Large cell neuroendocrine carcinoma(LCNEC)of lung is a rare neuroendocrine carcinoma subtype with difficulty in early diagnosis and poor prognosis which is treated with standard strategies of small cell lung cancer and non-small cell lung cancer.In recent years,the precise types of LCNEC and its response to therapy have been identified by next-generation sequencing.Some researches have also found the correlation between different subtypes of LCNEC and the efficacy of chemotherapy regimens.However,there is no consensual agreement of its therapy.Recently,immune checkpoint inhibitors(ICIs)has provided a new option for LCNEC patients based on some retrospective research data and case reports.In this review,we aimed to summarize the epidemiological characteristics,standard therapy,the advances of molecular subtypes and clinical applications of ICIs of LCNEC,so as to provide optimal systemic clinical decision-making for LCNEC patients.

Objective To conduct basic research on the structure and function of the heart in cynomolgus monkeys older than 10 years to provide data for animal selection in elderly disease research.Methods A total of 144 cynomolgus monkeys＞10 years old were selected as research subjects,including 37 females and 66 males in the 10～15 years group,and 21 females and 20 males in the 16～20 years group.Basic data on cardiac structure and function in middle-aged and elderly cynomolgus monkeys were obtained through comparative analysis of general indicators(body mass index,blood pressure,and heart rate),blood biochemical indicators(blood glucose,blood lipids,and ion indicators),and cardiac structure and function indicators.Results General indicators for the 10～15 years and 16～20 years groups were compared.As age increased,the blood pressure and heart rate of female and male monkeys increased,and there was a significant difference in blood pressure changes between male monkeys.A comparison of two sets of blood biochemical indicators showed that,as age increased,blood glucose,triglycerides,total cholesterol,low-density lipoprotein cholesterol,blood calcium,blood sodium,and blood potassium increased,while lactate dehydrogenase decreased,in female and male monkeys.Among these,blood glucose,triglycerides(males),total cholesterol,high-density lipoprotein cholesterol(males),low-density lipoprotein cholesterol(males),blood calcium,blood sodium,blood potassium,and lactate dehydrogenase showed significant changes.A comparison of cardiac contractile function between the two groups showed that,as age increased,the anterior and posterior diameters of the left atrium significantly decreased in both female and male monkeys.Female monkeys showed a significant decrease in the interventricular septal end systolic diameter,left ventricular end diastole and systolic diameters,left ventricular end diastolic and systolic volumes,and left ventricular mass index,while no significant changes were seen in male monkeys.A comparison of diastolic function between the two groups showed that,as age increased,the late diastolic velocity of the mitral valve decreased significantly in male monkeys,while the early diastolic velocity of the left ventricular sidewall increased significantly in female monkeys.Correlation analysis was conducted between the metabolic indicators and the cardiac structure and function indicators of female and male monkeys.The correlations between metabolic indicators and cardiac structure and function indicators were weak in female monkeys,for which the maximum absolute Γ value did not exceed 0.39.However,the correlations between metabolic indicators and cardiac structure and function indicators were relatively strong in male monkeys,for which the maximum absolute Γ value reached 0.66.Conclusions Based on ultrasound analysis combined with metabolic indicators,the heart function of cynomolgus monkeys was studied,and basic data related to the structure and function of the heart in middle-aged and elderly cynomolgus monkeys were obtained.As age increased,blood glucose and lipid indicators increased in cynomolgus monkeys,while cardiac systolic and diastolic functions show a downward trend,similar to changes in middle-aged and older adult human populations.These data provide support for animal selection in research on age-related diseases related to heart function.

BACKGROUND: Immune checkpoint inhibitors (ICIs) therapy lacks viable biomarkers for response and prognosis prediction. This study aimed to investigate the correlation of peripheral blood laboratory test results combined with lymphocyte subset ratios to the response and prognosis of immunotherapy in advanced lung cancer. METHODS: Advanced lung cancer patients admitted to West China Hospital, Sichuan University from May 2021 to July 2023 were prospectively enrolled in this study. Clinical data and peripheral blood were collected before and after treatment and lymphocyte subset ratios were analyzed by flow cytometry. Logistic regression was used to identify factors correlated to ICIs treatment efficacy. Cox modeling was applied to explore the prognostic factors. RESULTS: Logistic regression showed that the baseline level of transcription factor T cell factor 1 (TCF1)+CD8+ T cell ratio and peripheral white blood cell (WBC) count, lymphocyte percentage, cytokeratin 19 fragment (CYFRA21-1) after 1 cycle of ICIs treatment were the potential predictors for ICIs response (P<0.05). Cox regression analysis showed that the baseline level of TCF1+CD8+ T cell ratio (P=0.020) and peripheral WBC count after 1 cycle of ICIs treatment (P<0.001) were prognostic factors. CONCLUSIONS Patients with high baseline TCF1+CD8+ T cell ratio combined with low WBC counts and low CYFRA21-1 level after 1 cycle of ICIs treatment are more likely to benefit from ICIs therapy.
Humans ; Lung Neoplasms/drug therapy* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; T Cell Transcription Factor 1/genetics* ; Prognosis ; CD8-Positive T-Lymphocytes ; Immunotherapy

Immunotherapy has significantly improved clinical outcomes of non-small cell lung cancer (NSCLC), however, along with the popularization of immunotherapy, immune resistance has become an unavoidable problem. Immunotherapy can induce extensive cellular and molecular alterations in the tumor microenvironment. Considering the mechanisms of immune resistance are not yet fully understood and the efficacy of standard chemotherapy regimens is limited, more effective coping strategies based on resistance mechanisms are urgently needed. In this review, we intend to summarize the known mechanisms of immune resistance and feasible strategies, so as to provide a foundation for clinicians to develop more individualized and precise regimens and finally improve patients' prognosis.
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Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Prognosis ; Immunotherapy ; Tumor Microenvironment

Neoadjuvant chemoradiotherapy (nCRT)+ total mesorectal excision (TME) has become the standard mode of treatment for locally advanced rectal cancer(LARC). However, the sensitivity of different patients to nCRT varies greatly, some patients can get pathological complete response (pCR), and their long-term survival is significantly improved, Some patients'tumors continue to progress, therefore, accurate prediction of whether pCR can be achieved after nCRT is very important for guiding individualized treatment of patients. Current studies have shown that some accessible clinical factors, such as age, pathological types of tumors, TNM staging, circumferential extent of tumor, distance to the anal verge, CEA level, neutrophil lymphocyte ratio, can be used to predict whether pCR can be achieved.This article reviews the progress of clinical predictors of pCR in LARC after nCRT.

Objective:To explore the relationship between doing housework and gait speed(GS)in order to identify ways to maintain physical capability in elderly people.Methods:A nationwide cross-sectional survey was conducted from Jan.2011 to Dec.2011.Subjects in this survey, with a sample of 2 519 males and 2 541 females aged ≥60 years, came from six regions across the country and satisfactorily completed a GS test.A GS in the lower 20% of the reference population(<0.7 m/s)was used as the cut-off point to define slow GS(SGS). Housework was defined as activities such as house cleaning, shopping, cooking and taking care of grandchildren and a response of"often"(≥5 d/week)was considered as doing housework.Propensity Score Matching(PSM)was performed to select comparable sub-groups of the study population to evaluate the association between housework and GS.Results:There were 3 290 subjects(1 645 pairs)selected by PSM.Logistic regression analysis showed that doing housework was inversely associated with SGS, and housework activities reduced the risk of SGS by 60%( OR=0.40, 95% CI: 0.35-0.46, P<0.01). Conclusions:Elderly people who conduct housework often are more likely to maintain GS and therefore should be encouraged to engage in daily activities to help maintain adequate physical performance.

Objective To investigate the changes of coagulatory function in septic rats induced by cecal ligation and puncture(CLP). Methods Cecal ligation and puncture(CLP)were performed to induce sepsis in SD rats. Coagulation indexes were detected at 8,16 and 48 h after operation, and histopathological changes of the lung, kidney, liver and spleen were examined using HE staining. Results The 12-day survival rate of the CLP-induced septic rats was 30%,with an acute onset and high mortality. In the acute phase of disease development of the CLP rats, the activated partial thromboplastin time(APTT)was prolonged(P<0.05)at 8 h,the prothrombin time(PT)was prolonged at 16 h (P<0.05), the factor XII activity in the endogenous coagulation pathway and the factor VII activity in the extrinsic coagulation pathway showed a transient inhibition, the thrombin time(TT)was prolonged at 48 h(P<0.01), and the content of fibrinogen(FIB)was increased gradually from 16 h(P<0.001). Among the other important coagulation and anticoagulation indexes,the number of platelets(PLT)was decreased gradually from 8 h(P<0.01),while the number of vWF:Ag increased gradually from 8 h(P<0.001). The D-dimer amount gradually increased from 16 h(P<0.05),and the amount of PS:Ag significantly decreased until 48 h(P<0.001). However, there was no significant change in the antithrombin-III(AT-Ⅲ)content. The histopathological examination showed that there are different degrees of damages in the lung,kidney,liver and spleen tissues,but no obvious venous thrombosis and bleeding were found. Conclusions In the acute phase,there is coagulatory dysfunction in the septic rats,however,no histopathological changes such as venous thrombosis and bleeding were observed in the lung,kidney,liver and spleen tissues due to coagulatory dysfunction.

Objective Previous studies suggested that overerpression of Slit2 results in abnormal Alzheimer's disease-like behavior and cognition impairment in mice. The aim of this study is to investigate the relationship between overerpression of Slit2 and accumulation and clearance of amyloid-β in aging mice by comparing the differential expression of genes for accumulation and clearance of amyloid-β in aging Tg-Slit2 and Tg-2576 mice. Methods 14-month old male C57BL/6, Tg-Slit2 and Tg-2576 mice were used to detect the expression of Aβ1 - 40 and Aβ1 - 42 in brain by immunohistochemistry. Further, the total RNA in the brain of these mice were extracted, identified and inversely transcripted to cDNA, then the cDNA was detected by PCR array. The expression of genes in the brain of Tg-Slit2 and Tg-2576 mice were analyzed. Results Comparing with the Tg-2576 mice in the same age, accumulation of Aβ was not found in the brain of Tg-Slit2 and C57BL/6 mice. The result from PCR array analysis showed that comparing with the same aged C57BL/6 mice, there were 16 up-regulated genes and 8 down-regulated genes in the brain of Tg-Slit2 mice and 14 up-regulated genes and 17 down-regulated genes in the brain of Tg-Slit2 mice. The expression of amyloid beta precursor protein (APP) in the brain of the three group mice was not changed. The expression of presenilin 2 ( Psen2) related with Aβ production was significantly up-regulated in the Tg-2576 mice. In addition, the expression of low density lipoprotein receptor-related protein ( LRP) 6 and 9 were markedly decreased in the Tg-2576 mice. Notably, these genes were not changed in the brain of the aging Tg-Slit2 mice. Conclusions The accumulation of Aβ in the brain are not found in 14-month Tg-Slit2 mice, In addition, different from Tg-2576 mice, the significant changes of expression of Aβ-related genes is not found in the brain of Tg-Slit2 mice.

Objective To investigate the ultrasonographic characteristics,pathological diagnosis and surgical treatment strategy of follicular thyroid carcinoma (FTC).Methods The clinical data of 10 patients with FTC confirmed by histopathology from Jul.2013 to Oct.2017 in Beijing Friendship Hospital,Capital Medical University were retrospectively analyzed including 3 males and 7 females with mean age of 41.5 (15 to 68) years old.The clinical data including preoperative ultrasonographic features,fine needle aspiration results,intraoperative frozen section examination and surgical treatments of these 10 patients were retrospectively analyzed.Descriptive methods were used for Statistical analysis.Results Ultrasonography was performed in all 10 patients,and frozen section examination was performed in 6 patients,of which,5 were considered capsular invasion.Ipsilateral centralcompartment neck dissection was performed in 2 patients,no node metastasis was found.Reoperation were performed in 5 patients with total or near total thyroidectomy.No severe complications such as persistent hypoparathyroidism and recurrent laryngeal nerve injury occurred in all 10 patients.The median follow-up time was 34.4 months,and no one died during the follow-up period.Conclusions Preoperative diagnosis of FTC is difficult.The reoperation rate is higher than that of papillary thyroid carcinoma.Lobectomy plus isthmusectomy should be the initial surgical procedure for follicular tumors,while neck dissection is not recommended.

Background and objective Lung cancer is the most common malignancy and is the leading cause of cancer-related death worldwide. Thus, this disease severely threatens human health. This study aims to identify the relationships between serum albumin and urea level and the clinical pathological characteristics and survival time in patients with lung can-cer.Methods A total of 1,098 patients with lung cancer were diagnosed by pathology and tested the serum albumin and urea level in West China Hospital of Sichuan University during January 2008 to December 2013. According to the levels of albumin and urea, patients were divided into the normal level group (negative group) and abnormal level group (positive group). The differences of patients' clinical pathological characteristics and survival time in the two groups were analyzed.Results Differ-ences in age, sex, histological classification, liver metastasis and pleural metastasis were statistically significant between the two groups of serum albumin (P<0.05). Differences in age, intrapulmonary metastasis of 312 patients of squamous cell carcinoma and differences in age, sex, stages, pleural metastasis of 612 patients of adenocarcinoma between the two groups of serum al-bumin (P<0.05). There were no significant differences between the two groups of urea. In different histological classification between the two groups of serum albumin, the median survival period of squamous cell carcinoma was 36 months and 19 monthes, adenocarcinoma was 35 months and 15 monthes, the abnormal group were all significantly lower than those in the normal group. The median survival period was no significant difference between the two groups of urea.Conclusion The level of serum albumin is an important indicator for prognosis.