Objective:To evaluate the efficacy and safety of thoracic radiotherapy in the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) with different metastatic sites.Methods:A retrospective analysis was performed among 830 ES-SCLC patients who were admitted to our hospital from 2010 to 2019. They all received the first-line chemotherapy and had no progression after chemotherapy. 341 patients of them received thoracic radiotherapy after chemotherapy. The main endpoint was overall survival. The Chi-square test was used to compare the categorical data including gender and age, etc. Univariate survival analysis was estimated by Kaplan-Meier method and the log-rank test was used to compare the survival curves between two groups. A multivariate prognostic analysis was made by the Cox proportional hazard model.Results:In all the patients, the overall survival (OS) was 12.4 months. The patients with thoracic radiotherapy had significantly higher OS than the patients without thoracic radiotherapy (15.2 months vs.10.8 months, P<0.001). Thoracic radiotherapy significantly improved the OS in patients without liver metastasis (16.0 months vs.11.4 months, P<0.001) in the oligometastatic patients. But for the oligometastatic patients with liver metastasis, the OS benefit was not significant (14.2 months vs. 10.6 months, P=0.072). For polymetastatic patients without liver metastasis, thoracic radiotherapy offered significant OS benefits (14.5 months vs.10.9 months, P<0.001), but for the polymetastatic patients with liver metastasis, the OS was not improved with thoracic radiotherapy (10.2 months vs.9.2 months, P=0.715). Conclusions:In ES-SCLC patients, thoracic radiotherapy provides significant OS benefits in patients with oligometastases ES-SCLC without liver metastasis and for the liver metastatic patients may also benefit from thoracic radiotherapy based on the effectiveness of chemotherapy. In patients with multiple metastases, thoracic radiotherapy only improves the OS in patients without liver metastasis, but does not improve the prognosis in patients with liver metastasis.

The internal organs and meridians were associated with Yin and Yang, five elements, six qi, and time and space, based on the holistic view of heaven, earth and human, according to Huangdi Neijing. The syndrome differentiation system of six meridians and Zang Fu meridians were established by Shanghan Zabing Lun, on the basis of the three Yin, three Yang, six meridians, and five Zang system in Huangdi Neijing. We put forward the concept of the six meridians syndrome differentiation system of circular motion, considering that the six meridians syndrome differentiation system actually implies the theory of circular motion. The syndrome differentiation system was constructed with the circular model of one qi circulating around the road, rising left and falling right, corresponding up and down, and maintaining conservation in the middle as the core, integrating Yin and Yang, five elements, six qi, Zang Fu and meridians, qi, blood and body fluid, and the integration of heaven, earth and human, focusing on "disease location and disease nature", taking classical prescriptions as the main treatments, and cooperating with external treatments such as acupuncture and moxibustion. We organically combined the circular motion with the syndrome differentiation of the six meridians, systematically interpreted the physiological bases, pathological changes, progressive patterns, and the treatments, based on syndrome differentiation, by inheriting the classical thinking mode of Hetu, Luoshu,Zhouyi, Huangdi Neijing, ShennongHerbal Classic, and Shanghan Zabing Lun.

Objective:To explore the potential of dosiomics in predicting the incidence of radiation pneumonitis by extracting dosiomic features of definitive radiotherapy for lung cancer, and building a machine learning model.Methods:The clinical data, dose files of radiotherapy, planning CT and follow-up CT of 314 patients with lung cancer undergoing definitive radiotherapy were collected retrospectively. According to the clinical data and follow-up CT, the radiation pneumonia was graded, and the dosiomic features of the whole lung were extracted to establish a machine learning model. Dosiomic features associated with radiation pneumonia by LASSO-LR with 1000 bootstrap and AIC backward method with 1000 bootstraps were selected. Training cohort and validation cohort were randomly divided on the basis of 7:3.Logistic regression was used to establish the prediction model, and ROC curve and calibration curve were adopted to evaluate the performance of the model.Results:A total of 120 dosiomic features were extracted. After LASSO-LR dimensionality reduction, 12 features were selected into the "feature pool".After AIC, 6 dosiomic features were finally selected for model construction. The AUC of training cohort was 0.77(95% CI: 0.65 to 0.87), and the AUC of validation cohort was 0.72 (95% CI: 0.64 to 0.81). Conclusion:The dosiomics prediction model has the potential to predict the incidence of radiation pneumonia, but it still needs to include multicenter data and prospective data.

Objective:To evaluate whether whole brain radiation therapy(WBRT) could benefit small cell lung cancer (SCLC) patients with brain metastases.Methods:Clinical data of 245 patients who were diagnosed with extensive stage SCLC with brain metastases admitted to our hospital from 2010 to 2020 were retrospectively analyzed. Among them, 168 patients received WRBT (WBRT group, radiation dose: 30Gy in 10 fractions), and 77 patients did not receive WBRT (non-WBRT group). All patients received 4-6 cycles of chemotherapy, and the chemotherapy regimen included cisplatin (or carboplatin) plus etoposide. One hundred and fifteen patients received thoracic radiotherapy. The endpoint was overall survival after brain metastases(BM-OS). Chi-square test was used to compare categorical data, and stabilized inverse probability of treatment weighting(sIPTW) was used to match the factors between WBRT and no-WBRT groups. Survival analysis was estimated by Kaplan-Meier method, and the log-rank test was used to compare survival curves between two groups. Results:The median BM-OS for the whole group of patients was 9.1 months, and 10.6 months and 6.7 months in the WBRT and non-WBRT groups, respectively( P=0.003). After balanced influencing factors with stabilized sIPTW, significant difference still existed in BM-OS between two groups( P=0.02). In 118 patients with synchronous brain metastases, the median BM-OS in two groups were 13.0 months and 9.6 months( P=0.007); and in 127 patients with metachronous brain metastases, the median BM-OS were 8.0 months and 4.1 months( P=0.003). In 50 patients without extracranial metastases, the median BM-OS were 13.3 months and 10.9 months( P=0.259)in two groups; while in 195 patients with extracranial metastases, the median BM-OS were 9.5 months and 5.9 months( P=0.009)in two groups. Conclusions:WBRT could prolong the OS in extensive stage SCLC patients with brain metastases.

Objective:To compare the incidence of radiation pneumonitis (RP) between lung cancer patients from the European, American and Asian regions.Methods:The studies related to lung cancer and RP were searched from PubMed, Embase, and Cochrane library. According to the different places where the studies were conducted, the searched studies were divided into two types: Asian studies and European, American and Australian studies. The incidence of RP between two regions was summarized. Studies related to dosimetry parameters were searched from PubMed database.Results:A total of 3, 190 patients from 14studies were included. Meta-analysis results showed that the incidence of ≥ grade 3 RP was similar in patients from Asia and Europe, America and Australia (4.9% vs. 4.6%, P=0.895), whereas the incidence of grade 5 RP in Asia was significantly higher than that in Europe, America and Australia (1.5% vs. 0.2%, P=0.002). Moreover, the lung irradiation dose received by the patients in the Asian group was relatively low. Lung V 20Gy dose limitation standard was reported in 21studies. Further analysis found no statistical significance in lung V 20Gy dose limitation standard between two regions ( P=0.440), and the standard in Asian studies is likely to be even stricter. Conclusions:The incidence of RP after chemoradiotherapy in lung cancer patients in Asia is relatively higher compared with those in Europe, America and Australia. The differences in dose limitation standard should be noted when the thoracic radiation regimen based solely on the data from foreign studies is applied to the patients in Asia.

Objective:To investigate the role of concurrent chemoradiotherapy in the treatment of limited-stage small cell lung cancer (LS-SCLC) and the impact of the number of chemotherapy cycle during radiotherapy (RT) on clinical prognosis.Methods:Patients with LS-SCLC treated with definitive radiotherapy from May, 2008 to September, 2016 were included in the study. The primary endpoint was overall survival (OS), which was calculated from the start of treatment to the date of death or last follow-up. The effect of the number of concurrent chemotherapy cycle and other clinical factors on clinical efficacy was analyzed. Survival analysis was performed with Kaplan- Meier method, and multivariate analysis was performed with Cox regression model. Results:Three hundred and seventeen patients were eligible for the analysis. Among them, 129 patients received sequential chemoradiotherapy and 188 patients received concurrent chemoradiotherapy. Among patients receiving concurrent chemoradiotherapy, 86 patients received 1 cycle of concurrent chemotherapy and 102 cases of 2 cycles of concurrent chemotherapy. The median follow-up time was 22.47 months. Multivariate survival analysis showed that only clinical stage, timing of RT administration and prophylactic cranial irradiation (PCI) were the independent prognostic factor for OS. The median OS in patients who received 1 cycle and 2 cycles of concurrent chemotherapy during RT were 33.8 months and 30.4 months ( P=0.400). No matter in elder patients or in younger patients, in early RT group or in late RT group and application of PCI or not, the number of concurrent chemotherapy cycle exerted no significant impact on OS. The incidence of grade 3 or above adverse events was 20% in the 1-cycle concurrent chemotherapy group, and 13.7% in the 2-cycle concurrent chemotherapy group. Conclusions:Concurrent chemoradiotherapy is the standard treatment of LS-SCLC. Two cycles of concurrent chemotherapy during RT is not necessarily superior to 1 cycle of concurrent chemotherapy. The optimal number of concurrent chemotherapy cycle during RT need to be studied in a large prospective randomized clinical trial.

Objective:To analyze and explore the common radiomics features of radiation pneumonitis (RP) in patients with lung cancer and esophageal cancer, and then establish a prediction model that can predict the occurrence of RP in two types of cancer after radiotherapy.Methods:Clinical data of 100 patients with stage Ⅲ lung cancer and 100 patients with stage Ⅲ esophageal cancer who received radical radiotherapy were retrospectively analyzed. The RP was graded by imaging data and clinical information during follow-up, and the planning CT images were collected. The whole lung was used as the volume of interest to extract radiomics features. The radiomics features, clinical and dosimetric parameters related to RP were analyzed, and the model was constructed by machine learning.Results:A total of 1691 radiomics features were extracted from CT images. After ANOVA and LASSO dimensionality reduction in lung cancer and esophageal cancer patients, 8 and 6 radiomics features associated with RP were identified, and 5 of them were the same. Using the random forest to construct the prediction model, lung cancer and esophageal cancer were alternately used as the training and validation sets. The AUC values of esophageal cancer and lung cancer as the independent validation set were 0.662 and 0.645.Conclusions:It is feasible to construct a common prediction model of RP in patients with lung cancer and esophageal cancer. Nevertheless, it is necessary to further expand the sample size and include clinical and dosimetric parameters to increase its accuracy, stability and generalization ability.

Objective To investigate the consensus and controversies on the delineation of radiotherapy target volume for patients with locally advanced non-small cell lung cancer (LA-NSCLC).Methods Questionnaires including 15 questions on the delineation of radiotherapy target volume of NSCLC were sent to 12 radiation departments in China in November 2015.A patient with LA-NSCLC was selected by Fudan University Shanghai Cancer Center, and simulation CT images and medical history data were sent to the 12 radiation departments.Twelve radiation oncologists from the 12 radiation departments showed and explained the delineation of radiotherapy target volume of their own, and the patient was discussed by all experts in the sixth multidisciplinary summit forum of precise radiotherapy and chemotherapy for tumor and lung cancer.Results All receivers of the questionnaire answered the questions.The standard lung window width/level for the delineation of lung cancer was 800-1600/-600 to-750 HU, and the mediastinum window was 350-400/20-40 HU.Respiratory movement was measured by stimulator, 4D-CT, and stimulator+4D-CT with 2-5 mm expansion based on experience.The primary clinical target volume (CTV) was defined as gross target volume (GTV) plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma.The metastatic lesion of mediastinal lymph nodes was delineated as 5 mm plus primary lesion in 6 departments and as primary lesion in another 6 departments.Of the 12 departments, 10 applied 5 mm of set-up error, 1 applied 3 mm, and 1 applied 4-6 mm.For V20 of the lungs, 10 departments defined it as<30%, 1 as<35%, and 1 as 28%.Nine departments defined the radiation dose of concurrent chemoradiotherapy (CCRT) for LA-NSCLC as 60 Gy in 30 fractions, 62.7 Gy in 33 fractions in 1 department, 50-60 Gy in 25-30 fractions in 1 department, and 60-70 Gy in 25-30 fractions in 1 department.For the delineation of target volume for the LA-NSCLC patient treated with CCRT, the primary planning target volume (PTV) was defined as GTV plus organ movement (IGTV) and set-up error (GTV→IGTV→PTV) in 3 departments, as CTV plus organ movement (ITV) and set-up error (GTV→CTV→ITV→PTV) in 8 departments, and as CTV plus set-up error/IGTV plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma (CTV) and set-up error (GTV→CTV→PTV/GTV→IGTV→CTV→PTV) in 1 department.For the delineation of PTV in the mediastinal lymph node, GTV→IGTV→PTV was performed in 3 departments, GTV→CTV→ITV→PTV in 8 departments, and GTV→CTV→PTV in 1 department.For 10%-100% patients with LA-NSCLC, the radiation field needed to be replanned when 38-50 Gy was completed.There was no unified standard for the optimal standardized uptake value (SUV) of positron emission tomography (PET)-computed tomography (CT) simulation and delineation.Seven departments had applied magnetic resonance imaging (MRI) simulation and 10 departments had applied stereotactic body radiation therapy (SBRT) for the treatment of early-stage NSCLC.For the delineation of PTV for early-stage NSCLC (T1-2N0M0), GTV→IGTV→PTV was performed in 5 departments, IGTV→PTV in 3 departments, and GTV→CTV→ITV→PTV in 2 departments.In all the 12 departments, peripheral early-stage NSCLC was given 6.0-12.5 Gy/fraction, 3-12 fractions and central early-stage NSCLC was given 4.6-10.0 Gy/fraction, 5-10 fractions.The results of discussion on the delineation of target volume for the patient were as follows:respiratory movements should be measured by 4D-CT or simulator;the lung window width/level is 1600/-600 HU and the mediastinal window width/level is 400/20 HU;the primary controversy is whether the involved-field irradiation or elective nodal irradiation should be used for the delineation of CTVnd in the mediastinal lymph node.Conclusions Basic consensus is reached for the delineation of target volume in LANSCLC in these aspects:lung window width/level, respiratory movements and set-up error, primary lesion delineation, the radiation dose in CCRT, and the optimal time for replanning the radiation field.There are controversies on the optimal SUV in the delineation of target volume based on PET-CT simulation, the optimal dose fractionation in SBRT for early-stage NSCLC, and the delineation of CTVnd.

High-affinity α-glucosidase inhibitors were screened from Cichorium glundulosum Boiss.et Hout seed (CGS) extract by ultra-filtration affinity-liquid chromatography-mass spectrometry (UF-LC-MS) and molecular docking.By taking 4-nitrobenzene-α-D-glucopyranoside (PNPG) as substrate and acarbose as positive control to evaluate the inhibitory activity of CGS extract, IC50 of acarbose and CGS extract were 0.003 mg/mL and 0.447 mg/mL, respectively.Meanwhile, 4 compounds from CGS extract by UF-LC-MS were screened and identified.Then by using autodock software, the compounds that combined with α-glucosidase were well screened out, including chlorogenic acid and isochlorogenic acid A.The inhibitory activity of chlorogenic acid and chlorogenic acid A against α-glucosidase was verified in vitro.The results showed that the inhibitory activity of the compounds toward α-glucosidase presented the sequence of acarbose>isochlorogenic acid A>chlorogenic acid.The inhibition rate of isochlorogenic acid A was close to acarbose.The experimental results illustrated that UF-LC-MS and molecular docking could be used to screen high affinity enzyme inhibitors from CGS.

Objective To compare clinical effects of appendicectomy and conservative treatment of uncomplicated acute appendicitis.Methods Searched The Cochrane library,Medline,Pubmed,Embase,CBM,CNKI,VIP and Wan Fang database in any language.RCTs that compared conservative treatment with appendicectomy in patients with uncomplicated acute appendicitis were included from January 1983 to May 2013 and qualities of the trials were evaluated.Statistic analyses were carried out using RevMan 5.1 soft-ware.Results Four randomized trials met our inclusion criteria (821partiCI:pants).Antibiotics compared with appendicectomy resulted in similar outcomes with regards to the incidence of complicated appendicitis (RR:0.89,95％ CI:0.29-2.68) and intra-abdominal infection(RR:0.54,95％ CI:0.13-2.35).Antibiotics carries a lower risk of complications (RR 0.46,95％ CI:0.32-0.67),but requires more length of hospital stay (Mean Difference 0.52,95％ CI:0.16-0.88).Conclusions The effect of conservative treatment is safe and effective.But the recurrent uncomplicated appendicitis recommends operation.