Regulation of the mammalian maternal-to-embryonic transition by eukaryotic translation initiation factor 4E.

Eukaryotic translation initiation factor 4E (eIF4E) mediates cap-dependent translation. Genetic and inhibitor studies show that eIF4E expression is required for the successful transition from maternal to embryonic control of mouse embryo development. eIF4E was present in the oocyte and in the cytoplasm soon after fertilization and during each stage of early development. Functional knockout (Eif4e-/-) by PiggyBac [Act-RFP] transposition resulted in peri-implantation embryonic lethality because of the failure of normal epiblast formation. Maternal stores of eIF4E supported development up to the two- to four-cell stage, after which new expression occurred from both maternal and paternal inherited alleles. Inhibition of the maternally acquired stores of eIF4E (using the inhibitor 4EGI-1) resulted in a block at the two-cell stage. eIF4E activity was required for new protein synthesis in the two-cell embryo and Eif4e-/- embryos had lower translational activity compared with wild-type embryos. eIF4E-binding protein 1 (4E-BP1) is a hypophosphorylation-dependent negative regulator of eIF4E. mTOR activity was required for 4E-BP1 phosphorylation and inhibiting mTOR retarded embryo development. Thus, this study shows that eIF4E activity is regulated at key embryonic transitions in the mammalian embryo and is essential for the successful transition from maternal to embryonic control of development.

AI in medical education: the moderating role of the chilling effect and STARA awareness.

BACKGROUND: The rapid growth of artificial intelligence (AI) technologies has been driven by the latest advances in computing power. Although, there exists a dearth of research on the application of AI in medical education. METHODS: this study is based on the TAM-ISSM-UTAUT model and introduces STARA awareness and chilling effect as moderating variables. A total of 657 valid questionnaires were collected from students of a medical university in Dalian, China, and data were statistically described using SPSS version 26, Amos 3.0 software was used to validate the research model, as well as moderated effects analysis using Process (3.3.1) software, and Origin (2021) software. RESULTS: The findings reveal that both information quality and perceived usefulness are pivotal factors that positively influence the willingness to use AI products. It also uncovers the moderating influence of the chilling effect and STARA awareness. CONCLUSIONS: This suggests that enhancing information quality can be a key strategy to encourage the widespread use of AI products. Furthermore, this investigation offers valuable insights into the intersection of medical education and AI use from the standpoint of medical students. This research may prove to be pertinent in shaping the promotion of Medical Education Intelligence in the future.

Secondary Atomization and Micro-Explosion Effect Induced by Surfactant and Nanoparticles on Enhancing the Combustion Performance of Al/JP-10/OA Nanofluid Fuel.

Aluminum/tetrahydrodicyclopentadiene/oleic acid (Al/JP-10/OA) nanofluid fuel is considered a potential fuel for aircraft powered by aviation turbine engines. However, an optimized formula for an Al/JP-10/OA system inducing a secondary atomization and micro-explosion effect and improving the burning performance needs to be developed. With this aim, in this work, the combustion characteristics of pure JP-10, JP-10/OA, JP-10/Al, and Al/JP-10/OA were experimentally tested, and a comparative analysis was conducted. Specifically, the influence of the surfactant and nanoparticle concentrations on the combustion characteristics of Al/JP-10/OA nanofluid fuel, including the flame structure, the flame temperature, the burning rate, the secondary atomization and micro-explosion effect, etc., were evaluated in detail. The results demonstrate that the addition of OA surfactant and Al nanoparticles had a significant effect on the burning rate of fuel droplets. The OA had an inhibition effect, while the Al nanoparticles had a promotion effect. As both OA and Al nanoparticles were added to the JP-10, the synergetic effect had to be considered. At the optimum ratio of OA to Al for the best suspension stability, there is a critical Al concentration of 1.0 wt.% from promotion to inhibition with increases in the Al concentration. The addition of OA and Al nanoparticles induced the secondary atomization and micro-explosion, resulting in an unsteady combustion and chaotic flame structure. The transient flame temperature of hundreds of Kelvins increased, the high-temperature flame zone widened, and thus, the energy release was elevated. Therefore, the combustion performance and energy release of Al/JP-10/OA nanofluid fuel can be improved through the secondary atomization and micro-explosion effect induced by the surfactant and nanoparticles.

Benefit from luteal phase progestin-primed ovarian stimulation with clomiphene citrate supplementation in young women with diminished ovarian reserve: a retrospective study. / åµæ³¡æœŸå’Œé»„ä½“æœŸé«˜å­•æ¿€ç´ çŠ¶æ€ä¿ƒæŽ’åµæ–¹æ¡ˆåœ¨å¹´è½»åµå·¢å‚¨å¤‡åŠŸèƒ½å‡é€€å¥³æ€§ä¸­çš„åº”ç”¨.

OBJECTIVES: To compare the pregnant outcomes of luteal phase progestin-primed ovarian stimulation (PPOS) protocol with clomiphene citrate supplementation (LPPOS+CC) and follicular phase PPOS+CC protocol (FPPOS+CC) in young women with diminished ovarian reserve (DOR). METHODS: A total of 483 women aged ≤35 years with DOR, who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)/embryo transfer (ET) with controlled ovarian stimulation using LPPOS+CC (n=257) or FPPOS+CC (n=226) protocols during June 2018 and December 2021 at the First Affiliated Hospital of Wenzhou Medical University, were included in this retrospective study. The baseline characteristics, ovarian stimulation, endocrinological indicators, clinical outcomes between the two groups, and pregnancy outcomes of women achieved at least one high-quality cleavage-stage embryo or good-morphology blastocyst between the two groups were compared. RESULTS: No statistically significant differences were identified between the groups with respect to number of oocytes retrieved, oocyte maturation rate, high-quality cleavage-stage embryo cycle rate, the percentage of women with profound pituitary suppression, preterm birth rate, and live birth rate (P>0.05). Compared to FPPOS+CC group, the duration of stimulation [11.0 (9.0,12.0) vs. 9.0 (8.0,11.0) d, P<0.01] was significantly longer in the LPPOS+CC group. The LH levels on the day of trigger [4.0 (2.7,5.3) vs. 5.1 (3.2,7.2) IU/L, P<0.01], the percentage of women with LH levels of >10 IU/L on the trigger day (3.13% vs. 10.67%, P<0.01), and the two pronucleate (2PN) rate of ICSI oocytes (72.16% vs. 79.56%, P<0.05) were significantly lower in the LPPOS+CC group than those in the FPPOS+CC group. The consumption of total gonadotropin [2213 (1650,2700) vs. 2000 (1575,2325) IU, P<0.01], the progesterone levels on the day of trigger [1.3 (0.8,2.9) vs. 0.9 (0.6,1.2) ng/mL, P<0.01], the clinical pregnancy rate [61.88% vs. 46.84%, P<0.01], and implantation rate [42.20% vs. 31.07%, P<0.01] in the LPPOS+CC group were significantly higher than those in the FPPOS+CC group. CONCLUSIONS: Compared to FPPOS+CC, the LPPOS+CC protocol appears to have better pregnancy outcomes for young women with DOR undergoing IVF-ICSI-ET.

Identification of key modules and driving genes in nonalcoholic fatty liver disease by weighted gene co-expression network analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive liver fat deposition, and progresses to liver cirrhosis, and even hepatocellular carcinoma. However, the invasive diagnosis of NAFLD with histopathological evaluation remains risky. This study investigated potential genes correlated with NAFLD, which may serve as diagnostic biomarkers and even potential treatment targets. METHODS: The weighted gene co-expression network analysis (WGCNA) was constructed based on dataset E-MEXP-3291. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to evaluate the function of genes. RESULTS: Blue module was positively correlated, and turquoise module negatively correlated with the severity of NAFLD. Furthermore, 8 driving genes (ANXA9, FBXO2, ORAI3, NAGS, C/EBPα, CRYAA, GOLM1, TRIM14) were identified from the overlap of genes in blue module and GSE89632. And another 8 driving genes were identified from the overlap of turquoise module and GSE89632. Among these driving genes, C/EBPα (CCAAT/enhancer binding protein α) was the most notable. By validating the expression of C/EBPα in the liver of NAFLD mice using immunohistochemistry, we discovered a significant upregulation of C/EBPα protein in NAFLD. CONCLUSION: we identified two modules and 16 driving genes associated with the progression of NAFLD, and confirmed the protein expression of C/EBPα, which had been paid little attention to in the context of NAFLD, in the present study. Our study will advance the understanding of NAFLD. Moreover, these driving genes may serve as biomarkers and therapeutic targets of NAFLD.

Agonist long protocol improves outcomes of vitrified-warmed embryo transfer in repeatedly thin endometrium.

RESEARCH QUESTION: Does follicular stimulation using human menopausal gonadotrophin (HMG) after pituitary down-regulation by a GnRH agonist improve endometrial thickness (EMT) and clinical outcomes of frozen-thawed embryo transfer (FET; using vitrified-warmed embryos) in women with thin endometrium after intensified oestrogen administration (IOA)? DESIGN: This was a retrospective study. A total of 627 patients attempted 683 FET cycles with at least one previous history of thin endometrium. None of the cycles reached over 7 mm EMT after using oral and vaginal oestradiol for more than 21 days (IOA protocol). A total of 129 cycles proceeded with FET, 305 cycles were cancelled, and 249 cycles involved administration of HMG following GnRH agonist pituitary down-regulation (GnRH agonist + HMG protocol) for further endometrial preparation. RESULTS: EMT became significantly greater (7.18 ± 1.14 mm versus 6.13 ± 0.63 mm, P < 0.001) using GnRH agonist + HMG compared with previous IOA cycles, but this was not related to serum oestrogen concentrations. A total of 213 cycles after the GnRH agonist + HMG protocol proceeded with FET, showing a significantly increased clinical pregnancy rate, implantation rate and live birth rate compared with those after IOA. CONCLUSIONS: The GnRH agonist + HMG protocol for endometrial preparation in FET cycles improves EMT in women with a thin endometrium after IOA and showed significantly better clinical outcomes than IOA. The authors suggest that the GnRH agonist + HMG protocol should be used for EMT that is less than 7 mm after there has been no optimal response to IOA.

Association between serum progesterone levels on the day of frozen-thawed embryo transfer and pregnancy outcomes after artificial endometrial preparation.

BACKGROUND: Previous studies have examined that a range of optimal serum P level during the implantation period was associated with optimal live birth rates. However, those results obtained with vaginal or intramuscular route of progesterone administration for luteal phase support (LPS) alone. Is there a relationship between the serum progesterone (P) on the day of frozen-thawed embryo transfer (FET) with the likelihood of a live birth (LB) in artificial cycles (AC) when using a combination of oral dydrogesterone and vaginal progesterone for LPS? METHODS: This was a retrospective study of 3659 FET cycles with artificial endometrial preparation in a Chinese tertiary-care academic medical centre from January 2015 to February 2017. Endometrial preparation was performed using estradiol (E2) valerate (Fematon-red tablets) 8 mg/d beginning on day 3 of the cycle, followed by administration of P both orally (8 mg/d Fematon-yellow tablets) and vaginally (400 mg/d; Utrogestan). The primary endpoint was live birth rate (LBR). The association between the serum P level on the embryo transfer day and pregnancy outcomes was evaluated by univariable and multivariable logistic regression analysis. RESULTS: The LBRs according to the serum P quartiles were as follows: Q1: 35.7%; Q2: 37.4%; Q3: 39.1% and Q4: 38.9%. Logistic regression analysis showed that the odds of a LB were not significantly different between the low (P < 7.9 ng/mL) and high (P ≥ 7.9 ng/mL) progesterone groups before or after adjustment (crude OR = 0.89, 95% CI: 0.76-1.04; adjusted OR = 0.89, 95% CI: 0.75-1.04). CONCLUSION: The present study suggests that the serum P levels on the day of embryo transfer (ET) do not correlate with the likelihood of a LB in artificial cycles when using a combination of oral dydrogesterone and vaginal progesterone for luteal phase support.

Effect of exposed-to-air frequency of cryopreserved embryo on clinical outcomes of vitrified-warmed embryo transfer cycles: a retrospective analysis of 9,200 vitrified-warmed transfer cycles.

BACKGROUND: Cryopreservation of embryos plays a major role in the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment. However, the storage condition of the cryopreserved embryo can change temporarily due to repeated retrieval of the embryo from the liquid nitrogen (LN2) tank during the practical application during cryopreservation. Whether the implantation potential of a cryopreserved embryo will be damaged when the cane containing it is temporarily exposed to air due to the transfer between the LN2 tank and LN2 container is yet to be elucidated. Also, whether the exposed-to-air frequency (EAF) of cryopreserved embryos influences the clinical outcomes is unclear. OBJECTIVE: To investigate whether the EAF of cryopreserved embryo affects the clinical outcomes of vitrified-warmed embryo transfer. METHODS: A total of 9200 vitrified-warmed embryo transfer cycles were included in this study. All cycles were divided into five groups according to different EAFs (2, 4, 6, 8, or ≥ 10). Post-warming survival rates and clinical outcomes, including implantation, clinical pregnancy and live birth rates were investigated. Kruskal-Wallis test and Pearson's chi-squared tests were used to compare the patient characteristics and clinical outcomes among the five groups. Furthermore, multivariate logistic regression analyses were conducted to investigate the association between EAF and clinical outcomes. RESULTS: No significant differences were observed in the positive HCG rate, implantation rate and live birth rate (P > 0.05) among five EAF groups with respect to D3 embryo, D5 blastocyst and D6 blastocyst. Post-warmed survival rate of D3 embryos (P = 0.015) differed significantly among the five EAF groups, but it was not EAF-dependent. Although clinical pregnancy was different among the five groups with respect to D5 blastocyst (P = 0.042), multivariate logistic regression analysis adjusted for confounding variables suggested that EAF did not adversely affect clinical pregnancy or live birth. CONCLUSION: These findings indicated that human vitrified embryos in the open system could be repeatedly retrieved from the LN2 tank without affecting the implantation potential of the embryo.

Experiments and Numerical Simulation of N-decane/Ethanol Bi-Component Droplet Evaporation.

The evaporation characteristics of n-decane-based bi-component or multi-component droplets have been veiled for application in advanced combustion. This paper proposes to experimentally investigate the evaporation of n-decane/ethanol bi-component droplets settled in the convective hot air, and numerically simulate the key parameters affecting the evaporation charactersitics. It was found that the evaporation behavior was interactively affected by the mass fraction of ethanol and the ambient temperature. For mono-component n-decane droplets, the evaporation process included the transient heating (non-isothermal) and steady evaporation (isothermal) stages. In the isothermal stage, the evaporation rate followed d2-law. The evaporation rate constant linearly increased as the ambient temperature enhanced (573~873 K). For n-decane/ethanol bi-component droplets, at low mass fractions (≤0.2), the isothermal evaporation processes were steady due to the good miscibility between n-decane and ethanol, like mono-component n-decane, whereas at high mass fractions (≥0.4), the evaporation process experienced ultrashort heating and fluctuating evaporation stages. During the fluctuating evaporation, the bubbles formed inside the bi-component droplets and expanded, resulting in the occurrence of the microspray (secondary atomization) and the microexplosion. The evaporation rate constant of bi-component droplets increased as the ambient temperature enhanced, and showed a "V-shaped" trend with the increase of the mass fraction, and the evaporation rate constant was the smallest at 0.4. The evaporation rate constants based on the numerical simulation by using the multiphase flow model and Lee model showed reasonable agreement with the experimental ones, suggesting a potential of application in practical engineering.

Effect of Nanoparticle Addition on Evaporation of Jet Fuel Liquid Films and Nanoparticle Deposition Patterns during Evaporation.

Jet fuel-based nanofluid fuel has been proposed for improving the energy density and utilization efficiency of jet fuel that is widely applied in aircraft powered by aviation turbine engines. To recognize the evaporation behavior of the formed liquid film as a jet fuel-based nanofluid sprayed onto the engine wall or blades, this paper presents the evaporation and deposition characteristics of the jet fuel-based nanofluid liquid film adhering on the hydrophilic substrate. The changes in contact line, contact angle, volume, and deposition pattern during liquid film evaporation under different substrate temperatures, different nanoparticle concentrations, and different kinds of nanoparticle additions were investigated. The effect of nano-Al addition on the evaporation kinetics and deposition pattern of the nano-Al/jet fuel (nAl/JF) nanofluid fuel liquid film was explored. Repeated pinning and de-pinning of contact lines during evaporation occurred, resulting in the formation of concentric multi-ring deposition patterns. The addition of nano-Al increased the evaporation rate and shortened the evaporation lifetime, demonstrating a promotion effect on jet fuel liquid film evaporation. The existence of an energy barrier shows that the movement of three-phase contact lines on the hydrophilic solid surface presented not a continuous sliding behavior but a "stick-slip" behavior, and there were multiple jumps in contact lines and contact angles. Finally, a comparison was made with the deposition pattern of jet fuel liquid films with different graphite and Fe nanoparticle additions during evaporation. The mechanism of deposition phenomena was deeply revealed by the analysis of capillary flow and Marangoni recirculation.

A stent-based diverting technique after low anterior resection of rectal cancer: our preliminary experience.

BACKGROUND: Anastomotic leakage (AL) is a severe complication of rectal cancer low anterior resection (LAR). Ileostomy, the most common method to reduce the severity of AL, is associated with the risk of permanent stoma and an additional operation for stoma reversal. This purpose of this study is to develop a novel protective technique called the stent-based diverting technique (SDT) to protect the anastomosis following LAR. METHODS: From March 2020 to December 2020, thirty-four patients treated with LAR followed by SDT were enrolled prospectively at Sir Run Run Shaw Hospital. Demographic characteristics, laboratory test results, surgical outcomes, and oncological features were recorded. RESULTS: Overall, the median period of stent degradation was 21 (18-24) days. One patient (2.9%) had anastomotic leakage, and another patient (2.9%) had intestinal obstruction, while no other complications (e.g., intestinal volvulus, perforation, fistula) were observed in this study. CONCLUSIONS: The unique SDT may be a novel approach to prevent anastomotic leakage following low anterior resection of rectal cancer.

Fast Noninvasive Morphometric Characterization of Free Human Sperms Using Deep Learning.

The selection of high-quality sperms is critical to intracytoplasmic sperm injection, which accounts for 70­80% of in vitro fertilization (IVF) treatments. So far, sperm screening is usually performed manually by clinicians. However, the performance of manual screening is limited in its objectivity, consistency, and efficiency. To overcome these limitations, we have developed a fast and noninvasive three-stage method to characterize morphology of freely swimming human sperms in bright-field microscopy images using deep learning models. Specifically, we use an object detection model to identify sperm heads, a classification model to select in-focus images, and a segmentation model to extract geometry of sperm heads and vacuoles. The models achieve an F1-score of 0.951 in sperm head detection, a z-position estimation error within ±1.5 µm in in-focus image selection, and a Dice score of 0.948 in sperm head segmentation, respectively. Customized lightweight architectures are used for the models to achieve real-time analysis of 200 frames per second. Comprehensive morphological parameters are calculated from sperm head geometry extracted by image segmentation. Overall, our method provides a reliable and efficient tool to assist clinicians in selecting high-quality sperms for successful IVF. It also demonstrates the effectiveness of deep learning in real-time analysis of live bright-field microscopy images.

A Routing Optimization Method for Software-Defined Optical Transport Networks Based on Ensembles and Reinforcement Learning.

Optical transport networks (OTNs) are widely used in backbone- and metro-area transmission networks to increase network transmission capacity. In the OTN, it is particularly crucial to rationally allocate routes and maximize network capacities. By employing deep reinforcement learning (DRL)- and software-defined networking (SDN)-based solutions, the capacity of optical networks can be effectively increased. However, because most DRL-based routing optimization methods have low sample usage and difficulty in coping with sudden network connectivity changes, converging in software-defined OTN scenarios is challenging. Additionally, the generalization ability of these methods is weak. This paper proposes an ensembles- and message-passing neural-network-based Deep Q-Network (EMDQN) method for optical network routing optimization to address this problem. To effectively explore the environment and improve agent performance, the multiple EMDQN agents select actions based on the highest upper-confidence bounds. Furthermore, the EMDQN agent captures the network's spatial feature information using a message passing neural network (MPNN)-based DRL policy network, which enables the DRL agent to have generalization capability. The experimental results show that the EMDQN algorithm proposed in this paper performs better in terms of convergence. EMDQN effectively improves the throughput rate and link utilization of optical networks and has better generalization capabilities.

The Clinical Application of Growth Hormone and Its Biological and Molecular Mechanisms in Assisted Reproduction.

Growth hormone (GH) has been used as a co-gonadotrophin in assisted reproduction, particularly in poor ovarian responders. The application of GH has been alleged to activate primordial follicles and improve oocyte quality, embryo quality, and steroidogenesis. However, the effects of GH on the live birth rate among women is controversial. Additionally, although the basic biological mechanisms that lead to the above clinical differences have been investigated, they are not yet well understood. The actions of GH are mediated by GH receptors (GHRs) or insulin-like growth factors (IGFs). GH regulates the vital signal transduction pathways that are involved in primordial follicular activation, steroidogenesis, and oocyte maturation. However, the therapeutic windows and duration of GH administration during assisted reproductive technology require further investigation. The review aimed to clarify the role of GH in human fertility from a molecular and biological point of view to provide evidence for proper GH administration.

Diosgenin Derivatives as Potential Antitumor Agents: Synthesis, Cytotoxicity, and Mechanism of Action.

Thirty-two new diosgenin derivatives were designed, synthesized, and evaluated for their cytotoxic activities in three human cancer cell lines (A549, MCF-7, and HepG2) and normal human liver cells (L02) using an MTT assay in vitro. Most compounds, especially 8, 18, 26, and 30, were more potent when compared with diosgenin. The structure-activity relationship results suggested that the presence of a succinic acid or glutaric acid linker, a piperazinyl amide terminus, and lipophilic cations are all beneficial for promoting cytotoxic activity. Notably, compound 8 displayed excellent cytotoxic activity against HepG2 cells (IC50 = 1.9 µM) and showed relatively low toxicity against L02 cells (IC50 = 18.6 µM), showing some selectivity between normal and tumor cells. Studies on its cellular mechanism of action showed that compound 8 induces G0/G1 cell cycle arrest and apoptosis in HepG2 cells. Predictive studies indicated that p38α mitogen-activated protein kinase (MAPK) is the optimum target of 8 based on its 3D molecular similarity, and docking studies showed that compound 8 fits well into the active site of p38α-MAPK and forms relatively strong interactions with the surrounding amino acid residues. Accordingly, compound 8 may be used as a promising lead compound for the development of new antitumor agents.

Synthesis and Biological Evaluation of Celastrol Derivatives as Potential Immunosuppressive Agents.

Celastrol, a friedelane-type triterpenoid isolated from the genus Triperygium, possesses antitumor, anti-inflammatory, and immunosuppressive activities. A total of 42 celastrol derivatives (1a-1t, 2a-2l, and 3a-3j) were synthesized and evaluated for their immunosuppressive activities. Compounds 2a-2e showed immunosuppressive effects, with IC50 values ranging from 25 to 83 nM, and weak cytotoxicity (CC50 > 1 µM). Compound 2a, with a selectivity index value 31 times higher than that of celastrol, was selected as a lead compound. Further research showed that 2a exerted its immunosuppressive effects by inducing apoptosis and inhibiting cytokine secretion via Lck- and ZAP-70-mediated signaling pathways.

Immunomodulatory effect of oleoylethanolamide in dendritic cells via TRPV1/AMPK activation.

Oleoylethanolamide (OEA) is an endogenous lipid mediator involved in the control of feeding, body weight, and energy metabolism. However, whether OEA modulates maturation of dendritic cells (DCs) has never been addressed. Hence, we evaluated the effect of OEA on DCs maturation in bone marrow-derived DCs (BMDCs) in four aspects: (a) Cell surface markers were determined using flow cytometric analysis; (b) cell mobile ability was testified with the transwell assay; (c) stimulation of T cells proliferation was performed in a coculture system; and (d) cytokine production was measured using polymerase chain reaction (PCR). The result showed that, in mature BMDCs induced by lipopolysaccharides (LPS), the OEA treatment decreased expressions of cell surface markers, reduced cell migration, diminished the proliferation of cocultured T cells, and regulated cytokine production of BMDCs, indicating the modulatory effect of OEA on DCs maturation. Furthermore, to explore the underlying mechanism of the immunomodulatory effect of OEA, we used antagonists of transient receptor potential vanilloid-1 (TRPV1) and AMP-activated protein kinase (AMPK), determined the protein expressions of TRPV1/AMPK and Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) using western blot, and measured the intracellular calcium concentration using calcium imaging. The result illustrated that OEA downregulated TLR4/NF-κB, the classical pathway leading to DCs maturation induced by LPS, through the activation of TRPV1 and AMPK. Collectively, the present study suggests that OEA suppresses DCs maturation through the activation of TRPV1/AMPK. These findings increase our understanding of this endogenous lipid OEA.

Serum chitinase activity prognosticates metastasis of colorectal cancer.

BACKGROUND: This study aimed to evaluate the value of chitinase activity in prognosticating the occurrence of metastasis in and prognosis of patients with colorectal cancer (CRC). METHODS: The chitinase activity in four different groups, namely 335 CRC patients without distant metastasis at their first visit (Group 1), 51 patients with CRC having synchronous liver metastasis (Group 2), 100 healthy age-matched controls (Group 3) and 40 patients with liver cancer (Group 4), were assayed using an enzyme-linked immunosorbent assay. The Cox proportional hazards ratio model and Kaplan-Meier curve were used to identify the association between chitinase activity and the clinical outcome of CRC patients without metastasis in the training set and testing set at their first visit. An in vitro Transwell experiment was performed to evaluate the migration of colon cancer cells. RESULTS: Patients with high chitinase activity had a significantly higher metastasis risk than those with low chitinase activity in the training and testing sets during follow-up, both at stage I/II and stage III. Further, multivariate analysis revealed that chitinase activity was an independent risk factor prognosticating liver metastases (P = 0.001). The combination of chitinase activity and lymph node metastasis status increased the accuracy of the prognosis of liver metastases after radical resection (P = 0.454E-011). In addition, chitinase promoted CRC cell migration in vitro. CONCLUSIONS: Chitinase activity can prognosticate the occurrence of metastasis in patients with CRC. Moreover, the combination of chitinase activity and N stage increased the power of prognosticating the occurrence of metastasis. Inhibiting chitinase activity may serve as a new strategy to treat metastases of CRC.

Fast-track multidisciplinary treatment versus conventional treatment for colorectal cancer: a multicenter, open-label randomized controlled study.

BACKGROUND: Laparoscopic surgery, fast-track perioperative treatment and XELOX chemotherapy are effective strategies for shortening the duration of hospital stay for cancer patients. This trial aimed to clarify the safety and efficacy of the fast-track multidisciplinary treatment (FTMDT) model compared to conventional surgery combined with chemotherapy in Chinese colorectal cancer patients. METHODS: This trial was a prospective randomized controlled study with a 2 × 2 balanced factorial design and was conducted at six hospitals. Patients in group 1 (FTMDT) received fast-track perioperative treatment and XELOX adjuvant chemotherapy. Patients in group 2 (conventional treatment) received conventional perioperative treatment and mFOLFOX6 adjuvant chemotherapy. Subgroups 1a and 2a had laparoscopic surgery and subgroups 1b and 2b had open surgery. The primary endpoint was total length of hospital stay during treatment. RESULTS: A total of 374 patients were randomly assigned to the four subgroups, and 342 patients were finally analyzed, including 87 patients in subgroup 1a, 85 in subgroup 1b, 86 in subgroup 2a, and 84 in subgroup 2b. The total hospital stay of group 1 was shorter than that of group 2 [13 days, (IQR, 11-17 days) vs. 23.5 days (IQR, 15-42 days), P = 0.0001]. Compared to group 2, group 1 had lower surgical costs, fewer in-hospital complications and faster recovery (all P < 0.05). Subgroup 1a showed faster surgical recovery than that of subgroup 1b (all P < 0.05). There was no difference in 5-year overall survival between groups 1 and 2 [87.1% (95% CI, 80.7-91.5%) vs. 87.1% (95% CI, 80.8-91.4%), P = 0.7420]. CONCLUSIONS: The FTMDT model, which integrates laparoscopic surgery, fast-track treatment, and XELOX chemotherapy, was the superior model for enhancing the recovery of Chinese patients with colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01080547 , registered on March 4, 2010.

Does oral contraceptives pretreatment affect the pregnancy outcome in polycystic ovary syndrome women undergoing ART with GnRH agonist protocol?

This study aims to investigate whether oral contraceptive pills (OCP) pretreatment impairs pregnancy outcomes in polycystic ovary syndrome (PCOS) women undergoing GnRH agonist protocol. A total of 1025 couples underwent their first cycle of in vitro fertilization. Patients were divided into GnRH agonist protocol group (LP group) and OCP dual suppression GnRH agonist protocol group (OC-LP group). Logistic regressions were performed to estimate the risk factors affecting live birth following fresh embryo transfer between groups. Frozen-thawed embryos from the first oocyte retrieval cycle were replaced into uterus for women did not get live birth. Cumulative live birth rates between groups were compared by Kaplan-Meier survival analysis. Serum luteinizing hormone level, endometrial thickness, and live birth rate were significantly reduced in the OC-LP group in fresh cycle. Thinner endometrium, higher progesterone, and poorer embryo quality were independent risk factors for failure in getting live birth following fresh embryo transfer. However, cumulative live birth rate, medium embryo transfer attempts required to achieve live birth were comparable between groups. OCP pretreatment in GnRH agonist protocol does not seem to impair the pregnancy outcome when calculated by cumulative live birth rate in PCOS women.