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Sulfobutyl ether-beta-cyclodextrin sodium salt contained in the marketed intravenous voriconazole injection as a solubilizer may cause harmful accumulations. This study aimed to evaluate the safety, tolerability, and pharmacokinetics (PKs) of two intravenous voriconazole formulations containing excipients from different manufacturers using increasing dose administrations in healthy Chinese volunteers. A randomized, double-blind, placebo-controlled trial was conducted in three cohorts with 42 healthy Chinese volunteers. Each cohort of 14 volunteers was allocated in proportion (8:4:2) to test the formulation, reference voriconazole, or placebo successively by single-dose then multiple-dose administrations of 3, 4, and 6 mg/kg. Forty-one volunteers completed all drug administrations. The pharmacokinetics of test formulations are characterized by high interindividual variability (coefficient of variance of C

The metastatic or recurrent potential of localized human papillomavirus-associated endocervical adenocarcinoma (HPVA EAC) is difficult to predict, especially based upon biopsy alone. Recent analyses of small cohorts indicate that high tumor nuclear grade (TNG) and the presence of necrotic tumor debris (NTD) from HPVA EACs in cervical biopsy specimens are highly predictive of nodal metastasis (NM). In the present study, we aimed to investigate how reliably tumoral morphologic features from cervical biopsy specimens predict NM or tumor recurrence (TR) and patient outcomes in a large cohort of endocervical adenocarcinoma patients. A cohort comprised of 397 patients with HPVA EAC treated at 18 institutions was identified, and cervical biopsies were paired with their associated complete tumor resections for a total of 794 specimens. A variety of tumoral histologic features were examined for each paired specimen, including TNG (assessed on a 3-tiered scale of increasing abnormalities-TNG1, TNG2, TNG3) and NTD (defined by the presence of necrotic and apoptotic tumor cells within tumor glandular lumens admixed with granular and eosinophilic amorphous material and inflammatory cells), which were correlated with outcomes. The distribution of TNG in biopsies was as follows: 86 (21.7%) TNG1, 223 (56.2%) TNG2, and 88 (22.2%) TNG3. NTD was identified in 176 (44%) of the biopsy specimens. The sensitivity, specificity, positive predictive value, and negative predictive value of a TNG1 assignment in the biopsy being predictive of the same assignment in the full resection were 0.82 (95% confidence interval [CI]: 0.7-0.9), 0.895 (0.86-0.93), 0.593 (0.48-0.696), and 0.96 (0.94-0.98), respectively. Respective values for an NTD-negative status were 0.89 (95% CI: 0.83-0.92), 0.715 (0.64-0.77), 0.72 (0.65-0.77), and 0.89 (0.83-0.93), respectively. Compared with the other cases in each category, both TNG1 and an NTD-negative status were each significantly associated with lower rates of NM (odds ratio for TNG1=0.245, 95% CI: 0.070-0.857, P=0.0277; for NTD=0.199, 95% CI: 0.094-0.421, P

In this study, SnS/NC composite was successfully synthesized by using one-pot hydrothermal and annealing methods, and whose electrochemical storage performance was also investigated. SnS/NC composite material has a large surface area which is the result of the stacking of SnS nanosheets on the surface of the biomass carbon substrate and forming 3D layered porous network structure. The 3D layered porous network can improve the lithium-storage capacity. When used as anode material for lithium-ion batteries, the SnS/NC composite exhibits excellent electrochemical performance including long cycle life, good rate cycling, and high specific capacity. Impressively, the discharge specific capacity of the first cycle at 0.1 A g−1 could achieve 1433.0 mAh g−1. A large lithium-storage capacity of 839.8 mAh g−1 could achieve after 100 cycles at the current density of 0.1A g−1 and 479.0 mAh g−1 after 500 cycles at 2.0 A g−1.

Colposcopy is a visual technique to examine the cervix and determine selection of sites for biopsies and eligibility for treatment. It's always been a critical part of identifying preinvasive and early invasive cervical carcinoma. Unfortunately, challenges exist with regards to the accuracy of traditional colposcopy. Hence, to fully exploit the benefit of increasing diagnostic sensitivity, there is a pressing need to improve the performance of colposcopy by applying novel innovations and techniques. In this case report, we used a recently developed, high-resolution multispectral endoscopy and evaluated its performance by comparing colposcopic image features (the vascular pattern, in particular, depending upon the improved optics and illumination) with histology results. High-resolution multispectral endoscopy makes it easier to distinguish the features of pathological vessels, so that it has a higher sensitivity and specificity to detect cervical lesions, especially in discriminating the vascular pattern using multispectral technology.

BackgroundProgestin resistance is the main obstacle for the conservative therapy to maintain fertility in women with endometrial hyperplasia and cancer. Up to 30% of endometrial cancers fail to respond to progestin, a rate that has not significantly changed due to the lack of a detailed understanding of progestin resistance.MethodsCell Counting Kit-8 (CCK-8) assays were used to detect the synergistic effects of brusatol in combination with progestin. Using commercial kits, the conversion of progestin to 20α-dihydroxyprogesterone following btusatol treatment or AKR1C1 silence was investigated. The correlation betwwen AKR1C1 expression profile and prgestin response was further analyzed in paired endometrial hyperplasia and cancer samples from the same individuals before and after progestin therapy. The effects of brusatol-mediated reversal of progestin resistance was explored in both mouse xenograft and human organoid models. DNA dot blot, HMeDIP, and dural-luciferase reporter assays were performed to uncover the mechanism through which brusatol inhibits AKR1C1 and sensitizes endometrial hyperplasia and cancer to progestin.ResultsBrusatol sensitizes endometrial cancer cell to progestin by downregulating the expression of Nrf2 and its target AKR1C1. Increased AKR1C1 facilitated production of 20-α-dihydroxyprogeserone and was associated with declined progesterone. Suppression of AKR1C1 by brusatol resulted in decreased progesterone catabolism and maintained potent progesterone to inhibit endometrial cancer growth. Aberrant overexpression of AKR1C1 was found in paired endometrial hyperplasia and cancer samples from the same individuals with progestin resistance, whereas attenuated or loss of AKR1C1 was observed in post-treatment samples with well progestin response as compared with paired pre-treatment tissues. Tet1 was identified as a novel Nrf2 target gene. It in turn upregulated AKR1C1 expression by increasing hydroxymethylation levels in its promoter regions. ConclusionsWe found that Nrf2-Tet1-AKR1C1 axis plays an essential role in progestin resistance, and brusatol sensitizes endometrial hyperplasia and cancer to progestin by suppressing Nrf2-Tet1-AKR1C1-mediated progestin metabolism. Our findings suggest that AKR1C1 expression pattern may serve as an important biomarker of progestin resistance in endometrial hyperplasia and cancer .

Climate change has caused huge negative impacts on the ecosystem. Carbon tax policy is an important regulatory means to reduce carbon emissions and mitigate climate change. Based on the carbon tax policy, this study discusses a dual-channel supply chain consisting of one manufacturer, one online retailer, and one offline retailer. Considering retailers’ bidirectional fairness concerns, the optimal carbon emission reduction strategy and the optimal pricing strategy of centralized and decentralized decision-making are discussed under consumers’ channel preference, respectively. On this basis, a coordination contract is proposed to realize the Pareto improvement of the dual-channel supply chain. We find that dual-channel retailers’ profits and prices are negatively correlated with the horizontal fairness concern coefficient and positively correlated with the vertical fairness concern coefficient. The profit of the manufacturer, the carbon emission reduction, and the bargaining power of consumers are all positively correlated with the horizontal fairness concern coefficient and negatively correlated with the vertical fairness concern coefficient. Maintaining an appropriate service level can maximize the profits of enterprises and positively affect the development of enterprises. Through the coordination contract, the supply chain can be promoted to form a win-win mode of complementary advantages.

Purpose To investigate the recurrence patterns and prognostic factors of patients with recurrent cervical cancer after radical hysterectomy with node dissection (RHND) followed by adjuvant radiotherapy (RT)/concurrent radiochemotherapy (CCRT). Methods Between January 1, 2012 and May 31, 2018, the medical records of 153 patients with pre-operative FIGO stage IB-IIA disease treated with RHND followed by adjuvant RT/CCRT in Liaoning Cancer Hospital were retrospectively analyzed. Results The median disease progression-free survival (PFS) time was 16 months. 75.2% (115/153) patients had disease relapse within 2 years. The survival of patients with recurrences in multiple organs was signifificantly lower in comparison to those with recurrences in single organ ( P Conclusion Most cervical cancer patients who received initial RHND followed by adjuvant RT/CCRT occurred disease relapse within 2 years. Resection margin involvement, para-aortic and common iliac lymph node metastasis, DM, no treatment after recurrence and early disease relapse were found to be prognostic factors in patients with recurrent cervical cancer after RHND followed by adjuvant RT/CCRT.

To enhance the disruption of Hsp90-Cdc37, we designed and synthesized a series (27) of CEL-triazole derivatives. Most of the target compounds showed enhanced anti-proliferative activity on four cancer cell lines (MDA-MB-231, MCF-7, HepG2 and A459). Among them, compound 6 showed the best anti-proliferation (IC50 = 0.34 ± 0.01 μM) on MDA-MB-231. Pharmacological studies had found that compound 6 showed a higher ability to disrupt Hsp90-Cdc37 interaction in cells and inhibited the expression of the key Hsp90-Cdc37 clients in a concentration-dependent manner. Further studies indicated that an enhanced covalent binding between compound 6 and thiols (cysteine) might be one of the reasons for the increased activity. Furthermore, compound 6 arrested cells in the G0/G1 phase and induced tumor cell apoptosis significantly. Overall, for cancer treatment, compound 6 was worth further exploring.

Background: The metastatic or recurrent potential of clinically localized HPV-associated endocervical adenocarcinoma (HPVA EAC) is difficult to predict. There is a need to develop a practical method that can accurately distinguish apparently localized tumors with a high probability of nodal metastasis (NM) or tumor recurrence (TR) at the initial biopsy phase, where findings can be incorporated into management decisions. Methods: This retrospective study included 794 specimens from 397 patients with primary HPVA EAC treated at 19 institutions. For each patient, data from a paired cervical biopsy (prior to surgery, n=397) and resection specimen, including lymphadenectomy (n=397) were reviewed. A variety of tumoral pathologic/histologic features were examined in each paired-specimen, including tumor nuclear grade (TNG) and necrotic tumor debris (NTD). TNG was assigned on a three-tiered scale of increasing abnormalities (TNG1, TNG2, and TNG3). Any relationships with standard clinicopathologic variables and patient outcomes including NM and TR were evaluated. Findings: Biopsy tumors with low-risk histologic features (TNG1 and NTD-negative) showed markedly better outcomes, with a 0% rate of lymph node metastases or lymphovascular invasion (LVI) and a 1.4% (a single case) rate of tumor recurrence. In contrast, biopsies with TNG 2/3 and/or NTD-positive, showed significantly worse outcomes, with a rate of 19.1% NM, a rate of 12.9% TR, and a rate of 9.6% LVI. The findings remained statistically significant on multivariate analyses. Interpretation: The findings may be of potential clinical utility in the risk stratification of patients with HPVA EACs, and may allow patients with a minimal risk of nodal metastases and tumor recurrence to be identified at the biopsy phase, thereby facilitating more personalized, possibly fertility sparing management options. Funding: Mark and Jane Gibson Endowment fund and department start-up fund, UTSW Medical Center; Natural Science Grant of China and Cervical Cancer Research Award, Zhengzhou, China. Declaration of Interest: None to declare. Ethical Approval: The institutional review board at every participating institution approved this study.

Purpose Scutellarin, a flavonoid derived from the plant Erigeron breviscapus, is currently widely used to treat cerebrovascular diseases, liver-related diseases, and hyperlipidemia in china and other East Asian countries. This study was to investigate the effect of scutellarin on the uptake of rosuvastatin in HEK293T cells expressing human organic anion transporting polypeptide 1B3 (hOATP1B3) and rat OATP1B2 (rOATP1B2), respectively, and the effect of scutellarin on the pharmacokinetics of rosuvastatin in rats. Methods The newly established HEK293T cells expressing hOATP1B3 and rOATP1B2 were used to examine the effects of scutellarin and positive controls on in vitro rosuvastatin transport. After co-feeding with scutellarin, the rosuvastatin area under the plasma concentration-time curve (AUC0–24h), the peak plasma drug concentration (Cmax), elimination half-life (t1/2), time to reach Cmax (tmax), clearance (CL) and apparent clearance (CL/F) of rosuvastatin were determined in rats. Results Scutellarin inhibited hOATP1B3- and rOATP1B2-mediated rosuvastatin uptake (IC50: 45.54 ± 6.67 μM and 27.58 ± 3.97 μM) in vitro in a concentration-dependent manner. After co-feeding with scutellarin, the AUC0–24h and Cmax of rosuvastatin in rats increased to 27.4% and 37.7%, respectively. The t1/2 and tmax of rosuvastatin showed no significant change. Moreover, scutellarin caused 29.2% and 28.1% decrease in the CL and CL/F of rosuvastatin. Conclusion Scutellarin may inhibit the hOATP1B3- and rOATP1B2-mediated transport of rosuvastatin in vitro, and exerts a moderate inhibitory effect on the pharmacokinetics of rosuvastatin in rats. Scutellarin is highly likely to participate in drug-drug interactions, as mediated by OATP1B3 in humans.

Background Chemoresistance reduces the 5-year survival rate of endometrial cancer patient, which is the current major obstacle for cancer therapy. Increasing evidence state that Nrf2 contributes to chemoresistance in several kinds of cancer. However, its role in endometrial cancer cells remains unclarified. Methods Immunohistochemistry staining was used to detect the expression of Nrf2 in normal patient and endometrial cancer patient. Stable transfection Ishikawa cell line with high level of Nrf2 was established to evaluate its role in chemoresistance. Dot blot assays were used to assess global hydroxymethylation level after stigmasterol treatment. Cellular growth profile was detected by CCK8 assay. Western blot was used to evaluate the changes of the target molecules after various treatments. Results Nrf2 is overexpressed in endometrial cancer tissues compared with the normal endometrium. Overexpression of Nrf2 resulted in decrease sensitivity to cisplatin. In addition, stigmasterol has been identified as a novel Nrf2 inhibitor. It enhanced the sensitivity of endometrial cancer cells to cisplatin, and the underlying mechanism is that stigmasterol declines the Nrf2 protein level. Conclusions Our findings identified stigmasterol as a new potential inhibitor of Nrf2 and highlight a critical role of stigmasterol in overcoming chemoresistance in endometrial cancer therapy.

Cervical cancer is still one of the main causes of death in females. Conventional diagnostic tools such as colposcopy are still unsatisfactory, so accurate diagnostic tools for cervical diseases are needed. Therefore, the purpose of this study was to perform a clinical study to evaluate the value of microendoscopic imaging systems in the diagnosis of cervical precancerous lesions and cervical microinvasive carcinoma (MIC). Totally 106 patients ranging in age from 23 to 67 years were recruited. All patients had abnormal thin-layer cytology (TCT) results (≥ low-grade squamous intraepithelial lesions) and high-risk human papillomavirus (HPV) positivity. Each patient was first subjected to ordinary colposcopy, followed by microendoscopy and biopsy. All results of the colposcopy and microendoscopy images were compared to the histopathological diagnosis. Characteristics of pathological blood vessels were easily distinguished by microendoscopy compared with ordinary colposcopy. The diagnostic agreement rate of microendoscopy with the pathological diagnosis was higher (95.3%) than that of ordinary colposcopy (37.7%) (weighted kappa = 0.863, P

Cervical cancer is the most common malignant tumors in women leading to serious morbidity and mortality worldwide, especially among developing countries. A main cause of the disease is the high-risk human papillomavirus (HR-HPV) infection. HSIL usually progress to cervical cancer, and low-grade lesions, including LSIL and ASCUS, mostly turn to normal or benign lesions, but there are still a small number of patients who will progress to HSIL. Up to now there is no efficient biomarker clinically available to predict people with high risk to progress into HSIL. This study was conducted to evaluate the value of human papillomavirus (HPV) DNA, p16INK4a protein, and HPV L1 capsid protein in predicting HSIL and minimizing unnecessary colposcopy treatments. 1222 patients with HR-HPV infection or with abnormal Thinprep cytologic test (TCT) were chosen to conduct colposcopy in the cervical out-patient clinic of Shanghai First Maternity and Infant Hospital affiliated to Shanghai Tongji University from June 2014 to January 2017. TCT, cervical biopsy, HPV DNA and HPVL1 were performed on all patients. 110 patients were selected to detect p16INK4a protein. Hybrid capture 2 (HC-2) was used to detect HPV DNA, and their subgroups using gene typing system. Immunohistochemical technology was used to detect HPV L1 and p16. HPV DNA was positive in 1097 cases, with the positive rate of 89.7% (1097/1222). In particular, the positive expression rates of HPV DNA were 82.3, 95.7, 96.6 and 100% in Normal/CC, LSIL, HSIL and cervical cancer groups, respectively (p

Loss-of-function mutations in the FLG gene cause ichthyosis vulgaris (IV) and represent the major predisposing genetic risk factor for atopic dermatitis (AD). Although both conditions are characterized by epidermal barrier impairment, AD also exhibits signs of inflammation. This work was aimed at delineating the role of FLG loss-of-function mutations on eicosanoid metabolism in IV and AD. Using human epidermal equivalents (HEEs) generated with keratinocytes isolated from nonlesional skin of patients with FLG wild-type AD (WT/WT), FLG-mutated AD (FLG/WT), IV (FLG/FLG), or FLG WT control skin, we assessed the potential autocrine role of epidermal-derived eicosanoids in FLG-associated versus FLG-WT AD pathogenesis. Ultrastructural analyses demonstrated abnormal stratum corneum lipid architecture in AD and IV HEEs, independent of FLG genotype. Both AD (FLG/WT) and IV (FLG/FLG) HEEs showed impaired late epidermal differentiation. Only AD (FLG/WT) HEEs exhibited significantly increased levels of inflammatory cytokines. Analyses of lipid mediators revealed increased arachidonic acid and 12-lipoxygenase metabolites. Whereas treatment of control HEEs with arachidonic acid increased expression of inflammatory cytokines, 12-hydroxy-eicosatetraenoic acid attenuated expression of late differentiation markers. Thus, FLG mutations lead to alterations in epidermal eicosanoid metabolism that could serve as an autocrine trigger of inflammation and impaired late epidermal differentiation in AD.

Quasi-spherical β-LiFe5O8 nanoparticles were synthesized via a hydrothermal stripping route where an organic phase with Fe3+ and an aqua phase of lithium hydroxide were prepared as the raw materials. To reduce the environmental impact, both the organic extractant and residual aqueous solutions were reused in the new synthesis process. The effects of Li/Fe molar ratio and reaction temperature were investigated as well as the reaction mechanism. The samples prepared by Li/Fe = 15 at 150 °C exhibited a high initial discharge capacity of 200.0 mAh/g, which is not inferior to common cathodes and shows the significance in applied prospect. These results suggest that the low-temperature hydrothermal stripping route is promising to prepare β-LiFe5O8 nanoparticles.

To ensure better utilization of silicon anode materials, a simple synthesis method to prepare a novel propeller-like structure was adopted. Silicon@tungsten trioxide materials with special morphologies can improve electrochemical performance to a certain extent. Owing to the novel and stable nanocrystallite structure, electrochemical kinetics can be enhanced and the ionic/electronic transport paths can be shortened. We used glucose as the carbon source to form the shell of spherical nanoparticles to further improve the stabilization of the material. Such a nanocomposite material showed better cyclic capacity of 610 mAh g−1 at 1 A g−1 after 100 cycles.

In this study, we synthesized hierarchical bead chain ZnFe2O4-PEDOT composites with network of macroporous channels. For the first time, a ZnFe2(C2O4)3 precursor was prepared by co-precipitation using steel waste pickling liquor as a raw material, which was then sintered in air at 800 °C to yield monolithic ZnFe2O4. PEDOT was coated on the surface of ZnFe2O4 via in-situ polymerization of 3,4-ethylenedioxythiophene (EDOT). Electrochemical measurements showed that the 15 wt% PEDOT coated ZnFe2O4 composites (ZFPE-15) delivered a discharge capacity of 1510.5 mAh g−1 at 100 mA g−1 after 200 cycles, which was much larger than that of pure ZnFe2O4 (1055.9 mAh g−1), 10 wt% PEDOT coated ZnFe2O4 composites (ZFPE-10, 1264.2 mAh g−1), and 20 wt% coated ZnFe2O4 composites (ZFPE-20, 900.1 mAh g−1). Additionally, the ZFPE-15 composite exhibited a reversible capacity of 1004.7 mAh g−1, even at a large current density of 1 A g−1 after 200 cycles. These more desirable electrochemical properties can be attributed to the interconnected macroporous channels in the hierarchical bead chain skeleton, which can buffer volume expansion during circulation and inhibit particle agglomeration. Furthermore, the PEDOT nanoparticle coating produces a composite with greater mechanical strength and higher electrical conductivity, which provides higher electron transfer during the charge/discharge processes.

Cervical cancer is the most common malignant tumors in women leading to serious morbidity and mortality worldwide, especially among developing countries. A main cause of the disease is the high-risk human papillomavirus (HR-HPV) infection. HSIL usually progress to cervical cancer, and low-grade lesions, including LSIL and ASCUS, mostly turn to normal or benign lesions, but there are still a small number of patients who will progress to HSIL. Up to now there is no efficient biomarker clinically available to predict people with high risk to progress into HSIL. This study was conducted to evaluate the value of human papillomavirus (HPV) DNA, p161222 patients with HR-HPV infection or with abnormal Thinprep cytologic test (TCT) were chosen to conduct colposcopy in the cervical out-patient clinic of Shanghai First Maternity and Infant Hospital affiliated to Shanghai Tongji University from June 2014 to January 2017. TCT, cervical biopsy, HPV DNA and HPVL1 were performed on all patients. 110 patients were selected to detect p16HPV DNA was positive in 1097 cases, with the positive rate of 89.7% (1097/1222). In particular, the positive expression rates of HPV DNA were 82.3, 95.7, 96.6 and 100% in Normal/CC, LSIL, HSIL and cervical cancer groups, respectively (p 0.001). HPV L1 was negative in 781 cases with HR-HPV infection, and the overall negative rate is 71.1%. In patients with Normal/CC, LSIL and HSIL, the negative expression rates of HPV L1 were 91.3, 40 and 81.2%, respectively (p value 0.001). In the 110 patients, HPV L1 was negative in 98.1% (53/54) of Normal/CC, 42.9% (12/28) of LSIL and 85.1% (23/27) of HSIL (p value = 0.0043). P16-positive rates in patients with Normal/CC, LSIL and HSIL were 33.3% (18/54), 75% (21/28) and 96.2% (26/27), respectively (p value 0.001). 18 out of 28 cases express low positive (+) in LSIL, 25 out of 27 cases express strong positive (3+) in HSIL. Patients with L1(-) p16(+) including 18.5% (10/54) of normal/cervicitis, 60.7% (17/28) of LSIL and 85.1% (23/27) of HSIL (p value 0.005). Furthermore, patients with L1(-) p16(1+) included 37% (10/27) of normal/cervicitis 59.3% (16/27) of LSIL and 3.7% (1/27) of HSIL; patients with L1(-) p16(2+) consisted of 0% of normal/cervicitis/LSIL and 100% (1/1) of HSIL; patients with L1(-) p16(3+) were composed of 0% of normal/cervicitis, 4.5% (1/22) of LSIL and 95.5% (21/22) of HSIL (p value 0.005) (Table 6).With the increase in the degree of the cervical lesions, the expression of HPV DNA and p16 is up-regulated while HPV L1 protein is down-regulated. HPV DNA, HPV L1 and p16 are useful markers for the prediction of HSIL. Combined detection of these three markers has important potential to predicting HSIL and minimizing unnecessary colposcope examination.

Objective To establish a risk model for predicting the probability of endometrial carcinogenesis while diagnosed as AEH preoperatively. Study design 149 patients with AEH diagnosed by D&C specimens or hysteroscopy undergoing total hysterectomy were enrolled in this retrospective study. Patients were divided into two groups: 51 cases in AEH to AEH group and 98 cases in AEH to EC group. The clinical pathological characteristics were compared between the two groups. With the use of ROC curves, cutoff values of age, CA199, CA125 and uterine height were determined. The relationships of these evaluators with endometrial carcinogenesis were investigated by multivariate analysis with a logistic regression model. Results 65.8% (98/149) of preoperative AEH patients become EC after confirmed by paraffin hysterectomy specimens. The cutoff values were 51.5 years of age, 14.06U/ml of CA199, 14.30U/ml of CA125 and 45mm of uterine height, respectively. Logistic regression analysis demonstrated age (OR=0.58, 95% confidence interval [95%CI]: 0.08–3.94), CA199 (OR=7.27, 95%CI: 1.43–36.92), CA125 (OR=13.97, 95%CI: 2.49–78.37), uterine height (OR=0.49, 95%CI: 0.08–3.08) and abnormal uterine bleeding (OR=4.27, 95%CI: 0.53–34.52) were associated with endometrial carcinogenesis. However, only CA199 ( p =0.017) and CA125 ( p =0.003) revealed significant differences. Therefore, when entered into the risk model, CA199≥14.06U/ml and CA125≥14.30U/ml were considered as cogent predictors of endometrial carcinogenesis. Conclusions This risk model may well predict the probability of endometrial carcinogenesis when preoperatively diagnosed as AEH.

Objective: Neuroendocrine carcinoma (NEC) of the uterine cervix is a highly aggressive type of tumor. Therefore, recognition of its cytology and histopathology is important for early diagnosis. Study Design: We report 6 cases of small-cell and 6 cases of large-cell NEC of the uterine cervix, including 5 cytology slides. AE1/3, CEA, p63, p16, CD56, chromogranin and synaptophysin were detected. Results: Two cytology slides of small-cell NEC showed sheet-like clusters. The tumor cells were uniformly small, with finely granular chromatin, scant cytoplasm and absent nucleoli. Three large-cell NEC smears showed palisading, molding and abortive rosettes with prominent eosinophilic nucleoli. The tumor cells had either abundant cytoplasm or no cytoplasm at all. The histopathology analysis indicated a transition from dysplasia glands or adenocarcinoma in situ glands to NEC in 6 cases. Conclusion: Cervical cytology of NEC has many unique characteristics, distinct from the characteristics of other lesions. We also demonstrated a hypothesis of the histogenesis of some NECs.

Adenomatoid tumor is a relatively rare disease that predominantly involves male and female internal genital tracts. Although its clinical and pathologic features are well characterized, there is still controversy regarding its nature as a true neoplasm or a variant of mesothelial hyperplasia of a reactive nature. We sought to resolve this debate by investigating the clonality of uterine adenomatoid tumor from 13 female cases. The mesothelial cells and surrounding normal myometrium were precisely harvested using laser capture microdissection, and genomic DNA was extracted for clonal analysis by assessing the patterns of X-chromosome inactivation. Fluorescent polymerase chain reaction amplification of a highly polymorphic short tandem repeat of the human androgen receptor (HUMARA) gene with and without methylation-sensitive restriction endonuclease HpaII digestion was performed on DNA extracted from mesothelial cells, using normal myometrium and male blood sample as controls. Of the 13 cases successfully amplified, all 10 informative cases showed concordant nonrandom X-chromosome inactivation pattern consistent with monoclonality. In comparison, surrounding normal myometrium showed a polyclonal pattern of X-chromosome inactivation, and male blood sample failed to be amplified after HpaII treatment. Our results demonstrate that adenomatoid tumor is a monoclonal disease favoring a neoplastic process. This neoplastic rather than reactive nature probably accounts for its frequently observed infiltrative growth pattern and the occurrence of diffuse adenomatoid tumor, especially when host immunity is compromised. Additional studies with larger sample sizes will be needed to conclusively prove our conclusion.