Objective:To explore the predictive and prognostic value of prognostic nutritional index(PNI)for patients with locally advanced esophageal squamous cell carcinoma(ESCC)undergoing induction chemotherapy combined with immune sequential radiotherapy.Methods:A retrospective analysis was conducted on clinical data from 126 locally advanced ESCC patients who had undergone induction chemotherapy combined with immune sequential radiotherapy at Zhejiang Cancer Hospital between May 2019 and August 2023.Receiver operating characteristic(ROC)curves were used to determine optimal PNI cutoff values within 1 week before induction chemoimmunotherapy,within 1 week before radiotherapy,and at 4±1 weeks after radiotherapy initiation,with subsequent patient stratification.The Kaplan-Meier method was used to generate survival curves and the log-rank test was used to compare overall survival(OS)and progression-free survival(PFS)between groups.Cox regression analysis was employed to identify factors affecting the prognosis of locally advanced ESCC patients undergoing induction chemoimmunotherapy combined with sequential radiotherapy.Results:A total of 126 locally advanced ESCC patients,118 males and 8 females,with a median age of 65 years(44-78 years)were included.The optimal critical values of PNI before induction chemoimmunotherapy,before radiotherapy and during radiotherapy identified using ROC curves were 46.2,48.3 and 37.9.The median OS and PFS were 47.3 and 28.2 months in the group with PNI≥48.3 before radiotherapy,and 18.7 and 15.2 months in the group with PNI<48.3 before radiotherapy,respectively(P<0.01,P<0.05).The median OS was not reached and the median PFS was 25.7 months in the group with PNI≥37.9 in radiotherapy,and the median OS and PFS were 17.0 and 12.5 months in the group with PNI<37.9 in radiotherapy,respectively(P<0.01,P<0.05).The median OS was not reached and the median PFS was 28.4 months in the group with elevated PNI after induction chemoimmunization;the median OS and PFS were 20.4 and 16.0 months in the group with reduced PNI(P<0.01,P<0.05).Multifactorial analysis showed that PNI in radiotherapy[HR=2.292,95%CI(1.264,4.159),P<0.05],and change in PNI after induction of chemoimmunization[HR=2.120,95%CI(1.007,4.463),P<0.05]were factors affecting OS.Conclusion:PNI during radiotherapy and changes in PNI after induction chemoimmunity correlate with patients'treatment efficacy and prognosis,and can be used as important indicators to predict the benefits of induction chemoimmunization combined with sequential radiotherapy for ESCC.

Objective:To understand the influence of unhealthy lifestyle on diabetic dyslipidemia and the key influencing factors in occupational population and provided scientific evidence for the prevention of diabetic dyslipidemia.Methods:Based on baseline data and follow-up data of Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd. during 2021. Diabetic dyslipidemia was defined as diabetes plus one or more forms of dyslipidemia, and unhealthy lifestyle factors included smoking, alcohol consumption, unhealthy dietary patterns, low physical activity, and abnormal BMI. Multivariate logistic regression model was used to analyze the relationship between unhealthy lifestyle scores and diabetic dyslipidemia, network analysis was used to find and explore the key lifestyles influencing glycolipid metabolism.Results:A total of 25 631 subjects were included. People with unhealthy lifestyle score 2 and 3 were 1.93 (95% CI: 1.31-2.86) times and 2.37 (95% CI: 1.60-3.50) times more likely to have diabetes with ≥1 forms of dyslipidemia than those with scores of 0; People with unhealthy lifestyle score 1, 2 and 3 were 1.98 (95% CI: 1.08-3.61) times, 2.87 (95% CI: 1.60-5.14) times and 3.95 (95% CI: 2.22-7.06) times more likely to have diabetes with ≥2 forms of dyslipidemia than those with score 0. Network analysis found that abnormal BMI and HDL-C were the "bridge nodes" that link unhealthy lifestyles with diabetic dyslipidemia. Conclusion:The higher the score of unhealthy lifestyle, the higher the risk for diabetic dyslipidemia, abnormal BMI and HDL-C are key factors influencing the association between unhealthy lifestyle and diabetic dyslipidemia.

Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.

Objective:To analyze the failure patterns and survival after stereotactic body radiotherapy (SBRT) in patients with T 1-2N 0M 0 non-small cell lung carcinoma (NSCLC). Methods:Clinical data of early-stage NSCLC patients who received SBRT at Zhejiang Cancer Hospital from January 2012 to September 2018 were retrospectively analyzed. The primary observed endpoint was the pattern of disease progression, which was divided into intra-field recurrence, regional lymph node recurrence and distant metastasis. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier method. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox's model.Results:A total of 147 patients with 156 lesions were included. The median follow-up time was 44.0 months (16.5-95.5 months). A total of 57 patients (38.8%) progressed: 14 patients (24.5%) had recurrence with the 1-, 3-, and 5-year local recurrence rates of 2.0%, 10.9%, and 14.3%, respectively; 36 patients (63.2%) had Distant metastasis with the 1-, 3- and 5-year distant metastasis rates of 12.2%, 22.4% and 28.6%, respectively; and 7 patients (12.3%) had recurrence complicated with distant metastasis. The 3-, 5- and 7-year OS rates were 80.5%, 64.2% and 49.9% for all patients, respectively. The median OS was 78.4 months. The 3-, 5- and 7-year PFS rates were 64.8%,49.5% and 41.5%, with a median PFS of 57.9 months (95% CI: 42.3-73.5 months). Univariate and multivariate analyses showed that biologically equivalent dose and age were the factors affecting the efficacy of SBRT (both P<0.05). Conclusion:Distant metastasis is the main failure pattern in patients with T 1-2N 0M 0 NSCLC after SBRT. High-risk population should be selected for further systematic treatment to improve the efficacy.

Objective To establish a new model of indocyanine green (ICG) clearance test combined with total bilirubin actual resident rate (TBARR) for predicting the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) treated with artificial liver support system (ALSS) therapy. Methods A retrospective analysis was performed for the clinical data of 136 patients with HBV-ACLF who underwent ALSS therapy in Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, from June 2017 to July 2021, and according to the prognosis at 3-month follow-up, they were divided into survival group with 92 patients and death group with 44 patients. Related indicators were measured at the time of the confirmed diagnosis of ACLF, including biochemical parameters, coagulation, indocyanine green retention rate at 15 minutes (ICGR 15 ), and effective hepatic blood flow (EHBF), and related indices were calculated, including Model for End-Stage Liver Disease (MELD) score, MELD difference (ΔMELD), Child-Turcotte-Pugh (CTP) score, total bilirubin clearance rate (TBCR), total bilirubin rebound rate (TBRR), and TBARR. The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups; the chi-square test was used for comparison of categorical data between groups. A binary logistic regression analysis was used to establish a combined predictive model for the prognosis of HBV-ACLF after ALSS therapy. The area under the ROC curve (AUC) was used to compare the accuracy of various models in judging the short-term prognosis of patients with HBV-ACLF after ALSS therapy, and the Z test was used for comparison of AUC. Results There were significant differences between the death group and the survival group in MELD score, ΔMELD, CTP score, ICGR 15 , EHBF, TBRR, TBARR, neutrophil count, percentage of neutrophils, lymphocyte count, platelet count, alkaline phosphatase, gamma-glutamyl transpeptidase, total bilirubin, albumin, prothrombin time, international normalized ratio, prothrombin time activity, prealbumin, fibrinogen, serum sodium, age, and the incidence rate of hepatic encephalopathy (all P < 0.05). The multivariate logistic regression analysis showed that age (odds ratio [ OR ]=1.096, 95% confidence interval [ CI ]: 1.056-1.137, P < 0.001), neutrophil count ( OR =1.214, 95% CI : 1.044-1.411, P =0.012), TBRR ( OR =0.989, 95% CI : 0.982-0.996, P =0.001), TBARR ( OR =1.073, 95% CI : 1.049-1.098, P < 0.001), ΔMELD ( OR =1.480, 95% CI : 1.288-1.701, P < 0.001), CTP score ( OR =2.081, 95% CI : 1.585-2.732, P < 0.001), and ICGR 15 ( OR =1.116, 95% CI : 1.067-1.168, P < 0.001) were independent influencing factors for short-term mortality in patients with HBV-ACLF after ALSS therapy. The binary logistic regression analysis was used to establish four combined predictive models for predicting the prognosis of HBV-ACLF after ALSS therapy, i.e., TBRR-ICGR 15 , TBARR-ICGR 15 , TBARR-ICGR 15 -ΔMELD, and TBARR-ICGR 15 -ΔMELD-age, with an AUC of 0.830, 0.867, 0.900, and 0.917, respectively, and the combined predictive models had a larger AUC than each index alone (age, neutrophil count, TBRR, TBARR, ΔMELD, MELD score, CTP score, and ICGR 15 ), among which the TBARR-ICGR 15 -ΔMELD-age model had the largest AUC. The combined models TBARR-ICGR 15 -ΔMELD and TBARR-ICGR 15 -ΔMELD-age had sensitivities and specificities of > 80%. Conclusion The combined predictive model established by ICGR 15 and TBARR has a good value for in predicting the short-term prognosis of patients with HBV-ACLF after ALSS therapy, and the combined predictive model has a better accuracy than the single model in judging prognosis.

Objective:To evaluate the 5-year survival outcome of patients with unresectable locally advanced non-small cell lung cancer (NSCLC) treated with Endostar in combination with platinum-based concurrent chemoradiotherapy.Methods:From March 2009 to June 2015, 115 patients with the unresectable locally advanced NSCLC from two prospective studies[Clinical trials 2009-2012(ClinicalTrials.gov NCT01894) and 2012-2015(ClinicalTrials.gov, NCT01733589)] were treated with Endostar in combination with platinum-based concurrent chemoradiotherapy. A total dose of 60-66 Gy was delivered in 30-33 fractions. Endostar was given 1 week prior to the beginning of radiotherapy, and repeated fortnightly during the concurrent chemoradiotherapy. After long-term follow up, survival outcome was evaluated in 104 patients treated with radiation dose of ≥60 Gy. Kaplan-Meier method was used for survival analysis. Univariate survival analysis was performed using the log-rank test.Results:Of 104 eligible patients, 60.6% of them had squamous carcinoma and 65.4% were classified in stage Ⅲ B. All the patients received ≥2 cycles of Endostar and 93.3% of them received 4 cycles of Endostar. The median follow-up time was 68.3 months. The median overall survival (OS) and median progression-free survival (PFS) were 31.3 and 13.9 months, respectively. The 3-year and 5-year OS were 45.6% and 35.7%, respectively. The 3-year and 5-year PFS were 27.1% and 24.9%, respectively. Univariate analysis indicated that sex, ECOG, pathological type, clinical stage, radiotherapy technique, chemotherapy regimen, chemotherapy cycle and cycle of Endostar use were not associated with OS. Late radiation injury occurred in 14.4% of patients, and no grade 4-5 late injury was observed. Conclusion:Patients with unresectable locally advanced NSCLC treated with Endostar fortnightly in combination with platinum-based concurrent chemoradiotherapy achieve better OS than historical data with tolerable toxicities.

BACKGROUND: Chronic noise exposure is one environmental hazard that is associated with genetic susceptibility factors that increase Alzheimer's disease (AD) pathogenesis. However, the comprehensive understanding of the link between chronic noise stress and AD is limited. Herein, we investigated the effects of chronic noise exposure on AD-like changes in senescence-accelerated mouse prone 8 (SAMP8). METHODS: A total of 30 male SAMP8 mice were randomly divided into the noise-exposed group, the control group, and aging group (positive controls), and mice in the exposure group were exposed to 98 dB SPL white noise for 30 consecutive days. Transcriptome analysis and AD-like neuropathology of hippocampus were examined by RNA sequencing and immunoblotting. Enzyme-linked immunosorbent assay and real-time PCR were used to further determine the differential gene expression and explore the underlying mechanisms of chronic noise exposure in relation to AD at the genome level. RESULTS: Chronic noise exposure led to amyloid beta accumulation and increased the hyperphosphorylation of tau at the Ser202 and Ser404 sites in young SAMP8 mice; similar observations were noted in aging SAMP8 mice. We identified 21 protein-coding transcripts that were differentially expressed: 6 were downregulated and 15 were upregulated after chronic noise exposure; 8 genes were related to AD. qPCR results indicated that the expression of Arc, Egr1, Egr2, Fos, Nauk1, and Per2 were significantly high in the noise exposure group. These outcomes mirrored the results of the RNA sequencing data. CONCLUSIONS These findings further revealed that chronic noise exposure exacerbated aging-like impairment in the hippocampus of the SAMP8 mice and that the protein-coding transcripts discovered in the study may be key candidate regulators involved in environment-gene interactions.

Objective:To analyze the feasibility of hippocampal-avoidance (HA) prophylactic cranial irradiation (PCI) in small cell lung cancer patients (SCLC)(limited stage) after chemotherapy and thoracic radiation.Methods:From June 2016 to March 2019, 40 eligible SCLC patients were recruited and randomly divided into the routine PCI ( n=22) and hippocampal-avoidance PCI (HA-PCI) groups ( n=18). The HA zone was contoured according to the criteria of RTOG 0933. Volumetric-modulated arc therapy (VMAT) was adopted in the HA-PCI group. After radiotherapy, Hopkins verbal learning test (HVLT) and MRI were performed. Results:The average hippocampus volume was (4.01±1.57) cm 3, the average HA volume was (20.13±4.14) cm 3, HA D 100% was (7.19±0.38) Gy and HA D max was (14.38±1.18) Gy. During HVLT, 1-month-after-PCI vs. before-PCI (trial3, trial4, learning, percent retained), 1-month-after-PCI vs. after-PCI (trial3, learning), HA-PCI cohort showed advantages over PCI in HVLT scores. The average follow-up time was (17.00±8.47) months. Two patients with brain metastases which were out of the HAZ received routine PCI. Conclusions:PCI using VMAT technology to protect hippocampus is feasible in dosimetry. The test results indicate that the protective effect of hippocampus protection on memory is worthy of further promotion in clinical practice.

Objective To detect the frequency of BRAF/ KRAS and PIK3CA mutations in the small cell lung cancer (SCLC) specimens from a large population of Chinese patients and to analyze the gene mutation and clinical characteristics. Methods A total of 557 samples were collected from SCLC patients from 2009 to 2014.BRAF,KRAS,PIK3CA,NRAS and MEK1 gene mutations were detected by the dideoxy sequencing. Chi-square test was adopted to analyze the correlation between clinical factors and gene mutation. Kaplan-Meier method was utilized for survival analysis. Cox model was used for multivariate prognostic analysis. Results BRAF mutations were detected in 13 out of 557 specimens. The mutation types included V600E (n= 5) ,V600A (n= 2) ,V600M (n= 1) ,D594G (n= 1),G464E (n= 1),K601R (n= 2) and S605N (n= 1).KRAS mutation was detected in 6 cases including G12C (n= 3),G12A (n= 1),G12D (n=1) andG13D (n= 1).PIK3CA mutation was observed in 4 samples including E545G (n= 2) and H1047R (n= 2).Besides,NRAS mutation (Q61R) was detected in 1 case and MEK1 mutation (D61Y) was noted in 1 case. These gene mutations were not significantly correlated with the age, gender, smoking status and clinical staging of the patients. Univariate survival analysis demonstrated the median survival time of patients with gene mutation was (10.30±0. 751) months (95％CI:8. 829-11. 771 months),significantly shorter than (12.80±0. 543) months (95％CI:11. 736-13. 864 months) of their counterparts without gene mutation (P=0. 011). Conclusions BRAF/ KRAS and PIK3CA gene mutation is detected in a small proportion of SCLC patients. These gene mutations are not significantly correlated with the clinical characteristics. Univariate survival analysis demonstrates that negative these gene mutations are negatively correlated with the clinical prognosis of SCLC patients.

Objective In view of the controversy over radiotherapy target volume for patients with limited-stage small cell lung cancer ( SCLC), a prospective randomized controlled trial was conducted to compare the impact of different radiotherapy target volumes on prognosis. Methods After 2 cycles of EP chemotherapy,patients without progressive disease were randomly assigned to receive thoracic radiotherapy (TRT) to either the post-or pre-chemotherapy primary tumour extent as study arm or control. Involved field radiotherapy (IFRT) to the entire metastatic lymph node regions was applied for both arms. TRT consisted of 45 Gy/30Fx/19 d administered concurrently with cycle 3 chemotherapy. Prophylactic cranial irradiation was administered to patients achieved complete or partial remission. Kaplan-Meier method was used for survival analysis. Results Between June 2002 and December 2017,159 and 150 patients were randomly assigned to study arm and control respectively. The 1-,2-,and 5-year local/regional control rates were 79. 4%,61. 5% and 60. 1% respectively in the study arm versus 79. 8%,66. 5%,and 57. 3% in the control arm (P=0. 73). The median OS time was 22. 1 months in the study arm (95%CI,18. 2-26. 0 months) and 26. 9 months (95%CI,23. 5-30. 3 months) in the control arm,the 1-,3-,5-,and 7-year OS rates were 81. 1%,31. 6%, 23. 9% and 22. 2% respectively in the study arm versus 85. 3%,36. 6%,26. 1% and 20. 0% in the control arm (P=0. 51).Grade 2-3 acute esophagitis was developed in 32. 9% and 43. 2% of patients respectively in study arm and control arm (P=0. 01),while grade 2-3 pulmonary fibrosis was observed in 2. 0% and 10. 9% of patients ( P= 0. 01 ) respectively. Conclusions For patients with limited-stage SCLC who received induction chemotherapy,thoracic radiotherapy can be limited to post-chemotherapy tumour extent and IFRT can be routinely applied.