Objective To investigate the effect of exogenous protectin DX (PDX) on acute lung injury in septic mice.Methods Thirty male C57BL/6 mice,aged 6-8 weeks,weighing 20-25 g,were randomly divided into 3 groups (n =10 each) using a random number table:sham operation group (Sham group),sepsis group (S group) and PDX group.Sepsis was produced by cecum ligation and puncture (CLP) in the mice anesthetized with pentobarbital sodium.At 1 h after CLP,PDX 300 ng was injected intraperitoneally in PDX group,and the equal volume of normal saline was given in Sham and S groups.At 24 h after CLP,the mice were sacrificed,and the broncho-alveolar lavage fluid (BALF) was collected for determination of interleukin-1beta (IL-1β),tumor necrosis factor-alpha (TNF-α),IL-6 and IL-10 concentrations,and the lungs were removed for microscopic examination and for determination of the myeloperoxidase (MPO) activity,wet/dry lung weight ratio (W/D ratio) and phosphorylation of nuclear factor-kappa B (NF-κB) p65.Lung injury scores were calculated.Results Compared with Sham group,the lung injury score,MPO activity,W/D ratio,phosphorylation of NF-κB p65,and concentrations of protein and inflammatory factors in BALF were significantly increased in S and PDX groups (P＜0.05).Compared with S group,the lung injury score,MPO activity,W/D ratio,phosphorylation of NF-κB p65,and concentrations of protein,IL-1β,TNF-α and IL-6 in BALF were significantly decreased,and the concentration of IL-10 in BALF was significantly increased in PDX group (P＜0.05).Conclusion Exogenous PDX can alleviate acute lung injury through inhibiting NF-κB activity in the lung tissues of septic mice.

Objective To evaluate the clinical significance of the clinical diagnosis and efficacy monitoring of serum gastrin-releasing peptide precursor (ProGRP) in small cell lung cancer (SCLC) patients.Methods A total of 4032 patients were admitted to a hospital from March 2015 to August 2017, determining serum ProGRP concentrations of 144 patients with small cell lung cancer, 1618 patients with the non-small cell lung tumor group, 42 patients with benign lung tumors, 231 with extrapulmonary malignant tumors, 275 with extrapulmonary benign disease, 1, 402 with benign lung disease, and 320 healthy patients.Analysis and evaluation of ProGRP values before and after treatment in patients with SCLC changes and the correlation of tumor size.Results Serum ProGRP levels in small cell lung cancer group were higher than those in each group.U test shows P＜0.05 in each group.U test shows P＜0.05 in patients with renal failure and healthy controls;prolonged ProGRP values in patients with small cell lung cancer were higher than the limited period.U test shows P＜0.05.Serum ProGRP U-test shows P＜0.05 between before and after treatment in small cell lung cancer progression and remission groups.Serum ProGRP U-test shows P＞0.05 between before and after treatment in small cell lung cancer stable group.Serum ProGRP concentration and tumor mass in small cell lung cancer The size is consistent.Compared with healthy control group, the lung non-small cell tumor group, lung benign tumor group, extrapulmonary malignant tumor group, intrapulmonary benign disease group conduct U test, showing P＞0.05.Conclusion Serum ProGRP is a specific tumor marker of SCLC without the interference of renal failure.It can be used as an auxiliary basis for SCLC staging, monitoring prognosis, and evaluating clinical efficacy of important indicators.

OBJECTIVETo investigate the effect of 17-allylamino-demethoxygeldanamycin (17AAG) on the proliferative and invasive ability of gastric cancer cells and associated mechanism.

METHODSThe proliferative ability was tested by MTT method and the cell cycle was detected by flow cytometry(FCM) when 17AAG was used to treat gastric cancer cell SGC7901. Apoptosis was detected by FCM and PI-Annexin V double staining. The invasive ability was tested by transwell method. Expression of HSP90, HSP70, c-met and AKT was detected by Western blot.

RESULTSThe growth of SGC7901 cells was inhibited after the administration of 17AAG, and the inhibitation was dose- and time-dependent. The cell cycle was blocked at the G0/G1 phase. The apoptotic ratio in 17AAG group was much higher than that in blank group and DMSO group (P<0.01). The cellular invasive ability decreased significantly (P<0.01). The expression of HSP70 was elevated by 17AAG, and the expression of c-met and AKT was down-regulated, but no change of HSP90 was observed.

CONCLUSION17AAG can inhibit the proliferative and invasive ability of SGC7901 cells, and induces apoptosis through down-regulating the expression of HSP90 client proteins instead of the target HSP90 itself.

Apoptosis ; Benzoquinones ; pharmacology ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; HSP70 Heat-Shock Proteins ; HSP90 Heat-Shock Proteins ; Humans ; Lactams, Macrocyclic ; pharmacology ; Neoplasm Invasiveness ; Stomach Neoplasms ; pathology

Objective To investigate the effect of 17-allylamino-demethoxygeldanamycin (17AAG) on the proliferative and invasive ability of gastric cancer cells and associated mechanism. Methods The proliferative ability was tested by MTT method and the cell cycle was detected by flow cytometry (FCM) when 17AAG was used to treat gastric cancer cell SGC7901. Apoptosis was detected by FCM and PI-Annexin V double staining. The invasive ability was tested by transwell method. Expression of HSP90, HSP70, c-met and AKT was detected by Western blot. Results The growth of SGC7901 cells was inhibited after the administration of 17AAG, and the inhibitation was dose- and time-dependent. The cell cycle was blocked at the G0/G1 phase. The apoptotic ratio in 17AAG group was much higher than that in blank group and DMSO group (P<0.01). The cellular invasive ability decreased significantly (P<0.01). The expression of HSP70 was elevated by 17AAG, and the expression of c-met and AKT was down-regulated, but no change of HSP90 was observed. Conclusion 17AAG can inhibit the proliferative and invasive ability of SGC7901 cells , and induces apoptosis through down-regulating the expression of HSP90 client proteins instead of the target HSP90 itself.

Objective To investigate the effect of 17-allylamino-demethoxygeldanamycin (17AAG) on the proliferative and invasive ability of gastric cancer cells and associated mechanism. Methods The proliferative ability was tested by MTT method and the cell cycle was detected by flow cytometry (FCM) when 17AAG was used to treat gastric cancer cell SGC7901. Apoptosis was detected by FCM and PI-Annexin V double staining. The invasive ability was tested by transwell method. Expression of HSP90, HSP70, c-met and AKT was detected by Western blot. Results The growth of SGC7901 cells was inhibited after the administration of 17AAG, and the inhibitation was dose- and time-dependent. The cell cycle was blocked at the G0/G1 phase. The apoptotic ratio in 17AAG group was much higher than that in blank group and DMSO group (P<0.01). The cellular invasive ability decreased significantly (P<0.01). The expression of HSP70 was elevated by 17AAG, and the expression of c-met and AKT was down-regulated, but no change of HSP90 was observed. Conclusion 17AAG can inhibit the proliferative and invasive ability of SGC7901 cells , and induces apoptosis through down-regulating the expression of HSP90 client proteins instead of the target HSP90 itself.

OBJECTIVE: To develop a cell-based system for the diagnosis of vitamin K-dependent coagulation factor deficiency 1 (VKCFD1). METHODS: In HEK293 cells stably expressing the reporter gene FIX-Gla-PC, the gamma-glutamyl carboxylase (GGCX) gene was knocked out by using CRISPR/Cas9 technology. Enzyme-linked immunosorbent assay (ELISA), DNA sequencing and Western blotting were used to identify the GGCX gene knockout cells. A quickchange point variant method was used to construct the GGCX variant. ELISA was used to assess the influence of GGCX variant on the activity of reporter gene. RESULTS: Two monoclonal cell lines with no reporter activity by ELISA was identified. Edition and knockout of the GGCX gene was confirmed by DNA sequencing and Western blotting. The activity of the reporter gene was recovered by transfection of the wild-type GGCX gene. Thereby two monoclonal cells with GGCX knockout were obtained. By comparing the wild-type and pathogenic GGCX variants, the reporter activity was decreased in the pathogenic variants significantly. CONCLUSION A cell-based system for the detection of GGCX activity was successfully developed, which can be used for the diagnosis of VKCFD1 caused by GGCX variants.

The immune microenvironment plays an important role in the occurrence and development of breast cancer. The infiltrating immune cells and the produced inflammatory cytokines in the tumor microenvironment regulate the growth, proliferation and metastasis of breast cancer. In this article, the roles and related mechanisms of nonspecific immune microenvironment in breast cancer are summarized, focusing on the natural killer cells, dendritic cells, myeloid derived suppressor cells, tumor associated macrophages, interleukins, chemokines, tumor necrosis factor-α, transforming growth factor-β and so on.
Breast Neoplasms ; immunology ; physiopathology ; Chemokines ; immunology ; Dendritic Cells ; immunology ; Humans ; Macrophages ; immunology ; Research ; trends ; Tumor Microenvironment ; immunology

Objective To summarize the current research status and cutting-edge trends of the off-label drug use in China,with a view to providing reference for researchers in this field.Methods CNKI and SinoMed databases were searched to collect research of the off-label drug use in China,and used Microsoft Excel 2021,the R software Bibliometric,and VOSviewer 1.6.18 to visualize the time and trend of publication,province,issuing authors and units,journals,keywords,and topic evolution of the included studies.Results 1 475 papers were included in the research.A total of 2 808 authors from 31 provinces,cities and regions had conducted relevant studies on over-the-counter medication,with an overall increasing trend in the number of publications.Among them,Guangdong province published the most studies related to this field,the Straits Pharmacy Journal and China Pharmacy published the most studies in this field.Proprietary Chinese medicines,antimicrobials,antitumor drugs,and other drugs were the research hotspots.In addition,the patients in pediatrics,outpatient emergency,obstetrics and gynecology,psychiatry and other departments as a special sick population,the clinical use of medication exists in the overspecification situation was also a future research trend.Conclusion At present,research in this field focuses more on OLDU for special populations,special diseases,special drugs,etc.In the future,researchers should conduct evidence-based evaluation of drugs on the basis of more high-quality evidence in order to seek the best evidence for guiding the clinical use of medication.At the same time,drug administration and medical institutions should also develop standardized management policies and systems to promote the rational and safe use of medication in healthcare institutions.

Fibromyalgia syndrome after comprehensive treatment of breast cancer is rare and seldom reported. Here we present a case of a 50-year-old female patient,who was admitted to the hospital because of generalized fibromyalgia for 3 months and brain metastasis after the right breast carcinoma surgery for 1 month, and the clinical diagnosis was brain metastasis from breast carcinoma combined with fibromyalgia syndrome. The fibromyalgia were relieved with proper symptomatic treatment but the patient eventually died of tumor progression.
Brain Neoplasms ; mortality ; secondary ; Breast Neoplasms ; complications ; mortality ; therapy ; Carcinoma ; mortality ; therapy ; Female ; Fibromyalgia ; diagnosis ; etiology ; therapy ; Humans ; Middle Aged

Esophageal squamous-cell carcinoma (ESCC) is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies (GWAS) of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma (CCGD-ESCC) database, which contains the associations of 69,593 single nucleotide polymorphisms (SNPs) with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients (survival GWAS) and gene expression (expression quantitative trait loci, eQTL) in 94 ESCC patients. Moreover, this database also provides the associations between 8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http://db.cbi.pku.edu.cn/ccgd/ESCCdb.
Aged ; Asian Continental Ancestry Group ; genetics ; China ; epidemiology ; Databases, Genetic ; Esophageal Squamous Cell Carcinoma ; genetics ; Female ; Genetic Predisposition to Disease ; Genetic Variation ; Genome-Wide Association Study ; Humans ; Internet ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; User-Computer Interface