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1.
Biochem Biophys Res Commun ; 738: 150546, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39154554

ABSTRACT

A new cocrystalline form of metronidazole (MET) with propyl gallate (PRO), referred to as MET-PRO, has been successfully synthesized and characterized. Structural characterization reveals that MET and PRO are present in a 1:1 ratio within the cocrystal lattice, with one water molecule equivalent incorporated into the structure. This arrangement facilitates the formation of MET-PRO heterodimers and multiple stable units, collectively constructing a three-dimensional supramolecular network. The solubility and permeability of the current cocrystal, along with the parent drug MET, are evaluated under physiological pH conditions. Experimental findings reveal that MET within the cocrystal exhibits a 1.54-2.37 folds increase in solubility and approximately a threefold improvement in permeability compared to its standalone form. Intriguingly, these concurrent enhancements in the physicochemical properties of MET lead to augmented antibacterial activity in vitro, evidenced by a reduction in minimum inhibitory concentration. Even more intriguingly, the enhanced physicochemical properties observed in vitro for the current cocrystal translate into tangible pharmacokinetic benefits in vivo, characterized by prolonged half-life and enhanced bioavailability. Consequently, this research not only introduces a fresh crystal structure for antibacterial medication but also presents approach for optimizing drug properties across in vitro and in vivo settings, while concurrently bolstering the antibacterial effectiveness of MET through pharmaceutical cocrystallization techniques.

2.
Inorg Chem ; 63(7): 3436-3443, 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38306691

ABSTRACT

Developing efficient adsorbents for acetylene purification from multicomponent mixtures is of critical significance in the chemical industry, but the trade-off between regenerability and selectivity significantly restricts practical industrial applications. Here, we report ultramicroporous metal-organic frameworks with acetylene-affinity channels to enhance electrostatic interaction between C2H2 and frameworks for the efficient one-step purification of C2H2 from C2H2/CO2/C2H4 mixtures, in which the electrostatic interaction led to high regenerability. The obtained SNNU-277 exhibits significantly higher adsorption capacity for C2H2 than that for both C2H4 and CO2 at 298 K and 0.1 bar, while an ultrahigh selectivity of C2H2/C2H4 (100.6 at 298 K) and C2H2/CO2 (32.8 at 298 K) were achieved at 1 bar. Breakthrough experiments validated that SNNU-277 can efficiently separate C2H2 from C2H2/C2H4/CO2 mixtures. CO2 and C2H4 broke through the adsorption column at 4 and 14.8 min g-1, whereas C2H2 was detected until 177.6 min g-1 at 298 K. Theoretical calculations suggest that the framework is electrostatically compatible with C2H2 and electrostatically repels C2H4 and CO2 in the mixed components. This work highlights the importance of rational pore engineering for maximizing the electrostatic effect with the preferentially absorbed guest molecule for efficient multicomponent separation.

3.
Fa Yi Xue Za Zhi ; 40(1): 30-36, 2024 Feb 25.
Article in English, Zh | MEDLINE | ID: mdl-38500458

ABSTRACT

OBJECTIVES: To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF-MS). METHODS: The pretreatment conditions of solid phase extraction (SPE) were optimized by orthogonal experimental design and the surface water samples were concentrated and extracted by Oasis® HLB and Oasis® MCX SPE columns in series. The extracts were separated by Kinetex® EVO C18 column, with gradient elution of 0.1% formic acid aqueous solution and 0.1% formic acid methanol solution. Q-TOF-MS 'fullscan' and 'targeted MS/MS' modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion, product ion and retention times. RESULTS: The 34 emerging contaminants exhibited good linearity in the concentration range respectively and the correlation coefficients (r) were higher than 0.97. The limit of detection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%. The intra-day precision was 0.78%-18.70%. The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected, with a concentration range of 1.93-157.71 ng/L. CONCLUSIONS: The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.


Subject(s)
Tandem Mass Spectrometry , Water , Tandem Mass Spectrometry/methods , Chromatography, High Pressure Liquid/methods , Formates , Solid Phase Extraction/methods
4.
Environ Sci Technol ; 57(12): 4971-4983, 2023 03 28.
Article in English | MEDLINE | ID: mdl-36929874

ABSTRACT

Shigella flexneri infection is the main cause of diarrhea in humans worldwide. The emergence of antimicrobial resistance (AMR) of S. flexneri is a growing public health threat worldwide, while large-scale studies monitoring the longitudinal AMR trends of isolates remain scarce. Here, the AMR gene (ARG) profiles of 717 S. flexneri isolates from 1920 to 2020 worldwide were determined. The results showed that the average number of ARGs in isolates has increased significantly, from 19.2 ± 2.4 before 1970 to 29.6 ± 5.3 after 2010. In addition, mobile genetic elements were important contributors to ARGs in S. flexneri isolates. The results of the structural equation model showed that the human development index drove the consumption of antibiotics and indirectly promoted the antibiotic resistance. Finally, a machine learning algorithm was used to predict the antibiotic resistance risk of global terrestrial S. flexneri isolates and successfully map the antibiotic resistance threats in global land habitats with over 80% accuracy. Collectively, this study monitored the longitudinal AMR trends, quantitatively surveilled the health risk of S. flexneri AMR, and provided a theoretical basis for mitigating the threat of antibiotic resistance.


Subject(s)
Anti-Bacterial Agents , Dysentery, Bacillary , Humans , Anti-Bacterial Agents/pharmacology , Shigella flexneri/genetics , Drug Resistance, Bacterial/genetics , Microbial Sensitivity Tests , Dysentery, Bacillary/epidemiology , Dysentery, Bacillary/drug therapy
5.
J Nerv Ment Dis ; 211(6): 448-452, 2023 06 01.
Article in English | MEDLINE | ID: mdl-36943328

ABSTRACT

ABSTRACT: This study is a systematic review of characteristics and influencing factors of nonsuicidal self-injury behavior among adolescents with depressive disorder in China. PubMed, CNKI, WanFang Database, and VIP were searched for studies. Meta-analysis was performed using RevMan 5.1 software. Nineteen studies involving 707 subjects were included in the meta-analysis. Age, gender, only child or not, and residence were included in the analysis, of which age ( I2 = 0%, p = 0.42) and residence ( I2 = 0%, p = 0.84) were analyzed by fixed-effects model; gender ( I2 = 75%, p = 0.003) and only child or not ( I2 = 50%, p = 0.140) were analyzed by random-effects model. The evidence shows that, according to the common self-injury mode and location, the nonsuicidal self-injury behavior of young people with depressive disorder aged 15-18 years is paid attention to and guided, so as to achieve early detection and early diagnosis and treatment, and reduce the occurrence of serious harm.


Subject(s)
Depressive Disorder , Self-Injurious Behavior , Child , Humans , Adolescent , Self-Injurious Behavior/epidemiology , China/epidemiology , Databases, Factual , Depressive Disorder/epidemiology
6.
Chin Med Sci J ; 38(2): 147-158, 2023 Jun 30.
Article in English | MEDLINE | ID: mdl-37280723

ABSTRACT

Objective To systematically analyze the current status of outcomes reporting in clinical trials on treating stasis acute mastitis with Traditional Chinese Medicine breast massage.Methods We searched CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, Embase, Cochrane library, JBI, CINAHL, PsycINFO, Clinical Trials Registry Platform portal, Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, Center Watch Registry from inception to May 15, 2022 to find randomized controlled trials, non-randomized controlled trials, case series and cohort studies which reported the outcomes of stasis acute mastitis managed with Traditional Chinese Medicine breast massage, with search terms of mastitis, acute mastitis, lactation mastitis, puerperal mastitis, breast problem, breast engorgement, milk stasis, blocked ducked, breast pain, breast massage, and acupoint massage. Outcomes and the measurement schemes (measurement methods, timing of assessing outcome, frequency of assessing outcome, measurers) were extracted from the included studies. We used the Management of Otitis Media with Effusion in Children with Cleft Palate (MOMENT) to assess the quality of each study, then categorized outcomes derived from the included studies into different domains according to the Outcome Measures in Rheumatology Arthritis Clinic Trials (OMERACT) Filter 2.1 framework.Results We identified 85 clinical trials, in which 54 different outcomes were reported. A total of 81.2% (69/85) of studies were assessed as medium quality with a mean score of 2.6, and 18.8% (16/85) as low quality with a mean score of 0.9. These outcomes were organized in three core areas. Lump size (89.4%, 76/85) was the most frequently reported outcome, followed by breast pain (69.4%, 59/85) and milk excretion (68.2%, 58/85). Five methods were used to assess lump size and four methods to assess breast pain.Conclusions The outcomes reported in clinical trials regarding stasis acute mastitis treated by Traditional Chinese Medicine breast massage are heterogeneous. Developing a core outcome set to achieve consistent standards for reporting outcomes and modalities for validation of the outcomes is clearly warranted.


Subject(s)
Mastitis , Mastodynia , Child , Female , Humans , Australia , Massage , Mastitis/therapy , Medicine, Chinese Traditional
7.
Bioorg Chem ; 127: 105908, 2022 10.
Article in English | MEDLINE | ID: mdl-35728291

ABSTRACT

Thirty-two novel DG F-spiroacetal ring-opening derivatives, including 24 acetylated derivatives and 8 nitrogenous derivatives, were designed and synthesized from diosgenin (DG). The cytotoxicity of the novel derivatives was evaluated by MTT assay, except for compounds 4a, 4e, 4i, 4 l, 5a and 5 h, which were potentially cytotoxic to RAW264.7 cells, all the other derivatives had no significant cytotoxicity. The NO release inhibitory activities of novel derivatives were screened by Griess method. The results showed that the anti-inflammatory activity of the DG acetylated derivatives was stronger than the nitrogenous derivatives, and 4a-4 m containing acetyl groups at the 3-position may have better anti-inflammatory effects than 5a-5 k containing free hydroxyl groups. In ELISA assay, compound 4 m exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by LPS with IC50 values 0.449 ± 0.050 µM. The results of docking experiments showed that 4 m has a good affinity for p65 protein.


Subject(s)
Antineoplastic Agents , Diosgenin , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Diosgenin/pharmacology , Drug Design , Molecular Docking Simulation , Molecular Structure , Structure-Activity Relationship
8.
Acta Biochim Biophys Sin (Shanghai) ; 54(7): 974-986, 2022 Jul 25.
Article in English | MEDLINE | ID: mdl-35866605

ABSTRACT

Primary hepatic carcinoma is a common malignant tumor. The classic molecular targeted drug sorafenib is costly and is only effective for some patients. Therefore, it is of great clinical significance to search for new molecular targeted drugs. Eupalinolide B (EB) from Eupatorium lindleyanum DC. is used to treat chronic tracheitis in clinical practice. However, the role of EB in hepatic carcinoma is unknown. In this study, we first measure the effect of EB on tumor growth in a xenograft model and PDX model. The cell proliferation and migration are also detected in human hepatocarcinoma cell lines (SMMC-7721 and HCCLM3). Then, we investigate cell cycle, cell apoptosis, cell necrosis, cell autophagy, and ferroptosis by flow cytometry, western blot analysis and electron microscopy. The results demonstrate that EB exerts anti-proliferative activity in hepatic carcinoma by blocking cell cycle arrest at S phase and inducing ferroptosis mediated by endoplasmic reticulum (ER) stress, as well as HO-1 activation. When HO-1 is inhibited, EB-induced cell death and ER protein expression are rescued. The migration-related mechanism consists of activation of the ROS-ER-JNK signaling pathway and is not connected to ferroptosis. In summary, we first discover that EB inhibits cell proliferation and migration in hepatic carcinoma, and thus EB is a promising anti-tumor compound that can be used for hepatic carcinoma.


Subject(s)
Carcinoma, Hepatocellular , Ferroptosis , Liver Neoplasms , Carcinoma, Hepatocellular/pathology , Humans , Lactones , Liver Neoplasms/pathology , MAP Kinase Signaling System , Reactive Oxygen Species/metabolism , Sesquiterpenes, Germacrane , Sorafenib/pharmacology , Sorafenib/therapeutic use
9.
Angew Chem Int Ed Engl ; 61(29): e202204420, 2022 07 18.
Article in English | MEDLINE | ID: mdl-35543248

ABSTRACT

Acinetobacter baumannii is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram-negative bacteria. To explore the antigenic properties of A. baumannii LPS, four Kdo-containing inner core glycans from A. baumannii strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α-Kdo-(2→5)-Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via α-stereocontrolled coupling with 5,7-O-di-tert-butylsilylene or 5-O-benzoyl protected Kdo thioglycosides and 2-azido-2-deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5-branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against A. baumannii.


Subject(s)
Acinetobacter baumannii , Lipopolysaccharides , Carbohydrates , Disaccharides/chemistry , Humans , Lipopolysaccharides/chemistry , Oligosaccharides/chemistry , Polysaccharides
10.
Eur J Vasc Endovasc Surg ; 61(4): 648-655, 2021 04.
Article in English | MEDLINE | ID: mdl-33441270

ABSTRACT

OBJECTIVE: The aim of this study was to observe the spatial distribution and dynamic changes of matrix metalloproteinase (MMP)-2, MMP-9, and collagen in in stent restenosis (ISR) and to explore their influence on ISR. METHODS: Sixty Z type stents were implanted into the common iliac arteries of minipigs, which were divided into 10 groups (six in each group) according to euthanasia time (6 hours, and 1, 3, 7, 14, 28, 56, 84, 168, and 336 days). After the samples were harvested, haematoxylin and eosin staining, immunohistochemical staining, Western blotting, and Picrosirius red staining were performed for all groups. RESULTS: ISR occurred in all six minipigs in the 56 day group (percentage diameter stenosis range 71.6%-79.2%, mean ± standard deviation 75.6% ± 2.5%). The percentage diameter stenosis decreased to 38.3% ± 2.7% at 336 days (p < .001). Immunohistochemical staining showed that MMP-2 and MMP-9 were strongly stained near the internal elastic lamina or in the damaged parts of the intima, around the struts and neointimal lumen surface in the ISR process. The expression of MMP-2 and MMP-9 at 56 days was significantly lower compared with their peaks (seven days and one day [p < .001; p = .002], respectively). At 56 days, the collagen content reached its maximum (mean integrated optical density range 0.73-0.92, mean ± standard deviation 0.82 ± 0.09). From the 14 day group to the 336 day group, mature collagen in neointima was correlated negatively with MMP-2 (γ(36) = -0.816; p < .001) and MMP-9 expression (γ(36) = -0.853; p < .001). During the neointimal regression period, new collagen in neointima was positively correlated with MMP-2 (γ(24) = 0.683; p < .001) and MMP-9 (γ(24) = 0.873; p < .001). CONCLUSION: This study has demonstrated the spatial distribution of and dynamic changes in MMP-2, MMP-9, and collagen in ISR by simulating the process of neointima from generation to regression after stent implantation. When ISR occurred, MMP-2 and MMP-9 expression decreased and collagen content reached its maximum, which might contribute to ISR.


Subject(s)
Collagen/metabolism , Endovascular Procedures/instrumentation , Iliac Artery/enzymology , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Vascular Remodeling , Animals , Endovascular Procedures/adverse effects , Iliac Artery/pathology , Models, Animal , Neointima , Stents , Swine , Swine, Miniature , Time Factors , Up-Regulation
11.
Org Biomol Chem ; 19(25): 5521-5524, 2021 06 30.
Article in English | MEDLINE | ID: mdl-33904564

ABSTRACT

While water clusters play an essential role in the stability of biological structures, their ability to stabilize synthetic oligomers is less understood. We have synthesized a heptameric sheet-like aromatic oligoamide foldamer with ferrocene as turn unit. It shows strong interactions with water in the solid state and in solution. The water binding limits the fluxional processes resulting from the flexible ferrocene unit, highlighting the importance of such interactions for conformational studies on this class of molecule.

12.
Org Biomol Chem ; 19(25): 5658, 2021 Jun 30.
Article in English | MEDLINE | ID: mdl-34106117

ABSTRACT

Correction for 'Water binding stabilizes stacked conformations of ferrocene containing sheet-like aromatic oligoamides' by Ya-Zhou Liu et al., Org. Biomol. Chem., 2021, DOI: 10.1039/d1ob00580d.

13.
BMC Gastroenterol ; 21(1): 455, 2021 Dec 03.
Article in English | MEDLINE | ID: mdl-34861832

ABSTRACT

BACKGROUND: Human astrovirus (HAstV) and sapovirus (SaV) are common pathogens that can cause acute gastroenteritis (AGE). However, very few studies have reported the molecular epidemiology and clinical information on HAstV and SaV in China. This study aims to determine the molecular epidemiology and clinical features of HAstV and SaV in patients with AGE in Guangzhou, China. METHODS: For this study, 656 patients with AGE were enrolled. Their stool samples were screened for 15 enteropathogens using Luminex xTAG® Gastrointestinal Pathogen Panel. HAstV and SaV were detected through an in-house multiplex reverse transcriptase polymerase chain reaction followed by phylogenetic analysis. We described and compared clinical features of AGE in patients with HAstV and SaV. RESULTS: Of the 656 stool samples, 63.72% (418/656) were found to be positive, with 550 enteropathogens (296 bacteria and 254 viruses). HAstV and SaV were detected in 20 (3.0%) and 12 (1.8%) samples, respectively. Four genotypes (genotypes 1, 2, 3, and 8) of HAstV and three genotypes (GI.1, GI.2 and GIV) of SaV were identified. Coinfection was observed in ten HAstV-positive and two SaV-positive samples. HAstV was more likely to occur in winter, while SaV in early spring. The median age of the patients with single HAstV infection was higher than that of the patients with other viruses (rotavirus, norovirus, and enteric adenovirus; P = 0.0476) and unknown etiology (P = 0.006). Coinfection with HAstV or SaV were not associated with disease severity (P > 0.05). CONCLUSION: HAstV and SaV are the common causes of AGE in Guangzhou, China.


Subject(s)
Gastroenteritis , Mamastrovirus , Sapovirus , Feces , Gastroenteritis/epidemiology , Genotype , Humans , Infant , Mamastrovirus/genetics , Outpatients , Phylogeny , Sapovirus/genetics
14.
J Cell Mol Med ; 24(10): 5438-5445, 2020 05.
Article in English | MEDLINE | ID: mdl-32281724

ABSTRACT

Hepatocellular carcinoma (HCC) is the sixth most common malignant tumour, which has posed a heavy health and financial burden worldwide. Due to limited symptoms at the early stage and the limitation in current biomarkers, HCC patients are usually diagnosed at the advanced stage with a pessimistic overall survival rate. Circular RNAs (circRNAs) are a subclass of single-stranded RNAs characterized by a covalently closed loop structure without 3'- or 5'-end. With advances in high-throughput sequencing technology and bioinformatics, accumulating studies have demonstrated the promotor or suppressor roles of circRNAs in the carcinogenesis, progression, and metastasis of HCC. Moreover, circRNAs are characteristic of higher abundance, stability and conservation compared with linear RNAs. Therefore, circRNAs have emerged as one of the most promising diagnostic and prognostic biomarkers for HCC with reliable accuracy, sensitivity and specificity. In this review, we briefly introduce the characteristics of circRNAs and summarize the roles of circRNAs in the biological procedures of HCC. Furthermore, we provide an overview on the potential diagnostic and prognostic value of circRNAs as biomarkers for patients with HCC. Finally, we discuss future perspectives of circRNAs in cancer research.


Subject(s)
Biomarkers, Tumor , Carcinoma, Hepatocellular/diagnosis , Cell-Free Nucleic Acids , Liver Neoplasms/diagnosis , RNA, Circular , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/mortality , Disease Susceptibility , Humans , Liver Neoplasms/blood , Liver Neoplasms/mortality , Prognosis
15.
Chemistry ; 26(1): 181-185, 2020 Jan 02.
Article in English | MEDLINE | ID: mdl-31691432

ABSTRACT

A series of aromatic oligoamides incorporating an inherently flexible ferrocene dicarboxylic acid unit was synthesized. Solid state, solution, and computational studies on these systems indicated that the aromatic strands can adopt a syn parallel stacked conformation. This results in modular ß-sheet-like molecular clefts that display structure-dependent recognition of small polar molecules. NMR and theoretical studies of the host-guest interaction support an in cleft binding mode and allowed the selectivity of the oligomers to be rationalized on the basis of minor changes in functional-group presentation on the edge of the aromatic strands.

16.
Med Sci Monit ; 26: e922556, 2020 Mar 26.
Article in English | MEDLINE | ID: mdl-32214058

ABSTRACT

BACKGROUND The aim of this study was to compare changes in the extracellular matrix after implantation of a stent that elutes a matrix metalloproteinase (MMP) inhibitor (GM6001); and to determine the effects of the GM6001-eluting stent upon prevention of in-stent restenosis (ISR). MATERIAL AND METHODS We included 48 Guangxi Bama mini-pigs in this study. A GM6001-eluting stent was placed in one iliac artery and a stent that did not elute GM6001 was placed in the contralateral iliac artery. The iliac arteries were removed at 6 hours as well as 1, 7, 14, 56, 84, and 336 days after stent placement. Arteries were analyzed for morphometry, gelatinase content, different phenotypes of vascular smooth muscle cells (VSMCs), collagen content, apoptotic rate, and cell density. RESULTS The vascular lumen areas of the GM6001 group were significantly increased and the neointimal areas were significantly reduced compared with the control group from the 7 days to the 336 days. In the 2 groups, expression of MMP-2 and MMP-9 peaked simultaneously, but GM6001-eluting stents inhibited expression of MMP-2 and MMP-9 in the vascular media and neointima (especially around the struts) significantly. In the GM6001 group, expression of tissue inhibitor of matrix metalloproteinase (TIMP)-1, TIMP-2, myosin heavy chain 10 (MYH-10, marker of the proliferative phenotype of VSMCs), collagen content, percentage of apoptotic cells, and cell density were also decreased significantly compared with those in the control group. CONCLUSIONS Use of GM6001-eluting stents resulted in persistent and potent inhibition of intimal hyperplasia, an increase in luminal area, and no obvious thrombosis in the arteries of the mini-pigs.


Subject(s)
Coronary Restenosis/drug therapy , Drug-Eluting Stents , Matrix Metalloproteinase Inhibitors/therapeutic use , Animals , Apoptosis , Collagen/metabolism , Coronary Restenosis/complications , Coronary Restenosis/pathology , Female , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Myosin Heavy Chains/metabolism , Neointima/complications , Neointima/pathology , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Swine , Swine, Miniature , Time Factors , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tissue Inhibitor of Metalloproteinase-2/metabolism
17.
BMC Musculoskelet Disord ; 21(1): 271, 2020 Apr 27.
Article in English | MEDLINE | ID: mdl-32340622

ABSTRACT

BACKGROUND: Non-vascularized bone grafting is a promising head-preserving technique for younger patients diagnosed as non-traumatic osteonecrosis of the femoral head (NONFH). Among the various types of bone grafting techniques, "light-bulb" procedure grafting with synthetic bone substitute is an attractive option. We aimed to assess the effectiveness of using beta-tricalcium phosphate (ß-TCP) for the treatment of pre-collapse and early post-collapse lesions NONFH. METHODS: From April 2010 to June 2014, 33 patients (47 hips) with NONFH were treated using the afore-mentioned technique. The clinical and radiological outcomes were recorded and compared statistically between pre- and post-operation. Harris hip score (HHS) was used to evaluate the clinical results, and Association Research Circulation Osseous (ARCO) stage was applied to assess the radiological outcomes. RESULTS: The 5-years survival rate of using ß-TCP grafting was accounting for 25.5%. HHS was decreased from 78.47 to 52.87 points, and a very significant worsening of radiological results were revealed (P <  0.05). Two hips collapsed more than 2 mm were awaiting for THA, and 33 of the 47 hips had converted to THAs in an average time to failure of 24.24 months postoperatively. Meanwhile, only 4 hips survived without collapse, and 8 hips collapsed less than 2 mm. After surgery, the time onset of head collapse was 3.65 months on average, and the first conversion to THA was performed at 5 months postoperative. CONCLUSIONS: Our results suggest that "light-bulb" procedure grafting with ß-TCP sticks presented with a high failure rate in the early postoperative period. It is not proposed for the treatment of pre-collapse and early post-collapse lesions NONFH.


Subject(s)
Bone Substitutes/adverse effects , Calcium Phosphates/adverse effects , Femur Head Necrosis/surgery , Femur Head/transplantation , Adult , Bone Substitutes/pharmacology , Bone Transplantation/methods , Calcium Phosphates/pharmacology , Female , Femur Head/blood supply , Femur Head/pathology , Hip/diagnostic imaging , Humans , Male , Middle Aged , Observational Studies as Topic , Postoperative Period , Radiography/methods , Retrospective Studies , Treatment Failure , Treatment Outcome
18.
J Cell Physiol ; 234(6): 9045-9051, 2019 06.
Article in English | MEDLINE | ID: mdl-30317608

ABSTRACT

The molecular mechanism of liver fibrosis caused by hepatitis C virus (HCV) is not clear. The aim of this study is to understand the molecular mechanism of liver fibrosis induced by HCV and to identify potential therapeutic targets for hepatic fibrosis. We analyzed gene expression patterns between high liver fibrosis and low liver fibrosis samples, and identified genes related to liver fibrosis. We identified TAF1, HNF4A, and CALM2 were related to the development of liver fibrosis. HNF4A is important for hepatic fibrogenesis, and upregulation of HNF4A is an ideal choice for treating liver fibrosis. The gene expression of CALM2 is significantly lower in liver fibrosis samples than nonfibrotic samples. TAF1 may serve as a biomarker for liver fibrosis. The results were further validated by an independent data set GSE84044. In summary, our study described changes in the gene expression during the occurrence and development of liver fibrosis. The TAF1, HNF4A, and CALM2 may serve as novel targets for the treatment of liver fibrosis.


Subject(s)
Calmodulin/genetics , Hepatocyte Nuclear Factor 4/genetics , Histone Acetyltransferases/genetics , Liver Cirrhosis/genetics , Liver/metabolism , TATA-Binding Protein Associated Factors/genetics , Transcription Factor TFIID/genetics , Calmodulin/metabolism , Case-Control Studies , Databases, Genetic , Gene Expression Regulation , Gene Regulatory Networks , Hepatitis C/complications , Hepatitis C/virology , Hepatocyte Nuclear Factor 4/metabolism , Histone Acetyltransferases/metabolism , Humans , Liver/pathology , Liver/virology , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Liver Cirrhosis/virology , Protein Interaction Maps , Signal Transduction , TATA-Binding Protein Associated Factors/metabolism , Transcription Factor TFIID/metabolism
19.
Chin Med Sci J ; 34(4): 292-296, 2019 Nov 12.
Article in English | MEDLINE | ID: mdl-33906716

ABSTRACT

A 61-year-old Chinese woman was diagnosed as primary pulmonary adenocarcinoma of left superior lobe with epidermal growth factor receptor (EGFR) 19 del mutation positive. Treatment with icotinib was given, but her disease progressed after 6 months remission. CT-guide needle biopsy for the new lesion in inferior lobe of left lung demonstrated intrapulmonary metastasis, and EGFR gene panel by Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR) confirmed EGFR T790M mutation. Treatment with osimertinib was initiated. After 2 months remission, the disease progressed. Re-biopsy was performed for the tumor in the inferior lobe of left lung, and ARMS-PCR demonstrated no other gene mutation except EGFR 19 del. Icotinib was re-challenged, but disease progressed continuously. Bevacizumab was added, and partial response was achieved after 2-cycle of combination therapy. The non-small cell lung cancer (NSCLC) in this case maintained EGFR activating mutation and lost EGFR T790M mutation was a genetic change after osimertinib treatment. This case suggests the re-challenge of the first-generation EGFR-TKIs combined with bevacizumab may overcome the tumor resistance and prolong survival of NSCLC patient.


Subject(s)
Acrylamides/therapeutic use , Aniline Compounds/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Crown Ethers/therapeutic use , Drug Resistance, Neoplasm , Lung Neoplasms/drug therapy , Quinazolines/therapeutic use , Acrylamides/pharmacology , Adenocarcinoma of Lung/diagnostic imaging , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/pathology , Aniline Compounds/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Bevacizumab/pharmacology , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Crown Ethers/pharmacology , Drug Resistance, Neoplasm/drug effects , Female , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Middle Aged , Quinazolines/pharmacology , Tomography, X-Ray Computed , Treatment Outcome
20.
Sheng Li Xue Bao ; 69(2): 172-182, 2017 Apr 25.
Article in Zh | MEDLINE | ID: mdl-28435976

ABSTRACT

The present study is designed to explore the role of plasma cells in the change of protein C system (PCS) in ulcerative colitis (UC). Dextran sulfate sodium (DSS, 4% in concentration) was used to induce mouse UC model. The plasma cells and the type of immune complex in colon were observed by immunofluorescence. The amount and type of plasma cells separated from colonic mucosal lamina propria were detected by flow cytometry using anti-CD54+CD38+ and IgA/M/G antibodies, respectively. After stimulation of macrophages by IgG type immune complex, TNF-α and IL-6 levels were evaluated by ELISA. After co-incubation of microvascular endothelial cells with TNF-α or IL-6, the expressions of endothelial protein C receptor (EPCR) and thrombomodulin (TM), and the activity of activated protein C (APC) were examined. As the results showed, the IgG type plasma cells infiltration and the quantity of IgG type immune complex were increased in DSS group in comparison with control group. After incubation with IgG type immune complex, the levels of TNF-α and IL-6 in the supernatant of macrophages were increased (P < 0.01) in a concentration-dependent manner. Meanwhile, after incubation with TNF-α or IL-6, the expressions of EPCR and TM in the microvascular endothelial cells were decreased (P < 0.05 or P < 0.01), while the activity of APC was reduced (P < 0.05 or P < 0.01). These results suggested that the quantity of IgG type plasma cells increases in UC and forms immune complexes, which affect the secretion of cytokines from macrophage, thereby affecting the function of endothelial cells and finally inhibiting PCS in UC. Therefore, plasma cell may be a novel target for the treatment of UC.


Subject(s)
Antigen-Antibody Complex/immunology , Colitis, Ulcerative/immunology , Immunoglobulin G/immunology , Plasma Cells/immunology , Protein C/immunology , Animals , Colitis, Ulcerative/chemically induced , Colon/cytology , Dextran Sulfate , Disease Models, Animal , Interleukin-6/immunology , Intestinal Mucosa/cytology , Macrophages/immunology , Mice , Receptors, Cell Surface , Recombinant Proteins/immunology , Tumor Necrosis Factor-alpha/immunology
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