Objective:To evaluate the role of orphan nuclear receptor Nur77 in tunicamycin(TM)-induced injury to hippocampal neurons and the relationship with endoplasmic reticulum stress in mice.Methods:Mouse HT22 cells were divided into 4 groups ( n=10 each) using a random number table method: control group (C group), Nur77 specific agonist Csn-B group (Csn-B group), endoplasmic reticulum stress inducer TM group (TM group), and TM+ Csn-B group. Cells in C group were cultured for 24 h under normal condition. In Csn-B group, Csn-B at a final concentration of 10 μg/ml was added to the culture medium, and the cells were incubated for 24 h. In TM group, TM at a final concentration of 200 ng/ml was added to the culture medium and the cells were incubated for 24 h to induce cell endoplasmic reticulum stress injury. Cells in TM+ Csn-B group were pretreated with Csn-B at a final concentration of 10 μg/ml for 15 min, then TM at a final concentration of 200 ng/ml was added, and the cells were co-incubated for 24 h. The cell viability was examined by CCK-8 assay kit after treatment in each group. The expression of endoplasmic reticulum stress-related protein CCAAT/enhancer-binding protein homologous protein (CHOP), glucose regulated protein 78 (GRP78)and apoptosis-associated protein Bcl-2, Bax, caspase-3 and cleaved-caspase-3 was detected by Western blot. Results:Compared with C group, the cell viability was significantly decreased, and the expression of CHOP, GRP78, Bax and cleaved-caspase-3 was up-regulated, and the expression of Bcl-2 and caspase-3 was down-regulated in TM group ( P<0.05 or 0.01). Compared with TM group, the cell viability was significantly increased, the expression of CHOP, GRP78, Bax and cleaved-caspase-3 was down-regulated, and the expression of Bcl-2 and caspase-3 was up-regulated in TM+ Csn-B group ( P<0.05 or 0.01). Conclusions:Orphan nuclear receptor Nur77 is involved in TM-induced injury to hippocampal neurons, which is related to activation of the endoplasmic reticulum stress in mice.

Objective:To explore the clinical applications and therapeutic outcomes of immune checkpoint inhibitors(ICIs)on liver transplantation(LT)recipients after tumor development.Methods:Eight databases including PubMed, China National Knowledge Infrastructure, Wanfang Data, CQVIP, PubMed, EMBASE, Web of Science and Google scholar were accessed for searching the relevant literature articles in both Chinese and English from the establishment of databases to December 31, 2021. Disease response, adverse reactions and prognoses of patients with malignant tumors after LT and receiving ICIs were analyzed.Results:The patient was diagnosed as chronic rejection plus drug-induced liver injury by liver biopsy. After intermittent treatment with DPMAS plus plasma exchange and immunosuppressants, he finally died of tumor recurrence at 37 months after LT. After screening, a total of 28 articles on the application of ICIs after LT were retrieved. In these articles, there were 47 patients(37 males and 10 females)with a median age of 57(14-71)years and the predominant type of tumor after LT was hepatocellular carcinoma(28/47, 59.6%), followed by malignant melanoma in 11 cases (23.4%), non-small cell lung cancer in 3 cases(6.4%), colorectal cancer, cholangiocarcinoma, squamous cell carcinoma, hypopharyngeal squamous cell carcinoma and post transplant lymphoproliferative disease(PTLD) in 1 case(2.1%). The overall remission rate after ICI treatment was 29.8%(14/47)and the disease progression rate 68.1%(32/47). Among them, 31.9%(15/47)had immune rejection. Case fatality rate was 61.7%(29/47)and median survival time 6.5(0.3-48.0)months.Conclusions:Depending on existing publications, among those LT recipients with malignant tumors treated by ICIs, the rate of graft rejection and patient mortality are higher. ICIs should be carefully considered for LT patients and further researches are required.

Objective:To explore the clinical outcome of blastocysts with different developmental time and grades of preimplantation genetic testing for aneuploidies (PGT-A) embryo transfer cycles, and to compare and analyze their transcriptome characteristics.Methods:The clinical data of patients with euploid blastocyst transplantation selected by PGT-A in Center for Reproductive Medicine of Women Health Center of Shanxi from January 2017 to December 2021 were retrospectively analyzed. A total of 295 transplantation cycles were divided into groups according to the day of embryo blastulation [day 5 (D5) group and day 6 (D6) group] and blastocyst grade (good-quality group and fair-quality group) and their clinical outcomes were compared. By comparing the single-cell RNA sequencing (scRNA-seq) data of blastocysts of different developmental time and grades from GEO and ENA data platforms, the transcriptome level differences among different groups were analyzed.Results:1) There were no significant differences in age of male and female, type of infertility, infertility duration, body mass index (BMI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and number of oocytes retrieved between D5 and D6 groups (all P>0.05). The M Ⅱ oocyte rate [86.35% (2051/2375) vs. 82.71% (1770/2140), P=0.001], blastocyst formation rate [68.08% (725/1065) vs. 62.14% (540/869), P=0.006], implantation rate [72.78% (115/158) vs. 52.55% (72/137), P<0.001], clinical pregnancy rate [56.33% (89/158) vs. 43.80% (60/137), P=0.032] and live birth rate [53.80% (85/158) vs. 40.87% (56/137), P=0.027] in D5 group were significantly higher than those in D6 group, and the results of miscarriage rate, preterm birth rate, proportion of male and birth weight between the two groups were not statistically significant. 2) There were no significant differences in age of male and female, type of infertility, infertility duration, BMI, FSH, LH, estradiol and number of oocytes retrieved between good-quality and fair-quality groups (all P>0.05). The M Ⅱ oocyte rate [87.06% (1251/1437) vs. 83.50% (2570/3078), P=0.002], blastocyst formation rate [73.38% (499/680) vs. 61.08% (766/1254), P<0.001], implantation rate [77.90% (74/95) vs. 56.50% (113/200), P<0.001], clinical pregnancy rate [61.05% (58/95) vs. 45.50% (91/200), P=0.013] and live birth rate [56.84% (54/95) vs. 43.50% (87/200), P=0.032] in good-quality group were significantly higher than those in fair-quality group, and the results of miscarriage rate, preterm birth rate, proportion of male and birth weight between the two groups were not statistically significant. 3) Based on the scRNA-seq data from GEO and ENA data platforms, we mined differentially expressed genes (DEGs) in the inner cell mass (ICM) and trophectoderm (TE) of D5 and D6 blastocysts, good-quality blastocysts and fair-quality blastocysts. Compared with D6 group, KEGG enrichment analysis showed that DEGs up-regulated of ICM/TE in D5 group were significantly enriched in 285/288 signaling pathways. DEGs up-regulated of ICM/TE were significantly enriched in 207/3 signaling pathways in the good-quality group compared with the fair-quality group. Conclusion:In terms of implantation and clinical pregnancy ability, D5 blastocysts were better than D6 blastocysts, and good-quality blastocysts were better than fair-quality blastocysts. Transcriptome level analysis of blastocysts with different developmental time and grades showed significant differences in transcriptome characteristics. The analysis of blastocyst transcriptome level has predictive value for blastocyst implantation and clinical pregnancy ability.

Objective:To explore the clinical outcome of blastocysts with different developmental time and grades of preimplantation genetic testing for aneuploidies (PGT-A) embryo transfer cycles, and to compare and analyze their transcriptome characteristics.Methods:The clinical data of patients with euploid blastocyst transplantation selected by PGT-A in Center for Reproductive Medicine of Women Health Center of Shanxi from January 2017 to December 2021 were retrospectively analyzed. A total of 295 transplantation cycles were divided into groups according to the day of embryo blastulation [day 5 (D5) group and day 6 (D6) group] and blastocyst grade (good-quality group and fair-quality group) and their clinical outcomes were compared. By comparing the single-cell RNA sequencing (scRNA-seq) data of blastocysts of different developmental time and grades from GEO and ENA data platforms, the transcriptome level differences among different groups were analyzed.Results:1) There were no significant differences in age of male and female, type of infertility, infertility duration, body mass index (BMI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and number of oocytes retrieved between D5 and D6 groups (all P>0.05). The M Ⅱ oocyte rate [86.35% (2051/2375) vs. 82.71% (1770/2140), P=0.001], blastocyst formation rate [68.08% (725/1065) vs. 62.14% (540/869), P=0.006], implantation rate [72.78% (115/158) vs. 52.55% (72/137), P<0.001], clinical pregnancy rate [56.33% (89/158) vs. 43.80% (60/137), P=0.032] and live birth rate [53.80% (85/158) vs. 40.87% (56/137), P=0.027] in D5 group were significantly higher than those in D6 group, and the results of miscarriage rate, preterm birth rate, proportion of male and birth weight between the two groups were not statistically significant. 2) There were no significant differences in age of male and female, type of infertility, infertility duration, BMI, FSH, LH, estradiol and number of oocytes retrieved between good-quality and fair-quality groups (all P>0.05). The M Ⅱ oocyte rate [87.06% (1251/1437) vs. 83.50% (2570/3078), P=0.002], blastocyst formation rate [73.38% (499/680) vs. 61.08% (766/1254), P<0.001], implantation rate [77.90% (74/95) vs. 56.50% (113/200), P<0.001], clinical pregnancy rate [61.05% (58/95) vs. 45.50% (91/200), P=0.013] and live birth rate [56.84% (54/95) vs. 43.50% (87/200), P=0.032] in good-quality group were significantly higher than those in fair-quality group, and the results of miscarriage rate, preterm birth rate, proportion of male and birth weight between the two groups were not statistically significant. 3) Based on the scRNA-seq data from GEO and ENA data platforms, we mined differentially expressed genes (DEGs) in the inner cell mass (ICM) and trophectoderm (TE) of D5 and D6 blastocysts, good-quality blastocysts and fair-quality blastocysts. Compared with D6 group, KEGG enrichment analysis showed that DEGs up-regulated of ICM/TE in D5 group were significantly enriched in 285/288 signaling pathways. DEGs up-regulated of ICM/TE were significantly enriched in 207/3 signaling pathways in the good-quality group compared with the fair-quality group. Conclusion:In terms of implantation and clinical pregnancy ability, D5 blastocysts were better than D6 blastocysts, and good-quality blastocysts were better than fair-quality blastocysts. Transcriptome level analysis of blastocysts with different developmental time and grades showed significant differences in transcriptome characteristics. The analysis of blastocyst transcriptome level has predictive value for blastocyst implantation and clinical pregnancy ability.

Objective: To explore the prevalence of chronic diseases and related risk factors in Shaanxi province. Methods: Multi-stage stratified cluster random sampling was used to collect the sample from permanent residents in 10 national surveillance points in Shaanxi province in 2015. Behavioral risk factors (smoking, drinking, diet and physical activity) were investigated by face-to-face interviews and biological risk factors (BMI, blood pressure, blood glucose and blood lipid) were collected by physical measurements and laboratory tests. Designed weight, no response weight and post hierarchical weight were taken into account in the data analysis. Binary logistic regression models were used to examine the pair-wise associations among 8 risk factors. Results: A total of 6 174 persons were included in the analysis. The following weighted prevalence were noticed in Shaanxi province in 2015, that including current smoking as 28.19%, harmful use of alcohol as 6.20%, inadequate intake of vegetables and fruits as 55.62%, physical inactivity as 19.56%, overweight and obesity as 46.82%, hypertension as 31.12%, raised fasting blood glucose as 4.27%, and raised total cholesterol as 20.96%. Eight risk factors were found to be associated with each other. The mean numbers of risk factors were 2.41 per male and 1.85 per female, 1.94 per urban resident and 2.28 per rural resident. Conclusions Risk factors for chronic diseases among adults aged 18 or older were more than the national levels in Shaanxi province in 2015. Male and rural residents presented more risk factors than their counterparts. Correlations between risk factors implied that a combined package of interventions was needed to reduce these risk factors.