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The cases of feeling comfort during acupuncture and moxibustion treatment in literature were summarized and its biological basis was explored. A simple classification of comfort was made, and the importance of obtaining comfort in acupuncture treatment was pointed out. Considering the pursuit of less pain and harmlessness in modern clinical treatment, sugar needle should be advocated and popularized in current clinical practice of acupuncture and moxibustion.
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Açúcares , Moxibustão , Terapia por Acupuntura , Emoções , AgulhasRESUMO
To develop antimicrobials against Staphylococcus aureus by high throughput screening of drug library. The type of this study is experimental research. The clinical isolates of S. aureus were collected from the sputum samples of respiratory inpatient department of the Third Xiangya Hospital of Central South University. The anti-planktonic cells growth inhibition activity of FDA-approved drugs library (including 1 573 molecules) was assessed by building a planktonic cells screening platform; The biofilm inhibitory effect of the FDA-approved drugs was detected by building a biofilm screening platform combined with crystal violet staining; Minimal inhibitory concentrations of the selected hits were determined by broth microdilution assay. Finally, the cytotoxicity of the selected hits was detected by CCK-8 assay. The results showed that 218 hits were exhibited effective growth inhibitory effects against S. aureus by setting the concentrations of the molecules in the FDA-approved library to 100 μmol/L. These selected molecules are mainly anti-infective drugs, accounting for 118 hits; Followed by anti-cancer drugs, anti-inflammatory/-immune drugs, neurological drugs, cardiovascular drugs, endocrine drugs, and metabolic disease drugs, which accounts for 40, 19, 12, 9, 8, and 3 hits; Other unclassified drugs accounts for 9 hits. The top 10 hits exhibiting anti-planktonic cells activity against S. aureus were mainly including antitumor drugs, followed by neurological drugs and unclassified drugs like vitamin K3 with the inhibition rate of 99.65%-100%. Similarly, the top 10 hits showing biofilm inhibitory effects against S. aureus were also mainly including antitumor drugs, followed by neurological drugs and anti-inflammatory/-immune drugs with the inhibition rate of 50.22%-92.95%. The minimal inhibitory concentration (MIC) of the 51 hits by second round screening was determined by micro-dilution assay, which mainly include the antitumor drugs, cardiovascular drugs, endocrine drugs, anti-inflammatory/-immune drugs, metabolic disease drugs, neurological drugs and other unclassified drugs accounted for 22, 5, 3, 9, 2, 5 and 5 hits, respectively, with the MICs of 1.56-50 μmol/L, 6.25-25 μmol/L, 6.25-25 μmol/L, 0.2-50 μmol/L, 25-50 μmol/L, 1.56-50 μmol/L and 0.1-12.5 μmol/L, respectively. In conclusion, the minimum inhibitory concentrations of small molecules screened through high-throughput assay are at the level of micromolar with strong drug development potential and high modifiability. The high effective anti-planktonic cells and anti-biofilm activity by these molecules are expected to provide new ideas for the development of new antimicrobials against S. aureus.
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Humanos , Staphylococcus aureus , Antibacterianos/farmacologia , Ensaios de Triagem em Larga Escala , Infecções Estafilocócicas , Anti-Infecciosos/farmacologia , Testes de Sensibilidade Microbiana , Biofilmes , Antineoplásicos/farmacologia , Anti-Inflamatórios/farmacologia , Fármacos Cardiovasculares/farmacologia , Doenças MetabólicasRESUMO
To develop antimicrobials against Staphylococcus aureus by high throughput screening of drug library. The type of this study is experimental research. The clinical isolates of S. aureus were collected from the sputum samples of respiratory inpatient department of the Third Xiangya Hospital of Central South University. The anti-planktonic cells growth inhibition activity of FDA-approved drugs library (including 1 573 molecules) was assessed by building a planktonic cells screening platform; The biofilm inhibitory effect of the FDA-approved drugs was detected by building a biofilm screening platform combined with crystal violet staining; Minimal inhibitory concentrations of the selected hits were determined by broth microdilution assay. Finally, the cytotoxicity of the selected hits was detected by CCK-8 assay. The results showed that 218 hits were exhibited effective growth inhibitory effects against S. aureus by setting the concentrations of the molecules in the FDA-approved library to 100 μmol/L. These selected molecules are mainly anti-infective drugs, accounting for 118 hits; Followed by anti-cancer drugs, anti-inflammatory/-immune drugs, neurological drugs, cardiovascular drugs, endocrine drugs, and metabolic disease drugs, which accounts for 40, 19, 12, 9, 8, and 3 hits; Other unclassified drugs accounts for 9 hits. The top 10 hits exhibiting anti-planktonic cells activity against S. aureus were mainly including antitumor drugs, followed by neurological drugs and unclassified drugs like vitamin K3 with the inhibition rate of 99.65%-100%. Similarly, the top 10 hits showing biofilm inhibitory effects against S. aureus were also mainly including antitumor drugs, followed by neurological drugs and anti-inflammatory/-immune drugs with the inhibition rate of 50.22%-92.95%. The minimal inhibitory concentration (MIC) of the 51 hits by second round screening was determined by micro-dilution assay, which mainly include the antitumor drugs, cardiovascular drugs, endocrine drugs, anti-inflammatory/-immune drugs, metabolic disease drugs, neurological drugs and other unclassified drugs accounted for 22, 5, 3, 9, 2, 5 and 5 hits, respectively, with the MICs of 1.56-50 μmol/L, 6.25-25 μmol/L, 6.25-25 μmol/L, 0.2-50 μmol/L, 25-50 μmol/L, 1.56-50 μmol/L and 0.1-12.5 μmol/L, respectively. In conclusion, the minimum inhibitory concentrations of small molecules screened through high-throughput assay are at the level of micromolar with strong drug development potential and high modifiability. The high effective anti-planktonic cells and anti-biofilm activity by these molecules are expected to provide new ideas for the development of new antimicrobials against S. aureus.
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Humanos , Staphylococcus aureus , Antibacterianos/farmacologia , Ensaios de Triagem em Larga Escala , Infecções Estafilocócicas , Anti-Infecciosos/farmacologia , Testes de Sensibilidade Microbiana , Biofilmes , Antineoplásicos/farmacologia , Anti-Inflamatórios/farmacologia , Fármacos Cardiovasculares/farmacologia , Doenças MetabólicasRESUMO
BACKGROUND@#Long non-coding RNAs (lncRNAs) play key roles in human cancers. In our previous study, we demonstrated that lncRNA FKBP prolyl isomerase 9 pseudogene 1 (FKBP9P1) was highly expressed in head and neck squamous cell cancer (HNSCC) tissues. However, its functional significance remains poorly understood. In the present study, we identify the role and potential molecular biologic mechanisms of FKBP9P1 in HNSCC.@*METHODS@#Quantitative real-time polymerase chain reaction was used to detect the expression of FKBP9P1 in HNSCC tissues, matched adjacent normal tissues, human HNSCC cells (FaDu, Cal-27, SCC4, and SCC9), and human immortalized keratinocytes cell HaCaT (normal control). Cal-27 and SCC9 cells were transfected with sh-FKBP9P1-1, sh-FKBP9P1-2, and normal control (sh-NC) lentivirus. Cell counting kit-8 assay, colony formation assay, wound healing assay, and trans-well assay were used to explore the biologic function of FKBP9P1 in HNSCC cells. Furthermore, western blotting was used to determine the mechanism of FKBP9P1 in HNSCC progression. Chi-squared test was performed to assess the clinical significance among FKBP9P1 high-expression and low-expression groups. Survival analyses were performed using the Kaplan-Meier method and assessed using the log-rank test. The comparison between two groups was analyzed by Student t test, and comparisons among multiple samples were performed by one-way analysis of variance and a Bonferroni post hoc test.@*RESULTS@#FKBP9P1 expression was significantly up-regulated in HNSCC tissues (tumor vs. normal, 1.914 vs. 0.957, t = 7.746, P < 0.001) and cell lines (P < 0.01 in all HNSCC cell lines). Besides, the median FKBP9P1 expression of HNSCC tissues (1.677) was considered as the threshold. High FKBP9P1 level was correlated with advanced T stage (P = 0.022), advanced N stage (P = 0.036), advanced clinical stage (P = 0.018), and poor prognosis of HNSCC patients (overall survival, P = 0.002 and disease-free survival, P < 0.001). Knockdown of FKBP9P1 led to marked repression in proliferation, migration, and invasion of HNSCC cells in vitro (P all < 0.01). Mechanistically, silencing FKBP9P1 was observed to restrain the PI3K/AKT signaling pathway.@*CONCLUSIONS@#Silencing lncRNA FKBP9P1 represses HNSCC progression and inhibits PI3K/AKT (phosphatidylinositol 3 kinase/AKT Serine/Threonine Kinase) signaling in vitro. Therefore, FKBP9P1 could be a potential new target for the diagnosis and treatment of HNSCC patients.
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To analyze the differentially expressed genes related to the chemosensitivity with the TPF regimen for hypopharyngeal squamous cell carcinoma and to measure potential functional targeting genes expressions. Twenty-nine patients with primary hypopharyngeal cancer who underwent induction chemotherapy with TPF from January 2013 to December 2017 in Beijing Tongren Hospital were enrolled for microarray analysis, including 28 males and 1 female, aged from 43 to 73 years old. Among them, 16 patients were sensitive to chemotherapy while 13 patients were non-sensitive. Illumina Human HT-12 Bead Chip was applied to analyze the gene expressions and online bioinformatics analysis was used to analyze the differentially expressed genes. Reverse transcription and quantitative real-time PCR (RT-qPCR) was used to measure the mRNA expression of potential functional genes of TPF induction chemotherapy in 43 samples, 29 from original patients and 14 from additional patients. Graphpad prism 7.0 software was used for statistical analysis. A total of 1 381 significantly differentially expressed genes were screened out. By GO analysis, up-regulated genes included sequestering in extracellular matrix, chemokine receptor binding and potassium channel regulator activity; down-regulated genes included regulation of angiogenesis, calcium ion binding and natural killer cell activation involved in immune response. With KEGG database analysis, down-regulated pathways included ECM-receptor interaction and peroxisome and up-regulated pathways included Glutathione metabolism and PPAR signaling pathway. The expressions of CD44 and IL-6R were significantly different and appeared biologically significant. CD44 was significantly upregulated in insensitive tissues (0.54±0.06) compared with sensitive tissues (0.33±0.04)(0.01). IL-6R was significantly downregulated in insensitive tissues (0.44±0.03) compared with sensitive tissues. (0.68±0.03) (0.01). CD44 and IL-6R may be potentially functional genes of TPF induction chemotherapy in hypopharyngeal squamous cell carcinoma.
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OBJECTIVE@#To survey the cigarette smoking status and periodontal status, and to study the correlation between cigarette smoking and periodontal status.@*METHODS@#Questionnaires were distributed (including self-assessed periodontal status, such as bleeding while brushing teeth, oral odor, tooth loosening, gum swelling, etc.) and clinical periodontal examinations performed for parameters including probing depth (PD), bleeding index (BI), attachment loss (AL), plaque index (PLI) and amount of teeth loss, which was recorded in the population above 35 years of a community in Beijing. A total of 974 subjects were recruited in the study. The population was divided into current smokers and non-smokers, and the differences of self-assessed periodontal status and periodontal parameters between the groups analyzed.@*RESULTS@#The smokers had significantly less bleeding during toothbrushing, and in the meantime, had significantly more self-reported tooth loosening compared with the non-smokers. The smokers brushed their teeth less than the non-smokers (P<0.05). The self-reported gum swelling and oral odor had no significant difference between the smokers and non-smokers. The smokers had 0.565 times and 1.572 times the risk of bleeding during toothbrushing, self-reported tooth loosening and from Logistic regression analyses, respectively (P<0.05). The mean PD, AL, PLI and the amount of tooth loss of the smokers were significant higher than the non-smokers (P<0.05). However, the mean BI of the smokers was slightly less than the non-smokers' (1.93±0.540 vs. 1.94±0.512, P=0.707). The smokers had 2.129 times, 1.698 times and 1.933 times the risk of the mean PD>3 mm, the mean AL>3 mm, and the amount of tooth loss above 8, respectively compared with the non-smokers (P<0.05) from Logistic regression analyses.@*CONCLUSION@#The self-assessed periodontal status is different between smokers and non-smokers in the population of a community in Beijing. Smokers have less bleeding during toothbrushing but no significant difference with BI. Smokers also have more self-reported tooth loosening. Compared with non-smokers, smokers have more severe periodontal destruction.
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Adulto , Humanos , Pequim , Fumar Cigarros , Índice de Placa Dentária , Perda da Inserção Periodontal , Inquéritos e QuestionáriosRESUMO
The purpose of the present study was to investigate the effect of advanced glycated albumin (AGE-alb) on pyroptosis of macrophages and the underlying molecular mechanisms. RAW264.7 macrophages were treated with AGE-alb (1, 2, 4 and 6 g/L) and control albumin (C-alb, 4 g/L) for 24 h, or preincubated with MCC950 (1 μmol/L) for 1 h and then treated with AGE-alb (4 g/L) for 24 h. Cell viability and caspase-1 activity were measured by MTT and assay kits, respectively. Lactate dehydrogenase (LDH) activity and the levels of interleukin-1β (IL-1β) and IL-18 in media were detected. Cell death degree was evaluated by TUNEL and Hoechst 33342/PI staining. The protein levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), procaspase-1 and cleaved caspase-1 were assessed by Western blot. The results showed that AGE-alb treatment caused obvious decrease in cell viability and increases in LDH leakage and the percentages of TUNEL- or PI-positive cells in a concentration-dependent manner. Additionally, AGE-alb promoted IL-1β and IL-18 secretion, upregulated NLRP3 expression, and increased caspase-1 activity especially at the dose of 4 and 6 g/L. However, MCC950 (an NLRP3 inhibitor) pretreatment inhibited significantly the decrease in cell viability and the increases in LDH leakage and percentages of TUNEL- or PI-positive cells induced by AGE-alb. Furthermore, MCC950 attenuated obviously AGE-alb-induced IL-1β and IL-18 secretion and caspase-1 activation. These results indicate that AGE-alb may induce macrophage pyroptosis, and the mechanism is at least partially by activating NLRP3-caspase-1 pathway.
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Caspase 1 , Regulação da Expressão Gênica , Interleucina-1beta , Genética , Macrófagos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Genética , Piroptose , Albumina Sérica , FarmacologiaRESUMO
Objective To study the relationship between adolescent scoliosis and various biomechanical factors. Methods A total of 637 students in grade four to six in a primary school of Zhaoyang District in Zhaotong,Yunnan,Chi-na were screened for scoliosis in December,2016.Finally,a case control study of 19 patients with idiopathic sco-liosis who had been diagnosed by X-ray was carried out.According to the matching criteria,42 students were col-lected as control group.Then,eleven biomechanical factors were analyzed and evaluated in two groups.Those factors included unequal shoulders,cervical lateral flexion,cervical rotation,thoracic lateral flexion,thoracic ro-tation,lumbar lateral flexion,lumbar rotation,lateral tilt of pelvis,anterior and posterior pelvic tilt,leg inequality and flat foot. Eventually, the biomechanical factors were statistically analyzed with binary Logistic regression analysis. Results and Conclusion The unequal shoulders,thoracic rotation,lateral tilt of pelvis,leg inequality and flat foot were the risk factors for scoliosis(P<0.05).Detailed posture assessment should be carried out to find the biomechani-cal factors leading to abnormal posture,and achieve the goals of the more targeted medical intervention for the patients with spinal asymmetry.
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This study aimed to explore the outcomes of progestin-primed ovarian stimulation protocol (PPOS) in aged infertile women who failed to get pregnant in the first IVF/ICSI-ET cycles with GnRH-a long protocol.A self-controlled study was conducted to retrospectively investigate the clinical outcomes of 104 aged infertile patients who didn't get pregnant in the first IVF/ICSI-ET treatment by stimulating with GnRH-a long protocol (non-PPOS group),and underwent PPOS protocol (PPOS group) in the second cycle between January 2016 and December 2016 in the Center for Reproductive Medicine,Renmin Hospital of Wuhan University.The primary outcomes included clinical pregnancy rate of frozen-thawed embryos transfer (FET) in PPOS group,and good-quality embryo rate in both groups.The secondary outcomes were fertilization rate,egg utilization rate and cycle cancellation rate.The results showed that there were no significant differences in basal follicle stimulating hormone (bFSH),antral follicle count (AFC),duration and total dosage of gonadotropin (Gn),number of oocytes retrieved,intracytoplasmic sperm injection (ICSI) rate,fertilization rate,and cycle cancellation rate between the two groups (P>0.05).However,the oocyte utilization rate and good-quality embryo rate in PPOS group were significantly higher than those in non-PPOS group (P<0.05).By the end of April 2017,62 FET cycles were conducted in PPOS group.The clinical pregnancy rate and embryo implantation rate were 22.58% and 12.70%,respectively.In conclusion,PPOS protocol may provide better clinical outcomes by improving the oocyte utilization rate and good-quality embryo rate for aged infertile patients who failed to get pregnant in the first IVF/ICSI-ET cycles.
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This study aimed to explore the outcomes of progestin-primed ovarian stimulation protocol (PPOS) in aged infertile women who failed to get pregnant in the first IVF/ICSI-ET cycles with GnRH-a long protocol.A self-controlled study was conducted to retrospectively investigate the clinical outcomes of 104 aged infertile patients who didn't get pregnant in the first IVF/ICSI-ET treatment by stimulating with GnRH-a long protocol (non-PPOS group),and underwent PPOS protocol (PPOS group) in the second cycle between January 2016 and December 2016 in the Center for Reproductive Medicine,Renmin Hospital of Wuhan University.The primary outcomes included clinical pregnancy rate of frozen-thawed embryos transfer (FET) in PPOS group,and good-quality embryo rate in both groups.The secondary outcomes were fertilization rate,egg utilization rate and cycle cancellation rate.The results showed that there were no significant differences in basal follicle stimulating hormone (bFSH),antral follicle count (AFC),duration and total dosage of gonadotropin (Gn),number of oocytes retrieved,intracytoplasmic sperm injection (ICSI) rate,fertilization rate,and cycle cancellation rate between the two groups (P>0.05).However,the oocyte utilization rate and good-quality embryo rate in PPOS group were significantly higher than those in non-PPOS group (P<0.05).By the end of April 2017,62 FET cycles were conducted in PPOS group.The clinical pregnancy rate and embryo implantation rate were 22.58% and 12.70%,respectively.In conclusion,PPOS protocol may provide better clinical outcomes by improving the oocyte utilization rate and good-quality embryo rate for aged infertile patients who failed to get pregnant in the first IVF/ICSI-ET cycles.