AIM:To investigate the potential role of Sonic hedgehog (Shh) signaling pathways in the radioresistance of esophageal cancer.METHODS:Radioresistant cell line Eca109R was established by repeating X-ray irradiation at dose of 60 Gy in total using Eca109 cells as parental cells.The radiosensitivity of the parental and radioresistant cells was confirmed by colony formation assay.The cell viability was detected by CCK-8 assay.The intracellular protein levels of Shh and Gli1 were determined by Western blot and immunofluorescence.RESULTS:The survival fractions at dose of 2 Gy for Eca109R cells and Eca109 cells were 0.937±0.013 and 0.499±0.042, respectively.The inhibitory rate of cell viability decreased gradually in the Eca109R cells (P<0.05), suggesting that the radioresistant cell line was successfully established.The results of Western blot indicated that the protein expression of Shh and Gli1 was much higher in the Eca109R cells than that in the Eca109 cells (P<0.05).Immunofluorescence staining showed that Gli1 was expressed in the cytoplasm and nucleus, and presented nuclear clustering in the Eca109R cells.The positive rate of Gil1 expression in Eca109 cells was 52.3%± 0.035%, while that in Eca109R cells was 87.6%±0.021% (P<0.05).CONCLUSION:The radioresistance of esophageal cancer may be related to the activation of Shh signaling pathways with over-expression of Gli1 and other related proteins.

OBJECTIVETo evaluate the effect of penile frenulum lengthening in the treatment of premature ejaculation (PE).

METHODSThirty-four males with PE were enrolled in this study, of whom 8 had received circumcision six months before and 4 had redundant prepuce, all with short frenulum. Those with a history of circumcision underwent reconstruction and lengthening of the frenulum, and those without received frenulum lengthening only.

RESULTSCompared with the baseline, the intravaginal ejaculation latency time (IELT) was significantly increased at 1 month after operation ([1.35 ± 0.49] vs [5.71 ± 2.69] min, t = -9.42, P <0.01), (1.42 ± 0.5) vs (5.31 ± 2.74) min in the patients without circumcision (t = -7.41, P <0.01), (1.12 ± 0.35) vs (7.00 ± 2.20) min in those with circumcision (t = -7.24, P <0.01), and (1.50 ± 0.58) vs (4.75 ± 1.71) min in those with redundant prepuce (t = -3.81, P <0.05). Totally, 94% of the patients were satisfied with their sexual intercourse postoperatively.

CONCLUSIONPenile frenulum plays an important role in penile erection. Reconstruction and/or lengthening of the frenulum can prolong penile erection and IELT in PE patients.

Adult ; Circumcision, Male ; rehabilitation ; Coitus ; Ejaculation ; Foreskin ; surgery ; Humans ; Male ; Penile Erection ; Premature Ejaculation ; surgery ; Reconstructive Surgical Procedures ; methods

In this paper, based on the special influence of supramolecular chemistry on the basic theory of Chinese medicines ( CM) , the authors further analyzed the history of meridian tropism and natural origins of CM organisms and explained CM ingredients and the universal regularity of the automatic action of the supramolecular "imprinting templates" hole channel structure. After entering human bodies, CMs, as the aggregation of supramolecular "imprinting templates" , automatically seek supramolecular subjects that are matched with their "imprinting templates" in human meridians and organs for the purpose of self-recognition, self-organization, self-assembly and self-replication, so as to generate specific efficacy in meridians and organs, which is reflected as the meridian tropism phenomena at macro level. This regularity can be studied by in vitro and in vivo experimental studies. In vitro methods are mostly supra molecular structure analysis and kinetic and thermodynamic parameter calculation; Whereas in vivo methods are dominated by the analysis on object component distribution, chromatopharmacodynamic parameters and network chromatopharmacodynamic parameters; Particularly, the acupoint-medicine method can simplify to study the supramolecular subject-object relations. Consequently, CM's'meridian tropism reveals the universal regularity for interactions of macromolecular and micromolecular "imprinting templates" of subjects and objects in natural organisms. As the first barrier for the material base of the CM theory and breakthrough in the modernization of the basic CM theory, meridian tropism plays an important role in studies on basic theories of the basic CM theory.
Acupuncture Points ; Drug Therapy ; Drugs, Chinese Herbal ; chemistry ; Humans ; Medicine, Chinese Traditional ; Meridians

Background Noninvasive positive pressure ventilation (NIPPV) has been proposed to shorten the duration of mechanical ventilation in intubated patients,especially those who fail initial weaning from invasive mechanical ventilation (IMV).However,there are also some discrepancies in terms of weaning success or failure,incidence of re-intubation,complications observed during study and patient outcomes.The primary objective of this update was to specifically investigate the role of NIPPV on facilitating weaning and avoiding re-intubation in patients intubated for different etiologies of acute respiratory failure,by comparing with conventional invasive weaning approach.Methods We searched randomized controlled trials (RCTs) comparing noninvasive weaning of early extubation and immediate application of NIPPV with invasive weaning in intubated patients from PubMed,Embase,Cochrane Central Register of Controlled Trials,Web of Knowledge and Springerlink databases.Records from conference proceedings and reference lists of relevant studies were also identified.Results A total of 11 RCTs with 623 patients were available for the present analysis.Compared with IMV,NIPPV significantly increased weaning success rates (odds ratio (OR):2.50,95％ confidence interval (C/):1.46-4.30,P=0.0009),decreased mortality (OR:0.39,95％ CI:0.20-0.75,P=0.005),and reduced the incidence of ventilator associated pneumonia (VAP) (OR:0.17,95％ CI:0.08-0.37,P ＜0.00001) and complications (OR:0.22,95％ CI:0.07-0.72,P=0.01).However,effect of NIPPV on re-intubation did not reach statistical difference (OR:0.61,95％ CI:0.33-1.11,P=0.11).Conclusions Early extubation and immediate application of NIPPV is superior to conventional invasive weaning approach in increasing weaning success rates,decreasing the risk of mortality and reducing the incidence of VAP and complications,in patients who need weaning from IMV.However,it should be applied with caution,as there is insufficient beneficial evidence to definitely recommend it in terms of avoiding re-intubation.

The paper aimed to elucidate the specific impact of supramolecular chemistry on the Chinese medicine theories (CMT) in their modernization, after had summarized up the research status of supramolecular chemistry and analyzed the possible supramolecular forms of Chinese medicine (CM), as well as considered the problems in modernization of CM theories. On comparison of the classical chemistry that delt with chemical bonds among atoms, the supramolecular chemistry was rather concerned with varietes of weak noncovalent bonds intermolecules, and reflected the macro-apparent chemical properties of each molecules, and was the most appropriate chemical theories to explain the CMT and microcosmic materials. The molecules in the human body and Chinese material medica (CMM) formed supramolecules by way of self-assembly, self-organization, self-recognition and self-replication, with themselves or with complexation, composition, chelation, inclusion, neutralization etc. Meridian and Zang-fu viscera in CMT might be a space channel structure continuously consisted of unique molecules cavity that was imprinted with the supramolecularly template inside and outside of cells, through which the molecules in CMM interacted with the meridian and Zang-fu viscera. When small molecules in human body imprinted with macromolecules in meridian and Zang-fu viscera, in other words, they migrated along within imprinting channels of meridian and Zang-fu viscera on behavior of "Qi chromatography" impulsed by the heart beat, finally showed up on macroscopic the anisotropy of tissue and organ, as described namely as visceral manifestation in Chinese medical science. When small molecules in CMM interacted with imprinting channel on meridian and Zang-fu viscera, the natural properties and efficacy regularities of CMM was reflected on macroscopic. Therefore, the special representation forms of basic CMT is based on the macroscopic expression of "Qi chromatography" abided by imprinting effect regularities, and on whether the imprinted template of small molecules matched with cavity template of macromolecules in meridian and Zang-fu viscera, only is the adequate representation of supramolecular chemistry for them. The CMM materials is the mixture including single molecules and supramolecules. The compatibility for CM prescriptions can significantly change the function rules. Therefore in the study of basic CMT, we should pay special attention to the laws of supramolecular chemistry. It is the most essential differences of the CMT from the modern medicine which established by the laws of single molecular theories.
Chemistry, Pharmaceutical ; Drug Therapy ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Meridians ; Nanotechnology

AIM:To investigate the relationship between Sonic Hedgehog(Shh)signaling pathway and cell cycle and radioresistance of esophageal cancer by up-regulating Gli1,a key factor in Shh signaling pathway.METHODS:The human esophageal cancer cell line Eca 109 was transfected with plasmid to induce Gli 1 over-expression,which served as Eca109-ox-Gli1 group.In addition, Eca109 cells transfected with empty plasmid served as negative control group and the untreated Eca109 cells were used as normal control group.The expression of Gli1 was confirmed by real-time PCR and Western blot.The radiosensitivity of the cells in the 3 groups was determined by colony formation assay.The effect of irra-diation on the cell cycle was analyzed by flow cytometry.RESULTS:The expression of Gli1 in Eca109-ox-Gli1 group was higher than that in the other 2 groups(P<0.05).The survival fraction at dose of 2 Gy in Eca109-ox-Gli1 group was high-er than that in normal control group, indicating that the radioresistance of the Eca 109 cells transfected with Gli1 plasmid was increased.The cells in Eca109-ox-Gli1 group showed higher S phase proportion than that in normal control group and negative control group(P<0.01).After irradiation at dose of 6 Gy,all cells in the 3 groups found that the cell cycle was arrested at G2/M phase,while the cells in normal control group showed higher G 2/M phase proportion than that in Eca109-ox-Gli1 group(P<0.01).CONCLUSION: The up-regulation of Gli1 may enhance the radioresistance of esophageal cancer by regulating the cell cycle.

Objective:To identify the key genes involved in the development and progression of prostate cancer(PCa)and those associated with the prognosis of the malignancy.Methods:We obtained the single-cell sequencing data on 4 cases of PCa from the GSE156632 database.Using R language and the Seurat package,we performed cell clustering and annotation,selected the subpop-ulations of epithelial cells for differential analysis after quality control and cell type identification,and conducted enrichment analysis of the identified differential genes using the Hiplot website.Then we downloaded the single nucleotide polymorphism(SNP)loci corre-sponding to the expression quantitative trait loci(eQTL)of these genes from the UK Biobank(UKB)database,and the clinical data and corresponding gene expression data on PCa patients from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO),followed by univariate COX regression analysis of the impact of the genes on the prognosis of the patients after Mendelian ran-domization.Results:A total of 1 566 genes were identified and subjected to enrichment analysis,which indicated that the differenti-al genes might be enriched in the Ras,apoptosis and oxidative phosphorylation signaling pathways.Subsequent Mendelian randomiza-tion revealed 74 potential causal genes among the 1 566 genes,and univariate COX regression analysis of the 74 genes identified 4 pos-sibly related genes FAM3B,JUNB,TMEM59,and KRT5.Comparison of the results of Mendelian randomization and univariate COX regression showed that KRT5 might be the most important gene influencing PCa.Conclusion:FAM3B,JUNB,TMEM59 and KRT5 may play a role in the progression of PCa,and KRT5 may potentially serve as a prognostic predictor and therapeutic target for the malig-nancy.

OBJECTIVETo investigate the effect of phenyl-hexyl isothiocyanate (PHI) on acetylation and methylation of histone in acute lymphoblastic leukemia cell line Molt4.

METHODSThe inhibition of cell proliferation was observed by MTT method and clone suppression test. Apoptosis and cell cycle arrest were measured by flow cytometry. The alterations in histone acetyltransferase and acetylation and methylation of histones were detected by Western blot.

RESULTSPHI could up-regulate the expression of acetyltransferase (P300/CBP), markedly induced the accumulation of acetylated histone H3, H4 and methylated histone H3 lysine 4 (H3K4), and inhibited methylation on lysine 9 of H3 (H3K9). The epigenetic regulation resulted in cell cycle arrest at G0/G1 phase, and induction of apoptosis.

CONCLUSIONSPHI can modulate both histone methylation and acetylation. It may serve as a histone deacetylase inhibitor, and might be a potential novel anti-leukemia agent.

Acetylation ; drug effects ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Epigenesis, Genetic ; Histone Deacetylases ; metabolism ; Histones ; metabolism ; Humans ; Isothiocyanates ; pharmacology ; Methylation ; drug effects

BACKGROUNDAscorbic acid has important antioxidant properties, and may play a role in the protective effects of ischemic preconditioning on later ischemia-reperfusion. Herein, we examined the role of endogenous extracellular ascorbic acid in ischemic preconditioning in the kidney.

METHODSWe developed a solitary rabbit kidney model where animals received ischemia-reperfusion only (ischemia-reperfusion group, n = 15) or ischemic preconditioning followed by ischemia-reperfusion (ischemic preconditioning group, n = 15). Ischemia-reperfusion was induced by occluding and loosening of the renal pedicle. The process of ischemic preconditioning included 15-minute brief ischemia and 10-minute reperfusion. In vivo microdialysis coupled with online electrochemical detection was used to determine levels of endogenous extracellular ascorbic acid in both groups. The extent of tissue damage was determined in kidney sections stained with hematoxylin and eosin. Serum creatinine and urea nitrogen were also detected to assess renal function.

RESULTSDuring ischemia-reperfusion, the extracellular ascorbic acid concentration during ischemia increased rapidly to the peak level ((130.01 +/- 9.98)%), and then decreased slowly to near basal levels. Similar changes were observed during reperfusion (peak level, (126.78 +/- 18.24)%). In the ischemic preconditioning group there was a similar pattern of extracellular ascorbic acid concentration during ischemic preconditioning. However, the ascorbic acid level was significantly lower during the ischemia and early reperfusion stage compared to the ischemia-reperfusion group. Additionally, the extent of glomerular ischemic collapse, tubular dilation, tubular denudation, and loss of brush border were markedly attenuated in the ischemic preconditioning group. Levels of serum creatinine and urea nitrogen were also decreased significantly in the ischemic preconditioning group.

CONCLUSIONSIschemic preconditioning may protect renal tissue against ischemia-reperfusion injury via use of extracellular ascorbic acid. In vivo microdialysis coupled with online electrochemical detection is effective for continuous monitoring extracellular ascorbic acid in the renal cortex.

Animals ; Ascorbic Acid ; metabolism ; Disease Models, Animal ; Ischemic Preconditioning ; methods ; Kidney ; metabolism ; pathology ; Rabbits ; Reperfusion Injury ; prevention & control

The paper, based on the previous publication as special impact of Chinese medicine theories on supramolcular chemistry, aims to analyze the natural origination for the Chinese medicine and to explain the special impact of "Qi chromatography" reaction on "imprinting templates" in supramolcular host of human being with Chinese medicine, in order to reveal the CM's properties of "medical element" with "imprinting templates" autonomisation generally took place in natural supramolecules, and also to discover that the CM's pharmacology are satisfied with its own approaches different form western pharmacology. It was decided, for CM's pharmacology guided by CM's theories, to "Qi chromatography" relations between the CM's ingredient groups and the meridian zang-fu viscera. The supramolcular chemistry played an all-through role in procession of making macro-regularities and special presentation on behavior of "Qi chromatography" impulse owning to the matching action of all kinds of ingredients on the meridian zang-fu viscera with similar "imprinting templates". The CM's pharmacology were guided by CM's theories, owing to its interpretation of supramolecular chemistry. The pharmacology was achieved to construct up completely on base of classical chemical single molecular bonds whereas the CM's pharmacology be configured to big building by way of "imprinting templates" as multi-weak bonds among "supramolecular society". CM's pharmacology was supramolcular pharmacology dealt with "molecular society" on the base of western pharmacology, and employed to double research approaches both math-physical quantitative representation on macroscope and qualitative analyses in microscope.
Animals ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Meridians ; Molecular Imprinting ; Qi