Aim To explore whether platelet-derived growth factor C(PDGFC)derived from cancer-associat-ed fibroblasts(CAFs)can promote resistance of breast cancer cells to doxorubicin(DOX)and the underlying mechanisms.Methods CAFs and normal fibroblasts(NFs)were extracted from freshly resected breast cancer tissue and adjacent normal breast tissue respec-tively.Conditioned medium(CM)from CAFs and NFs was collected and co-cultured with breast cancer cells.Cell proliferation and toxicity were assessed using a Cell Counting Kit-8(CCK-8).The expression of PDG-FC in CAFs,NFs and corresponding CM was detected by Western blot and ELISA respectively.The influence of CAFs-CM on intracellular doxorubicin content in breast cancer cells was observed by fluorescence mi-croscopy.The impact of CAFs-CM on apoptosis-related proteins BAX and BCL2 was predicted and valifated u-sing the Starbase database and Western blot.The changes in ROS levels,mitochondrial membrane po-tential,and mitochondrial membrane proteins TOM20 and COX Ⅳ in breast cancer cells were measured using DCFH-DA fluorescence staining,JC-1 assay,and Western blot.Results CAFs-CM decreased the intra-cellular doxorubicin content and inhibited the sensitivi-ty of breast cancer cells to doxorubicin.Additionally,the expression of apoptosis protein BAX decreased while the anti-apoptotic protein BCL2 increased in breast cancer cells cultured with CAFs-CM.Further-more,CAFs-CM led to decreased ROS levels and in-creased mitochondrial membrane potential in breast cancer cells accompanied with elevated expression of mitochondrial membrane proteins TOM20 and COX Ⅳ.Further study found that PDGEF was highly expressed in CAFs and CAFs-CM,recombinant human PDGFC produced resistance of breast cancer cells to DOX simi-lar to CAFs-CM,and the specific inhibitors of PDGFRα significantly inhibited CAFs-CM.Further mechanistic studies revealed that PDGFC in CAFs-CM induced chemoresistance by activating PI3K-mTOR signaling pathway.Conclusion PDGFC secreted by CAFs promotes doxorubicin resistance in breast cancer cells through PI3K-mTOR signaling pathway,which provides a new perspective for the development of anti-cancer drugs targeting CAFs.

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1β(IL-1β). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1β, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.
Animals ; Mice ; Network Pharmacology ; Vascular Endothelial Growth Factor A ; Molecular Docking Simulation ; Arthritis, Rheumatoid/genetics* ; Tumor Necrosis Factor-alpha ; NF-kappa B ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional

To investigate the prevalence of diabetes mellitus (DM) among residents in Chongchuan district, Nantong city in 2012 and 2018, and evaluate the effectiveness of community comprehensive management of DM. Based on the data of 17 780 and 13 382 residents in the cross-sectional surveys of the " National Demonstration Area for Comprehensive Prevention and Control of Chronic Diseases " project in Chongchuan District of Nantong City, Jiangsu Province in 2012 and 2018, 4 583 and 3 996 DM-related information were obtained. The population of Jiangsu Province in 2012 and 2018 was used as the reference for standardization. The rates of prevalence and management (including awareness, treatment, treatment of patients who knew their diabetic situation, control and control of patients under treatment) of DM in the two surveys were compared using chi-square test. The results showed that in 2012 and 2018, the prevalence rates of DM were 12.0% and 15.7% (χ²=24.25, P<0.05), and the standardized rates were 10.1% and 10.8% (χ²=1.05, P=0.306). The incidence rates were 5.7% and 2.3%, respectively (χ²=55.60, P<0.05). The standardized prevalence rates in the two surveys were 9.7% and 11.6% for males (χ²=3.66, P=0.056) and 10.5% and 9.9% for females (χ²=0.50, P=0.481), 7.2% and 6.5% (χ²=0.85, P=0.357) for people aged 18-59 years old and 20.6% and 21.9% (χ²=0.91, P=0.339) for people aged 60 years and over, respectively. The standardized rates of awareness, treatment, treatment of patients who knew their diabetic situation, control, and control of patients under treatment in 2018 were 84.4%, 80.3%, 95.2%, 58.4%, and 70.2%, respectively, higher than 47.2%, 23.4%, 44.8%, 30.4% and 59.4% in 2012 (χ²=183.33, χ²=380.65, χ²=282.99, χ²=93.24, χ²=6.22, all P<0.05). Among men, the standardized rates of awareness, treatment, treatment of patients who knew their diabetic situation, and control in 2018 were 85.8%, 78.8%, 91.8% and 62.7%, higher than 50.5%, 37.5%, 72.3% and 32.6% in 2012 (χ²=78.40, χ²=96.17, χ²=27.55, χ²=48.96, all P<0.05). Similarly, the standardized management rates in 2018 were 83.0%, 81.7%, 98.5%, 54.1% and 65.1%, higher than 44.0%, 10.0%, 18.3%, 28.2% and 48.8% in 2012 among women (χ²=105.52, χ²=326.36, χ²=317.22, χ²=43.34, χ²=3.87, all P<0.05). The standardized rates of awareness, treatment, treatment of patients who knew their diabetic situation, and control of people aged 18-59 and 60 years and over were 82.9%, 79.7%, 96.1%, 55.0% and 88.0%, 81.8%, 93.0% and 67.2%, higher than 42.6%, 19.8%, 42.2%, 27.5% and 63.9%, 36.8%, 53.9%, 40.8% in 2012 (χ²=44.51, χ²=102.17, χ²=57.78, χ²=21.65, all P<0.05; χ²=71.18, χ²=181.55, χ²=146.26, χ²=59.23, all P<0.05). The comprehensive prevention and control system of chronic diseases, which comprehensively covered the life of community residents, had good management effect on DM, and effectively promoted health education and health promotion.
Adolescent ; Adult ; Aged ; Cross-Sectional Studies ; Diabetes Mellitus/prevention & control* ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Prevalence ; Rural Population ; Young Adult

Aim To investigate the protective effect of sinomenine(SIN)against dibutyltin(DBT)induced injury in HL02 cells and explore the potential mechanism.Methods HL02 cells were cultured and divided into control,model and SIN-treated groups.Cell proliferation was detected by MTT method.Cell morphology was observed.Cell apoptosis was detected by Acridine orange/ethidium bromide(AO/EB)fluorescent staining and Annexin V-FITC/PI double staining.Meanwhile,intracellular reactive oxygen species(ROS)concentration was detected by DCFH-DA staining.Mitochondrial membrane potential(MMP)was tested by JC-1 dye.Moreover,the mRNA expression of apoptosis-related proteins was detected by qRT-PCR,and the protein expression of Bcl-2,Bax,caspase-9,cleaved-caspase-3 were measured via Western blot.Results The pretreatment with SIN increased the cell viability and decreased morphological changes induced by DBT in a dose-dependent manner.Meanwhile,cell apoptotic rates and intracellular ROS decreased,and the loss of MMP was partially restored.Compared to DBT-treated group,SIN treatment could increase the mRNA levels of Bcl-2,Bcl-xL and decrease the mRNA levels of Bax,Bad,cytochrome-c,Apaf-1,caspase-9 and caspase-3.Furthermore,SIN could significantly up-regulated the DBT-induced decrease in Bcl-2/Bax ratio,and down-regulated the DBT-induced over-expressions of caspase-9 and cleaved-caspase-3.Conclusions SIN could protect HL02 cells against DBT-induced cell injury,which is related to the inhibition of ROS-mediated mitochondrial apoptosis.

Breast Neoplasms/surgery* ; China ; Female ; Humans ; Mastectomy ; Risk Assessment

The development of quality Chinese medicine is an important way to improve the quality of Chinese medicine, and ensure the safety and effectiveness of Chinese medicine. This article systematically elaborates the definition, classification, standard and mana-gement certification strategy of quality Chinese medicine. We present the quality Chinese medicine which is higher quality than that of eligible Chinese medicine based on quality control standards. Quality Chinese medicine is strictly in accordance with management procedures, likely GAP and GMP et al, during the productive process, which quality indicators is higher than that of the current relevant national quality standards, such as Chinese Pharmacopoeia(ChP) et al; its limited indicators such as exogenous pollutants and endogenous toxic substances are lower than that of the current relevant national quality standards, likely ChP et al; meanwhile these Chinese herbal medicine, medicinal pieces, patent medicines, and health products and foods with Chinese medicine raw materials are been certificated by quality Chinese medicine. At the same time, this article systematically expounds the five major management systems of quality Chinese medicine, including technical training management for practitioners, productive process management, standard mana-gement, quality inspection and certification management, and product traceability management. And we put forward strategies to improve the supervision and management system, and promote the standardization and development of quality Chinese medicine by improving the technical management system of quality Chinese medicine, strengthening the quality management system and six sigma(6σ) management in the company. These strategies will provide a reliable basis and effective way to improve the quality of Chinese medicine.
Drugs, Chinese Herbal ; Food ; Medicine, Chinese Traditional ; Quality Control ; Reference Standards

Objective: To explore the possibility of using artificial intelligence (AI) technology based on convolutional neural network (CNN) to assist the clinical diagnosis of laryngeal squamous cell carcinoma (LSCC) through deep learning algorithm. Methods: A deep CNN was developed and applied in narrow band imaging (NBI) endoscopy of 4 799 patients with laryngeal lesions, including 3 168 males and 1 631 females, aged from 21 to 87 years, from 2015 to 2017 in Beijing Tongren Hospital, Capital Medical University. A simple randomization method was used to select the laryngeal NBI images of 2 427 patients (1 388 benign lesions and 1 039 LSCC lesions) for the training and correction the CNN model. The remaining laryngeal NBI images of 2 372 patients (including 1 276 benign lesions and 1 096 LSCC lesions) were used as validation data set to compare performance between CNN and otolaryngologists. SPSS 21.0 software was used for Chi-square test to calculate the accuracy, sensitivity and specificity of AI and otolaryngologists. The area under the curve (AUC) of receiver operating curve (ROC) was used to evaluate the diagnostic ability of the algorithm for NBI images. Results: The accuracy, sensitivity and specificity for NBI predictions were respectively 90.91% (AUC=0.96), 90.12% and 91.53%, which were equivalent to those for otolaryngologists' predictions (accuracy, sensitivity and specificity were (91.93±3.20)%, (91.33±3.25)% and (93.02±2.59)%, t values were 0.64, 0.75 and 1.17, and P values were 0.32, 0.28 and 0.21, respectively). The diagnostic efficiency of CNN was significantly higher than that of otolaryngologists (0.01 vs. 5.50, t =9.15, P<0.001). Conclusion: AI based on deep CNN is effective for using in the laryngeal NBI image diagnosis, showing a good application prospect in the diagnosis of LSCC.
Adult ; Aged ; Aged, 80 and over ; Artificial Intelligence ; Endoscopy ; Female ; Head and Neck Neoplasms ; Humans ; Male ; Middle Aged ; Narrow Band Imaging ; Neural Networks, Computer ; Sensitivity and Specificity ; Squamous Cell Carcinoma of Head and Neck ; Young Adult

OBJECTIVETo investigate the presence of leukemia stem cells (LSC) in acute myeloid leukemia (AML) and find out the relative position of leukemia cells in the figures of flow cytometry, and to analyze the relationship between minimal residual diseases (MRD) and the level of LSC, so as to explore the correlation of LSC changes with the curative effect and the prognosis during chemical therapy.

METHODSA total of 85 samples were collected from 50 AML (except M3) patients, including 50 samples from the newly diagnosed patients, 7 samples of AML patients with non-remission and 28 samples of AML patients with complete remission. All samples were used for detection of LSC from immune phenotype of CD34/CD38/CD123 by flow cytometry. The detection of immune phenotypic of leukemia cells was performed in the newly diagnosed patients. The detection of leukemia- associated immune phenotypes (LAIP) was implemented in the non-newly diagnosed patients.

RESULTSThe LSC was identified in the CD34/ CD38/ CD123 in AML and consistent with the relative position of the leukemia cell in flow cytometry figures. Statistical analysis showed significant difference in LSC content between the newly diagnosed AML group and the post-chemotherapy complete remission group(P<0.01),but did not between the newly diagnosed AML group and the post-chemotherapy non-remission group(P>0.05).There was significant positive correlation between the LSC content and MRD level in 28 AML patients with complete remission (r=0.680,P<0.01).

CONCLUSIONLSC exist in AML and the relative position are consistent with the leukemia cells in flow cytometry figures, the size characteristics and weak expression of CD45 are also similar to leukemia cells. The proportion of LSC decreases after chemotherapy. Detecting and tracking the LSC changes in bone marrow and combination with detecting minimal resident disease(MRD) may contribute to evaluate the theraputic efficacy and prognosis of leukemia patients.

Norovirus (NoV) is a pathogen that commonly causes viral diarrhea in children. Studies indicate that NoV recognizes human histo-blood group antigens (HBGAs) as cell attachment factors. In order to explore the correlation between of NoV infection and HBGAs, a cross-sectional study was conducted in children less than five years old who were hospitalized with diarrhea in two areas of China between November 2014 and February 2015. Of the paired stool and saliva samples taken from 424 children, NoV was detected in 24 (6%) children, with viral genotypes GII.3 (n=5), GII.4 (n=14), GII.12 (n=1), and GII.17 (n=4). All of the individuals having NoV infection were either secretors (Lea-b+/Lex-y+) or partial secretors (Lea+b+/Lex+y+) except one GII.3 infection of a non-secretor (Lea+b-/Lex+y-). These results suggest that secretor positive is associated with NoV infection, although non-secretors are not absolutely protected from NoV infection.
Blood Group Antigens ; genetics ; Caliciviridae Infections ; blood ; complications ; virology ; Child, Preschool ; China ; Cross-Sectional Studies ; Diarrhea ; blood ; etiology ; virology ; Feces ; virology ; Gastroenteritis ; blood ; virology ; Genotype ; Humans ; Infant ; Norovirus ; physiology

In the present study, the complete genomes of four common (4/EV71/Wenzhou/CHN/2014, 15/ EV71/Wenzhou/CHN/2014, 116/EV71/Wenzhou/ CHN/2014, and 120/EV71/Wenzhou/CHN/2014) and two virulent (11/EV71/Wenzhou/CHN/2014 and 109/EV71/Wenzhou/CHN/2014) enterovirus 71 (EV71) isolates were sequenced and described. They are 7405 bp in length and belong to EV71 sub-genotype C4 (C4a cluster). Nucleotide sequence alignment revealed six nucleotide variations (GP151→TP151, GP199→AP199, GP261→TP261, AP328→CP328, GP422→AP422, and GP437→TP437) in the two virulent isolates within the 5'UTR of the IRES element. RNA secondary structure predictions of IRES and FCE indicated that the common isolates shared similar structures, which were different from those of the virulent isolates. Moreover, the GP114→CP114 and GP151→TP151 mutations in the virulent isolates contributed to the formation of the unique RNA secondary structures in SL II. Furthermore, nucleotide/amino acid sequence alignments of 82 EV71 isolates indicated that six sites (TP488 and CP577 in the 5'UTR; AsnP57 in 2A; IleP56 in 3C; CP10 and AP47 in the 3'UTR) are potentially associated with the neurovirulence of EV71. Finally, the 3D structures of 2A were analogous, whereas the structures of VP1 and 3C were variable.
Base Sequence ; Central Nervous System ; virology ; Enterovirus A, Human ; classification ; genetics ; isolation & purification ; pathogenicity ; Enterovirus Infections ; virology ; Genome, Viral ; Genomics ; Genotype ; Humans ; Molecular Sequence Data ; Nucleic Acid Conformation ; Phylogeny ; RNA, Viral ; chemistry ; genetics ; Virulence