RBBP4 promotes colon cancer malignant progression via regulating Wnt/β-catenin pathway

BACKGROUND Our previous study demonstrated that RBBP4 was upregulated in colon cancer and correlated with poor prognosis of colon cancer and hepatic metastasis.However,the potential biological function of RBBP4 in colon cancer is still unknown.AIM To investigate the biological role and the potential mechanisms of RBBP4 in colon cancer progression.METHODS Real-time polymerase chain reaction and western blot analysis were used to detect the expression of RBBP4 in colon cancer cell lines.The cell proliferation and viability of SW620 and HCT116 cells with RBBP4 knockdown was detected by Cell Counting Kit-8 and 5-ethynyl-2’-deoxyuridine staining.The transwell assay was used to detect the invasion and migration capabilities of colon cancer cells with RBBP4 knockdown.Flow cytometry apoptosis assay was used to detect the apoptosis of colon cancer cells.Western blotting analysis was used to detect the expression of epithelial-mesenchymal transition and apoptosis related markers in colon cancer.The nuclear translocation ofβ-catenin was examined by Western blotting analysis in colon cancer cells with RBBP4 knockdown.The TOPFlash luciferase assay was used to detect the effect of RBBP4 on Wnt/β-catenin activation.The rescue experiments were performed in colon cancer cells treated with Wnt/β-catenin activator LiCl and RBBP4 knockdown.RESULTS We found that RBBP4 was highly expressed in colon cancer cell lines.The 5-ethynyl-2’-deoxyuridine assay showed that knockdown of RBBP4 significantly inhibited cell proliferation.RBBP4 inhibition reduced cell invasion and migration via regulating proteins related to epithelial-mesenchymal transition.Knockdown of RBBP4 significantly inhibited survivin-mediated apoptosis.Mechanistically,the TOPFlash assay showed that RBBP4 knockdown increased activity of the Wnt/β-catenin pathway.Meanwhile,RBBP4 knockdown suppressed nuclear translocation ofβ-catenin.With Wnt/β-catenin activator,rescue experiments suggested that the role of RBBP4 in colon cancer progression was dependent on Wnt/β-catenin pathway.CONCLUSION RBBP4 promotes colon cancer development via increasing activity of the Wnt/β-catenin pathway.RBBP4 may serve as a novel therapeutic target in colon cancer.

Enterostomy can decrease the mortality of patients with Fournier gangrene

AIM:To determine the significance of enterostomy in the emergency management of Fournier gangrene.METHODS:The clinical data of 51 patients(49 men and 2 women)with Fournier gangrene who were treated at our hospital over the past 12 years were retrospectively analyzed.The patients were divided into two groups according the surgical technique performed:enterostomy combined with debridement(the enterostomy group,n=28)or debridement alone(the control group,n=23).Patients in the enterostomy group received thorough debridement during surgery and adequate local drainage after surgery,as well as administration of broad-spectrum antibiotics.The clinical data and outcomes in both groups were analyzed.RESULTS:The surgical procedures were successful in both patient groups.In the enterostomy group,10 (35.8%)patients required skin grafting with a total of six debridement procedures.While in the control group,six(26.1%)patients required four debridement procedures.However,this difference was not statistically significant.Following surgery,the time to normal body temperature(6 d vs 8 d,P<0.05)and average length of hospital stay(14.3±7.8 d vs 20.1±8.9 d,P<0.05)were shorter in the enterostomy group.The case fatality rate was lower in the enterostomy group than that in the control group(3.6%vs 21.7%,P<0.05).CONCLUSION:Enterostomy can decrease the case fatality rate of patients with Fournier gangrene.

Correlation between invasive microbiota in margin-surrounding mucosa and anastomotic healing in patients with colorectal cancer

BACKGROUND Impaired anastomotic healing is one of the major complications resulting from radical resection in colorectal cancer(CRC).Accumulating evidence suggests that intestinal microbiota is correlated with anastomotic healing.AIM To explore the microbiota structural shift in margin-surrounding mucosa and evaluate the predictive ability of selected bacterial taxa for impaired anastomotic healing.METHODS Margin-surrounding mucosa samples derived from 37 patients were collected to characterize the microbial community structure by 16 s r RNA gene sequencing.The patients were divided into two groups according to the healing status of anastomoses:well-healing group(n=30)and impaired-healing group(n=7).Statistic differences in bacteria taxa were compared by Wilcoxon test and chisquared test.The predictive ability of the selected bacterial taxa for the healing status of anastomoses was evaluated by the area under the receiver operator characteristic curve.RESULTS Community structure shifts were observed in the impaired-healing group andwell-healing group.Six bacterial species were found to be significantly correlated with anastomotic healing,and among these species,Alistipes shahii,Dialister pneumosintes,and Corynebacterium suicordis were considered as the predictive factors.Taking the known risk factor age into consideration,Alistipes shahii,Dialister pneumosintes,and Corynebacterium suicordis improved predictive ability for the healing status of anastomoses.CONCLUSION These data show that Alistipes shahii,Dialister pneumosintes,and Corynebacterium suicordis could be considered as supplementary factors in the prediction of anastomosis healing status in patients after CRC radical resection.

Application of 4% formaldehyde under electronic colonoscope as a minimally invasive treatment of chronic hemorrhagic radiation proctitis

BACKGROUND: To investigate the effectiveness of topical application of 4% formaldehyde as a minimally invasive treatment of rectal bleeding due to chronic radiation proctitis(CRP) under direct vision of electronic colonoscope.METHODS: The clinical data of 13 CRP patients complicated with ≥ grade Ⅱ bleeding admitted to our hospital between January 2003 and December 2018 were retrospectively analyzed. Under the guidance of electronic colonoscope,4% formaldehyde combined with 5-aminosalicylic acid(5-ASA) suppositories was topically applied. Patients were followed up for two months after treatment,and the therapeutic effectiveness was observed and analyzed.RESULTS: The rectal bleeding due to CRP was markedly reduced after topical application of 4% formaldehyde under colonoscope in all 13 patients. The bleeding stopped after one treatment session in 11 patients and after the second session in 2 patients. 5-ASA was also applied along with the use of 4% formaldehyde. The therapeutic effectiveness was satisfactory during the 1-and 2-month follow-up period.CONCLUSION: Topical application of 4% formaldehyde under the direct vision of colonoscope as a minimally invasive treatment for CRB-induced bleeding is a simple,effective,affordable,and repeatable technique without obvious complications,which deserves further exploration and promotion.

脑源性神经营养因子基因多态性对腹腔镜子宫切除术患者右美托咪定麻醉苏醒期的影响

目的探讨脑源性神经营养因子(BDNF)基因多态性对腹腔镜子宫切除术患者右美托咪定麻醉苏醒期的影响。方法选取2019年8月—2021年1月济宁医学院附属医院行腹腔镜子宫切除术患者98例。所有患者均应用右美托咪定。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测患者BDNF基因rs6265位点的单核苷酸多态性(SNP),按照基因型分为GG组、GA组、AA组。比较3组患者基本特征、疼痛程度、舒适度、苏醒质量及不良反应。结果BDNF基因rs6265位点的基因型频率符合Hardy-Weinberg平衡(P>0.05);BDNF基因rs6265位点GG组、GA组、AA组患者的年龄、体重指数(BMI)、美国麻醉医师协会(ASA)分级、疾病类型及手术时间、术中出血量比较,差异无统计学意义(P>0.05);GG组、GA组、AA组术后4 h、12 h、24 h的VAS及BCS评分比较,采用重复测量设计的方差分析,不同时间点的VAS及BCS评分有差异(P<0.05);3组的VAS评分及BCS评分有差异(P<0.05),相比GG组、GA组,AA组VAS评分较高、BCS评分较低,相对镇痛效果、舒适度较差;3组的VAS评分及BCS评分的变化趋势有差异(P<0.05);苏醒时间、自主呼吸恢复时间、拔管时间AA组>GA组>GG组,Steward苏醒评分、麻醉苏醒后MMSE评分AA组<GA组<GG组(P<0.05);AA组不良反应发生率(41.38%)比GG组(17.86%)、GA组(14.63%)高(P<0.05)。结论BDNF基因rs6265位点多态性与右美托咪定在腹腔镜子宫切除术的麻醉效果关系密切,携带A等位基因的基因型(AA+AG)可能延长苏醒时间,增加疼痛程度及不良反应,降低舒适度,影响术后认知功能。

Changes in gut microbiota composition and diversity associated with post-cholecystectomy diarrhea

BACKGROUND Post-cholecystectomy diarrhea(PCD)frequently occurs in patients following gallbladder removal.PCD is part of the post-cholecystectomy(PC)syndrome,and is difficult to treat.After cholecystectomy,bile enters the duodenum directly,independent of the timing of meals.The interaction between the bile acids and the intestinal microbes is changed.Therefore,the occurrence of PCD may be related to the change in microbiota.However,little is known about the relationship between the gut microbiota and PCD.AIM To better understand the role of the gut microbiota in PCD patients.METHODS Fecal DNA was isolated.The diversity and profiles of the gut microbiota were analyzed by performing high-throughput 16S rRNA gene sequencing.The gut microbiota were characterized in a healthy control(HC)group and a PC group.Subsequently,the PC group was further divided into a PCD group and a postcholecystectomy non-diarrhea group(PCND)according to the patients’clinical symptoms.The composition,diversity and richness of microbial communities were determined and compared.RESULTS In the PC and HC groups,720 operational taxonomic units(OTUs)were identified.The PC group had fewer OTUs than the HC group.β-diversity was decreased in the PC group.This indicated decreased microbial diversity in the PC group.Fifteen taxa with differential abundance between the HC and PC groups were identified.In the PCD group compared to the PCND group,significant decreases in microbial diversity,Firmicutes/Bacteroidetes ratio,and richness of probiotic microbiota(Bifidobacterium and Lactococcus),and an increase in detrimental microbiota(Prevotella and Sutterella)were observed.Moreover,a negative correlation was found between Prevotella and Bifidobacterium.Using a Kyoto Encyclopedia of Genes and Genomes functional analysis,it was found that the abundances of gut microbiota involved in lipid metabolism pathways were markedly lower in the PCD group compared to the PCND group.CONCLUSION This study demonstrated that gut dysbiosis may play a critical role in PCD,which provides new insights into therapeutic options for PCD patients.

GABA stimulates human hepatocellular carcinoma growth through overexpressed GABAA receptor theta subunit

AIM: To investigate the function of gamma-aminobutyric acid (GABA) and gamma-aminobutyric acid A receptor θ subunit (GABRQ) in hepatocellular carcinoma (HCC). METHODS: Semiquantitative polymerase chain reaction was used for detecting the expression of GABRQ receptor among HCC cell line HepG2, normal liver cell line L-02, non-malignant Chang's liver cells, 8 samples of HCC tissues and paired non-cancerous tissues. HepG2 cells were treated with GABA at serial concentrations (0, 1, 10, 20, 40 and 60 μmol/L), and their proliferating abilities were analyzed with the methyl thiazolyl tetrazolium assay, cell cycle analysis and tumor implanted in nude mice. Small interfering RNA was used for knocking down the endogenous GABRQ in HepG2. Proliferating abilities of these cells treated with or without GABA were analyzed. RESULTS: We identified the overexpression of GABRQ in HCC cell lines and half of the tested HCC tissues. Knockdown of endogenous GABRQ expression in HepG2 attenuated HCC cell growth, suggesting its role in HCC cell viability. We studied the effect of GABA in the proliferation of GABRQ-positive cell lines in vitro and in vivo , and found that GABA increased HCC growth in a dosedependent manner. Notably, the addition of GABA into the cell culture medium promoted the proliferation of GABRQ-expressing HepG2 cells, but not GABRQ-knockdown HepG2 cells, which means that GABA stimulates HepG2 cell growth through GABRQ. CONCLUSION: GABRQ play important roles in HCC development and progression and could be a promising molecular target for the development of new diagnostic and therapeutic strategies of HCC.

Retinoblastoma binding protein 4 up-regulation is correlated with hepatic metastasis and poor prognosis in colon cancer patients

Background: Retinoblastoma binding protein 4 (RBBP4) plays an essential role in the development of multiple cancers. However, its relationship with prognosis in colon cancer and colon cancer hepatic metastasis has not been elucidated. The aim of this study was to explore the relationship between RBBP4 expression and prognosis of colon cancer patients and to evaluate RBBP4 as a new prognostic marker in these patients. Methods: Eighty colon cancer patients underwent surgical resection of the colon were enrolled. Among them, forty colon cancer patients suffered with hepatic metastasis. The colon cancer tissues, para-colon cancer tissues, and hepatic metastatic cancer tissues were collected from the pathological department for further analysis. The expression of RBBP4 proteins was examined by immunohistochemistry and correlated with clinicopathological parameters. The Cancer Genome Atlas (TCGA) database was used to validate the expression and explore its relationship with clinical characteristics. Results: RBBP4 was up-regulated in the colon cancer tissues compared with the para-colon cancer tissues. The analysis of TCGA database verified the upregulation of RBBP4 in the colon cancer tissues and RBBP4 overexpression was correlated with nerve invasion and poor outcomes of chemotherapy. Moreover, the positive rate of RBBP4 expression in 40 colon cancer patients with hepatic metastasis was higher in the hepatic metastatic cancer tissues (39/40, 97.5%) than in the colon cancer tissues (26/40, 65.0%). Our clinicopathological analysis showed that RBBP4 expression was significantly correlated with vascular invasion, hepatic metastasis, and lymph node involvement (all P < 0.05). Additionally, the survival analysis demonstrated that RBBP4 over-expression was correlated with poor prognosis. Conclusions: RBBP4 was upregulated in the colon cancer. RBBP4 may be a novel predictor for poor prognosis of colon cancer and colon cancer hepatic metastasis.

Excisional hemorrhoidal surgery and its effect on anal continence

AIM:To investigate the role of anal cushions in hemorrhoidectomy and its effect on anal continence of the patients.METHODS:Seventy-six consecutive patients(33 men and 43 women) with a mean age of 44 years were included.They underwent Milligan-Morgan hemorrhoidectomy because of symptomatic third-and fourth-degree hemorrhoids and failure in conservative treatment for years.Wexner score was recorded and liquid continence test was performed for each patient before and two months after operation using the techniques described in our previous work.The speed-constant rectal lavage apparatus was prepared in our laboratory.The device could output a pulsed and speed-constant saline stream with a high pressure,which is capable of overcoming any rectal resistance change.The patients were divided into three groups,group A(< 900 mL),group B(900-1200 mL) and group C(> 1200 mL) according to the results of the preoperative liquid continence test.RESULTS:All the patients completed the study.The average number of hemorrhoidal masses excised was 2.4.Most patients presented with hemorrhoidal symptoms for more than one year,including a mean duration of incontinence of 5.2 years.The most common symptoms before surgery were anal bleeding(n = 55),prolapsed lesion(n = 34),anal pain(n = 12) and constipation(n = 17).There were grade Ⅲ hemorrhoids in 39(51.3%) patients,and grade Ⅳ in 37(48.7%) patients according to Goligher classification.Five patients had experienced hemorrhoid surgery at least once.Compared with postoperative results,the retained volume in the preoperative liquid continence test was higher in 40 patients,lower in 27 patients,and similar in the other 9 patients.The overall preoperative retained volume in the liquid continence test was 1130.61 ± 78.35 mL,and postoperative volume was slightly decreased(991.27 ± 42.77 mL),but there was no significant difference(P = 0.057).Difference was significant in the test value before and after hemorrhoidectomy in group A(858.24 ± 32.01 mL vs 574.18 ± 60.28 mL,P = 0.011),but no obvious difference was noted in group B or group C.There was no significant difference in Wexner score before and after operation(1.68 ± 0.13 vs 2.10 ± 0.17,P = 0.064).By further stratified analysis,there was significant difference before and 2 months after operation in group A(2.71 ± 0.30 vs 3.58 ± 0.40,P = 0.003).In contrast,there were no significant differences in group B or group C(1.89 ± 0.15 vs 2.11 ± 0.19,P = 0.179;0.98 ± 0.11 vs 1.34 ± 0.19,P = 0.123).CONCLUSION:There is no difference in the continence status of patients before and after Milligan-Morgan hemorrhoidectomy.However,patients with preoperative compromised continence may have further deterioration of their continence,hence Milligan-Morgan hemorrhoidectomy should be avoided in such patients.

Dexmedetomidine-midazolam versus Sufentanil-midazolam for Awake Fiberoptic Nasotracheal Intubation： A Randomized Double-blind Study

Background： Awake fiberoptic intubation （AFOI） is usually performed in the management of the predicted difficult airway. The aim of this study was to evaluate the feasibility of dexmedetomidine with midazolam （DM） and sufentanil with midazolam （SM） for sedation for awake fiberoptic nasotracheal intubation. Methods： Fifty patients with limited mouth opening scheduled for AFOI were randomly assigned to two groups （n = 25 per group） by a computer-generated randomization schedule. All subjects received midazolam 0.02 mg/kg as premedication and airway topical anesthesia with a modified ＂spray-as-you-go＂ technique. Group DM received dexmedetomidine at a loading dose of 0.5 μg/kg over 10 min followed by a continuous infllsion of 0.25 μg.kg^-1.h ^-1, whereas Group SM received sufentanil at a loading dose of 0.2 μg/kg over 10 rain followed by a continuous infusion of 0.1 μg.kg^-1.h ^-1. As necessary, since the end of the administration of the loading dose of the study drug, an additional dose ofmidazolam 0.5 mg at 2-min intervals was given to achieve a modified Observers＇Assessment of Alertness/Sedation of 2-3. The quality of intubation conditions and adverse events were observed.Results： The scores of ease of the AFOI procedure, patient＇s reaction during AFOI, coughing severity, tolerance after intubation, recall of the procedure and discomfort during the procedure were comparable in both groups （z = 0.572, 0.664, 1.297, 0.467, 0.895, and 0.188, respectively, P 〉 0.05）. Hypoxic episodes similarly occurred in the two groups, but the first partial pressure of end-tidal CO, after intubation was higher in Group SM than that in Group DM （45.2 ± 4.2 mmHg vs. 42.2 ±4.3 mmHg, t = 2.495, P 〈 0.05）. Conclusions： Both dexmedetomidine and sufentanil are effective as an adjuvant for AFOI under airway topical anesthesia combined with midazolam sedation, but respiratory depression is still a potential risk in the sufentanil regimen.

A Coupled Thermodynamic Model for Prediction of Inclusions Precipitation during Solidification of Heat-resistant Steel Containing Cerium

A coupled thermodynamic model of inclusions precipitation both in liquid and solid phase and microseg- regation of solute elements during solidification of heat-resistant steel containing cerium was established. Then the model was validated by the SEM analysis of the industrial products. The type and amount of inclusions in solidifica- tion structure of 253MA heat-resistant steel were predicted by the model, and the valuable results for the inclusions controlling in 253MA steel were obtained. When the cerium addition increases, the types of inclusions transform from SiO2 and MnS to Ce2 O3 and Ce2O2 S in 253MA steel and the precipitation temperature of SiO2 and MnS decrea- ses. The inclusions CeS and CeN convert to Ce2 O3 and Ce2 O2 S as the oxygen content increases and Ce2 O3 and CeN convert to Ce2 O2 S, Ce3 S4, and MnS as the sulfur content increases. The formation temperature of SiO2 increases when the oxygen content increases and the MnS precipitation temperature increases when the sulfur content increa ses. There is only a small quantity of inclusions containing cerium in 253MA steel with high cleanliness, i. e. , low oxygen and sulfur contents. By contrast, a mass of SiO2 , MnS and Ce2 O2 S are formed in steel when the oxygen and sulfur contents are high enough. The condition that MnS precipitates in 253MA steel is 1.2wEo[O] ＋W[s]〉0. 01% and SiO2 precipitates when 2w[O] ＋wrs[S]〉0. 017% （W[S]0. 005%） and w[O]〉0. 006% （w[S]〉0. 005%）.

Scalable and Privacy-Preserving Data Sharing Based on Blockchain

With the development of network technology and cloud computing, data sharing is becoming increasingly popular, and many scholars have conducted in-depth research to promote its flourish. As the scale of data sharing expands, its privacy protection has become a hot issue in research. Moreover, in data sharing, the data is usually maintained in multiple parties, which brings new challenges to protect the privacy of these multi-party data. In this paper, we propose a trusted data sharing scheme using blockchain. We use blockchain to prevent the shared data from being tampered, and use the Paillier cryptosystem to realize the confidentiality of the shared data. In the proposed scheme, the shared data can be traded, and the transaction information is protected by using the （p, t）-threshold Paillier cryptosystem. We conduct experiments in cloud storage scenarios and the experimental results demonstrate the efficiency and effectiveness of the proposed scheme.

Authors＇ Reply to Letter to the Editor ＂Comparing Sedation Regimens for Awake Fiberoptic Intubation＂

We appreciate Prof. Xue et al. for their thoughtful comments on our studyJ H We agree with them that history of smoking and respiratory comorbidities can increase airway reactivity to airway irritation, resulting in an increased severity of cough. In our study, patients with a history of smoking and respiratory comorbidities were excluded and the demographic data of patients were comparable between tile groups.