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Background Because of dismal prognosis in gastric cancer, identifying relevant prognostic factors is necessary. Phosphoserine phosphatase (PSPH) exhibits different expression patterns in many cancers and has been reported to affect the prognosis of patients with cancer. In this study, we examined the prognostic role of metabolic gene PSPH in gastric cancer based on the TCGA dataset and our hospital–based cohort cases. Methods We collected and analysed RNA-seq data of Pan-cancer and gastric cancer in the TCGA dataset and PSPH expression data obtained from immunohistochemical analysis of 243 patients with gastric cancer from Sun Yat-sen University cancer center. Further, Kaplan–Meier survival analysis and Cox analysis were used to assess the effect of PSPH on prognosis. The ESTIMATE and Cibersort algorithms were used to elucidate the relationship between PSPH and the abundance of immune cells using the TCGA dataset. Results We observed that PSPH expression displayed considerably high in gastric cancer and it was significantly associated with inferior prognosis (P = 0.043). Surprisingly, there was a significant relationship between lower immune scores and high expression of PSPH (P P = 0.046). The expression of PSPH significantly increased in activated memory CD4 T cells, resting NK cells and M0 macrophages (P = 0.037, Conclusions This study highlighted that PSPH influences the prognosis of patients with gastric cancer, and this is associated with the infiltration of tumour immune cells, indicating that PSPH may be a new immune-related target for treating gastric cancer.

Background Dental anxiety is associated with negative experiences of dental treatment and dental-visiting behavior. The Modified Dental Anxiety Scale (MDAS) is widely used for assessing dental anxiety. The study aims to establish the psychometric properties of a Chinese version of the MDAS based on the Taiwan sample (i.e., T-MDAS). Methods The T-MDAS and dental-visiting behavior and experience were assessed for 402 adult subjects recruited from community and clinical sites. The following psychometric properties were assessed: (a) internal consistency, (b) temporal stability, (c) criterion-related validity (i.e., the association with the score of Index of Dental Anxiety and Fear, IDAF-4C), (d) discrimination validity (i.e., the difference in scores between the subjects with and without a habit of a regular dental visit, and (e) the construct validity from a confirmatory factor analysis (CFA). Results. The T-MDAS showed good internal consistency (Cronbach’s α = 0.88) and temporal stability (ρ = 0.69, p p Conclusions The T-MDAS is a valid tool for assessing adult dental anxiety. The score is highly associated with dental-visiting behavior and experience of dental patients.

Background To investigate whether the endometrial thickness change ratio from the progesterone administration day to the blastocyst transfer day is associated with pregnancy outcomes in a single frozen-thawed euploid blastocyst transfer cycle. Methods All patients used natural cycles with luteal support for endometrial preparation and selected a single euploid blastocyst for transfer after a biopsy for preimplantation genetic testing. The endometrial thickness was measured by transvaginal ultrasound on the progesterone administration day and the transfer day, the change in endometrial thickness was measured, and the endometrial thickness change ratio was calculated. According to the change rate of endometrial thickness, the patients were divided into three groups: the endometrial thickness compaction group, endometrial thickness non-change group and endometrial thickness expansion group. Among them, the endometrial thickness non-change and expansion groups were combined into the endometrial thickness noncompaction group. Results Ultrasound images of the endometrium in 219 frozen-thawed euploid blastocyst transfer cycles were evaluated. The clinical pregnancy rate increased with the increase in endometrial thickness change ratio, while the miscarriage rate and live birth rate were comparable among the groups. The multiple logistic regression results showed that in the fully adjusted model a higher endometrial thickness change ratio (per 10%) was associated with a higher clinical pregnancy rate (adjusted odds ratio [aOR] 1.29; 95% confidence interval [CI], 1.01–1.64; P = .040). Similarly, when the patients were divided into three groups according to the change rate of endometrial thickness, the endometrial thickness noncompaction group had a significant positive effect on the clinical pregnancy rate compared with the endometrial thickness compaction group after adjusting for all covariates. Conclusions In frozen-thawed euploid blastocyst transfer cycles in which the endometrium was prepared by natural cycles with luteal support, the clinical pregnancy rate was higher in cycles without endometrial compaction after progesterone administration.

Background Obesity is associated with the development of polycystic ovary syndrome (PCOS) and contributes substantially to metabolic abnormalities in women with PCOS. The study aimed to describe and compare the practices of physicians in the diagnosis, evaluation, and treatment of obesity in patients with PCOS. Methods Reproductive endocrinologists (Repro-Endo) and obstetrician-gynecologists (non-reproductive medicine specialty, OB-Gyn) in China participated in a survey, and their responses were analyzed using χ2 tests, Fisher exact tests, and multivariable logistic regression analysis. Results The study analyzed 1318 survey responses (85.8% OB-Gyn; 97.3% women). Body mass index was the most common diagnostic criterion for obesity; only 1.3% of participants measured waist circumference to identify abdominal obesity. More Repro-Endo participants (25% of all participants) enquired about the psychological problems of patients with obesity than OB-Gyn participants, and 42.5% of participants reported ordering both a lipid profile and oral glucose tolerance test (OGTT) for patients with obesity and PCOS. Multivariable analysis, that included physician’s specialty, age, hospital grade, and number of patients with PCOS seen annually, revealed that OB-Gyn participants were less likely to order OGTT (OR, 0.3; 95% CI, 0.2–0.4) and lipid profile (OR, 0.2; 95% CI, 0.1–0.3) than Repro-Endo participants. The most common treatments for patients with PCOS were lifestyle modification (> 95%) and metformin (> 80%). More Repro-Endo participants prescribed metformin at a dose of 1.5 g/day compared with OB-Gyn (47.6% vs. 26.3%), and more OB-Gyn participants reported being unclear about the appropriate dosage of metformin for patients with obesity and PCOS (8.9% vs. 1.6%). Conclusion Our survey identified knowledge gaps in metabolic screening for patients with obesity and PCOS and a disparity in the evaluation and treatment of obesity in PCOS among different specialties. Similarly, it highlights the need to improve obesity management education for physicians caring for women with PCOS.

Background: Extensive clinical evidence suggests that a preventive screening of coronary heart disease (CHD) at an earlier stage can greatly reduce the mortality rate. We use 64 two-dimensional speckle tracking echocardiography (2D-STE) features and seven clinical features to predict whether one has CHD. Methods: We develop a machine learning approach that integrates a number of popular classification methods together by model stacking, and generalize the traditional stacking method to a two-step stacking method to improve the diagnostic performance. Results: By borrowing strengths from multiple classification models through the proposed method, we improve the CHD classification accuracy from around 70% to 87.7% on the testing set. The sensitivity of the proposed method is 0.903 and the specificity is 0.843, with an AUC of 0.904, which is significantly higher than those of the individual classification models. Conclusions: Our work lays a foundation for the deployment of speckle tracking echocardiography-based screening tools for coronary heart disease., 30 pages, 5 figures, 5 tables

Background Granulocyte-macrophage colony stimulating factor (GM-CSF) is a cytokine that is used as an immunopotentiator for anti-tumor therapies in recent years. We found that some of the extranodal natural killer/T cell lymphoma (ENKTL) patients with the treatment of hGM-CSF rapidly experienced disease progression, but the underlying mechanisms remain to be elucidated. Here, we aimed to explore the mechanisms of disease progression triggered by GM-CSF in ENKTL. Methods The mouse models bearing EL4 cell tumors were established to investigate the effects of GM-CSF on tumor growth and T cell infiltration and function. Human ENKTL cell lines including NK-YS, SNK-6, and SNT-8 were used to explore the expression of programmed death-ligand 1 (PD-L1) induced by GM-CSF. To further study the mechanisms of disease progression of ENKTL in detail, the mutations and gene expression profile were examined by next-generation sequence (NGS) in the ENKTL patient’s tumor tissue samples. Results The mouse-bearing EL4 cell tumor exhibited a faster tumor growth rate and poorer survival in the treatment with GM-CSF alone than in treatment with IgG or the combination of GM-CSF and PD-1 antibody. The PD-L1 expression at mRNA and protein levels was significantly increased in ENKTL cells treated with GM-CSF. STAT5A high-frequency mutation including p.R131G, p.D475N, p.F706fs, p.V707E, and p.S710F was found in 12 ENKTL cases with baseline tissue samples. Importantly, STAT5A-V706fs mutation tumor cells exhibited increased activation of STAT5A pathway and PD-L1 overexpression in the presence of GM-CSF. Conclusions These findings demonstrate that GM-CSF potentially triggers the loss of tumor immune surveillance in ENKTL patients and promotes disease progression, which is associated with STAT5 mutations and JAK2 hyperphosphorylation and then upregulates the expression of PD-L1. These may provide new concepts for GM-CSF application and new strategies for the treatment of ENKTL.

Background Serine hydroxymethyltransferase 2 (SHMT2) is a vital metabolic enzyme in one carbon metabolism catalyzing the conversion of serine to glycine, which has been reported to play a crucial role in the progression of tumors. However, its function in tongue squamous cell carcinoma (TSCC) remains unclear. Methods SHMT2 expression was analyzed using samples in online databases, and was assessed through immunohistochemistry staining of collected clinical specimens. The correlation between SHMT2 expression and the cell cycle was predicted through bioinformatic analysis, including weighted gene co-expression network analysis (WGCNA) and gene set enrichment analysis (GSEA). After transfection with siRNA, CCK8 assay, Edu staining, flow cytometry, trans-well assay, and wound healing experiments were performed to verify the functional role of SHMT2 in vitro. A stable cell line with SHMT2 silencing was established to detect the oncogenic function of SHMT2 in vivo. Results The expression of SHMT2 was up-regulated in TSCC tissues and cell lines compared with normal groups, and highly expressed SHMT2 significantly indicated a poorer clinical outcome for TSCC patients. Bioinformatic analysis found that high expression of SHMT2 was closely related with biologic process including cell cycle and cell cycle G1/S transition. Down regulating of SHMT2 significantly suppressed the proliferation, invasive and migrative ability of TSCC cells, and induced the prolongation of the G1 phase of the cell cycle in vitro. Furthermore, western blot showed that cell cycle-related regulators such as cyclin-dependent kinase 4 (CDK4) and cyclinD1 expression levels were decreased, while the expression levels of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 were increased after SHMT2 knockdown. Silencing SHMT2 in the HN6 cell line using short hairpin RNA also impeded tumor growth in vivo. Conclusions Overexpression of SHMT2 in TSCC indicated low survival rates, and was associated with aggressive behaviors of TSCC. It was also found to be involved in cell cycle regulation of TSCC cells. SHMT2 may serve as a novel prognostic indicator of TSCC.

Background Minqin is suffering from a serious desertification, whereas the knowledge about its bacterial community is limited. Herein, based on Nitraria tangutorum and Haloxylon ammodendron from Minqin, the bacterial community diversities in fixed sandy land, semi-fixed sandy land and shifting sandy land were investigated by combining with culture-dependent and culture-independent methods. Results Minqin stressed with high salinity and poor nutrition is an oligotrophic environment. Bacterial community in Minqin was shaped primarily by the presence of host plants, whereas the type of plant and sandy land had no marked effect on those, which displayed a better survival in the rhizospheres of N. tangutorum and H. ammodendron. The dominant groups at phyla level were Actinobacteria, Firmicutes, Proteobacteria, Bacteroidetes, Planctomycetes, Chloroflexi, Acidobacteria and Candidate_division_TM7. The abundance of Firmicutes with ability of desiccation-tolerance was significantly higher in harsh environment, whereas Bacteroidetes were mainly distributed in areas with high nutrient content. The abundances of Proteobacteria and Bacteroidetes were relatively high in the rhizospheres of N. tangutorum and H. ammodendron, which had more plant-growth promoting rhizobacteria. A large number of Actinobacteria were detected, of which the most abundant genus was Streptomyces. The physicochemical factors related to the diversity and distribution of the bacterial community were comprehensively analyzed, such as pH, electrical conductivity, soil organic matter, C/N and sand, and the results indicated that Minqin was more suitable for the growth of N. tangutorum, which should be one of most important sand-fixing plants in Minqin. Conclusions The bacterial community diversities in different types of sandy lands of Minqin were comprehensively and systematically investigated by culture-dependent and culture-independent approaches, which has a great significance in maintaining/restoring biological diversity.

Background Severe, steroid-resistant asthma (SSRA) is a serious clinical problem in asthma management. Affected patients have severe clinical symptoms, worsened quality of life, and do not respond to steroid, a mainstay steroid treatment of asthma. Thus, effective therapies are urgently needed. Exosomes derived from mesenchymal stem cell (MSC-Exo) has become attractive candidates for the lung inflammatory diseases through its immunomodulatory effects. In this study, we explored the therapeutic effects of MSC-Exo in SSRA and identified the therapeutic mechanism of MSC-Exo. Method Exosomes from human umbilical cord mesenchymal stem cell (hUCMSC) were isolated and characterized by transmission electron microscopy, nanoparticle tracking analysis and flow cytometry analysis. Effects of MSC-Exo on airway hyper responsiveness (AHR), inflammation, histopathology, and macrophage polarization in SSRA in mice were evaluated. Systematic depletion of macrophages determined the role of macrophages in the therapeutic effect of SSRA in mice. LPS-stimulated RAW 264.7 cell model was constructed to determine the underlying mechanism of MSC-Exo on macrophage polarization. qRT-PCR, Western blotting, immunofluorescence, and flow cytometry were performed to evaluate the expression of M1 or M2 markers. Tandem mass tags (TMT)-labeled quantitative proteomics were applied to explore the central protein during the regulation effect of MSC-Exo on macrophage polarization. Knockdown and overexpression of TRAF1 were used to further clarify the role of the central protein on macrophage polarization. Result We successfully isolated and characterized exosomes from hUCMSCs. We verified that the intratracheal administration of MSC-Exo reversed AHR, histopathology changes, and inflammation in SSRA mice. Systematic depletion of macrophages weakened the therapeutic effect of MSC-Exo. We found that MSC-Exo treatment inhibited M1 polarization and promoted M2 polarization in LPS-stimulated RAW 264.7 cells. Subsequently, tumor necrosis factor receptor-associated factor 1 (TRAF1) was determined as the central protein which may be closely related to the regulation of macrophage polarization from TMT-labeled quantitative proteomics analysis. Knockdown and overexpression of TRAF1 demonstrated that the effect of MSC-Exo treatment on macrophage polarization, NF-κB and PI3K/AKT signaling was dependent on TRAF1. Conclusion MSC-Exo can ameliorate SSRA by moderating inflammation, which is achieved by reshaping macrophage polarization via inhibition of TRAF1.

We present a Minimal Event Distance Aneuploidy Lineage Tree (MEDALT) algorithm that infers the evolution history of a cell population based on single-cell copy number (SCCN) profiles, and a statistical routine named lineage speciation analysis (LSA), whichty facilitates discovery of fitness-associated alterations and genes from SCCN lineage trees. MEDALT appears more accurate than phylogenetics approaches in reconstructing copy number lineage. From data from 20 triple-negative breast cancer patients, our approaches effectively prioritize genes that are essential for breast cancer cell fitness and predict patient survival, including those implicating convergent evolution.The source code of our study is available at https://github.com/KChen-lab/MEDALT.

Mouse homozygous mutants in Wnt/planar cell polarity (PCP) pathway genes have been shown to cause neural tube defects (NTDs) through the disruption of normal morphogenetic processes critical to neural tube closure (NTC). Knockout mice that are heterozygotes of single PCP genes likely fail to produce NTD phenotypes, yet damaging variants detected in human NTDs are almost always heterozygous, suggesting that other deleterious interacting variants are likely to be present. Nonetheless, the Wnt/PCP pathway remains a genetic hotspot. Addressing these issues is essential for understanding the genetic etiology of human NTDs.We performed targeted next-generation sequencing (NGS) on 30 NTD-predisposing Wnt/PCP pathway genes in 184 Chinese NTD cases. We subsequently replicated our findings for the CELSR1 gene in an independent cohort of 292 Caucasian NTD samples from the USA. Functional validations were confirmed using in vitro assays.CELSR1, CELSR2 and CELSR3 genes were significantly clustered with rare driver coding mutations (q-value 0.05) demonstrated by OncodriveCLUST. During the validation stage, the number of rare loss of function (LoF) variants in CELSR1 was significantly enriched in NTDs compared with the LoF counts in the ExAC database (p 0.001). Functional studies indicated compound heterozygote variants of CELSR2 p.Thr2026Met and DVL3 p.Asp403Asn result in down regulation of PCP signals.These data indicate rare damaging variants of the CELSR genes, identified in ~ 14% of NTD cases, are expected to be driver genes in the Wnt/PCP pathway. Compound damaging variants of CELSR genes and other Wnt/PCP genes, which were observed in 3.3% of the studied NTD cohort, are also expected to amplify these effects at the pathway level.

Background Oral lichen planus (OLP) is a chronic mucocutaneous disease characterized by adult predominance and a prolonged course. However, it is rare in the pediatric population with familial aggregation. Case presentation A 3-year-old boy presented with pain and irritation on the oral mucosa while contacting spicy food for 2 months. Oral examination showed widespread whitish reticular and papular lesions on the lips, the dorsum of the tongue, and bilateral buccal mucosa, with diffuse erosions covered with pseudomembrane on the buccal mucosa. The boy’s parents were examined to exhibit white reticular and plaque-like lesions on their oral mucosa. The three patients were clinically diagnosed as affected by OLP and histopathologically confirmed. The boy underwent topical treatment with recombinant bovine basic fibroblast growth factor (rb-bFGF) gel, and oral lesions gradually resolved and healed. Neither of his parents received treatment. During the subsequent follow-ups, none of three patients underwent any medical treatment. Fortunately, their lesions had almost faded over 8 years. Conclusions Our case emphasizes that pediatric OLP should be recorded with family history. Besides, long-term periodic follow-up is recommended in pediatric patients with OLP for monitoring any changes in lesions.

Background The prevalence of diabetes mellitus (DM) among patients with chronic kidney disease (CKD) has been increasing in recent years in China. This study aimed to evaluate the association between DM and health-related quality of life (HRQOL) in patients with CKD. Methods In our study, participants with CKD stage 1 to 4 from 39 centers in China were screened and enrolled. The Kidney Disease Quality of Life (KDQOL™-36) questionnaire was used to assess HRQOL. Participants were divided into a diabetic group and a non-diabetic group. Demographic data, clinical data, and HRQOL scores were compared between the two groups. Multivariable robust regression was used to analyze the factors related to HRQOL in CKD patients. Results A population of 2742 CKD patients was included in this study. CKD patients with DM were older and had lower education level, longer treatment periods and a higher prevalence of cardiovascular disease than CKD patients without DM (P P < 0.05). DM was negatively correlated with the symptoms and problems (regression coefficient for log transformed [175-score] = 0.010) and the SF-12 physical function dimension (regression coefficient = − 2.18) (all P Conclusion HRQOL of diabetic patients with CKD was worse than that of non-diabetic patients with CKD. DM was an independent and negative factor affecting HRQOL in patients with CKD.

Background To assess whether preimplantation genetic testing for aneuploidy with next generation sequencing (NGS) outweighs single nucleotide polymorphism (SNP) array in improving clinical outcomes. Methods A retrospective analysis of the clinical outcomes of patients who underwent PGT-A treatment in a single center from January 2013 to December 2017.A total of 1418 couples who underwent PGT-A treatment were enrolled, of which 805 couples used NGS for PGT-A, while the remaining 613 couples used SNP array for PGT-A. Clinical pregnancy rate, miscarriage rate and healthy baby rate were compared between the MALBAC-NGS-PGT-A and MDA-SNP-PGT-A groups. Results After testing karyotypes of 5771 biopsied blastocysts, 32.2% (1861/5771) were identified as chromosomally normal, while 67.8% were chromosomally abnormal. In terms of clinical outcomes, women in the MALBAC-NGS-PGT-A group had a significantly higher clinical pregnancy rate (50.5% vs 41.7%, p = 0.002) and healthy baby rate (39.6% vs 31.4%, p = 0.003), and a lower miscarriage rate (15.5% vs 22.8%, p = 0.036). Conclusion This is the largest study reporting the extensive application of NGS-based PGT-A, whilst comparing the clinical outcomes of MALBAC-NGS-PGT-A and MDA-SNP-PGT-A. The results provide greater evidence supporting the wider use of NGS in PGT-A, not only for its lower cost but also for its improved clinical outcomes compared to SNP-based PGT-A.

Background Wild sugarcane Saccharum spontaneum plants vary in ploidy, which complicates the utilization of its germplasm in sugarcane breeding. Investigations on cold tolerance in relation to different ploidies in S. spontaneum may promote the exploitation of its germplasm and accelerate the improvement of sugarcane varieties. Results A hypoploid clone 12–23 (2n = 54) and hyperploid clone 15–28 (2n = 92) of S. spontaneum were analysed under cold stress from morphological, physiological, and transcriptomic perspectives. Compared with clone 15–28, clone 12–23 plants had lower plant height, leaf length, internode length, stem diameter, and leaf width; depressed stomata and prominent bristles and papillae; and thick leaves with higher bulliform cell groups and thicker adaxial epidermis. Compared with clone 15–28, clone 12–23 showed significantly lower electrical conductivity, significantly higher water content, soluble protein content, and superoxide dismutase activity, and significantly higher soluble sugar content and peroxidase activity. Under cold stress, the number of upregulated genes and downregulated genes of clone 12–23 was higher than clone 15–28, and many stress response genes and pathways were affected and enriched to varying degrees, particularly sugar and starch metabolic pathways and plant hormone signalling pathways. Under cold stress, the activity of 6-phosphate glucose trehalose synthase, trehalose phosphate phosphatase, and brassinosteroid-signalling kinase and the content of trehalose and brassinosteroids of clone 12–23 increased. Conclusions Compared with hyperploid clone 15–28, hypoploid clone 12–23 maintained a more robust osmotic adjustment system through sugar accumulation and hormonal regulation, which resulted in stronger cold tolerance.

Background The novel coronavirus disease 2019(COVID-19) broke out globally. Early prediction of the clinical progression was essential but still unclear. We aimed to evaluate the timeline of COVID-19 development and analyze risk factors of disease progression.Methods In this retrospective study, we included 333 patients with laboratory-confirmed COVID-19 infection hospitalized in the Third People's Hospital of Shenzhen from 10 January to 10 February 2020. Epidemiological feature, clinical records, laboratory and radiology manifestations were collected and analyzed. 323 patients with mild-moderate symptoms on admission were observed to determine whether they exacerbated to severe-critically ill conditions (progressive group) or not (stable group). We used logistic regression to identify the risk factors associated with clinical progression.Results Of all the 333 patients, 70(21.0%) patients progressed into severe-critically ill conditions during hospitalization and assigned to the progressive group, 253(76.0%) patients belonged to the stable group, another 10 patients were severe before admission. we found that the clinical features of aged over 40 (3.80[1.72, 8.52]), males (2.21[1.20, 4.07]), with comorbidities (1.78[1.13, 2.81]) certain exposure history (0.38[0.20, 0.71]), abnormal radiology manifestations (3.56[1.13, 11.40]), low level of T lymphocytes (0.99[0.997, 0.999]), high level of NLR (0.99[0.97, 1.01]), IL-6 (1.05[1.03, 1.07]) and CRP (1.67[1.12, 2.47]) were the risk factors of disease progression by logistic regression.Conclusions the potential risk factors of males, older age, with comorbidities, low T lymphocyte level and high level of NLR, CRP, IL-6 can help to predict clinical progression of COVID-19 at an early stage.

Background Statistical data on burden of kidney cancer and the relavant risk factors are valuable for policy-making. This study aims to estimate kidney cancer deaths and high body-mass index (BMI) attributable to the deaths by gender and age group in China adults, compared with U.S. Methods We extracted kidney cancer data (1990–2017) about the age-standardized rates using the comparative risk assessment framework of the 2017 Global Burden of Disease study. We performed an age-period-cohort (APC) analysis to estimate trends of kidney cancer mortality attributable to high BMI. Results During 1990–2017, age-standardized mortality rate of kidney cancer was increasing in China but decreasing in U.S. The mortality attributable to high BMI in China showed a general increasing trend, while that in U.S. men was increasing and tended to be stable in women since 1995. APC analysis showed a similar pattern of age effect between China and U.S. adults, which substantially increased from 20 to 24 to 90–94 age group. Differently, the period effect rapidly increased in China than U.S. adults during 1990–2017. The cohort effect peaked in the earlier cohort born in 1902–1906 in China, and it declined consistently in U.S. with exception of 1902–1906 and 1907–1911 birth cohort. Conclusions The kidney cancer deaths attributable to high BMI, and period effect have been generally increasing in China adults, compared with U.S. adults in which the trend tends to be stable in recent years. The rapid aging may also intensify the increasing trend of kidney cancer death in China. Effective measures should be conducted on body weight control and care for kidney cancer prevention.

Background Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of ovarian stimulation. Prevention and early recognition of OHSS are important to ensure patient safety. Case presentation In this case, we reported a patient who underwent controlled ovarian hyperstimulation (COH) and in vitro fertilization (IVF). All embryos were cryopreserved to reduce possible OHSS. However, OHSS still occurred after the patient had a frozen-thawed embryo transfer (FET) with hormone replacement therapy (HRT) and obtained a dichorionic diamniotic triplet pregnancy. After multifetal pregnancy reduction (MFPR) and supportive treatment, all the symptoms regressed. Conclusions Prompt recognition of OHSS, especially in patients who have no history of ovulation induction and fresh embryo transfer, is very important. Multiple pregnancies may lead to severe OHSS because of the high level of human chorionic gonadotropin (hCG) in the early stages. We suggest that a single embryo transfer may be necessary and beneficial for patients.

Background This study aims to investigate the prevalence and associated factors of major depressive disorder (MDD) and generalized anxiety disorder (GAD) by gender in Chinese rural adults. Methods A total of 29,993 participants aged from 18 to 79 years from the Henan Rural Cohort Study were included in this study. The Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder-2 (GAD-2) were used to assess MDD and GAD through a face-to-face interview. Multivariate logistic regression model was conducted to analyze the associated factors for MDD and GAD. Results The age-standardized prevalence of MDD and GAD (and 95%CI) in the total sample were 5.41% (5.17–5.66%) and 4.94% (4.71–5.18%), respectively. Besides, the crude prevalence in women were significantly higher than men for both MDD (6.81% vs. 4.77%) and GAD (6.63% vs. 3.93%) (both P r = 0.88, P = 0.01). Further analysis revealed that age, sex, marital status, educational level, per capita monthly income, drinking, physical activity, and body mass index were associated with MDD and GAD in the overall sample. Gender difference was found among age groups for MDD (Pinteraction Conclusions These findings showed that Chinese rural adults were at low risk for prevalence of MDD and GAD. Women had higher prevalence and risks for MDD and GAD compared with men, indicating that women deserved more attention. Gender-specific interventions on the modifiable associated factors are urgently needed to improve the mental conditions for Chinese rural population. Clinical trial registration The Henan Rural Cohort Study has been registered in the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 2015-07-06.

Background Chemotherapy is a widely used treatment for cancer. However, the development of acquired multidrug resistance (MDR) is a serious issue. Emerging evidence has shown that the extracellular vesicles (EVs) mediate MDR, but the underlying mechanism remains unclear, especially the effects of chemotherapeutic agents on this process. Methods Extracellular vesicles isolation was performed by differential centrifugation. The recipient cells that acquired ATP-binding cassette sub-family B member 1 (ABCB1) proteins were sorted out from co-cultures according to a stringent multi-parameter gating strategy by fluorescence-activated cell sorting (FACS). The transfer rate of ABCB1 was measured by flow cytometry. The xenograft tumor models in mice were established to evaluate the transfer of ABCB1 in vivo. Gene expression was detected by real-time PCR and Western blotting. Results Herein, we show that a transient exposure to chemotherapeutic agents can strikingly increase Rab8B-mediated release of extracellular vesicles (EVs) containing ABCB1 from drug-resistant cells, and accelerate these EVs to circulate back onto plasma membrane of sensitive tumor cells via the down-regulation of Rab5. Therefore, intercellular ABCB1 transfer is significantly enhanced; sensitive recipient cells acquire a rapid but unsustainable resistance to evade the cytotoxicity of chemotherapeutic agents. More fascinatingly, in the xenograft tumor models, chemotherapeutical drugs also locally or distantly increase the transfer of ABCB1 molecules. Furthermore, some Non-small-cell lung carcinoma (NSCLC) patients who are undergoing primary chemotherapy have a rapid increase of ABCB1 protein in their monocytes, and this is obviously associated with poor chemotherapeutic efficacy. Conclusions Chemotherapeutic agents stimulate the secretion and recycling of ABCB1-enriched EVs through the dysregulation of Rab8B and Rab5, leading to a significant increase of ABCB1 intercellular transfer, thus assisting sensitive cancer cells to develop an urgent resistant phenotype. Our findings provide a new molecular mechanism of how chemotherapeutic drugs assist sensitive cancer cells in acquiring an urgent resistance.

Background Ependymal tumors are pathologically defined intrinsic neoplasms originating in the intracranial compartments or the spinal cord that affect both children and adults. The recently integrated classification of ependymomas based on both histological and molecular characteristics is capable of subgrouping patients with various prognoses. However, the application of histological and molecular markers in Chinese patients with ependymomas has rarely been reported. We aimed to demonstrate the significance of histological characteristics, the v-relavian reticuloendotheliosis viral oncogene homolog A (RELA) fusions and other molecular features in ependymal tumors. Methods We reviewed the histological characteristics of ependymal tumors using conventional pathological slides and investigate the RELA fusions and Cylclin D1 (CCND1) amplification by Fluorescence in situ hybridization (FISH) and trimethylation of histone 3 lysine 27 (H3K27me3) expression by immunohistochemistry (IHC) methods. SPSS software was used to analyze the data. Results We demonstrated that hypercellularity, atypia, microvascular proliferation, necrosis, mitosis, and an elevated Ki-67 index, were tightly associated with an advanced tumor grade. Tumor location, necrosis, mitosis and the Ki-67 index were related to the survival of the ependymomas, but Ki67 was the only independent prognostic factor. Additionally, RELA fusions, mostly presented in pediatric grade III intracranial ependymomas, indicated decreased survival times of patients, and closely related to the patients’ age, tumor grade, cellularity, cellular atypia, necrosis and Ki67 index in the intracranial ependymal tumors, whereas reduction of H3K27me3 predicted the worse prognosis in ependymal tumors. Conclusions Histological and molecular features facilitate tumor grading and prognostic predictions for ependymal tumors in Chinese patients.

We have previously reported that adiponectin (AD), an adipokine that is secreted by adipocytes, correlates well with progressive bone erosion in rheumatoid arthritis (RA). The exact mechanism of AD in promoting joint destruction remains unclear. Osteopontin (OPN) is required for osteoclast recruitment. We hypothesized that AD exacerbates bone erosion by inducing OPN expression in synovial tissue. This study aimed to evaluate a novel role for AD in RA.The serum levels of AD and OPN were determined in 38 patients with RA, 40 patients with osteoarthritis (OA), and 20 healthy controls using enzyme-linked immunosorbent assay (ELISA). AD and OPN production were measured by double immunofluorescence in RA and OA synovial tissue. Quantitative real-time PCR and immunofluorescence were used to evaluate the mRNA and protein expression levels of OPN in RA synovial fibroblasts (RASFs) and OA synovial fibroblasts after pre-incubation with AD, respectively. Migration of the RAW264.7 osteoclast precursor cell line was assessed using the Transwell migration assay and co-culture system. Bone destruction and osteoclastogenesis were assessed by immunohistochemical staining, microcomputed tomography and tartrate-resistant acid phosphatase (TRAP) staining in AD-treated collagen-induced arthritis (CIA) mice with or without OPN silencing. The expression levels of OPN and integrin αOur results indicated that the AD and OPN expression levels increased noticeably and were associated with each other in the RA serum. The AD distribution was coincident with that of OPN in the RA synovial tissue. AD stimulation of RASFs increased OPN production in a dose-dependent manner. AD-treated RASFs promoted RAW264.7 cell migration, and the effect was blocked with a specific antibody against OPN. Silencing of OPN using lentiviral-OPN short hairpin RNA reduced the number of TRAP-positive osteoclasts and the extent of bone erosion in the AD-treated CIA mice. When bound to integrin αOur study provides new evidence of AD involvement in bone erosion. AD induces the expression of OPN, which recruits osteoclasts and initiates bone erosion. These data highlight AD as a novel target for RA treatment.

Background SALL1 is a multi-zinc finger transcription factor that regulates organogenesis and stem cell development, but the role of SALL1 in tumor biology and tumorigenesis remains largely unknown. Methods We analyzed SALL1 expression levels in human and murine breast cancer cells as well as cancer tissues from different types of breast cancer patients. Using both in vitro co-culture system and in vivo breast tumor models, we investigated how SALL1 expression in breast cancer cells affects tumor cell growth and proliferation, metastasis, and cell fate. Using the gain-of function and loss-of-function strategies, we dissected the molecular mechanism responsible for SALL1 tumor suppressor functions. Results We demonstrated that SALL1 functions as a tumor suppressor in breast cancer, which is significantly down-regulated in the basal like breast cancer and in estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2) triple negative breast cancer patients. SALL1 expression in human and murine breast cancer cells inhibited cancer cell growth and proliferation, metastasis, and promoted cell cycle arrest. Knockdown of SALL1 in breast cancer cells promoted cancer cell growth, proliferation, and colony formation. Our studies revealed that tumor suppression was mediated by recruitment of the Nucleosome Remodeling and Deacetylase (NuRD) complex by SALL1, which promoted cancer cell senescence. We further demonstrated that the mechanism of inhibition of breast cancer cell growth and invasion by SALL1-NuRD depends on the p38 MAPK, ERK1/2, and mTOR signaling pathways. Conclusion Our studies indicate that the developmental control gene SALL1 plays a critical role in tumor suppression by recruiting the NuRD complex and thereby inducing cell senescence in breast cancer cells.

Background Mouse homozygous mutants in Wnt/planar cell polarity (PCP) pathway genes have been shown to cause neural tube defects (NTDs) through the disruption of normal morphogenetic processes critical to neural tube closure (NTC). Knockout mice that are heterozygotes of single PCP genes likely fail to produce NTD phenotypes, yet damaging variants detected in human NTDs are almost always heterozygous, suggesting that other deleterious interacting variants are likely to be present. Nonetheless, the Wnt/PCP pathway remains a genetic hotspot. Addressing these issues is essential for understanding the genetic etiology of human NTDs. Methods We performed targeted next-generation sequencing (NGS) on 30 NTD-predisposing Wnt/PCP pathway genes in 184 Chinese NTD cases. We subsequently replicated our findings for the CELSR1 gene in an independent cohort of 292 Caucasian NTD samples from the USA. Functional validations were confirmed using in vitro assays. Results CELSR1, CELSR2 and CELSR3 genes were significantly clustered with rare driver coding mutations (q-valueCELSR1 was significantly enriched in NTDs compared with the LoF counts in the ExAC database (p CELSR2 p.Thr2026Met and DVL3 p.Asp403Asn result in down regulation of PCP signals. Conclusions These data indicate rare damaging variants of the CELSR genes, identified in ~ 14% of NTD cases, are expected to be driver genes in the Wnt/PCP pathway. Compound damaging variants of CELSR genes and other Wnt/PCP genes, which were observed in 3.3% of the studied NTD cohort, are also expected to amplify these effects at the pathway level.

Background Long noncoding RNAs (lncRNAs) have recently emerged as important regulators in governing fundamental biological processes, and many of which are likely to have functional roles in tumorigenesis. Maternally expressed gene 3 (MEG3) gene encodes a lncRNA whose expression is lost in an expanding list of primary human tumors and tumor cell lines, however its biological role and regulatory mechanism in gastric cancer (GC) development and progression are poorly defined. Methods Quantitative RT-PCR analysis was used to determine whether aberrant MEG3 expression was associated with GC patients pTNM stage and pM state. Furthermore, the effect of ectopic expression of MEG3 on cell proliferation, migration, invasion and cell apoptosis was assessed by using CCK-8, wound healing, transwell invasion assays and flow cytometric analysis, respectively, in GC cell lines HGC-27 and MGC-803. Moreover, the competing endogenous RNA (ceRNA) activity of MEG3 on miR-181a was investigated via luciferase reporter assay and immunoblot analysis. Results MEG3 is decreased in GC patients and cell lines, and its expression was associated with metastatic GC. Furthermore, ectopic expression of MEG3 in HGC-27 and MGC-803 cells inhibited cell proliferation, migration, invasion, and promoted cell apoptosis, which might be due to MEG3 sequestering oncogenic miR-181 s in GC cells. Furthermore, MEG3 could up-regulated Bcl-2 via its competing endogenous RNA (ceRNA) activity on miR-181a. Conclusions These findings suggest that lncRNA MEG3, a ceRNA of miR-181 s, could regulate gastric carcinogenesis and may serve as a potential target for antineoplastic therapies.

Background To investigate the association of a coronary artery disease (CAD) risk SNP rs6903956 with asymptomatic hyperuricemia (aHU) susceptibility in Han Chinese. Methods Two hundred and twenty one patients with aHU and 447 healthy controls were recruited for this study. SNP rs6903956 were genotyped using TaqMan probe. Results The overall genotype and allele frequency distribution of the rs6903956 showed significant difference between aHU cases and controls (p