1. Fetal growth, fetal development, and placental features in women with polycystic ovary syndrome: analysis based on fetal and placental magnetic resonance imaging
Journal of Zhejiang University. Science. B 2020;21(12):977-989
Objective: Polycystic ovary syndrome (PCOS), a common endocrine-metabolic dysfunction in reproductiveaged women, may be involved in compromised pregnancy and offspring outcomes. This study aimed to investigate whether maternal PCOS affects fetal growth, fetal development, and placental features. Methods: This retrospective case-control study included 60 pregnant women with PCOS (PCOS group) and 120 healthy pregnant women without PCOS (control group). Fetal magnetic resonance imaging (MRI) was performed followed by an ultrasound examination and indications for imaging, including known or suspected fetal pathology, history of fetal abnormality in previous pregnancy or in a family member, and concern for placenta accreta. Fetal MRI images were analyzed for head circumference (HC), abdomen circumference (AC), lung-to-liver signal intensity ratio (LLSIR, a prenatal marker of fetal lung maturity), lengths of liver and kidney diameters in fetuses, and placental relative signal intensity on T2-weighted single-shot fast spin echo (SSFSE) imaging (rSISSFSE), and placental relative apparent diffusion coefficient value (rADC). Data on height and weight of offspring were collected through telephone follow-up. Results: Compared to the control group, the PCOS group showed the following characteristics: (1) smaller biparietal diameter and femur length in fetuses (P=0.026 and P=0.005, respectively), (2) smaller HC in fetuses (evident after 32 weeks; P=0.044), (3) lower LLSIR and smaller dorsoventral length of liver in fetuses (evident before 32 weeks; P=0.005 and P=0.019, respectively), and (4) smaller placental thickness (evident before 32 weeks; P=0.017). No significant differences in placental rSISSFSE or rADC were observed between the groups (all P>0.05). No significant differences in height and weight of offspring during childhood existed between the groups (all P>0.05). Conclusions: There exist alterations of fetal growth, fetal development, and placental features from women with PCOS.
2. Detection of human papillomavirus in oropharyngeal squamous cell carcinoma
Journal of Zhejiang University. Science. B 2020;21(12):961-976
Worldwide there has been a significant increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) etiologically attributed to oncogenic human papillomavirus (HPV). Reliable and accurate identification and detection tools are important as the incidence of HPV-related cancer is on the rise. Several HPV detection methods for OPSCC have been developed and each has its own advantages and disadvantages in regard to sensitivity, specificity, and technical difficulty. This review summarizes our current knowledge of molecular methods for detecting HPV in OPSCC, including HPV DNA/RNA polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), p16 immunohistochemistry (IHC), and DNA/RNA in situ hybridization (ISH) assays. This summary may facilitate the selection of a suitable method for detecting HPV infection, and therefore may help in the early diagnosis of HPV-related carcinoma to reduce its mortality, incidence, and morbidity.
3. Silencing of DsbA-L gene impairs the PPARγ agonist function of improving insulin resistance in a high-glucose cell model
Journal of Zhejiang University. Science. B 2020;21(12):990-998
Disulfide-bond A oxidoreductase-like protein (DsbA-L) is a molecular chaperone involved in the multimerization of adiponectin. Recent studies have found that DsbA-L is related to metabolic diseases including gestational diabetes mellitus (GDM), and can be regulated by peroxisome proliferator-activated receptor γ (PPARγ) agonists; the specific mechanism, however, is uncertain. Furthermore, the relationship between DsbA-L and the novel adipokine chemerin is also unclear. This article aims to investigate the role of DsbA-L in the improvement of insulin resistance by PPARγ agonists in trophoblast cells cultured by the high-glucose simulation of GDM placenta. Immunohistochemistry and western blot were used to detect differences between GDM patients and normal pregnant women in DsbA-L expression in the adipose tissue. The western blot technique was performed to verify the relationship between PPARγ agonists and DsbA-L, and to explore changes in key molecules of the insulin signaling pathway, as well as the effect of chemerin on DsbA-L. Results showed that DsbA-L was significantly downregulated in the adipose tissue of GDM patients. Both PPARγ agonists and chemerin could upregulate the level of DsbA-L. Silencing DsbA-L affected the function of rosiglitazone to promote the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB)/AKT pathway. Therefore, it is plausible to speculate that DsbA-L is essential in the environment of PPARγ agonists for raising insulin sensitivity. Overall, we further clarified the mechanism by which PPARγ agonists improve insulin resistance.
4. Factors associated with a SARS-CoV-2 recurrence after hospital discharge among patients with COVID-19: systematic review and meta-analysis
Journal of Zhejiang University. Science. B 2020;21(12):940-947
Background: The proportion of recurrences after discharge among patients with coronavirus disease 2019 (COVID-19) was reported to be between 9.1% and 31.0%. Little is known about this issue, however, so we performed a meta-analysis to summarize the demographical, clinical, and laboratorial characteristics of non-recurrence and recurrence groups. Methods: Comprehensive searches were conducted using eight electronic databases. Data regarding the demographic, clinical, and laboratorial characteristics of both recurrence and non-recurrence groups were extracted, and quantitative and qualitative analyses were conducted. Results: Ten studies involving 2071 COVID-19 cases were included in this analysis. The proportion of recurrence cases involving patients with COVID-19 was 17.65% (between 12.38% and 25.16%) while older patients were more likely to experience recurrence (weighted mean difference (WMD)=1.67, range between 0.08 and 3.26). The time from discharge to recurrence was 13.38 d (between 12.08 and 14.69 d). Patients were categorized as having moderate severity (odds ratio (OR)=2.69, range between 1.30 and 5.58), while those with clinical symptoms including cough (OR=5.52, range between 3.18 and 9.60), sputum production (OR=5.10, range between 2.60 and 9.97), headache (OR=3.57, range between 1.36 and 9.35), and dizziness (OR=3.17, range between 1.12 and 8.96) were more likely to be associated with recurrence. Patients presenting with bilateral pulmonary infiltration and decreased leucocyte, platelet, and CD4+ T counts were at risk of COVID-19 recurrence (OR=1.71, range between 1.07 and 2.75; WMD=−1.06, range between −1.55 and −0.57, WMD=−40.39, range between −80.20 and −0.48, and WMD=−55.26, range between −105.92 and −4.60, respectively). Conclusions: The main factors associated with the recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after hospital discharge were older age, moderate severity, bilateral pulmonary infiltration, laboratory findings including decreased leucocytes, platelets, and CD4+ T counts, and clinical symptoms including cough, sputum production, headache, and dizziness. These factors can be considered warning indicators for the recurrence of SARS-CoV-2 and might help the development of specific management strategies.
5. Weathering the storm: COVID-19 infection in patients with hematological malignancies
Journal of Zhejiang University. Science. B 2020;21(12):921-939
The Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within a matter of months, this highly contagious novel virus has led to a global outbreak and is still spreading rapidly across continents. In patients with COVID-19, underlying chronic diseases and comorbidities are associated with dismal treatment outcomes. Owing to their immunosuppressive status, patients with hematological malignancies (HMs) are at an increased risk of infection and have a worse prognosis than patients without HMs. Accordingly, intensive attention should be paid to this cohort. In this review, we summarize and analyze specific clinical manifestations for patients with coexisting COVID-19 and HMs. Furthermore, we briefly describe customized management strategies and interventions for this susceptible cohort. This review is intended to guide clinical practice.
6. Application of antigenic biomarkers for Mycobacterium tuberculosis
Journal of Zhejiang University. Science. B 2020;21(11):856-870
The study and characterization of biomolecules involved in the interaction between mycobacteria and their hosts are crucial to determine their roles in the invasion process and provide basic knowledge about the biology and pathogenesis of disease. Promising new biomarkers for diagnosis and immunotherapy have emerged recently. My-cobacterium is an ancient pathogen that has developed complex strategies for its persistence in the host and environment, likely based on the complexity of the network of interactions between the molecules involved in infection. Several biomarkers have received recent attention in the process of developing rapid and reliable detection techniques for tuberculosis. Among the most widely investigated antigens are CFP-10 (10-kDa culture filtrate protein), ESAT-6 (6-kDa early secretory antigenic target), Ag85A, Ag85B, CFP-7, and PPE18. Some of these antigens have been proposed as biomarkers to assess the key elements of the response to infection of both the pathogen and host. The design of novel and accurate diagnostic methods is essential for the control of tuberculosis worldwide. Presently, the diagnostic methods are based on the identification of molecules in the humoral response in infected individuals. Therefore, these tests depend on the capacity of the host to develop an immune response, which usually is heterogeneous. In the last 20 years, special attention has been given to the design of multiantigenic diagnostic methods to improve the levels of sensitivity and specificity. In this review, we summarize the state of the art in the study and use of mycobacterium biomolecules with the potential to support novel tuberculosis control strategies.
7. Novel ACADVL variants resulting in mitochondrial defects in long-chain acyl-CoA dehydrogenase deficiency
Journal of Zhejiang University. Science. B 2020;21(11):885-896
The pathogenesis of very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is highly heterogeneous and still unclear. Additional novel variants have been recently detected in the population. The molecular and cellular effects of these previously unreported variants are still poorly understood and require further characterization. To address this problem, we have evaluated the various functions and biochemical consequences of six novel missense variants that lead to mild VLCAD deficiency. Marked deficiencies in fatty acid oxidation (FAO) and other mitochondrial defects were observed in cells carrying one of these six variants (c.541C>T, c.863T>G, c.895A>G, c.1238T>C, c.1276G>A, and c.1505T>A), including reductions in mitochondrial respiratory-chain function and adenosine triphosphate (ATP) production, and increased levels of mitochondrial reactive oxygen species (ROS). Intriguingly, higher apoptosis levels were found in cells carrying the mutant VLCAD under glucose-limited stress. Moreover, the stability of the mutant homodimer was disturbed, and major conformational changes in each mutant VLCAD structure were predicted by molecular dynamics (MD) simulation. The data presented here may provide valuable information for improving management of diagnosis and treatment of VLCAD deficiency and for a better understanding of the general molecular bases of disease variability.
8. Diagnostic value of optic disc retinal nerve fiber layer thickness for diabetic peripheral neuropathy
Journal of Zhejiang University. Science. B 2020;21(11):911-920
Objective: To investigate the value of optic disc retinal nerve fiber layer (RNFL) thickness in the diagnosis of diabetic peripheral neuropathy (DPN). Methods: Ninety patients with type 2 diabetes, including 60 patients without DPN (NDPN group) and 30 patients with DPN (DPN group), and 30 healthy participants (normal group) were enrolled. Optical coherence tomography (OCT) was used to measure the four quadrants and the overall average RNFL thickness of the optic disc. The receiver operator characteristic curve was drawn and the area under the curve (AUC) was calculated to evaluate the diagnostic value of RNFL thickness in the optic disc area for DPN. Results: The RNFL thickness of the DPN group was thinner than those of the normal and NDPN groups in the overall average ((101.07± 12.40) µm vs. (111.07±6.99) µm and (109.25±6.90) µm), superior quadrant ((123.00±19.04) µm vs. (138.93±14.16) µm and (134.47±14.34) µm), and inferior quadrant ((129.37±17.50) µm vs. (143.60±12.22) µm and (144.48±14.10) µm), and the differences were statistically significant. The diagnostic efficiencies of the overall average, superior quadrant, and inferior quadrant RNFL thicknesses, and a combined index of superior and inferior quadrant RNFL thicknesses were similar, and the AUCs were 0.739 (95% confidence interval (CI) 0.635–0.826), 0.683 (95% CI 0.576–0.778), 0.755 (95% CI 0.652–0.840), and 0.773 (95% CI 0.672–0.854), respectively. The diagnostic sensitivity of RNFL thickness in the superior quadrant reached 93.33%. Conclusions: The thickness of the RNFL in the optic disc can be used as a diagnostic method for DPN.
9. Hydrogen agronomy: research progress and prospects
Journal of Zhejiang University. Science. B 2020;21(11):841-855
Agriculture is the foundation of social development. Under the pressure of population growth, natural disasters, environmental pollution, climate change, and food safety, the interdisciplinary “new agriculture” is becoming an important trend of modern agriculture. In fact, new agriculture is not only the foundation of great health and new energy sources, but is also the cornerstone of national food security, energy security, and biosafety. Hydrogen agronomy focuses mainly on the mechanism of hydrogen gas (H2) biology effects in agriculture, and provides a theoretical foundation for the practice of hydrogen agriculture, a component of the new agriculture. Previous research on the biological effects of H2 focused chiefly on medicine. The mechanism of selective antioxidant is the main theoretical basis of hydrogen medicine. Subsequent experiments have demonstrated that H2 can regulate the growth and development of plant crops, edible fungus, and livestock, and enhance the tolerance of these agriculturally important organisms against abiotic and biotic stresses. Even more importantly, H2 can regulate the growth and development of crops by changing the soil microbial community composition and structure. Use of H2 can also improve the nutritional value and postharvest quality of agricultural products. Researchers have also shown that the biological functions of molecular hydrogen are mediated by modulating reactive oxygen species (ROS), nitric oxide (NO), and carbon monoxide (CO) signaling cascades in plants and microbes. This review summarizes and clarifies the history of hydrogen agronomy and describes recent progress in the field. We also argue that emerging hydrogen agriculture will be an important direction in the new agriculture. Further, we discuss several scientific problems in hydrogen agronomy, and suggest that the future of hydrogen agronomy depends on contributions by multiple disciplines. Important future research directions of hydrogen agronomy include hydrogen agriculture in special environments, such as islands, reefs, aircraft, and outer space.
10. A near-infrared spectroscopy-based end-point determination method for the blending process of Dahuang soda tablets
Journal of Zhejiang University. Science. B 2020;21(11):897-910
Objectives: This study is aimed to explore the blending process of Dahuang soda tablets. These are composed of two active pharmaceutical ingredients (APIs, emodin and emodin methyl ether) and four kinds of excipients (sodium bicarbonate, starch, sucrose, and magnesium stearate). Also, the objective is to develop a more robust model to determine the blending end-point. Methods: Qualitative and quantitative methods based on near-infrared (NIR) spectroscopy were established to monitor the homogeneity of the powder during the blending process. A calibration set consisting of samples from 15 batches was used to develop two types of calibration models with the partial least squares regression (PLSR) method to explore the influence of density on the model robustness. The principal component analysis-moving block standard deviation (PCA-MBSD) method was used for the end-point determination of the blending with the process spectra. Results: The model with different densities showed better prediction performance and robustness than the model with fixed powder density. In addition, the blending end-points of APIs and excipients were inconsistent because of the differences in the physical properties and chemical contents among the materials of the design batches. For the complex systems of multi-components, using the PCA-MBSD method to determine the blending end-point of each component is difficult. In these conditions, a quantitative method is a more suitable alternative. Conclusions: Our results demonstrated that the effect of density plays an important role in improving the performance of the model, and a robust modeling method has been developed.