Effects of testosterone dose on depression-like behavior among castrated adult male rats.

Previous research has shown a decrease in serum testosterone levels in male patients with depression. In recent years, the results of testosterone replacement therapy (TRT) to improve depression have been mixed. Using the classic CUMS model, we induced depressive-like behaviors in rats and observed a decrease in their serum testosterone levels along with an increase in androgen receptor expression in the hippocampus. We then performed castration and sham surgery on male rats and found that testosterone deprivation led to the manifestation of depressive-like behavior that could be ameliorated by TRT. Through a repeated measures experiment consisting of five blocks over a period of 25 days, we discovered that the reduction in depressive-like behavior in testosterone-deprived rats began 22 days after drug administration (0.5 and 0.25 mg/rat). Furthermore, rats in 0.5mgT group showed the most significant improvements. Subsequently, this dose was used in CUMS rats and reduced the occurrence of depressive-like behaviors. Our study has demonstrated the complex interplay between depression and testosterone, as well as the intricate dose-response relationship between TRT and reduction in depression. Our research supports the use of TRT to alleviate depression, but dosage and duration of treatment are critical factors in determining efficacy.

Prediction of injury localization in preoperative patients with gastrointestinal perforation: a multiomics model analysis.

BACKGROUND: The location of gastrointestinal perforation is essential for severity evaluation and optimizing the treatment approach. We aimed to retrospectively analyze the clinical characteristics, laboratory parameters, and imaging features of patients with gastrointestinal perforation and construct a predictive model to distinguish the location of upper and lower gastrointestinal perforation. METHODS: A total of 367 patients with gastrointestinal perforation admitted to the department of emergency surgery in Fujian Medical University Union Hospital between March 2014 and December 2020 were collected. Patients were randomly divided into training set and test set in a ratio of 7:3 to establish and verify the prediction model by logistic regression. The receiver operating characteristic curve, calibration map, and clinical decision curve were used to evaluate the discrimination, calibration, and clinical applicability of the prediction model, respectively. The multiomics model was validated by stratification analysis in the prediction of severity and prognosis of patients with gastrointestinal perforation. RESULTS: The following variables were identified as independent predictors in lower gastrointestinal perforation: monocyte absolute value, mean platelet volume, albumin, fibrinogen, pain duration, rebound tenderness, free air in peritoneal cavity by univariate logistic regression analysis and stepwise regression analysis. The area under the receiver operating characteristic curve of the prediction model was 0.886 (95% confidence interval, 0.840-0.933). The calibration curve shows that the prediction accuracy and the calibration ability of the prediction model are effective. Meanwhile, the decision curve results show that the net benefits of the training and test sets are greater than those of the two extreme models as the threshold probability is 20-100%. The multiomics model score can be calculated via nomogram. The higher the stratification of risk score array, the higher the number of transferred patients who were admitted to the intensive care unit (P < 0.001). CONCLUSION: The developed multiomics model including monocyte absolute value, mean platelet volume, albumin, fibrinogen, pain duration, rebound tenderness, and free air in the peritoneal cavity has good discrimination and calibration. This model can assist surgeons in distinguishing between upper and lower gastrointestinal perforation and to assess the severity of the condition.

Frontoparietal network homogeneity as a biomarker for mania and remitted bipolar disorder and a predictor of early treatment response in bipolar mania patient.

OBJECTIVE: Previous studies have revealed the frontoparietal network (FPN) plays a key role in the imaging pathophysiology of bipolar disorder (BD). However, network homogeneity (NH) in the FPN among bipolar mania (BipM), remitted bipolar disorder (rBD), and healthy controls (HCs) remains unknown. The present study aimed to explore whether NH within the FPN can be used as an imaging biomarker to differentiate BipM from rBD and to predict treatment efficacy for patients with BipM. METHODS: Sixty-six patients with BD (38 BipM and 28 rBD) and 60 HCs participated in resting-state functional magnetic resonance imaging and neuropsychological tests. Independent component analysis and NH analysis were applied to analyze the imaging data. RESULTS: Relative to HCs, BipM patients displayed increased NH in the left middle frontal gyrus (MFG), and rBD patients displayed increased NH in the right inferior parietal lobule (IPL). Compared to rBD patients, BipM patients displayed reduced NH in the right IPL. Furthermore, support vector machine results exhibited that NH values in the right IPL could distinguish BipM patients from rBD patients with 69.70 %, 57.89 %, and 91.67 % for accuracy, sensitivity, and specificity, respectively, and support vector regression results exhibited a significant association between predicted and actual symptomatic improvement based on the reduction ratio of the Young` Mania Rating Scale total scores (r = 0.466, p < 0.01). CONCLUSION: The study demonstrated distinct NH values in the FPN could serve as a valuable neuroimaging biomarker capable of differentiating patients with BipM and rBD, and NH values of the left MFG as a potential predictor of early treatment response in patients with BipM.

Roles of N-linked glycosylation and glycan-binding proteins in placentation: trophoblast infiltration, immunomodulation, angiogenesis, and pathophysiology.

Protein N-linked glycosylation is a structurally diverse post-translational modification that stores biological information in a larger order of magnitude than other post-translational modifications such as phosphorylation, ubiquitination and acetylation. This gives N-glycosylated proteins a diverse range of properties and allows glyco-codes (glycan-related information) to be deciphered by glycan-binding proteins (GBPs). The intervillous space of the placenta is richly populated with membrane-bound and secreted glycoproteins. Evidence exists to suggest that altering the structural nature of their N-glycans can impact several trophoblast functions, which include those related to interactions with decidual cells. This review summarizes trophoblast-related activities influenced by N-glycan-GBP recognition, exploring how different subtypes of trophoblasts actively adapt to characteristics of the decidualized endometrium through cell-specific expression of N-glycosylated proteins, and how these cells receive decidua-derived signals via N-glycan-GBP interactions. We highlight work on how changes in N-glycosylation relates to the success of trophoblast infiltration, interactions of immunomodulators, and uterine angiogenesis. We also discuss studies that suggest aberrant N-glycosylation of trophoblasts may contribute to the pathogenesis of pregnancy complications (e.g. pre-eclampsia, early spontaneous miscarriages and hydatidiform mole). We propose that a more in-depth understanding of how N-glycosylation shapes trophoblast phenotype during early pregnancy has the potential to improve our approach to predicting, diagnosing and alleviating poor maternal/fetal outcomes associated with placental dysfunction.

Comparison between Clinical Utility of CXCL-8 and Clinical Practice Tumor Markers for Colorectal Cancer Diagnosis.

Owing to the high incidence and mortality rates of colorectal cancer (CRC), novel biomarkers for CRC diagnosis are critically needed. Therefore, this study is aimed at exploring the clinical utility of serum C-X-C motif chemokine 8 (CXCL-8) for CRC diagnosis and progression compared to the routinely used biomarkers, carcinoembryonic antigen (CEA), and carbohydrate antigen-19-9 (CA19-9). This study included 227 patients with CRC, 110 patients with colorectal adenoma (CA), and 123 healthy participants, who were recruited from the Fujian Medical University Union Hospital from July 1, 2019 to October 31, 2020. Serum concentrations of CXCL-8, CEA, and CA19-9 were detected using enzyme-linked immunosorbent assay and chemiluminescent microparticle immunoassay. Clinicopathological features of patients with CRC were collected and analyzed. The diagnostic efficacy of CXCL-8, CEA, and CA19-9 for CRC was evaluated using receiver operating characteristic (ROC) curves. We found that the serum concentrations of CXCL-8, CEA, and CA19-9 were significantly higher in patients with CRC than those in patients with CA and healthy controls. The diagnostic sensitivity of CXCL-8 alone was higher than those of CEA and CA19-9 both and when combined; thus, CXCL-8 may be better at discriminating patients with CRC from healthy controls and patients with CA. Moreover, combining CXCL-8 with CEA or CA19-9 improved their respective diagnostic performances in distinguishing patients with CRC from CA patients and healthy participants. Notably, we also found that serum concentrations of CXCL-8 were positively correlated with metastases and tumor size. Therefore, our study suggests that serum CXCL-8 may serve as an improved biomarker for CRC diagnosis compared to the traditional tumor markers CEA and CA19-9. Moreover, our findings indicate the potential efficacy of serum CXCL-8 levels as a CRC prognostic biomarker.

Methylated Septin 9 as a Promising Biomarker in the Diagnosis and Recurrence Monitoring of Colorectal Cancer.

Purpose: The clinical utility of plasma methylated septin 9 (mSEPT9) DNA in screening and recurrence monitoring for colorectal cancer (CRC) is highly promising. The present study was performed to determine the diagnostic value of mSEPT9 in CRC detection and recurrence monitoring in Chinese patients. Methods: Overall, 616 patients newly diagnosed with CRC and 122 individuals with no evidence of disease were recruited from October 1, 2019, to May 31, 2021, at Fujian Medical University Union Hospital. Plasma and serum samples were collected for analyzing mSEPT9, carcinoembryonic antigen (CEA), and carbohydrate antigen-19-9 (CA19-9). Data on clinicopathological characteristics were collected and analyzed. Sensitivity and specificity were calculated to evaluate the diagnostic potential of each marker; the receiver operating characteristic (ROC) curve was applied for the assessment of diagnostic value, and comparisons among mSEPT9, CEA, CA19-9, and their combination were assessed via ROC curves. Results: mSEPT9 achieved an overall sensitivity and specificity of 72.94% and 81.97%, respectively, with an area under the curve (AUC) value of 0.826, which were higher than those of CEA (sensitivity: 43.96%; specificity: 96.72%; AUC: 0.789) and CA19-9 (sensitivity: 14.99%; specificity: 96.61%; AUC: 0.590). The combination of mSEPT9, CEA, and CA19-9 further improved sensitivity, specificity, and AUC value (sensitivity: 78.43%; specificity: 86.07%; AUC: 0.878), respectively. Notably, the mSEPT9 positivity rate was significantly associated with TNM stage, T stage, N stage, tumor size, vascular invasion, and nerve invasion among patients with CRC. A 100% correlation was observed between the positive results of the mSEPT9 test and recurrence or metastasis in patients after therapeutic intervention. Conclusion: Our findings suggest that mSEPT9 may represent a potential biomarker for the diagnosis and prognosis of CRC compared with CEA and CA19-9. Postoperative mSEPT9 status may represent the first noninvasive marker of CRC recurrence or metastasis.

Predictive effect of Bayes discrimination in the level of serum protein factors and cognitive dysfunction in schizophrenia.

Finding molecular biomarkers that can be related to the degree of cognitive dysfunction in schizophrenia remains a challenge. The levels of 6 Serum Protein Factors (NGF, BDNF, IL-6, TNF-α, S100ß, GFAP) in peripheral blood of patients with schizophrenia were measured. The cognitive function of patients with schizophrenia was assessed by MATRICS Consensus Cognitive Battery (MCCB), a systematic assessment tool of international gold standard for cognitive function assessment of schizophrenia. To explore the correlation between these 6 biomarkers and the degree of cognitive dysfunction in schizophrenia,78 schizophrenic patients and 71 healthy controls were included in the study. The serum concentrations of BDNF and GFAP were lower in the patient group, but the concentrations of IL-6, TNF-α and S100ß were higher. The speed of information processing, word learning, reasoning and problem solving, visual learning T-score of the patient group were lower than the control group. Bayes discriminant function model has a high correct discriminant rate for the severity of cognitive dysfunction in schizophrenia. The level of serum protein factor and clinical symptom score of schizophrenia may forecast the degree of cognitive dysfunction, which is expected to be a potential biomarker to identify the degree of cognitive dysfunction of schizophrenia, and provide objective basis for the clinical diagnosis and treatment of patients with schizophrenia.

Estrogen Receptor Function: Impact on the Human Endometrium.

The physiological role of estrogen in the female endometrium is well established. On the basis of responses to steroid hormones (progesterone, androgen, and estrogen), the endometrium is considered to have proliferative and secretory phases. Estrogen can act in the endometrium by interacting with estrogen receptors (ERs) to induce mucosal proliferation during the proliferative phase and progesterone receptor (PR) synthesis, which prepare the endometrium for the secretory phase. Mouse knockout studies have shown that ER expression, including ERα, ERß, and G-protein-coupled estrogen receptor (GPER) in the endometrium is critical for normal menstrual cycles and subsequent pregnancy. Incorrect expression of ERs can produce many diseases that can cause endometriosis, endometrial hyperplasia (EH), and endometrial cancer (EC), which affect numerous women of reproductive age. ERα promotes uterine cell proliferation and is strongly associated with an increased risk of EC, while ERß has the opposite effects on ERα function. GPER is highly expressed in abnormal EH, but its expression in EC patients is paradoxical. Effective treatments for endometrium-related diseases depend on understanding the physiological function of ERs; however, much less is known about the signaling pathways through which ERs functions in the normal endometrium or in endometrial diseases. Given the important roles of ERs in the endometrium, we reviewed the published literature to elaborate the regulatory role of estrogen and its nuclear and membrane-associated receptors in maintaining the function of endometrium and to provide references for protecting female reproduction. Additionally, the role of drugs such as tamoxifen, raloxifene, fulvestrant and G-15 in the endometrium are also described. Future studies should focus on evaluating new therapeutic strategies that precisely target specific ERs and their related growth factor signaling pathways.

Estrogen Biosynthesis and Signal Transduction in Ovarian Disease.

Estrogen mainly binds to estrogen receptors (ERs) to regulate menstrual cycles and reproduction. The expression of ERalpha (ERα), ERbeta (ERß), and G-protein-coupled estrogen receptor (GPER) mRNA could be detected in ovary, suggesting that they play an important role in estrogen signal transduction in ovary. And many studies have revealed that abnormal expression of estrogen and its receptors is closely related to ovarian disease or malignant tumors. With the continuous development and research of animal models, tissue-specific roles of both ERα and ERß have been demonstrated in animals, which enable people to have a deeper understanding of the potential role of ER in regulating female reproductive diseases. Nevertheless, our current understanding of ERs expression and function in ovarian disease is, however, incomplete. To elucidate the biological mechanism behind ERs in the ovary, this review will focus on the role of ERα and ERß in polycystic ovary syndrome (PCOS), ovarian cancer and premature ovarian failure (POF) and discuss the major challenges of existing therapies to provide a reference for the treatment of estrogen target tissue ovarian diseases.

Classification of infinitesimal homeostasis in four-node input-output networks.

An input-output network has an input node [Formula: see text], an output node o, and regulatory nodes [Formula: see text]. Such a network is a core network if each [Formula: see text] is downstream from [Formula: see text] and upstream from o. Wang et al. (J Math Biol 82:62, 2021. https://doi.org/10.1007/s00285-021-01614-1 ) show that infinitesimal homeostasis can be classified in biochemical networks through infinitesimal homeostasis in core subnetworks. Golubitsky and Wang (J Math Biol 10:1-23, 2020) show that there are three types of 3-node core networks and three types of infinitesimal homeostasis in 3-node core networks. This paper uses the theory developed in Wang et al. (2021) to show that there are twenty types of 4-node core networks (Theorem 1.3) and seventeen types of infinitesimal homeostasis in 4-node core networks (Theorem 1.7). Biological contexts illustrate the classification theorems and show that the theory can be an aid when calculating homeostasis in specific biochemical networks.

TNFRSF11B Suppresses Memory CD4+ T Cell Infiltration in the Colon Cancer Microenvironment: A Multiomics Integrative Analysis.

Background: Colorectal cancer is a lethal cancer worldwide. Due to the low tumor mutation burden and low proportion of tumor-infiltrating lymphocytes in the microenvironment of most patients, innovative immunotherapeutic approaches need to be identified. Methods: Using the TCGA-COAD dataset (n = 514), we identified TNFRSF11B as a prognostic factor of colon cancer. An immunohistochemistry (IHC) dataset (n = 86), 290 single colorectal cancer cells (GSE81861), and 31 paired colon cancer transcriptional datasets were further applied to validate the function of TNFRSF11B, which was confirmed via fluorescence-activated cell sorting (FACS) analysis. Results: A risk score system consisting of eight immune-related genes (IRGs) (FGFR2, ZC3HAV1L, TNFRSF11B, CD79A, IGHV3-11, IGHV3-21, IGKV2D-30, and IGKV6D-21) was constructed to predict the prognosis of colon cancer patients. Only TNFRSF11B was closely correlated with late-stage lymph node metastasis and worse survival outcomes (p = 0.010, p = 0.014, and p = 0.0061). In our IHC dataset, 72.09% (62/86) of the colon cancer patients had TNFRSF11B overexpression with significantly shorter overall survival times (p = 0.072). High TNFRSF11B expression typically had a later TNM stage (p = 0.067), a higher frequency of lymph node (p = 0.029) and lymphovascular (p = 0.007) invasion, and a higher incidence of pneumonia (p = 0.056) than their counterparts. The expression of six genes (KRT18, ARPC5L, ACTG1, ARPC2, EZR, and YWHAZ) related to pathogenic E. coli infection was simultaneously increased with TNFRSF11B overexpression via gene set enrichment analysis (GSEA). These genes are involved in the regulation of the actin cytoskeleton, shigellosis, bacterial invasion of epithelial cells, and Salmonella infection. Finally, only activated memory CD4+ T cells (p = 0.017) were significantly decreased in the high TNFRSF11B expression group via CIBERSORT comparison, which was confirmed by TIMER2.0 analysis of the TCGA-COAD dataset. We also performed FACS analysis to show that TNFRSF11B decreased the infiltration of central memory CD4+ T cells and effector memory CD4+ T cells in the colorectal cancer microenvironment (all p <0.001). Conclusion: TNFRSF11B acts as a prognostic factor for colon cancer patients and could affect the colon cancer immune response. TNFRSF11B was closely related to lymph node invasion and pathogenic E. coli. infection, which may negatively affect memory-activated CD4+ T cell infiltration in colon cancer.

The structure of infinitesimal homeostasis in input-output networks.

Homeostasis refers to a phenomenon whereby the output [Formula: see text] of a system is approximately constant on variation of an input [Formula: see text]. Homeostasis occurs frequently in biochemical networks and in other networks of interacting elements where mathematical models are based on differential equations associated to the network. These networks can be abstracted as digraphs [Formula: see text] with a distinguished input node [Formula: see text], a different distinguished output node o, and a number of regulatory nodes [Formula: see text]. In these models the input-output map [Formula: see text] is defined by a stable equilibrium [Formula: see text] at [Formula: see text]. Stability implies that there is a stable equilibrium [Formula: see text] for each [Formula: see text] near [Formula: see text] and infinitesimal homeostasis occurs at [Formula: see text] when [Formula: see text]. We show that there is an [Formula: see text] homeostasis matrix [Formula: see text] for which [Formula: see text] if and only if [Formula: see text]. We note that the entries in H are linearized couplings and [Formula: see text] is a homogeneous polynomial of degree [Formula: see text] in these entries. We use combinatorial matrix theory to factor the polynomial [Formula: see text] and thereby determine a menu of different types of possible homeostasis associated with each digraph [Formula: see text]. Specifically, we prove that each factor corresponds to a subnetwork of [Formula: see text]. The factors divide into two combinatorially defined classes: structural and appendage. Structural factors correspond to feedforward motifs and appendage factors correspond to feedback motifs. Finally, we discover an algorithm for determining the homeostasis subnetwork motif corresponding to each factor of [Formula: see text] without performing numerical simulations on model equations. The algorithm allows us to classify low degree factors of [Formula: see text]. There are two types of degree 1 homeostasis (negative feedback loops and kinetic or Haldane motifs) and there are two types of degree 2 homeostasis (feedforward loops and a degree two appendage motif).

Procyanidin B2 Improves Oocyte Maturation and Subsequent Development in Type 1 Diabetic Mice by Promoting Mitochondrial Function.

Type 1 diabetes (T1D) results in decreased oocyte quality and compromised early embryonic development. Procyanidin B2 (PB2) is a natural compound extracted from grape seeds and has strong antioxidant activity in vivo. This study evaluated the effect of PB2 on oocyte maturation in diabetic mice. Diabetic mice were induced by streptozotocin (STZ) injection. PB2 was supplemented in the in vitro maturation medium, and the ratio of germinal vesicle breakdown (GVBD) and polar body extrusion (PBE), reactive oxygen species (ROS) levels, mitochondrial function, developmental ability, as well as crotonylation at H4K5 were determined in oocytes. PB2 can promote the extrusion of PBE (88.34% vs. 75.02%, P < 0.05); reduce the generation of ROS (1.12 vs. 1.96, P < 0.05); and improve the level of mitochondrial membrane potential (0.87 vs. 0.79 Δφm, P < 0.05), ATP level (1.31 vs. 0.71 pmol, P < 0.05), and mitochondria temperature (618.25 vs. 697.39 pixels, P < 0.05). The addition of PB2 also improved the level of oocyte crotonylation at H4K5 (crH4K5) (47.26 vs. 59.68 pixels, P < 0.05) and increased the blastocyst rate (61.51% vs. 36.07%, P < 0.05) after parthenogenetic activation. Our results are the first to reveal a role for PB2 in promoting the viability of oocytes by regulating the mitochondrial function. Moreover, we uncover that PB2 can improve the level of crH4K5, which provides a new strategy to combat the decline in oocyte quality of diabetic.

Different serum protein factor levels in first-episode drug-naive patients with schizophrenia characterized by positive and negative symptoms.

AIM: The clinical features of schizophrenia can be mainly divided into two symptom domains: positive and negative. Patients in each symptom domain respond differently to treatments, and their prognoses vary accordingly. Serum protein factors, such as nerve growth factor (NGF), neurotrophin-3 (NT-3), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), and the calcium-binding protein, S100ß, have been reported to be involved in the pathogenesis of schizophrenia. However, their roles in the positive and negative symptom domains have not been determined. In this study, we investigated whether the serum levels of these five protein factors differed among first-episode drug-naive schizophrenia patients in each symptom domain and in healthy controls. METHODS: Double-antibody sandwich ELISA were used to quantify the amounts of the five protein factors in serum. RESULTS: Compared with the levels in the controls (n = 60), increased serum levels of IL-6, IL-1ß, and S100ß and decreased serum levels of NGF and NT-3 were observed in first-episode drug-naive schizophrenia patients. Additionally, the serum levels of IL-6 and IL-1ß were significantly higher in schizophrenia patients characterized by negative symptoms (negative group, n = 37) than in those characterized by positive symptoms (positive group, n = 46). Based on multivariate regression analyses, serum levels of IL-1ß were positively associated with the Negative Symptom subscore of the Positive and Negative Syndrome Scale in the negative group and in all patients with schizophrenia. CONCLUSION: The two subtypes of schizophrenia may have different pathological mechanisms. Patients characterized by negative symptoms probably have more serious disturbances in neuroimmunology.

Primary Care Cluster RCT to Increase Diabetes Prevention Program Referrals.

INTRODUCTION: The Diabetes Prevention Program, an intensive lifestyle change program, effectively reduces the risk of progression from prediabetes to type 2 diabetes but is underutilized. An implementation study using formative research was undertaken to increase Diabetes Prevention Program referrals at a primary care clinic. STUDY DESIGN: A pragmatic, cluster randomized, mixed-methods study. SETTING/PARTICPANTS: Clusters were teams of primary care clinicians from 2 primary care clinics. The 3 intervention clusters had 8-11 clinicians, and the 3 control clusters had 7-20 clinicians. INTERVENTION: Implementation activities occurred from December 2017 to February 2019. The activities included targeted clinician education, a prediabetes clinician champion, and a custom electronic health record report identifying patients with prediabetes. MAIN OUTCOME MEASURES: The primary outcome was referral of patients with prediabetes to the institutional Diabetes Prevention Program. Study data, including patient demographic and clinical variables, came from electronic health record. Interviews with clinicians evaluated the implementation strategies. Generalized estimating equation analyses that accounted for multiple levels of correlation and interview content analysis occurred in 2019. RESULTS: Study clinicians cared for 2,992 patients with a prediabetes diagnosis or HbA1c indicative of prediabetes (5.7%-6.4%). Clinicians in the intervention clusters referred 6.9% (87 of 1,262) of patients with prediabetes to the Diabetes Prevention Program and those in the control clusters referred 1.5% (26 of 1,730). When adjusted for patient age, sex, race, HbA1c value, HbA1c test location, and insurance type, intervention clinicians had 3.85 (95% CI=0.40, 36.78) greater odds of referring a patient with prediabetes to the Diabetes Prevention Program. The 11 interviewed intervention clinicians had mixed opinions about the utility of the interventions, reporting the prediabetes clinic champion (n=7, 64%) and educational presentations (n=6, 55%) as most helpful. CONCLUSIONS: Intervention clinicians were more likely to make Diabetes Prevention Program referrals; however, the study lacked power to achieve statistical significance. Clinician interviews suggested that intervention components that triggered Diabetes Prevention Program referrals varied among clinicians.

The impacts of laser zona thinning on hatching and implantation of vitrified-warmed mouse embryos.

Embryo vitrification has advantages in assisted reproduction yet it also induces zona hardening. Laser zona thinning (LZT) is considered as a solution yet its efficacy and security have not been well studied. In this study, we used vitrified-warmed morulae from 2-month-old and 10-month-old ICR female mice as model to investigate the impacts that LZT treatment brings to the in vitro hatching process and implantation by analyzing hatching rate, implantation rate, and blastocyst quality. The results showed that the fully hatched rate was significantly higher after LZT treatment for both young (25.7% vs. 16.2%, P < 0.05) and aged (36.6% vs. 13.2%, P < 0.01) mice. For zona-thinned morulae in young mice, its onset of hatching occurred earlier (28.6% vs. 8.8%, P < 0.01) at D4 and with a greater percentage of U-shaped hatching at D5 (48.3% vs. 33.0%, P < 0.05). LZT treatment did not induce expression change of apoptosis-related genes in all groups (P > 0.05), but for young mice, the total cell number of day 5 blastocyst in zona-thinned group was significantly less than that of the control group (40.6 ± 5.1 vs. 59.9 ± 14.5, P < 0.01). At last, there was an increasing implantation rate in zona-thinned compared to the control group for young (63.8% vs. 52.5%, P > 0.05) and aged (55.6% vs. 47.2%; P > 0.05) mice after embryos were bilaterally transferred in the same recipient. In conclusion, the significant increase of fully hatched rate after LZT treatment is related to the advanced onset of hatching as well as the enhancement of superior hatching structure, and LZT also lead to a better implantation after embryo transfer.

Clinical Usefulness and Prognostic Value of Red Cell Distribution Width in Colorectal Cancer.

Red blood cell distribution width (RDW) indicates the heterogeneity in the size of circulating red blood cells. Increasing studies showed that RDW may be a diagnostic and prognostic marker in various tumors. To investigate the value of RDW as a biomarker in the diagnosis and prognosis of colorectal cancer (CRC), we evaluated 783 newly diagnosed CRC patients, 463 colorectal adenomas (CA) patients, and 331 healthy controls from June 2015 to October 2017 at Fujian Medical University Union Hospital. We found that RDW levels were significantly higher in CRC groups compared with both the CA and healthy control groups (P<0.001). Receiver-operating characteristic (ROC) analysis showed that the area under the ROC curve (AUC) for RDW, CEA, and CA19-9 was 0.643, 0.742, and 0.629 in discriminating CRC patients from healthy controls, respectively. When RDW cut-off value of 13.95 was applied, we distinguished CRC patients from healthy controls with a sensitivity of 41% and a specificity of 94%. Moreover, combined detection of RDW, CEA, and CA19-9 appeared to be a better diagnostic performance with a sensitivity of 56% and a specificity of 99%. However, RDW had little diagnostic value in the differential diagnosis between CRC patients and CA patients. More importantly, RDW levels were significantly associated with TNM stage, pT stage, pM stage, and tumor size among CRC patients. Overall, our study suggested that RDW might be an auxiliary biomarker for diagnosis and prognosis of CRC.

RNA-Seq transcriptome profiling of mouse oocytes after in vitro maturation and/or vitrification.

In vitro maturation (IVM) and vitrification have been widely used to prepare oocytes before fertilization; however, potential effects of these procedures, such as expression profile changes, are poorly understood. In this study, mouse oocytes were divided into four groups and subjected to combinations of in vitro maturation and/or vitrification treatments. RNA-seq and in silico pathway analysis were used to identify differentially expressed genes (DEGs) that may be involved in oocyte viability after in vitro maturation and/or vitrification. Our results showed that 1) 69 genes were differentially expressed after IVM, 66 of which were up-regulated. Atp5e and Atp5o were enriched in the most significant gene ontology term "mitochondrial membrane part"; thus, these genes may be promising candidate biomarkers for oocyte viability after IVM. 2) The influence of vitrification on the transcriptome of oocytes was negligible, as no DEGs were found between vitrified and fresh oocytes. 3) The MII stage is more suitable for oocyte vitrification with respect to the transcriptome. This study provides a valuable new theoretical basis to further improve the efficiency of in vitro maturation and/or oocyte vitrification.

Investigation of treatment methods in obstructive colorectal cancer.

PURPOSE: The aim of this study was to explore the treatment strategies for patients with obstructive colorectal cancer at different sites. METHODS: Treatment strategies were adopted according to the location of colorectal cancer and the condition of the patients when they were admitted to the hospital. Among a total of 134 patients, 29 patients were subjected to stent placement to relieve the obstruction before undergoing colorectal resection, 15 patients underwent per anum ileus catheterization to alleviate the symptoms of obstruction and waited for removal of the tumor within a limited time; 39 underwent intraoperative colonic lavage and colon resection with anastomosis and the remaining 51 patients were subjected to emergency surgery due to strangulation of the bowel, perforation, septic shock or other conditions before surgery. RESULTS: Stent placement was successfully performed on 23 patients, with a success rate of 79%. Ninety-five of 134 patients (71% had stage I anastomosis and only one case had anastomotic fistula. Infection of incision happened in 9 (7%) cases and 2 (1.5%) patients died of infection. CONCLUSIONS: Individualized treatment for patients with obstructive colorectal cancer can lead to tumor resection and stage I anastomosis, thereby avoiding the suffering of second-stage surgery or colostomy.

Single-incision laparoscopic appendectomy versus conventional 3-port laparoscopic appendectomy for appendicitis: an updated meta-analysis of randomized controlled trials.

PURPOSE: To compare the efficacy and safety of single-incision laparoscopic appendectomy (SILA) and conventional 3-port laparoscopic appendectomy (3-port LA) for appendectomy. METHODS: We searched the PubMed, Embase, Springer link, and the Cochrane library databases up to April, 2014, for relevant randomized controlled trials (RCTs). Data were pooled by weighted mean differences (WMDs) or odds ratios (ORs) with their 95% confidence intervals (CIs). RESULTS: We found 11 RCTs, with a collective total of 731 patients treated with SILA and 725 patients treated with 3-point LA. Results indicated no significant differences between SILA and 3-port LA in primary outcomes, including wound infection, intra-abdominal abscess, postoperative ileus, and total postoperative complications, and some secondary outcomes, including postoperative pain scores and length of hospital stay. However, SILA was associated with significantly longer operative times (WMD = 6.78, 95% CI = 3.78-9.79, P < 0.00001) and higher doses of analgesia (WMD = 0.96, 95% CI = 0.45-1.47, P = 0.0002) than the 3-port LA. CONCLUSION: Although there was no significant difference in the safety of SILA vs. that of 3-port LA, our findings do not support the application of SILA because of its significantly longer operative times and the higher doses of analgesia required compared with those for 3-point LA.