Toll like receptors (TLRs) are the most characteristic of pathogen recognition receptors.TLR signal pathway affects the outcome of cervical HPV infection,and plays double roles of promoting or inhibiting tumor in immune regulation for the process from high-risk HPV infection to cervical cancer.The polymorphism of TLR gene is closely related to the occurrence of cervical cancer.

Objective To investigate the number and distribution of dendritic cells in normal endometrium of reproductive age during the normal menstrual cycle .Methods Normal endometrial samples were collected from 40 women of reproductive age . 20 endometrium samples at the proliferative phase (day 6th to 10th) and 20 endometrium samples at the window of implantation(day 20th to 24th) were obtained .These patients underwent intrauterine exploration before IVF and ET resulting from tubal resec-tion or male factor infertility .Endometrial tissue was collected with a pipelle aspirator .Sections were stained with hematoxylin-eosin (HE) to identify the morphological characteristics of endometrial tissues .The Envision two-step immunohistochemical staining technique was used to detect the expression of CD1a and CD83 in the endometrium .Normal human skin and tonsil were used as pos-itive control tissues for CD1a and CD83 ,respectively .The serum levels of ovarian steroid hormones were measured to analyze their relationship with the expression of CD1a and CD83 .Results CD1a + DCs were found in all samples of window of implantationand most samples of the proliferative phase (18/20 ,90% ) .DCs showed irregular shape with different processes and were buffy in cell membrane ,mainly in stroma around grand and blood vessels .The density of CD1a + DCs at the window of implantation were (18 .2 ± 5 .76)cells/mm2 ,significantly higher than that at the proliferative phase [(6 .5 ± 4 .05)cells/mm2 ,P < 0 .05] .CD83 was considered as the marker for mature DCs .However ,immunohistochemistry with specific antibody revealed no CD83 + DCs were found in human emdometrium in the present study .During the menstrual cycle ,the expression of CD1a+ DCs in endometrium (the density of CD1a + DCs) correlated with serum progesterone level(r= 0 .630 ,P< 0 .01) .Serum estradiol showed no correlation with the density of CD1a + DCs(P> 0 .05) .Conclusion Increased CD1a+ immature DCs at the window of implantation in endometri-um may play an important role in the establishment of maternal-fetal tolerance .

Objective To study the clinical characteristics, diagnosis, and treatment of patients with persistent low levels of β-hCG. Methods To analyze the clinical data of 6 patients with persistent low level of β-hCG retrospectively and review the relevant literature. Results The periods of low levels of β-hCG in the 6 patients were 10-53 months. The range of β-hCG was 3～637 U/L. The last pregnancy were hydatidiform mole in 5 cases and abortion in 1 case. After hydatidiform mole 5 cases were received multi-chemotherapy. Normal level of β-hCG maintained 1-12 months after chemotherapy, then β-hCG titer has gone up again, One patient developed lung metastases after 30 months and then cured by surgery and chemotherapy. There were no clinical evidence of malignancy in the other 4 cases, and 1 case received no therapy after abortion during course of therapy and following up. Conclusion Persistent low level of hCG was a special kind of disease with poor response to chemotherapy, but the majority were with stable status. Therapy should be restrained if there was no evidence of malignancy.

Objective To study the association between metabolic syndrome (MS) and prognosis of endometrioid carcinoma.Methods A total of 256 patients with endometrioid carcinoma at,Zhejiang Cancer Hospital between January,2001 and December,2008 were chosen.The deadline for follow up was December 2008.The general conditions(including age and body mass index),whether coupled with MS and it's risk factors(including waist circumference,fasting plasma glucose,triglycerides,high-densitylipoprotein,systolic and diastolic blood pressure) were analyzed.The outcome of 256 patients whether coupled with MS were analyzed using Kaplan-Meier curve.Relative risks were estimated using Cox proportional hazards regression model.Results A total of 256 cases were followed-up successfully.Sixtyfour (33.0％) cases coupled with MS among the 194 patients survived,while thirty-two (51.6％)coupled with MS from 62 cases died,there was significant difference between them (x2=6.953,P=0.008).The total fiveyear survival rate was 75.8％,the survival time was (78.0±3.4) months.The rate and the survival time of patients coupled with MS [66.7％,(67.0±2.4) months] were significatly lower than those coupled with no MS [81.3％,(85.0±4.0) months;P＜0.05].The Cox proportional hazards regression results showed that coupled with MS,body mass index ≥25 kg/m2,waist circumference＞80 cm,abnormol systolic and diastolic blood pressure,abnormal fasting plasma glucose and more than two components of definitions of MS were related to bad prognosis of endometrioid carcinoma(P＜0.05).Conclusion Metabolic syndrome may be lead to a bad prognosis of endometrioid carcinoma.

Objective To investigate the efficacy of postoperative concurrent chemoradiotherapy for early-stage cervical adenosquamous carcinoma and adenocarcinoma.Methods A total of 62 patients with cervical adenosquamous carcinoma,149 patients with cervical adenocarcinoma,and 2687 patients with cervical squamous cell carcinoma,all of whom were in stage Ⅰ B-Ⅱ A and were treated from 2006 to 2012,were enrolled,and some of them received postoperative pelvic radiotherapy ± para-aortic extended field radiation ±afterloading radiotherapy.The chemotherapy regimen consisting of DDP,TP,and FP was given to these patients.The chi-square test was used for comparison of general clinical data,the Kaplan-Meier method was used for calculating survival rates,and the log-rank test was used for survival difference analysis.Results Cervical adenosquamous carcinoma and adenocarcinoma had no significant differences in clinicopathological features (P=0.107-0.639).The high-risk patients with adenocarcinoma had a higher recurrence rate than their low-risk counterparts even after adjuvant radiotherapy or chemoradiotherapy (P=0.000).In the patients treated with surgery and radiotherapy,those with adenosquamous carcinoma had the shortest median survival time,followed by those with adenocarcinoma and squamous cell carcinoma (P =0.134,0.787);in the patients treated with surgery and concurrent chemoradiotherapy,those with adenocarcinoma had the shortest median survival time,followed by those with adenosquamous carcinoma and squamous cell carcinoma (P=0.131,0.643),and the median survival time showed a significant difference between the patients with adenocarcinoma and those with squamous cell carcinoma (P =0.000).In the patients with adenosquamous carcinoma and adenocarcinoma,the patients treated with postoperative concurrent chemoradiotherapy had higher incidence rates of short-term adverse reactions than those treated with postoperative radiotherapy (P=0.037,0.003),but the incidence rates of long-term adverse reactions showed no difference between the two groups of patients (P=0.861,0.655).In the patients with adenosquamous carcinoma,the patients treated with postoperative concurrent chemoradiotherapy had a lower rate of distant metastasis (P =0.003) and prolonged median overall survival and disease-free survival (both increased by 17 months) (P=0.811,0.799),as compared with those treated with postoperative radiotherapy,while in the patients with adenocarcinoma,the median overall survival and disease-free survival were reduced by 11 and 9 months,respectively (P=0.330,0.115).Conclusions Compared with postoperative radiotherapy,postoperative concurrent chemoradiotherapy for early-stage high-risk cervical adenosquamous carcinoma can reduce the rate of distance metastasis.Compared with radiotherapy,postoperative concurrent chemoradiotherapy for adenosquamous carcinoma and adenocarcinoma cannot improve survival time.

Objective To investigate the value of serum proteomic profiling in cervical cancer detected pre-surgery and post-surgery. Methods Magnetic bead and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) were used to detect the serum samples from 54 cases with cervical cancer before and after surgery and 53 serum samples from healthy women. The results of spectra were analyzed by Biomarker Wizard software. Results Significant variation of proteomic profiling between pre-surgery and post-surgery were analyzed. There were 22 proteins with different mass/charge (M/Z) values significantly different (P<0.01) at the M/Z value range from 1500 to 50 000, among of which relative content of proteins with M/Z 3981, 4290, and 28 066 in pre-surgery cervical cancer patients were higher than those in health women [(1.51±1.78)% vs (0.83±0.38)%, (2.70±2.19)% vs (1.72±0.91)%, (1.99±1.70)% vs (0.92±0.95)%; P<0.01], while in the post-surgery patients, relative content of these three proteins significantly decreased to (0.59±0.45)%, (1.01±0.64)%, (0.54±0.37)%, respectively. But the relative content of another three proteins with M/Z 11 487, 11 529, and 11 678 were significantly increased in post-surgery patients [(0.38±1.41)% vs (2.74±3.67)%, (0.16±0.46)% vs (2.00±1.76)%, (1.02±1.67)% vs (7.71±9.46)%; P<0.01]. Conclusion Serum proteomic profiling could screen out the proteins which had significant variation between pre-surgery and post-surgery serum, of which with M/Z 3981, 4290, and 28 066 may be related with tumor burden, while with M/Z 11 487, 11 529, and 11 678 may be response to surgical stress.

Objective To study the difference between intensity-modulated radiation therapy (IMRT) and three dimensional conformal radiation therapy (3D-CRT) for pelvic radiation of post-operative treatment with gynecologic malignant tumor. Methods A prospective investigation study was conducted on 183 patients of post-operative patients with whole pelvic radiation therapy of cervical cancer or endometrial cancer in Zhejiang Cancer Hospital [IMRT group (n=85) and 3D-CRT group (n=98)] from Oct. 2015 to Oct. 2016. The two groups received same dose (45 Gy in 25 fractions). Comparison of two groups with radiation dosimetry:the score according to the Radiation Therapy Oncology Group (RTOG) acute radiation injury grading standards before and after radiotherapy reaction, the score from functional assessment of cancer therapy scale-cervix (FACT-Cx) scale and expanded prostate cancer index composite for clinical practice (EPIC-CP) scale were also analyzed. Results (1) There were no significant effect with age, culture level, family economic condition and ratio of radiochemotherapy between two groups (all P>0.05). (2) Dosimetric comparison for IMRT vs 3D-CRT:the average dose of planning target volume (PTV) decreased(46.1 ± 0.4) vs(46.4 ± 0.5)Gy, V45 dose percentage increased(95.2 ± 1.0)%vs (93.3 ± 2.0)%, intestinal bag dose of V40 decreased(24.4 ± 6.8)%vs (36.5 ± 15.9)%, rectal V40 dose percentage decreased(73.9 ± 12.3)%vs (85.4 ± 8.4)%, and lower rectal V45 dose percentage(32.8 ± 13.4)%vs (71.5 ± 13.7)%, bladder V40 dose percentage decreased(55.5 ± 13.0)% vs (84.4 ± 13.0)%. Bone marrow V20 lower:(67.9 ± 5.4)% vs (79.5 ± 6.6)%, V10 lower:(82.1 ± 6.0)% vs (86.3 ± 6.6)%; there were significant differences (all P<0.05). There was no significant difference between the dose of V45 in the intestinal pouch and bladder (P>0.05). (3) Acute radiation injury classification for IMRT vs 3D-CRT:big or small intestine:Ⅱ-Ⅲreaction [13%(11/85) vs 24% (24/98); χ2=3.925, P=0.048], there was significant difference. Bladder: Ⅲ reaction [19% (16/85) vs 26% (25/98); χ2=1.171, P=0.279], there was no significant difference. Radiochemotherapy of bone marrow suppression:Ⅲ-Ⅳreaction (14/20), the incidence rate [26%(14/54) vs 31%(20/65);χ2=0.339, P=0.562], the difference was not statistically significant. (4) Quality of life scale by FACT-Cx scale in IMRT vs 3D-CRT:there were no significant difference before radiotherapy (82 ± 16 vs 85 ± 16;t=1.279, P=0.203), while there was significant difference after radiotherapy (76 ± 14 vs 71 ± 18;t=-2.160, P=0.032). EPIC-CP scale score:before radiotherapy they were (16±7 vs 15±6;t=-0.174, P=0.862) ,but after radiotherapy (18±7 vs 22± 7; t=3.158, P=0.002), there was significant difference between them. Before and after radiotherapy, the increased EPIC-CP scale of the IMRT group vs 3D-CRT group were 3 ± 4 and 6 ± 4, the 3D-CRT group was significantly higher, the difference was statistically significant (t=5.500, P=0.000). Conclusion IMRT has shown that there are a significant benefit for the post-operative patients with cervical cancer and endometrial cancer compared to 3D-CRT.

The treatment of advanced or recurrent cervical cancer is difficult in clinic.Most of the patients have lost the opportunities for surgery or radiotherapy.Palliative treatment with chemotherapy is the main treatment.In recent years,the intensive studies on molecular targeted therapy and immunotherapy have provided a new treatment strategy for patients with advanced or recurrent cervical cancer,improving the efficacy and quality of life of patients.

Objective To explore the prognosis and risk factors for cervical cancer in elderly patients. Methods Clinical data of 337 elderly patients (≥ 65 years old )admitted into Zhejiang Cancer Hospital from June 2008 to June 2013 were retrospectively analyzed.Clinical data and the follow-up information were collected. The correlation of prognosis with age ,performance status score , International Federation of Gynecology and Obstetrics (FIGO )staging ,tumor size ,pathological type , treatment and comorbidities were analyzed. Results Among 337 elderly patients ,the 5-year overall survival(OS )rates for patients with stage Ⅰ,Ⅱ,Ⅲ,Ⅳ were 81.8% ,62.3% ,53.5% and 0.0% , respectively (χ2=63.414 ,P=0.000) ;local recurrence rate was 33.5% ;the 5-year OS rate of patients with and without comorbidities were 54.0% and 70.0% ,respectively(χ2=8.907 ,P=0.003).Among 119 cervical cancer patients with stage ⅠA-ⅡA ,5-year OS for surgery group and radiotherapy group were 83.5% and 55.0% ,respectively(χ2=13.161 ,P=0.000).Among 218 advanced cervical cancer patients ,the 5 year OS for chemoradiotherapy and radiotherapy groups were 69.7% and 51.9% , respectively(χ2=4.030 ,P=0.045). The acute toxicity reactions of radiotherapy and chemoradiotherapy groups were as follows. The incidences of acute grades 3-4 hematological toxicity were 9.7% and 42.4% in radiotherapy group and chemoradiotherapy groups respectively (χ2=21.362 ,P=0.000) ,and the incidences of acute grade 3 gastrointestinal toxicity were 5.9% and 9.1% (χ2=0.086 ,P=0.769)in radiotherapy group and chemoradiotherapy group ,respectively.No grade 4 gastrointestinal toxicity was found.Multivariate Cox regression analysis showed that age ,PS score , FIGO staging ,pathological type ,treatment and comorbidities were influencing factors for prognosis in elderly patients with cervical cancer (P＜0.05). Conclusions Elderly cervical cancer patients have a good tolerance to treatment. The comorbidity is one of negatively influencing factors for prognosis. The efficacy of definitive radiotherapy is inferior to surgery in elderly patients with early stage cervical cancer due to the high proportion of comorbidities.Concurrent chemoradiotherapy can improve the prognosis of middle and advanced cervical cancer in elderly patients.

Objective:To compare the clinical efficacy and toxicity of intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) in radical radiotherapy for cervical cancer.Methods:Clinical data of 1002 patients with cervical cancer treated with radical radiotherapy at Zhejiang Cancer Hospital from September 2013 to December 2016 were retrospectively analyzed. All patients were divided into the IMRT group and 3D-CRT group according to the technology of external beam radiation therapy (EBRT). After 1∶1 propensity score matching (PSM), clinical prognosis of patients receiving IMRT or 3D-CRT was compared. Continuous data were expressed as Mean ± SD or median . Categorical data were described by case number (percentage). Quantitative data were compared by t-test. Qualitative data were compared by chi-square test or Fisher's exact test. Survival rates in two groups were calculated by Kaplan-Meier method and log-rank test. Results:The percentage of patients who received pelvic and para-aortic radiotherapy in the IMRT group was significantly higher than that in the 3D-CRT group (14.9% vs. 1.2%, P<0.001). The percentage of patients whose positive lymph nodes dose reached 55 Gy or more in the IMRT group was significantly higher than that in the 3D-CRT group (26.6% vs. 15.5%, P=0.002). In the IMRT group, the 5-year disease-free survival (DFS) rate (74.6% vs. 68.9%, P=0.084) and overall survival (OS) rate (79.4% vs. 74.9%, P=0.270) were slightly higher than those in the 3D-CRT group, but there were no significant differences between two groups. In the IMRT group, the local recurrence (3.0% vs. 6.9%, P=0.020) and distant lymph node metastasis rates (4.2% vs. 9.0%, P=0.013) were significantly lower compared with those in the 3D-CRT group. In terms of acute radiotherapy toxicities, grade 3-4 leukopenia (46.3% vs. 37.9%, P=0.028) and anemia (18.8% vs. 14.0%, P<0.001) occurred significantly more frequently in the IMRT group than in the 3D-CRT group. Conclusions:Both IMRT and 3D-CRT could achieve good therapeutic outcomes in radical radiotherapy of cervical cancer. IMRT can boost the radiation dose of metastatic lymph nodes and has significant advantages in reducing local recurrence and distant lymph node metastasis.