Clinical research progress of immunotherapy for nasopharyngeal carcinoma / 国际肿瘤学杂志

Immunotherapy mainly uses the effector units of the body's immune system to overcome the immune escape or adaptive immune resistance of tumors, accurately identify and remove tumor cells, and normalize or enhance the function of the immune system, which mainly includes cytokine therapy, immune checkpoint inhibition therapy, adoptive cell immunotherapy, tumor vaccine and antibody targeted therapy. The immune characteristics of nasopharyngeal carcinoma make the patients potentially suitable for immunotherapy or combined therapy with radiotherapy and chemotherapy. In recent years, PD-1 inhibitors alone and in combination with chemotherapy have shown good anti-tumor activity and safety in the treatment of recurrent/metastatic nasopharyngeal carcinoma. The incorporation of immune checkpoint inhibitors into the treatment paradigms of nasopharyngeal carcinoma has become a clinical research hot spot.

Epidemiological analysis on the susceptibility of CXCR3 gene polymorphism to COPD in the elderly population in Liangjiang New Area of Chongqing / 公共卫生与预防医学

Objective To explore and analyze the epidemiology of susceptibility to chronic obstructive pulmonary disease (COPD) among the elderly population in Liangjiang New Area of Chongqing based on CXC chemokine receptor 3 (CXCR3) gene polymorphism. Methods From January 2020 to September 2022, the Medical Laboratory Department of Chongqing Liangjiang New Area People's Hospital selected COPD patients and received treatment. Among the 276 patients who met the criteria were included in the study and included in the observation group. Among the 512 patients with healthy pulmonary function in the same period were included in the control group. The data of the two groups of patients were analyzed, and the genotypes were detected by SBaPhotoshot technology to analyze the relationship between gene polymorphism and the susceptibility and clinical characteristics of COPD. Results There was no significant difference between the two groups in age, sex, BMI and blood eosinophil granulocyte levels, which was comparable (P>0.05). There were significant differences in smoking history, pulmonary function index , MMP-9 and TIMP-1 levels (P0.05). In the observation group, the MMP-9 level of rs2280964 locus was significantly different (P=0.003), while the TIMP-1 level was not significantly different (P=0.187); There was no significant difference in MMP-9 and TIMP-1 levels among the three genes at rs34334103 locus (all P>0.05). The level of MMP-9 in homozygous TT patients with rs2280964 locus was significantly higher than that in homozygous CC patients (P=0.024). There were differences in FEV1/FVC of patients with CXCR3 rs34,334,103 gene distribution (P=0.008), among which there were significant differences in CC+CT and TT recessive models (P0.05). Conclusion CXCR3 gene polymorphism is significantly associated with the susceptibility to COPD, and also with the serum levels of MMP-9 and FEV1/FVC, which can be used as a new target for clinical research and treatment.

Logistic regression analysis of positive rate of serum Mycoplasma pneumoniae IgM antibody in patients with acute exacerbation of AECOPD in Liangjiang New Area of Chongqing / 公共卫生与预防医学

Objective To analyze the positive rate of serum mycoplasma pneumoniae antibody IgM in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Liangjiang New Area of Chongqing and the related risk factors, so as to provide a theoretical basis for clinical diagnosis and treatment of AECOPD. Methods Retrospective analysis of 728 cases of AECOPD patients from January 2020 to December 2021 in Chongqing Liangjiang New Area Third Class Hospital. ELISA was used to determine Mycoplasma pneumoniae IgM antibodies. According to the detection of Mycoplasma pneumoniae IgM antibodies, the patients were divided into infection group and non-MP infection group. Clinical data such as gender, age, length of stay, place of residence, smoking status, home oxygen therapy, GOLD grade of COPD, number of acute exacerbations in the previous year, mechanical ventilation, and application of anti-infective drugs were collected. Univariate analysis and logistic regression were used to analyze the risk factors of MP infection in AECOPD patients. Results The positive rate of MP-IgM in 728 AECOPD patients was 15.38% (112/728), including 67 males and 45 females. There was no significant difference in the positive rate of MP-IgM in AECOPD patients between different seasons (χ2=2.840, P>0.05). Age ≥60 (OR=3.243), smoking (OR=2.559) and GOLD grade 3-4 (OR=3.760) were independent risk factors for MP infection in AECOPD patients. Conclusion The incidence of MP infection in AECOPD patients in Liangjiang New Area of Chongqing is relatively high, especially in AECOPD patients with age ≥ 60, smoking, GOLD grade 3-4, which should be warned of the possibility of mycoplasma pneumoniae infection , and targeted treatment measures can improve the cure rate.

Effects of Onodera′s prognostic nutritional index on the prognosis of locally advanced oropharyngeal squamous cell carcinoma after induction chemotherapy followed by sequential chemoradiotherapy / 中华放射医学与防护杂志

Objective:To explore the effects of Onodera′s prognostic nutritional index (PNI) on the prognosis of locally advanced oropharyngeal squamous cell carcinoma (LA-OPSCC) after induction chemotherapy followed by sequential chemoradiotherapy.Methods:A retrospective analysis was conducted on the clinical data of 52 LA-OPSCC patients receiving induction chemotherapy followed by sequential chemoradiotherapy in The Affiliated Cancer Hospital of Guizhou Medical University during 2014-2018. The PNI values of all the patients at different treatment phases were statistically analyzed, and the ROC curve was employed to determine the optimal critical value of PNI. The patients in this study were divided into a well-nourished group ( n = 27) and a poorly-nourished group ( n = 25). The Kaplan-Meier method was used for survival analysis. The Cox proportional hazards model was utilized to analyze the relationships between different nutritional status and prognosis. Clinical features and adverse reactions were compared between the two groups. Results:The PNI values decreased significantly after radiotherapy, with an optimal critical value of 42.4. The 5-year overall survival (OS) and progression-free survival (PFS) of the well-nourished group (PNI ≥ 42.4) were 62.6% and 60.9%, respectively, which were significantly higher than those (30.1% and 29.7%) of the poorly-nourished group (PNI < 42.4, χ2 = 11.12, 5.74, P < 0.05). The multivariate analysis showed that PNI was an independent prognostic factor for the OS after radiotherapy ( HR = 2.752, 95% CI: 1.095-6.917, P = 0.031). The LA-OPSCC patients aged over 60 years or those who did not respond to induction chemotherapy accounted for a higher proportion of malnutrition after chemoradiotherapy ( χ2 = 4.89, 5.05, P < 0.05). Conclusions:PNI after radiotherapy can be used as a prognostic factor in the evaluation of LA-OPSCC patients receiving induction chemotherapy followed by sequential chemoradiotherapy. The LA-OPSCC patients aged over 60 years or those who do not respond to induction chemotherapy should receive more nutritional support during the chemoradiotherapy.

Protective effect of icariin on Aβ25-35-induced HT22 cell injury by ameliorating glycolytic dysfunction through activating Wnt/β-catenin signaling pathway / 中国药理学与毒理学杂志

OBJECTIVE To investigate whether icari-in(ICA)plays a neuroprotective role by improving glyco-lytic function through activating Wnt/β-catenin signaling pathway.METHODS HT22 cells were treated with Aβ25-35 for 24 h to establish AD cell model,ICA was added in 2 h before Aβ25-35 and the DKK1(a specific inhibitor of the Wnt signaling pathway)was added in 0.5 h before ICA.Pharmacodynamic study:HT22 cells were divided into control group,ICA group(ICA 10 μmol·L-1),model group(Aβ25-3520 μmol·L-1),model + ICA group(Aβ25-3520 μmol·L-1 +ICA 2.5,5,10 μmol·L-1);Mechanism study:HT22 cells were divided into control group,model group,Aβ25-35+ICA 10 μmol·L-1 group,Aβ25-35+DKK1 group,Aβ25-35+DKK1+ ICA group.The cell viability was detected by MTT assay and the cell morphology was obtained by microscope,the lactate content was detected by lactate assay,the ATP content was measured with the chemiluminescence method,the expression levels of HK1,PKM1 and the pro-tein expression of molecules related to the Wnt/β-catenin signaling pathway(Wnt3a,GSK3β,pGSK3β Try216,pGSK3β Ser9,β-catenin,pβ-catenin Ser33/37 Thr41,Active β-catenin and nuclear β-catenin)was assayed by Western blotting.The nuclear translocation of β-catenin was observed by immunofluorescent staining.RESULTS Compared with the control group,the viability of cells in the model group was reduced,the morphology of cells was significantly damaged,the ATP content and lactate content were significantly decreased,and the glycolytic key enzymes:the protein levels of HK1,PKM1 and the protein levels of Wnt3a,pGSK3β Ser9,active β-catenin and nuclear β-catenin were significantly reduced,and the phosphorylation levels of β-catenin Ser33/37 Thr41 were significantly increased.Compared with the model group,the cell morphology was significantly improved and the viability was significantly increased,the ATP and lactate content were significantly increased,the expressions of HK1,PKM1 and Wnt3a,pGSK3β Ser9,active β-catenin and nuclear β-catenin protein were significantly upregulat-ed,and the phosphorylation levels of β-catenin Ser33/37 Thr41 were significantly reduced after ICA treatment.However,when the canonical Wnt signaling was inhibited by DKK1,the above effects of ICA on glycolysis were abolished.CONCLUSION ICA exerts neuroprotective effects on Aβ25-35-induced HT22 cell injury by enhancing the glycolysis function through the activation of the Wnt/β-catenin signaling pathway.

Protective effect of gastrodin on A β 25-35-induced HT22 cell injury by improving glycolytic function through activating PI3K/Akt/BACH1 signaling axis / 中国药理学与毒理学杂志

OBJECTIVE To investigate whether gas-trodin(GAS)plays a neuroprotective role by activating PI3K/Akt/BACH1 signaling axis to improve glycolytic func-tion.METHODS HT22 cells were treated with Aβ25-35 for 24 h to establish cell damage model.GAS pretreated HT22 cells for 2 h,and Akt agonist SC79,Akt inhibitor MK2206,PI3K inhibitor LY294002 were added 0.5 h before GAS treatment to detect their protective mecha-nisms.Pharmacodynamic research of GAS in this model were divided into six groups:control group,GAS group(GAS 10 μmol·L-1),model group(Aβ25-35 20 μmol·L-1),model +GAS 2.5,5 and 10 μ mol·L-1 group).Mecha-nism research of GAS in this model was divided into 6 groups:control group,Aβ25-35 20 μmol·L-1 group,Aβ25-35 20 μmol·L-1 + GAS 10 μmol·L-1 group,Aβ25-35 + SC79 group(Aβ25-35 20 μmol·L-1 +SC79 10 μmol·L-1),Aβ25-35+MK2206+GAS group(A β 25-35 20 μ mol·L-1 +MK2206 10 μmol·L-1+GAS 10 μmol·L-1),Aβ25-35+LY294002+GAS group(Aβ25-35 20 μmol·L-1+LY294002 10 μmol·L-1+GAS 10 μmol·L-1).Cell viability was detected by MTT,mor-phological changes of cells were observed by micro-scope,ATP content was detected by chemilumines-cence,and pyruvate(PA)content was detected by colo-rimetry.Western blotting was used to detect the protein levels of transcription factor BACH1,key glycolysis enzyme hexokinase(HK1)and PI3K/Akt signaling path-way related proteins PI3K,p-PI3K,Akt and p-Akt.RESULTS The results showed that compared with the control group,the cell morphology of HT22 cells damaged by Aβ25-35 was damaged,the number of cells decreased,the cell body became smaller,the number of dead cells increased,the cell survival rate,ATP and PA contents decreased significantly,and the protein expressions of p-PI3K,p-Akt,BACH1 and HK1 were significantly down-regulated.GAS treatmentcansignificantlyimprovethemor-phology of HT22 cells damaged by Aβ25-35,increase cell survival rate,ATP and PA contents,and up-regulate the expression of p-PI3K,p-Akt,BACH1 and HK1 proteins.SC79 also significantly increased cell survival rate,ATP content,protein expression of BACH1 and HK1.However,the above ameliorative effect of GAS on HT22 cell dam-age induced by Aβ25-35 was antagonized by LY294002 and MK2206.CONCLUSION GAS exerts a neuroprotec-tive effect on Aβ25-35-induced HT22 cell injury by improv-ing glycolytic function through activating PI3K/Akt/BACH1 signaling axis.

Application of "three-dimensional knowledge-objective" teaching combined with immersive clinical experience in nursing practice teaching in the operating room of department of ophthalmology and otorhinolaryngology / 中华医学教育探索杂志

Objective:To investigate the application of "three-dimensional knowledge-objective" teaching combined with immersive clinical experience in nursing practice teaching in the operating room of department of ophthalmology and otorhinolaryngology.Methods:A total of 86 nursing students who received practice teaching in the operating room of Department of Ophthalmology and Otorhinolaryngology in our hospital were selected as research subjects and were divided into control group and observation group using a simple random number table, with 43 students in each group. The students in the control group received traditional teaching, and those in the observation group received "three-dimensional knowledge-objective" teaching and immersive clinical experience. The two groups were assessed in terms of the effectiveness of classroom teaching, nursing quality score, and the score of the ability to handle nurse-patient dispute. SPSS 22.0 was used to perform the chi-square test and the t-test. Results:After training, both groups had significant increases in the scores of basic nursing, specialized nursing, equipment management, equipment coordination ability, patrol coordination ability, and document recording ability and the total score of all dimensions, and the observation group had significantly higher scores than the control group ( P<0.05). After training, both groups had significant increases in the scores of dispute identification ability, the ability of emergency response to dispute, nurse-patient communication skills, the awareness of nursing laws and regulations, and psychological stress adjustment ability and the total score of all dimensions, and the observation group had significantly higher scores than the control group ( P<0.05). Conclusion:In the nursing practice teaching in the operating room of the department of ophthalmology and otorhinolaryngology, "three-dimensional knowledge-objective" teaching combined with immersive clinical experience can improve the effectiveness of classroom teaching, enhance nursing quality, and strengthen the ability to handle nurse-patient dispute.

Finite element analysis of 14-year-old adolescent after spinal foraminoplasty at L / 解剖学报

Objective To establish the three-dimensional finite element model of lumbar spine(L) 3-5 segments of the normal spine of 14-year-old adolescents to analyze the biomechanical changes of the lumbar spine after different degrees of lumbar foraminal plasty, and to provide reference for improvement of adolescent foraminoplasty. Methods A14-year-old female volunteer with no previous history of lumbar spine was selected to collect lumbar CT image data and we imported it into Mimics 16.0 software for modeling. ABAQUS software was used to conduct finite element model force analysis. Models M

Recent advances of DJ-1 regulating mitochondrial function / 中国药理学通报

Dj-l is a protein encoded by PARK7 gene, a member of the peptidase C56 protein family. Defects in PARK7 gene may lead to autosomal recessive early-onset Parkinson ' s disease. Dj-1 is a multifunctional protein that acts as an active androgen receptor-mediated transcriptional regulator, a REDOX sensitive molecular chaperone, an oxidative stress sensor, and it also protects neurons from oxidative stress and cell death. In addition, DJ-1 is also associated with mitochondria, energy metabolism, mitochondrial homeostasis, mitophagy mitochondria-associated endoplasmic reticulum membranes and other life processes. However, the precise function of DJ-1 protein is not well understood. This paper reviews the effect, mechanism and molecular basis of DJ-1 protein in regulating mitochondrial function, and discusses its potential value in combination with clinical diseases. It has good timeliness, necessity, innovation and science, and also helps to provide new targets and ideas for clinical drug development.

The biological clock gene BMAL1 inhibits the proliferation, migration and invasion of radiation-resistant nasopharyngeal carcinoma cell line 5-8FR by regulating PI3K/Akt/MMP-2/9 signaling pathway / 中华放射肿瘤学杂志

Objective:To investigate the effect of BMAL1 gene on the proliferation, migration and invasion ability of radiation-resistant nasopharyngeal carcinoma cell line (5-8FR) and the molecular mechanism. Methods:A multi-target click model was constructed for radiation-resistant nasopharyngeal carcinoma cell line 5-8FR by low-dose fractionated irradiation, and the results of clone formation assay were used to fit the multi-target click model and calculate the sensitization ratio of radiotherapy. The expression levels of PI3K/Akt/MMP-2/9 signaling pathway-related proteins in 5-8FR and control 5-8F cell lines were detected by Western blot. The overexpression and knockdown vectors of BMAL1 gene were constructed and transfected with 5-8F and 5-8F cell lines, respectively. The BMAL1 gene overexpression (pcDNA-BMAL1) and its control (pcDNA) and interference (BMAL1-shRNA) and control (con-shRNA) cell lines were stably transfected with nasopharyngeal carcinoma cell line 5-8F and radiation-resistant cell line 5-8FR, respectively. Western blot was performed to verify the infection efficiency and detect the changes of PI3K/Akt/MMP-2/9 signaling pathway-related proteins after overexpression or interference of BMAL1 gene in both groups of cells. CCK-8 assay, cell scratch test and Transwell chamber test were conducted to investigate the proliferation, migration and invasion capabilities of 5-8FR cell line after overexpression or interference of BMAL1 gene. Results:BMAL1 gene expression was down-regulated, and those of PI3K/Akt pathway proteins and downstream related molecules of MMP-2 and MMP-9 were up-regulated, and TIMP-2 and TIMP-1 expression was down-regulated in nasopharyngeal carcinoma radiation-resistant cell lines. Overexpression of BMAL1 gene inhibited the expression of PI3K/Akt pathway proteins and downstream related molecules of MMP-2 and MMP-9, promoted the expression of TIMP-2 and TIMP-1, and inhibited the proliferation, migration and invasion capabilities of radiation-resistant nasopharyngeal carcinoma cells, while interference with BMAL1 gene yielded the opposite results. Conclusions:BMAL1 gene can reverse the expression of PI3K/Akt/MMP-2/9 signaling pathway-related proteins in radiation-resistant nasopharyngeal carcinoma cell lines and inhibit the proliferation, migration and invasion capabilities of radiation-resistant nasopharyngeal carcinoma cell lines.

Effect of Buyang Huanwutang on Keap1/Nrf2/HO-1 Antioxidant Signaling Pathway in Rats with Idiopathic Pulmonary Fibrosis / 中国实验方剂学杂志

ObjectiveTo study the effect of Buyang Huanwutang on Kelch-like Ech-related protein 1 （Keap1）/nuclear factor E2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） antioxidant signaling pathway in rats with idiopathic pulmonary fibrosis （IPF） and explore the mechanism of this prescription in the treatment of IPF. MethodForty SPF-grade male SD rats were assigned into a sham operation group， a model group， a Buyang Huanwutang group， and a nintedanib group according to random number table method， with 10 rats in each group. IPF rat model was established by intratracheal infusion of bleomycin （0.005 g·kg-1） in other groups except the sham operation group. Buyang Huanwutang group was administrated with Buyang Huanwutang (14.84 g·kg-1)，intragastric administration of nitedanib suspension (0.1 g·kg-1)，sham operation group and model group were given equal volume of normal saline， for 28 days. After lung function test， serum and lung tissue samples were collected. Hematoxylin-eosin （HE） staining and Masson trichrome staining were employed to observe the pathological changes of the lung tissue. The content of hydroxyproline （HYP） in lung tissue was detected. The levels of malondialdehyde （MDA） in serum and lung tissue， and the activities of superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px） and catalase （CAT） were determined. The mRNA and protein levels of Keap1， Nrf2， and HO-1 was determined by Real-time fluorescent quantitative polymerase chain reaction， immunohistochemical staining， and Western blot. ResultCompared with the sham operation group， the modeling increased the resistance and elasticity and decreased the compliance of respiratory system （P<0.01）， elevated the lung index， pathological score， and HYP content in lung tissue （P<0.01）， and enriched MDA in serum and lung tissue， while it decreased the activities of SOD， GSH-Px， and CAT （P<0.01）. Furthermore， the modeling down-regulated the mRNA and protein levels of Keap1 and up-regulated those of Nrf2 and HO-1 in lung tissue （P<0.01）. Compared with the model group， Buyang Huanwutang decreased the resistance and elasticity and increased the compliance of respiratory system （P<0.01）， lowered the lung index， pathological score， and HYP content in lung tissue （P<0.01）， and reduced MDA in serum and lung tissue， while it increased the activities of SOD， GSH-Px， and CAT （P<0.01）. Additionally， Buyang Huanwutang down-regulated the expression of Keap1 and up-regulated that of Nrf2 and HO-1 in lung tissue （P<0.05， P<0.01）. ConclusionBuyang Huanwutang can activate Keap1/Nrf2/HO-1 signaling pathway to enhance the antioxidant capacity and slow down the pathological process of IPF in rats.

IRE1α deficiency impairs autophagy in chondrocytes by upregulating calcium homeostasis endoplasmic reticulum protein / 南方医科大学学报

OBJECTIVE@#To explore the mechanism by which inositol-requiring enzyme-1α (IRE1α) regulates autophagy function of chondrocytes through calcium homeostasis endoplasmic reticulum protein (CHERP).@*METHODS@#Cultured human chondrocytes (C28/I2 cells) were treated with tunicamycin, 4μ8c, rapamycin, or both 4μ8c and rapamycin, and the expressions of endoplasmic reticulum (ER) stress- and autophagy-related proteins were detected with Western blotting. Primary chondrocytes from ERN1 knockout (ERN1 CKO) mice and wild-type mice were examined for ATG5 and ATG7 mRNA expressions, IRE1α and p-IRE1α protein expressions, and intracellular calcium ion content using qPCR, Western blotting and flow cytometry. The effect of bafilomycin A1 treatment on LC3 Ⅱ/LC3 Ⅰ ratio in the isolated chondrocytes was assessed with Western blotting. Changes in autophagic flux of the chondrocytes in response to rapamycin treatment were detected using autophagy dual fluorescent virus. The changes in autophagy level in C28/I2 cells overexpressing CHERP and IRE1α were detected using immunofluorescence assay.@*RESULTS@#Tunicamycin treatment significantly up-regulated ER stress-related proteins and LC3 Ⅱ/LC3 Ⅰ ratio and down-regulated the expression of p62 in C28/I2 cells (P < 0.05). Rapamycin obviously up-regulated LC3 Ⅱ/LC3 Ⅰ ratio (P < 0.001) in C28/I2 cells, but this effect was significantly attenuated by co-treatment with 4μ8c (P < 0.05). Compared with the cells from the wild-type mice, the primary chondrocytes from ERN1 knockout mice showed significantly down-regulated mRNA levels of ERN1 (P < 0.01), ATG5 (P < 0.001) and ATG7 (P < 0.001), lowered or even lost expressions of IRE1α and p-IRE1α proteins (PP < 0.01), and increased expression of CHERP (P < 0.05) and intracellular calcium ion content (P < 0.001). Bafilomycin A1 treatment obviously increased LC3 Ⅱ/ LC3 Ⅰ ratio in the chondrocytes from both wild-type and ERN1 knockout mice (P < 0.01 or 0.05), but the increment was more obvious in the wild-type chondrocytes (P < 0.05). Treatment with autophagy dual-fluorescence virus resulted in a significantly greater fluorescence intensity of LC3-GFP in rapamycin-treated ERN1 CKO chondrocytes than in wild-type chondrocytes (P < 0.05). In C28/I2 cells, overexpression of CHERP obviously decreased the fluorescence intensity of LC3, and overexpression of IRE1α enhanced the fluorescence intensity and partially rescued the fluorescence reduction of LC3 caused by CHERP.@*CONCLUSION@#IRE1α deficiency impairs autophagy in chondrocytes by upregulating CHERP and increasing intracellular calcium ion content.

Clinical significance and prognostic value of fibrinogen in the treatment of locally advanced head and neck squamous cell carcinoma treated with induction chemotherapy combined with radiotherapy / 中华放射医学与防护杂志

Objective:To explore the clinical significance and prognostic value of fibrinogen (FIB) in the treatment of locally advanced head and neck squamous cell carcinoma with induction chemotherapy combined with radiotherapy.Methods:A retrospective analysis was conducted for the clinical data of 114 patients with locally advanced head and neck squamous cell carcinoma receiving non-surgical treatment in the Department of Head and Neck Oncology, the Affiliated Cancer Hospital of Guizhou Medical University from May 2011 to May 2021. The FIB critical value was determined based on the median FIB level before induction chemotherapy, by which patients were divided into high-FIB and low-FIB groups. The ROC curves were used to determine the optimal cut-off value for other hematologic-related parameters such as neutrophils, lymphocytes, and platelets. Statistical methods were used to analyze the results. The enumeration data were analyzed by Chi-square test or Fisher exact probability method. Survival curves for OS and PFS were plotted by Kalplan-Meier method and tested by Log-rank method. Prognostic factors were evaluated by Cox proportional hazard regression model.Results:There were 59 cases in the high-FIB group (FIB > 3.6 g/L) and 55 cases in the low-FIB group (FIB ≤ 3.6 g/L). The high FIB group had higher neutrophils, platelets, NLR, and PLR ( χ2= 7.84, 12.80, 15.04, 9.14; P<0.05) than the low FIB group. The 3- and 5-year overall survival (OS) rates were significantly longer in the low FIB group than those in the high-FIB group (62.9% vs. 39.6%; 46.9% vs. 25.8%), and progression-free survival (PFS) rates of the low FIB group significantly longer than those of the high-FIB group (63.3% vs. 40.3%; 48.1% vs. 26.2%). The univariate analysis showed that the OS and PFS in patients with locally advanced head and neck squamous cell carcinoma were related to FIB, the application of concurrent chemoradiotherapy, and the efficacy of radiotherapy for lymph nodes. The multivariate analysis showed that FIB, the application of concurrent chemoradiotherapy, and the efficacy of radiotherapy for lymph nodes were independent prognostic factors of the OS [ HR (95% CI): 1.89 (1.08-3.31), 3.76 (1.12-12.65), 2.14 (1.09-4.21), P < 0.05]and PFS HR (95% CI): 1.92 (1.90-3.36), 3.93 (1.01-11.34), 2.15 (1.09-4.22), P < 0.05]of patients with locally advanced head and neck squamous cell carcinoma. Conclusions:Patients with low FIB receive high OS and PFS rates after induction chemotherapy combined with radiotherapy. Therefore, FIB can be used as a prognostic factor in the evaluation of non-surgical treatment of patients with locally advanced head and neck squamous cell carcinoma.

Clinical significance of expression of tumor immunogenic cell death related molecules / 国际肿瘤学杂志

Tumor immunogenic cell death is a type of regulatory cell death, which is driven by stress including chemotherapy drugs, radiotherapy, oncolytic virus, nano carrier drugs and photodynamic force. It can induce specific immune response to tumor death cell antigen. The further study can provide theoretical basis and new ideas for anti-tumor immunity and clinical immunotherapy of tumor.

The Role of NEDD4-1 in Tumorigenesis of the Digestive System / 中国生物化学与分子生物学报

Neural precursor cell Expressed‚Developmentally Down-regulated protein 4 (NEDD4-1‚ also known as NEDD4 in some papers) is a tumor-related protein that has attracted much attention in recent years. It belongs to the E3 HECT (homologous to E6 associated protein C terminus) ubiquitin ligase‚ which could ubiquitinate various proteins that are subsequently degraded in lysosomes or proteasomes‚ or mediate their nuclear-cytoplasmic translocation‚ or indirectly affect various signaling pathways of different malignant tumors. With the deepening of a large number of tumor-related experiments‚ it has been found that NEDD4-1 can affect the biological behavior of tumors by regulating cell cycle‚ invasion and metastasis of cancer cells‚ antagonize drug resistance and many other pathways. In digestive system tumors‚ NEDD4-1 mainly promotes the proliferation‚ invasion and migration of hepatocellular carcinoma through multiple pathways such as PTEN/ PI3K/ Akt‚ TGF-β‚ Hippo and LDLRAD4. In pancreatic cancer‚ NEDD4-1 acted as an oncogene in the PI3K/ Akt signaling pathway‚ but acted as a tumor suppressor gene in the Myc-Sirt2 signaling circuit. In gastric and colorectal cancer‚ the NEDD4-1-related signaling pathways are different from other digestive system tumors. NEDD4-1 promotes gastric cancer progression and metastasis (via the EGFR signaling pathway) and inhibits colorectal cancer tumor growth (via the Wnt signaling pathway) independently of the PTEN/ PI3K/ Akt pathway. NEDD4-1 has become a hot research direction for therapeutic purposes. In this paper‚ we summarize the functions‚ signaling pathways and potential inhibitors of NEDD4-1 in different digestive system tumors‚ and discuss the relationship between NEDD4-1 and different signaling pathways‚ aiming to provide important reference data for cancer therapy.

Finite element analysis of facet joint between normal and lumbar disc hemiation in adolescents / 解剖学报

Objective To investigate the effect of facet joint asymmetry on lumbar biomechanics in normal and patients with adolescent lumbar disc hemiation (ALDH). Methods Mimics 21.0, 3-Matic Medical 13.0, Geomagic Wrap 2017, HyperMesh 2019 and finite element software ABAQUS 2021 were combined to establish three-dimensional finite element models of nonnal lower lumbar spine and adolescent lumbar disc hemiation. According to the difference between the left and right facet joints, three cases of nonnal and ALDH patients aged 13-18 years old were selected, with a total of 6 cases. The stress of intervertebral disc under different torque loads (neutral position, lateral flexion and rotation) was analyzed and compared. Results 1. Three dimensional finite element models of L3-L, segments were established in 6 male nonnal and adolescent patients with lumbar disc herniation, and the stress and displacement nephogram of lumbar disc hemiation in nonnal neutral position, flexion, extension, lateral flexion and rotation were obtained; 2. The stress of L4_, annulus fibrosus increased when the facet joint angle of nonnal adolescents was symmetrical in the neutral position; 3. The stress of annulus fibrosus was greater than that of nucleus pulposus under different conditions, and the stress of annulus fibrosus was flexion > neutral position > extension; 4. In patients with ALDH, the left side of the facet joint was larger than the right 10 ° model, and the stress in the posterior side of the annulus fibrosus of L4_, segment increased significantly under extension condition. Under lateral flexion condition, the left stress of the left annulus fibrosus was compared with the right stress of the right annulus fibrosus, t = l. 575, P<0. 05, the difference was statistically significant, the right stress of the right annulus fibrosus was greater than the left stress of the left annulus fibrosus. Under the rotating condition, the stress on the left and right sides of the fiber ring was greater than that on the back side. Conclusion 1. Compared with nonnal and patients with ALDH, the stress of intervertebral disc increases under different postures, which ma)' increase the shear load of intervertebral disc and aggravate the process of intervertebral disc degeneration; 2. When the degree of left-right asymmetry of facet joint is more than 10 degrees, the stress on the side with small degree is greater. Facet joint asymmetry can lead to the overload of vertebral bod)' and intervertebral disc, leading to spinal instability; 3. The stress of intervertebral disc in extension is less than that in neutral position and flexion. Extension can relieve the pressure of intervertebral disc and play an auxiliary role in the recovery of patients with ALDH.

Effect of Buyang Huanwutang on Protein Expression of MAP-2， NF-M and GAP-43 After Sciatic Nerve Transection Anastomosis in Rats / 中国实验方剂学杂志

Objective:To investigate the effects of Buyang Huanwutang on the expression of microtubule-associated protein-2（MAP-2）， neurofilament-M（NF-M）， and growth associated protein-43（GAP-43）in rat sciatic nerve after sciatic nerve transection and anastomosis. To explore the mechanism of Buyang Huanwutang promoting peripheral nerve regeneration. Method:SD rats were selected as the experimental subjects， and sciatic nerve transection model was selected as the experimental model. They were randomly divided into model group， sham operation group， Buyang Huanwutang group high， medium and low dose （29.6， 14.8， 7.4 g·kg^-1）group， and mecobalamin （0.156 mg·kg^-1）group， the model group and the sham operation group were given distilled water intragastric administration. After successful modeling， each group was treated with relevant drugs for 4 weeks. After 4 weeks， sciatic nerve function index（SFI）， degree of inclined plate test and hematoxylin-eosin（HE）of sciatic nerve in each group were tested. The expression levels of MAP-2， NF-M， and GAP-43 at the sciatic nerve anastomosis site were detected by immunohistochemistry and Western blot. Result:Compared with sham operation group， the expression levels of SFI， inclined plate test， MAP-2， NF-M and GAP-43 in model group were significantly increased （<italic>P</italic><0.01）. Compared with model group， the expression levels of SFI， inclined plate test， MAP-2， NF-M and GAP-43 in Buyang Huanwutang high， medium and low-dose groups were significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:Buyang Huanwutang has a positive effect on nerve regeneration after sciatic nerve transection and anastomosis in rats.

Effect and Mechanism of Shaofu Zhuyutang on Endothelial Injury of Rats with Cold Coagulation and Blood Stasis Syndrome Based on Nrf2/ARE Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the effect of Shaofu Zhuyutang on nuclear factor erythroid-2-related factor 2 （Nrf2） /antioxidant response element （ARE） signaling pathway in blood vessels by establishing the model of rats with cold coagulation and blood stasis syndrome， and to explore the protective effect and mechanism of Shaofu Zhuyutang on vascular endothelial injury. Method:The 50 SPF rats were randomly divided into high dose group （4.8 g·kg-1）， middle dose group （2.4 g·kg-1）， low dose group （1.2 g·kg-1）， model group and normal group （ten of each group）. The rat model of cold coagulation and blood stasis syndrome was established by subcutaneous injection of epinephrine hydrochloride combined with ice bath. At the same time of modeling， the drug was administered by gavage. After 28 days of continuous administration， the hemorheology indexes were detected by automatic hemorheology instrument. Levels of nitric oxide （NO）， endothelin （ET）-1， superoxide dismutase （SOD）， glutathione （GSH-Px）， intercellular adhesion molecule-1（ICAM-1）， vascular cell adhesion molecule-1（VCAM-1）， von Willebrand factor （vWF） in serum were determined by ELISA. Hematoxylin and eosin （HE） staining was used to observe the endothelial injury of vascular tissue of thoracic aorta. The protein expression of Nrf2 and HO-1 in vascular tissue of thoracic aorta was detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）was used to observe the expression of Nrf2 and heme oxygenase-1 （HO-1） mRNA in vascular tissue of thoracic aorta. Result:Compared with the blank group， model group rats whole blood viscosity and plasma viscosity were significantly increased （P<0.05，P<0.01）， vWF， ICAM 1， VCAM 1 content increased significantly （P<0.01）， NO， SOD， gsh-px levels decreased significantly （P<0.01）， significantly increased the content of ET-1（P<0.01）， thoracic aorta vascular tissue Nrf2， HO-1 mRNA expression was significantly increased （P<0.01）， Nrf2 protein expression in the cell nucleus increased significantly （P<0.05）， The protein expression level of Nrf2 in cytoplasm was significantly decreased （P<0.05）， while the protein expression level of HO-1 was significantly increased （P<0.01）. Compared with model group， the whole blood viscosity （high and middle cut）， plasma viscosity， were significantly reduced in high and meduim-dose Shaofu Zhuyutang groups（P<0.05，P<0.01）. The levels of vWF， ICAM-1， VCAM-1 and ET-1 in serum were significantly reduced （P<0.05，P<0.01）， NO， SOD and GSH-Px increased significantly （P<0.05，P<0.01）. The pathological changes such as hyperplasia， swelling and shedding of endothelial cells of thoracic aorta， rupture of internal elastic membrane and disorder of smooth muscle arrangement were improved. The expression levels of Nrf2， HO-1 protein and gene were significantly increased in vascular tissue of thoracic aorta （P<0.01）. Conclusion:Shaofu Zhuyutang has a protective effect on vascular endothelial injury in rats with cold coagulation and blood stasis syndrome. The mechanism of action is related to the activation of Nrf2/ARE signaling pathway， which leading to the increased expression of antioxidant enzymes and decreased the expression of adhesion factors.

Clinical information and management status of de novo stage IV breast cancer patients: a Chinese multicenter investigation (CSBrS-002) / 中华医学杂志(英文版)

BACKGROUND@#Although de novo stage IV breast cancer is so far incurable, it has entered an era of individualized treatment and chronic disease management. Based on systemic treatment, whether the surgical resection of primary or metastatic foci of de novo stage IV breast cancer can bring survival benefits is currently controversial. We aimed to explore the clinicopathological factors and current status of the management of de novo stage IV breast cancer in China to provide a reference for clinical decisions.@*METHODS@#Based on the assistance of Chinese Society of Breast Surgery, a retrospective study was conducted to analyze the clinical data of patients with de novo stage IV breast cancer in 33 centers from January 2017 to December 2018. The relationship between basic characteristic (age, menstrual status, family history, reproductive history, pathological type, estrogen receptor [ER] status, progesterone receptor [PR] status, human epidermal growth factor receptor 2 [HER2] status, Ki-67 percentage, and molecular subtype), and metastasis sites (lung metastasis, liver metastasis, and bone metastasis) was examined by Pearson Chi-square tests.@*RESULTS@#A total of 468 patients with de novo stage IV breast cancer were enrolled. The median age of the enrolled patients was 51.5 years. The most common pathological type of primary lesion was invasive carcinoma (97.1%). Luminal A, luminal B, HER2 overexpressing, and triple-negative subtypes accounted for 14.3%, 51.8%, 22.1%, and 11.8% of all cases, respectively. Age, PR status, and HER2 status were correlated with lung metastasis (χ2 = 6.576, 4.117, and 8.643 and P = 0.037, 0.043, and 0.003, respectively). Pathological type, ER status, PR status, and molecular subtype were correlated with bone metastasis (χ2 = 5.117, 37.511, 5.224, and 11.603 and P = 0.024, <0.001, 0.022, and 0.009, respectively). Age, PR status, HER2 status, Ki-67 percentage, and molecular subtype were correlated with liver metastasis (χ2 = 11.153, 13.378, 10.692, 21.206, and 17.684 and P = 0.004, <0.001, 0.001, <0.001, and 0.001, respectively). Combined treatment with paclitaxel and anthracycline was the most common first-line chemotherapy regimen for patients with de novo stage IV breast cancer (51.7%). Overall, 91.5% of patients used paclitaxel-containing regimens. Moreover, 59.3% of hormone receptor-positive patients underwent endocrine therapy.@*CONCLUSIONS@#In 2018, 1.07% of patients from all studied centers were diagnosed with de novo stage IV breast cancer. This study indicated that 95.1% of patients received systemic therapy and 54.2% of patients underwent surgical removal of the primary lesion in China.

SPOP-mediated Non-degradative Ubiquitination / 中国生物化学与分子生物学报

Protein post-translational modification is a precondition guaranteeing normal exertion of protein functions. Ubiquitination is an important post-translational modification that maintains normal protein levels and activity. Numerous researches show that the E3 ubiquitin ligase speckle-type POZ protein (SPOP) displays mutations in many tumors and genetic diseases. Mainly concentrated in the MATH structural domain that recognizes substrates, these mutations influence the binding between SPOP and substrates, and further influence their protein levels, positioning and activities, thus disturbing the normal physiological functions. Wild-type SPOP binds the substrates, most of which enter the proteasome pathway for decomposition after being ubiquitinated by SPOP, but some substrates are also influenced functionally. Herein we review the ubiquitination types and functions of SPOP substrates, including the ubiquitin-proteasome system (UPS), structure, functions and molecular pathways of SPOP, and non-degradative ubiquitinated modification of SPOP. The emphasis will be laid on the molecular mechanisms of the signaling pathways mediated by the three non-degradative substrates of SPOP, that is, myeloid differentiation primary response gene 88 (MyD88)-mediated NF-κB pathway, X-chromosome silence signal pathway of histone macroH2A1 (macroH2A. 1 histone, macroH2A1), and inverted formin 2 (INF2)mediated chondriokinesis pathway, in inhibiting tumorigenesis and development. We expect to provide a new perspective for precise targeted therapies of tumors.