Long non-coding RNAs (lncRNAs) play important roles in carcinogenesis and drug efficacy. Platinum-based chemotherapy is first-line treatment for lung cancer chemotherapy. In this study, we aimed to investigate the association of well-characterized lung cancer lncRNA genetic polymorphisms with the lung cancer susceptibility and platinum-based chemotherapy response. A total of 498 lung cancer patients and 213 healthy controls were recruited in the study. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Thirteen polymorphisms in HOXA distal transcript antisense RNA (HOTTIP), HOX transcript antisense intergenic RNA (HOTAIR), H19, CDKN2B antisense RNA 1 (ANRIL), colon cancer-associated transcript 2 (CCAT2), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and maternally expressed gene 3 (MEG3) genes were genotyped by allele-specific MALDI-TOF mass spectrometry. We found that patients with HOTTIP rs5883064 C allele or rs1859168 A allele had increased lung cancer risk (P = 0.01, P = 0.01, respectively). CCAT2 rs6983267 (P = 0.02, adenocarcinoma) and H19 rs2107425 (P = 0.02, age under 50 years) showed strong relationship with lung cancer susceptibility. CCAT2 rs6983267, H19 rs2839698, MALAT1 rs619586, and HOTAIR rs7958904 were associated with platinum-based chemotherapy response in dominant model ((P = 0.02, P = 0.04, P = 0.04, P = 0.01, respectively). ANRIL rs10120688 (P = 0.02, adenocarcinoma) and rs1333049 (P = 0.04, small-cell lung cancer), H19 rs2107425 (P = 0.02, small-cell lung cancer) and HOTAIR rs1899663 (P = 0.03, male; P = 0.03, smoker) were associated with response to platinum-based chemotherapy. HOTTIP, CCAT2, H19, HOTAIR, MALATI, ANRIL genetic polymorphisms were significantly associated with lung cancer susceptibility or platinum-based chemotherapy response. They may be potential clinical biomarkers to predict lung cancer risk and platinum-based chemotherapy response.

High-grade serous ovarian carcinoma (HGSOC) originates mainly from the fallopian tube (FT) epithelium and always carries early TP53 mutations. We previously reported that tumors initiate in the FT fimbria epithelium because of apoptotic failure and the expansion of cells with DNA double-strand breaks (DSB) caused by bathing of the FT epithelial cells in reactive oxygen species (ROSs) and hemoglobin-rich follicular fluid (FF) after ovulation. Because ovulation is frequent and HGSOC is rare, we hypothesized that luteal-phase progesterone (P4) could eliminate p53-defective FT cells. Here we show that P4, via P4 receptors (PRs), induces necroptosis in Trp53 mouse oviduct epithelium and in immortalized human p53-defective fimbrial epithelium through the TNF-α/RIPK1/RIPK3/MLKL pathway. Necroptosis occurs specifically at diestrus, recovers at the proestrus phase of the estrus cycle, and can be augmented with P4 supplementation. These results reveal the mechanism of the well-known ability of progesterone to prevent ovarian cancer.

Our previous studied indicated that eukaryotic translation initiation factor 3a (eIF3a) increases the sensitive of platinum-based chemotherapy in lung cancer. MiRNAs play an important role in lung carcinogenesis and drug response. In this study, we aimed to identify potential endogenous miRNAs that inhibit eIF3a expression and determine their influence of this inhibition on cisplatin resistance. Using bioinformatics analysis prediction and confirmation with dual-luciferase reporter assays, we found that miRNA-488 inhibited eIF3a expression by directly binding to the 3’UTR of eIF3a. In addition, the overexpression of miRNA-488 inhibited cell migration and invasion in A549 cells, and also inhibited cell proliferation, cell cycle progression by elevated P27 expression. Compared to the parental cell line, A549/cisplatin (DDP) resistant cells exhibited a higher level of miRNA-488. Moreover, we found that miRNA-488 was associated with cisplatin resistance in three NSCLC cells (A549, H1299 and SK-MES-1). The mechanism of miRNA-488 induced cisplatin resistance was that miRNA-488 activated nucleotide excision repair (NER) by increasing the expression of Replication Protein A (RPA) 14 and Xeroderma pigmentosum group C (XPC). In conclusion, our results demonstrated that miRNA-488 is a tumor suppressor miRNA that acts by targeting eIF3a. Moreover, miRNA-488 also participates in eIF3a mediated cisplatin resistance in NSCLC cells.

The harsh urine microenvironment (UME), as an inherent hurdle, endangers and renders urethral repair unreachable. Innovatively, the unfavorable UME is utilized as the design source to construct a UME‐responsive 3D‐printed hydrogel patch for realizing scarless memory repair, wherein laser‐excited reactive oxygen species (ROS) production and mechanical strength elevation using chemically crosslinked silicon quantum dots are accessible. Intriguingly, the proposed composite scaffolds can respond to Ca2+ in urine, cause structure reconfiguration, and repress swelling to further enhance scaffold stiffness. Systematic experiments validate that ROS birth and unexpected stiffness elevation in such UME‐responsive scaffolds can realize scarless memory repair of the urethra in vivo. Comprehensive mechanism explorations uncover that the activations of cell proliferation and collagen‐related genes (e.g., MMP‐1 and COL3A1) and the dampening of fibrosis‐related (e.g., TGF‐β/Smad) and mechanosensitive genes (e.g., YAP/TAZ) are responsible for the scarless memory repair of such UME‐responsive scaffolds via enhancing collagen deposition, recalling mechanical memory, decreasing fibrosis and inflammation, and accelerating angiogenesis. The design rationales (e.g., UME‐initiated structure reconfiguration and antiswelling) can serve as an instructive and general approach for urethra repair.

MicroRNA (miR)-138 was found to have suppressive effects on the growth and metastasis of different human cancers. In this study, we aimed to investigate the regulatory mechanism of miR-138 in non-small cell lung cancer (NSCLC). We applied the Quantitative real-time PCR (qRT-PCR) to detect the miR-138 levels in NSCLC tissues (n=21) and cell lines, Bioinformatical predication, luciferase reporter assay and western blot to identify the target gene of miR-138. We also applied Cell transfection, MTT, transwell, and wound healing assays to reveal the role of miR-138 in NSCLC cell proliferation and malignant transformation. We observed that miR-138 expression level was significantly decreased in NSCLC tissues compared to their matched adjacent normal tissues. It was also downregulated in tissues with poor differentiation, advanced stage or lymph nodes metastasis, as well as in several NSCLC cell lines compared to normal lung epithelial cell. We further identified YAP1 as a direct target gene of miR-138, and observed that the protein level of YAP1 was negatively mediated by miR-138 in NSCLC A549 cells. Moreover, overexpression of miR-138 significantly inhibited A549 cell growth, invasion and migration, while knockdown of miR-138 enhanced such capacities. Further investigation showed that the cell proliferation capacity was higher in the miR-138+YAP1 group, when compared with that in the miR-138 group, suggesting that overexpression of YAP1 rescued the suppressive effects of miR-138 upregulation on NSCLC cell proliferation. However, we found no difference of cell invasion and migration capacities between miR-138+YAP1 group and miR-138 group. Finally, YAP1 was markedly upregulated in NSCLC tissues compared to their marched adjacent normal tissues. Its mRNA levels were reversely correlated with the miR-138 levels in NSCLC tissues. In summary, our study suggests that miR-138 may play a suppressive role in the growth and metastasis of NSCLC cells partly at least by targeting YAP1.

High-grade serous carcinoma is the most common and devastating type of ovarian cancer; its etiology, mechanism of malignant transformation, and origin remain controversial. Recent studies have identified secretory cells at the fimbria of the fallopian tube as the cell-of-origin of high-grade serous carcinoma, acquiring TP53 mutation, evolving to tubal precursor lesions, including "p53 signature" and serous tubal intraepithelial carcinoma, and metastasizing to the ovary as clinically evident ovarian cancer. The etiological mechanisms associated with known epidemiological risk factors, i.e., ovulation and retrograde menstruation, have also been suggested. Mutagens and transforming growth factors, such as reactive oxygen species and insulin-like growth factor axis proteins, as well as the apoptosis-rescuing protein hemoglobin are abundantly present in the ovulatory follicular fluid and peritoneum fluid, which bathes the fimbrial epithelium, and induces malignant transformation after repeated exposure. In accordance with the proposed cleansing effect of progesterone from studies on oral contraceptive use or term pregnancy, a recent study indicated that the p53-null tubal epithelial cells are selectively cleared by progesterone depending on its progesterone receptor. In this report, by analyzing different time effects of oral contraceptive use or pregnancy in the prevention of ovarian cancer and by aligning them with the carcinogenic and cleansing clearance concepts of ovulation and progesterone, as well as the fact of progressive loss of progesterone receptor during tubal transformation, we deduced the natural history of ovarian high-grade serous carcinoma. The natural history begins at the first ovulation and spans for more than 30 years, taking 10 years from the normal tubal epithelium to the "p53 signature" status, another 15 years to progesterone receptor negative serous tubal intraepithelial carcinoma, and a final 5+ years to highgrade serous carcinoma. The estimated natural history may help understand the pathogenesis of high-grade serous carcinoma and defines the window for early detection and chemoprevention.

Objectives Few studies have investigated the prophylactic efficacy of dexmedetomidine (DEX) in postpartum depressive symptoms (PDS). A randomized double‐blind placebo‐controlled trial was conducted to investigate whether the administration of DEX, immediately after delivery and for patient‐controlled intravenous analgesia (PCIA), can attenuate PDS. Methods A total of 600 parturients scheduled for elective cesarean delivery under spinal anesthesia were randomly allocated into the control group (infusion with 0.9% normal saline after delivery and PCIA with sufentanil) and the DEX group (DEX infusion 0.5 μg/kg after delivery and PCIA with DEX plus sufentanil). The prevalence of postpartum depressive disorders was indicated by the Edinburgh Postnatal Depression Scale (EPDS). Postoperative analgesia, sedation, and sleep quality of parturients were also assessed. Results Postpartum blues and PDS prevalence in the DEX, versus control, group were significantly lower (5.0% vs 14.1%, p<0.001; 5.7% vs 16.3%, p<0.001, respectively), especially in parturients with antenatal depression or moderate stress during pregnancy. Compared with the control group, the EPDS score at postpartum days 7 and 42 in the DEX group was significantly lower (4.23 ± 4.37 vs 1.93 ± 3.36, p<0.001; 4.68 ± 4.78 vs 1.99 ± 3.18, p<0.001, respectively), as was the incidence of postpartum self‐harm ideation at postpartum days 7 and 42 in the DEX group versus the control group (1.1% vs 4.0%, p=0.03; 0.4% vs 2.9%, p=0.04, respectively). The pain score and the sleep quality in the DEX group were better than that in the control group (p<0.001). Conclusion The application of DEX in the early postpartum period can significantly attenuate the incidence of postpartum depressive disorders.

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