Objective:To investigate the effect of subacute exposure of Di(2-ethylhexyl)phthalate(DEHP)on endometrial decidualization and early pregnancy miscarriage in mice.Methods:CD1 mice were orally administrated with 300(low-dose group),1000(medium-dose group),or 3000 mg·kg-1·d-1 DEHP(1/10 LD50,high-dose group)for 28 days,respectively.An early natural pregnancy model and an artificially induced decidualization model were established.The uterine tissues were collected on D7 of natural pregnancy and D8 of artificially induced decidualization,respectively.The effects of a subacute exposure to DEHP on the decidualization of mice were detected by HE staining,Masson staining,TUNEL assay,and Western blotting.A model of spontaneous abortion was constructed in mice after subacute exposure to 300 mg·kg-1·d-1 DEHP,and the effect of impaired decidualization on pregnancy was investigated by observing the pregnancy outcome on the 10th day of gestation.Results:Compared with the control group,the conception rate was significantly decreased in the high-dose DEHP subacute exposure group(P＜0.05).HE staining showed that,compared with the control group,the decidual stromal cells in the low-and medium-dose exposure groups were disorganized,the nuclei of the cells were irregular,the cytoplasmic staining was uneven,and the number of polymorphonuclear cells was significantly reduced.Masson staining showed that compared with the control group,the collagen fibers in the decidua region of the DEHP low-dose group and the medium-dose group were more distributed,more abundant and more disorderly.TUNEL assay showed increased apoptosis in the decidua area compared to the control group.Western blotting showed that the expression of BMP2,a marker molecule for endometrial decidualization,was significantly reduced(P＜0.05 or P＜0.01).The abortion rate and embryo resorption rate were increased,and the number of embryos,uterine wet weight,uterine area and placenta wet weight were decreased in DEHP low-dose group compared to the control group stimulated by mifepristone,an abortifacient drug(P＜0.05 or P＜0.01).Conclusion:Subacute exposure to DEHP leads to impaired endometrial decidualization during early pregnancy and exacerbates the risk of adverse pregnancy outcomes in mice.

Objective: To investigate factors influencing adolescent idiopathic scoliosis (AIS), and to provide a scientific basis for effective prevention and treatment programs. Methods: A questionnaire survey was conducted among 6 757 students who participated in the scoliosis screening program for primary and middle school students in Zhongshan City, China from April 2019 to March 2020. Visual examination and Adams flexion test were used to measure the rotation angle of trunk. For each student, individual and family demographics, family history of scoliosis, daily postural habits, school bag carrying habits, vision, health, school environment, and physical activity were collected by questionnaire. Factors influencing AIS were analyzed using Chi square test and multivariate Logistic regression. Results: The positive screening rate for AIS was 2.0%(135 cases). Multivariate Logistic regression analysis revealed that female gender, no family history of AIS, standing with lumbar spine tilted forward, habit of leaning to the left when seated, and a monthly family income of >10 000 yuan were related to the occurrence of AIS in adolescents ( OR =3.01, 0.38, 2.29, 1.74, 0.44, P <0.05). Conclusion Female students aged 10-16 years with a family history of scoliosis in Zhongshan are identified as a high risk group for scoliosis screening. Developing proper standing and sitting habits helps to reduce the risk of AIS in adolescents.

Objective Using event-related potentials(ERPs),to study the effect and mechanism of negative emotion accumulation hepatic insufficiency on working memory in normal people.Methods Fifty subjects in each of the emotionally stable group and emotionally unstable group were given two load tasks(0-back and 1-back)in the N-back paradigm,the reaction time and correct rate were recorded,and the ERPs components N200 and P300 were detected.The latency and amplitude of P300 were analyzed statistically.Results ①Compared with the emotionally stable group,the emotionally unstable group had a longer reaction time(P<0.05).②Compared with the emotionally stable group,the subjects in the emotionally unstable group had prolonged N200 latency,decreased P300 amplitude significantly(P<0.05),and P300 latency had a tendency to extend(P<0.1).Conclusion Long-term accumulation of negative emotions and liver failure in normal people have the performance of decreased working memory,which may be related to the reduction of attention resource allocation and the impairment of cognitive processing function.

Objective:To investigate and understand current status of radiotherapy resources in the Association of Southeast Asian Nations (ASEAN) and analyze the radiotherapy needs of ASEAN countries, aiming to provide suggestions for China's radiotherapy technology international assistance work.Methods:We created a database of 10 ASEAN countries using open-source data, including data on population size, per capita gross national income, new cancer cases, and radiotherapy equipment (megavolt units). We also estimated the number of cases requiring radiotherapy and the demand for radiotherapy equipment. Descriptive statistics were used to present aggregate data and national data.Results:In 2020, the number of new cancer cases in ASEAN countries was 1.0992 million, and the estimated total number of cancer patients requiring radiotherapy was 700 300. The number of radiotherapy equipment required was 1 406. At present, the actual number of radiotherapy equipment in ASEAN countries is 564, and there is a certain gap between the existing radiotherapy resources in some ASEAN countries and the actual needs of cancer patients in their own countries. In 2040, the estimated number of new cancer cases in ASEAN countries will be 1.803 million, and the estimated total number of cancer patients who need radiotherapy in ASEAN countries will be 1.141 2 million. The number of required radiotherapy equipment will be 2 287. By 2040, the growth rate of radiation therapy equipment demand in ASEAN countries will be 305%, and all ASEAN countries need to allocate more radiotherapy resources to cope with the increase in the number of cancer patients and radiotherapy demand.Conclusions:ASEAN countries have a huge demand for radiotherapy in the next two decades, while there are significant differences among different countries. China's precision radiotherapy science and technology have huge potential for ASEAN countries. Radiotherapy science and technology international assistance work based on the needs of ASEAN countries will help China's radiotherapy continue to exert influence and promote the health and well-being of people in ASEAN countries.

Objective:To evaluate the prognostic value of pretreatment systemic immune-inflammation index (SII) and lactate dehydrogenase (LDH) in non-metastatic nasopharyngeal carcinoma (NPC).Methods:We retrospectively collected the data of 839 patients with non-metastatic NPC from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Sun Yat-sen University Cancer Center between January 2007 and October 2015. All patients received intensity modulated radiation based treatment. Optimal cutoff value of SII and LDH were determined by X-title software. The association between SII, LDH and clinical prognosis of non-metastatic NPC patients were analyzed. Kaplan-Meier method was used for survival analysis, and Log rank test was used for comparison of survival rates between groups. Propensity score matching (PSM) analysis was carried out to minimize the effects of confounding factors. The risk stratification model of prognosis by combining N stage, SII and LDH was constructed to compare the prognosis of patients in high risk group, middle risk group and low risk group, and the receiver operating characteristic (ROC) curve analysis was used to evaluate its prognostic value.Results:The optimal cutoff value of SII is 447.2×10 9/L for predicting the 5-year overall survival (OS) of NPC patients, and the best cutoff value of LDH is 198.9 U/L. The proportion of patients with stage T3-4 and stage III-IVB in high SII group was higher than that in low SII group ( P<0.001). Multivariate Cox regression analysis showed that N stage, SII and LDH were independent factors of OS, progression-free survival (PFS) and distant metastasis-free survival (DMFS) of NPC patients (N stage, HR=1.705, 95% CI: 1.247-2.332; HR=1.755, 95% CI: 1.342-2.295; HR=2.161, 95% CI: 1.515-3.082. SII, HR=1.525, 95% CI: 1.097-2.119; HR=1.518, 95% CI: 1.150-2.004; HR=1.837, 95% CI: 1.272-2.653. LDH, HR=2.041, 95% CI: 1.403-2.968; HR=1.725, 95% CI: 1.233-2.414; HR=2.492, 95% CI: 1.690-3.672, respectively). After PSM, SII was still an independent prognostic factor of OS, PFS and DMFS in NPC patients ( HR=1.52, 95% CI: 1.09-2.12; HR=1.52, 95% CI: 1.15-2.00; HR=1.82, 95% CI: 1.26-2.63, respectively). Combined with N 2-3 stage, SII (>447.2×10 9/L), and LDH (>198.9 U/L), patients were divided into high-(3 risk factors), intermediate- (2 risk factors) and low-risk (0-1 risk factors) groups. The 5-year OS rates of patients in low-, intermediate- and high-risk groups were 86.1%, 79.8% and 41.2% respectively, the 5-year PFS rates were 80.7%, 70.2% and 33.9% respectively, and the 5-year DMFS rates were 88.9%, 79.2% and 47.5% respectively. There were significant differences in OS, PFS and DMFS among these three groups ( P<0.001). Distant metastasis was the main failure pattern in low-, intermediate- and high-risk groups, and the highest rate of distant metastasis was 83.3% (15/31) in high-risk group. ROC curve of the risk stratification model for predicting 5-year OS of NPC patients is 0.610, which is higher than TNM stage (0.609), SII (0.574) and LDH (0.558). Conclusions:Pretreatment SII and LDH are significantly correlated with the prognosis of patients with non-metastatic NPC. The combination of SII, LDH and N stage can stratify the prognostic risk of NPC patients. The risk stratification model can enhance the accuracy of prognosis.

Objective:To evaluate the prognostic value of pretreatment systemic immune-inflammation index (SII) and lactate dehydrogenase (LDH) in non-metastatic nasopharyngeal carcinoma (NPC).Methods:We retrospectively collected the data of 839 patients with non-metastatic NPC from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Sun Yat-sen University Cancer Center between January 2007 and October 2015. All patients received intensity modulated radiation based treatment. Optimal cutoff value of SII and LDH were determined by X-title software. The association between SII, LDH and clinical prognosis of non-metastatic NPC patients were analyzed. Kaplan-Meier method was used for survival analysis, and Log rank test was used for comparison of survival rates between groups. Propensity score matching (PSM) analysis was carried out to minimize the effects of confounding factors. The risk stratification model of prognosis by combining N stage, SII and LDH was constructed to compare the prognosis of patients in high risk group, middle risk group and low risk group, and the receiver operating characteristic (ROC) curve analysis was used to evaluate its prognostic value.Results:The optimal cutoff value of SII is 447.2×10 9/L for predicting the 5-year overall survival (OS) of NPC patients, and the best cutoff value of LDH is 198.9 U/L. The proportion of patients with stage T3-4 and stage III-IVB in high SII group was higher than that in low SII group ( P<0.001). Multivariate Cox regression analysis showed that N stage, SII and LDH were independent factors of OS, progression-free survival (PFS) and distant metastasis-free survival (DMFS) of NPC patients (N stage, HR=1.705, 95% CI: 1.247-2.332; HR=1.755, 95% CI: 1.342-2.295; HR=2.161, 95% CI: 1.515-3.082. SII, HR=1.525, 95% CI: 1.097-2.119; HR=1.518, 95% CI: 1.150-2.004; HR=1.837, 95% CI: 1.272-2.653. LDH, HR=2.041, 95% CI: 1.403-2.968; HR=1.725, 95% CI: 1.233-2.414; HR=2.492, 95% CI: 1.690-3.672, respectively). After PSM, SII was still an independent prognostic factor of OS, PFS and DMFS in NPC patients ( HR=1.52, 95% CI: 1.09-2.12; HR=1.52, 95% CI: 1.15-2.00; HR=1.82, 95% CI: 1.26-2.63, respectively). Combined with N 2-3 stage, SII (>447.2×10 9/L), and LDH (>198.9 U/L), patients were divided into high-(3 risk factors), intermediate- (2 risk factors) and low-risk (0-1 risk factors) groups. The 5-year OS rates of patients in low-, intermediate- and high-risk groups were 86.1%, 79.8% and 41.2% respectively, the 5-year PFS rates were 80.7%, 70.2% and 33.9% respectively, and the 5-year DMFS rates were 88.9%, 79.2% and 47.5% respectively. There were significant differences in OS, PFS and DMFS among these three groups ( P<0.001). Distant metastasis was the main failure pattern in low-, intermediate- and high-risk groups, and the highest rate of distant metastasis was 83.3% (15/31) in high-risk group. ROC curve of the risk stratification model for predicting 5-year OS of NPC patients is 0.610, which is higher than TNM stage (0.609), SII (0.574) and LDH (0.558). Conclusions:Pretreatment SII and LDH are significantly correlated with the prognosis of patients with non-metastatic NPC. The combination of SII, LDH and N stage can stratify the prognostic risk of NPC patients. The risk stratification model can enhance the accuracy of prognosis.

Objective:To identify the population who can obtain clinical benefit from concurrent chemoradiotherapy through the survival analysis during concurrent chemoradiotherapy in different subgroups.Methods:All data from a phase Ⅲ randomized controlled clinical trial were collected to compare the efficacy between preoperative concurrent chemoradiotherapy and preoperative radiotherapy from 2002 to 2012 in Cancer Hospital of the Chinese Academy of Medical Sciences. A total of 222 patients received radiation therapy with a median dose of 69.96 Gy (27.56-76.00 Gy). The cisplatin chemotherapy regimen was adopted and the median dose was 250 mg (100-570 mg). In total, 98 patients received intensity-modulated radiotherapy (IMRT). The survival analysis was conducted with Kaplan- Meier method and univariate analysis was performed with log-rank test. The multivariate prognostic analysis was conducted with Cox’s regression model. Results:The median follow-up time was 59 months (7-139 months). Among them, 104 patients were assigned in the chemoradiotherapy group and 118 patients in the radiotherapy alone group. The local and regional recurrence rates did not significantly differ between two groups (both P>0.05), while chemoradiotherapy tended to decrease the distant metastasis rate compared with the radiotherapy alone (14.4% vs. 24.6, P=0.058). Univariate analysis showed that concurrent chemoradiotherapy significantly increased the local recurrence-free survival in the early N stage subgroup ( P=0.009), and there was an increasing trend in patients aged≤55 years and female patients ( P=0.052, 0.066). The distant metastasis-free survival was significantly improved in T 4( P=0.048), N 3( P=0.005), non-IMRT treatment ( P=0.001) and hypopharyngeal carcinoma ( P=0.004) subgroups, there was an increasing trend in male ( P=0.064), high-and moderate-grade squamous cell carcinoma ( P=0.076) and non-surgical treatment subgroups ( P=0.063). Multivariate analyses showed that concurrent chemoradiotherapy significantly prolonged the progression-free survival and overall survival in patients aged≤55 years ( P=0.017 and 0.039), women ( P=0.041 and 0.039), high-and moderate-grade squamous cell carcinoma ( P=0.006 and 0.022), N 3 stage ( P=0.001 and 0.017), non-surgical treatment ( P=0.007 and 0.033) and non-IMRT treatment subgroups ( P=0.030 and 0.024), and it significantly increased the progression-free survival in patients with hypopharyngeal carcinoma ( P=0.022). Conclusion:Concurrent chemoradiotherapy can be actively delivered for young age, female, high-and moderate-grade squamous cell carcinoma, N 3 stage, non-surgical treatment and non-IMRT treatment patients.

Objective:To compare the effects of comprehensive treatment with different combinations of radiotherapy, chemotherapy and surgery on the survival of patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC).Methods:From September 2002 to May 2012, 222 patients were enrolled in a randomized controlled clinical trial to compare the clinical efficacy between preoperative radiotherapy and preoperative concurrent chemoradiotherapy. The chemotherapy was performed at the beginning of the radiotherapy, with cisplatin 30 mg/m 2 every week. Conventional radiotherapy or intensity-modulated radiotherapy (IMRT) was adopted. Clinical efficacy was evaluated during radiotherapy to 50 Gy in all patients. Whether surgery or original treatment regime was given was determined according to the clinical efficacy. The survival of different therapeutic methods was analyzed by Kaplan- Meier method. Results:The median follow-up time was 59 months (7-139 months). All patients were divided into four groups: radiotherapy group (R group, n=84), concurrent chemo-radiotherapy group (R+ C group, n=67), preoperative radiotherapy group (R+ S group, n=34) and preoperative concurrent chemoradiotherapy group (R+ C+ S group, n=37). The 5-year overall survival rates were 32%, 44%, 51%, and 52%, respectively (R+ C+ S group vs. R group, P=0.047). The 5-year progression-free survival rates were 34%, 48%, 49%, and 61%, respectively (R+ C Group vs. R group, P=0.081; R+ C+ S group vs. R group, P=0.035). The 5-yeal distant metastasis-free survival rates were 70%, 85%, 65%, and 73%, respectively (R+ C group vs. R+ S group, P=0.064; R+ C group vs. R+ S group, P=0.016). Conclusions:Compared with radiotherapy alone, comprehensive treatment with different combinations can improve the long-term survival of LA-HNSCC patients. Radiotherapy combined with chemotherapy has a tendency to improve the distant metastasis-free survival rate, The optimal comprehensive treatment modality that improves the overall survival of LA-HNSCC patients remains to be explored.

Objective:To analyze the incidence and high-risk factors of lymph node metastasis in the retropharyngeal region of hypopharyngeal squamous cell carcinoma based on magnetic resonance imaging (MRI), aiming to guide the delineation of clinical target area.Methods:Clinical data of patients who were pathologically diagnosed with hypopharyngeal carcinoma from January 2012 to September 2018 in our center were retrospectively analyzed. All patients received head and neck MRI before treatment. The diagnosis of lymph node metastasis and the delineation of primary gross target volume (GTV p) and lymph nodes target volume (GTV nd) were determined by all the radiation oncologists in head and neck group through twice weekly general round discussion. The cut-off points of GTV p and GTV nd were defined by establishing the receiver operating characteristic curve. All patients were divided into the high GTV p, low GTV p and high GTV nd and low GTV nd groups. Chi-square test was used for univariate analysis and logistic regression was utilized for multivariate analysis to analyze the high-risk factors of patients with retropharyngeal lymph node metastasis. Results:A total of 326 patients were included in this study, 295 of whom were diagnosed with cervical lymph node metastasis, accounting for 90.5%. The most common involved area was Level Ⅱ a, followed by Level Ⅲ, Level Ⅱ b, Level IV, Level Ⅶ a (retropharyngeal), Level V a, and Level V b. The incidence of retropharyngeal lymph node metastasis was 21.5%, and the incidence was 53.1% in patients with primary tumor located in the posterior pharyngeal wall. Univariate and multivariate analyses showed that patients with tumor originated from the posterior pharyngeal wall ( P=0.002), bilateral cervical lymph node metastasis ( P=0.020), larger GTV p (greater than 47 cm 3, P=0.003), and larger GTV nd (greater than 22 cm 3, P=0.023) were significantly associated with the occurrence of retropharyngeal lymph node metastasis. Conclusions:The incidence of retropharyngeal lymph node metastasis is high in hypopharyngeal carcinoma, especially in patients with primary tumors in the posterior pharyngeal wall, bilateral cervical lymph node metastasis and larger primary burden. Therefore, for patients with these risk factors, it is highly recommended that the clinical target area should be delineated to include the retropharyngeal lymph node drainage area.

Objective:To investigate the patterns of regional lymphatic spread and the value of elective neck treatment (ENT) in oral mucosal melanoma (OMM).Methods:In this retrospective analysis, 61 OMM patients with no distant metastasis treated in Cancer Hospital of Chinese Academy of Medical Sciences between 1984 and 2016 were recruitred. The regional lymph node distribution of cN+ disease, the value of ENT in cN 0 disease, the failure patterns and prognostic factors were retrospectively analyzed. Results:Overall, 55.7% of the patients were clinical/pathological cN+ . The most frequently involved locations were the level Ⅰ b (76%), followed by level Ⅱ and level Ⅲ. For cN 0 patients, the 5-year regional failure-free survival rate was 91.7% in patients who received at least ipsilateral level Ⅰ b-Ⅲ ENT and 52.4% in patients who did not receive at least ipsilateral level Ⅰ b-Ⅲ ENT ( P=0.036). The regional failure rate was 6% for patients treated with at least ipsilateral leve Ⅰ b-Ⅲ ENT, while in their counterparts who did not receive at least ipsilateral level Ⅰ b-Ⅲ ENT was 46%( P=0.035). For the regional failure pattern, the most frequently failure sites were level Ⅰ b (93%), level Ⅱ(50%) and level Ⅲ(36%). Conclusions:The cervical lymph node metastasis rate is relatively high in OMM patients. The pathway of regional LN spread follows a regular pattern. The most frequently involved regions for clinical/pathological cN+ and regional failure are both level Ⅰ b-Ⅲ. Elective treatment including at least ipsilateral level Ⅰ b-Ⅲ ENT should be recommended for OMM patients with cN 0.