Management of oral leukoplakia by ablative fractional laser-assisted photodynamic therapy: A 3-year retrospective study of 48 patients.

OBJECTIVES: This study aimed to review the results of oral leucoplakia (OL) using ablative fractional laser-assisted photodynamic therapy (AFL-PDT) and to further evaluate the risk factors for recurrence and malignant transformation. MATERIALS AND METHODS: Forty-eight patients diagnosed with OL using histopathology were enrolled in this study. All patients received one session of AFL-PDT. Therapeutic efficacy was evaluated 1 month posttreatment. Follow-up was scheduled every 3 months in the first year and every 6 months thereafter. RESULTS: An overall positive response rate of 87.5% (42/48) was achieved, including 62.5% (30/48) complete responses and 25.0% (12/48) partial responses. During the 3-year follow-up period, the recurrence and malignant transformation rates were 37.5% (18/48) and 8.3% (4/48), respectively. Lesions on gingiva/palate seemed to be associated with recurrence (p < 0.001; odds ratio [OR]: 1.64, 95% confidence interval [CI]: 1.13-2.37). The severity of epithelial dysplasia (p = 0.02; OR: 2.93, 95% CI: 1.96-4.42) and recurrence (p = 0.016; OR: 3.14, 95% CI: 2.04-4.84) were associated with a predisposition to malignant transformation. CONCLUSIONS: AFL-PDT is an effective management of OL, but requires close follow-up. OL lesions on the gingiva/palate are predisposed to recurrence. OLs that recur with moderate/severe epithelial dysplasia have a higher risk of transforming into oral squamous cell carcinoma.

First report of a successful pregnancy by preimplantation genetic testing for Beckwith-Wiedemann syndrome.

OBJECTIVE: Beckwith-Wiedemann syndrome (BWS) is a rare imprinting gene disorder. Maternal CDKN1C mutation comprises 5% of etiologies of BWS. There is no successful report of preventing BWS by preimplantation genetic testing for monogenic disease (PGT-M) in the literature. Is PGT-M applicable for preventing BWS ? CASE REPORT: This 39-year-old woman conceived naturally and delivered a boy who was diagnosed of BWS. The genetic testing of her son revealed CDKN1C gene mutation, and of the mother showed a carrier of the same mutation. She underwent controlled ovarian stimulation, oocyte pickup, and intracytoplasmic sperm injection. Trophectoderm biopsies were performed and samples were checked for PGT. Two wild-type and euploid embryos were thawed and transferred. One intrauterine pregnancy was achieved. The patient delivered a healthy female baby at 37 weeks of gestation. CONCLUSION: In this case, we first report a successful pregnancy with a wild-type CDKN1C gene baby achieved by PGT-M.

Multidisciplinary and Comprehensive Chinese Medicine for Advanced Non-Small Cell Lung Cancer Patients: A Retrospective Study of 855 Cases.

OBJECTIVE: To investigate the effects of multidisciplinary and comprehensive Chinese medicine (CM) treatments on progression-free survival (PFS) and median survival time (MST) in patients with advanced non-small cell lung cancer (NSCLC) and identify factors that influence progression and prognosis. METHODS: Clinical data of 855 patients with advanced NSCLC who received multidisciplinary and comprehensive CM treatments at Longhua Hospital from January 2009 to December 2018 were retrospectively analyzed. Univariate analysis was performed by the Kaplan-Meier method and log-rank sequential inspection. Multivariate analysis of significant variables from the univariate analysis was performed with Cox regression modeling. Key factors correlated to progression and prognosis were screened out, and a Cox proportional hazard model was established to calculate the prognostic index. RESULTS: The PFS and MST of 855 advanced NSCLC patients were 9.0 and 26.0 months, respectively. The 1-, 2-, 3-, and 5-year survival rates were 79.2%, 54%, 36.2%, and 17.1%, respectively. Gender, pathologic type, and clinical stage were independent prognostic risk factors; surgical history, radiotherapy, treatment course of Chinese patent medicine, intravenous drip of Chinese herbal preparation, duration of oral administration of Chinese herbal decoction (CHD), and intervention measures were independent prognostic protective factors. Gender was an independent risk factor for progression, while operation history and oral CHD administration duration were independent protective factors (all P<0.05). Women with stage IIIb-IIIc lung adenocarcinoma had the best outcomes. CONCLUSIONS: Female patients have lower progression risk and better prognoses than male patients, younger patients have higher progression risk but better long-term prognoses than the elderlys, and patients with lower performance status scores are at lower risk for progression and have better prognoses. Comprehensive CM treatments could significantly reduce progression risk, improve prognosis, and prolong survival time for patients with advanced NSCLC. This treatment mode offers additional advantages over supportive care alone.

MicroRNA-134 inhibits tumor stem cell migration and invasion in oral squamous cell carcinomas via downregulation of PI3K-Akt signaling pathway by inhibiting LAMC2 expression.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the mouth. Some studies have found that multiple microRNAs (miRs) participate in OSCC physiological and pathological processes. METHODS: We explored the mechanism of action of miR-134 in OSCC involving the PI3K-Akt signaling pathway. Different bioinformatics methods were used to analyze the potential genes and their related miRs in OSCC. Tumor stem cells were separated from OSCCs through magnetic cell sorting. Regulatory pattern between miR-134 and LAMC2 in OSCC was evaluated by ectopic expression, knockdown and reporter assay experiments. The expression of miR-134, LAMC2, genes in PI3K-Akt signaling pathway, and apoptosis-related genes was detected. Cell proliferation was assessed by MTT assay, cell invasion by scratch test, cell migration by Transwell assay, cell cycle and apoptosis by flow cytometry, and cell growth and migration by xenograft tumor in nude mice. LAMC2 was predicted as the crucial factor related to OSCC using different chip data, and miR-134 was predicted to specifically bind LAMC2 in all five databases. RESULTS: Overexpressed miR-134 or silenced LAMC2 was observed to inhibit cell proliferation, migration, invasion of OSCC cells, growth of subcutaneous xenograft in nude mice, as well as promote OSCC cell apoptosis. LAMC2, a target gene of miR-134, decreased following miR-134 promotion, while the PI3K-Akt signaling pathway was inactivated following LAMC2 knockdown. Furthermore, we also observed that the effect of overexpressed miR-134 was enhanced when LAMC2 was knocked down. CONCLUSIONS: Taken together, these findings suggest that miR-134-mediated direct downregulation of LAMC2 inhibits migration and invasion of tumor stem cells in OSCC by suppressing the PI3K-Akt signaling pathway.

[Treatment of Radical Resected NSCLC by Chinese Medicine Combined with Adjuvant Chemother- apy: a Clinical Study].

OBJECTIVE: To evaluate the efficacy of Chinese medicine (CM) combined adjuvant chemotherapy in postponing relapse and metastasis of radical resected Ib-IIIa stage non-small cell lung cancer (NSCLC) patients, and to explore its effect in improving their quality of life (QOL) and clinical symptoms. METHODS: We designed a cohort study of 336 radical resected Ib-IIIa NSCLC patients by analyzing disease free survival (DFS) using Log-rank test. They were randomly assigned to the control group (155 cases, treated by adjuvant chemotherapy group) and the test group (181 cases, treated by adjuvant chemotherapy combined CM). By using controlled method, 60 radical resected NSCLC patients undergoing NP/NC program in 2012 (vinorelbine 25 mg/m2, combined with cisplatin 75 mg/m2 on day 1 and day 8/on day 1 or on day 1, 2, and 3; or carboplatin AUC = 5 on day 1) were assigned to the control group (29 cases) and the test group (31 cases). QOL scores (using EORTC QLQ-LC43 questionnaire) and TCM symptoms scores were compared between the two groups before chemotherapy, peri-chemotherapy (one day before the 2nd course of chemotherapy) , and after chemotherapy (20 days after ending the 4th course of chemotherapy). RESULTS: (1) The median DFS was longer in the test group than in the control group, but with no statistical difference between the two groups (42.73 months vs 35.57 months , P = 0.179). In the subgroup analysis, there was statistical difference in IIIa stage DFS. The median IIIa stage DFS of was longer in the test group than in the control group with statistical difference (27.87 months vs 19. 93 months, P = 0.047). (2) In the control study, repeated measured data indicated there was significant difference in physical functions between the two groups (P < 0.05). Total scores for health states decreased more in the test group than in the control group, but with no statistical difference (P > 0.05). Scores for constipation and CM syndrome scores were higher in the test group than in the control group (P < 0.05). CONCLUSIONS: CM had advantages in postponing DFS of radical resected NSCLC patients, especially in IIIa stage. CM could improve their QOL and clinical symptoms during adjuvant chemotherapy.

Live birth after single embryo transfer of autologous cryopreserved oocytes from a patient with myelodysplastic syndrome who underwent allogenic peripheral blood stem cell transplantation.

We report a live birth after single embryo transfer derived from autologous cryopreserved oocytes of a patient with myelodysplastic syndrome who had undergone allogenic peripheral blood stem cell transplantation (PBSCT). In 2006, a 24-year-old female diagnosed with myelodysplastic syndrome was referred for fertility preservation before she underwent PBSCT. After controlled ovarian stimulation, 38 oocytes were retrieved for cryopreservation using a slow-freezing protocol. She was cured by PBSCT and entered menopause. After seven years, she requested thawing of the oocytes. She was prepared for a thawing cycle using hormone replacement therapy. Twenty-two cryopreserved oocytes were thawed, and 20 (91%) oocytes survived. Thirteen mature oocytes were inseminated by intracytoplasmic sperm injection. Ten (77%) oocytes were normally fertilized and 6 (60%) oocytes developed into blastocysts. Embryo transfer to her own uterus with one blastocyst was performed. Five blastocysts were vitrified. A sonographic exam at 7 weeks of gestation revealed one gestational sac with positive cardiac motion. A normal female baby weighing 2704 g was delivered at 40 weeks of gestation. A successful pregnancy from autologous cryopreserved oocytes is encouraging for cancer patients undergoing fertility preservation. For infertile cancer patients after PBSCT, we suggest the transfer of one embryo to reduce the risk of multiple pregnancies.

The duration of pre-ovulatory serum progesterone elevation before hCG administration affects the outcome of IVF/ICSI cycles.

STUDY QUESTION: During controlled ovarian stimulation (COS), does the duration of premature serum progesterone (P) elevation before administration of hCG affect the outcomes of IVF/ICSI embryo transfer (-ET) cycles? SUMMARY ANSWER: The duration of the premature serum P elevation is inversely related to the clinical pregnancy rate of IVF/ICSI-ET cycles. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: The majority of the previous studies only considered a single serum P measurement made on the day of hCG administration and the results of attempts to relate this to IVF/ICSI-ET outcomes were controversial. However, the effect of the duration of premature serum P elevation before the hCG administration on the outcomes of IVF/ICSI-ET cycles has not been studied well. Here we demonstrate that the duration of premature serum P elevation has a more significant inverse correlation than the absolute serum P concentration on the day of hCG administration with IVF/ICSI-ET outcomes. DESIGN: It is a retrospective, single-centre cohort study. A total of 1784 IVF and/or ICSI-ET cycles were included from October 2005 to June 2011. PARTICIPANTS AND SETTING: A total of 1784 patients underwent their IVF and/or ICSI-ET cycles in a university hospital IVF unit. The inclusion criteria include (i) age between 20 and 42 years and (ii) eligible indications for COS before IVF/ICSI. MAIN RESULTS AND THE ROLE OF CHANCE: The duration of premature serum P elevation to >1 ng/ml is significantly inversely associated with the probability of clinical pregnancy (odds ratio = 0.773, 95% confidence interval: 0.660-0.891, P < 0.001), after adjustment for possible confounders with multivariate logistic regression analysis. However, the significance of inverse correlation between the absolute serum P concentration on the day of hCG administration with clinical pregnancy rate decreased after adjustment. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: The cutoff value we chose to define premature serum P elevation (P > 1.0 ng/ml) might not be able to be applied to different immunoassay kits and study population. The retrospective nature of this study inevitably might be influenced by some selection bias. GENERALIZABILITY TO OTHER POPULATIONS: Older patients (>42 years) are excluded from our study.

Inhibition of Japanese encephalitis virus entry into the cells by the envelope glycoprotein domain III (EDIII) and the loop3 peptide derived from EDIII.

Japanese encephalitis virus (JEV) infection is a major cause of acute viral encephalitis both in humans and animals. The domain III of virus envelope protein (EDIII) plays important roles in interacting with host cell receptors to facilitate virus entry. In this study, recombinant JEV EDIII was expressed and purified. The protein showed the ability to inhibit JEV infection in BHK-21 cells with 50% inhibition at a concentration of 25µg/ml. Based on NMR structure of JEV EDIII, we chose several loop peptides that were reported to be related to receptor binding to test their possible inhibitory activities on virus infection. Our in vitro experiments demonstrated that one of the loop peptides (loop3) can prevent JEV infection with 50% inhibition at concentration of 10µM by interfering in virus attachment to the cells. Our in vivo experiments on mice showed the loop3 was the most protective peptide when administered before virus challenge. Therefore, the loop3 peptide may be served as basis for the development of novel antiviral agents against Japanese encephalitis virus or other flaviviruses infection.