Perinatal depression is a psychological disorder that occurs during pregnancy and within one year of delivery, which can seriously affect the physical and mental health of pregnant and postpartum women, as well as the cognitive and behavioral abilities of offspring, with potential multigenerational effects. Therefore, it is important to identify its potential modifiable risk factors. Phthalic acid esters (PAEs), as common environmental endocrine disruptors, can affect maternal estrogen through multiple mechanisms and are important potential modifiable risk factors for developing maternal perinatal depression. At present, studies on the correlation between PAEs and perinatal depression are still very limited, and the mechanisms by which PAEs affect perinatal depression have not been clarified. Based on existing epidemiological and toxicological studies at home and abroad, the article briefly introduced the characteristics of multiple pathways, high doses, and long-term exposure to maternal PAEs, focused on reviewing the current status of epidemiological studies, pointed out the possible associations between some specific PAEs exposure and elevated risk of perinatal depression. It also summarized the potential roles of hormone-neurotransmitter pathway, inflammation mediation, gene regulation, and other possible mechanisms in the association between exposure to PAEs and perinatal depression. The article concluded with a look at how future research on the association between exposure to PAEs and perinatal depression can be scientifically validated, with a view to providing more high-quality evidence for the scientific prevention of the onset and progression of maternal depressive symptoms.

Objective:To analyze the radiotherapy-related factors affecting the survival of non-small cell lung cancer (NSCLC) patients complicated with malignant pleural effusion (MPE)(MPE-NSCLC).Methods:From 2007 to 2019, 256 patients pathologically diagnosed with MPE-NSCLC received primary treatment. Among them, 117 cases were enrolled in this study. All patients were divided into two groups according to the radiation dose (<63 Gy and≥63 Gy). Propensity score matching (PSM) was performed to further adjust the confounding factors (Calipers value=0.1). The impact of radiotherapy-related factors on the overall survival (OS) was analyzed by Kaplan—Meier method, log-rank test and Cox’s regression model. Results:Primary tumor radiotherapy significantly prolonged the OS ( P<0.001). The radiation dose escalation (36.0-44.1 Gy, 45.0-62.1 Gy, 63.0-71.1 Gy) of primary tumor significantly prolonged the OS ( P<0.001). The corresponding median OS were 5, 13 and 18 months, respectively. Before the PSM, univariate analysis suggested that radiation dose ≥63 Gy, gross tumor volume (GTV)<157.7 cm 3 and stations of metastatic lymph node (S-mlN)≤5 were significantly associated with better OS (all P<0.05) and T 4N 3 was significantly associated with worse OS ( P=0.018). After the PSM, univariate analysis indicated that radiation dose ≥63 Gy was significantly associated with better OS ( P=0.013) and S-mlN ≤5 had a tendency to prolong the OS ( P=0.098). Prior to the PSM, multivariate analysis showed that radiation dose ≥63 Gy was an independent favorable factor of OS ( HR=0.566, 95% CI 0.368-0.871, P=0.010) and GTV<157.7 cm 3 had a tendency to prolong the OS ( HR=0.679, 95% CI 0.450-1.024, P=0.065). After the PSM, multivariate analysis revealed that radiation dose ≥63 Gy was still an independent favorable factor of OS ( HR=0.547, 95% CI 0.333~0.899, P=0.017). No ≥grade 4 radiation toxicity occurred. The incidence rates of grade 3 radiation esophagitis and pneumonitis were 9.4% and 5.1%, respectively. Conclusion:For MPE-NSCLC, radiotherapy dose of primary tumor may play a key role in improving OS on the basis of controllable MPE.

Objective:To explore the establishment of radiation-induced heart damage (RIDH) SD rat models caused by irradiation of 15Gy/3f and the changes in early detection indicators, and evaluate the effect of irradiation combined with recombinant human endostatin (Endostar).Methods:75 adult male SD rats were randomly divided into the blank control group (C group), Endostar group (E group), 25Gy irradiation group (MHD 25 group), 15Gy irradiation group (MHD 15 group) and 15Gy irradiation combined with Endostar group (MHD 15+ E group), respectively. Blood sample was taken to measure the CK, CK-MB, LDH and CRP at 24h, 48h and 15d after corresponding interventions. After cardiac echocardiography at 1, 3 and 6 months, 5 rats in each group were randomly sacrificed and myocardial tissues were collected for HE and Masson staining. Two-way ANOVA was employed for statistical analysis. Results:Compared with group C, myocardial fibrosis were observed in the MHD 15 group at 6 months ( P<0.05), which occurred later than that in the MHD 25 group. Ejection fraction (EF) and fractional shortening (FS) were significantly decreased after 3 months in each irradiation group (all P<0.05), whereas the degree of decrease was similar among all groups (all P>0.05). The expression levels of myocardial enzymes and inflammatory cytokines did not significantly differ among different groups (all P>0.05). Conclusions:In the early stage, exposure to 15Gy/3f irradiation can cause cardiac function damage in SD rat hearts, such as the reduction of EF and FS, and even lead to myocardial fibrosis in the late stage, which is delayed and less severe than high-dose irradiation. Irradiation combined with Endostar has no significant effect on radiation myocardial injury in rats.

In recent years, heavy ion beams have received great attention in the field of malignant tumor radiotherapy due to their radiation physics and biological characteristics. The high rate of local tumor control is one of its advantages, but the control rate of metastatic lesions is still crucial in the treatment of most malignant tumors. Clinical studies on the combined conventional radiotherapy and immunotherapy suggest that the combination of the two can not only control the primary lesions, but may also reduce or completely eliminate distant metastatic lesions. High linear energy transfer radiation, especially heavy ion beams, may have stronger potential in combined immunotherapy. Therefore, this article focuses on the basic research progress of heavy ion beams regulating anti-tumor immune effects and their combined application with immunotherapy.

Objective To investigate the impact of the changes of posttreatment karnofsky performance status (KPSpost) on the overall survival (OS) for patients with stage Ⅳ non-small cell lung cancer (NSCLC) underwent concurrent chemoradiation.Methods A total of 279 patients (male 198 and female 81) with histological confirmed stage Ⅳ NSCLC were enrolled in this study with a median age of 58 years old (range 22 to 80 years old).There were 166 cases of squamous carcinoma,87 cases of adenocarcinoma,and 22 cases of unclassified carcinoma,respectively.All enrolled patients received more than 2 cycles of chemotherapy and more than 36 Gy of concurrent radiotherapy.Kaplan-Meier method and Log-rank test were applied to evaluate OS.Multivariate analyses were carried out by the Cox proportionalhazard model.Chi-square test and logistic regression analysis were used to explore the related factors of KPSpost.Results There were 198 patients with improved KPSpost and 81 patients with decreased KPSpost,respectively.Univariate and multivariate analyses indicated that the improvement of KPSpost was associated with longer OS.Logistic regression analysis showed that the improvement of KPSpost was positively related with treatment of more than 4-6 cycles chemotherapy concurrent with over 63 Gy radiation to primary tumor.The improvement of KPSpost also correlated positively with disease control rate (DCR),but negatively with PLT toxicity and radiation esophagitis.Conclusions KPSpost was an independent prognostic factor of OS for patients with stage Ⅳ NSCLC underwent concurrent chemoradiation.Chemotherapy of 4-6 cycles and concurrent over 63 Gy radiotherapy dose to primary tumor,as well as DCR were positive factors for KPSpost improvement.However,stage 3-4 PLT toxicities and radiation esophagitis decreased the KPSpost.

Objective:The experimental animal model was established to unravel the mechanism of radiation-induced myocardial fibrosis and validate the role of recombinant human endostatin in aggravating the process of radiation-induced myocardial fibrosis via the TGF-β 1, Smad 2 and Smad 3 signaling pathways. Methods:Sixty male adult Sprague-Dawley rats were randomly divided into the following groups: radiotherapy (RT)25 Gy, recombinant human endostatin (RE) 6 mg/kg, RE 12 mg/kg, RT 25 Gy+ RE 6 mg/kg, RT 25 Gy+ RE 12 mg/kg and blank control groups. Five rats were sacrificed in each group at 1 and 3 months after interventions. The myocardial tissues were collected. The pathological changes were observed by Hematoxylin and eosin staining. The degree of fibrosis was assessed by Masson trichrome staining. The expression levels of TGF-β 1, Smad 2, Smad 3 and Collagen-I mRNA and protein were quantitatively measured by real-time PCR and Western blotting. Results:At 3 months after intervention, Masson trichrome staining revealed that the collagen deposition in the RT 25Gy and RT 25Gy+ RE (6 and 12 mg/kg) groups was more significant than that in the control group. In addition, The expression levels of TGF-β 1, Smad 2, Smad 3 and Collagen-I mRNA and protein in these groups were significantly up-regulated compared with those in the control group. Conclusions:Radiation with a total physical dose of 25 Gy can induce myocardial fibrosis in the SD rat models. TGF-β 1 and Smad 2 signaling pathways are the common signaling pathways of myocardial fibrosis induced by radiation combined with recombinant human endostatin.

Objective:To study the relationship between endoplasmic reticulum stress (ERS) and apoptotic protein and myocardial pathological changes in rats after endostar combined with low-dose X-ray irradiation.Methods:Forty SD rats were evenly divided into four groups: control group (intraperitoneal injection of equal volume physiological saline, once per day, 14 d), endostar group (intraperitoneal injection of endostar 6 mg/kg, once per day, 14 d), irradiation group (15 Gy divided into 3 times X-ray irradiation) and combination group (intraperitoneal injection of endostar after irradiation at the same dose and time as the endostar group). At 1 and 6 months after treatment, myocardial tissues of rats were prepared for HE staining and Masson staining to observe the myocardial histological changes. TUNEL assay was used to detect myocardial cell apoptosis, and ImageJ software was utilized to calculate myocardial collagen volume fraction (CVF). The expression levels of ERS and apoptotic protein glucose-regulated protein 78 (GRP78), protein kinase-like endoplasmic reticulum kinases (PERK), CCAAT/enhancer binding protein homologous protein (CHOP) and cysteine-containing aspartate-specific protease-12 (Caspase-12) were detected by Western blot. One-way ANOVA was conducted using GraphPad Prism 8.0.1 software, and comparison between two groups was conducted using t-test. Results:At 6 months after treatment, the myocardial interstitium in the irradiation and combination groups was widened, showing strip-like or reticular fibrosis changes, and the myocardial interstitium had diffuse collagen fiber deposition. Compared with the control group, CVF was increased significantly (both P<0.01). At 1 and 6 months after treatment, the apoptotic index of myocardial cells in the combination group was significantly higher than that in the control group ( P<0.05, <0.001). At 1 and 6 months after treatment, the expression levels of GRP78 protein in the irradiation and combination groups were increased (all P<0.01), and the expression levels of PERK and CHOP proteins in the combination group were increased compared to those in the control group (both P<0.05). At 6 months after treatment, the expression levels of PERK and CHOP proteins in the irradiation group were increased compared to those in the control group (both P<0.05). Compared with the control group, Caspase-12 expression levels at 1 and 6 months after treatment were increased in the endostar, irradiation and combination groups (all P<0.05). Conclusions:The expression levels of ERS and apoptotic proteins are related to cardiac injury caused by irradiation in rats. After low-dose X-ray combined with endostar treatment, ERS is aggravated and myocardial apoptosis is increased.

Objective To evaluate the clinical efficacy and toxicity of concurrent pemetrexed-cisplatin (PP) or docetaxel-cisplatin (DP) with intensity-modulated radiation therapy (IMRT) in patients with stageⅠV lung adenocarcinoma. Methods Stage IV lung adenocarcinoma patients with unknown EGFR mutation status or wild-type admitted to Guizhou Cancer Hospital from 2011 to 2016 were randomly assigned into the PP (n=50) and DP groups (n=51).All patients received concurrent IMRT of the chest at a prescription dose of 60-70 Gy. Primary endpoint was 1-year survival rate, and secondary endpoint was acute toxicity. Results The overall response rate was 68. 0％ and 72. 5％ in the PP and DP groups (χ2=0. 250, P=0. 617) . The median survival time was 19. 6 months ( 95％CI 13. 9-25. 3) versus 12. 1 months ( 95％CI 10. 7-13. 5) in the PP and DP groups. The 1-, 2-and 3-year overall survival rates were 72. 0％ versus 52. 9％, 28. 0％ versus 17. 6％, and 16. 0％ versus 13. 7％, respectively in the PP and DP groups ( P=0. 049) . In the PP and DP groups, the incidence of grade 3-4 leukopenia was declined by 48％ and 63％( P=0. 098) , and the incidence of grade 3-4 neutropenia was decreased by 34％ and 65％( P=0. 002) , the incidence of grade 3-4 anemia was reduced by 38％ and 10％(P=0. 024), and the incidence of grade 3-4 thrombocytopenia was declined by 40％ and 14％( P=0. 003) . The incidence rate of grade 2 pneumonitis ( P=0. 625) and grade 3 esophagitis ( P=0. 484) were similar in both groups. No patients experienced ≥grade 3 pneumonitis or ≥ grade 4 radiation esophagitis. Conclusions Pemetrexed-cisplatin combined with chemoradiotherapy yields higher clinical efficacy compared with docetaxel-cisplatin plus concurrent chemoradiation in the treatment of stageⅠV lung adenocarcinoma. The incidence of radiation pneumonitis and esophagitis is similar. The incidence and severity of hematological toxicity does not significantly differ between two groups.Treatment-related toxicity is tolerable in both groups. Clinical Trial Registration Chinese Clinical Trial Registry ( ChiCTR-TRC-13004184) .

Objective To analyze the survival and toxicity after concurrent chemoradiotherapy in patients of different ages with stage Ⅳ non-small cell lung cancer (NSCLC).Methods Clinical data of 282 NSCLC patients in two prospective studies were retrospectively analyzed,who completed the protocol (at least 2 cycles of chemotherapy and thoracic radiation doses of ≥36 Gy).Among them,44 patients were assigned into in the young group (≤ 45 years old),161 patients in the middle-age group (46-64 years old) and 77 patients in the elderly group (≥ 65 years old).The clinical characteristics of patients among different groups were analyzed by x2 test.The overall survival (OS) was calculated by Kaplan-Meier method.Stratified analysis was performed by Log-rank test.Multi-factor prognosis analysis was conducted by Cox's proportional hazards regression model.Results The incidence of NSCLC in the male patients in the elderly group was higher than that in the middle-age and young groups.The 1-,2-,3-and 5-year OS did not significantly differ among different groups (P=0.810).The OS did not significantly differ among patients of the same gender,pathological type,T stage,N stage,metastasis status,same chemotherapy cycle,primary tumor dose and comprehensive treatment and short-term response (all P＞0.05).The incidence of adverse events did not considerably differ among different groups.Multivariate analysis demonstrated that age was not an independent factor for survival (P＞ O.05).Conclusion Patients of different ages with stage Ⅳ NSCLC obtain similar survival benefits and adverse events after concurrent chemoradiotherapy.

The prognosis of patients with brain metastases from non-small cell lung cancer (NSCLC) is poor. Tyrosine kinase inhibitor (TKI) significantly improves the prognosis of patients with epidermal growth factor receptor (EGFR) sensitive mutation. EGFR sensitive mutations are associated with the incidence of brain metastases in NSCLC and may affect the efficacy of radiotherapy and TKI therapy. Both EGFR-TKI and radiotherapy are effective for EGFR-mutant NSCLC with brain metastases. Whether the combination of EGFR-TKI and radiotherapy may improve the prognosis compared with EGFR-TKI or radiotherapy alone has been studied. Retrospective studies have indicated that upfront radiotherapy, especially upfront stereotaxic radiosurgery combined with EGFR-TKI may be more advantageous in improving the prognosis, but it is still controversial. Therefore, clinical research progresses on the radiotherapy for EGFR-mutant NSCLC patients with brain metastases were reviewed.