Aim To investigate the effects of bone-forming protein BMP9 on aerobic glycolysis,migration and invasion ability in triple-negative breast cancer MDA-MB-231 cells and the underlying mechanisms.Methods The experimental group infected MDA-MB-231 cells with human BMP9 recombinant adenovirus(AdBMP9),while the control group infected cells with empty GFP adenovirus.Lactate,glucose and ATP as-say kits were used to detect glucose uptake,lactate and ATP production.The correlation between BMP9 and key glycolytic enzyme genes in pancarcinoma was ana-lyzed using GEPIA2 database.The mRNA expression levels of GLUT1,HK2,PKM2 and LDHA in MDA-MB-231 cells after overexpression of BMP9 were detec-ted by qRT-PCR.Potential targets of BMP9 inhibiting MDA-MB-231 aerobic glycolysis were analyzed in STRING database.The expression levels of HIF-1αand downstream protein were detected by Western blot.The changes of cell migration and invasion ability after different treatments were evaluated by the scratch heal-ing assay and Transwell assay.Results Compared with the control group,BMP9 down-regulated glucose uptake,lactate production,ATP level(P＜0.01),and inhibited HIF-1α and its downstream protein ex-pression in MDA-MB-231 cells.Overexpression of HIF-1α in rescue experiment reversed the inhibitory effect of BMP9 on aerobic glycolysis,migration and in-vasion of MDA-MB-231 breast cancer cells.Conclu-sion BMP9 down-regulates HIF-1α to inhibit the aer-obic glycolysis and migration and invasion ability of MDA-MB-231 breast cancer cells.

Aim To investigate the effects of autophagy regula-ted by LncRNA SNHG3 on the proliferation,migration,invasion and EMT of human breast cancer cell line MCF-7.Methods The expression of SNHG3 in breast cancer and breast cancer cell line MCF-7 was analyzed by bioinformatics and real-time fluores-cent quantitative PCR(RT-qPCR);RNAi technology was used to construct MCF-7 recombinant cell lines with knockdown SNHG3(siSNHG3)and control(siNC),and Western blot and cellular immunofluorescence were applied to detect autophagy markers;autophagosome lysosomal fusion inhibitor BafA1 or ear-ly autophagosome formation inhibitor 3-MA was employed to treat MCF-7 cells with or without SNHG3 knockdown,Western blot was used to detect the expression of LC3-Ⅱ or p62,and the effect on autophagic vesicle formation or autophagic degradation was observed;clone formation experiment,CCK8 experiment,wound healing experiment,and Transwell experiment were used to detect the effects of siSNHG3 combined or not combined with BafA1 or 3-MA on the proliferation,lateral migration,longitudi-nal migration,and invasion of MCF-7 cells.Western blot was used to detect its effect on the EMT of MCF-7 cells.Results Bioinformatics analysis and RT-qPCR confirmed that SNHG3 was highly expressed in breast cancer and breast cancer cell line MCF-7;Western blot and cellular immunofluorescence confirmed that knockdown of SNHG3 could activate autophagy in breast cancer;the clone formation,CCK-8,wound healing,and Tran-swell experiment confirmed that downregulation of SNHG3 ex-pression could inhibit tumor proliferation,migration,and inva-sion by activating autophagy;Western blot confirmed that SNHG3 promoted EMT process of breast cancer through negative regulation of autophagy.Conclusions SNHG3 is abnormally overexpressed in breast cancer and negatively regulates autoph-agy,and can enhance the proliferation,migration,invasion and EMT process of breast cancer cells through negatively regulating autophagy,suggesting that SNHG3 is a potential target for diag-nosis and treatment of breast cancer.

Hepatic fibrosis(HF)is a pathophysiological outcome of chronic liver injury and is characterized by excessive accumulation of extracellular matrix protein.A number of studies have confirmed that the signaling pathways formed by transforming growth factor-β1(TGF-β1)and its downstream Smad family play an important role in the occurrence and development of HF,and the traditional Chinese medicine(TCM)research targeting this pathway is currently a hot spot in the reversal of HF.Therefore,taking TGF-β1/Smads signaling pathway as the entry point,this paper reviewed the mechanism of action of TCM compound formula and single drug extract in intervening TGF-β1/Smad pathway and related factors upstream and downstream of the pathway to reverse HF in recent years,revealed the targeted therapeutic effect of TCM,and provided new strategies for clarifying the mechanism of TCM.

Objective To explore the medication rules of Professor HUANG Li for the treatment of recurrent angina pectoris after percutaneous coronary intervention(PCI)for coronary heart disease by data mining method.Methods The prescriptions for effective cases of recurrent angina pectoris after PCI for coronary heart disease treated by Professor HUANG Li in the outpatient department of China-Japan Friendship Hospital were collected.SPSS Statistics 26.0 software and SPSS Modeler 18.0 software were used for frequency statistics,analysis of the therapeutic actions,properties,flavors and meridian tropism of the prescribed herbs as well as association rule analysis,cluster analysis and factor analysis of the herbs.Results A total of 344 Chinese medicine prescriptions were obtained,involving 209 herbs,with a cumulative frequency of 5 874 times.The top 30 Chinese medicinals were named as the high-frequency Chinese medicines,and the herbs with the frequency over 100 times in descending order were Astragali Radix,Chuanxiong Rhizoma,Puerariae Lobatae Radix,Rhodiolae Crenulatae Radix et Rhizoma,Notoginseng Radix et Rhizoma,Poria,Dalbergiae Odoriferae Lignum,Atractylodis Macrocephalae Rhizoma,Curcumae Rhizoma,Sparganii Rhizoma,Dioscoreae Rhizoma,Citri Reticulatae Pericarpium,Pinelliae Rhizoma Praeparatum,Codonopsis Radix,and Glycyrrhizae Radix et Rhizoma.The high-frequency Chinese medicinals were mostly classified as blood-activating and stasis-resolving drugs and qi-replenishing drugs.The medicinal properties of the drugs were characterized by being warm,mild,or cold,the flavors were predominated by being sweet,pungent or bitter,and the medicinals usually had the meridian tropism of the spleen,lung and liver meridians.A total of 30 association rules were mined out,cluster analysis yielded 5 herbal groups,and factor analysis yielded 11 groups of common factors.Conclusion For the treatment of cardiovascular diseases,Professor HUANG Li follows the theory of qi,blood and water,and especially pays more attention to the ascending and descending of qi movement.For qi deficiency and blood stasis contribute to the basic pathogenesis of recurrent angina pectoris after PCI,the therapy of benefiting qi,activating blood and removing stasis is recommended.Moreover,the simultaneous regulation of five zang-organs and simultaneous use of the cold and warm herbs are performed,and the herbs of benefiting qi and invigorating spleen,resolving phlegm and inducing diuresis,tranquilizing mind,promoting qi and dissipating masses,and activating blood to eliminate stasis are used for adjuvant therapy.

The current production of Chinese herbal decoction pieces faces several issues including strong subjectivity,unstable quality,low production efficiency,and a lack of intelligent systems.In order to expedite the intelligent transformation and upgrading of Chinese medicine processing,this paper delves deeply into the problems and challenges encountered in establishing a digital and intel-ligent production model for Chinese herbal pieces.Addressing the slow progress in fundamental research on traditional Chinese medi-cine processing mechanisms,the absence of online digital quality characterization techniques,the low level of production equipment in-telligence,and the lack of evaluation standards for high-quality decoction pieces,this paper proposes a"New Quality Productive Forces"formation approach driven by technological innovation.Through interdisciplinary integration methods,the paper explores the mechanisms of Chinese medicine processing in depth,clarifies the correlation between the processing procedures and the"medicinal properties-quality"relationship,and employs bionic sensing and artificial intelligence to achieve a holistic quality characterization of decoction pieces.Additionally,the use of cloud-edge collaborative big data systems is proposed to enhance intelligent upgrades of the production lines.The paper also aims to establish a high-quality decoction piece evaluation system integrating"physical-chemical-bio-logical"multimodal data fusion.This approach aims to steer the Chinese medicine processing towards becoming more efficient,precise,and sustainable,thereby promoting high-quality sustainable development of the Chinese herbal decoction industry and providing both theoretical and practical support for the modernization of traditional Chinese medicine.

Transient forebrain ischemia-reperfusion(I/R);Brain-derived neurotrophic factor(BDNF);Histone deacetylase 3(HDAC3);Hippocampus Objective To evaluate the effect of transient forebrain ischemia-reperfusion(I/R)on the binding of brainderived neurotrophic factor(BDNF)promoters to histone deacetylase 3(HDAC3)in the hippocampus of rat and investigate its mechanism.Methods The I/R model of SD rats(I/R group)was established by Pulsinelli four-vessel clamping method,and sham operation group(Sham group)was set at the same time,which were observed for the survival of neurons in the hippocampus of rats by Nissl staining,detected for the binding of BDNF promoters(Bdnf-p1,Bdnf-p2,Bdnf-p4 and Bdnf-p6)to HDAC3 by chromatin immunoprecipitation(ChIP)and determined for the expression of brain derived neurotrophic factor antisense(BDNF-AS)by qPCR.Results Compared with Sham group,the quantity of neurons in hippocampal CA1 region of rats decreased significantly in I/R group,while those in CA3 region and DG region showed no significant changes.The binding levels of Bdnf-p1 and Bdnf-p2 to HDAC3 in hippocampal CA1 region decreased significantly in I/R Group(t = 2.575 and 2.241 respectively,each P<0.05),while there was no significant difference in the binding levels of Bdnf-p4 and Bdnf-p6 to HDAC3(t = 1.033 and 0.348 respectively,each P>0.05);The binding levels of Bdnf-p1 and Bdnf-p2 to HDAC3 in CA3 region increased significantly(t = 12.600 and 3.191,P<0.001 and<0.05,respectively),while the binding level of Bdnf-p6 to HDAC3 decreased significantly(t = 4.029,P<0.05)and no significant difference was observed in the binding level of Bdnf-p4 to HDAC3(t = 0.175,P>0.05);In DG region,the binding level of each BDNF promoter to HDAC3 showed no significantly difference(t = 0.630 ～ 1.687,each P>0.05).Meanwhile,the expression level of BDNF-AS in hippocampal CA1 region of rats decreased significantly(t = 2.560,P<0.05),but increased significantly in hippocampal CA3 and DG regions(t = 3.543 and 3.637 respectively,each P<0.01)in I/R group.Conclusion I/R showed a significant effect on the binding level of BDNF promoter to HDAC3 in rat hippocampus,which may play a role by changing the expression level of BDNF-AS.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Given the dual role of autophagy presenting in tumorigenesis and inhibition, we established an autophagy-related gene prognostic index (ARGPI) with validation to well predict the biochemical recurrence (BCR), metastasis, as well as chemoresistance for patients with prostate cancer (PCa) who underwent radical radiotherapy or prostatectomy. Then, Lasso and COX regression was used to develop the ARGPI. We performed the whole analyses through R packages (version 3.6.3). Secreted phosphoprotein 1 (SPP1), single-minded 2 (SIM2), serine protease inhibitor b5 (SERPINB5), aldehyde dehydrogenase 2 (ALDH2), and acyl-CoA synthetase long-chain 3 (ACSL3) were eventually used to establish the ARGPI score. Patients were divided into two different-risk groups based on the median ARGPI score, high-risk patients with a higher risk of BCR than low-risk patients (hazard ratio [HR]: 5.46, 95% confidence interval [CI]: 3.23-9.24). The risk of metastasis of high-risk patients was higher than low-risk patients (HR: 11.31, 95% CI: 4.89-26.12). In The Cancer Genome Atlas (TCGA) dataset, we observed similar prognostic value of ARGPI in terms of BCR-free survival (HR: 1.79, 95% CI: 1.07-2.99) and metastasis-free survival (HR: 1.80, 95% CI: 1.16-2.78). ARGPI score showed a diagnostic accuracy of 0.703 for drug resistance. Analysis of gene set enrichment analysis (GSEA) indicated that patients in the high-risk group were significantly positively related to interleukin (IL)-18 signaling pathway. Moreover, ARGPI score was significantly related to cancer-related fibroblasts (CAFs; r = 0.36), macrophages (r = 0.28), stromal score (r = 0.38), immune score (r = 0.35), estimate score (r = 0.39), as well as tumor purity (r = -0.39; all P < 0.05). Drug analysis showed that PI-103 was the common sensitive drug and cell line analysis indicated that PC3 was the common cell line of PI-103 and the definitive gene. In conclusion, we found that ARGPI could predict BCR, metastasis, and chemoresistance in PCa patients who underwent radical radiotherapy or prostatectomy.
Male ; Humans ; Prognosis ; Neoplasm Recurrence, Local/pathology* ; Prostatic Neoplasms/pathology* ; Prostatectomy ; Drug Resistance ; Aldehyde Dehydrogenase, Mitochondrial

Aim To investigate the involvement and mechanism of miR-619-5p in the proliferation, migration and invasion of human breast cancer cells. Methods The expression of miR-619-5p in breast cancer and normal breast tissue and cells was detected using bioinformatic analysis or qRT-PCR. After transfection with miR-619-5p mimics or inhibitors, the expression of miR-619-5p and EMT-related molecule mRNA was determined by qRT-PCR. Cell proliferation was detected using CCK-8 assay; cell migration and invasion capacity was estimated by the wound healing assay and Transwell assay. The protein levels of EMT-related molecules were analyzed by Western blot. The target genes of miR-619-5p were analyzed by bioinformatic a-nalysis, and a preliminary analysis of the potential target gene CREB1 was carried out. Results miR-619-5p was low expressed in breast cancer tissues and breast cancer cells. Compared with the control group, over-expression of miR-619-5p resulted in up-regula-tion of miR-619-5p expression levels and EMT epithelial markers, down-regulation of pro-EMT molecules and mesenchymal markers, impairment of cell proliferation, migration and invasion, and down-regulation of CREB1 expression. The results of the low miR-619-5p expression group were opposite to the above results. Conclusions In breast cancer tissue and cells, miR-619-5p expression is lower. miR-619-5p inhibits the proliferation, migration, invasion and EMT of breast cancer cells, and its possible mechanism of the effects may be targeting CREB1.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China