[Value of surgery combined chemotherapy and radiation therapy in locally advanced neuroendocrine carcinoma of the cervix: a single-center retrospective cohort study].

Objective: To evaluate the surgery combined chemotherapy and radiation in locally advanced neuroendocrine carcinoma of the cervix (NECC) . Methods: This is a single-center retrospective cohort study. Locally advanced NECC patients admitted to Peking Union Medical College Hospital, Chinese Acadmy of Medical Sciences from January 2011 to April 2022 were enrolled. They were divided into concurrent chemoradiotherapy group, and surgery combined with chemotherapy and radiation group. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Forty-six cases were included, 22 in concurrent chemoradiotherapy group, 24 in surgery combined chemotherapy and radiation group. With 16 patients (35%, 16/46) received neoadjuvant chemotherapy (NACT), the NACT effective rate was 15/16. (2) The median follow-up time was 27.5 months (range: 10-106 months), with 26 (57%, 26/46) experienced recurrences. There were 4 (9%, 4/46) pelvic recurrences and 25 (54%, 25/46) distant recurrences, and 3 (7%, 3/46) both pelvic and distant recurrences. Compared with concurrent chemoradiotherapy group, surgery combined chemotherapy and radiation group had lower pelvic recurrence rate [14% (3/22) vs 4% (1/24); χ2=1.296, P=0.255] but without statistic difference. Both groups had similar distant recurrence rate [55% (12/22) vs 54% (13/24); χ2=0.001, P=0.979] and overall recurrence rate [59% (13/22) vs 54% (13/24); χ2=0.113, P=0.736]. (3) During the follow-up period, 22 cases (48%, 22/46) died, with 11 cases (50%, 11/22) in concurrent chemoradiotherapy group and 11 cases (46%, 11/24) in surgery combined chemotherapy and radiation group, without significant difference (χ2=0.080, P=0.777). The postoperative 3-year and 5-year OS rates were 62.3% and 36.9%. Compared with concurrent chemoradiotherapy group, the patients in surgery combined chemotherapy and radiation group showed an extended trend in PFS (17.0 vs 32.0 months) and OS (37.0 vs 50.0 months) but without statistic differences (P=0.287, P=0.125). Both groups had similar 3-year OS rate (54.2% vs 69.9%; P=0.138) and 5-year OS rate (36.1% vs 38.8%; P=0.217). Conclusions: Our study supports the multi-modality treatment strategy (including surgery, chemotherapy and radiation) as an important component in the treatment of locally advanced NECC. The combination of surgery, chemotherapy and radiation seems to have advantages in the treatment of locally advanced NECC, but needs to be confirmed by further multicenter studies.

[Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumors: a report of 15 cases in a national medical center].

Objective: To evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.

Development and validation of a nomogram for urinary tract infection in geriatric patients with hip fracture: a retrospective study.

OBJECTIVE: This study aims to develop and validate a risk nomogram for urinary tract infections (UTIs) in geriatric patients with hip fractures. PATIENTS AND METHODS: A total of 900 geriatric patients who underwent hip fracture surgery at Dandong Central Hospital between June 2017 and June 2023 were systematically collected. The cohort was randomly divided into a training set (70%, n=632) and a validation set (30%, n=268) for model development and validation, respectively. Univariate and multivariate logistic regression analyses were conducted to identify the independent risk factors associated with UTIs. Based on the results of the multivariate analysis, a UTI nomogram prediction model was developed and evaluated in the training and validation sets using the C-index, ROC curve, calibration curve, and decision curve analysis to assess discrimination, calibration, and clinical utility, respectively. RESULTS: Out of the 900 participants, 24.6% were diagnosed with UTIs. The nomogram was developed based on 9 predictors that were found to be independently associated with UTI. The area under the curve (AUC) for predicting UTI in geriatric patients with hip fractures was 0.829 in the training set and 0.803 in the validation set. Following internal verification, the modified C-index remained at 0.829. Furthermore, the nomogram's calibration plot and decision curve analysis demonstrated good performance in both the training and validation sets. CONCLUSIONS: The established and validated nomogram provides a reliable and convenient tool for predicting UTI risk in geriatric patients with hip fractures. This model facilitates the early identification of high-risk patients and offers guidance for implementing targeted preventive interventions.

[Prognostic comparison of active surveillance and adjuvant chemotherapy in the treatment of patients with stage â ovarian immature teratoma after fertility-sparing surgery].

Objective: To compare the survival outcomes between surveillance and adjuvant chemotherapy in patients with stage Ⅰ ovarian immature teratoma (IMT) underwent fertility-sparing surgery. Methods: Clinical and pathological records of patients with stage Ⅰ ovarian IMT between Jan. 2011 to Feb. 2023 were collected from Peking Union Medical College Hospital, except stage Ⅰa grade 1. The consultation of risks and benefits regarding adjuvant chemotherapy was conducted by gynecologic oncologists. A shared decision about surveillance or chemotherapy was made by physician and patients or their guardians. Patients who finally decided to undergo surveillance were included in the surveillance group (n=40), the others were included in the adjuvant chemotherapy group (n=63). Clinical characteristics, treatment and survival outcomes were analyzed and compared between two groups. Results: A total of 103 patients were included. The median age of initial diagnosis was 20 years old (range: 3-39 years old), and the median follow-up time was 31 months (range: 1-254 months). The age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathological grade, surgical method, and preoperative and postoperative alpha-fetoprotein levels in the surveillance group and the adjuvant chemotherapy group were similar (all P>0.05). The surgical approach and maximum tumor diameter between two groups were significantly different (all P<0.05). Forty patients of the surveillance group were identified, only one patient with stage Ⅰa grade 2 IMT who underwent cystectomy had malignant recurrence on the same ovary. Another 63 patients received adjuvant chemotherapy after surgery, five patients had malignant recurrence, and two of them died of disease progression after relapsed. There were no significant differences in disease-free survival (DFS;20 vs 36 months) and overall survival (OS; 23 vs 39 months) between the surveillance group and the adjuvant chemotherapy group (follow-up time censored at 72 months; DFS: P=0.325, OS: P=0.278). Conclusions: There are no differences in survival outcomes between patients with stage Ⅰ ovarian IMT underwent adjuvant chemotherapy or not. Active surveillance might be safe and preferable in stage Ⅰ IMT patients underwent complete resection of tumor.

[Value of postoperative radiotherapy and analysis of prognostic factors in early-stage neuroendocrine carcinoma of cervix].

Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P=0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P=0.150) and overall recurrence rate (33% vs 41%; P=0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P<0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence (OR=23.03, 95%CI: 3.55-149.39, P=0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference (P=0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P=0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences (P=0.704, P=0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P=0.860) and OS (56.2 vs 62.4 months; P=0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.

A study on the mechanism of PP2A in the recovery of SCI in rats through downregulation of MMP-9 via MAPK signaling pathway.

OBJECTIVE: The aim of this study was to investigate the mechanism of action of protein phosphatase 2A (PP2A) in the recovery of spinal cord injury (SCI) in rats by downregulating matrix metalloproteinase 9 (MMP-9) via the mitogen-activated protein kinase (MAPK) signaling pathway. MATERIALS AND METHODS: A model of SCI was first successfully established in rats. A total of three groups were set, including: sham operation group (A group), SCI group (B group) and PP2A group (C group). The Basso, Beattie and Bresnahan (BBB) motor function score and inclined plane test were adopted to evaluate the motor ability and limb muscle strength of rats in each group. The water content in spinal cord tissues was detected as well. Quantitative Polymerase Chain Reaction (qPCR) assay was performed to analyze the messenger ribonucleic acid (mRNA) expression levels of MAPK, MMP-2, and MMP-9 in spinal cord tissues. The expressions of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 in each group of rats were determined via enzyme-linked immunosorbent assay (ELISA). Western blotting (WB) was employed to measure the protein expression levels of MAPK, MMP-2 and MMP-9 in each group of rats. Additionally, the apoptosis of nerve cells in spinal cord tissues was analyzed through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. RESULTS: The BBB score was 8.8 points in C group at 5 d after operation, which was significantly different from that in B group (p<0.05). The slope in B and C groups was clearly lower than that in A group at each time point (p<0.001). Meanwhile, it was significantly higher in C group than that in B group at 5, 7 and 9 d (p<0.05). The edema rate rose notably in B group compared with A group (p<0.001). However, spinal cord edema was remarkably relieved after treatment with FRY720 (p<0.01), suggesting that PP2A agonist could treat SCI in rats. The levels of cytokines TNF-α, IL-1ß and IL-6 were markedly higher in B group than those in A group (p<0.01). However, they were significantly reduced after treatment with PP2A agonist (p<0.01). In comparison with A group, B group exhibited remarkably decreased mRNA expression of MAPK and elevated mRNA expressions of MMP-2 and MMP-9 (p<0.01). However, C group exhibited an upregulated mRNA expression of MAPK (p<0.05), a downregulated mRNA expression of MMP-9 (p<0.01), and an undifferentiated mRNA expression of MMP-2 (p>0.05). Compared with B group, the protein expression level of MAPK significantly increased (p<0.05), while that of MMP-9 evidently decreased in C group (p<0.05). Besides, no statistically significant difference was observed in the protein expression level of MMP-2 between C group and B group (p>0.05). Compared with that in A group, the apoptosis rate significantly increased in B group (p<0.001). In addition, the apoptosis rate was significantly lower in C group than that in B group, showing a statistically significant difference (p<0.01). CONCLUSIONS: PP2A downregulates MMP-9 through the MAPK signaling pathway, thereby conducing to the recovery of SCI in rats.

[GnRH-a combined fertility-sparing re-treatment in women with endometrial carcinoma or atypical endomertial hyperplasia who failed to oral progestin therapy].

Objective: To analyze the clinical efficacy and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based fertility-sparing re-treatment in women with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) who failed with oral progestin therapy. Methods: Forty cases with EC or AEH who failed to respond to oral progestin were included from January 2012 to December 2020 at Peking Union Medical College Hospital. Combination of GnRH-a with levonorgestrel-releasing intrauterine system (group GLI: a subcutaneous injection of GnRH-a every 4 weeks and LNG-IUS insertion constantly) or the combination of GnRH-a with aromatase inhibitor (group GAI: a subcutaneous injection of GnRH-a every 4 weeks and oral letrozole 2.5 mg, daily) were used for these patients. Histological evaluation were performed at the end of each course (every 3-4 months) by hysteroscopy and curettage. After the complete remission (CR), all patients were followed up regularly. Results: (1) Clinical characteristics:among the 40 patients with EC or AEH, the median age at diagnosis was 31 years (range: 22-40 years) and the median body mass index was 24.7 kg/m2 (range: 18.9-39.5 kg/m2). (2) Efficacy of fertility-sparing re-treatment: 37 (92%, 37/40) patients achieved CR, 6 (6/7) in AEH and 31 (94%, 31/33) in EC patients. The CR rate was 93% (26/28) and 11/12 in group GLI and GAI, respectively. The median time to CR was 5 months (range: 3-12 months). At the end of the first therapy course, the CR rates in AEH and EC were 5/7 and 42% (14/33), at the second course, the CR rates were 6/7 and 82% (27/33), respectively. (3) Recurrence: after 25 months of median follow-up duration (range: 10-75 months), 8 (22%, 8/37) women developed recurrence, 1/6 in AEH and 7 (23%, 7/31) in EC patients, with the median recurrence time of 18 months (range: 9-26 months). Among them, two cases who had completed childbirth chose to receive hysterectomy directly. Six patients met the criteria of fertility-preserving therapy and received conservative treatment again and 5 (5/6) of them achieved CR. (4) Pregnancy: of the 37 patients with CR, 33 desired to conceive. Ten women attempted to get pregnancy spontaneously and 23 cases with assisted reproductive technology. Fourteen (42%, 14/33) patients became pregnant, including 9 (27%, 9/33) live births, 3 (9%, 3/33) missed abortions, and 2 (6%, 2/33) miscarriages at the second trimester. Conclusions: GnRH-a based fertility-sparing re-treatment in AEH or EC patients who failed with oral progestin therapy achieved good treatment effect and reproductive outcomes. It is an encouraging alternative regime for patients who failed with oral progestin therapy.

Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial☆.

BACKGROUND: This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer. PATIENTS AND METHODS: In this phase III, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/µl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review. RESULTS: Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 [95% confidence interval (CI), 10.9-not evaluable] versus 5.4 (95% CI, 3.7-5.7) months [hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001], and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%). CONCLUSIONS: Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.

Circ-PRMT5 stimulates migration in esophageal cancer by binding miR-203.

OBJECTIVE: The study aimed to uncover the role of circ-PRMT5 in triggering the migratory ability of esophageal cancer by regulating microRNA-203 (miR-203) level. PATIENTS AND METHODS: Circ-PRMT5 levels in 56 matched esophageal cancer tissues and paracancerous ones were detected. The relationship between circ-PRMT5 level and clinical data of esophageal cancer patients was analyzed. Migratory abilities in TE-1 and OE33 cells influenced by circ-PRMT5 were evaluated by transwell and wound healing assay. Regulatory effect of circ-PRMT5 on miR-203 level, and the involvement of miR-203 in the development of esophageal cancer were determined through Dual-Luciferase reporter assay and rescue experiments. RESULTS: Circ-PRMT5 was upregulated in esophageal cancer tissues and cell lines. The expression level of circ-PRMT5 was positively correlated to the rates of lymphatic metastasis and distant metastasis of esophageal cancer. Knockdown of circ-PRMT5 attenuated migratory abilities in TE-1 and OE33 cells. MiR-203 was verified to be the target gene binding circ-PRMT5, with a negative correlation between each other. Notably, miR-203 was responsible for the regulatory effect of circ-PRMT5 on migratory ability in esophageal cancer. CONCLUSIONS: Circ-PRMT5 is positively correlated to the rates of lymphatic metastasis and distant metastasis of esophageal cancer. It promotes migratory ability in esophageal cancer by targeting miR-203.

[Association of cadmium pollution with liver function of population in mineral polluted areas of Guangxi].

Objective: To investigate the association of cadmium exposure with liver function among adults in a non-ferrous metal mining area in Guangxi. Methods: A total of 310 residents aged 18 and above were recruited from 5 heavy metals polluted villages in a non-ferrous metal mining area in Guangxi from 2013 to 2014. The general demographic characteristics, blood cadmium levels and indicators of liver function index [Total bilirubin (TBIL), Glutamic oxaloacetic transaminase (AST), Alanine transaminase (ALT) and Glutamine transaminase (GGT)] were obtained by using questionnaire, physical examination and laboratory test. The blood cadmium levels were divided into quartiles as Q1-Q4 groups (using Q1 group as the reference).Multivariate logistic regression model was used to analyze the correlation between the blood cadmium level and functional liver index. Results: The age of subjects was (49.2±15.4) years, and 112 (36.1%) subjects were male residents. The prevalence of abnormal rates of TBIL,AST,ALT and GGT were 17.4% (54), 19.7% (61), 10.7% (33) and 11.9% (37), respectively. The geometric mean value of cadmium levels in adults was 3.72(95%CI: 3.43-4.02) µg/L. After adjusting for age, gender, body mass index (BMI), smoking, drinking, total cholesterol, hypertriglyceridemia and other factors, the risk of abnormal AST index in the highest concentration of blood cadmium group (Q4) was higher than that in the lowest concentration of blood cadmium group (Q1) (OR=2.92, 95%CI:1.07-7.98). Conclusion: The level of blood cadmium exposure is higher than the reference value of general population in China, and the elevated cadmium exposure is related to the increasing risk of AST abnormality.

[Effects of miR-141-3p on proliferation, migration and NF-κB signaling pathways in gastric cancer cells].

Objective: To investigate the effects of miR-141-3p on proliferation and migration of gastric cancer cells and nuclear factor-κB (NF-κB) signaling pathway. Methods: Human gastric cancer cell line BGC-823 was cultured, and miR-141-3p mimetic (miR-141-3p mimics) was transfected into BGC-823 cells by lipofection. The miR-141-3p overexpressed BGC was constructed. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the transfection effect. The proliferation of BGC-823 cells was determined by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Transwell assay was used to detect the effect of miR-141-3p on BGC-823 cell migration. The expressions of NF-κB p65, p-IKK-α and p-IKB-α protein in NF-κB signaling pathway were detected by western blot. Results: Compared with the control group and the negative control group, the expression level of miR-141-3p in BGC-823 cells of the miR-141-3p group was (2.39±0.27), which was higher than (1.00±0.09) of the control group and (1.01±0.10) of the negative control group (P<0.05). The number of migrating cells in the miR-141-3p group was (47.64±5.65), which was lower than (106.22±12.14) in the control group and (110.40±12.26) in the negative control group (P<0.05). The expression levels of NF-κB p65, p-IKK-α and p-IKB-α protein in BGC-823 cells were down-regulated (P<0.05). Conclusion: MiR-141-3p can inhibit the proliferation and migration of human gastric cancer BGC-823 cells, which may be related to the inhibition of NF-κB signaling pathway activation.

LncRNA FOXC2-AS1 regulated proliferation and apoptosis of vascular smooth muscle cell through targeting miR-1253/FOXF1 axis in atherosclerosis.

OBJECTIVE: Atherosclerosis (AS) is the most dangerous factor for human death, which is responsible for coronary heart disease. Growing evidence has showed that long non-coding RNAs (lncRNAs) are involved in the development of AS. In this study, we mainly aimed at investigating the roles of FOXC2-AS1 in AS patients. PATIENTS AND METHODS: RT-PCR was performed to detect the expressions of FOXC2-AS1 and miR-1253 in serum samples of AS patients (n=35) and healthy volunteer (n=35). The correlation between FOXC2-AS1 and miR-1253 was further analyzed. Human vascular smooth muscle cells (VSMCs) were respectively treated with ox-LDL, IL-6, CRP, TNF-α and IL-8 to explore the affecting factors. P-FOXC2-AS1 was constructed and transfected into VSMCs. Cell proliferation abilities were measured by CCK-8 assay. Cell apoptotic rates were measured by flow cytometry (FACS) analysis. Western blot (WB) was performed to detect protein levels of FOXF1, Bcl-2, Bax and Cleaved Caspase3. Finally, luciferase gene reporter assay was performed to prove the relationships between FOXC2-AS1 and miR-1253, miR-1253 and FOXF1. RESULTS: We found that FOXC2-AS1 was significantly upregulated in AS patients, which could be induced by ox-LDL and IL-6 in VSMCs. MiR-1253 was decreased in AS patients, which was negatively correlated with FOXC2-AS1. Furthermore, FOXC2-AS1 overexpression promoted proliferation and inhibited apoptosis in VSMCs. Luciferase gene reporter assay showed that FOXC2-AS1 could bind to miR-1253 in VSMCs and 293 cells. Moreover, miR-1253 overexpression inhibited proliferation and promoted apoptosis of VSMCs. Luciferase reporter assay proved that miR-1253 could target at FOXF1 in VSMCs and 293 cells, which was reported to be associated with cell proliferation and apoptosis in some cancers. Additionally, miR-1253 mimic or GSK343, a FOXF1 inhibitor, was respectively transfected into VSMCs with p-FOXC2-AS1. Results showed that the promoted cell proliferation and inhibited cell apoptosis were reversed as well, confirming that FOXC2-AS1 promoted cell proliferation and inhibited apoptosis via miR-1253/FOXF1 signaling axis in AS patients. CONCLUSIONS: According to the results, we found that FOXC2-AS1 was upregulated in AS patients; furthermore, FOXC2-AS1 overexpression promoted cell proliferation and inhibited cell apoptosis via targeting miR-1253/FOXF1 signaling axis. Our results elucidated a potential mechanism underlying the role of FOXC2-AS1, which might be used as a promising marker and a potential target for AS patients.

Quercetin improves immune function in Arbor Acre broilers through activation of NF-κB signaling pathway.

Quercetin, the main component of flavonoids, has a wide range of biological actions. Quercetin can be made into a variety of additives for practice, because of the stable chemical structure and water-soluble derivatives. This study was intended to explore the effects of quercetin on immune function and its regulatory mechanism in Arbor Acre broiler to provide a practical basis for improving poultry immune function and figure out the optimum supplementation as functional feed additives. A total of 240 one-day-old healthy Arbor Acre broilers, similar in body weight, were randomly allotted to 4 treatments with 6 replicates, 10 broilers in each replicate and fed with diets containing quercetin at 0, 0.02, 0.04, and 0.06% for 6 wk. Blood and immune organs (spleen, thymus, and bursa) were collected from chickens at the end of the experiment. Growth performance, immune organs indexes, contents of serum immune molecules, splenic T lymphocyte proliferative responses, and expression of immune related genes were evaluated. The results showed that dietary quercetin had no significant effect (P > 0.05) on growth performance of broilers. Compared with control, 0.06% quercetin supplementation in diet significantly increased spleen index and thymus index (P < 0.05). It also increased the secretion of immune molecules including immunoglobulin A (IgA), interleukin-4 (IL-4) (P < 0.001), immunoglobulin M (IgM) (P = 0.007), complement component 4 (C4) (P = 0.001), and tumor necrosis factor-α (TNF-α) (P < 0.05). On the other hand, 0.02% quercetin supplementation significantly increased complement component 3 (C3) (P < 0.05). Additionally, both 0.04 and 0.06% quercetin supplementation significantly increased expression of TNF-α, TNF receptor associated factor-2 (TRAF-2), TNF receptor superfamily member 1B (TNFRSF1B), nuclear factor kappa-B p65 subunit (NF-κBp65), and interferon-γ (IFN-γ) mRNA (P < 0.05), and expression of NF-κB inhibitor-alpha (IκB-α) mRNA were significantly decreased (P < 0.05). Thus, quercetin improved immune function via NF-κB signaling pathway triggered by TNF-α.

[Clinicopathological features and prognosis of patients in endometrial cancer with bone metastases].

Objective: To analyze the clinicopathological features and prognosis of patients in endometrial cancer with bone metastases. Methods: A retrospective review of medical records was performed to analyze patients with endometrial cancer who developed bone metastases at Peking Union Medical College Hospital (PUMCH) from January 2004 to December 2017, including patients with bone metastases at the diagnosis of endometrial cancer and at recurrence of endometrial cancer. The patient's clinicopathological features, bone metastasis characteristics, treatment process and prognoses were also analyzed. Results: The incidence of bone metastasis of endometrial cancer in PUMCH from 2004 to 2017 was 0.57% (14/2 458). (1) General clinical pathological features: the median age of the 7 patients with bone metastases diagnosed at the time of initial diagnosis was 50 years old, and the main pathological type was endometrioid carcinoma (n=5). The median age of the other 7 patients was 57 years old, with no significant difference comparing to the former groups (P=0.559). (2) The majority site of bone metastasis in endometrial cancer were discovered in pelvic bones, followed by the tibia. (3) Treatment: according to the staging of endometrial cancer, a comprehensive treatment based on surgery was performed, and one patient with isolated bone metastases underwent resection of bone metastasis. (4) Prognosis: nine out of the 14 patients died during the follow-up period. The median over all survival time was 25.5 months (range: 7.7-258.0 months). The median survival of population after diagnosis of bone metastases was 15.0 months (range: 3.0-51.0 months). The survival rate of endometrial cancer at 1-year after diagnosis of bone metastasis was 71.4%. The 2-year survival rate was 40.8%. (5) No independent prognostic factors affecting survival was found (P>0.05). Conclusions: The incidence of bone metastasis in endometrial cancer is less than 1%. Bone metastasis could occur at the diagnosis of endometrial cancer or recurrence of endometrial cancer. Bone metastasis suggests a poor prognosis. There is no standard follow-up and treatment protocols so that individualized treatment is needed.

MicroRNA-95-3p promoted the development of prostatic cancer via regulating DKK3 and activating Wnt/ß-catenin pathway.

OBJECTIVE: Previous studies have shown that microRNA-95-3p (miR-95-3p) plays a crucial role in multiple human cancers except for prostatic cancer (PCa). Therefore, the function of miR-95-3p was investigated in PCa in the present work. PATIENTS AND METHODS: The expression of miR-95-3p was measured by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) assay. Western blot assay was used to examine the protein expression of epithelial-mesenchymal transition (EMT) markers. In addition, the function of miR-95-3p was detected through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell assays. Dual Luciferase assay was applied to confirm the relationship between miR-95-3p and dickkopf-3 (DKK3). The tumor growth was observed through xenograft tumor formation assay. RESULTS: The upregulation of miR-95-3p was detected in PCa tissues and cell lines, which predicted poor prognosis of PCa patients. Moreover, miR-95-3p promoted cell proliferation, migration and invasion in PCa by targeting DKK3 and activating the Wnt/ß-catenin pathway. MiR-95-3p also promoted the tumor growth of PCa in vivo. Besides that, downregulation of DKK3 was identified in PCa and low DKK3 expression predicted poor prognosis of PCa patients. CONCLUSIONS: MiR-95-3p promoted the development of PCa via targeting DKK3 and activating the Wnt/ß-catenin pathway.

[Clinicopathologic and survival analysis of synchronous primary endometrial and ovarian cancer].

Objective: To demonstrate the clinicopathological characteristics and determine the prognostic factors for women with synchronous primary endometrial and ovarian cancer (SEOC) . Methods: A retrospective analysis of 63 pathologically proven cases of SEOC diagnosed in Peking Union Medical College Hospital from January 2000 to May 2018 was carried out. Results: (1) Clinical features: mean age at diagnosis was (48.3±10.0) years, and the mean body mass index (BMI) was (23.4±3.7) kg/m(2). The most common presenting symptom was abnormal uterine bleeding with a ratio of 73% (46/63). Forty-three patients (68%, 43/63) were premenopausal, and 30% (19/63) were nulliparous. (2) Pathological features: for the endometrial cancer, 90% patients were diagnosed at stage Ⅰ, and 81% were low grade tumors (G(1)-G(2)). The histological type of endometrial cancer was mainly endometrioid carcinoma (86%) and majority (81%) of patients were proved without or with superficial myometrial invasion. For the ovarian cancer, 70% patients were diagnosed at stage Ⅰ and 65% were low grade tumors (G(1)-G(2)). Sixty-two percent of ovarian cancers were endometrioid carcinoma and 68% of patients had unilateral involvement of the ovaries. (3) Treatment and prognosis: all patients underwent surgery, of which 56 (89%) underwent staging surgery including retroperitoneal lymphadenectomy, and 57 (90%) received postoperative adjuvant therapy. The median follow-up time was 48.0 months (range, 2-176 months) , and 13% of the patients experienced tumor recurrence during the follow-up period. The median time to recurrence was 38.5 months, and 6 patients (10%) died of tumor recurrence. The 5-year progression-free survival (PFS) and 5-year overall survival (OS) for all patients were 69% and 80%, respectively. (4) Prognostic factors: univariate analysis showed that the presence of lymphovascular space invasion (LVSI) , non-endometrioid histology of ovarian cancer and stage of ovarian cancer above stage Ⅰ were associated with significantly worse PFS (P<0.05). LVSI, high grade of endometrial cancer, and above stage Ⅰ of ovarian cancer were associated with significantly worse OS (P<0.05). On multivariate analysis, LVSI, non-endometrioid type ovarian cancer and stage of ovarian cancer above stage Ⅰwere associated with significantly worse PFS (P<0.05). In addition, LVSI and stage of ovarian cancer above stage Ⅰ were also associated with significantly worse OS (P<0.05) . Conclusions: Women with SEOC are young, premenopausal and have a favorable overall prognosis. Presence of LVSI, non-endometrioid type ovarian cancer and stage of ovarian cancer above stage Ⅰ are independent prognostic factors for PFS, and stage of ovarian cancer above stage Ⅰare independent prognostic factors for OS.

Praseodymium ion doped K+-Na+ thermal ion-exchangeable waveguide-adaptive aluminum germanate glasses.

Intense multi-peak red fluorescence and effective near-infrared (NIR) ultra-broadband emission have been observed in Pr3+ doped ion-exchangeable aluminum germanate (NMAG) glasses. The maximum emission cross section for P03→F23 red emission is up to 100.58×10-21 cm2, and the NIR emission corresponding to D21→G41 transition possesses a full-width at half-maximum (FWHM) of 210 nm. Although the obvious cross-relaxation (CR) process at high concentration causes a decrease of the quantum efficiency, the CR broadens the spectral FWHM effectively from another perspective. The admirable red fluorescence trace and the NIR single-mode transmission confirm that Pr3+ doped NMAG glass planar waveguides can support the generation of visible fluorescence and the amplification of infrared signal. For a waveguide channel ion-exchanged in molten KNO3 for 2 h, the single-mode field diameters at 1.55 µm are identified to be 10.4 µm in the horizontal direction and 6.5 µm in the vertical direction, implying an acceptable overlap with a standard single-mode fiber. Effective red fluorescence and broad NIR emission demonstrate that Pr3+ doped NMAG glasses are a promising substrate in developing irradiative luminescence sources and ultra-broadband waveguide amplifiers, especially operating at the entire S-, C-, and L- bands.