Resistance to Naïve and Formative Pluripotency Conversion in RSeT Human Embryonic Stem Cells.

One of the most important properties of human embryonic stem cells (hESCs) is related to their primed and naïve pluripotent states. Our previous meta-analysis indicates the existence of heterogeneous pluripotent states derived from diverse naïve protocols. In this study, we have characterized a commercial medium (RSeT)-based pluripotent state under various growth conditions. Notably, RSeT hESCs can circumvent hypoxic growth conditions as required by naïve hESCs, in which some RSeT cells (e.g., H1 cells) exhibit much lower single cell plating efficiency, having altered or much retarded cell growth under both normoxia and hypoxia. Evidently, hPSCs lack many transcriptomic hallmarks of naïve and formative pluripotency (a phase between naive and primed states). Integrative transcriptome analysis suggests our primed and RSeT hESCs are close to the early stage of post-implantation embryos, similar to the previously reported primary hESCs and early hESC cultures. Moreover, RSeT hESCs did not express naïve surface markers such as CD75, SUSD2, and CD130 at a significant level. Biochemically, RSeT hESCs exhibit a differential dependency of FGF2 and co-independency of both Janus kinase (JAK) and TGFß signaling in a cell-line-specific manner. Thus, RSeT hESCs represent a previously unrecognized pluripotent state downstream of formative pluripotency. Our data suggest that human naïve pluripotent potentials may be restricted in RSeT medium. Hence, this study provides new insights into pluripotent state transitions in vitro.

GDF15 deficiency hinders human trophoblast invasion to mediate pregnancy loss through downregulating Smad1/5 phosphorylation.

Growth differentiation factor 15 (GDF15) belongs to the Transforming growth factor ß(TGF-ß) superfamily. The decrease of GDF15 in the serum of pregnant women was associated with miscarriage. Both IHC and ELISA assays showed that GDF15 in trophoblast tissue and serum of pregnant women who miscarried was significantly lower than in those who had a live birth. GDF15 deficiency was associated with embryo resorption in GDF15 knockout mice through CRIPSR editing. In addition, the migration and invasion ability of HTR-8/SVneo and JEG-3 cells were promoted by GDF15. Mechanistically, GDF15 increased Smad1/5 phosphorylation, resulting in upregulating SNAI1/2, VIMENTIN and downregulating E-CADHERIN. A dual-luciferase reporter assay confirmed that Smad-binding elements (SBE) and/or GC-rich motifs were activated and target genes such as SNAI1/2, SERPINE1, and TIMP3 were transcriptionally regulated by GDF15/Smad5 signaling. Therefore, our data revealed a crucial role of GDF15 on invasion of trophoblast by upregulating the activity of TGF-ß/Smad1/5 pathway.

Systematic review of subsequent pregnancy outcomes in couples with parental abnormal chromosomal karyotypes and recurrent pregnancy loss.

OBJECTIVE: To evaluate the current evidence of pregnancy outcomes among couples with recurrent pregnancy loss (RPL) with abnormal karyotypes vs. those with normal karyotypes and among couples with RPL and abnormal karyotypes after receiving expectant management vs. preimplantation genetic diagnosis (PGD). DESIGN: Systematic review and meta-analysis. SETTING: Academic medical centers. PATIENT(S): Pregnancy outcomes in 6,301 couples with RPL who conceived without medical intervention in 11 studies were analyzed. However, only 2 studies addressed the outcomes of couples with RPL and abnormal karyotypes after expectant management (75 cases) vs. PGD (50 cases). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The pregnancy outcomes in couples with RPL with abnormal and normal karyotypes across included studies were evaluated. RESULT(S): Compared with those with a normal karyotype, a significantly lower first pregnancy live birth rate (LBR) was found in couples with RPL with abnormal karyotypes (58.5% vs. 71.9%; odds ratio [OR], 0.55; 95% confidence interval [CI], 0.46-0.65; I2 =27%). A markedly decreased first pregnancy LBR was found in couples with a translocation (52.9% vs. 72.4%; OR, 0.44; 95% CI, 0.31-0.61; I2 =33%) but not in couples with an inversion. However, the differences in accumulated LBR (81.4% vs. 74.8%; OR, 0.96; 95% CI, 0.90-1.03; I2 = 0) were nonsignificant, whereas the miscarriage rate was distinctly higher in couples with RPL and abnormal karyotypes (53.0% vs. 34.7%; OR, 2.21; 95% CI, 1.69-2.89; I2 = 0). Compared with those who chose expectant management, differences in accumulated LBR were nonsignificant (60% vs. 68%; OR, 0.55; 95% CI, 0.11-2.62; I2 =71%), whereas the miscarriage rate (24% vs. 65.3%; OR, 0.15; 95% CI, 0.04-0.51; I2 = 45) was markedly low in couples with RPL and abnormal karyotypes who chose PGD. CONCLUSION(S): Couples with RPL and abnormal karyotypes had a higher miscarriage rate than couples with normal karyotypes but achieved a noninferior accumulated LBR through multiple conception attempts. In couples with RPL and abnormal karyotypes, PGD treatment did not increase the accumulated LBR but markedly reduced miscarriage rate compared with expectant management.

Two layered galloborates from centric to acentric structures: syntheses and NLO properties.

Two layered galloborates (GBOs), Na3GaB4O9 (1) and Na5Ga[B7O12(OH)]2·2B(OH)3 (2), have been solvothermally made. 1 exhibits an unprecedented layer built by GaO4 tetrahedra and B4O9 clusters. 2 was made by raising the ratio of B/Ga and the reaction temperature of 1, featuring a 2D acentric layer built by GaO4 groups and B7O13(OH) clusters. 2 shows the highest second-harmonic generation (SHG) response of 4.6 times that of KDP (KH2PO4) among main group metal borates (MBOs).

Two new Cu-based borate catalysts with cubic supramolecular cages for efficient catalytic hydrogen evolution.

Focusing on renewable energy, we are devoted to developping efficient, robust and low cost water reduction catalysts (WRCs). Two new Cu-based borate catalysts, namely H2Na2K2[(µ4-O)Cu4@B20O32(OH)8]·21H2O (1) and H2Rb1.6K2.4[(µ4-O)Cu4@B20O32 (OH)8]·15H2O (2), with cubic supramolecular cages were synthesized under a hydrothermal condition. Moreover, new copper complexes were applied as water reduction catalysts (WRCs) in the presence of [Ir(ppy)2(dtbbpy)][PF6] as photosensitizer and triethanolamine (TEOA) as the sacrificial electron donor. Nevertheless, the main active place is attributed to the centre of Borates [(µ4-O)Cu4@B20O32(OH)8], and the atomic radius of the counter cation would be the critical factor of the photocatalytic activity. Increasing the atomic radius from the Na atom to the Rb atom, causes the photocatalytic activity to decrease efficiently. The experimental results match well with the density functional theory (DFT) conclusion. It is noteworthy to mention that our research not only enriches the Cu-based borate chemistry, but also investigates the photocatalytic activity of Cu-based borates. This would guide us through the borate synthesis and to develop their applications toward energy and the environment.

Serum interleukin-33 as a novel marker for long-term prognosis and recurrence in acute ischemic stroke patients.

OBJECTIVES: Interleukin-33, a newly identified member of interleukin-1 family, had been confirmed to play a crucial role in regulating inflammatory responses in various disease. However, the exact role of interleukin-33 in the disease process of acute ischemic stroke still remains unclear. This study aims to demonstrate the relationship between interleukin-33 levels and long-term functional outcome as well as ischemic stroke recurrence. METHODS: Three hundred and four first-ever acute ischemic stroke patients were recruited and basic information and history of all subjects taken within 72 hr on admission. The functional outcome was estimated by Barthel index. The multivariate logistic regression was used to analyze the prognosis, while the Cox proportional hazard model was applied to assess the recurrence risk. RESULTS: Out of 304 subjects, 259 patients successfully completed scheduled two-year follow-up. We found that higher interleukin-33 levels correlated positively with better prognosis as compared with those with lower interleukin-33 levels who presented with poorer outcome (62.45 ± 20.50 ng/ml vs. 51.58 ± 19.16 ng/ml, p < .001). After adjustment of all confounders, interleukin-33 was associated with the one-year prognosis with an adjusted odds ratio of 0.956 (95% confidence interval, 0.937-0.976, p < .001). Furthermore, interleukin-33 levels were also closely related to recurrent ischemic stroke with an adjusted hazard ratio of 0.979 (95% confidence interval, 0.961-0.997, p = .025). CONCLUSIONS: IL-33 can be used to predict the long-term outcomes and ischemic stroke recurrence in first-ever acute ischemic stroke patients.

The association of matrix metalloproteinase-1 genetic polymorphism (-1607 1G>2G) with colorectal cancer: a meta-analysis.

Several case-control studies on the relation between matrix metalloproteinase (MMP)-1 gene -1607 1G>2G polymorphism and colorectal cancer do not have similar conclusions. The previous two meta-analyses focusing on the same issue also were inconsistent. To further evaluate the relation between the MMP-l gene polymorphism and colorectal cancer, we selected eight case-control studies related to MMP-1 gene polymorphism and colorectal cancer by searching MEDLINE, Embase, CANCERLIT, American Association for Cancer Research, Chinese Biomedical Literature Database, Chinese CNKI, and Wanfang database. Q test and I (2) test were used to test the heterogeneity. We utilized the random effects model to calculate the odds ratio (OR), 95% confidence interval (CI), and the overall effect of P value using the RevMan 5.2 software. The present study included 1,403 patients with colorectal cancer and 1,754 healthy control subjects. Both -1607 2G/2G genotype carriers [OR = 1.59, 95 % CI (1.27-2.01); P < 0.001] and the -1607 2G allele carriers [OR = 1.26, 95% CI (1.05-1.51); P = 0.01] were found to have an increased risk of colorectal cancer. Therefore, we concluded that MMP-1 -1607 1G>2G polymorphism was associated with colorectal cancer.

CD146 expression correlates with epithelial-mesenchymal transition markers and a poor prognosis in gastric cancer.

CD146 has been regarded as a novel potential therapeutic target for multiple cancers. The aim of the study was to investigate the expression of CD146 in gastric cancer and evaluate its clinical-pathological and prognostic significance. The expression of CD146 and three epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, ß-catenin and vimentin) was examined in 144 gastric cancers by immunohistochemistry. Fifty-nine cases (41.0%) were defined as positive for CD146 expression. We found that CD146 expression correlated positively with lymph node involvement and a poor prognosis, and retained an independent prognostic factor for gastric cancer patients. Furthermore, positive expression of CD146 was strongly associated with loss of the epithelial marker E-cadherin and acquisition of the expression of the mesenchymal markers nuclear ß-catenin and vimentin. These findings suggest that CD146 might promote EMT and progression in gastric cancer, and thus may be a potential therapeutic target for patients with gastric cancers.

[Pharmacokinetics and bioequivalence of domestic trimetazidine formulations].

OBJECTIVE: To compare the pharmacokinetics and bioequivalence between domestic hydrochloric trimetazidine capsules and imported hydrochloric trimetazidine tablets in healthy male Chinese volunteers after single oral administration. METHODS: A single oral dose (test and reference formulations) was given to 24 healthy male Chinese subjects according to an open randomized crossover design. The blood samples were collected before and after administration. Plasma trimetazidine concentration was determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated by WinNonlin Ver 6.2.1 software. RESULTS: The main pharmacokinetic parameters of domestic and imported formulation of trimetazidine were similar: C(max) (70.9 ± 15.3), (66.4 ± 13.8) µg/ml; t(max) (1.70 ± 0.72), (1.85 ± 0.55) h; t(1/2z) (4.70 ± 1.75), (4.77 ± 1.96) h; AUC(0-24 h) (481 ± 176), (469 ± 171) µg×h×ml(-1); AUC(0-∞) (511 ± 189), (500 ± 188) µg×h×ml(-1). The estimated 90% CIs for the ratio of C(max) and AUC(0-24 h) were also similar: 101.9% - 112.5% and 99.4% - 104.9%. The relative bioavailability of domestic formulation was (102.2 ± 8.3)%. CONCLUSION: The results demonstrates that the domestic hydrochloric trimetazidine capsules and imported hydrochloric trimetazidine tablets are bioequivalent.

Isolated pancreatic granulocytic sarcoma: a case report and review of the literature.

Granulocytic sarcoma (GS) is an extramedullary tumor mass consisting of immature myeloid cells. Isolated pancreatic granulocyte sarcoma is extremely rare. We report a very unusual pancreatic granulocytic sarcoma in a patient without acute myeloid leukemia. The patient presented with acute epigastric pain because of splenic infarction due to a mass consisting of myeloblasts in the pancreatic tail. The patients underwent splenectomy and distal pancreatectomy. Pathology and immunohistochemistry suggested a GS. Despite local surgery, an isolated tumor recurred 2 mo after operation and the patient died 3 mo after removal of the tumor. Only 7 reported cases of pancreatic GS were identified in the literature and the mass was located in the pancreatic head. This is the first report of GS in the pancreatic tail with splenic infarction.

Pharmacokinetic interaction between cefaclor and bromhexine in healthy Chinese volunteers.

OBJECTIVE: To determine the pharmacokinetic interaction between cefaclor and bromhexine in healthy Chinese volunteers. METHODS: Twelve subjects received a cefaclor (CEF) treatment, a bromhexine (BHX) treatment, and a co-treatment of CEF and BHX with a 3 x 3 Latin square design. The wash-out time between periods was 14 days. The plasma and urine drug concentrations of CEF and BHX were detected by HPLC-UV and LC/MS, respectively. RESULTS: All the 12 volunteers completed the study. There were no significant differences in AUC 0-t and Cmax of CEF in logarithm between the single administration group of CEF and the co-administration group of CEF with BHX. Two one sided t-test showed that CEF was bioequivalent in the 2 groups. There were no significant differences in tmax, MRT, t1/2, and Clr between the 2 groups. Vd/F was significantly lower in the single CEF group than in the co-administration group of CEF and BHX. There were no significant differences of AUC 0-t and Cmax of BHX in logarithm between the single administration group of BHX and the co-administration group of BHX with CEF. Two one sided t-test showed that BHX was bioequivalent in the 2 groups. There were no significant differences in tmax, MRT, t1/2, Vd/F, and Clr between the 2 groups. CONCLUSION: There is no significant pharmacokinetic parameter change in the drug absorption, metabolism, and excretion, but Vd/F of CEF significant increases in the co-administration of CEF with BHX. The co-administration of CEF and BHX has no adverse drug interaction. The increase of Vd/F may be a favorable drug interaction, which may be the mechanism of the synergistic effect of the 2 drugs.

[The fabrication and chroma study of a kind of custom shade guide with metal substrate].

PURPOSE: This study was to explore the chroma of a custom shade guide with metal substrate. METHODS: A custom shade guide sample was fabricated using the central maxillary incisor as a model,which was corresponding to the colour of VITAPAN shade guide.The colour of each shade tab was measured with PR-650 spectrophotometer when every porcelain was added. RESULTS: From the opaque to glaze, the lightness was decreased and the chroma was increased distinctively; When the body porcelain were baked over their corresponding opaque, the lightness was decreased and the chroma was increased; When the enamel porcelain and the translucent porcelain were added on, the lightness and chroma were decreased slightly; the glaze could increase the lightness. CONCLUSION: The "add on" porcelain can affect the final color of the restoration, and the effects of each porcelain layer were different from each other.

[Comparison of color character of VITA shade guide and the custom shade guide].

OBJECTIVE: To compare the color character of VITA shade guide and the custom shade guide with metal substrate. METHODS: Color of 9 sites of 5 series of VITA shade guides and custom shade guides with metal substrate were measured by means of PR-650 spectrophotometer. RESULTS: The color range of VITA shade guide were that L* was 56.86-73.86, a* was-1.29-3.69, b* was 7.09-21.94, and the transparence was 3.20-7.59. The color range of the custom shade guide was that L* was 60.59-78.54, a* was -1.09-4.99, b* was 7.60-22.35, and the transparence was 0.23-10.98. L*, a* and b* of the custom shade guide with metal substrate were higher than VITA shade guide, and the transparence was differet. The color difference of homonymy shade tab between custom shade guide and VITA shade guide was larger than 1.5 NBS. CONCLUSION: There is color difference between VITA shade guide and custom shade guide. Metal substrate has effects on the color of cero-metal prosthesis, and color selection in clinic should be carefully considered.

[Lymph node micrometastases and expression of metastasis-related gene proteins in patients with colorectal cancer].

OBJECTIVE: To study lymph node micrometastases (LNMM), expression of nm23-H(1), MMP(9), TIMP(2) proteins, and their relationship and clinical significance in patients with stage Dukes B colorectal cancer. METHODS: Thirty patients with stage Dukes B colorectal cancer were studied. LNMM in these patients was detected by immunohistochemical anti-cytokeratin 20 (CK20) staining. The expression of nm23-H(1), MMP(9) and TIMP(2) proteins in primary tumors was examined by Strept-avidin-biotin complex method. Clinical-pathological data and survival of each patient were recorded and analyzed. RESULTS: (1) The positive dyeing of CK20 was observed in 26.7% for cases and in 7.8% for lymph nodes of 30 patients with stage Dukes B colorectal cancer. (2) Different expression of nm23-H(1) and MMP(9) proteins in the patients between stage Dukes B and stage Dukes CD was observed (P < 0.05). The decreased nm23-H(1) expression, and/or the increased MMP(9) expression in primary stage Dukes B tumors were significantly associated with LNMM (P < 0.05). Sensitivity and specificity for detection of LNMM by using nm23-H(1) or MMP(9) were respectively 62.5% and 81.8% or 75.0% and 69.8%. If by combining nm23-H(1) with MMP(9), specificity for detection of LNMM became 90.9%. The expression of TIMP(2) protein was not related with stage Dukes and LNMM. (3) The percent of tumor recurrence and/or metastasis for the stage Dukes B patients with LNMM was significantly higher than that for the patients without LNMM (P < 0.05), but the survival percent for the patients with LNMM was significantly lower than that for the patients without LNMM. The outcome for the patients with nm23-H(1) (-) LNMM (+) or MMP(9) (+) LNMM (+) was significantly worse than that for patients with nm23-H(1) (+) LNMM (-) or MMP(9) (+) LNMM (-) (P < 0.05). CONCLUSIONS: LNMM is detected by immunohistochemical anti-CK20 staining. The expression of nm23-H(1) and MMP(9) in primary stage Dukes B tumors was significantly associated with LNMM. The outcome in the LNMM patients with nm23-H(1) (-) and/or MMP(9) (+) were worse. Combining examination of CK20 for lymph nodes with expression of nm23-H(1) and MMP(9) for primary tumors is of important clinical significance for staging of Dukes, selection of adjuvant treatment and evaluation of prognosis in patients with colorectal cancer.