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Combating climate change is a global endeavor, requiring participation from every industry including healthcare. A team comprising of radiologists, radiographers and administrators from the National University Hospital Department of Diagnostic Imaging came together to examine key contributors of carbon emission in a radiology department. Three contributors, namely high electrical consumption from reporting workstations, excessive paper usage and insufficient recycling were identified through data logging and workflow process reviews. Given the high electrical consumption of reporting workstations, automatic shutdown via IT control was implemented after office hours. Educational posters were placed in various locations to remind end-users to shut down their workstations when not in use. Paperless workflow was introduced by implementing electronic documentation through a functionality upgrade of the current Radiology Information System (RIS), procurement of mobile workstations and transitioning staff towards electronic documentation and consent-taking. Lastly, recycling was introduced to bring down the volume of disposed general waste. Clean plastic waste such as expended contrast syringe packages were consolidated for recycling; coupled with end user education, inculcating a culture of reuse, reduce and recycle within the department. End results were measured and compared to baseline readings before implementation. The green solutions implemented brought about a 50% reduction in electrical consumption of reporting workstation, 30% reduction off paper usage and approximately 20 Tonnes in reduction of CO 2 carbon footprint emission. Secondary benefits include monetary savings from reduction in paper procurement and energy cost and improved patient safety from paperless workflow. We must continuously review established workflow and processes to drive sustainability. Apart from using a top-down approach for green practices, the concept of sustainability should be infused into the department culture for positive change to combat climate change. [ABSTRACT FROM AUTHOR]

Objective: This study sought to explore the efficiency of para-aortic and pelvic lymphadenectomy in the treatment of locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastasis., Methods: A total of 171 LACC patients with imaging-confirmed pelvic lymph node metastasis were included in this study. These patients were divided into two groups: the surgical staging group, comprising 58 patients who had received para-aortic and pelvic lymphadenectomy (surgical staging) along with concurrent chemoradiation therapy (CCRT), and the imaging staging group, comprising 113 patients who had received only CCRT. The two groups' progression-free survival (PFS), overall survival (OS) and treatment-related complications were compared., Results: The surgical staging group started radiotherapy 10.2 days (range 9-12 days) later than the imaging staging group. The overall incidence of lymphatic cysts was 9.30%. In the surgical staging group, para-aortic lymph node metastasis was identified in 34.48% (20/58) of patients, while pathology-negative PLN was observed in 12.07% (7/58). Over a median follow-up period of 52 months, no significant differences in PFS and OS rates were found between the two groups (p > 0.05). Subgroup analysis of patients with lymph node diameters of ≥ 1.5 cm revealed a five-year PFS rate of 75.0% and an OS rate of 80.0% in the surgical staging group, compared to 41.5% and 50.1% in the imaging staging group, respectively, showing statistically significant differences (p = 0.022, HR:0.34 [0.13, 0.90] and p = 0.038, HR: 0.34 [0.12,0.94], respectively for PFS and OS). Additionally, in patients with two or more metastatic lymph nodes, the five-year PFS and OS rates were 69.2% and 73.1% in the surgical staging group, versus 41.0% and 48.4% in the imaging staging group, with these differences also being statistically significant (p = 0.025, HR: 0.41[0.19,0.93] and p = 0.046, HR: 0.42[0.18,0.98], respectively)., Conclusion: Performing surgical staging before CCRT is safe and delivers accurate lymph node details crucial for tailoring radiotherapy. This approach merits further investigation, particularly in women with pelvic lymph nodes measuring 1.5 cm or more in diameter or patients with two or more imaging-positive PLNs., (© 2024. The Author(s).)

Objective: The aim of this study was to compare the therapeutic value and treatment-related complications of radical hysterectomy with those of concurrent chemoradiotherapy (CCRT) for locally resectable (T1a2-T2a1) stage IIIC1r cervical cancer., Methods: A total of 213 patients with locally resectable stage IIIC1r cervical cancer who had been treated at Jiangxi Maternal and Child Health Care Hospital between January 2013 and December 2021 were included in the study and classified into two groups: surgery (148 patients) and CCRT (65 patients). The disease-free survival (DFS) rate, overall survival (OS) rate, side effects, and economic costs associated with the two groups were compared., Results: 43.9% (65/148) patients in the surgical group had no pelvic lymph node metastasis, and 21of them did not require supplementary treatment after surgery due to a low risk of postoperative pathology. The median follow-up time was 46 months (range: 7-108 months). The five-year DFS and OS rates of the surgery group were slightly higher than those of the CCRT group (80.7% vs. 75.1% and 81.6% vs. 80.6%, respectively; p > 0.05). The incidences of grade III-IV gastrointestinal reactions in the surgery and CCRT groups were 5.5% and 9.2%, respectively (p = 0.332). Grade III-IV myelosuppression was identified in 27.6% of the surgery group and 26.2% of the CCRT group (p = 0.836). The per capita treatment cost was higher for the surgery group than for the CCRT group (RMB 123, 918.6 0 vs. RMB 101, 880.90, p = 0.001)., Conclusion: The therapeutic effects and treatment-related complications of hysterectomy and CCRT are equivalent in patients with locally resectable stage IIIC1r cervical cancer, but surgery can provide accurate lymph node information and benefit patients with unnecessary radiation., (© 2024. The Author(s).)

Ulcerative colitis (UC) is a chronic recurrent inflammatory bowel disease. Despite ongoing advances in our understanding of UC, its pathogenesis is yet unelucidated, underscoring the urgent need for novel treatment strategies for patients with UC. Exosomes are nanoscale membrane particles that mediate intercellular communication by carrying various bioactive molecules, such as proteins, RNAs, DNA, and metabolites. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a cytosolic tripartite protein complex whose activation induces the maturation and secretion of proinflammatory cytokines interleukin-1β (IL-1β) and IL-18, triggering the inflammatory response to a pathogenic agent or injury. Growing evidence suggests that exosomes are new modulators of the NLRP3 inflammasome, with vital roles in the pathological process of UC. Here, recent evidence is reviewed on the role of exosomes and NLRP3 inflammasome in UC. First, the dual role of exosomes on NLRP3 inflammasome and the effect of NLRP3 inflammasome on exosome secretion are summarized. Finally, an outlook on the directions of exosome-NLRP3 inflammasome crosstalk research in the context of UC is proposed and areas of further research on this topic are highlighted., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Chemotherapy resistance is a leading cause of treatment failure in cases of cervical adenocarcinoma (ADC), and no effective treatment approach has yet been found. We previously identified the differentially expressed kynureninase (KYNU) mRNA in cervical adenocarcinoma cells (HeLa) and cervical adenocarcinoma cisplatin resistance cells (HeLa/DDP) using gene chips. However, the role and potential mechanism of KYNU in the cisplatin resistance of cervical adenocarcinoma remain unclear., Methods: We verified the expression of KYNU in the cells and tissues of ADC patients and analyzed its correlation with patient prognosis. A stable HeLa/DDP cell line with KYNU mRNA knockdown was constructed. We then used a CCK8 assay to detect cell survival, a transwell assay to evaluate cell migration and proliferation and flow cytometry to measure apoptosis. The effect of KYNU silence on cisplatin sensitivity was evaluated in an orthotopic model of metastatic ADC. Immunohistochemistry was performed to determine the changes in relevant drug resistance-associated protein expression, aiming to explore the underlying mechanism of KYNU-mediated drug resistance., Results: KYNU is overexpressed in HeLa/DDP cells and tissues and is associated with the poor prognoses of patients with ADC. After KYNU mRNA knockdown, the invasion, migration, and proliferation of HeLa/DDP cells in the cisplatin environment significantly reduced, while the apoptosis rate of HeLa/DDP cells significantly increased. Meanwhile, KYNU knockdown improved the DDP sensitivity of ADC in vivo. Furthermore, silencing KYNU decreased the expressions of CD34 and the drug-resistance related proteins P-gp, MRP1, and GST-π and increased the level of the proapoptotic regulatory protein Bax., Conclusion: KYNU deficiency enhanced DDP sensitivity by suppressing cell proliferation, migration, and invasion and promoting apoptosis in DDP-resistant ADC cells in vitro. Furthermore, KYNU knockdown improved the drug sensitivity of ADC in vivo. The results showed that KYNU is involved in the chemotherapy resistance of cervical adenocarcinoma., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: The aim of this study was to evaluate the therapeutic value and treatment-related complications of adjuvant chemotherapy after concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC)., Design: The medical records of LACC patients who underwent CCRT were reviewed retrospectively., Methods: A total of 1,138 patients with LACC who had been treated at our hospital between January 2013 and December 2017 were included in the study and classified into two groups: the CCRT group, comprising 726 patients who had received only CCRT, and the CCRT + adjuvant chemotherapy (ACT) group, comprising 412 patients who had received three cycles of adjuvant chemotherapy after CCRT. 39 patients in the CCRT group and 50 patients in the CCRT + ACT group had undergone lymphadenectomy, which revealed pathology-positive lymph nodes in 22 patients and 35 patients, respectively. Progression-free survival (PFS), overall survival (OS), and adverse events were compared., Results: The median follow-up time was 61 months (range: 2-96 months). No significant differences in PFS and OS were found between the two groups (p > 0.05), but more grade 3-4 acute hematologic toxicities were observed in the CCRT + ACT group than in the CCRT group (24.8% vs. 31.8%, p = 0.01). A subgroup analysis of patients with pathology-positive lymph nodes showed that the 5-year PFS and OS rates were 76.5% and 74.9%, respectively, for the CCRT + ACT group and 45.0% and 49.2%, respectively, for the CCRT group; the differences were statistically significant (p = 0.015 and 0.042, respectively)., Limitations: First, the sample size of the subgroup of patients with pathology-positive lymph nodes was too small for a confirmative conclusion. The heterogeneous population and the selection bias resulting from the retrospective design were the other flaws of our study., Conclusion: The application of adjuvant chemotherapy after CCRT may be worth investigating further for women with LACC and pathology-positive lymph nodes, but this approach is associated with an increase in acute hematology toxicities., (© 2023 S. Karger AG, Basel.)

This study was conducted to determine the effect of feeding frequency on growth performance, carcass traits, and apparent nutrient digestibility in geese from 28 to 70 D of age. In experiment 1, a total of 240 geese were distributed in a completely randomized design into 4 treatments and 6 replicates of 10 birds each. The treatments were free access to the feeder (ad libitum) and access to the feeder 3, 4, and 5 times daily. Geese fed 3 times daily had a lower (P < 0.05) BW, ADG, and ADFI and a higher (P = 0.064) feed conversion ratio (FCR) from 28 to 41 D of age compared with the other groups. Geese fed 4 times daily had a higher (P < 0.05) ADG and ADFI and a lower (P < 0.05) FCR from 42 to 55 D of age compared with ad libitum fed geese. Geese fed 3 times daily had a higher (P < 0.05) ADG from 56 to 69 D of age than geese fed ad libitum and 4 times daily. No differences (P > 0.05) in BW, ADFI, ADG, and FCR were observed between ad libitum and feeding frequency groups from 28 to 69 D of age. Carcass traits and gastrointestinal development were not affected (P > 0.05) by feeding frequency. In experiment 2, the apparent nutrient digestibility in geese from 71 to 77 D of age fed using different feeding frequencies was determined using the total fecal collection method. Feeding frequency did not affect (P > 0.05) the apparent digestibility of DM, CP, crude ash, calcium, phosphorous, or ether extract in geese. Our study demonstrates for the first time that compensatory growth can be gained by enhancing feed intake when a lower feeding frequency is imposed on geese. Both ad libitum feeding and fixed feeding frequency for 3 to 5 times daily are suitable for geese from 28 to 70 D of age to achieve optimum production., (Copyright © 2020. Published by Elsevier Inc.)

Objective: Post-operative concurrent chemoradiotherapy has become the standard treatment for patients with positive lymph nodes after radical surgery. The aim of this study was to explore the efficiency and safety of consolidation chemotherapy in early-stage cervical cancer patients with lymph node metastasis after radical hysterectomy., Method: We reviewed the medical records of patients with early-stage cervical cancer with lymph node metastasis after radical hysterectomy from January 2010 to January 2017. All patients underwent adjuvant concurrent chemoradiotherapy (n=49) or three cycles of platinum-based consolidation chemotherapy following concurrent chemoradiotherapy (n=89). The primary end points of the study were disease-free survival and overall survival., Results: The median follow-up time was 51 months (range 10-109). No significant difference was noted in disease-free survival, overall survival, or grade 3/4 gastrointestinal disorder between the consolidation chemotherapy group (78.1% vs 83.1% vs 6.7%) and the concurrent chemoradiotherapy alone group (75.4% vs 75.3% vs 4.1%), (p=0.42, 0.26, 0.80, respectively). However, the grade 3/4 myelosuppression rate in the consolidation group was higher than in the concurrent chemoradiotherapy alone group (40.4% vs 22.4%, p=0.03). For patients with >3 positive lymph nodes or patients with >2 positive lymph nodes+lymphovascular space invasion/≥1/3 stromal invasion, disease-free survival and overall survival were superior in the consolidation chemotherapy group compared with the concurrent chemoradiotherapy alone group (p<0.05)., Conclusion: In patients with >3 positive lymph nodes or patients with >2 positive lymph nodes, lymphovascular space invasion, and greater than 1/3 stromal invasion, disease-free survival and overall survival were superior with consolidation chemotherapy. However, consolidation chemotherapy was also associated with an increased grade 3/4 myelosuppression rate., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: Uterine leiomyoma (UL) is the most common benign smooth muscle tumor of the uterus in reproductive women. Prior studies indicated that methyl-CpG-binding domain proteins (MBDs) may be involved in the pathogenesis of UL. Materials and Methods: In this study, UL tissues and paired adjacent myometrium were collected from a total of 51 patients. The expression of MBD mRNAs and their cognate proteins were analyzed via quantitative polymerase chain reaction assays and western blotting, respectively. The relationships between the MBD expression levels and the patients' clinicopathologic variables were assessed using Student's t test, nonparametric tests, or Pearson χ 2 methods. Results: Our results show that both the mRNA and protein levels of MBD2 were significantly decreased in ULs compared to the adjacent myometrium. In addition, MBD6 protein expression was also decreased significantly in UL samples when compared to the adjacent myometrium. There was, however, no significant difference on the mRNA expression of MBD6 between these two groups. Neither the mRNA nor the protein levels of the other MBD members (MBD1, MBD3, MBD4, MBD5, and MeCP2) showed any significant differences between ULs and the adjacent myometria. The decreased expression of the MBD6 protein was correlated with the tumor size of ULs. Conclusions: These results suggest that the dysregulated expression of MBD2 and MBD6 in ULs may play a role in their development; however, a larger sample size together with cellular functional assays should be carried out to further elucidate the precise role of MBD6 in ULs.

Background: To investigate the role of P16 (INK4a)-extracellular signal related kinase 1/2 (ERK1/2) signaling pathway in cisplatin (DDP) resistance induced by multidrug resistance protein 1 (MDR1), also known as P-glycoprotein (P-gp), in cervical adenocarcinoma., Methods: A human DDP-resistant HeLa cell line (HeLa/DDP) was constructed using the combination of incremental and intermittent administration of DDP. Cell Counting Kit-8 (CCK-8) assay was used to measure the IC50 and resistance index (RI) of cells. The morphological changes and population doubling time were observed under an inverted microscope. Plate cloning formation assay was performed to evaluate the cell proliferation and tumorigenic ability. Cell invasion and migration were determined by transwell assays. Besides, the expression of P16, phosphorylated extracellular signal related kinase 1 and 2 (pERK1/2), total ERK1/2 and MDR1 were measured using western blot analysis. The ERK-specific inhibitor U0126 and agonist TPA was used to explore the role of ERK., Results: The DDP-resistant cervical adenocarcinoma HeLa/DDP cell line was successfully established, which showed stronger cell growth, invasion, and migration. In the HeLa/DDP cells, pERK1/2 was downregulated, P-gp was upregulated and P16 was downregulated. Overexpression of P16 led to a significant decrease in the proliferation rate, migration ability, and invasion ability of the HeLa/DDP cells. Furthermore, overexpression of P16 increased and the decreased expression of pERK1/2 and P-gp in the HeLa/DDP cells, respectively. Treatment of HeLa/DDP cells transfected with P16 plasmid with ERK-specific inhibitor U0126 significantly decreased the expression of pERK1/2 and increased the expression of P-gp from 6 h to 48 h. Moreover, after 72 h, the expression of pERK1/2 was up-regulated and the expression of P-gp was inhibited., Conclusion: Overexpression of P16 could partially reverse the MDR1-mediated DDP resistance in the cervical adenocarcinoma by the enhancement of phosphorylation of ERK signaling pathway, which provided a theoretical basis for the treatment of DDP resistance in cervical adenocarcinoma., Competing Interests: Competing interestsAll authors declare that they have no competing interests.

Objective: To explore the indication and surgery scope for laparoscopic extraperitoneal lymphadenectomy in locally advanced cervical cancer. Methods: Laparoscopic extraperitoneal lymphadenectomy was initially performed on patients with locally advanced cervical cancer. The results of preoperative computed tomography (CT) images and serum level of squamous cell carcinoma antigen (SCC-Ag) were analyzed, and the diagnostic efficiencies of the minimum axial diameter (MAD) of lymph node on CT≥0.5 cm, ≥1.0 cm, serum level of SCC-Ag alone or combined to predict the extraperitoneal lymph node metastases were compared. The high-risk factors of common iliac lymph node (CILN) and para-aortic lymph node (PALN) metastases were also analyzed. Results: The lymph node metastasis rate of 81 patients who received the laparoscopic extraperitoneal lymphadenectomy was 59.3% (48/81). The CILN and/or PALN metastasis rate was 24.7%(20/81), and among them, the MAD of CILN and/or PALN ≥0.5 cm on CT images were in only 7 patients. The threshold of SCC-Ag for evaluating lymph node metastasis was 4.8 ng/ml. The accuracy, specificity and Youden index of SCC-Ag≥4.8+ MAD≥1.0 cm group for predicting lymph node metastasis were 78.3%, 100% and 0.6, respectively, and were significantly higher than 57.9%, 12.1% and 0.1 of MAD≥0.5 cm group, 71.1%, 75.8% and 0.4 of MAD≥1.0 cm group, 65.0%, 57.7% and 0.3 of SCC-Ag≥4.8 ng/ml group and 68.3%, 65.4% and 0.4 of SCC-Ag≥4.8 ng/ml+ MAD≥0.5 cm group ( P <0.05). All of the 21 patients in SCC-Ag≥4.8 ng/ml+ MAD≥1.0 cm group were detected to occur lymph node metastases, and the metastasis rate of CILN and/or PALN was 38.1%. While only 4 cases of 17 patients in SCC-Ag<4.8 ng/ml+ MAD<1 cm group were confirmed to occur CILN metastases. The difference of lymph node metastasis rate between these two groups was statistically significant ( P <0.001). The pathological type, the number of PLN with MAD≥1.0 cm, at least one of the PLN MAD≥1.0 cm and/or MAD of CILN and/or PALN was 0.5~1.0 cm were associated with the CILN and/or PALN metastases (all P <0.05). Conclusions: Those patients with MAD≥1.0 cm+ SCC-Ag≥4.8 ng/ml and with high-risk factors of CILN and/or PALN metastases should undergo laparoscopic extraperitoneal lymphadenectomy to provide explicit guidance for the subsequent therapy. However, the incidence of lymph node metastasis of patients with SCC-Ag<4.8 ng/ml combined with MAD<1.0 cm is low, therefore these patients can accept concurrent chemoradiotherapy directly.

Objective: To introduce the laparoscopic type C1 hysterectomy based on the anatomic landmark of the uterus deep vein and its branched and to evaluate its feasibility and safety for cervical cancer and its effect to bladder function and to provide some reference to simplify the surgical procedures of laparoscopic type C1 hysterectomy. Methods: The clinicopathologic data of the patients with stage ⅠA2~ⅡB cervical cancer and who underwent the laparoscopic C1 hysterectomy based on anatomic landmark of the uterus deep vein and its branches between March 2010 and December 2015 was retrospectively analysed. Results: A total of 99 patients received laparoscopic type C1 hysterectomy based on the anatomic landmark of the uterus deep vein and its branches, in which 93 patients reserved unilateral or bilateral pelvic autonomic nerve successfully, the other 6 patients were transfered to receive type C2 hysterectomy due to adhesions, bleeding or the low possibility of curative resection. The failure rate of the surgery was 6.1% (6/99). The average age of these 93 patients was 44.4±8.2 years (range 25~61 years) and there was one case of stage ⅠA2, 84 stage ⅠB1, 2 stage ⅠB2, 5 stage ⅡA1 and 1 stage ⅡB. The number of patients with squamous cell carcinoma was 67, adenocarcinoma was 19, adenosquamous carcinoma was 3, small cell neuroendocrine carcinoma was 3 and mixed type was 1. The average operation time was 4.1±0.5 h, the average amount of intraoperative blood loss was 103.8±84.0 ml and the mean number of excisional pelvic lymph nodes was 29.7±8.9. There was no patient with positive parametrial margin, positive vaginal margin or intraoperative ureteral injury. The postoperative catheter extraction time was 20.3±8.4 d. The median follow-up time was 20 months (rang 5~44 months), the long-term bladder dysfunction rate was 8.6% (8/93). The numbers of locally uncontrolled and distantly metastasis case were both one and both patients died. The fatality rate were 2.2% (2/93). The two-year disease-free survival and overall survival rate were 97.6% and 96.2%, respectively. Conclusion: Laparoscopic type C1 hysterectomy based on the anatomic landmark of the uterus deep vein and its branches is a safe and feasible treatment method for cervical cancer and it provides a new approach for simplifying the surgical procedures of laparoscopic type C1 hysterectomy.

Objective: MicroRNAs (miRNAs) play a vital role in pathogenesis and progression of many cancers, including cervical cancer. However, importance of serum level of miR-101 in cervical cancer has rarely been studied. In the present study, clinical significance and prognostic value of serum miR-101 for cervical cancer was investigated., Methods: Association between miR-101 level in cervical cancer tissues and prognosis of patients was analyzed by using data retrieved from The Cancer Genome Atlas (TCGA) database, which was followed with our clinical study in which miR-101 serum level comparison between cervical cancer patients and healthy controls was conducted by real-time quantitative polymerase chain reaction (PCR)., Results: TCGA database demonstrated that miR-101 was down-regulated in cervical cancer tissues compared with normal cervical tissues, and univariate Cox regression analysis indicated that decreased miR-101 expression was a highly significant negative risk factor. Similar trend was found in the serum miR-101. Serum level of miR-101 was associated with International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.003), lymph node metastasis (p=0.001), and serum squamous cell carcinoma antigen (SCC-Ag) level >4 (p=0.007). The overall survival time of cervical cancer patients with a higher level of serum miR-101 was significantly longer than that of patients with a lower level of serum miR-101. Moreover, multivariate Cox regression analysis indicated that the down-regulated serum level of miR-101 was an independent predictor for the unfavorable prognosis of cervical cancer., Conclusion: Serum level of miR-101 is closely associated with metastasis and prognosis of cervical cancer; and, hence could be a potential biomarker and prognostic predictor for cervical cancer., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology)

Objective: To analyze the clinicopathologic feature of Stage I A I squamous carcinoma of the cervix (SCC) and to explore the outcome of different surgical methods., Materials and Methods: Clinicopathological data of 346 cases with Stage I Al SCC diagnosed between November 2nd, 1995 and December 31st, 2011 were reviewed and analyzed., Results: As major diagnostic method, 44.5% (154/346) patients accepted cold knife conization (CKC), while 58.1% (201/346) patient took total hysterectomy (TH) as their final surgical methods. The trend in treatment methods from 1995 to 2011 revealed that increasing cases were treated with CKC, modified radical hysterectomy (MRH) obviously reduced, while the proportion treated by TH remained unchanged. Due to a small number of cases receiving vaginal trachelectomy (VT) and radical trachelectomy (RT), the authors did not find any obvious changes., Prognosis: The overall recurrence rate was 1.2% (4/346). The overall survival rates for CKC, VT, TH, MRH, and RT were 100%, 100%, 98.2%, 100%, and 100%, and the difference was not statistically significant (p = 0.819). The incidence rate of LVSI was 4.9% (17/346), the overall survival rates for patients with LVSI and without LVSI were 99.3% and 93.3%, respectively, and there was statistical difference between them (p = 0.003). Univariate analysis showed that only LVSI was an important predictor for survival (p = 0.030)., Conclusions: the treatments for Stage I Al SCC are becoming more conservative, and individualized therapy and more frequent surveillance should be administrated to those patients with LVSI.

Pregnenolone (P5) is a neurosteroid that improves memory and neurological recovery. It is also required for zebrafish embryonic development. However, its mode of action is unclear. Here we show that P5 promotes cell migration and microtubule polymerization by binding a microtubule plus end-tracking protein, cytoplasmic linker protein 1 (CLIP-170). We captured CLIP-170 from zebrafish embryonic extract using a P5 photoaffinity probe conjugated to diaminobenzophenone. P5 interacted with CLIP-170 at its coiled-coil domain and changed it into an extended conformation. This increased CLIP-170 interaction with microtubules, dynactin subunit p150(Glued) and LIS1; it also promoted CLIP-170-dependent microtubule polymerization. CLIP-170 was essential for P5 to promote microtubule abundance and zebrafish epiboly cell migration during embryogenesis, and overexpression of the P5-binding region of CLIP-170 delayed this migration. P5 also sustained migration directionality of cultured mammalian cells. Our results show that P5 activates CLIP-170 to promote microtubule polymerization and cell migration.

S100A8 and S100A9 play important roles in immune and inflammatory disorders. The role of the two proteins in systemic sclerosis (SSc) remains unknown. Fifty-seven diffuse cutaneous SSc (dcSSc) patients, 31 limited cutaneous SSc (lcSSc) patients were recruited in the present study. The expression of S100A8 and S100A9 in plasma was measured using an enzyme-linked immunosorbent assay and the mRNA levels in peripheral blood were assessed using reverse transcriptase quantitative PCR. The expression and distribution of S100A8, S100A9, and receptor for advanced glycation end products (RAGE), in skin tissues was analyzed by immunohistochemistry. The plasma concentrations of S100A8 and S100A9 were significantly higher in dcSSc patients than in normal controls and lcSSc patients. Both S100A8 and S100A9 levels were significantly increased in dcSSc patients with lung or kidney involvement. Increased plasma levels of S100A8 and S100A9 in dcSSc patients were associated with several autoantibodies. Transcription levels of S100A8 and S100A9 in peripheral blood were found elevated in both dcSSc and lcSSc patients than normal controls. Immunohistochemistry demonstrated higher S100A8 and S100A9 expression in sclerotic skin than in normal skin. The number of S100A8, S100A9, or RAGE positive fibroblasts was also significantly increased. Highly elevated expression of both S100A8 and S100A9 was found in dcSSc patients. There was close correlation with disease severity and serological abnormalities, suggesting that the two proteins may play important roles in the development of systemic sclerosis.

Objective: To analyze the clinicopathologic features of mucinous cervical adenocarcinoma (ADC) and supply some reference for its diagnosis, treatment and prognosis., Methods: Totally 88 cases with primary mucinous ADC diagnosed between January 2003 and December 2007 in Jiangxi Maternal and Child Health Hospital were retrieved. Their clinical and pathological data were reviewed and analyzed., Results: Among 88 patients, 70 cases of them were endocervical ADC, 11 cases were minimal deviation adenocarcinoma (MDA), 2 cases were intestinal subtype and 5 cases were villoglandular ADC. The positive rate of cervical Pap smear cytology was only 28% (10/36). There were 10 cases were performed several times of cervical Pap smear cytology test and biopsies, while still no abnormality was found. Finally, 7 cases of them were diagnosed by cervical excisional biopsy and endocervical curettage, including 5 cases with endocervical ADC and 2 cases with MDA; 2 cases (1 case with stage Ib1 endocervical ADC and 1 case with Ib1 MDA) were diagnosed by cold knife conization, and 1 case with stageIb1 endocervical were diagnosed by uteroscopically directed biopsy. The overall 5-year survival rate was 60.0%. Using univariate analysis results showed that age (P = 0.046), stage (P = 0.007), tumor size (P = 0.007) and therapeutic methods (P = 0.009) were significant prognostic factors. Multivariate analysis showed that therapeutic methods was an independent predictor for survival (P = 0.013). Stage IIb-IIIb MDA patients occupied 7/11 of all MDA patient, while there was only one such patient of 5 cases with villoglandular ADC. The overall HPV infection rate was 65% (57/88), and there was no obvious differences about the HPV infection rates among different types of mucinous ADC., Conclusions: Cervical smear cytology is of little significance to the diagnosis of mucinous cervical adenocarcinoma. Early stage mucinous ADC is difficult to be detected, especially for MDA. Cervical excisional biopsy, endocervical curettage, cold knife conization, uteroscope are beneficial to its diagnosis. Therapeutic methods is an important prognostic factor for mucinous ADC and comprehensive treatment should be given to those patients with risky postsurgical factors.

Objective: To explore the feasibility and safety of transvaginal external fascia trachelectomy to conservatively treat patients with stage Ia1 squamous carcinoma of the uterine cervix (SCC) and cervical intraepithelial neoplasia (CIN) III, who are not suitable to take cold knife conization (CKC)., Methods: From July 2002 to September 2010, those patients who had a strong desire to preserve the uterus or fertility but also are confronted with following situations received transvaginal external fascia trachelectomy: CIN III with large area lesion (colposcopically observed lesion area was larger than 3/4 of the cervix), or patients with CIN II-III suffered recurrence or had persistent lesion or positive margin after CKC or LEEP, or patients with CIN II-III upgraded into stage Ia1 SCC through LEEP and pathological confirmation (except for those with lymphovascular space invasion), or CIN III patients complicated with upper vaginal intraepithelial neoplasia (VAIN). Their clinical information and data were reviewed and analyzed., Results: Among the 79 cases, who underwent transvaginal external fascia trachelectomy, six were stage Ia1 SCC, 61 were CIN III with a large area lesion (23 cases had glandular involvement), three were CIN III complicated with VAIN, six were CIN III with persistent lesion after LEEP, two were CIN III with positive margins after LEEP, and one case had recurrence after conization. The median age of these patients was 33 years old, ranging from 23 to 40 years old. The mean operation time was 39 min (rang 20-60 min), the average amount of bleeding was 40 ml (rang 1-300 ml) and the mean hospital stay was 10 d ( rang 6-17 d). The CIN III patients complicated with VAIN received this surgery with resection of the adjacent vaginal mucosa more than 2 cm in 3.8% (3/79). The median follow-up time was 49 months (8-85 months) and none of these patients had ureteral injury or large amount of intraoperative or postoperative bleeding or post-operative recurrence. No patient complained any effect on their sexual life. Among the five patients with reproductive desire, one was at her 22 w gestation after one induced abortion and one spontaneous abortion, four patients experienced term birth in which three were cesarean section and one was natural labour., Conclusions: Transvaginal external fascia trachelectomy is a safe and effective conservative treatment for stage Ia1 SCC, CIN III with large area lesion, CIN III complicated with VAIN and CIN II-III suffering recurrence, persistent lesion or positive margins after CKC and others that are not suitable to take CKC.

We developed mesoporous silica nanoparticle (MSN) as a multifunctional vehicle for enzyme delivery. Enhanced transmembrane delivery of a superoxide dismutase (SOD) enzyme embedded in MSN was demonstrated. Conjugation of the cell-penetrating peptide derived from the human immunodeficiency virus 1 (HIV) transactivator protein (TAT) to mesoporous silica nanoparticle is shown to be an effective way to enhance transmembrane delivery of nanoparticles for intracellular and molecular therapy. Cu,Zn-superoxide dismutase (SOD) is a key antioxidant enzyme that detoxifies intracellular reactive oxygen species, ROS, thereby protecting cells from oxidative damage. In this study, we fused a human Cu,Zn-SOD gene with TAT in a bacterial expression vector to produce a genetic in-frame His-tagged TAT-SOD fusion protein. The His-tagged TAT-SOD fusion protein was expressed in E. coli using IPTG induction and purified using FMSN-Ni-NTA. The purified TAT-SOD was conjugated to FITC-MSN forming FMSN-TAT-SOD. The effectiveness of FMSN-TAT-SOD as an agent against ROS was investigated, which included the level of ROS and apoptosis after free radicals induction and functional recovery after ROS damage. Confocal microscopy on live unfixed cells and flow cytometry analysis showed characteristic nonendosomal distribution of FMSN-TAT-SOD. Results suggested that FMSN-TAT-SOD may provide a strategy for the therapeutic delivery of antioxidant enzymes that protect cells from ROS damage.

Objective: The aim of this was study to offer some reference for the treatment of cervical intraepithelial neoplasia (CIN) by comparing complication rates and treatment failure rates of different surgical methods of CIN., Methods: 1,256 cases of CIN diagnosed by punch biopsy and pathological confirmation of postoperative specimens between January 2002 and June 2007 were reviewed and analyzed, in which 74 cases underwent the loop electrosurgical excision procedure (LEEP), 869 patients adopted cold knife conization (CKC), 49 patients received vaginal enlarged amputation of cervix, and 264 patients accepted extrafascial hysterectomy. The chi-square test was used to compare the rate of complication and treatment failure of different surgical methods., Results: The rates of surgical complications for LEEP, CKC, vaginal enlarged amputation of the cervix and extrafascial hysterectomy were, respectively, 8.1% (6/74) 6.2% (54/869) 6.1% (3/49) and 2.3% (8/264), but this difference was not statistically significant. The treatment failure incidences for LEEP, CKC, vaginal enlarged amputation of cervix and external fascia hysterectomy were, respectively, 4.1% (3/74), 0.2% (2/869), 0.0% (0/49) and 0.4% (1/264). When comparing among the groups, the treatment failure incidence was higher in LEEP than that in CKC (p = 0.004) and extrafascial hysterectomy (p = 0.034); there was no statistically significant difference between CKC and extrafascial hysterectomy, and no significant difference was revealed between vaginal enlarged amputation of cervix and any other group., Conclusion: LEEP, CKC, vaginal enlarged amputation of cervix and extrafascial hysterectomy are all secure and effective procedures for patients with CIN, and patients can make their own individual choice depending on different conditions.

Six nitriolotriacetic-acid-modified ordered mesoporous silicas (NTA-OMPSs) with different pore sizes and surface features for specific and reversible protein immobilization were fabricated and characterized. Specific immobilization of a genetically engineered undecaprenyl pyrophosphate synthase (UPPs) from cell lysate and a chemically modified His-tagged horseradish peroxidase (HRP) in these Ni-NTA-OMPSs through histidine coordination to the nickelated NTA was demonstrated and confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and sodium dodecyl sulfate polyacrylamide gel electrophoresis. Negligible leakage of these enzymes over a wide range of acidic conditions was observed. Moreover, histidine tags with different lengths (His6, His4, His3, and His2) applied to HRP were evaluated to find the minimum length for effective complexation. Enzymatic assessment studies indicated that the pore size of the OMPSs has minimal influence on the enzymatic activity, whereas chemical entities such as unreacted mercapto groups tailored on the interior surfaces of the OMPSs played certain roles in inhibiting the enzymatic activity and stability. On MCF-S-NTA, SBA-S-NTA, and film-S-NTA, which contained unreacted mercaptopropyl groups on the interior surface, immobilized His-tagged HRP showed lower catalytic activity and stability than on MCF-NTA, film-NTA, and SBA-NTA. Selective hydroxylation of optically pure L-tyrosine to (S)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid (L-DOPA) by the immobilized HRP was also demonstrated.

One single material that emits white light is of paramount interest for the development of white light-emitting diodes (WLEDs). Here we report a novel nanocomposite, in which a new type of excited-sate intramolecular proton transfer (ESIPT) molecule, namely 5-(1,2-dithiolan-3-yl)-N-(2-{[4-(3-hydroxy-4-oxo-4H-chromen-2-yl)phenyl](methyl)amino}ethyl)pentanamide (HF-N-LA), is anchored onto the surface of ultrasmall CdSe quantum dots through dithiol functionality. Authentic white light with a CIE coordinate of (0.33, 0.33) could then be generated by confluence of 440 nm emission from CdSe and 570 nm proton-transfer tautomer emission from HF-N-LA. Moreover, linear color tunability could be achieved simply by altering relative amount of the two species, i.e., number of HF-N-LA onto CdSe, in one single nanocomposite, thus opening an innovative route toward applying nanocrystals in the field of WLEDs.

Objective: To compare the rate of surgical complications and surgical failure of different surgical treatments in cervical intraepithelial neoplasia (CIN) III., Methods: From Jan 2002 to Jun 2007, 1256 patients with CIN III confirmed by histopathologic punch biopsy and excision biopsy of cervical specimens were analyzed retrospectively. Among them, 74 patients accepted loop electrosurgical excision procedure (LEEP), 869 patients adopted cold knife conization (CKC), 49 patients received vaginal enlarged amputation of cervix, as well as 264 patients accepted external fascia hysterectomy, Chi-square test was used to compare the rate of surgical efficacy and complications of different surgical treatments., Results: The surgical failure incidence of LEEP, CKC, vaginal enlarged amputation of cervix and external fascia hysterectomy were 4.1% (3/74), 0.2% (2/869), 0 and 0.4% (1/264) respectively, which was significantly higher in LEEP than that in CKC (P = 0.004) and external fascia hysterectomy (P = 0.034), while there was no statistical difference between CKC and external fascia hysterectomy (P = 0.549). The rate of surgical complications of LEEP, CKC, vaginal enlarged amputation of cervix and external fascia hysterectomy were 8.1% (6/74), 6.2% (54/869), 6.1% (3/49) and 2.3% (6/264) respectively, which were not statistically significant (P = 0.067) among them., Conclusion: LEEP, CKC, vaginal enlarged amputation of cervix and external fascia hysterectomy are all secure and effective procedures for patients with CIN III, who can take the individual choice depending on their different conditions.

Objective: To analyze the changes in epidemiology and treatment of hospitalized patients with cervical cancer during 1990-2007., Methods: Overall, 4648 patients with cervical cancer were diagnosed in our hospital from Jan 1990 to Nov 2007, but only 4223 patients with initial treatment in our hospital were studied retrospectively. Pearson Chi-square test was used to compare the age, stage, histopathologic type and treatment methods between different times., Results: (1) The mean age of cervical cancer patients gradually decreased over the past 18 years, from 54.4 years during 1990-1999 to 47.2 years during 2000-2007; the proportion of young patients aged < or = 35 years increased from 4.77% (89/1865) during 1990-1999 to 11.75% (277/2358) during 2000-2007. (2) The proportion of patients with cervical cancer (stage I a-II a) increased from 14. 32% (267/1865) during 1990-1999 to 40.75% (961/2358) during 2000-2007, whereas the proportion of patients with cervical cancer (stage II b-IV) decreased from 85.68% (1598/1865) during 1990-1999 to 59.25% (1397/2358) during 2000-2007. (3) There was no significant change in histopathologic type of cervical cancer, and squamous cell carcinoma of cervix remained the main type of cervical cancer. (4) The treatment pattern of cervical cancer changed significantly: radiotherapy was the main method (75.28%) for cervical cancer during 1990-1999, but during 2000-2007, it was replaced by concurrent chemoradiotherapy (35.79%)., Conclusions: The proportion of young women with cervical cancer was increased during 1990-2007, and at the same period early stage cervical cancer increased, but late stage cervical cancer decreased. It is obvious that chemotherapy has become the important therapy in cervical cancer.

Objective: To evaluate the feasibility and safety of vaginal enlarged amputation of cervix to treat patients with cervical cancer of stage Ia1 and cervical intraepithelial neoplasia grade III (CIN III) who were unfit for conization surgery., Methods: From July 2002 to May 2007, patients with cervical cancer at stage Ia1, diagnosed by pathology after loop electrosurgical excision procedure (LEEP), large area CIN III (the area of lesion>or=3/4 on colposcopy), CIN III coexisted with vaginal intraepithelial neoplasia (VAIN) in the superior segment of vagina, CIN II-III recurrence or with residual lesion, positive margin after conization of cervix, who wanted to preserve fertility and (or) corpus uteri were selected to receive vaginal enlarged amputation of cervix., Results: Forty-eight cases including 5 with cervical cancer in stage Ia1, 38 with large area CIN III (9 with gland involvement), 2 with residual lesion and 2 with positive margin after LEEP, 1 recurrence after cold knife conization, received the procedure successfully. The median age was 34 years (range 27-40), median operation time was 60 minutes (range 30-100), median blood loss was 40 ml (range 5-300), and median hospital stay was 10 days (range 7-17). After follow-up 1-39 months, no patient had postoperative complications and recurrence, and all patients resumed normal menstrual cycle and sexual life., Conclusion: Vaginal enlarged amputation of cervix appears to be a safe and feasible procedure for patients with cervical cancer at stage Ia1 and CIN III who are unfit for conization surgery.

Embryonic cell movement is essential for morphogenesis and the establishment of body shapes, but little is known about its mechanism. Here we report that pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc), functions in promoting cell migration during epiboly. Epiboly is a process in which embryonic cells spread from the animal pole to cover the underlying yolk. During epiboly, cyp11a1 is expressed in an extra-embryonic yolk syncytial layer. Reducing cyp11a1 expression in zebrafish using antisense morpholino oligonucleotides did not perturb cell fates, but caused epibolic delay. This epibolic defect was partially rescued by the injection of cyp11a1 RNA or the supplementation of pregnenolone. We show that the epibolic delay is accompanied by a decrease in the level of polymerized microtubules, and that pregnenolone can rescue this microtubule defect. Our results indicate that pregnenolone preserves microtubule abundance and promotes cell movement during epiboly.

The development of vehicles driving foreign DNA into the cell nucleus is essential for effective cellular gene transfer applications. We report that noncovalent binding of nuclear localization signal (NLS) peptides to plasmid DNA enhances nuclear uptake of the DNA and promotes germline integration, inheritance, and expression of a single copy of a luciferase reporter gene in zebrafish. As few as 10 DNA-NLS complexes (0.06 fg plasmid DNA) cytoplasmically injected are sufficient to produce germline-transgenic zebrafish bearing a single copy of the transgene. This corresponds to a 10(5)-fold reduction in DNA concentration compared to commonly used procedures. Use of 10(3) or 10(4) DNA-NLS complexes augments the number of transgene integrations, which occur mostly within 1-4 distinct insertion sites in the genome. In situ hybridization analyses and transmission studies show that transgene integration into the germline and somatic tissues is mosaic, and that the extent of mosaicism is negatively correlated with the amount of DNA-NLS injected. In addition, a larger proportion of zebrafish harboring a single copy of the transgene expresses luciferase, albeit at a 10-fold lower level than those containing numerous transgene insertions. The data demonstrate the potential use of nuclear targeting peptides noncovalently bound to vector DNA to enhance the efficiency of biotechnological nonviral gene transfer applications., (Copyright 2000 Wiley-Liss, Inc.)

We have investigated the functional organization of active and silent integrated luciferase transgenes in zebrafish, with the aim of accounting for the variegation of transgene expression in this species. We demonstrate the enrichment of transcriptionally active transgenes in acetylated histone H4 and the dynamic association of the transgenes with splicing factor SC35 and RNA Pol II. Analysis of interphase nuclei and extended chromatin fibers by immunofluorescence and in situ hybridization reveals a co-localization of transgenes with acetylated H4 in luciferase-expressing animals only. Enrichment of expressed transgenes in acetylated H4 is further demonstrated by their co-precipitation from chromatin using anti-acetylated H4 antibodies. Little correlation exists, however, between the level of histone acetylation and the degree of transgene expression. In transgene-expressing zebrafish, most transgenes co-localize with Pol II and SC35, whereas no such association occurs in non-expressing individuals. Inhibition of Pol II abolishes transgene expression and disrupts association of transgenes with SC35, although inactivated transgenes remains enriched in acetylated histones. Exposure of embryos to the histone deacetylation inhibitor TSA induces expression of most silent transgenes. Chromatin containing activated transgenes becomes enriched in acetylated histones and the transgenes recruit SC35 and Pol II. The results demonstrate a correlation between H4 acetylation and transgene activity, and argue that active transgenes dynamically recruit splicing factors and Pol II. The data also suggest that dissociation of splicing factors from transgenes upon Pol II inhibition is not a consequence of changes in H4 acetylation.