Objective:To compare the clinical outcomes of single oral dydrogesterone with vaginal progesterone gel plus oral dydrogesterone in gonadotropin-releasing hormone (GnRH) antagonist cycles with fresh embryo transfer.Methods:This study retrospectively analyzed 658 treatment cycles of fresh embryo transfer cycle with GnRH antagonist protocol from December 2015 to December 2020 in the Center of Reproductive Medicine of the University of Hong Kong-Shenzhen Hospital. Each cycle was the first fresh stimulation cycle of the patients. The patients were divided into two groups according to different luteal support regimens. Group A included 368 cycles with a regimen of 30 mg dydrogesterone tablets orally daily, while group B included 290 cycles with a regimen of 90 mg vaginal progesterone gel vaginally daily combined with 20 mg dydrogesterone tablets orally daily. A 1∶1 propensity score matching (PSM) was carried out to adjust for numerical differences and to balance between the two groups, and further they were divided into cleavage stage embryo transfer cycles and the blastocyst transfer cycles according to the different type of embryo for layer analysis, and the laboratory results and assisted reproductive outcomes of the two groups were compared.Results:After matching, the baseline characteristics were comparable between the two groups, with 251 cycles remaining in each group for retrospective analysis. After PSM, statistically significant differences were observed between group A and group B in laboratory data including the number of fertilized oocytes [5 (2, 7) vs. 6 (3, 9), P=0.002], cleavage rate [100.0% (86.31%, 100.0%) vs. 87.28% (75.32%, 100.0%), P<0.001], and available embryo rate [80.18% (54.64%, 100.0%) vs. 67.48% (50.62%, 100.0%), P=0.019]. However, there were no significantly statistical differences in other laboratory data and clinical outcomes (all P>0.05). If we divided the data into two comparison according to the different type of embryo, there were no significantly statistical differences in clinical pregnancy rate, embryo implantation rate, live birth rate, miscarriage rate, multiple pregnancy rate, ovarian hyperstimulation syndrome incidence, and ectopic pregnancy rate neither in day 2 cleavage stage embryo transfer cycles nor in the blastocyst transfer cycles. Conclusion:In this study, the clinical outcomes are similar between taking 30 mg of dydrogesterone tablets orally alone and taking 20 mg of dydrogesterone tablets orally combined with vaginal progesterone gel in the fresh embryo transfer cycle of the GnRH antagonist protocol. Moreover, taking dydrogesterone tablets orally alone can be a new option for luteal support in the fresh cycle of the GnRH antagonist protocol.

Objective:To compare the clinical outcomes of single oral dydrogesterone with vaginal progesterone gel plus oral dydrogesterone in gonadotropin-releasing hormone (GnRH) antagonist cycles with fresh embryo transfer.Methods:This study retrospectively analyzed 658 treatment cycles of fresh embryo transfer cycle with GnRH antagonist protocol from December 2015 to December 2020 in the Center of Reproductive Medicine of the University of Hong Kong-Shenzhen Hospital. Each cycle was the first fresh stimulation cycle of the patients. The patients were divided into two groups according to different luteal support regimens. Group A included 368 cycles with a regimen of 30 mg dydrogesterone tablets orally daily, while group B included 290 cycles with a regimen of 90 mg vaginal progesterone gel vaginally daily combined with 20 mg dydrogesterone tablets orally daily. A 1∶1 propensity score matching (PSM) was carried out to adjust for numerical differences and to balance between the two groups, and further they were divided into cleavage stage embryo transfer cycles and the blastocyst transfer cycles according to the different type of embryo for layer analysis, and the laboratory results and assisted reproductive outcomes of the two groups were compared.Results:After matching, the baseline characteristics were comparable between the two groups, with 251 cycles remaining in each group for retrospective analysis. After PSM, statistically significant differences were observed between group A and group B in laboratory data including the number of fertilized oocytes [5 (2, 7) vs. 6 (3, 9), P=0.002], cleavage rate [100.0% (86.31%, 100.0%) vs. 87.28% (75.32%, 100.0%), P<0.001], and available embryo rate [80.18% (54.64%, 100.0%) vs. 67.48% (50.62%, 100.0%), P=0.019]. However, there were no significantly statistical differences in other laboratory data and clinical outcomes (all P>0.05). If we divided the data into two comparison according to the different type of embryo, there were no significantly statistical differences in clinical pregnancy rate, embryo implantation rate, live birth rate, miscarriage rate, multiple pregnancy rate, ovarian hyperstimulation syndrome incidence, and ectopic pregnancy rate neither in day 2 cleavage stage embryo transfer cycles nor in the blastocyst transfer cycles. Conclusion:In this study, the clinical outcomes are similar between taking 30 mg of dydrogesterone tablets orally alone and taking 20 mg of dydrogesterone tablets orally combined with vaginal progesterone gel in the fresh embryo transfer cycle of the GnRH antagonist protocol. Moreover, taking dydrogesterone tablets orally alone can be a new option for luteal support in the fresh cycle of the GnRH antagonist protocol.

Objective: To explore the differences in the gut microbiota of primary school students with different levels of sugar sweetened beverage intake, so as to provide scientific evidence for better identification of health risks in children and the development of targeted health policies. Methods: In June 2022, a total of 192 healthy primary school students from Chengdu were selected using a stratified cluster random sampling method. The sugar sweetened beverage intake was assessed through a dietary frequency questionnaire. Based on the median daily sugar sweetened beverage intake, primary school students were categorized into a low intake group ( n =96) and a high intake group ( n =96). The gut microbiota in fresh fecal samples from the two groups of primary school students was analyzed using 16S rRNA high throughput sequencing, and the diversity and community structure differences in the gut microbiota were compared. Results: Children in the low intake group had a sugar sweetened beverage intake of (21.3±1.6) mL/d, while the high intake group had an intake of (269.6±37.3) mL/d. Diversity analysis results showed that there were no statistically significant differences between the low intake and the high intake group in terms of α diversity metrics: Observed_otus index [298.50 (259.75, 342.25), 305.50 (244.25, 367.75)], Goods_coverage index [1.00 (1.00, 1.00), 1.00 (1.00, 1.00)], Chao index [304.18 (260.75, 348.78), 305.88 (245.68, 370.88)], Shannon index [5.88 (5.29, 6.45), 5.71 (4.89, 6.28)] and Simpson index [0.95 (0.91, 0.97), 0.94 (0.88, 0.97)] ( Z =-0.64, -0.76, -0.54, -1.76, -1.67, P >0.05). Furthermore, no statistically significant difference was observed in β diversity between the two groups ( R 2=0.006, P >0.05). At the genus level, the abundance of Blautia [0.033 (0.018, 0.055)] and Fusicatenibacter [0.009 (0.005, 0.015)] were higher in the low intake group compared to the high intake group [0.024 (0.013, 0.041),0.006 (0.003, 0.011)]and differences were statistically significant ( Z =-2.52, -2.81, P <0.05). LEfSe analysis highlighted intergroup differences primarily in Blautia, Fusicatenibacter and Sarcina( LDA= 3.56,3.12,3.53, P <0.05). Conclusions There is no significant difference in the diversity and overall structure of the gut microbiota in primary school students with different levels of sugar sweetened beverage intake. However, there are species variations at the genus level. The information can serve as a scientific basis for identifying health risks in primary school students and formulating targeted health strategies.

Objective To explore the impact of the intervention model based on self-efficacy theory on fear of progression (FoP), negative emotions, and cancer-related fatigue in patients with hepatocellular carcinoma undergoing transcatheter arterial chemoembolization (TACE). Methods The clinical data of 94 patients with primary liver cancer were retrospectively analyzed. The patients were divided into control group and observation group according to different intervention methods, with 47 patients in each group. The control group received routine nursing mode after discharge, while the observation group received intervention model based on self-efficacy theory. Both groups were intervened for 3 months after discharge. The self-efficacy[General Self-Efficacy Scale (GSES)]at discharge and one- and three-month after discharge, FoP[Fear of Progression Questionnaire-Short Form (FoP-Q-SF)], negative emotions[Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS)], cancer-related fatigue[Revised Piper Fatigue Scale (R-PFS)], and quality of life[Quality of Life Questionnaire for Liver Cancer Patients (QOL-LC V2.0)] at discharge and three-month after discharge were compared between the two groups. Results One month and three months after discharge, the GSES scores of both groups gradually increased compared to those at discharge, and the scores of the observation group were higher than those of the control group (P < 0.05). Three months after discharge, the total and sub-dimension scores of FoP-Q-SF, SAS scores, SDS scores, and R-PFS were lower in both groups compared to those at discharge, and the observation group had lower scores than the control group (P < 0.05). Three months after discharge, the total and sub-dimension scores of QOL-LC V2.0 were higher in both groups compared to those at discharge, and the observation group had higher scores than the control group (P < 0.05). Conclusion The intervention model based on self-efficacy theory can enhance the self-efficacy of patients with primary liver cancer after TACE, relieve negative emotions and severity of FoP, improve cancer-related fatigue, and enhance the quality of life.

Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut-liver axis.

Farnesoid X receptor (FXR) is a nuclear receptor activated by bile acid that is involved in regulating gene expression related to bile acid, fat, glucose, and amino acid metabolism. The activity of FXR is regulated by a variety of post-translational modifications. Common post-translational modifications of FXR include O-GlcNAcylation, phosphorylation, acetylation, sumoylation, methylation, etc. These post-translational modifications may affect FXR binding of DNA and ligand, heterodimerization, and subcellular localization, and may specifically regulate downstream gene transcription and expression. Different post-translational modifications can lead to changes in FXR stability and biological function, which are closely related to the occurrence of diseases. This paper aims to review the post-translational modification of FXR in the past five years and the mechanisms involved in disease regulation, to explore the effects of post-translational modification on the physiological function of FXR and to provide a theoretical basis for mechanism research targeting FXR.

Humans ; Transcriptome/genetics* ; East Asian People ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Pulmonary Disease, Chronic Obstructive/genetics* ; Polymorphism, Single Nucleotide/genetics*

Objective:To evaluate the role of spinal cord microglia in chronic pain after chronic heart failure (CHF) in mice.Methods:Eighteen SPF healthy male C57BL/6 mice, aged 8-12 weeks, weighing 20-25 g, were divided into 3 groups ( n=6 each) using a random number table method: sham operation group (Sham group), CHF group, and CHF+ microglia inhibitor PLX3397 group (CHF+ PLX group). The model of chronic heart failure was prepared by ligating the anterior descending branch of the left coronary artery in anesthetized mice. Mice were continuously fed a PLX3397-containing diet from 7 days before preparing the model to 28 days after preparing the model in CHF + PLX group. The cardiac function was evaluated using echocardiography at 28 days after surgery. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured on 1 day before developing the model (T 0) and 1, 3, 7, 14 and 28 days after developing the model (T 1-5). The mice were sacrificed under deep anesthesia after the pain threshold was measured at T 5, and the spinal cord tissues of the lumbar segment (T 2-6 and L 4-6) were removed for determination of the expression of microglial marker Iba1 in the spinal dorsal horn (by immunofluorescence method). Results:Compared with Sham group, the left ventricular ejection fraction and left ventricular short axis shortening rate were significantly decreased, and the left ventricular internal diameter at end-diastole and the left ventricular internal diameter at end-systole were increased, the TWL was shortened and MWT was decreased at T 4-5, and the expression of Iba1 in the spinal dorsal horn was up-regulated in CHF group ( P<0.05). Compared with CHF group, the left ventricular ejection fraction and left ventricular short axis shortening rate were significantly increased, and the left ventricular internal diameter at end-diastole and the left ventricular internal diameter at end-systole were decreased, the TWL was prolong and MWT was increased at T 2-5, and the expression of Iba1 in the spinal dorsal horn was down-regulated in CHF+ PLX group ( P<0.05). Conclusions:The chronic pain after CHF may be related to microglial activation in the spinal cord of mice.

Objective:To investigate the role of Caveolin (Cav-3)/extracellular signal-regulated kinase (ERK) signaling pathway in reduction of myocardial ischemia-reperfusion (I/R) injury by morphine preconditioning in rats with chronic heart failure.Methods:Clean-grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, were used in this study.Chronic heart failure was induced by ligating the left anterior descending coronary artery for 6 weeks.Thirty-six Langendorff-perfused hearts with chronic heart failure were divided into 4 groups ( n=9 each) by a random number table method: myocardial I/R group (group IR), morphine preconditioning group (group MP), morphine preconditioning plus methyl-β-cyclodextrin group (group MP+ MβCD), and methyl-β-cyclodextrin group (group MβCD). Global myocardial I/R was induced by 30 min ischemia followed by 120 min reperfusion.In group MP, after 15 min of equilibration, hearts were subjected to 3 cycles of 5 min perfusion with K-H solution containing 1 μmol/L morphine for preconditioning followed by 5 min perfusion with K-H solution, 30 min in total, and after the end of treatment, hearts were subjected to 30 min ischemia followed by 120 min reperfusion.In group MP+ MβCD, hearts were perfused with K-H solution containing 200 μmol/L methyl-β-cyclodextrin at 10 min before preconditioning with morphine, and the other treatments were similar to those previously described in group MP.In group MβCD, hearts were perfused with K-H solution containing 200 μmol/L methyl-β-cyclodextrin at 40 min before ischemia, and the other treatments were similar to those previously described in group IR.At the end of 15 min of equilibration (T 0) and 5 and 10 min of reperfusion (T 1, 2), coronary outflow was collected for determination of actate dehydrogenase (LDH) activity by chemical colorimetry.Myocardial infarct size (IS) and area at risk (AAR) were measured, and IS/AAR was calculated at the end of 120 min reperfusion.Myocardial tissues of left ventricle were taken to detect the expression of Cav-3, ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) by Western blot, and p-ERK1/2/ERK1/2 ratio was calculated. Results:Compared with group IR, IS, IS/AAR and LDH activity in coronary outflow were significantly decreased, the expression of Cav-3 was up-regulated, and p-ERK1/2/ERK1/2 ratio was increased in group MP ( P<0.05). Compared with group MP, IS, IS/AAR and LDH activity in coronary outflow were significantly increased, the expression of Cav-3 was down-regulated, and p-ERK1/2/ERK1/2 ratio was decreased in group MP+ MβCD ( P<0.05). Conclusions:The mechanism by which morphine preconditioning reduces I/R injury may be related to activation of Cav-3/ERK signaling pathway in rats with chronic heart failure.