Two naturally derived small molecules disrupt the sineoculis homeobox homolog 1-eyes absent homolog 1 (SIX1-EYA1) interaction to inhibit colorectal cancer cell growth / 中华医学杂志(英文版)

BACKGROUND@#Emerging evidence indicates that the sineoculis homeobox homolog 1-eyes absent homolog 1 (SIX1-EYA1) transcriptional complex significantly contributes to the pathogenesis of multiple cancers by mediating the expression of genes involved in different biological processes, such as cell-cycle progression and metastasis. However, the roles of the SIX1-EYA1 transcriptional complex and its targets in colorectal cancer (CRC) are still being investigated. This study aimed to investigate the roles of SIX1-EYA1 in the pathogenesis of CRC, to screen inhibitors disrupting the SIX1-EYA1 interaction and to evaluate the efficiency of small molecules in the inhibition of CRC cell growth.@*METHODS@#Real-time quantitative polymerase chain reaction and western blotting were performed to examine gene and protein levels in CRC cells and clinical tissues (collected from CRC patients who underwent surgery in the Department of Integrated Traditional and Western Medicine, West China Hospital of Sichuan University, between 2016 and 2018, n = 24). In vivo immunoprecipitation and in vitro pulldown assays were carried out to determine SIX1-EYA1 interaction. Cell proliferation, cell survival, and cell invasion were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, clonogenic assay, and Boyden chamber assay, respectively. The Amplified Luminescent Proximity Homogeneous Assay Screen (AlphaScreen) method was used to obtain small molecules that specifically disrupted SIX1-EYA1 interaction. CRC cells harboring different levels of SIX1/EYA1 were injected into nude mice to establish tumor xenografts, and small molecules were also injected into mice to evaluate their efficiency to inhibit tumor growth.@*RESULTS@#Both SIX1 and EYA1 were overexpressed in CRC cancerous tissues (for SIX1, 7.47 ± 3.54 vs.1.88 ± 0.35, t = 4.92, P = 0.008; for EYA1, 7.61 ± 2.03 vs. 2.22 ± 0.45, t = 6.73, P = 0.005). The SIX1/EYA1 complex could mediate the expression of two important genes including cyclin A1 (CCNA1) and transforming growth factor beta 1 (TGFB1) by binding to the myocyte enhancer factor 3 consensus. Knockdown of both SIX1 and EYA1 could decrease cell proliferation, cell invasion, tumor growth, and in vivo tumor growth (all P < 0.01). Two small molecules, NSC0191 and NSC0933, were obtained using AlphaScreen and they could significantly inhibit the SIX1-EYA1 interaction with a half-maximal inhibitory concentration (IC50) of 12.60 ± 1.15 μmol/L and 83.43 ± 7.24 μmol/L, respectively. Administration of these two compounds could significantly repress the expression of CCNA1 and TGFB1 and inhibit the growth of CRC cells in vitro and in vivo.@*CONCLUSIONS@#Overexpression of the SIX1/EYA1 complex transactivated the expression of CCNA1 and TGFB1, causing the pathogenesis of CRC. Pharmacological inhibition of the SIX1-EYA1 interaction with NSC0191 and NSC0933 significantly inhibited CRC cell growth by affecting cell-cycle progression and metastasis.

Influence of acupuncture and moxibustion on defecation in postoperative patients of anal fissure: a randomized controlled trial / 中国针灸

<p><b>OBJECTIVE</b>To verify the clinical efficacy of acupuncture and moxibustion on defecating and pain symptoms in postoperative patient of anal fissure.</p><p><b>METHODS</b>Two hundred cases of postoperation of anal fissure were randomly divided into an acupuncture-moxibustion group and a medication group, 100 cases in each one. The basic treatment after the surgery was the same in two groups, besides, acupuncture was applied at Zhongliao (BL 33) and Xialiao (BL 34) in the morning of first 5 days of postoperative 24 h in the acupuncture-moxibustion group, and suspended moxibusiton was applied at Changqiang (GV 1) within 5 to 10 min after defecation; while two bags of forlax was orally administrated in the morning of first 5 days of postoperative 24 h in the medication group. The pain intensity, defecation willingness, defecation difficulty and stool texture during postoperative defecation were observed.</p><p><b>RESULTS</b>The defecation pain on the first two days after the treatment was not statistically significant between two groups (both P > 0.05). From the third day of treatment, the improvements of defecation pain in acupuncture-moxibustion group were more obvious than those in the medication group (all P < 0.05). The patients in the acupuncture-moxibustion group had more positive defecation willingness than those in the medication group (all P < 0.05). The differences of defecation difficulty and stool properties in two groups had no statistical significance (both P > 0.05).</p><p><b>CONCLUSION</b>The intervention treatment of acupuncture and moxibustion has clinical significance on relieving pain symptoms and improving defecation willingness in postoperative patient of anal fissure.</p>

Clinical observation of urinary retention after hemorrhoid and fistula operation treated with suspen-ding moxibustion / 中国针灸

<p><b>OBJECTIVE</b>To compare the therapeutic effects among moxibustion, local hot compress and infrared irradiation on urinary retention after hemorrhoid and fistula operation so as to provide the clinical evidences for the promotion and application of moxibustion.</p><p><b>METHODS</b>The randomized controlled trial method was adopted to divide 60 cases of post-operative urinary retention into moxibustion group, hot compress group and infrared irradiation group, 20 cases in each group. In moxibustion group, suspending moxibustion was applied on Qihai (CV 6) and Zhongji (CV 3). In hot compress group, hot compress was applied on the bladder region above the symphysis pubis of the lower abdomen. In infrared irradiation group, MF-C701 multi-source infrared apparatus was used on the bladder region above the symphysis pubis of the lower abdomen. One intervention therapy was administered for the cases of post-operative urinary retention. The efficacy was assessed based on the numbers of urethral catheterization indwelled in 24 h after treatment.</p><p><b>RESULTS</b>There were 2 cases (10.0%) with urethral catheterization in moxibustion group, 10 cases (50.0%) in hot compress group and 9 cases (45.0%) in infrared irradiation group. The urethral catheterization rate in moxibustion group was lower than that of the other two treatment programs (both P < 0.05).</p><p><b>CONCLUSION</b>Moxibustion can reduce much effectively the rate of urethral catheterization indwelled for urinary retention after hemorrhoid and fistula operation as compared with local hot compress therapy and infrared irradiation on the lower abdomen.</p>

Observation on therapeutic effect of electroacupuncture at Tianshu (ST 25) with deep needling technique on functional constipation / 中国针灸

<p><b>OBJECTIVE</b>To probe into a better therapeutic method for functional constipation.</p><p><b>METHODS</b>Ninety-five cases of functional constipation were randomly divided into deep puncture at ST 25 group (48 cases), shallow puncture at ST 25 group (24 cases) and medication group (23 cases). In deep puncture at ST 25 group, Tianshu (ST 25) was punctured deeply to the peritoneum, with electric stimulation. In shallow puncture at ST 25 group, Tianshu (ST 25) was punctured shallowly, 5 mm beneath the skin, with electric stimulation. In medication group, Duphalac was administered orally. These cases were treated continuously for 4 weeks in 3 groups and followed up for 6 months. It was to observe the numbers of person who had defecation 4 times a week, difference in weekly defecation frequency and the difference in the Cleveland Clinic Score (CCS).</p><p><b>RESULTS</b>In deep puncture at ST 25 group, the frequency of weekly defecation and the numbers of person who had defecation 4 times a week increased and CCS decreased, which were similar to the efficacy in shallow puncture at ST 25 group (all P > 0.05). But the efficacy of both ST 25 groups was superior to that in medication group (both P < 0.05). In comparison, the deep puncture at ST 25 group acted more quickly than either shallow puncture at ST 25 group or medication group and its efficacy remained much longer.</p><p><b>CONCLUSION</b>The deep puncture at ST 25 with electric stimulation presents similar efficacy on functional constipation as shallow puncture at ST 25, but it acts more quickly than shallow puncture at ST 25, both of them are more advantageous than medication and the long-term efficacy is better.</p>

Observation on therapeutic effect of electroacupuncture at Chengshan (BL 57) and Changqiang (GV 1) on hemorrhoidal pain / 中国针灸

<p><b>OBJECTIVE</b>To assess the clinical effect of combination of far with near acupoints, Chengshan (BL 57) and Changqiang (GV 1), for acupuncture treatment of hemorrhoidal pain.</p><p><b>METHODS</b>One hundred and twenty cases of hemorrhoids with pain were randomly divided into 2 groups, an electroacupuncture group and a medication group, 60 cases in each group. The electroacupuncture group were treated by electroacupuncture at Changqiang (GV 1) and Chengshan (BL 57) with sparse-dense wave, frequency 2/100 Hz; and the medication group with oral administration of Tramadol and rectal application of Mayinglong Shexiang Zhichuang Suppository. The two group were treated for five days. Changes of pain were assessed by Visual Analogue Scale (VAS) scores at the defecation each day.</p><p><b>RESULTS</b>In the electroacupuncture group, VAS score was 6.64 +/- 3.66 before treatment and 5.65 +/- 2.21 on the second day of treatment with a significant decrease (P < 0.05), and 1.85 +/- 1.24 on the fifth day after treatment end. In the medication group, VAS score was 6.58 +/- 3.18 before treatment and 4.86 +/- 2.04 on the third day after treatment with significant decrease compared with that before treatment, and 2.24 +/- 1.46 on the fifth day. There was no significant difference between the two groups in the pain score on the fifth day after the treatment end.</p><p><b>CONCLUSION</b>Combination of Chengshan (BL 57) with Changqiang (GV 1) is effective for improvement of hemorrhoidal pain in defecation.</p>

Denaturant gradient gel electrophoresis in the genetic diagnosis of hereditary multiple exostoses / 中南大学学报(医学版)

OBJECTIVE@#To detect the mutations of EXT2 gene in hereditary multiple exostoses (HME) families and to investigate the sensitivity of denaturant gradient gel electrophoresis (DGGE) in screening the mutations in EXT2 gene.@*METHODS@#Five HME families and 3 sporadic patients were screened for the mutation detection in all exons of EXT2 gene covering the coding sequence and the flanking intronic sequence by DGGE, and DNA sequencing was performed for products with abnormal conformation.@*RESULTS@#Among these HME patients, we found 2 disease-causing mutations: A313T (nonsense mutation) and 319 insGT (frameshift mutation).@*CONCLUSION@#Two mutations of EXT2 gene are identified in the sample. DGGE can be an ideal choice for gene diagnoses of HME.

Infection of intervertebral space and the interventional therapy / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of interventional therapy in the treatment of intervertebral space infection.@*METHODS@#The needle was punctured into the infected intervertebral space from the post-lateral side of the spine monitored by X-rays. The pus was drained, the degenerative disc tissues and necrosis tissues were excised and taken out, and at the end a drainaging catheter was put into the space through the needle. The patient should lie in bed absolutely. The antibiotics was injected into the space through the silicon catheter every day. Three to four weeks later, the catheter was removed.@*RESULTS@#All the 8 patients got good results after the therapy. The low back pain was dramatically alleviated instantly at the day of operation. Erythrocyte sedimental rate gradually descended. After 3 approximately 4 weeks of treatment,the catheter was removed.@*CONCLUSION@#Interventional therapy of the intervertebral space infection has notable advantage over the open operation.

Novel mutation of Y271H in EXT1 gene causes multiple exostoses / 中南大学学报(医学版)

OBJECTIVE@#To explore the disease associated gene mutation of multiple exostoses by family analysis.@*METHODS@#Polymerase chain reaction and DNA sequencing were used to detect the mutation hot spot regions of EXT1 and EXT2 gene, while restriction fragment length polymorphism was performed to screen the mutation.@*RESULTS@#We found a novel heterozygous mutation c.811T ->C in EXT1 gene of patients, which resulted in the substitution of histidine for tyrosine at codon 271 in this hereditary multiple exostoses family. The mutation was not found in the unaffected family members, nor in the 100 unrelated normal individual, which was unreported before.@*CONCLUSION@#The novel mutation Y271H is the disease-causing mutation in the hereditary multiple exostoses family.