Sjögren's syndrome and Parkinson's Disease: A bidirectional two-sample Mendelian randomization study.

BACKGROUND: Previous observational studies have reported an association between Sjögren's syndrome (SS) and an increased risk of Parkinson's Disease (PD). However, the causal relationship between these conditions remains unclear. The objective of this study was to investigate the causal impact of SS on the risk of developing PD, utilizing the Mendelian randomization (MR) approach. METHODS: We conducted a bidirectional MR analysis using publicly available genome-wide association studies (GWAS) data. The primary analysis utilized the inverse-variance weighted (IVW) method. Complementary methods, such as MR-Egger regression, weighted mode, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO), were utilized to identify and correct for the presence of horizontal pleiotropy. RESULTS: The IVW MR analysis revealed no significant association between SS and PD (IVW: OR = 1.00, 95% CI = 0.94-1.07, P = 0.95). Likewise, the reverse MR analysis did not identify any significant causal relationship between PD and SS (IVW: OR = 0.98, 95% CI = 0.85-1.12, P = 0.73). The results from MR-Egger regression, weighted median, and weighted mode approaches were consistent with the IVW method. Sensitivity analyses suggested that horizontal pleiotropy is unlikely to introduce bias to the causal estimates. CONCLUSION: This study does not provide evidence to support the assertion that SS has a conclusive impact on the risk of PD, which contradicts numerous existing observational reports. Further investigation is necessary to determine the possible mechanisms behind the associations observed in these observational studies.

Diradical-Based Strategy in Designing Narrowband Thermally Activated Delayed Fluorescence Molecules with Tunable Emission Wavelengths.

In the design of thermally activated delayed fluorescence (TADF) materials, narrow-band emission is of particular importance for the development of organic light-emitting diodes (OLEDs). In this work, we proposed a new strategy for designing TADF molecules utilizing degenerate nonbonding (NB) orbitals of diradical parent molecules, and these designed molecules are termed NB-TADF molecules. Based on this strategy, a series of NB-TADF molecules is finely designed and systematically studied by theoretical calculations. Taking advantage of the nonbonding properties, these NB-TADF molecules exhibit desirable narrowband emissions and high quantum yields. More importantly, the emission bands can be easily tuned from blue to near-infrared by changing the conjugate length of the parent group in the NB-TADF molecules. We hope that this new strategy can open a new door for the design of novel TADF materials.

The value of lung ultrasound score in neonatal respiratory distress syndrome: a prospective diagnostic cohort study.

Rationale: The accurate diagnosis of critically ill patients with respiratory failure can be achieved through lung ultrasound (LUS) score. Considering its characteristics, it is speculated that this technique might also be useful for patients with neonatal respiratory distress syndrome (NRDS). Thus, there is a need for precise imaging tools to monitor such patients. Objectives: This double-blind randomized cohort study aims to investigate the impact of LUS and related scores on the severity of NRDS patients. Methods: This study was conducted as a prospective double-blind randomized study. Bivariate correlation analysis was conducted to investigate the relationship between LUS score and Oxygenation Index (OI), Respiratory Index (RI), and Sequential Organ Failure Assessment (SOFA) score. Spearman's correlation coefficient was used to generate correlation heat maps, elucidating the associations between LUS and respective parameters in different cohorts. Receiver Operating Characteristic (ROC) curves were employed to calculate the predictive values, sensitivity, and specificity of different scores in determining the severity of NRDS. Results: This study ultimately included 134 patients admitted to the intensive care unit (ICU) between December 2020 and June 2022. Among these patients, 72 were included in the NRDS cohort, while 62 were included in the Non-NRDS (N-NRDS) cohort. There were significant differences in the mean LUS scores between NRDS and N-NRDS patients (p < 0.01). The LUS score was significantly negatively correlated with the OI (p < 0.01), while it was significantly positively correlated with the RI and SOFA scores (p < 0.01). The correlation heatmap revealed the highest positive correlation coefficient between LUS and RI (0.82), while the highest negative correlation coefficient was observed between LUS and OI (-0.8). ROC curves for different scores demonstrated that LUS score had the highest area under the curve (0.91, 95% CI: 0.84-0.98) in predicting the severity of patients' conditions. The combination of LUS and other scores can more accurately predict the severity of NRDS patients, with the highest AUC value of 0.93, significantly higher than using a single indicator alone (p < 0.01). Conclusion: Our double-blind randomized cohort study demonstrates that LUS, RI, OI, and SOFA scores can effectively monitor the lung ventilation and function in NRDS. Moreover, these parameters and their combination have significant predictive value in evaluating the severity and prognosis of NRDS patients. Therefore, these results provide crucial insights for future research endeavors.

Comparison of ultrasonic shear wave elastography, AngioPLUS planewave ultrasensitive imaging, and optimized high-resolution magnetic resonance imaging in evaluating carotid plaque stability.

Objective: This study aimed to compare the efficiency of evaluating carotid plaque stability using ultrasonic shear wave elastography (SWE), AngioPLUS planewave ultrasensitive imaging (AP), and optimized high-resolution magnetic resonance imaging (MRI). Methods: A total of 100 patients who underwent carotid endarterectomy at our hospital from October 2019 to August 2022 were enrolled. Based on the final clinical diagnosis, these patients were divided into vulnerable (n = 62) and stable (n = 38) plaque groups. All patients were examined using ultrasound SWE, AP, and optimized high-resolution MRI before surgery. The clinical data and ultrasound characteristics of patients of the two groups were compared. Considering the final clinical diagnosis as the gold standard, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of SWE, AP, high-resolution MRI, and the final clinical diagnosis of vulnerable plaque were calculated. Pearson's correlation test was used to analyze the correlations of AP, SWE, and MRI results with the grading results of carotid artery stenosis. Results: Statistically significant differences were noticed in terms of the history of smoking and coronary heart disease, plaque thickness, surface rules, calcified nodules, low echo area, and the degree of carotid artery stenosis between the two groups (P < 0.05). Considering the final clinical diagnosis as the gold standard, the sensitivity, specificity, PPV, and NPV of SWE-based detection of carotid artery vulnerability were 87.10% (54/62), 76.32% (29/38), 85.71% (54/63) and 78.38% (29/37), respectively, showing a general consistency with the final clinical results (Kappa = 0.637, P < 0.05). Considering the final clinical diagnosis as the gold standard, the sensitivity, specificity, PPV and NPV of AP-based detection of carotid artery vulnerability were 93.55% (58/62), 84.21% (32/38), 90.63% (58/64), and 88.89% (32/36), respectively, which agreed with the final clinical detection results (Kappa = 0.786, P < 0.05). Considering the final clinical diagnosis as the gold standard, the sensitivity, specificity, PPV and NPV of high-resolution MRI-based detection of carotid artery vulnerability were 88.71% (55/62), 78.95% (30/38), 87.30% (55/63), and 81.08% (30/37), respectively, showing consistency with the final clinical results (Kappa = 0.680, P < 0.05). AP, SWE, and MRI results were positively correlated with the results of carotid artery stenosis grading (P < 0.05). Conclusion: AP technology is a non-invasive, inexpensive, and highly sensitive method to evaluate the stability of carotid artery plaques. This method can dynamically display the flow of blood in new vessels of plaque in real time and provide a reference for clinical diagnosis and treatment.

Controlling the repair mechanisms of oxetanes through functional group substitution.

Intersystem crossing (ISC) plays a key role in the photolysis processes of oxetanes formed by benzophenone (BP)-like and thymine structures. In this work, we systematically explored the photophysical processes of oxetanes and ring-splitting products and investigated the effect of substituents on the repair mechanisms of oxetanes. The regioselectivity of oxetanes (head-to-head, HH and head-to-tail, HT) and the electron-donating and electron-withdrawing substituents, including CH3, OCH3 and NO2, were considered. It was found that the substituents influence the ISC rates of these compounds more by changing their spin-orbit coupling (SOC) coefficients rather than energy gaps. The SOC coefficients of HH-oxetanes are more affected by these groups than HT-oxetanes and products, and they have greater ISC rates on the whole. Besides, the insertion of substituents can alter the radiative and nonradiative decay rates, thereby transforming the photoinduced cycloreversion mechanisms of oxetanes. The ring-splitting reactions of non-substituted oxetanes could occur via two pathways of singlet and triplet manifolds. Furthermore, oxetanes with NO2 at the X site have the largest ISC rates but hardly undergo repair processes, while the introduction of electron-donating substituents can effectively promote the repair of oxetanes. The singlet ring-splitting reactions of HH-oxetanes are more inclined to occur after introducing CH3 and OCH3 at two sites. However, HT-oxeatnes with CH3 are more likely to undergo triplet repair processes and OCH3-substituted structures tend to originate cycloreversion in the singlet manifolds. Moreover, the introduction of CH3 and OCH3 at the Y site rather than the X site can more significantly accelerate the repair processes of HH-oxetanes. Contrarily, HT-oxetanes with electron-donating groups at the X site exhibit faster repair rates than those at the Y site. We hope this work can provide valuable insights into BP-like drugs and photosensitive DNA repair.

Delineating the twin role of autophagy in lung cancer.

Autophagy represents an intracellular defense mechanism equipped within each eukaryotic cells to enable them to cope with variety of physical, chemical, and biological stresses. This mechanism helps to restore the homeostasis and preserve the cellular integrity and function of the cells. In these conditions, such as hypoxia, nutrient deprivation, inhibition of protein synthesis or microbial attack, the process of autophagy is upregulated to maintain cellular homeostasis. The role of autophagy in cancer is an intriguing topic which needs further exploration. This process of autophagy has been many times referred as a double-edged sword in the process of tumorigenesis. In the initial stages, it may act as a tumor suppressor and enable to quench the damaged organelles and harmful molecules generated. In more advanced stages, autophagy has been shown to act as a tumor-promoting system as it may help the cancer cells to cope better with stressful microenvironments. Besides this, autophagy has been associated with development of resistance to anticancer drugs as well as promoting the immune evasion in cancer cells, representing a serious obstacle in cancer treatment and its outcome. Also, autophagy is associated with hallmarks of cancer that may lead to activation of invasion and metastasis. The information on this twin role needs further exploration and deeper understanding of the pathways involved. In this review, we discuss the various aspects of autophagy during tumor development, from early to late stages of tumor growth. Both the protective role of autophagy in preventing tumor growth and the underlying mechanisms adopted with evidence from past studies have been detailed. Further, the role of autophagy in conferring resistance to distinct lung cancer treatment and immune shielding properties has also been discussed. This is essential for further improving on treatment outcome and success rates.

The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study.

Objective: Osteoarthritis (OA) is the most prevalent joint disease globally, serving as a primary cause of pain and disability. However, the pathological processes underlying OA remain incompletely understood. Several studies have noted an association between cytokines and OA, yet the causal link between them remains ambiguous. This study aims to identify cytokines potentially causally related to OA using Mendelian randomization (MR) analysis, informing early clinical diagnosis and treatment decisions. Methods: We conducted a genome-wide association study (GWAS) on 12 OA traits involving 177,517 cases and 649,173 controls from 9 international cohorts. For discovery MR analysis, we used 103 cytokines from two European populations as instrumental variables (IVs). Concurrently, another European population OA GWAS database (36,185 cases and 135,185 controls) was used to replicate MR analysis, employing the inverse variance weighted (IVW) method as the primary analytic approach. Additional methods tested included MR Egger, Weighted median, and Weighted mode. We merged the MR findings through meta-analysis. Heterogeneity testing, level pleiotropy testing (MR Egger intercept test and MRPRESSO), and sensitivity analysis via Leave One Out (LOO) were conducted to verify result robustness. Lastly, reverse MR analysis was performed. Results: The meta-analysis merger revealed a correlation between CX3CL1 cycle levels and increased OA risk (OR=1.070, 95% CI: 1.040-1.110; P<0.010). We also observed associations between MCP4 (OR=0.930, 95% CI: 0.890-0.970; P<0.010) and CCL25 (OR=0.930, 95% CI: 0.890-0.970; P<0.010) with reduced OA risk. The sensitivity analysis results corroborate the robustness of these findings. Conclusion: Our MR analysis indicates a potential causal relationship between CX3CL1, MCP4, CCL25, and OA risk changes. Further research is warranted to explore the influence of cytokines on OA development.

Ratiometric SERS quantitative analysis of tyrosinase activity based on gold-gold hybrid nanoparticles with Prussian blue as an internal standard.

Tyrosinase (TYR) is a polyphenol oxidase that regulates melanin biosynthesis. Abnormal levels of TYR have been confirmed closely associated with melanoma cancer and other diseases, making the establishment of highly sensitive and accurate quantitative detection of TYR is thus essential for fundamental research and clinical applications. Herein, we proposed a new strategy that combines surface-enhanced Raman scattering (SERS) with Dopamine (DA) and Prussian blue (PB) functionalized gold-gold hybrid nanoparticles for TYR detection. DA is oxidized to dopaquinone with the presence of TYR, leading to the consumption of DA in the reaction solution and the corresponding decrease in DA characteristic peak intensity at 1480 cm-1. Our SERS quantitative assay of TYR with "on-off" sensing strategy yields an excellent limit of detection (LOD) of 3 × 10-3 U mL-1 in a linear range of 10-3 to 100 U mL-1. In particular, the intensity ratio of 1480 cm-1 to 2121 cm-1 allows us to achieve remarkably reliable quantitative detection of TYR, with the 2121 cm-1 peak intensity of the standard internal (IS) molecule PB being used to correct SERS signal fluctuations. Furthermore, our proposed assay has been successfully demonstrated to quantify TYR spiked in human serum samples, with excellent percentage recovery of 90.0-110.6 %. The potential of our ratiometric SERS strategy for the performance evaluation of TYR inhibitors has also been verified. Our work is therefore expected to provide a new route for accurate and reliable monitoring of TYR activity in the complex biological environment.

De novo balanced reciprocal translocation mosaic t(1;3)(q42;q25) detected by prenatal genetic diagnosis: a fetus conceived using preimplantation genetic testing due to a t(12;14)(q22;q13) balanced paternal reciprocal translocation.

INTRODUCTION: De novo balanced reciprocal translocations mosaicism in fetus conceived using preimplantation genetic testing from a different balanced translocation carrier parent has been rarely reported. METHODS: Chromosomal microarray analysis, karyotype analysis and fluorescent in situ hybridization were performed to verify the type and heredity of the rearrangement. STR analysis was conducted to identify potential contamination and verify kinship. In addition, a local BLAST engine was performed to locate potentially homologous segments which might contribute to the translocation in breakpoints of chromosome. RESULTS: A rare de novo balanced reciprocal translocations mosaicism mos 46,XY,t(1;3)(q42;q25)[40]/46,XY[39] was diagnosed in a fetus conceived using preimplantation genetic testing due to a 46,XY,t(12;14)(q22;q13) balanced translocation carrier father through multiplatform genetic techniques. Two of the largest continuous high homology segments were identified in chromosomal band 1q42.12 and 3q25.2. At the 21-months follow up, infant has achieved all psychomotor development milestones as well as growth within the normal reference range. CONCLUSION: We present a prenatal diagnosis of a rare de novo balanced reciprocal translocations mosaicism in a fetus who conceived by preimplantation genetic testing. The most reasonable driving mechanism was that a de novo mitotic error caused by nonallelic homologous recombination between 1q42.12 and 3q25.2 in a zygote within the first or early cell divisions, which results in a mosaic embryo with the variant present in a half proportion of cells.

Application value of Doppler ultrasound combined with CA125 and CA19.9 in the early diagnosis of epithelial ovarian cancer.

PURPOSE: An early diagnosis is of great significance in improving the survival rate of patients. At present, the application values of different diagnostic methods in ovarian cancer are different, and the clinical diagnosis alone is not ideal. Therefore, this study explored the application value of Doppler ultrasound combined with CA125 and CA19.9 in the early diagnosis of epithelial ovarian cancer. METHODS: A total of 58 patients with ovarian diseases were divided into an observation group (epithelial ovarian cancer group, n=29) and a control group (benign ovarian tumour group, n=29). Doppler ultrasound results and serum CA125 and CA19.9 detection results of the two groups were collected to analyse and compare the application values of ultrasound and different kinds of tumour markers in the early diagnosis of epithelial ovarian cancer. RESULTS: The results of Doppler ultrasound showed that the resistance index of the blood flow in the observation group was lower than that in the control group, and the ultrasound score was higher than that in the control group (p<0.05). The levels of serum tumour markers CA125 and CA19.9 in the observation group were significantly higher than those in the control group (p<0.05). The results of the repeated measurement analysis of variance showed that there were significant differences in the ultrasound score, blood flow resistance index, and CA125 and CA19.9 levels in different stages of ovarian cancer (p<0.05). There was no difference in the ultrasonographic score between stage I and the partum stage, while the stages of menstruation and implantation showed a gradually increasing trend (p<0.05). The blood flow resistance index and CA125 and CA19.9 levels increased gradually with the stage (p<0.05). The sensitivity (93.1%), specificity (96.55%), positive predictive value (96.43%), negative predictive value (93.33%) and diagnosis rate (94.83%) of Doppler ultrasonography combined with CA125 and CA19.9 in the diagnosis of epithelial ovarian cancer were higher than those of the single indicator detection method or the two combined diagnostic detection methods. CONCLUSION: Doppler ultrasound combined with CA125 and CA19.9 has high sensitivity, high specificity and high coincidence rate and can improve the early clinical diagnosis of epithelial ovarian cancer.

CTLA-4 +49 A/G Polymorphism and the Risk of Lung Cancer: a Meta-analysis.

BACKGROUND: Lung cancer is one of the malignant tumors. Gene mutations associated with cellular immune function and regulating the activation and proliferation of immune cells. Several publications have explored the relationship between cytotoxic T lymphocyte antigen-4 (CTLA-4) +49 adenine (A)/guanine (G) polymorphism and susceptibility of lung cancer, but the results remain controversial. Thus, we performed this meta-analysis to derive a more comprehensive estimation of the relationship. METHODS: All articles addressed lung cancer and polymorphisms of CTLA-4 were searched from the PubMed, EMBASE databases published up to June 29, 2019. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Publication bias of relevant studies was examined via Begg's test and funnel plots. RESULTS: The meta-analysis included 8 case-control studies covering 4,430 lung cancer patients and 5,198 healthy controls from September 2008 to April 2020. The overall eligible data indicated that CTLA-4 +49A/G polymorphisms did not correlate with the elevated lung cancer risk in all genetic comparison models (dominant model: OR=1.037, 95%CI: 0.925-1.161; recessive model: OR=0.968, 95%CI: 0.888-1.055; allele model: OR=0.992, 95%CI: 0.933-1.054; homozygous model: OR=0.980, 95%CI: 0.857-1.121; heterozygous model: OR=1.023, 95%CI: 0.906-1.154). In further stratified analyses, CTLA-4 +49A/G polymorphism was found to be significantly associated with susceptibility to NSCLC in these models (dominant model: OR=1.404, 95%CI: 1.074-1.836; allele model: OR=1.273, 95%CI: 1.034-1.565; homozygous model: OR=1.553, 95%CI: 1.044-2.310; heterozygous model: OR=1.308, 95%CI: 1.062-1.611). CONCLUSIONS: CTLA-4 +49A/G polymorphism were not associated with the risk of lung cancer but might be a risk factor only in NSCLC.

cfDNA deconvolution via NIPT of a pregnant woman after bone marrow transplant and donor egg IVF.

Cell-free DNA is known to be a mixture of DNA fragments originating from various tissue types and organs of the human body and can be utilized for several clinical applications and potentially more to be created. Non-invasive prenatal testing (NIPT), by high throughput sequencing of cell-free DNA (cfDNA), has been successfully applied in the clinical screening of fetal chromosomal aneuploidies, with more extended coverage under active research.In this study, via a quite unique and rare NIPT sample, who has undergone both bone marrow transplant and donor egg IVF, we investigated the sources of oddness observed in the NIPT result using a combination of molecular genetics and genomic methods and eventually had the case fully resolved. Along the process, we devised a clinically viable process to dissect the sample mixture.Eventually, we used the proposed scheme to evaluate the relatedness of individuals and the demultiplexed sample components following modified population genetics concepts, exemplifying a noninvasive prenatal paternity test prototype. For NIPT specific applicational concern, more thorough and detailed clinical information should therefore be collected prior to cfDNA-based screening procedure like NIPT and systematically reviewed when an abnormal report is obtained to improve genetic counseling and overall patient care.

Regulatory mechanisms and therapeutic targeting of vasculogenic mimicry in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a typical hyper-vascular solid tumor; aberrantly rich in tumor vascular network contributes to its malignancy. Conventional anti-angiogenic therapies seem promising but transitory and incomplete efficacy on HCC. Vasculogenic mimicry (VM) is one of functional microcirculation patterns independent of endothelial vessels which describes the plasticity of highly aggressive tumor cells to form vasculogenic-like networks providing sufficient blood supply for tumor growth and metastasis. As a pivotal alternative mechanism for tumor vascularization when tumor cells undergo lack of oxygen and nutrients, VM has an association with the malignant phenotype and poor clinical outcome for HCC, and may challenge the classic anti-angiogenic treatment of HCC. Current studies have contributed numerous findings illustrating the underlying molecular mechanisms and signaling pathways supporting VM in HCC. In this review, we summarize the correlation between epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and VM, the role of hypoxia and extracellular matrix remodeling in VM, the involvement of adjacent non-cancerous cells, cytokines and growth factors in VM, as well as the regulatory influence of non-coding RNAs on VM in HCC. Moreover, we discuss the clinical significance of VM in practice and the potential therapeutic strategies targeting VM for HCC. A better understanding of the mechanism underlying VM formation in HCC may optimize anti-angiogenic treatment modalities for HCC.

Regorafenib inhibits migration, invasion, and vasculogenic mimicry of hepatocellular carcinoma via targeting ID1-mediated EMT.

Regorafenib is approved for patients with unresectable hepatocellular carcinoma (HCC) following sorafenib. However, the effect of regorafenib on HCC metastasis and its mechanism are poorly understood. Here, our data showed that regorafenib significantly restrained the migration, invasion and vasculogenic mimicry (VM) of HCC cells, and downregulated the expression of epithelial-to-mesenchymal transition (EMT)/VM-related molecules. Using RNA-seq and cellular thermal shift assays, we found that inhibitor of differentiation 1 (ID1) was a key target of regorafenib. In HCC tissues, the protein expression of ID1 was positively correlated with EMT and VM formation (CD34- /PAS+ ). Functionally, ID1 knockdown inhibited HCC cell migration, invasion, metastasis, and VM formation in vitro and in vivo, with upregulation of E-cadherin and downregulation of Snail and VE-cadherin. Moreover, Snail overexpression promoted the migration, invasion, and VM formation of ID1 knockdown cells. Snail knockdown reduced the migration, invasion, and VM formation of ID1 overexpression cells. Finally, regorafenib suppressed VM formation and decreased the expression of ID1, VE-cadherin and Snail in HCC PDX model. In conclusion, we manifested that regorafenib distinctly inhibited EMT in HCC cells via targeting ID1, leading to the suppression of cell migration, invasion and VM formation. These findings suggest that regorafenib may be developed as a suitable therapeutic agent for HCC metastasis.

Resection of a huge mediastinal well-differentiated liposarcoma involving left thoracic cavity.

BACKGROUND: Mediastinal lipoma/liposarcoma is a rare tumor of the mediastinum. CASE PRESENTATION: This article reported one case of giant anterior superior mediastinum well-differentiated liposarcoma involving the left thoracic cavity with symptom of dysphagia. The mediastinum liposarcoma was completely resected through a left thoracotomy. Histologic examination and molecular pathological test clarified the diagnosis as well-differentiated mediastinal liposarcoma. There has been no evidence of recurrence during the 8 months follow-up. CONCLUSION: Molecular pathological examination of the MDM2, CDK4 and p16 gene in tumors provides the diagnostic gold standard in distinguishing well-differentiated liposarcoma from lipoma. Complete surgical resection is the first-line treatment choice for mediastinal lipoma/ liposarcoma.

Prenatal diagnosis of de novo monosomy 18p deletion syndrome by chromosome microarray analysis: Three case reports.

RATIONALE: Monosomy 18p deletion syndrome refers to a rare chromosomal disorder resulting from the part deletion of the short arm of chromosome 18. Prenatal diagnosis of de novo 18p deletion syndrome is a challenge due to its low incidence and untypical prenatal clinical presentation. PATIENT CONCERNS: Three cases received amniocentesis due to increased nuchal translucency (INT), high risk for Down syndrome, and INT combined intrauterine growth retardation (IUGR), respectively. DIAGNOSIS: The 3 cases were diagnosed with de novo monosomy 18p deletion syndrome by amniocentesis and chromosome microarray analysis (CMA). INTERVENTIONS: Karyotype analysis and CMA were used to analyze the abnormal chromosome. OUTCOMES: Case 1 and case 2 revealed 13.87 and 12.68 Mb deletions by array-CGH analysis, respectively. Case 3 revealed 6.9 Mb deletions in 18p11.32p11.31 and 7.5 Mb deletions in 18p11.23p11.21 by single nucleotide polymorphism array. All of the pregnancies were terminated due to the abnormal chromosome. LESSONS: The fetal phenotype of monosomy 18p deletion syndrome shows great variability and may not be evident during the pregnancy. CMA may be served as an effective tool for the diagnosis of prenatal monosomy 18p deletion syndrome diagnosis.

A Novel Method for Low-Contrast and High-Noise Vessel Segmentation and Location in Venipuncture.

Blood sampling is the most common medical technique, and vessel detection is of crucial interest for automated venipuncture systems. In this paper, we propose a new convex-regional-based gradient model that uses contextually related regional information, including vessel width size and gray distribution, to segment and locate vessels in a near-infrared image. A convex function with the interval size of vessel width is constructed and utilized for its edge-preserving superiority. Moreover, white and linear noise independences are derived. The region-based gradient decreases the number of local extreme in the cross-sectional profile of the vessel to realize its single global minimum in a low-contrast, noisy image. We demonstrate the performance of the proposed model via quantitative tests and comparisons between different methods. Results show the advantages of the model on the continuity and smoothness of segmented vessel. The proposed model is evaluated with receiver operating characteristic curves, which have a corresponding area under the curve of 88.8%. The proposed model will be a powerful method in automated venipuncture system and medical image analysis.

The effects of screening and intervention of subclinical hypothyroidism on pregnancy outcomes: a prospective multicenter single-blind, randomized, controlled study of thyroid function screening test during pregnancy.

PURPOSE: To evaluate the effect of subclinical hypothyroidism (SCH) screening and intervention on pregnancy outcomes and explore the significance of thyroid function during early pregnancy. METHODS: Pregnant women were recruited from Peking Union Medical College Hospital (screening group for measuring thyroid function and thyroid antibody in early pregnancy) and Haidian Maternal & Child Health Hospital (control group whose serum was stored and measured shortly after delivery) from July 2011 to December 2012. Thyrotropin levels 2.5-10 mIU/L and free T4 levels in normal range were considered SCH. Some of the screening group were treated with levothyroxine and adjusted. The others did not take medicine but kept a regular follow-up visit to doctors after antenatal clinic. The pregnancy outcomes and complications were compared. RESULTS: 1671 women (675 in screening group and 996 in control group) were recruited. 419 (167 from screening group) women was diagnosed as SCH. In screening group, 105 SCH and 4 hypothyroid women received thyroid hormone replacement therapy. The miscarriage and fetal macrosomia risks were lower, and cesarean was higher in screening group than control. CONCLUSION: Screening and intervention of SCH can significantly reduce the incidence rate of miscarriage.

Production of polyhydroxyalkanoates by Escherichia coli mutants with defected mixed acid fermentation pathways.

A series of Escherichia coli BW25113 mutants with reduced mixed acid fermentation were constructed. Genes ackA-pta, poxB, ldhA, adhE, and pflB encoding acetate kinase, phosphate acetyltransferase, pyruvate oxidase, D: -lactate dehydrogenase, acetaldehyde dehydrogenase, and pyruvate formate-lyase, respectively, were deleted successively. When grown under microaerobic condition, the mutants reduced approximately 90% acetate excretion after the deletion of genes ackA-pta and poxB. Production of lactate, ethanol, and formate was also significantly reduced after the deletion of genes ldhA, adhE, and pflB, respectively. The accumulation of biomass and poly(3-hydroxybutyrate) (PHB) were significantly enhanced after deleting the mixed acid fermentation. E. coli mutant BWapld with deletions of ackA-pta, poxB, ldhA, and adhE produced twice the cell dry weight (CDW) and 3.5 times of PHB compared with its wild-type under microaerobic conditions. E. coli mutant BWapl with deletions of ackA-pta, poxB, and ldhA also achieved nearly twice CDW and three times of PHB content in comparison to the wild-type during 48 h static cultivation. Production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] was observed in the mutants under static cultivation. E. coli mutant BWapld could produce approximately 50 wt.% P(3HB-co-3HV) consisting of 5 mol% of 3-hydroxyvalerate (3HV) under aerobic conditions, when the seed culture was inoculated at an appropriate time. When ackA-pta, poxB, ldhA, adhE, and pflB were deleted, E. coli mutant BWapldf accumulated over 70 wt.% P(3HB-co-3HV) consisting of 8 mol% 3HV under aerobic conditions.