Clinical and socioeconomic factors predicting return-to-work times after cholecystectomy.

BACKGROUND: Cholecystectomy, a type of surgery commonly performed globally, has possible mutual effects on the socioeconomic conditions of different countries due to various postoperative recovery times. AIMS: This study evaluated the medical and socioeconomic factors affecting delayed return-to-work (RTW) time after elective cholecystectomy. METHODS: This retrospective study analysed patients who underwent elective cholecystectomy for benign gallbladder diseases from January 2022 to April 2023. The patients' medical and socioeconomic data were collected to investigate the clinical and socioeconomic factors correlated with RTW time of >30 days after surgery. RESULTS: This study included 180 consecutive patients. Significant correlations were found between delayed RTW time (>30 days) and age (odds ratio [OR]: 1.059, 95% confidence interval [CI] 1.008-1.113, P = 0.024), lack of medical insurance (OR: 2.935, 95% CI 1.189-7.249, P = 0.02) and high-intensity labour jobs (OR: 3.649, 95% CI 1.495-8.909, P = 0.004). Patients without medical insurance (26.6 versus 18.9 days) and those with high-intensity labour jobs (23.9 versus 18.8 days) had a higher mean RTW time than those with insurance and a less-intense labour job (P < 0.001). CONCLUSIONS: After cholecystectomy, older age, lack of medical insurance and high-intensity labour job were correlated with a delayed RTW time. Informing patients about their expected RTW time after surgery can help reduce costs.

[Comparing the prognostic value of 3 diagnostic criteria of bronchopulmonary dysplasia in preterm infants].

Objective: To compare the prognostic value of 3 diagnostic criteria of bronchopulmonary dysplasia (BPD) in preterm infants with gestational age<32 weeks. Methods: The retrospective cohort study was conducted to collect the clinical data of 285 preterm infants with BPD admitted to the Department of Neonatology, Children's Hospital Affiliated to Zhengzhou University from January 2019 to September 2021, who were followed up regularly after discharge. The primary composite adverse outcome was defined as death or severe respiratory morbidity from 36 weeks of corrected gestational age to 18 months of corrected age, and the secondary composite adverse outcome was defined as death or neurodevelopmental impairment. According to the primary or secondary composite adverse outcomes, the preterm infants were divided into the adverse prognosis group and the non-adverse prognosis group. The 2001 National Institute of Child Health and Human Development (NICHD) criteria, 2018 NICHD criteria, and 2019 Neonatal Research Network (NRN) criteria were used to diagnose and grade BPD in preterm infants. Chi-square test, Logistic regression analysis, receiver operating characteristic (ROC) curve and Delong test were used to analyze the prognostic value of the 3 diagnostic criteria. Results: The 285 preterm infants had a gestational age of 29.4 (28.1, 30.6) weeks and birth weight of 1 230 (1 000, 1 465) g, including 167 males (58.6%). Among 285 premature infants who completed follow-up, the primary composite adverse outcome occurred in 124 preterm infants (43.5%), and the secondary composite adverse outcome occurred in 40 preterm infants (14.0%). Multivariate Logistic regression analysis showed that severe BPD according to the 2001 NICHD criteria, gradeⅡand Ⅲ BPD according to the 2018 NICHD criteria and grade 2 and 3 BPD according to the 2019 NRN criteria were all risk factors for primary composite adverse outcomes (all P<0.05). ROC curve showed that the area under the curve (AUC) of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.70 and 0.70 vs. 0.61, Z=4.49 and 3.35, both P<0.001), but there was no significant difference between the 2018 NICHD and 2019 NRN criteria (Z=0.38, P=0.702). Multivariate Logistic regression analysis showed that the secondary composite adverse outcomes were all associated with grade Ⅲ BPD according to the 2018 NICHD criteria and grade 3 BPD according to the 2019 NRN criteria (both P<0.05). ROC curve showed that the AUC of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.71 and 0.71 vs. 0.58, Z=2.93 and 3.67, both P<0.001), but there was no statistically significant difference between the 2018 NICHD and 2019 NRN criteria (Z=0.02, P=0.984). Conclusion: The 2018 NICHD and 2019 NRN criteria demonstrate good and comparable predictive value for the primary and secondary composite adverse outcomes in preterm infants with BPD, surpassing the predictive efficacy of the 2001 NICHD criteria.

[Preliminary evaluation of immunogenicity and protective effect of multicomponent recombinant protein vaccine EPRHP014 against tuberculosis].

Objective: To evaluate the immunogenicity and protective effect of a multicomponent recombinant protein vaccine EPRHP014 constructed independently and provide a scientific basis for developing new tuberculosis (TB) vaccine and effective prevention and control of TB. Methods: Three full-length Mycobacterium (M.) tuberculosis protein antigens (EsxH, Rv2628, and HspX) and two epitope-predicted and optimized epitope-dominant protein antigens (nPPE18 and nPstS1) were selected, from which five protein antigens were used to construct a protein antigen composition EPRHP014, including a fusion expression multi-component protein antigen (EPRHP014f) and a multi-component mixed protein antigen (EPRHP014m) formed with the five single protein using clone, purification, and purification respectively. Multicomponent protein vaccines EPRHP014f and EPRHP014m were prepared with aluminum adjuvant, and the BCG vaccine was used as a control. ELISA detected the titer of serum-specific antibodies, the secretion of various cytokines was detected by ELISpot and Luminex, and immune protection was observed by the M. tuberculosis growth inhibition test in vitro. The results were statistically analyzed by t-test or rank sum test, and P<0.05 was considered a statistically significant difference. Results: Mice Immunized with EPRHP014m and EPRHP014f could produce highly effective IgG antibodies and their subtypes IgG1 and IgG2a, and the antibody titers were similar to those of mice immunized with BCG, with no statistical significance (P>0.05). The number of spot-forming cells (SFC) secreting IFN-γ and IL-4 induced by EPRHP014f group was significantly higher than those by EPRHP014m group and BCG group (P<0.05), but there was no significant difference in the number of SFC for IFN-γ and IL-4 induced between EPRHP014m group and BCG group (P>0.05). The secretion levels of GM-CSF and IL-12p70 induced by the EPRHP014m group were higher than those of the BCG group (P<0.05), but there was no significant difference in the levels of IL-6 and IL-10 induced between EPRHP014m group and BCG group (P>0.05). There was no significant difference in the secretions of IL-6, IL-10, IL-12, and GM-CSF between the EPRHP014f and BCG groups (P>0.05). EPRHP014m group, EPRHP014f group, and BCG group had obvious antibacterial effects in vitro, and the difference was insignificant (P>0.05). Conclusion: Both EPRHP014f and EPRHP014m can induce strong humoral and cellular immune responses in mice after immunization, and have a strong ability to inhibit the growth of M. tuberculosis in vitro, indicating that the antigen composition EPRHP014 has good potential in the development and application of TB vaccine.

[Clinical characteristics of patients with rheumatic diseases and abnormal liver function].

Objective: To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities. Methods: Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups. Results: A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)]. Conclusions: The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients' liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.

[Clinical characteristics and prognostic analysis of female patients with Stanford type B aortic dissection].

Objective: To explore the clinical characteristics and prognostic factors of female patients with Stanford type B aortic dissection. Methods: This is a single-centre retrospective study. Consecutive patients diagnosed with Stanford type B aortic dissection in General Hospital of Northern Theater Command from June 2002 to August 2021 were enrolled, and grouped based on sex. According to the general clinical conditions and complications of aortic dissection tear, patients were treated with thoracic endovascular aortic repair, surgery, or optimal medication. The clinical characteristics and aortic imaging data of the patients at different stages were collected, adverse events including all-cause deaths, stroke, and occurrence of aortic-related adverse events were obtained during hospitalization and within 30 days and at 1 and 5 years after discharge. According to the time of death, death was classified as in-hospital death, out-of-hospital death, and in-hospital death was divided into preoperative death, intraoperative death and postoperative death. According to the cause of death, death was classified as aortic death, cardiac death and other causes of death. Aortic-related adverse events within 30 days after discharge included new paraplegia, post-luminal repair syndrome, and aortic death; long-term (≥1 year after discharge) aortic-related adverse events included aortic death, recurrent aortic dissection, endoleak and distal ulcer events. The clinical characteristics, short-term and long-term prognosis was compared between the groups. Logistic regression analysis was used to explore the association between different clinical factors and all-cause mortality within 30 days in female and male groups separately. Results: A total of 1 094 patients with Stanford type B aortic dissection were enrolled, mean age was (53.9±12.1) years, and 861 (78.7%) were male and 233 (21.3%) were female. (1) Clinical characteristics: compared with male patients, female patients were featured with older average age, higher proportion of aged≥60 years old, back pain, anemia, optimal medication treatment, and higher cholesterol level; while lower proportion of smoking and drinking history, body mass index, calcium antagonists use, creatine kinase level, and white blood cell count (all P<0.05). However, there was no significant difference in dissection tear and clinical stage, history of coronary heart disease, diabetes, hypertension, and cerebrovascular disease between female and male patients (all P>0.05). (2) Follow-up result: compared with male patients, female patients had a higher rate of 30-day death [6.9% (16/233) vs. 3.8% (33/861), P=0.047], in-hospital death (5.6% (13/233) vs. 2.7% (23/861), P=0.027), preoperative death (3.9% (9/233) vs. 1.5% (12/861), P=0.023) and aorta death (6.0% (14/233) vs. 3.1% (27/861), P=0.041). The 1-year and 5-year follow-up results demonstrated that there were no significant differences in death, cerebrovascular disease, and aorta-related adverse events between the two groups (all P>0.05). (3) Prognostic factors: the results of the univariate logistic regression analysis showed that body mass index>24 kg/m2 (HR=1.087, 95%CI 1.029-1.149, P=0.013), history of anemia (HR=2.987, 95%CI 1.054-8.468, P=0.032), hypertension (HR=1.094, 95%CI 1.047-1.143, P=0.040) and troponin-T>0.05 µg/L (HR=5.818, 95%CI 1.611-21.018, P=0.003)were associated with an increased risk of all-cause mortality within 30 days in female patients. Conclusions: Female patients with Stanford type B aortic dissection have specific clinical characteristics, such as older age at presentation, higher rates of anemia and combined back pain, and higher total cholesterol levels. The risk of death within 1 month is higher in female patients than in male patients, which may be associated with body mass index, hypertension, anemia and troponin-T, but the long-term prognosis for both female and male patients is comparable.

[Expression and regulatory role of ultraconserved long non-coding RNA uc.77 in lung cancer].

Objective: To investigate the effect and molecular mechanism of ultra-conservative long non-coding RNA uc.77 in lung cancer. Methods: Lung cancer tissues and adjacent normal tissues were obtained from 61 patients with lung cancer who were diagnosed with lung cancer and underwent surgery from 2014 to 2016 in the General Hospital of the Southern Theater Command of the People's Liberation Army. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the uc.77 relative expressions in normal human bronchial epithelial cells 16HBE, lung cancer cell lines, and 61 pair lung cancer tissues. Uc.77 siRNA was transfected into lung cancer cells to interfere with the expression of uc.77, qRT-PCR was used to verify the interference effect, CCK8 method and clone formation experiment were used to detect cell proliferation ability, flow cytometry was used to detect apoptosis and cell cycle changes. H1299 cells transfected with uc.77 siRNA were injected into the subcutaneous right side of BALB/c nude mice to construct a tumor-bearing model for exploring the role of uc.77 on tumor growth. Western blot and qRT-PCR methods were used to detect the protein and mRNA expressions of p21. Results: The relative expression levels of uc.77 in lung cancer cell lines 95D, H1299, A549, H460, H446 and 16HBE-T were significantly higher than that of 16HBE cells (P<0.05). The uc.77 RNA expression levels of lung cancer tissues was significantly higher than that of the adjacent normal tissues (P<0.001). In addition, increased lncRNA uc.77 expression was significantly associated with big tumor size, lymph node metastasis and advanced TNM stage (P<0.05). After transfection with uc.77 siRNA, the expressions of uc.77 in H1299, 95-D and 16HBE-T cells were reduced (P<0.05), and the cell proliferation capacities were reduced at 48 hours and 72 hours (P<0.05). After transfection with uc.77 siRNA-1, the G(0)/G(1) phase cell ratio of H1299 siRNA-1 group [(71.86±3.46)%] was higher than those of H1299-control group [(47.62±5.48)%] and H1299 siRNA-NC group [(61.38±5.62)%, P<0.05], S phase cell ratio of H1299 siRNA-1 group [(14.99±3.61)%] was lower than those of H1299-control group [(34.95±7.05)%] and H1299 siRNA-NC group [(23.75±5.87)%, P<0.05], the apoptosis rate of H1299 siRNA-1 group [(4.90±1.80)%] was higher than those of H1299-control group [(3.30±0.80)%] and H1299 siRNA-NC group [(2.80±1.20)%, P<0.05], the colony formation rate of H1299 siRNA-1 group [(19.20±2.00)%] was lower than those of H1299 control group [(32.60±2.00)%] and H1299 siRNA-NC group [(34.40±1.00)%, P<0.05]. The results of the nude mice tumor formation experiment showed that the tumor volume of the H1299 siRNA-1 group was significantly lower than those of the H1299-control group and the H1299-negative control group (P<0.05), the average tumor weight of H1299 siRNA-1 group was significantly lower than those of H1299-control group and H1299-negative control group (P<0.05), tumor cell growth marker Ki-67 in the H1299 siRNA-1 group showed weak positive, and Ki-67 in the H1299-control group and H1299-negative control group showed positive. The result of qRT-PCR analysis showed that the mRNA expression level of p21 in H1299 siRNA-1 group (2.57±0.45) was higher than those in H1299 control group (1.00±0.00, P=0.001) and H1299 siRNA-NC group (1.52±0.37, P=0.009). The result of western blotting analysis also showed that the expression of p21 protein level in H1299 siRNA-1 group increased. Conclusions: The expression of ultraconserved long non-coding RNA uc.77 is elevated in lung cancer cell lines and lung cancer tissues. Silencing the expression of ultraconservative long noncoding RNA uc.77 can inhibit tumor growth, and blocking uc.77 expression may be a potential therapeutic target for lung cancer.

Effect of Hepatocyte Targeting Nanopreparation Syringopicroside on Duck Hepatitis B Virus and Evaluation of Its Safety.

Syringopicroside is a kind of iridoid monomer compound isolated from Syringa oblata exhibiting a potent effect against hepatitis B virus (HBV). The therapeutic effect and safety of syringopicroside-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (SYR-NP) were studied on the model of HBV-infected ducklings and on cultured HepG2.2.15 cells. HBV DNA in ducklings was assessed by fluorescence quantitative PCR. In HepG2.2.15 cells, the content of HBsAg and HBeAg were assayed. Acute toxicity of SYR-NP was studied in ICR mice in 12 h and 7 days after SYR-NP administration. The serum levels of HBV DNA in ducklings treated with SYR-NP in a high dose was significantly lower than in the control. In HepG2.2.15 cells treated with different doses of SYR-NP, the concentrations of HBsAg and HBeAg were significantly below the control. Acute toxicity test showed high safety of SYR-NP. Thus, SYR-NP can inhibit replication of HBV DNA and protect the liver tissue.

Aligning tumor mutational burden (TMB) quantification across diagnostic platforms: phase II of the Friends of Cancer Research TMB Harmonization Project.

BACKGROUND: Tumor mutational burden (TMB) measurements aid in identifying patients who are likely to benefit from immunotherapy; however, there is empirical variability across panel assays and factors contributing to this variability have not been comprehensively investigated. Identifying sources of variability can help facilitate comparability across different panel assays, which may aid in broader adoption of panel assays and development of clinical applications. MATERIALS AND METHODS: Twenty-nine tumor samples and 10 human-derived cell lines were processed and distributed to 16 laboratories; each used their own bioinformatics pipelines to calculate TMB and compare to whole exome results. Additionally, theoretical positive percent agreement (PPA) and negative percent agreement (NPA) of TMB were estimated. The impact of filtering pathogenic and germline variants on TMB estimates was assessed. Calibration curves specific to each panel assay were developed to facilitate translation of panel TMB values to whole exome sequencing (WES) TMB values. RESULTS: Panel sizes >667 Kb are necessary to maintain adequate PPA and NPA for calling TMB high versus TMB low across the range of cut-offs used in practice. Failure to filter out pathogenic variants when estimating panel TMB resulted in overestimating TMB relative to WES for all assays. Filtering out potential germline variants at >0% population minor allele frequency resulted in the strongest correlation to WES TMB. Application of a calibration approach derived from The Cancer Genome Atlas data, tailored to each panel assay, reduced the spread of panel TMB values around the WES TMB as reflected in lower root mean squared error (RMSE) for 26/29 (90%) of the clinical samples. CONCLUSIONS: Estimation of TMB varies across different panels, with panel size, gene content, and bioinformatics pipelines contributing to empirical variability. Statistical calibration can achieve more consistent results across panels and allows for comparison of TMB values across various panel assays. To promote reproducibility and comparability across assays, a software tool was developed and made publicly available.

Author Correction: A functional Cis-eQTL locus in lncRNA ZNRD1-AS1 contributes to the susceptibility of endometrial cancer.

Correction to: European Review for Medical and Pharmacological Sciences 2019; 23 (18): 7802-7807-DOI: 10.26355/eurrev_201909_18989-PMID: 31599404, published online 15 September, 2020. The authors state that "to compare the results with those of bladder cancer in the literature we reported the study by Li D, Song L, Wen Z, Li X, Jie J, Wang Y, Peng L. Strong evidence for LncRNA ZNRD1-AS1, and its functional Cis- eQTL locus contributing more to the susceptibility of lung cancer. Oncotarget 2016; 7: 35813-35817. In particular, we referred to their table format, but we misused the reference table as the official table in the manuscript". In addition to Table I, the authors make the following corrections: • in the abstract results change "(OR: 1.33; 95% CI: 1.09-1.61; p = 0.004)" to "(OR: 1.31; 95% CI: 1.08-1.6; p=0.007)." • in the "Association of tagSNPs of the Cis-eQTL for ZNRD1 in ZNRD1-AS1 Gene Region With EC Susceptibility" paragraph change "(OR: 1.33; 95% CI: 1.09-1.61; p = 0.004)" to "(OR: 1.31; 95% CI: 1.08-1.6; p=0.007), "1.71 (95% CI: 1.11-2.64)" to "1.67 (95% CI: 1.07-2.59)", and "(0.004 × 3 = 0.012 < 0.05)" to "(0.007*3=0.021<0.05)". There are amendements to this paper.  The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18989.

[The effect of operative approach selection on the protection of parathyroid function in thyroid cancer].

Objective: To investigate the effect of endoscopic thyroidectomy and open thyroidectomy on parathyroid function in patients with thyroid cancer. Methods: The clinical data of 73 patients with thyroid cancer who met the inclusion criteria in Zhengzhou Central Hospital Affiliated to Zhengzhou University from July 2018 to September 2019 were retrospectively analyzed, including 17 males and 56 females, aged 19-55 years. The patients underwent routine thyroidectomy (group A, n=31), oral endoscopic thyroidectomy by vestibular approach (group B, n=19) or transthoracic thyroidectomy (group C, n=23), and all patients received central neck dissection. The levels of parathyroid hormone (PTH) and serum calcium after operation were compared among three groups. SPSS 21.0 software and GraphPad Prism v6.01 were used for statistical analysis. Results: After operation, the mean levels of PTH and serum calcium in three groups were significantly decreased (all P<0.05). On the first day after operation, the mean level of PTH in group C was lower than that in group A [(12.3±9.0) vs. (22.2±13.2) pg/ml, t=3.04, P=0.004] or group B [(12.3±9.0) vs. (20.0±14.1) pg/ml, t=2.09, P=0.043], and also the level of serum calcium in group C was lower than that in group A [(1.89±0.11) vs. (2.02±0.16) mmol/L, t=3.24, P=0.002] or group B [(1.89±0.11) vs. (2.01±0.15) mmol/L, t=2.72, P=0.010], with no significant difference in the mean levels of PTH or serum calcium between group A and group B (t=0.54, 0.29, respectively, both P>0.05). The incidences of permanent hypoparathyroidism/persistent hypocalcemia were 3.2% (1/31) in group A, 5.3% (1/19) in group B and 21.7% (5/23) in group C, and the incidence of group C was significantly higher than that (4%, 2/50) of both group A and group B (χ(2)=5.251, P=0.022). Conclusion: The postoperative parathyroid function and serum calcium level have different degrees of change and they are significantly associated with thyroidectomy approaches, the protection of parathyroid by oral endoscopic thyroidectomy and routine thyroidectomy can achieve the same effect, and is better than that of transthoracic thyroidectomy.

[Advances in immunotherapy of extranodal NK/T cell lymphoma].

Extranodal NK/T-cell lymphoma (ENKTCL) is a relatively rare group of highly aggressive non-Hodgkin's lymphoma (NHL). The disease has rapid clinical progress, high degree of malignancy and poor prognosis. Traditional chemoradiotherapy regimens have not shown good efficacy. In recent years, the immunotherapy of tumors has developed rapidly. At present, it has shown strong therapeutic activity in the treatment of various solid tumors such as non-small cell lung cancer, prostate cancer, melanoma and kidney cancer. Multiple tumor immunotherapy drugs have been approved by the US Food and Drug Administration (FDA) for clinical use. This article reviews recent novel immunotherapeutic regimens of ENKTCL, hoping to change the treatment modality of this malignant disease.

[Prospective controlled observation ofeffect of adjuvant chemotherapy onsurvival and prognosis ofhigh-risk upper tract urothelial carcinoma patients underwent radical nephroureterectomy].

Objective: To assess the oncologic outcomes of radical nephroureterectomy (RNU) combined with adjuvant chemotherapy (ACT) in patients with high risk upper tract urothelial carcinoma (UTUC). Methods: From January 2014, all high-risk UTUC patients after RNU surgery were enrolled in this prospective comparative trial. And these patients were randomized to ACT group (Gemcitabine+Cisplatin three weeks regimen) and observing group. Cox proportional hazard modeling and Kaplan-Meier analysis were used to determine overall survival (OS), cancer specific survival (CSS) and disease-free survival (PFS) in the cohort. Results: The median follow-up duration was36 months (range: 6-54) in the ACT group (n=94) and 30 months (range: 6-54) in the observing group (n=82). Oncologic outcomes of RNU treated high-risk UTUC patients were improved much significantly by ACT: OS [P=0.0397, HR: 1.39(0.91-1.75)], CSS [P=0.0255, HR: 1.26(1.07-1.45)] and PFS [P=0.0033, HR: 3.78(3.13-4.55)]. The further analysis in lymph node positive cohort displayed that median times of oncologic events were prolonged in the ACT group compared with the observing group: OS (26.8mon vs 36.3mon, P=0.0255), CSS (28.2mon vs39.3mon, P=0.0197) and PFS (11.4mon vs 31.9mon, P=0.0018). Additionally in T3/4 cohort, the significant growth in the median times of OS (20.6mon vs 32.2mon, P=0.0183), CSS (21.9mon vs 38.4mon, P=0.0226) and PFS (13.9mon vs 36.3mon, P=0.0217) were observed in ACT group. Conclusion: ACT could play the important synergistic role in improving the OS, CSS and PFS of high-risk UTUC patients after RNU.

A functional Cis-eQTL locus in lncRNA ZNRD1-AS1 contributes to the susceptibility of endometrial cancer.

OBJECTIVE: Endometrial cancer (EC) remains one of the most common gynecologic malignancies worldwide. However, the exact etiology is still unknown. Human Zinc ribbon domain containing 1 (ZNRD1) was involved in carcinogenesis and progression of multiple cancers, including EC. ZNRD1-AS1, a long noncoding RNA (lncRNA) located in the upstream of ZNRD1, has been reported as an essential component in carcinogenesis. However, the underlying relations of ZNRD1-AS1 with development of EC remain obscure. This study aims to evaluate the potential role of ZNRD1-AS1 and Cis-eQTL loci of ZNRD1 in the occurrence of EC. PATIENTS AND METHODS: We first evaluated the expression of ZNRD1-AS1 and ZNRD1 among EC tissues and corresponding normal tissues using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then, to reveal the underlying mechanisms, we investigated the associations between Cis-eQTL loci of ZNRD1 in ZNRD1-AS1 and the susceptibility of EC. Further, in vitro experiments were conducted to evaluate the regulation role of rs9261204 on the expression of ZNRD1gene. RESULTS: Higher expression of ZNRD1-AS1 and lower expression of ZNRD1 were detected in the EC tissues, compared to the normal tissues. Minor allele of rs9261204 was significantly associated with increased risk of EC (OR: 1.31; 95% CI: 1.08-1.6; p=0.007) [corrected]. Furthermore, in vitro experiments confirmed that Ishikawa cells with rs9261204 G allele had lower mRNA level of ZNRD1, compared to the A allele. CONCLUSIONS: Our findings first showed the contribution of LncRNA ZNRD1-AS1 and Cis-eQTL loci of ZNRD1 to the development of EC. Further studies incorporating larger populations and functional assays are warranted.

Fermentation of flaxseed cake increases its nutritional value and utilization in ducklings.

Flaxseed cake (FSC) is a potential alternative feed source in poultry. However, cyanogenetic glycosides limit its widespread use in feed. In this study, we optimized the parameters of fermentation by Aspergillus niger and Candida utilis and compared the growth performance, serum lipid parameters, and organ indexes of Cherry Valley duckling feed with unfermented FSC (UFSC) or fermented FSC (FFSC). A total of 420 one-day-old male Cherry Valley ducklings were randomly assigned into a 1 plus 2 × 3 factorial design including 2 different FSC resources (UFSC and FFSC) at 3 levels (50, 100, or 150 g/kg) for 3 wk. Each treatment group included 6 pens with 10 ducklings per pen. The hydrocyanic acid (HCN) level was reduced under the following conditions: 1:0.8 FSC:water (w:v), inoculum ratio of 1 mL:1 mL, 30°C, and 60 h. FFSC had higher crude protein (CP) and calcium (Ca) levels and lower HCN levels compared with UFSC (P < 0.05). There was no interactive effect between FSC sources and levels on growth performance. Final body weight (FBW), average daily feed intake (ADFI), and average daily gain (ADG) in UFSC groups and ADFI in FFSC groups decreased linearly with increasing FSC levels (P < 0.01). There were no differences in FBW, ADG, or feed:gain ratio (F/G) among FFSC groups, and all 7 FSC groups had no differences in the F/G ratio (P > 0.05). Dietary FSC supplementation decreased triglyceride (TG) (P < 0.01), total cholesterol (TC) (P < 0.01), high-density lipoprotein (HDL) (P = 0.01), and low-density lipoprotein (LDL) (P < 0.01). No interactive effect between FSC levels and sources was observed for serum TG, TC, HDL, or LDL. Ducklings fed FFSC had lower TG (P < 0.01), TC (P = 0.05), and LDL (P < 0.01) levels compared with ducklings fed UFSC. The 150 g/kg FFSC group had the lowest TG, TC, HDL, and LDL levels among all 7 groups. Flaxseed cake supplementation decreased the relative weight of the left breast, but FFSC increased the relative weight of the gizzard compared with UFSC. In conclusion, fermentation could increase the nutritional value and usage of FSC in ducklings.

[Mechanism of androgen in improving erectile dysfunction in castrated rats by regulating androgen receptor/vascular endothelial growth factor].

Objective: To explore the mechanism of androgen in improving erectile dysfunction in castrated rats. Methods: Forty 8-week-old male Sprague-Dawley (SD) rats were randomly divided into 4 groups:normal control group (Group A); castration group (Group B, in which rats were castrated); intervention groups (group C and D), in which rats were treated with different concentrations of testosterone undecanoate orally every day at 10 mg/kg (low dose) and 20 mg/kg (high dose), respectively after being castrated. Animals in group A and B were given 0.9% NS instead. After 8-week treatment, the level of serum testosterone, intra cavernous pressure (ICP) and mean arterial pressure (MAP) were detected, and the expression of androgen receptor (AR)and vascular endothelial growth factor (VEGF) were detected in the penis by Immunohistochemistry and Western blot. Results: The level of serum testosterone was significantly lower in group B [(1.3±0.6) nmol/L] than in group A [(17.1±1.5) nmol/L] (P<0.05).After testosterone supplementation, serum testosterone levels in group C [(8.7±1.2) nmol/L] and group D [(15.5±1.6) nmol/L] were higher than that in group B (all P<0.05). Max ICP/MAP of group C and D were higher than that in group B (all P<0.05). Immunohistochemistry and Western blot showed that the expression levels of AR and VEGF in group B were significantly lower than those in group A, C and D, and group D > group C (all P<0.05). Conclusion: Androgen replacement therapy with testosterone undecanoate can improve the erectile function of castrated rats by protecting the integrity of endothelial cells through AR/VEGF pathway.

[Derepression of CXCR7 indicates resistance to enzalutamide in castration resistant prostate cancer].

Objective: To investigate the effect of the derepression of chemokine receptor-7 (CXCR7) in prostatic tissues from patients with Castration Resistant Prostate Cancer (CRPC) on the resistance to enzalutamide (Enza). Methods: During the period of January 2015 to December 2017 all CRPC cases who underwent radical radiotherapy or androgen deprivation therapy (ADT) were evaluated. After prostatic puncture biopsy, the tissues were treated for immunostaining with CXCR7. Cox proportional hazard modeling and Kaplan-Meier analysis were used to determine PSA Progression-Free Survival (PSAP-FS) and Clinical or Radiographic Progression-Free Survival (CRP-FS) in the cohort. At last, PSA response rates and progression outcomes in CXCR7 negative cases and CXCR7 positive cases were analyzed. Results: Total 39 CRPC patients were enrolled in this study. And 23 cases derepress CXCR7, 16 cases negatively express CXCR7. The median follow-up duration was 12 months (range: 6-18) in the cohort. Chi-square analysis confirmed that PSA response rates after Enza treatment were significantly associated with CXCR7 derepression (χ(2)=22.129, P=0.000 06). Compared with CXCR7 positive expression group, CXCR7 negative expression group displayed improved median PSAP-FS (4.4 mon vs 11.7 mon, P=0.040 8) and CRP-FS (5.2 mon vs 13.1 mon, P=0.036 2) after Enza treatment. Conclusion: Derepression of CXCR7 in CRPC patients may be associated with resistance to enzalutamide. This protein may be novel target for treatment of CRPC.