Objective:To analyze the treatment efficacy, safety and dose parameters of optimized hippocampus-avoidance prophylactic cranial irradiation (HA-PCI) in limited-stage small cell lung cancer (LS-SCLC) and explore the corresponding dosimetric parameters under the condition of narrowing the hippocampus avoidance region as hippocampus region plus 2 mm in three dimensions.Methods:Clinical data of patients with LS-SCLC receiving HA-PCI (hippocampus avoidance region defined as hippocampus region plus 2 mm in three dimensions) in Cancer Hospital Chinese Academy of Medical Sciences from August 2014 to June 2020 were retrospectively analyzed. Dose parameters of HA-PCI and adverse events were analyzed using descriptive statistics analysis. Changes of neurocognitive function, such as mini-mental state examination (MMSE) and Hopkins verbal learning test-revised (HVLT-R) scores, were evaluated by analysis of variance and Kruskal-Wallis H test. Overall survival (OS), progression-free survival (PFS) and intracranial PFS (iPFS) were calculated using Kaplan-Meier method. The cumulative incidence of local-regional recurrence (LRR), extracranial distant metastases (EDM), and locoregional recurrence (LR) were investigated under competing risk analysis. Results:A total of 112 patients were included, the median follow-up time was 50 months (95% CI: 45.61-54.38). The median volume of hippocampus was 4.85 ml (range: 2.65-8.34 ml), with the average dose ≤9 Gy in 106 patients (94.6%), ≤8 Gy in 92 patients (82.1%). The median volume of hippocampus avoidance area was 15.00 ml (range: 8.61-28.06 ml), with the average dose ≤12 Gy in 109 patients (97.3%), ≤10 Gy in 101 patients (90.2%). The 2-year cumulative LRR, EDM, LR rates were 16.9%, 23.2% and 28.5%, respectively. The 5-year cumulative LRR, EDM, LR rates were 23.2%, 26.9% and 33.3%, respectively. The 2-year iPFS, PFS and OS rates were 66.1% (95% CI: 57.9%-75.4%), 53.6% (95% CI: 45.1%-63.7%) and 80.4% (95% CI: 73.3%-88.1%), respectively. The most common grade I-Ⅱ adverse events were nausea (33.9%) and dizziness (31.3%), and only 1 patient developed grade Ⅲ nausea and dizziness. MMSE ( n=57) and HVLT-R tests ( n=56) showed no significant decline. Conclusions:Optimized HA-PCI can achieve similar dose limitation with favorable efficacy and light toxicity. No significant decline is observed in short-term neurocognitive function in evaluable patients.

Objective:To evaluate the safety and efficacy of thoracic radiotherapy (TRT) for extensive-stage small cell lung cancer (ES-SCLC) patients in the era of first-line chemoimmunotherapy.Methods:Medical records of 56 patients with ES-SCLC who received thoracic radiotherapy after first-line platinum-based chemotherapy plus immunotherapy in Cancer Hospital Chinese Academy of Medical Sciences from January 2018 to December 2021 were retrospectively analyzed. The control group was not established for clinical causes. The overall survival (OS), progression-free survival (PFS) and local recurrence-free survival (LRFS) were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were employed to identify prognostic factors using the Cox proportional hazards model. The cumulative incidence of local regional recurrence (LRR) was estimated using the Fine-Grey competing risks regression model.Results:Among 56 patients in our cohort, 47 patients received consolidative TRT (cTRT) before progression and 9 patients received salvage TRT after progression. The median follow-up time was 21 months (95% CI=19.8-22.2 months), the median OS was not reached, the median PFS was 9 months (95% CI=7.0-13.0 months), and the 1-year and 18-month OS rates were 84.9%, 62.1%. In the cTRT group, the 1-year and 18-month OS rates were 84.1%, 64.5%, with the median PFS of 10 months; 1-year and 18-month LRFS rates were 73.6% and 66.0%, respectively; the cumulative incidence of LRR at 1-year and 2-year were 24.9% and 30.8%, respectively. No other 4-5 grade adverse events (AE) were reported except 6 patients presenting with 4 grade hematologic toxicities. Three grade radiation esophagitis occurred in 3 patients (5%). Ten patients (18%) developed 1-2 grade treatment-related pneumonitis, including 5 (9%) patients with immune related pneumonitis and 5 (9%) patients with radiation pneumonitis. Conclusion:The application of TRT after first-line chemoimmunotherapy is safe and may has potential survival benefit for patients with ES-SCLC.

Objective:To investigate the microecological structure changes and correlation in blood, lung tissue and fecal intestine of mice with sepsis and acute lung injury.Methods:A total of 12 healthy male C57BL/6J mice were divided into the cecal ligation and perforation (CLP) group and sham operation (sham) group by random number table method, with six mice in each group. In the CLP group, acute lung injury model of sepsis mice was prepared by CLP method. In the sham group, only laparotomy but no perforation of cecal ligation was performed. Eye blood, lung tissue, and feces were collected from mice in each group 24 h after surgery. Lung tissue morphological changes were observed by HE staining, and 16s ribosome RNA sequencing was used to analyze the structural changes of microecology of the bacterial flora at each site in sepsis mice and find out the correlation.Results:(1) HE staining showed that mice in the CLP group had exudation into the alveolar cavity of the lung, disordered lung tissue structure, accompanied by a large number of inflammatory cell infiltration, and the lung histopathological score was significantly higher than that in the sham group ( P < 0.01). (2)α diversity analysis showed that there was no statistical significance in blood and fecal samples between the sham group and CLP group, while Ace index, Chao index and Simpson index in lung tissue samples were statistically significant ( P < 0.05). (3) β diversity analysis showed that the differences in blood and fecal samples were greater between the sham group and CLP group than that within the group, and analysis of Bray Curtis, weighted, and unweighted indexes were statistically significant ( P < 0.05). (4) At the phylum level, compared with the sham group, the abundance of Proteobacteria gradually increased, and the abundance of Firmicutes and actinobacteria was decreased in the CLP group. At the genus level, the sham group was dominated by Acinetobacter and Duchenne, while the CLP group was dominated by Escherichia coli and unclassified Enterobacter. Blood flora was more similar to lung tissue flora composition as compared with fecal flora. Conclusions:The distribution of bacterial flora in blood, lung tissue and intestine of sepsis mice with acute lung injury is partially overlapped.

Objective:To evaluate the efficacy and safety of hippocampal avoidance whole-brain irradiation with simultaneous integrated boost in the treatment of brain metastases of lung cancer.Methods:Forty lung cancer patients with brain metastases who received whole-brain radiotherapy with simultaneous integrated boost and hippocampal avoidance in Cancer Hospital, Chinese Academy of Medical Sciences from 2014 to 2020 were enrolled in this study. Brain MRI, survival follow-up and evaluation of side effects were performed before radiotherapy and at 1, 3, 6 and 12 months after radiotherapy, respectively. Overall survival (OS), progression-free survival (PFS) and changes in cognitive function were analyzed. Continuous data were described as Mean ± SD. Categorical data were described by frequency and composition ratio or percentage. Survival analysis was conducted by Kaplan-Meier method. Influencing factors of survival were identified by univariate and multivariate Cox's regression analyses.Results:A total of 40 patients were enrolled in the study. The median follow-up time was 14.2 months and the median OS, PFS and intracranial PFS of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis showed that male gender and newly diagnosed stage Ⅳ disease were associated with worse OS and PFS, respectively. The Hopkins verbal learning test-revised (HVLT-R) scores at baseline and 1, 3 and 6 months after radiotherapy were 21.94±2.99, 20.88±3.12, 20.03±3.14, and 19.78±2.98, respectively. The HVLT-R score at 6 months after radiotherapy was decreased by approximately 9.8% compared with the baseline. No grade 3 or above toxic and side effect occurred in the entire cohort.Conclusion:Hippocampal avoidance whole-brain irradiation with simultaneous integrated boost is a safe and effective treatment for brain metastases of lung cancer, which is expected to reduce the impact of radiotherapy on cognitive function.

Objective:To evaluate the new model of group screening combined with opportunistic screening for the diagnosis and treatment of gastric cancer.Methods:Group screening combined with opportunistic screening was used for gastric cancer screening. (1) Group screening. Cluster sampling was used to screen gastric cancer by endoscopy in high-risk population (aged 40-<70 years) of rural residents in Weihai from July 2017 to December 2020, and biopsy was obtained for histopathology if necessary. Main collection parameters included the detection rate of advanced gastric cancer, early gastric cancer and high-grade intraepithelial neoplasia (HGIN). (2) Opportunistic screening. The changes of the detection rates of early gastric cancer in opportunistic screening in 2 hospitals in Weihai area were observed during the same period of time.Results:(1) In group screening, from July 2017 to December 2020, the first batch of 8 000 cases of gastric cancer screening were completed. The cases of advanced gastric cancer, early gastric cancer and HGIN were 36, 28, and 62, respectively. The detection rates of gastric cancer and early gastric cancer were 0.80% (64/8 000) and 43.75% (28/64), respectively. The proportion of early gastric cancer+HGIN who received endoscopic submucosal dissection (ESD) was 77.78% (70/90), and the rate of curative resection was 100.00%(70/70). (2) Opportunistic screening: from July 2017 to December 2020, the annual early gastric cancer detection rates in opportunistic screening in Wendeng District Traditional Chinese and Western Medicine Hospital were 16.67% (1/6), 20.00% (3/15), 23.53% (4/17), and 33.33% (6/18) in the consecutive 4 years, respectively. The annual detection rates of early gastric cancer in opportunistic screening in Ru Shan Peoples Hospital were 14.74% (14/95), 23.80% (60/252), 25.49% (65/255), and 24.04% (50/208), respectively. The detection rates of opportunistic screening for early gastric cancer in hospitals in Weihai city increased year by year.Conclusion:In areas with high incidence of gastric cancer, a certain scale of group screening can lead to a wider range of opportunistic screening, resulting in the increase of the detection rate of early gastric cancer. The new model of diagnosis and treatment of gastric cancer is worth recommendation.

Objective:To explore the effect of short-chain fatty acid (SCFA) on acute lung injury (ALI) in sepsis via macrophage polarization.Methods:① Clinical trial: 30 sepsis patients admitted to the intensive care unit (ICU) of General Hospital of Ningxia Medical University from January to December in 2022 and 10 non-sepsis patients in the same period were enrolled, stool samples were collected on the first day of admission, and SCFA butyric acid level in the two groups were studied by targeted metabolomics. ② Animal experiment: male C57BL/6J mice were selected and randomly divided into sham operation group (Sham group), sepsis caused by cecal ligation and perforation (CLP group) and SCFA intervention group (SCFA group, sodium butyrate 25 mg/kg was given by gavage 1 hour after CLP), with 6 animals in each group. Twenty-four hours after molding, the state of mice was evaluated by mouse sepsis score (MSS), the degree of pulmonary edema was evaluated by calculating the wet/dry ratio (W/D), and the pathological changes of lung tissue were observed by hematoxylin-eosin (HE) staining, and lung injury score was performed. The serum levels of tumor necrosis factor-α (TNF-α), interleukins (IL-1β, IL-6, IL-10), nuclear factor-κB (NF-κB), and transforming growth factor-β (TGF-β) were detected by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to measure the mRNA expressions of inflammatory factors TNF-α, IL-1β, IL-6 and antioxidant factor nuclear factor E2-related factor 2 (Nrf2) in lung tissue. The expressions of macrophage polarization markers arginin-1 (ARG-1), CD206, inducible nitric oxide synthase (iNOS) and IL-1β in lung tissue were detected by immunohistochemistry.Results:① Compared with non-sepsis patients, SCFA-butyric acid level was significantly reduced in patients with sepsis (μg/g: 34.56±6.61 vs. 1 150.67±381.90, P < 0.01). ② Compared with the Sham group, MSS, lung W/D ratio, lung injury score, the levels of serum inflammatory factors TNF-α, TGF-β, NF-κB, IL-10, IL-6, IL-1β, the mRNA expressions of lung tissue inflammatory factors and antioxidant factor Nrf2, M1 macrophage polarization markers ARG-1, CD206 and M2 macrophage polarization markers iNOS and IL-1β were significantly increased in the CLP group. Compared with the CLP group, MSS, lung W/D ratio, lung injury score, the levels of serum inflammatory factors TNF-α, TGF-β, NF-κB, IL-10, IL-6, IL-1β, the mRNA expressions of lung tissue inflammatory factors and antioxidant factors Nrf2, and M1 macrophage polarization markers ARG-1 and CD206 were significantly reduced [MSS: 14.50±3.16 vs. 20.00±1.55, lung W/D ratio: 4.60±0.18 vs. 5.51±0.59, lung injury score: 47.56±2.36 vs. 88.30±6.04, serum TNF-α (ng/L): 27.99±0.58 vs. 69.55±18.53, serum TGF-β (μg/L): 9.82±2.16 vs. 18.73±1.83, serum NF-κB (μg/L): 1.23±0.09 vs. 1.95±0.28, serum IL-10 (ng/L): 78.39±2.29 vs. 140.22±19.82, serum IL-6 (ng/L): 300.64±77.60 vs. 1 442.52±494.14, serum IL-1β (ng/L): 33.13±0.99 vs. 38.39±1.31, lung IL-1β mRNA expression (IL-1β/β-actin): 1.01±0.01 vs. 2.24±0.62, lung IL-6 mRNA expression (IL-6/β-actin): 0.63±0.09 vs. 1.46±0.31, lung TNF-α mRNA expression (TNF-α/β-actin): 0.81±0.33 vs. 2.57±0.64, lung Nrf2 mRNA expression (Nrf2/β-actin): 1.59±0.25 vs. 2.96±0.89, ARG-1 positive area: (36.27±2.89)% vs. (49.75±5.03)%, CD206 positive area: (20.02±3.26)% vs. (44.24±3.61)%, all P < 0.05]. However, there was no significant difference in M2 macrophage polarization markers iNOS and IL-1β expression [iNOS positive area: (18.32±2.23)% vs. (21.77±3.57)%, IL-1β positive area: (40.42±4.78)% vs. (42.14±4.22)%, both P > 0.05]. Conclusion:SCFA may alleviate ALI in sepsis by reducing M1 polarization of pulmonary macrophages.

Objective:To evaluate the safety and tolerance of sequential thoracic radiotherapy combined with PD-1/PD-L1 inhibitors in patients with extensive-stage small cell lung cancer (ES-SCLC) after induction systemic therapy.Methods:ES-SCLC patients from a phase I trial and a real-world study were enrolled for those who received thoracic radiotherapy after induction systemic treatment (chemotherapy/chemotherapy combined with PD-1/PD-L1 inhibitors) and consolidated with PD-1/PD-L1 inhibitors. These two studies were both approved by the Ethics Committee of Chinese Academy of Medical Sciences Cancer Hospital (Clinical Trials.gov number, NCT03971214, NCT04947774).Results:Between January 2019 and March 2021, a total of 11 patients with ES-SCLC were analyzed, aged 52-73 years, with a median age of 62 years. Among them, five patients (45.5%) received induction chemotherapy and six patients (54.5%) received chemotherapy combined with PD-1/PD-L1 inhibitor, and then all received intensity-modulated thoracic radiotherapy after evaluation of systemic treatment efficacy. Two patients developed treatment-related grade G3-5 toxicity (18.2%, 1 treatment-related pneumonitis and 1 radiation esophagitis). G 1-G 2 hematologic toxicity, pneumonia, and anorexia were common mild toxicities. Only one patient (9.1%) terminated immunotherapy due to immune-related pneumonitis. During a median follow-up time of 12.5 months (range: 3.5-16.4 months), the median disease progression-free survival and overall survival was 7.4 months (95% CI: 6.9-8.0 months) and 14.6 months (95% CI: 9.0-20.2 months), respectively. Conclusions:Sequential thoracic radiotherapy followed by PD-1/PD-L1 inhibitor is safe and feasible in patients with ES-SCLC after induction therapy. Given that both thoracic radiotherapy and immunotherapy benefits the ES-SCLC in survival, this comprehensive treatment modality warrants further investigation.

Objective:Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy.Methods:Patients diagnosed with treatment-naive and confirmed limited-stage SCLC were eligible. Participants were randomly assigned (1: 1) to receive simultaneous integrated boost radiotherapy (PGTV 60.2 Gy/2.15 Gy/28F, PTV 50.4 Gy/1.8 Gy/28F) or conventional fractionated radiotherapy (PTV 60 Gy/2 Gy/30F). The primary endpoint was 2-year progression-free survival, and the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity.Results:Between February 2017 and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among whom 106 patients in the conventional fractionated radiotherapy group and 110 patients in the simultaneous integrated boost radiotherapy group. The median follow-up time was 37 months (95% CI: 35.2-38.7). The 2-year progression-free survival rates were 45.2% vs. 38.2%( HR=1.22, 95% CI: 0.87-1.72, P=0.2). The 2-year overall survival rates were 73.5% vs. 60.9%( HR=1.35, 95% CI: 0.90-2.04, P=0.14). The 2-year local-regional recurrence-free survival rates were 68.7% vs. 69.9%( HR=0.98, 95% CI: 0.62-1.56, P=1.0). Multivariate analysis showed that early radiotherapy yielded better 2-year progression-free survival, overall survival and local-regional recurrence-free survival than delayed radiotherapy in two groups ( HR=1.69, 95% CI: 1.18-2.41, P=0.003; HR=1.72, 95% CI: 1.09-2.70, P=0.018; HR=1.66, 95% CI: 1.01-2.73, P=0.046). Tumor staging was an influencing factor of overall survival (stage Ⅲ vs. stage Ⅰ-Ⅱ, HR=3.64, 95% CI: 1.15-11.57, P=0.028). The most common grade 3-4 adverse events were myelosuppression (21.7% vs. 15.4%, P=0.83), radiation pneumonitis (4.7% vs. 2.7%, P=0.44) and radiation esophagitis (3.8% vs. 1.8%, P=0.51). Conclusions:Simultaneous integrated boost radiotherapy yields equivalent efficacy and toxicities to conventional fractionated radiotherapy for limited-stage small cell lung cancer. Early radiotherapy can enhance clinical prognosis.

Objective:To explore the effect of pretreatment body mass index (BMI) on the prognosis of patients with unresectable locally advanced non-small cell lung cancer (NSCLC) after chemoradiotherapy.Methods:The clinical data of 711 patients with locally advanced NSCLC treated with radiotherapy, sequential chemoradiotherapy or concurrent chemoradiotherapy from January 2013 to December 2017 in Cancer Hospital of Chinese Academy of Medical Science and Peking Union Medical College were retrospectively analyzed. Radiotherapy was performed with intensity-modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT), and the chemotherapy regimens were paclitaxel+carboplatin, pemetrexed+cisplatin or etoposide+cisplatin. The effects of pretreatment BMI and other clinical factors on overall survival (OS) of patients were analyzed. Survival analysis was performed by using Kaplan-Meier method; univariate and multivariate analyses were performed by using Cox proportional hazards model.Results:According to the World Health Organization (WHO) recommended BMI grouping method for Asian, the median OS time of low BMI group (<18.5 kg/m 2, 23 cases), normal BMI group (18.5-23.9 kg/m 2, 293 cases) and high BMI group (≥24.0 kg/m 2, 395 cases) was 17 months (95% CI 11-29 months), 29 months (95% CI 22-36 months) and 30 months (95% CI 27-34 months), respectively. OS in the low BMI group was poorer than that in the normal BMI group and high BMI group ( χ2 = 11.20, P = 0.004). Maximally selected rank statistics was used to determine the optimal cut-off value of BMI for prediction of survival as 21.31 kg/m 2, according to which patients were divided into low BMI group (BMI<21.31 kg/m 2, 130 cases) and high BMI group (BMI≥21.31 kg/m 2, 581 cases), the median OS time of the two groups was 20 months (95% CI 17-27 months) and 32 months (95% CI 28-35 months), respectively. OS in the low BMI group was poorer than that in the high BMI group ( χ2 = 12.30, P < 0.001). Multivariate analysis showed that age ≥ 65 years old, male, Karnofsky score < 80 points, low BMI, smoking, histological type of squamous cell carcinoma and radiotherapy alone were independent risk factors for OS (all P < 0.05). Conclusions:For patients with unresectable locally advanced NSCLC who received chemoradiotherapy, those with low pretreatment BMI have poor prognosis.

Objective:To analyze the clinical characteristics, risk factors and prognosis of early septic patients with bloodstream infection (BSI) in department of critical care medicine of Ningxia Medical University General Hospital.Methods:Patients with sepsis admitted to department of critical care medicine of Ningxia Medical University General Hospital from November 1, 2019 to August 31, 2021 were included in a prospective observational study. Blood samples were collected for culture within 24 hours of sepsis diagnosis. General information, laboratory test indicators and blood culture results within 24 hours of sepsis diagnosis were recorded. Patients were followed up and prognostic indicators [mechanical ventilation time, length of intensive care unit (ICU) stay, and 28-day survival] were observed. According to blood culture results, patients were divided into BSI group and non-BSI group. Univariate and multivariate Logistic regression analysis were performed on the general clinical characteristics of patients in the two groups to screen the risk factors of early BSI in septic patients. Receiver operator characteristic curve (ROC) was drawn to evaluate the predictive value of risk factors for early BSI in septic patients.Results:A total of 202 septic patients were included in this study, with 62 patients in BSI group and 140 patients in non-BSI group. The majority of patients in the BSI group were associated with abdominal infection (61.3%), and the majority of patients in the non-BSI group were associated with pulmonary infection (49.3%). A total of 76 strains were isolated from septic patients in BSI group, and the most common pathogens were Escherichia coli (26 strains, 34.2%), Klebsiella pneumoniae (11 strains, 14.4%), Enterococcus (7 strains, 9.2%), Bacteroides fragilis (6 strains, 7.9%) and Staphylococcus aureus (6 strains, 7.9%). There were no significant differences in mechanical ventilation time, the length of ICU stay and 28-day mortality between the BSI group and the non-BSI group. The difference of variables was statistically significant between two group according to Univariate analysis, which included body temperature, acute physiology and chronic health score Ⅱ (APACHEⅡ), use of antibiotics before admission to ICU, abdominal infection, hypersensitivity C-reactive protein (hs-CRP), serum creatinine (SCr), total bilirubin (TBil), platelet count (PLT), blood lactic acid (Lac) and hypercalcitonin (PCT). Multivariate analysis showed that low PLT [odds ratio ( OR) = 1.004, P = 0.019], high Lac ( OR = 1.314, P = 0.002), high body temperature ( OR = 1.482, P = 0.027), concomitant abdominal infection ( OR = 2.354, P = 0.040), no use of antibiotics before admission to ICU ( OR = 2.260, P = 0.049) were independent risk factors for early BSI in septic patients. The area under ROC curve (AUC) of PLT, Lac, body temperature, abdominal infection and no use of antibiotics before admission to ICU for predicting early BSI in septic patients were 0.711, 0.686, 0.594, 0.592 and 0.590, respectively. Youden index was used to calculate the optimal cut-off values, which was PLT 122.50×10 9/L, Lac 2.95 mmol/L, body temperature 39.45 ℃, respectively. The highest level of AUC was 0.754, the sensitivity was 75.8%, and the specificity was 68.8%, which were observed when the 5 items were combined. Conclusions:Early septic patients with BSI are more serious than those without BSI. Low PLT, high Lac, high temperature, concomitant abdominal infection and no use of antibiotics before admission to ICU are independent risk factors for early BSI in septic patients, and the combination of these five factors has good predictive value.