Mesenchymal stem cells (MSCs) have an inhibitory effect on tumor proliferation, but the precise mechanisms are not fully understood. Here, we identified DKK-1 (dickkopf-1), secreted by MSCs and acting as a negative regulator of WNT signaling pathway, to be one of the molecules responsible for the inhibitory effect. When DKK-1 was neutralized by anti-DKK-1 antibodies, or when the expression of DKK-1 was downregulated by RNA interference (RNAi), the inhibitory effects of MSCs on K562 cell proliferation were attenuated. We also provide evidence that the expression of DKK-1 by MSCs is regulated by NANOG, a transcriptional factor ubiquitously expressed in some stem cells. Using the Cellmax artificial capillary modules that eliminate the immunosuppressive properties of MSCs, we further showed that MSCs were able to inhibit proliferation of K562 cells in a humoral microenvironment. Meanwhile, we recapture this effect of MSCs on primary leukemic hematopoietic progenitors from patients. MSCs probably have a general inhibitory effect on their neighboring cells, including malignant cells, en route to achieving tissue homeostasis.

Tumor behavior is not entirely determined by tumor cells. Studies have demonstrated that a variety of non-tumor cells in the tumor microenvironment affect tumor behavior; thus, a new focus of cancer research has been the development of novel cancer treatment ideas and therapeutic targets based on the effects of these cells. Mesenchymal stem cells (MSCs) are an important component of the tumor microenvironment; however, previous studies have produced controversial results regarding whether MSCs promote or inhibit tumor growth and progression. In particular, Naïve MSCs and tumor-derived MSCs (T-MSCs) have different functions. Naïve MSCs could exert bidirectional effects on tumors because these cells can both promote and inhibit tumor progression while T-MSCs promote tumor progression due to influences from the tumor itself and from the inflammatory tumor microenvironment. As an unhealed wound, tumor produces a continuous source of inflammatory mediators and causes aggregation of numerous inflammatory cells, which constitute an inflammatory microenvironment. Inflammatory factors can induce homing of circulating MSCs and MSCs in adjacent tissues into tumors, which are then being “educated” by the tumor microenvironment to support tumor growth. T-MSCs could recruit more immune cells into the tumor microenvironment, increase the proportion of cancer stem cells and promote tumor angiogenesis, further supporting tumor progression. However, as plasticity is a fundamental feature of MSCs, MSCs can also inhibit tumors by activating various MSC-based signaling pathways. Studies of the mechanisms by which interactions among tumors, MSCs, and the inflammatory microenvironment occur and methods to disrupt these interactions will likely reveal new targets for cancer therapy.

SUMMARY Tumor suppressor PTEN controls genomic stability and inhibits tumorigenesis. The N-terminal phosphatase domain of PTEN antagonizes the PI3K/AKT pathway, but its C-terminal function is less defined. Here we describe a knock-in mouse model of a nonsense mutation that results in deletion of the entire Pten C-terminal region, referred to as PtenΔC. Mice heterozygous for PtenΔC develop multiple spontaneous tumors, including cancers and B cell lymphoma. Heterozygous deletion of the Pten C-terminal domain also causes genomic instability and common fragile site rearrangement. We found that Pten C terminal disruption induces p53 and its downstream targets. Simultaneous depletion of p53 promotes metastasis without influencing initiation of tumors, suggesting that p53 mainly suppresses tumor progression. Our data highlight the essential role of the PTEN C-terminus in the maintenance of genomic stability and suppression of tumorigenesis.

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In order to study the impact of procedures of IVF/ICSI technology on sex ratio in China, we conducted this multi-center retrospective study including 121,247 babies born to 93,895 women in China. There were 62,700 male babies and 58,477 female babies, making the sex ratio being 51.8% (Male: Female  = 107∶100). In univariate logistic regression analysis, sex ratio was imbalance toward females of 50.3% when ICSI was preformed compared to 47.7% when IVF was used (P<0.01). The sex ratio in IVF/ICSI babies was significantly higher toward males in transfers of blastocyst (54.9%) and thawed embryo (52.4%) when compared with transfers of cleavage stage embryo (51.4%) and fresh embryo (51.5%), respectively. Multiple delivery was not associated with sex ratio. However, in multivariable logistic regression analysis after controlling for related factors, only ICSI (adjusted OR = 0.90, 95%CI: 0.88–0.93; P<0.01) and blastocyst transfer (adjusted OR = 1.14, 95% CI: 1.09–1.20; P<0.01) were associated with sex ratio in IVF/ICSI babies. In conclusion, the live birth sex ratio in IVF/ICSI babies was influenced by the use of ICSI, which may decrease the percentage of male offspring, or the use of blastocyst transfer, which may increase the percentage of male offspring.

Background Primary hyperparathyroidism (pHPT) in pregnancy is a rare event, but it poses a significant risk to mothers and fetuses. The optimal treatment strategy remains controversial. Methods We present a consecutive series of twelve pregnant women with pHPT. Results Twelve women were diagnosed with pHPT during pregnancy or in the postpartum period. Four of them presented no symptoms or mild symptoms. Four patients experienced serious complications, including hypercalcaemic crisis, acute pancreatitis, and eclampsia. Another four patients were identified postpartum as the result of neonatal convulsion with hypocalcaemia. Minimally invasive parathyroidectomy (MIP) under cervical plexus block was successfully performed in 11 of them during pregnancy or postpartum. The serum levels of ionized calcium and intact parathyroid hormone (iPTH) were much higher in patients with severe complications in this cohort than those in the group of patients with no symptoms or mild symptoms and patients who were diagnosed postpartum. Conclusions MIP under cervical plexus block might be a safe and effective treatment for pregnant women with pHPT. Even though both conservative and surgical treatments are applicable for most mothers and fetuses with asymptomatic and mild hyperparathyroidism, serious complications may have catastrophic consequences for both.

Background:The effect of ovarian hyperstimulation syndrome (OHSS) on pregnancy outcomes of in vitro fertilization (IVF) patients is still ambiguous. This study aimed to analyze pregnancy outcomes of IVF with or without OHSS in Chinese patients.Methods:A retrospective cohort study was undertaken to compare pregnancy outcomes between 190 women with OHSS and 197 women without OHSS. We examined the rates of clinical pregnancy, multiple pregnancies, miscarriage, live birth, preterm delivery, preterm birth before 34 weeks’ gestation, cesarean delivery, low birth weight (LBW), and small-for-gestational age (SGA) between the two groups. Odds ratios (ORs) and 95% confidence intervals (CIs) of measure of clinical pregnancy were also analyzed.Results:The clinical pregnancy rate of OHSS patients was significantly higher than that of non-OHSS patients (91.8% vs. 43.5%, P < 0.001). After controlling for drug protocol and causes of infertility, the adjusted ORs of moderate OHSS and severe/critical OHSS for clinical pregnancy were 4.65 (95% CI, 1.86–11.61) and 5.83 (95% CI, 3.45–9.86), respectively. There were no significant differences in rates of multiple pregnancy (4.0% vs. 3.7%) and miscarriage (16.1% vs. 17.5%) between the two groups. With regard to ongoing clinical pregnancy, we also found no significant differences in the rates of live birth (82.1% vs. 78.8%), preterm delivery (20.9% vs. 17.5%), preterm birth before 34 weeks’ gestation (8.6% vs. 7.9%), cesarean delivery (84.9% vs. 66.3%), LBW (30.2% vs. 23.5%), and SGA (21.9% vs. 17.6%) between the two groups.Conclusion:OHSS, which occurs in the luteal phase or early pregnancy in IVF patients and represents abnormal transient hemodynamics, does not exert any obviously adverse effect on the subsequent pregnancy.

Background Inconsistent results according to numerous studies that had investigated the association between serum zinc levels and lung cancer risk were reported. The aim of this study was to explore whether serum zinc levels were lower in lung cancer patients than that in controls. Methods We systematically retrieved the databases of PubMed, Wanfang, Cochrane, ScienceDirect website, CNKI, and SinoMed databases for comprehensive relevant studies published before December 2018 and conducted a meta-analysis. Standard mean differences (SMD) were pooled using a random effects model. Results Thirty-two articles were eligible to investigate the correlation between serum zinc levels and lung cancer risk, involving 2894 cases and 9419 controls. The pooled results showed sufficient evidence approving the association between serum zinc levels and lung cancer risk. And the serum zinc levels in lung cancer were significantly lower than that in controls (summary SMD = − 0.88, 95% confidence interval (CI) = − 0.94, − 0.82). Meanwhile, consistent results were obtained both in European populations and Asian populations. No publication bias was detected in our analysis. Conclusions The present meta-analysis suggested that serum zinc levels were significantly lower in lung cancer patients than that in controls.