclampsia negative (n = 147). The serum levels of sFlt-1, BUN, Cre, UA, Cysc, and PAPP-A2 were significantly elevated, and the PlGF level was significantly decreased in the preeclampsia-positive patients. In the receiver operating characteristics (ROC) analyses, the area under the curves were listed in the order of decreasing values: 0.73 (UA), 0.67 (sFlt-1/PlGF), 0.66 (Cysc), 0.65 (GlyFn/PlGF), 0.64 (PAPP-A2/PlGF), 0.63 (BUN), 0.63 (Cre), and 0.60 (PAPP-A2). The positive predictive values of these serum markers were between 33.1% and 58.5%, and the negative predictive values were between 80.9% and 89.5%. CONCLUSIONS: The serum markers investigated in current study showed better performance in ruling out than ruling in PE. Absence of pre-defined latency period between blood draw and the onset of PE limits the clinical utility of these markers.