Research Progress on Combination of Radiotherapy and Immunotherapy on Advanced Non-small Cell Lung Cancer with Negative Driver Genes / 肿瘤防治研究

A large proportion of patients with non-small cell lung cancer (NSCLC) are diagnosed with metastatic and incurable advanced lung cancer at the time of discovery, so these patients are given no surgical opportunity and have a low 5-year survival rate. In the era of immunotherapy, many kinds of immune checkpoint inhibitors (ICIs) have been approved as the first/second-line treatment for patients with advanced NSCLC with negative driving genes and have been combined with radiotherapy as an important treatment strategy for patients with advanced NSCLC. The innovative strategy of combining radiotherapy and immunotherapy has shown feasibility as supported by practical evidence in clinical research. A preclinical experiment of observing the immune mechanism at the molecular and cellular levels preliminarily revealed the interaction among tumor, radiation, and immune system. This paper briefly reviews the progress of combined radiotherapy and immunotherapy in the treatment of advanced NSCLC with negative drvier genes.

Correlation analysis of third lumbar skeletal muscle index and inflammatory factors and other factors in peripheral blood in gastric cancer patients / 中华临床营养杂志

Objective:To study the correlation between third lumbar skeletal muscle index(LSMI) and inflammatory factors and other factors in peripheral blood in gastric cancer patients.Methods:From October 2017 to December 2019, patients with gastric cancer admitted to West China Hospital Sichuan University were included. The LSMI of patients was obtained by dividing the area of skeletal muscle at the third lumbar vertebra level by the square of the height based on preoperative abdominal imaging data. The correlation between preoperative LSMI and inflammatory factors and other factors in peripheral blood were analyzed by person correlation analysis.Results:This study included 132 patients with gastric cancer. Among them, 39 were classified as stage Ⅰ, 36 were stage Ⅱ, and 57 were stage Ⅲ, respectively. Pearson correlation analysis suggested that the LSMI of gastric cancer patients was positively correlated with peripheral red blood cell count( P<0.01), hemoglobin( P<0.01), and prealbumin( P<0.01), and negatively correlated with interleukin-6(IL-6, P=0.027) and C-reactive protein(CRP, P= 0.014). Conclusion:Our study suggested that LSMI can be used as a nutritional index in gastric cancer patients and IL-6 and CRP played an important in the occurrence and development of sarcopenia in gastric cancer patients.

Effect of renal fibrosis after macrophage depletion in C3-deficient unilateral ureteral obstruction mice / 中华肾脏病杂志

Objective@#To investigate the effect and mechanism of renal fibrosis after macrophage depletion in C3-deficient unilateral ureteral obstruction mice.@*Methods@#Renal interstitial fibrosis model was established by unilateral ureteral obstruction (UUO) in male C3-deficient mice and age-matched C57BL/6 WT mice (8-12 weeks of age). Mice were randomly divided into 4 groups, including sham operation in wild type group (WT/sham) (n=18), UUO operation in wild type group (WT/UUO) (n=18), sham operation in C3-deficient group (C3KO/sham) (n=18), and UUO operation in C3-deficient group (C3KO/UUO) (n=18). The expression of complement C3 was detected by immunohistochemical staining and renal interstitial macrophages were assessed by immunofluorescence staining. Tubulointerstitial fibrosis was observed by both HE staining and Masson staining after 14 days of UUO. Collagen accumulation and score of tubulointerstitial injury were obtained. Wild type and C3-deficient UUO mice were treated by liposome clodronate in early or late stage respectively and then interstitially infiltrated macrophages and renal fibrosis were analysed. Mice were sacrificed randomly at 3,7,14 days after UUO and obstructed kidneys were collected. Macrophage phenotype was detected by double-labeling immunofluorescence with F4/80 and iNOS for the M1, F4/80 and CD206 for the M2 macrophage subpopulation. iNOS, Arg-1 and CD206 were also detected by western blot.@*Results@#C3 deficient mice exhibited attenuated renal fibrosis, reduced collagen accumulation and tubulointerstitial injury score compared with WT mice (P<0.01). Meanwhile, macrophage depletion in early or late stage of UUO reduced renal fibrosis in WT mice, but had no effect on C3-deficient UUO mice. Decreased accumulation of M1 macrophages and expression of iNOS, increased accumulation of M2 macrophages and expression of Arg-1, CD206 were found in C3 deficient mice compared with WT mice in early stage of UUO (P<0.01).@*Conclusion@#Renal fibrosis is not reduced after depletion of macrophages in C3 deficient UUO mice due to the altered macrophage polarization.

Effect of renal fibrosis after macrophage depletion in C3 - deficient unilateral ureteral obstruction mice / 中华肾脏病杂志

Objective To investigate the effect and mechanism of renal fibrosis after macrophage depletion in C3 - deficient unilateral ureteral obstruction mice. Methods Renal interstitial fibrosis model was established by unilateral ureteral obstruction (UUO) in male C3-deficient mice and age-matched C57BL/6 WT mice (8-12 weeks of age). Mice were randomly divided into 4 groups, including sham operation in wild type group(WT/sham)(n=18), UUO operation in wild type group(WT/UUO)(n=18), sham operation in C3-deficient group(C3KO/sham)(n=18), and UUO operation in C3-deficient group(C3KO/UUO)(n=18). The expression of complement C3 was detected by immunohistochemical staining and renal interstitial macrophages were assessed by immunofluorescence staining. Tubulointerstitial fibrosis was observed by both HE staining and Masson staining after 14 days of UUO. Collagen accumulation and score of tubulointerstitial injury were obtained. Wild type and C3-deficient UUO mice were treated by liposome clodronate in early or late stage respectively and then interstitially infiltrated macrophages and renal fibrosis were analysed. Mice were sacrificed randomly at 3,7,14 days after UUO and obstructed kidneys were collected. Macrophage phenotype was detected by double-labeling immunofluorescence with F4/80 and iNOS for the M1, F4/80 and CD206 for the M2 macrophage subpopulation. iNOS, Arg-1 and CD206 were also detected by western blot. Results C3 deficient mice exhibited attenuated renal fibrosis, reduced collagen accumulation and tubulointerstitial injury score compared with WT mice (P<0.01). Meanwhile, macrophage depletion in early or late stage of UUO reduced renal fibrosis in WT mice, but had no effect on C3-deficient UUO mice. Decreased accumulation of M1 macrophages and expression of iNOS, increased accumulation of M2 macrophages and expression of Arg-1, CD206 were found in C3 deficient mice compared with WT mice in early stage of UUO (P<0.01). Conclusion Renal fibrosis is not reduced after depletion of macrophages in C3 deficient UUO mice due to the altered macrophage polarization.

Effect of dopamine on the activity of matrix metalloproteinases and degradation of dentin collagen / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the inhibition effect of dopamine on the activity of matrix metalloproteinases (MMP) and the effect of dopamine on degradation of dentin collagen for its potential use in caries treatment and dentin adhesive.</p><p><b>METHODS</b>In the experiment of MMP activity test, 2.0 g/L dopamine + 1.0 g/L highly purified collagenase type VIII from Clostridium histolyticum served as the experimental group, and deionized water + 1.0 g/L highly purified collagenase type VIII from Clostridium histolyticum served as the negative control group, and 2% chlorhexidine + 1.0 g/L highly purified collagenase type VIII from Clostridium histolyticum served as the positive control group, and the mixture volume ratio of the two ingredients in every group was 1:9. After 15 minutes, the enzyme activity of each sample was tested by MMP activity colerimetric quantitative detection kits, and the test was repeated 5 times in each group. In the experiment of collagen degradation, the dentin slices were demineralized with 37% phosphoric acid for 1 min. In sequence, 2 dentin slices were used to observe the morphology, and the remaining 30 dentine slices were randomly divided into three groups (n = 10) according to random number table: the negative control ones were stored in 100 µl deionized water and 900 µl collagenase (7 days, 37 °C), the positive control ones were stored in 100 µl chlorhexidine and 900 µl collagenase (7 days, 37 °C) and the experimental specimens were stored in 100 µl dopamine and 900 µl collagenase (7 days, 37 °C). The degraded collagen was investigated by assaying hydroxyproline. The framework of collagen was evaluated with field emission scanning electron microscope (FE-SEM).</p><p><b>RESULTS</b>The statistical results of completely random design ANOVA showed that the MMP activity and the amount of degraded collagen of the negative control group [(0.089 ± 0.011) µmol · min⁻¹ · mg⁻¹ and (2 837 ± 201) µg/cm²] were significantly higher than those of the positive control group [(0.038 ± 0.006) µmol · min⁻¹ · mg⁻¹ and (1 288 ± 172) µg/cm²] and the experimental group [(0.030 ± 0.009) µmol · min⁻¹ · mg⁻¹ and (1 389 ± 255) µg/cm²] (P < 0.05). SEM observation indicated that the structural integrity of the collagen network on dentin still existed in experiment samples and positive control groups, however, collagen fibrils were destructed and the structural integrity disappeared in the negative control groups.</p><p><b>CONCLUSIONS</b>Dopamine may inhibit MMP activity and reduce the amount of degraded collagen.</p>

Introduction to Effects and Clinical Applications of Enteral Immunonutrition / 中国普外基础与临床杂志

Objective To study the effects and mechanisms of major immune nutrients and to introduce the progresses of clinical applications about enteral immunonutrition.Methods The related literatures about the effects and clinical applications of enteral immunonutrition were reviewed.Results Infection rate can be reduced and the hospitalization can be shortened as a result of the improved nutritional status and immune competence of patients which can be enhanced by reasonable enteral immune nutrition.Most of the patients suffering from serious diseases can benefit from enteral immunonutrition,such as gastrointestinal cancers,post-transplantation complications,chronic liver disorders,acute pancreatitis and so on.However,as a new nutrition therapy,the clinical use of enteral immunonutrition in critically ill patients is still controversial.Conclusions Enteral immunonutrition plays an important role in the nutritional support of patients with serious diseases,such as gastrointestinal cancers,organ failures.However,much work remains to be done.

Effect of Short-Term Administration of Growth Hormone on Serum IGF-1 and Nutritional Status in Patients after Gastrointestinal Surgery / 中国普外基础与临床杂志

0.05),but improved significantly the rise from day 3 to day 10 of serum fibronectin level 〔(22.8?5.8) mg/L vs.(9.6?3.6) mg/L,P

Effect of Cholecystokinine on Nervous System / 中国普外基础与临床杂志

Objective To review the biologic characteristics and biologic effect of cholecystokinine (CCK) on the central nervous system. Methods The literatures of recent years on research advancement of cholecystokinine as neurotransmitters/peptides in signal transduction, neuron protection and pain management in the central nervous system are reviewed. Results CCK possesses the ability to suppress the convulsant effects of convulsants. CCK8 is able to reduce the neural damage caused and delay the neural aging. CCK antagonists play an important role in human pain transduction. Conclusion CCK has been proven to be one of the richest neurotransmitters/neuropeptides as well as an important signal factor in the brain, and its important biologic effect is being confirmed.

Expression of hypoxia-inducible factor 1 alpha and glucose transporter 1 and its significance in human breast carcinoma / 肿瘤研究与临床

Objective To investigate the expression of hypoxia-inducible 1 alpha(HIF-lα)and glucose transporter 1(Glut1)in human breast cancer and its relationship to proliferating cell nuclear antigen (PCNA)protein and clinical pathologic factors.Methods Immunohistochemical staining was used to measure the expression of HIF-lα.Glut1 and PCNA in human breast fibroadenoma,usual hyperplasia and breast carcinoma.Results HIF-1α expression was not found in breast fibroadenoma and hyperplastic Iesions.In contrast.the positive rate of HIF-1α was found in the ductal carcinoma in situ 55%(DCIS,11/20)and the invasive breast carcinoma 85%(51/60).Glut1 positivity in breast carcinoma was 58.8%(47/80).The totsl positive rate of PCNA in breast carcinoma was 75%(60/80),that in DCIS was 65%(13/20)and that in invasive carcinoma was 78.3%(47/60).There was a positive correlation between HIF-lα and Glut 1 level (r=0.653,P＜0.01),a positive correlation between HIF-1α and PCNA level(r=0.693,P＜0.01);and also a positive correlation between Glutl and PCNA level(t=0.742.P＜0.01).conclusion The overexpression of HIF-lα and its target gene Glut1 played important roles in carcinogenesis and progression of breast carcinoma and closely correlated with cell proliferation of breast carcinoma and may become a new target for treatment of breast carcinoma.

The expression of HGF and c-Met in gastric carcinoma / 中华普通外科杂志

Objective To investigate the relationship between HGF/c-Met and biological behavior and prognosis of gastric carcinoma.Methods The expression of HGF.c-Met.microvessel density and microlymphatic densitv in 58 cases of gastric carcinoma and 27 cases of gastric ulcer were evaluated by immunohistochemistry，using monoclonal antibodies for HGF，c-Met，CD34 and Lyve-1 respectively.Results HGF and c-Met protein were overexpressed in gastric carcinoma，and were significantly higher than those in the mucosa of gastric ulcer(P＜0.01).The microvessel density and microlymphatic density of gastric carcinoma were significantlv different between those with and those without lymphatic metastasis and distant metastasis(all P＜0.05)：The positive expression of HGF and c-Met in those with lymph node metastasis(86％，80％)was significantly higher than those without lymph node metastasis(57％，36％)，P＜0.05.That with distant metastasis(100％.94％)was higher than that without(71％，60％)，P＜0.01.The 5 year survival rate in patients with positive HGF and c-Met expression was much lower than that with negative expression(P=0.019，P＜0.01)，Multivariate analysis indicated HGF and c-Met expression，depth of invasion.lymph node metastasis.distant metastasis，microvessel density and microlymphatic density were all independent prognostic factors of gastric carcinoma.ConclusionsExpression of HGF and c-Met closely correlated with carcinogenesis，development and prognosis of gastric carcinoma.

Improve the efficacy of nutritional support in infectious patients / 中华消化外科杂志

The aim of nutritional support is to maintain the metabolic function of cells, organs and the whole body, and also to reduce the total energy consumption, finally promotes the patients to recover. Infectious patients are often in the status of high catabolism and negative nitrogen balance. It is necessary for such patients to receive nutritional support, however, the performance is difficult because of the high catabolism status and disorder of physiological function. What is more, inappropriate performance may lead to even worse outcome. Accordingly, the current clinical researches focus on how to improve the effects of nutritional support in infectious patients. Several aspects on this issue including the time, route, dose, metabolic intervention and immune modulation are discussed.

Research Progression of Molecular Mechanism of Peritoneal Dissemination of Gastric Cancer / 中国普外基础与临床杂志

Objective To investigate the molecular mechanism of peritoneal dissemination of gastric cancer. Methods Literatures in recent years about mechanisms of peritoneal metastasis in gastric cancer were reviewed and summarized.Results Peritoneal metastasis related to viability of cancer cells and peritoneal characteristics. Moreover, it is necessary that many adhesive moleculars, protein hydrolase, cell factors and vascular factors involved in peritoneal metastasis.Conclusion Peritoneal metastasis of gastric cancer was induced by multiple factors together.

Intestinal Rehabilitation Therapy in Short Bowel Syndrome / 中国普外基础与临床杂志

To investigate the role of rehabilitation therapy both on nutritional status and intestinal adaptation of patients with short bowel syndrome (SBS). Methods The literatures about rehabilitation therapy for SBS were reviewed. Results Intestinal rehabilitation refers to the process of restoring enteral autonomy, in order to get rid of parenteral nutrition, usually by means of dietary, medical, and surgical treatment. Recent researches showed that medication and the use of specific nutrients and growth factors could stimulate intestinal absorption and might be useful in the medical management of SBS. Conclusion Intestinal rehabilitation is of benefit in the treatment of SBS and would play a greater role in the future.

Expression of PCNA in Gastric Cancer and Its Relationship with Telomerase Activity of Peritoneal Washings and Peritoneal Dissemination / 中国普外基础与临床杂志

Objective To investigate the expression of PCNA in gastric cancer and its relationship with telomerase activity of peritoneal washings and peritoneal dissemination, and to compare the efficacy of telomerase activity and cytology of peritoneal washings for prediction of peritoneal metastasis of gastric cancer. Methods Telomeric repeated amplification protocol (TRAP)-enzyme-linked immunosorbent assay (ELISA) was performed to measure the telomerase activity of peritoneal washings collected from 60 patients with gastric cancer. Exfoliate cytologic analysis of the corresponding samples was used for comparison.Expression of PCNA was measured with immunohistochemical staining.Their relationship with clinicopathologic features were evaluated. Results The positive rate of telomerase activity in peritoneal washing collected from patients with gastric cancer was 41.7%,which well related to serosal invasion, histology types, depth of infiltration and peritoneal metastasis of gastric cancer. The positive rate of telomerase activity increased with the increased depth of infiltration and serosal involvement areas (P

The clinical value of serum fibronectin and prealbumin as markers for nutritional assessment in nutrition support / 肠外与肠内营养

Objective: To evaluate the clinical significance of serum fibronectin and prealbumin as nutritional parameters in nutrition support after abdominal surgery.Methods: Serum albumin,transferrin,prealbumin and fibronectin were determined respectively before and 7 days after nutrition support in abdominal surgery patients,and nitrogen balance was calculated daily during nutrition support.Results: Compared with before nutrition support,the levels of serum transferrin,prealbumin and fibronectin were significantly increased after nutrition support.Furthermore,the change of prealbumin was correlated with that of fibronectin.Conclusion: Measurement of serum transferrin and prealbumin can be recommended as valuable indicators in assessing the nutritional status of surgery patients receiving nutritional support.

Expression of Presenilin-2 and Glutathione S Transferase ? and Their Clinical Significance in Infiltrating Ductal Breast Carcinoma / 中国普外基础与临床杂志

Objective To investigate the expression of presenilin-2(PS2) and glutathione S transferase ?(GST?) and their role in the prognosis and therapy of infiltrating ductal breast carcinoma. Methods The expression of PS2 and GST? in tumor tissues from 210 patients with infiltrating ductal breast carcinoma confirmed by pathologic examination and treated with modified radical mastectomy was examined by using LSAB immunohistochemical method. Results The expression rate of PS2 was 49.5%(104/210) and the expression rate of GST? was 48.1%(101/210). The grade of the postoperative 5-year survival rate and 10-year survival rate in four groups of 210 patients, from high to low, was the group 1 (PS2 positive expression/GST? negative expression), the group 2 (PS2 positive expression/GST? positive expression), the group 3 (PS2 negative expression/GST? negative expression) and the group 4 (PS2 negative expression/GST? positive expression). Conclusion The prognosis of the group 1 is the best, the group 2 better, the group 3 good and the group 4 the worst. The results suggest that reasonable use of endocrinotherapy and chemotherapy in infiltrating ductal breast carcinoma is necessary.

The Protective Effect of Hepatocyte Growth Factor on Grafted Structure after Small Bowel Transplantation in Rat / 中国普外基础与临床杂志

Objective To study the protective effect of hepatocyte growth factor(HGF) on grafted mucous membrane of transplanted small bowel.Methods Total small bowel transplantation was made in inbred Wistar (RT1 k) rats heterotopically,either total parenteral nutrition (control group, n =10) or hepatocyte growth factor supplemented TPN (HGF group, n =10) was given to the recipients from the 2nd day to the 10th day postoperatively. Morphological parameters of the transplanted intestinal mucosa, such as mucosal villous height, villous width, crypt depth, mucosal thickness and villous surface area were observed. Variation of ultrastructure of transplanted epithelial cells was observed. Composition of mucosal protein and DNA content were tested. Results Comparison between HGF group and the control group were as follows. Mucosal villous height (298.79?22.31) ?m vs (176.45? 14.62) ?m, P =0.001, villous width (107.46? 12.34) ?m vs (74.20?16.85) ?m, P =0.004, crypt depth (104.56?11.17) ?m vs (74.45?8.34) ?m, P =0.000 5, mucosal thickness (409.53?35.83) ?m vs (259.38?24.65) ?m, P =0.003, and villous surface area (0.101? 0.011) mm 2 vs (0.041?0.005) mm 2, P =0.001 were found significantly increased in HGF group compared with control group, there were no obvious difference decrease as compared to pretransplant parameters.Mucosal protein composition was higher in HGF group than that in control group (89.65? 9.28) mg/g wet wt vs (53.73? 11.45) mg/g wet wt, P =0.012, baseline (92.64?10.52) mg/g wet wt, nearly equal to baseline; DNA composition was also high in HGF group (0.89?0.09) mg/g wet wt vs (0.51?0.06) mg/g wet wt, P =0.008, baseline (0.91? 0.09) mg/g wet wt. Nearly normal ultrastructure of the graft was maintained in HGF group, atrophied microvilli and broken mitochondrial crista were observed in control group.Conclusion Hepatocyte growth factor can improve mucosal structure, preserve enterocyte ultrastructure of isograft after small bowel transplantation in rat.

Retaining of Spleen and Sweeping of Lymph Nodes of No.10 and No.11 During the Operation of Gastric Carcinoma / 中国普外基础与临床杂志

Objective To study the indication and means in dissection lymph nodes of the No.10 and No.11 without splenectomy in radical gastrectomy for gastric cancer. Methods According to the location, type of pathology, clinical and pathological classification, lymphatic drainage and spread of gastric carcinoma togather with the immunological function of spleen, selection of operative procedure without splenectomy should be considered, so the related literatures were reviewed. Results Retained spleen had been shown to improve 5 year survival of patients with gastric cancer of stage Ⅰ,Ⅱ and Ⅲ,splenectomy had been shown to improve 5 year survival of patients with gastric cancer of stage Ⅳ,whose carcinoma was infiltrating splenic and the lymph nodes of the No.10. The complications of different means of dissection of the lymph nodes made no difference.Conclusion Dissection of the lymph node without retained spleen or allogenic spleen transplantation is indicated for the patients with cancer of stage Ⅳ,whose spleen is invaded by the tumor.

Lymphangiogenic Factors and Gastrointestinal Tract Malignant Neoplasmas / 中国普外基础与临床杂志

Objective To introduce the current studies of the role of vascular endothelial growth factor-C(VEGF-C) and VEGF-D in lymphangiogenesis and lymph node metastasis of gastrointestinal neoplasma.Methods The related literatures in recent 5 years were reviewed.Results The growth factors VEGF-C and VEGF-D enhance lymphangiogenic metastasis of gastrointestinal neoplasma with the property of angiogenesis and lymphangiogenesis.In gastric adenocarcinoma,VEGF-C mRNA and tissue protein expression correlate with lymphatic invasion,lymph node metastasis,venous invasion and reduced 5-year survival rates.The role of VEGF-C in esophageal squamous cancer and colorectal cancer and VEGF-D in colorectal cancer is not certain,with conflicting reports in the published literatures.Conclusion The VEGF-C,VEGF-D/VEGFR-3 signal pathway may become the ideal target for inhibition of tumor proliferation and metastases,antilymphangiogenesis therapy may be a novel potential strategy in tumor biological therapy.

Galectin-3 and Tumour Metastasis / 中国普外基础与临床杂志

Objective To investigate the relationship between galectin-3 and tumour metastasis, and the future prospect of galectin-3 in clinic.Methods Related articles were reviewed. Results Galectin-3, a member of the ?-galactoside-binding proteins, is expressed widely in epithelial and immune cells, and interacts with intracellular glycoproteins, cell surface molecules and extracellular matrix proteins. Galectin-3 is involved in various biological phenomena including cell growth, adhesion, differentiation, angiogenesis and apoptosis, and is associated with invasion and metastasis of tumour. Conclusion Because of the correlation between galectin-3 and tumour invasion and metastasis, galectin-3 may act as the diagnostic marker for tumour metastasis and one of the target proteins for cancer treatment.