Identification of pyruvic and maleic acid as potential markers for disease activity and prognosis in chronic urticaria.

BACKGROUND: Population-based studies have highlighted the link between chronic urticaria (CU) and metabolic syndrome, and metabolic alterations have been revealed in CU. However, to our knowledge, a comprehensive metabolomics study on a large cohort of patients with CU has not been reported. OBJECTIVE: We sought to explore the underlying metabolic subtypes and novel metabolite biomarkers for CU diagnosis and therapy. METHODS: Plasma samples from 80 patients with CU and 82 healthy controls were collected for metabolomics quantification and bioinformatics analysis. Another independent cohort consisting of 144 patients with CU was studied to validate the findings. Bone marrow-derived mast cells and mice with IgE-induced passive cutaneous anaphylaxis were used for in vitro and in vivo experiments, respectively. RESULTS: We observed clear metabolome differences between CU patients and healthy controls. Meanwhile, differential metabolites N6-acetyl-l-lysine, l-aspartate, maleic acid, and pyruvic acid were used to construct random forest classifiers and achieved area under receiver operating characteristic curve values greater than 0.85, suggesting their potential as diagnostic biomarkers of CU. More importantly, by exploring the underlying metabolic subtypes of CU, we found that the low abundance of pyruvic acid and maleic acid was significantly related to the activity of CU, poor efficacy of second-generation H1 antihistamines, and short relapse-free time. The results were validated in the independent cohort. Moreover, supplementation with pyruvate or maleate could significantly attenuate IgE-mediated mast cell activation in vitro and in vivo. CONCLUSIONS: Plasma pyruvic acid and maleic acid may be effective biomarkers for predicting disease activity, therapeutic efficacy, and prognosis for patients with CU.

Impact of closed-off management due to COVID-19 rebound on maternal depression during pregnancy.

BACKGROUND: This study aimed to assess the impacts of closed-off measures with different strictness levels (lockdown, partial lockdown and non-lockdown) and geographic proximity to patients with coronavirus disease 2019 (COVID-19) on prenatal depression during an epidemic rebound of COVID-19. METHODS: This was a cross-sectional web-based survey including 880 pregnant women. Depressive symptoms were measured by Self-Rating Depression Scale (SDS) and geographic proximity was calculated using Geographic Information Systems. Linear and logistic regression were used to assess the associations of closed-off measures and geographic proximity with SDS scores and depressive symptoms. Restricted cubic splines were used to model non-linear associations between geographic proximity and depression symptoms. RESULTS: Compared with those living in non-lockdown areas, women in lockdown areas had higher SDS scores (adjusted ß: 3.51, 95% CI: 1.80, 5.21) and greater risk of depressive symptoms (adjusted OR: 4.00, 95% CI: 2.18, 7.35), but evidence for partial lockdown was not obvious. A progressive increase in the risk of depressive symptoms was found with decreasing distance to COVID-19 patients when geographic proximity was <8 kilometers. Compared to those in the 5th quintile of geographic proximity, women in the first, second and third quintiles had at least 6 times higher risk of depressive symptoms. CONCLUSIONS: Pregnant women under strict closed-off management during COVID-19 epidemic have high risk of depression. A specific range around the residences of reported COVID-19 patients should be underlined as potential clustering of high prenatal depression levels. Our findings highlight the importance of enhancing mental health management during the COVID-19 epidemic for pregnant women.

Empirical Evidence That Complexity Limits Horizontal Gene Transfer.

Horizontal gene transfer (HGT) is a major contributor to bacterial genome evolution, generating phenotypic diversity, driving the expansion of protein families, and facilitating the evolution of new phenotypes, new metabolic pathways, and new species. Comparative studies of gene gain in bacteria suggest that the frequency with which individual genes successfully undergo HGT varies considerably and may be associated with the number of protein-protein interactions in which the gene participates, that is, its connectivity. Two nonexclusive hypotheses have emerged to explain why transferability should decrease with connectivity: the complexity hypothesis (Jain R, Rivera MC, Lake JA. 1999. Horizontal gene transfer among genomes: the complexity hypothesis. Proc Natl Acad Sci U S A. 96:3801-3806.) and the balance hypothesis (Papp B, Pál C, Hurst LD. 2003. Dosage sensitivity and the evolution of gene families in yeast. Nature 424:194-197.). These hypotheses predict that the functional costs of HGT arise from a failure of divergent homologs to make normal protein-protein interactions or from gene misexpression, respectively. Here we describe genome-wide assessments of these hypotheses in which we used 74 existing prokaryotic whole genome shotgun libraries to estimate rates of horizontal transfer of genes from taxonomically diverse prokaryotic donors into Escherichia coli. We show that 1) transferability declines as connectivity increases, 2) transferability declines as the divergence between donor and recipient orthologs increases, and that 3) the magnitude of this negative effect of divergence on transferability increases with connectivity. These effects are particularly robust among the translational proteins, which span the widest range of connectivities. Whereas the complexity hypothesis explains all three of these observations, the balance hypothesis explains only the first one.

Difficult and complicated oral ulceration: an expert consensus guideline for diagnosis.

The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists. The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers, based on factors such as detailed clinical medical history inquiry, histopathological examination, and ulceration-related systemic diseases screening. Not only it can provide a standardized procedure of oral ulceration, but also it can improve the diagnostic efficiency, in order to avoid misdiagnosis and missed diagnosis.

tRNA-derived small RNAs: novel regulators of cancer hallmarks and targets of clinical application.

tRNAs are a group of conventional noncoding RNAs (ncRNAs) with critical roles in the biological synthesis of proteins. Recently, tRNA-derived small RNAs (tsRNAs) were found to have important biological functions in the development of human diseases including carcinomas, rather than just being considered pure degradation material. tsRNAs not only are abnormally expressed in the cancer tissues and serum of cancer patients, but also have been suggested to regulate various vital cancer hallmarks. On the other hand, the application of tsRNAs as biomarkers and therapeutic targets is promising. In this review, we focused on the basic characteristics of tsRNAs, and their biological functions known thus far, and explored the regulatory roles of tsRNAs in cancer hallmarks including proliferation, apoptosis, metastasis, tumor microenvironment, drug resistance, cancer stem cell phenotype, and cancer cell metabolism. In addition, we also discussed the research progress on the application of tsRNAs as tumor biomarkers and therapeutic targets.

Expression profiles of tRNA-derived small RNA and their potential roles in oral submucous fibrosis.

BACKGROUND: Although transfer RNA (tRNA) has been found to be the main source of a rich class of noncoding RNA, the tRNA-derived small RNA (tsRNA) has been proved to play an irreplaceable role in the human body, and its dynamic imbalance could affect the progress of the disease. However, the research on tsRNA in oral submucous fibrosis (OSF) is still scarce. METHODS: We sequenced the OSF and validated it by PCR. We found that there were significant differences in their expression levels in OSF. Furthermore, bioinformatic analysis was performed to explore the roles of these fragments in oral submucous fibrosis. RESULTS: Of 126 tsRNAs in OSF were dysregulated, including 73 upregulated tsRNAs and 53 downregulated tsRNAs. The downregulated tiRNA-Val-CAC-002, tRF-Asn-GTT-005, tRF-Trp-CCA-007 and upregulated tRF-Gly-TCC-016, tRF-Pro-TGG-009 showed significant differences by qRT-PCR validation, which were consistent with the results of RNA sequencing. Gene ontology and pathway analysis revealed that tRF-Gly-TCC-016 would possibly promote the formation and progress of OSF through cytokine-cytokine receptor interaction and cAMP signal pathway, while tiRNA-Val-CAC-002 could be primarily concerned with the transition from OSF to oral squamous cell carcinoma (OSCC). CONCLUSION: tRNA-derived fragments are dysregulated and could be involved in the pathogenesis of oral submucous fibrosis. tRF-Gly-TCC-016 and tiRNA-Val-CAC-002 may be new regulatory molecules that could affect the process of OSF by regulating signal pathways through interacting with multiple genes.

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OBJECTIVES: The mouth restriction of patients with oral submucous fibrosis (OSF) seriously affects their eating food and the quality of life. There are few reports about improving the oral opening degree in patients with OSF. This study aims to explore the effect of oral opening training on the improvement of mouth opening limitation in patients with OSF treated with local injection. METHODS: A total of 220 outpatients with limited mouth opening of OSF were collected from the Center of Stomatology, Xiangya Hospital, Central South University, and randomly divided into a control group and an experiment group (n=110). The control group were treated with local injection of Salvia miltiorrhiza and triamcinolone acetonide, once a week, and 8 times a course. The experimental group were treated with local injection combined with mouth opening training for 2 years. The degree of mouth opening was compared between the 2 groups at the end of local injection treatment, 1 year and 2 years after the treatment. The curative effect was evaluated according to the size of the opening, the lamellar structure of the mucosa, and the condition of the cords. RESULTS: A total of 197 patients completed the whole course of treatment, with 107 in the experimental group and 90 in the control group. At the end of treatment, 1 year and 2 years after the treatment, the degree of mouth opening in the experimental group was (36.14±2.62), (39.67±2.67), and (39.80±2.57) mm, respectively, which was significantly higher than that in the control group (24.71±1.97), (22.82±2.13), and (22.02±2.09) mm, respectively. The difference was significant (P<0.05). The increase of mouth opening in the experimental group was significantly better than that in the control group. Two years after local injection treatment, the effective rate of the experimental group was 97.1%, which was significantly higher than that of the control group (47.8%, P<0.05). CONCLUSIONS: Mouth opening training can significantly increase the degree of mouth opening in patients with OSF treated with local injection.

XBP1- IGFBP3 Signaling Pathway Promotes NSCLC Invasion and Metastasis.

Lung cancer is the most frequently diagnosed cancer and the main cause of cancer death in the world. X-box binding protein 1 (XBP1), which is an important transcription factor involved in regulating the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress, might act as a potent oncogenic protein in the processes of tumorigenesis, tumor proliferation and metastasis in various cancers. However, the clinical significance and pathological role of XBP1 in non-small cell lung cancer (NSCLC) remains unknown. In this study, we investigated the expression of XBP1s protein in the 104 NSCLC tumor tissues and matched adjacent normal lung tissues (ANLT) by Immunohistochemical (IHC), and we found overexpressed XBP1s protein was associated with NSCLC TNM stages, lymph node metastasis and poor prognosis. The further gain-and loss-of-function experiments indicated overexpression of XBP1s protein promoted cell invasion, migration and metastasis both in vitro and in vivo. Further study showed XBP1s protein could upregulate insulin-like growth factor binding protein-3 (IGFBP3) expression, and regulated NSCLC cells invasion and metastasis by regulating IGFBP3. Taken together, XBP1s protein is markedly overexpressed in NSCLC and serves as an oncogene that play a critical role in NSCLC tumorigenesis and development. Importantly, XBP1s protein might not only be a potential biomarker for metastasis and prognosis but also a potential therapeutic target in NSCLC.

Fine particulate matter (PM2.5) promotes IgE-mediated mast cell activation through ROS/Gadd45b/JNK axis.

BACKGROUND: Mast cells play an important role in allergic responses and persistently exposure to environmental fine particulate matter (PM2.5) exacerbates allergic diseases,but the details remained elucidative. OBJECTIVES: To investigate the effect of PM2.5 on IgE-mediated mast cell responses through an IgE-mediated mouse model and mast cell activation. METHODS: The ß-hexosaminidase release and a BALB/c model of passive cutaneous anaphylaxis (PCA) was used to test IgE-mediated mast cells activation in vitro and in vivo. RNA-Seq technique was conducted to study the gene expression profile. Reactive oxygen species (ROS) production was measured by flow-cytometry. RT-PCR,WB and ELISA were performed to examine targeting molecules expression. RESULTS: PM2.5 facilitated IgE-mediated degranulation and increased cytokines expression in mast cells. Meanwhile, the Evan's blue extravasation as well as serum cytokines in mice was increased after treatment with PM2.5. Furthermore, PM2.5 treatment dramatically increased the expression of Gadd45b which is an oxidative stress molecule that directly activates down-stream pathway, such as MEKK4/JNK. PM2.5 treatment activated MEKK4, JNK1/2 but not ERK1/2 and p38. Meanwhile, Knockdown of Gadd45b significantly attenuated PM2.5-mediated JNK1/2 activation and expression of cytokines. In addition, a JNK1/2-specific inhibitor SP600125 blocked IgE-mediated mast cell activation and cytokine release in PCA model mice. Moreover, PM2.5 treatment increased the ROS level and ROS inhibitor dramatically blocked the PM2.5-induced ROS production and reversed the PM2.5-mediated gene expression in the mitochondrial respiratory chain. CONCLUSIONS: PM2.5 regulates ROS production through Gadd45b/MEKK4/JNK pathway, facilitating IgE-mediated mast cell activation.

Oral submucous fibrosis transforming into squamous cell carcinoma: a prospective study over 31 years in mainland China.

OBJECTIVE: Oral submucous fibrosis (OSF) is an oral mucous disease caused by betel quid chewing. It is controversial whether OSF can transform into oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: In this prospective study, a group of 567 patients with OSF were enrolled from 1986 to 2017 and followed-up until 2019. The cancerous information was collected and analyzed. RESULTS: OSF transformed into OSCC in 32 cases (32/567, 5.6%). The patient's age ranged from 20 to 69 years, and the average age was 52 years. The time taken for transformation ranged from 2 to 24 years, the average being 8.6 years. The cancerous transformation occurred in 18 patients (56%) from years 2 to 9, in 13 patients (41%) from years 10-19 and in 1 patient (3%) from 24 years. We analyzed the betel quid chewing habits and found all 32 patients with OSCC-chewed betel quid. Betel quid chewing was most prevalent in patients aged 40-69 years. Sixteen patients had chewed betel quid for 10-19 years (16/32, 50%) and 19 patients (60%) chewed 10-19 slices each day. The OSCC was located in the left or right buccal regions in 23 patients (23/32; 72%) and in the left or right lingual regions in 4 patients (4/32; 12%). Well, moderately and poorly differentiated squamous cell carcinoma was present in 23 patients (23/32; 72%), 4 patients (3/32; 9%), and 5 patients (5/32; 16%), respectively. CONCLUSION: Our findings supported that OSF is a real oral premalignant disorder. CLINICAL RELEVANCE: The long duration of the transformation from the OSF to OSCC suggests more frequent examinations and corresponding treatments are necessary for OSF patients.

Effect of Postoperative Radiotherapy in Thymoma Patients: A SEER-Based Study.

INTRODUCTION: The role of postoperative radiation therapy (PORT) for thymoma is under debate, especially in patients aged ≥60 years with an advanced stage (Masaoka stages III and IV). We aimed to evaluate the efficacy of PORT for thymoma in a population-based registry. METHODS: A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database was conducted to compare the outcomes of thymoma patients with or without PORT. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS). Conditional inference tree analyses were performed for risk classification according to the study variables. Cox regression was performed to evaluate the prognostic effect of PORT in the specific subgroups. RESULTS: A total of 2,236 patients were included. The conditional inference tree analysis identified that an age ≥60, a Masaoka stage ≥3, and the year of diagnosis were important factors when classifying patients into prognostic subgroups. PORT was found to be a protective predictor of OS in patients aged ≥60 years, those with a Masaoka stage III-IV, and those diagnosed after 2005. Further subgroup analyses revealed that PORT was significantly associated with a better OS (HR = 0.77) in patients aged ≥60 years, whereas it was not significantly associated with CSS. CONCLUSIONS: An older age (≥60 years) is critical for predicting survival outcomes in thymoma patients. Moreover, patients aged ≥60 years could benefit from PORT in terms of OS.

Complete remission in a patient with advanced renal pelvis carcinoma with lung metastasis treated with durvalumab immunotherapy: a case report.

For early-stage upper urothelial carcinoma, total nephroureterectomy combined with bladder sleeve resection is the standard treatment. However, for patients with advanced disease, there is a lack of effective therapeutic strategies. In recent years, with an increased understanding of cancer immunobiology, systemic immunotherapies targeting immune checkpoint inhibition has been explored and clinically used in the area of urothelial carcinoma. The programmed cell death 1 receptor (PD-1) and its ligand (PD-L1) are important negative regulators of immune activity, preventing the destruction of normal tissues and autoimmunity. Nowadays, five immune checkpoint inhibitors blocking PD-1 (pembrolizumab, nivolumab) or PD-L1 (atezolizumab, durvalumab, and avelumab) have been approved by the United States Food and Drug Administration (US FDA) for the first- or second-line use in urothelial carcinoma, based on durable response and manageable safety profiles observed in relevant clinical trials. In this study, we present the case of a 64-year-old patient with renal pelvis carcinoma who went on to develop lung metastasis after postoperative chemotherapy. CT scan showed multiple scattered solid small nodule foci in both lungs (considered as metastasis). The patient received immunotherapy with PD-L1 monoclonal antibody (Durvalumab) alone, and achieved complete remission (CR) after 3 cycles of treatment. During the treatment, slight weakness was reported, and no nausea, fever and other adverse events were observed. This case shows that durvalumab could effectively and safely treat a case of renal pelvis carcinoma with lung metastases.

Role of autophagy and apoptosis in atrophic epithelium in oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a serious, potentially malignant oral disorder. It is histopathologically characterized by chronic inflammation and atrophic epithelium accompanied by the accumulation of collagen fibers in the lamina propria. The molecular mechanisms leading to atrophic epithelium remain poorly understood. Therefore, the present study investigated the role of autophagy and apoptosis in atrophic epithelium in OSF. The expression of Caspase-3 and autophagy-related proteins (LC3 and P62) in OSF epithelial tissues was quantified by immunohistochemistry. The analysis demonstrated that, compared with normal oral mucosal tissues, autophagy and apoptosis increased with the progression of OSF. Flow cytometry and Western blotting showed that arecoline induces apoptosis in human oral keratinocytes (HOKs) in a time-dependent manner in vitro. Arecoline-induced autophagy was confirmed by transmission electron microscopy and Western blotting. When chloroquine was used as an inhibitor of autophagy, the apoptosis rate and Caspase-3 expression decreased compared with the use of arecoline alone. Thus, autophagy and apoptosis may be involved in atrophic epithelium in OSF, and arecoline-induced autophagy promotes apoptosis in HOKs.

The push out bond strength of polydimethylsiloxane endodontic sealers to dentin.

BACKGROUND: The purpose of this experiment was to assess the push out bond strength of Polydimethylsiloxane sealers (GuttaFlow 2 and GuttaFlow Bioseal by Colte'ne/Whaledent, Altstätten, Switzerland). AH Plus (Dentsply, DeTrey, Konstanz, Germany) was used as a reference material for comparison. METHODS: Thirty root slices were prepared from the middle third of 10 mandibular premolars. Each slice was 1 ± 0.1 mm thick. Three holes, 0.8 mm wide each, were drilled on the axial side of each root slice. These holes were subjected to standardized irrigations and then dried using paper points. Finally, for each root slice, each hole was filled with exactly one of the following three root canal sealers: AH Plus, GuttaFlow 2 and GuttaFlow Bioseal. After all the holes were filled in that way, the root slices were stored on top of phosphate-buffered saline solution (pH 7.2) soaked gauze for 7 days at the temperature of 37 degrees Celsius. Then, for each root canal sealer on a root slice, the universal testing machine was used to measure the push out bond strength. The differences in push out bond strengths between the three sealer samples were assessed using the Friedman test, while the paired comparisons were assessed using Wilcoxon signed rank test with Bonferroni correction. All statistical tests were two-tailed and the significance level was set at the 5%. RESULTS: According to the Friedman test the distributions of push out bond strengths of AH Plus, GuttaFlow 2 and GuttaFlow Bioseal were different (P < 0.05). Paired comparisons indicated that AH Plus had a significantly superior push out bond strength than GuttaFlow 2 and GuttaFlow Bioseal, while the push out bond strength of GuttaFlow Bioseal was significantly stronger than that of GuttaFlow 2 (P < 0.01). CONCLUSIONS: Based on these findings, AH Plus is a better root canal sealer than GuttaFlow 2 and GuttaFlow Bioseal.

Influence of in vitro differentiation status on the in vivo bone regeneration of cell/chitosan microspheres using a rat cranial defect model.

The aim of this study was to investigate the influence of the in vitro osteogenic differentiation status on the in vivo bone regeneration of cell/chitosan microspheres qualitatively and quantitatively. To this end, rat bone-marrow-derived mesenchymal stromal cells (BMSCs) were seeded onto apatite-coated chitosan microspheres. The constructs were osteogenically differentiated for 0, 7, 14, and 21 days followed by calvarial defect implantation in vivo for up to 8 weeks. In vitro studies showed that BMSCs in the constructs proliferated from day 0 to day 7. The activity and gene expression of alkaline phosphatise increased from day 0 to day 14 and then decreased. The gene expression of collagen type I and osteocalcin peaked at day 21. In vivo, constructs retrieved from day 0 group were filled with fibrous tissues and capillaries, but no bone formation was observed. Constructs retrieved from day 7 and day 21 groups showed progressive bone formation, whereas those retrieved from day 14 group had the highest percentage of bone formation. These data suggested that to generate a substantial amount of bone in vivo, not only the in vitro osteogenic differentiation was necessary, but also the period of pre-differentiation was important for the cell-scaffold constructs. The period of pre-differentiation for 14 days was found to be the most suitable for chitosan microspheres.

Role of autophagy induced by arecoline in angiogenesis of oral submucous fibrosis.

OBJECTIVES: To detect the expression of protein light chain 3 (LC3) and p62-SQSTM1 (p62) in the lamina propria of oral submucous fibrosis (OSF) and to determine the association of autophagy with OSF. To investigate the role of autophagy in angiogenesis of human umbilical vein endothelial cells (HUVECs) and to assess whether this effect was induced by arecoline. METHODS: LC3 and p62 expression was detected in OSF tissue through immunohistochemistry (IHC). Transmission electron microscopy (TEM) and Western blot were used to investigate the expression of autophagy in HUVECs. The role of autophagy in angiogenesis in HUVECs was investigated using the Matrigel assay. RESULTS: 1: LC3 expression was upregulated in OSF samples. In contrast, p62 was downregulated in early and intermediate stages but upregulated in advanced stages of OSF. 2: HUVECs treated with arecoline exhibited increased autophagosomes, LC3 expression and reduced p62 expression, when co-treated with chloroquine (CQ), which is a specific autophagy inhibitor, revealed the opposite trend. 3: Autophagy inhibited angiogenesis in HUVECs. CONCLUSIONS: Our findings suggest that arecoline induces autophagy in HUVECs. The high level of autophagy could reduce cell viability and inhibit angiogenesis in HUVECs, potentially promoting the development of OSF.

Connections between the human gut microbiome and gestational diabetes mellitus.

The human gut microbiome can modulate metabolic health and affect insulin resistance, and it may play an important role in the etiology of gestational diabetes mellitus (GDM). Here, we compared the gut microbial composition of 43 GDM patients and 81 healthy pregnant women via whole-metagenome shotgun sequencing of their fecal samples, collected at 21-29 weeks, to explore associations between GDM and the composition of microbial taxonomic units and functional genes. A metagenome-wide association study identified 154 837 genes, which clustered into 129 metagenome linkage groups (MLGs) for species description, with significant relative abundance differences between the 2 cohorts. Parabacteroides distasonis, Klebsiella variicola, etc., were enriched in GDM patients, whereas Methanobrevibacter smithii, Alistipes spp., Bifidobacterium spp., and Eubacterium spp. were enriched in controls. The ratios of the gross abundances of GDM-enriched MLGs to control-enriched MLGs were positively correlated with blood glucose levels. A random forest model shows that fecal MLGs have excellent discriminatory power to predict GDM status. Our study discovered novel relationships between the gut microbiome and GDM status and suggests that changes in microbial composition may potentially be used to identify individuals at risk for GDM.

Proteomic identification of cyclophilin A as a potential biomarker and therapeutic target in oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a pre-cancerous lesion, which is characterized by fibrosis of the oral submucosa. Despite large body of studies focusing on this disease, the molecular mechanisms underlying the progression of OSF remained unclear. In this study, 2-DE-based proteomic approaches were employed to identify the differently expressed proteins between OSF and normal tissues. In total, 88 proteins were identified with altered expression levels, including CypA. Upregulation of CypA was further validated through immunohistochemistry staining combined with Q-PCR and western blot by using clinical samples. Statistical analyses reveal that CypA expression level is correlated to the progression of OSF. Finally, functional study reveals a pro-proliferative property of CypA in fibroblast cells by using multiple in vitro models. The present data suggest that CypA might be a potential biomarker and therapeutic target for OSF, and will lead to a better understanding of OSF pathogenesis.

Validity and Reproducibility of a Dietary Questionnaire for Consumption Frequencies of Foods during Pregnancy in the Born in Guangzhou Cohort Study (BIGCS).

This study aimed to examine the reproducibility and validity of a new food frequency questionnaire (FFQ) used in a birth cohort study to estimate the usual consumption frequencies of foods during pregnancy. The reference measure was the average of three inconsecutive 24 h diet recalls (24 HR) administrated between two FFQs, and the reproducibility was measured by repeating the first FFQ (FFQ1) approximately eight weeks later (FFQ2). A total of 210 pregnant women from the Born in Guangzhou Cohort Study (BIGCS) with full data were included in the analysis. The Spearman's correlation coefficients of FFQ1 and FFQ2 ranged from 0.33 to 0.71. The intraclass correlation coefficients of the two FFQs ranged from 0.22 to 0.71. The Spearman's correlation coefficients of the 24 HR and FFQ2 ranged from 0.23 to 0.62. Cross-classification analysis showed 65.1% of participants were classified into same and contiguous quintiles, while only 3.2% were misclassified into the distant quintiles. Bland-Altman methods showed good agreement for most food groups across the range of frequencies between FFQ1 and FFQ2. Our findings indicated that the reproducibility and validity of the FFQ used in BIGCS for assessing the usual consumption frequencies of foods during pregnancy were acceptable.