Regulatory role of exosomes in colorectal cancer progression and potential as biomarkers

Colorectal cancer(CRC)remains an enormous challenge to human health worldwide.Unfortunately,the mechanism underlying CRC progression is not well understood.Mounting evidence has confirmed that exosomes play a vital role in CRC progression,which has attracted extensive attention among researchers.In addition to acting as messengers between CRC cells,exosomes also participate in the CRC immunomodulatory process and reshape immune function.As stable message carriers and liquid biopsy option under development,exosomes are promising biomarkers in the diagnosis or treatment of CRC.In this review we have described and analyzed the biogenesis and release of exosomes and current research on the role of exosomes in immune regulation and metastasis of CRC.Moreover,we have discussed candidate exosomal molecules as potential biomarkers to diagnose CRC,predict CRC progression,or determine CRC chemoresistance,and described the significance of exosomes in the immunotherapy of CRC.This review provides insight to further understand the role of exosomes in CRC progression and identify valuable biomarkers that facilitate the clinical management of CRC patients.

The pathology of unusual subtypes of prostate cancer

There are some current literatures describing the morphologic change of prostate carcinoma variants. Some subtypes do not respond to hormone deprivation therapy, for example adenosquamous and squamous cell carcinoma （SQCC）, basaloid and adenoid cystic carcinoma （ACC）, small cell carcinoma （SmCC）, sarcomatoid carcinoma, urothelial carcinoma; some are defined in special Gleason grade, some develop different prognosis. So, it is very important to identify these rare subtypes to avoid misdiagnosis. In this review, we aim to describe the typical clinicopathological features of the rare variants of prostate cancer, including prostate acinar adenocarcinoma morphologic variants.

Conversion therapy of a giant hepatocellular carcinoma with portal vein thrombus and inferior vena cava thrombus:A case report and review of literature

BACKGROUND The prognosis of hepatocellular carcinoma(HCC)combined with portal and hepatic vein cancerous thrombosis is poor,for unresectable patients the combination of targeted therapy and immune therapy was the first-line recommended treatment for advanced HCC,with a median survival time of only about 2.7-6 months.In this case report,we present the case of a patient with portal and hepatic vein cancerous thrombosis who achieved pathologic complete response after conversion therapy.CASE SUMMARY In our center,a patient with giant HCC combined with portal vein tumor thrombus and hepatic vein tumor thrombus was treated with transcatheter arterial chemoembolization(TACE),radiotherapy,targeted therapy and immunotherapy,and was continuously given icaritin soft capsules for oral regulation.After 7 months of conversion therapy,the patient's tumor shrank and the tumor thrombus subsided significantly.The pathology of surgical resection was in complete remission,and there was no progression in the postoperative follow-up for 7 months,which provided a basis for the future strategy of combined conversion therapy.CONCLUSION In this case,atezolizumab,bevacizumab,icaritin soft capsules combined with radiotherapy and TACE had a good effect.For patients with hepatocellular carcinoma combined with hepatic vein/inferior vena cava tumor thrombus,adopting a high-intensity,multimodal proactive strategy under the guidance of multidisciplinary team(MDT)is an important attempt to break through the current treatment dilemma.

PCA3 and TMPRSS2-ERG gene fusions as diagnostic biomarkers for prostate cancer

The incidence of prostate cancer （PCa） is rising steadily among males in many countries. Serum prostate-specific antigen （PSA） is widely applied to clinical diagnosis and screening of PCa. However, the so-called grey area of PSA levels 4.0-10.0 ng/mL has a low specificity of 25-40% resulting in a high rate of negative biopsy and overtreatment. So in order to treat PCa patients in early stage, there is an urgent need for new biomarkers in PCa diagnosis. The PCA3 gene, a non-coding RNA （ncRNA） that is highly expressed in prostate cancer （PCa） cells, has been identified as a molecular biomarkers to detect PCa, of which PCA3 has already under clinical application. PCA3 is strongly overexpressed in malignant prostate tissue compared to benign or normal adjacent one. Newly, PCA3 is considered to be a promising biomarker in clinical diagnosis and targeted therapy. The diagnostic significance of PCA3, however, is awaiting further researches. Moreover, it has been demonstrated recently that TMPRSS2-ERG gene fusion is identified as the predominant genetic change in patients diagnosed with PCa. Recent study revealed that combination of the PC43 and TMPRSS2-ERG gene fusion test optimizes PCa detection compared with that of single biomarker, which would lead to a considerable reduction of the number of prostate biopsies. In this review, we focused on the potential use of PCA3 and TMPRSS2-ERG gene fusion detection in the diagnosis of PCa.

Antisense angiopoietin-1 inhibits tumorigenesis and angiogenesis of gastric cancer

瞄准：在生物行为在试管内和人的胃的癌症房间的血管生成在试管内上调查 angiopoietin-1 (Ang-1 ) 的效果。方法：人的全身的 Ang-1 基因被 RT-PCR 方法从人的胎盘的纸巾克隆。Recombinant 人的 Ang-1 反察觉到真核细胞的表示向量被与高 Ang-1 表示水平的进人的胃的癌症线 SGC7901 的由 lipofectin 方法的方向性的克隆，和 transfected 构造。抑制效率被半证实 -- 量的 PCR 和西方的污点方法。房间生长曲线和房间周期分别地与 MTT 试金和流动血细胞计数被观察。裸体老鼠 tumorigenicity 测试被采用把房间的在试管内肿瘤发生与 Ang-1 抑制作比较。植入的肿瘤纸巾的 Microvessel 密度(MVD ) 被免疫组织化学为第八因子染色分析。结果：全身的 Ang-1 基因成功地被克隆，稳定的 transfectants 被建立，也就是为为空向量 transfected 的 antisenseiand 7901P 的 7Ang1- 。7Ang1- 房间显示出下面调整的 Ang-1 表示，当它的在试管内增长和房间周期分发显著地没被改变时。相反，在裸体老鼠的 7Ang1- 房间的异种皮移植在 30 白天与 7901P 相比与 MVD 6.00+/-1.73 伴有更少的容器形成的培植(P【0.01， 293.00+/-95.54 mg 对 624.00+/-77.78 mg ) 以后 7901P 比那些让更低的体积和重量组织 8.44+/-1.33 (P【0.01 ) 。结论：Ang-1 可以在胃的癌症的肿瘤发生和血管生成起一个重要作用，并且指向它的表示可能为胃的癌症的治疗有益。

Synthesis and Evaluation of a Novel Small-molecule Compound as an Anticancer Inhibitor of CD147

Objective Cancer is a serious threat to human health. Despite extensive research on cancer treatment,there is a growing demand for new therapies. CD147 is widely involved in tumor development, but it is unclear whether cancer cell malignancy is affected by CD147 expression level. The first compound(AC-73) targeting CD147 could only act on advanced tumors and inhibit metastasis. Therefore, new compounds with better anticancer activity should be explored.Methods Wst-1 assays were used to confirm the effect of novel compounds on proliferation.Apoptosis tests were used to evaluate their proapoptotic capacity. A nude mouse model was used to demonstrate in vivo anticancer activity and safety of the compounds. Western blots were used to suggest a molecule mechanism.Results There is a positive correlation between CD147 expression and tumor cell proliferation. A new compound, HA-08, was synthesized and proved to be more active than AC-73. HA-08 could inhibit cancer cell viability and promote cancer cell apoptosis both in vitro and in vivo. HA-08 induces cancer apoptosis, mainly by disrupting the CD147-CD44 interaction and then down-regulating the JAK/STAT3/Bcl-2 signaling pathway.Conclusion Our results have clarified the tumor specificity of CD147 and its drug target characteristics.The biological profile of HA-08 suggests that this compound could be developed as a potential anticancer agent.

Prognostic value of modified Lauren classification in gastric cancer

BACKGROUND It remains controversial as to which pathological classification is most valuable in predicting the overall survival(OS)of patients with gastric cancer(GC).AIM To assess the prognostic performances of three pathological classifications in GC and develop a novel prognostic nomogram for individually predicting OS.METHODS Patients were identified from the Surveillance,Epidemiology,and End Results program.Univariate and multivariate analyses were performed to identify the independent prognostic factors.Model discrimination and model fitting were evaluated by receiver operating characteristic curves and Akaike information criteria.Decision curve analysis was performed to assess clinical usefulness.The independent prognostic factors identified by multivariate analysis were further applied to develop a novel prognostic nomogram.RESULTS A total of 2718 eligible GC patients were identified.The modified Lauren classification was identified as one of the independent prognostic factors for OS.It showed superior model discriminative ability and model-fitting performance over the other pathological classifications,and similar results were obtained in various patient settings.In addition,it showed superior net benefits over the Lauren classification and tumor differentiation grade in predicting 3-and 5-year OS.A novel prognostic nomogram incorporating the modified Lauren classification showed superior model discriminative ability,model-fitting performance,and net benefits over the American Joint Committee on Cancer 8th edition tumor-nodemetastasis classification.CONCLUSION The modified Lauren classification shows superior net benefits over the Lauren classification and tumor differentiation grade in predicting OS.A novel prognostic nomogram incorporating the modified Lauren classification shows good model discriminative ability,model-fitting performance,and net benefits.

Multicenter case-control study of the risk factors for ulcerative colitis in China

AIM:To evaluate potential risk factors in the development of ulcerative colitis(UC) in China.METHODS:A total of 1308 patients with UC and 1308 age-matched and sex-matched controls were prospectively studied in China.The UC cases were collected from 17 hospitals in China from April 2007 to April 2010.Uniform questionnaires were designed to investigate risk factors including smoking,appendectomy,stress,socio-economic conditions,nonsteroidal antiinflammatory drugs(NSAIDs),oral contraceptives,diet,breastfeeding,infections and family sanitary conditions.Group comparisons by each factor were done using simple logistic regression analysis.Conditional logistic regression was used for multivariate analysis.RESULTS:By univariate analysis,the variables predictive of UC included feeling stress,light and heavy alcoholic drinking,spicy food,sugar consumption and infectious diarrhea,while heavy tea intake and tap water consumption were protective against UC.On multivariate analysis,the protective factor for UC was tap water consumption [odds ratios(OR) = 0.424,95%CI:0.302-0.594,P < 0.001];while the potential risk factors for UC were heavy sugar consumption(OR = 1.632,95%CI:1.156-2.305,P < 0.001),spicy food(light intake:OR = 3.329,95%CI:2.282-4.857,P < 0.001;heavy intake:OR = 3.979,95%CI:2.700-5.863,P < 0.001),and often feeling stress(OR = 1.981,95%CI:1.447-2.711,P < 0.001).Other factors,such as smoking habit,appendectomy,breastfeeding,a history of measles,rural or urban residence,education,oral contraceptives,and NSAID use have not been found to have a significant association with the development of UC in the present study.CONCLUSION:Our study showed tap water consumption was a protective factor for UC,while spicy food,heavy sugar consumption and often feeling stress were risk factors for UC in this Chinese population.

CacyBP/SIP nuclear translocation induced by gastrin promotes gastric cancer cell proliferation

AIM:To investigate the role of nuclear translocation of calcyclin binding protein,also called Siah-1 interacting protein(CacyBP/SIP),in gastric carcinogenesis.METHODS:The expression of CacyBP/SIP protein in gastric cancer cell lines was detected by Western blot.Immunofluorescence experiments were performed on gastric cancer cell lines that had been either unstimulated or stimulated with gastrin.To confirm the immunofluorescence findings,the relative abundance of CacyBP/SIP in nuclear and cytoplasmic compartments was assessed by Western blot.The effect of nuclear translocation of CacyBP/SIP on cell proliferation was examined using MTT assay.The colony formation assay was used to measure clonogenic cell survival.The effect of CacyBP/SIP nuclear translocation on cell cycle progression was investigated.Two CacyBP/SIPspecific siRNA vectors were designed and constructed to inhibit CacyBP/SIP expression in order to reduce the nuclear translocation of CacyBP/SIP,and the expression of CacyBP/SIP in stably transfected cells was determined by Western blot.The effect of inhibiting CacyBP/SIP nuclear translocation on cell proliferation was then assessed.RESULTS:CacyBP/SIP protein was present in most of gastric cancer cell lines.In unstimulated cells,CacyBP/SIP was distributed throughout the cytoplasm;while in stimulated cells,CacyBP/SIP was found mainly in the perinuclear region.CacyBP/SIP nuclear translocation generated a growth-stimulatory effect on cells.The number of colonies in the CacyBP/SIP nuclear translocation group was significantly higher than that in the control group.The percentage of stimulated cells in G1phase was significantly lower than that of control cells(69.70%±0.46%and 65.80%±0.60%,control cells and gastrin-treated SGC7901 cells,P=0.008;72.99%±0.46%and 69.36%±0.51%,control cells and gastrin-treated MKN45 cells,P=0.022).CacyBP/SIPsi1effectively down-regulated the expression of CacyBP/SIP,and cells stably transfected by CacyBP/SIPsi1 were then chosen for further cellular assays.In CacyBP/SIPsi1 stably transfected cells,CacyBP/SIP was shown to be distributed throughout the cytoplasm,irregardless of whether they were stimulated or not.After CacyBP/SIP nuclear translocation was reduced,there had no major effect on cell proliferation,as shown by MTT assay.There had no enhanced anchoragedependent growth upon stimulation,as indicated by colony formation in flat plates.No changes appeared in the percentage of cells in G0-G1 phase in either cell line(71.09%±0.16%and 70.86%±0.25%,control cells and gastrin-treated SGC7901-CacyBP/SIPsi1 cells,P=0.101;74.17%±1.04%and 73.07%±1.00%,control cells and gastrin-treated MKN45-CacyBP/SIPsi1cells,P=0.225).CONCLUSION:CacyBP/SIP nuclear translocation promotes the proliferation and cell cycle progression of gastric cancer cells.

Association of systemic inflammation and body mass index with survival in patients with resectable gastric or gastroesophageal junction adenocarcinomas

Objective:The systemic inflammation index and body mass index(BMI)are easily accessible markers that can predict mortality.However,the prognostic value of the combined use of these two markers remains unclear.The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer.Methods:A total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included.Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio(NLR).High systemic inflammation was defined as NLR≥3,and underweight was defined as BMI<18.5 kg/m2.Results:Among 2,542 patients,NLR≥3 and underweight were common[627(25%)and 349(14%),respectively].In the entire cohort,NLR≥3 or underweight independently predicted overall survival(OS)[hazard ratio(HR):1.236,95%confidence interval(95%CI):1.069–1.430;and HR:1.600,95%CI:1.350–1.897,respectively]and recurrence-free survival(RFS)(HR:1.230,95%CI:1.054–1.434;and HR:1.658,95%CI:1.389–1.979,respectively).Patients with both NLR≥3 and underweight(vs.neither)had much worse OS(HR:2.445,95%CI:1.853–3.225)and RFS(HR:2.405,95%CI:1.802–3.209).Furthermore,we observed similar results in subgroup analyses according to pathological stage,age,and postoperative chemotherapy.Conclusions:Our results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival.Underweight combined with severe inflammation could enhance prognostication.Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.

Predictive value of alarm symptoms in patients with Rome IV dyspepsia: A cross-sectional study

BACKGROUND No studies have evaluated the predictive value of alarm symptoms for organic dyspepsia and organic upper gastrointestinal(GI)diseases based on Rome IV criteria in the Chinese population.AIM To evaluate the predictive value of alarm symptoms for dyspeptic patients based on Rome IV criteria.METHODS We performed a cross-sectional study of dyspepsia patients who met the inclusion and exclusion criteria at two academic urban tertiary-care centers from March 2018 to January 2019.Basic demographic data,dyspeptic information,alarm symptoms,lifestyle,examination results,family history and outpatient cost information were collected.Dyspepsia patients with normal findings on upper GI endoscopy,epigastric ultrasound and laboratory examination and without Helicobacter pylori-associated dyspepsia were classified as functional dyspepsia.RESULTS A total of 381 patients were enrolled in the study,including 266 functional dyspepsia patients and 115 organic dyspepsia patients.There were 24 patients with organic upper GI disease among patients with organic dyspepsia.We found that based on the Rome IV criteria,alarm symptoms were of limited value in differentiating organic dyspepsia and organic upper GI diseases from functional dyspepsia.Age(odds ratio(OR)=1.056,P=0.012),smoking(OR=4.714,P=0.006)and anemia(OR=88.270,P<0.001)were independent predictors for organic upper GI diseases.For the comparison of epigastric pain syndrome,postprandial distress syndrome and epigastric pain syndrome combined with postprandial distress syndrome,the results showed that there were statistically significant differences in anorexia(P=0.021)and previous visits(P=0.012).The ClinicalTrials.gov number is NCT 03479528.CONCLUSION Most alarm symptoms had poor predictive value for organic dyspepsia and organic upper GI diseases based on Rome IV criteria.Gastroscopic screening should not be based solely on alarm symptoms.

Detection of H pylori antibody profile in serum by protein array

瞄准：检测多重 H。在带 H 的个人的浆液样品的 pylori 抗体。由蛋白质数组的 pylori。方法：Recombinant H。pylori 抗原，脲酶 B 子单元(UreB ) ， vacuolating 毒素 A (VacA ) 和细胞毒素在由绑特定的免疫球蛋白 G (IgG ) 的机器人学的硝化纤维素膜上的矩阵联系了基因 A 蛋白质(CagA ) ，被准备并且使不能调动在浆液的抗体。胶体黄金标记的葡萄球菌蛋白质 A (矿泉) 被用来集成免疫建筑群并且给了颜色表明的红。扫描仪能基于电荷耦合的设备(电荷耦合器件) 收集图象信号并且把它变换成数字信号。结果：当人的 IgG 在增加集中在膜上被打印并且与免疫孵化了黄金时，一条线性剂量反应曲线被获得，为 IgG 的察觉限制是大约 0.025 ng。分别地，截止价值，加 3 次标准偏差被定义为吝啬的灰水平，作为有否定 H 的 400 件人的浆液样品是 27.183， 28.546 和 27.402，为 anti-UreB IgG， anti-CagA IgG 和 anti-VacA IgG。pylori 抗体被蛋白质数组检测。当从医院里的病人的 180 件浆液样品对 UreB， CagA 和 VacA 为 IgG 的察觉被采用时，蛋白质数组的敏感是 93.4% ， 95.4% ， 96.0% ，并且分别地，特性作为与 ELISA 获得的结果相比是 94.8% ， 94.4% 和 97.5% 。试金也显示出高重制度，一致性和稳定性，并且结果在 30 min 以内是可得到的。结论：蛋白质数组是为在浆液样品的多重抗体的快速的察觉的一个很实际的方法。它为 H 的感染的大规模流行病学调查是特别有用的。pylori。

Bioinformatics Analysis Raises Candidate Genes in Blood for Early Screening of Parkinson's Disease

Parkinson＇s disease （PD） is a typical degenerative disease, which is characterized by the most obvious symptoms of movement dysfunction, including shaking, rigidity, slowness of movement and difficulty in walking and gait. This disease can not be clearly identified through laboratory tests at present, thus application of high-throughput technique in studying the expression profiles of PD helps to find the genetic markers for its early diagnosis. Studies on expression profiles of neurodegenerative diseases have revealed the novel genes and pathways involved in the progress of illness. In this study, the expression profiles of PD in blood were compared, showing that 181 differentially expressed genes （DEG） exhibit a similar expression trend both in patients and in normal controls.

Relevance of MICA Alleles Matching Rate and Posttransplant Rejection in Clinical LRD Organ Transplantations

Objective: Recipients usually undergo posttransplant rejection in HLA-identical transplantations. Recent studies have shown that MHC class I related chain A (MICA) has been found to be associated with allograft survival. The goal of this study is to investigate the correlation between matching rate of MICA alleles and posttransplant rejection in clinical living related donor transplantation (LRD) organ transplantations. Methods: Twenty pairs of blood samples were detected for HLA/MICA matching through polymerase chain reaction with sequence specific primers and for anti-MICA Abs using Luminex. At the same time, pathologic biopsies of all recipients were diagnosed and classified into different levels by the unified standard. Univariate Spearman’s analysis was established. Log-Rank analysis was performed twice, and Kaplan-Meier survival curves were generated to assess the relationship between MICA matching rates and posttransplant rejection in living-related donor transplantations. Results-The result showed that HLA matching of all recipients and donors were identical, whereas MICA matching was not. There was statistical difference between pathological classification and survival

In vivo bioluminescence imaging of hyperglycemia exacerbating stem cells on choroidal neovascularization in mice

AIM： To investigate the influence of hyperglycemia on the severity of choroidal neovascularization（CNV）,especially the involvement of bone marrow-derived cells（BMCs） and underlying mechanisms.·METHODS： BMCs from firefly luciferase（Fluc）/green fluorescent protein（GFP） double transgenic mice were transplanted into C57BL/6J wide-type mice. The recipient mice were injected intraperitoneally with streptozotocin（STZ） daily for 5 consecutive days to induce diabetes mellitus（DM）, followed by CNV laser photocoagulation.The BMCs recruitment in CNV exposed to hyperglycemia was firstly examined in Fluc/GFP chimeric mice by in vivo optical bioluminescence imaging（BLI） and in vitro Fluc assays. The CNV severity was evaluated by H＆E staining and choroidal flatmount. The expression of vascular endothelial growth factor（VEGF） and stromal cell derived factor-1（SDF-1） was detected by Western blot.·RESULTS： BLI showed that the BMCs exerted dynamic effects in CNV model in Fluc/GFP chimeric mice exposed to hyperglycemia. The signal intensity of transplanted Fluc＋GFP＋BMCs in the DM chimeric mice was significantly higher than that in the control chimeric mice with CNV induction at days 5, 7, 14 and 21（121861.67 ±9948.81 vs 144998.33 ±13787.13 photons/second/cm2/sr for control and DM mice, P5d〈0.05; 178791.67±30350.8 vs240166.67 ±22605.3, P7d〈0.05; 124176.67 ±16253.52 vs196376.67 ±18556.79, P14d〈0.05; 97951.60 ±10343.09 vs119510.00 ±14383.76, P21d〈0.05）, which was consistent with in vitro Fluc assay at day 7 [relative light units of Fluc（RLU1）], 215.00±52.05 vs 707.33±88.65, P 〈0.05; RLU1/relative light units of renilla luciferase（RLU2）, 0.90 ±0.17 vs 1.83 ±0.17, P 〈0.05]. The CNVs in the DM mice were wider than those in the control group at days 5, 7, 14 and21（147.83±17.36 vs 220.33±20.17 μm, P5d〈0.05; 212.17 ±24.63 vs 326.83 ±19.49, P7d〈0.05; 163.17 ±18.24 vs265.17 ±20.55, P14d〈0.05; 132.00 ±10.88 vs 205.33 ±12.98,P21d〈0.05）. The average area of CNV in the DM group was larger at 7d（20688.67±3644.96 vs 32218.00±4132.69 μm2,P 〈0.05）. The expression of VEGF and SDF-1 was enhanced in the DM mice.·CONCLUSION： Hyperglycemia promots the vasculo-genesis of CNV, especially the contribution of BMCs,which might be triggered by VEGF and SDF-1 production.

Routine clinical administration of 4-week alverine citrate and simeticone combination relief global IBS symptoms

Introduction: The primary treatment aim for irritable bowel syndrome (IBS) is to relieve overall symptoms which can significantly impair the patient’s quality of life (QOL);however, it generally requires a high pill burden that may be improved by administration of combinatorial formulations. Thus, the effectiveness of alverine citrate and simeticone combination (ACS) for global symptom relief for IBS was investigated in this non-interventional study. Patients and Methods: ROME III IBS patients (n = 640;52.3% male: mean age: 43.6 ± 12.5 years) with abdominal pain and discomfort ≥60 of 0-100 visual analogue scale (VAS) were included in a prospective, multicenter, non-interventional study at 26 Chinese sites from December 2010 to January 2012. Patients received alverine citrate (60 mg) with simeticone (300 mg) (ACS) 3× daily for 4 weeks. Pain/discomfort and bloating/distension were assessed by VAS. Global symptoms and QOL were assessed by 7-point and 5-point Likert scales, respectively. Post-treatment bowel function was assessed by Bristol Stool Form Scale (BSFS) and treatment-related adverse events (AEs) were recorded. Results: Of 640 patients, 540 (84.4%) completed the study, and 100 (15.6%) withdrew. In total, 87.5% reported bloating at baseline. After 4-week ACS treatment, 89.1% reported global symptom improvement. Furthermore, 4-week ACS treatment reduced pain and bloated VAS scores significantly from 78.4 ± 9.9 to 32.1 ± 21.0 and from 63.2 ± 27.2 to 22.6 ± 20.9, respectively (both p < 0.001), decreased diarrhea or constipation occurrence from 67.2% to 10.2% (p < 0.001), and reduced IBS impact on QOL with only 2 treatment-related AEs. Conclusion: Routine clinical administration of ACS for IBS over a 4-week period provides effective relief of IBS symptoms and improves QOL in IBS patients.

Plexiform Angiomyxoid Myofibroblastic Tumor of the Stomach

Plexiform angiomyxoid myofibroblastic tumor (PAMT) is a recently described gastric tumor with a peculiar plexiform pattern, bland spindle cells and a myxoid stroma rich in arborizing blood vessels. PAMT of the stomach is a very rare tumor without distinctive clinical manifestations. In this study, we report a new case of PAMT which is the first Chinese case in English literature. A 47-year-old Chinese woman was admitted with a 6-month history of intermittent epigastric discomfort, and abdominal pain for 2 months. Gastroscopy showed an elevated mass in the anterior wall of the gastric antrum. Endoscopic ultrasound revealed a focal hypoechoic lesion protruding into the lumen. A laparoscopic distal gastrectomy was performed, and the patient made an uneventful recovery and remains well 1.5 years later. A diagnosis of PAMT was made by histopathology and immunochemistry.

CacyBP/SIP nuclear translocation regulates p27Kip1 stability in gastric cancer cells

AIM: To investigate the mechanism of calcyclin binding protein/Siah-1 interacting protein(Cacy BP/SIP) nuclear translocation in promoting the proliferation of gastric cancer(GC) cells. METHODS: The effect of Cacy BP/SIP nuclear translocation on cell cycle was investigated by cell cycle analysis. Western blot analysis was used to assess the change in expression of cell cycle regulatory proteins and proteasome-mediated degradation of p27Kip1. Coimmunoprecipitation(co-IP) analysis was performed to examine the binding of Cacy BP/SIP with Skp1. A Cacy BP/SIP truncation mutant which lacked the Skp1 binding site was constructed and fused to a fluorescent protein. Subsequently, the effect on Skp1 binding with the fusion protein was examined by co-IP, while localization of fluorescent fusion protein observed by confocal laser microscopy, and change in p27Kip1protein expression assessed by Western blot analysis.RESULTS: Cacy BP/SIP nuclear translocation induced by gastrin promoted progression of GC cells from G1 phase. However, while Cacy BP/SIP nuclear translocation was inhibited using si RNA to suppress Cacy BP/SIP expression, cell cycle was clearly inhibited. Cacy BP/SIP nuclear translocation significantly decreased the level of cell cycle inhibitor p27Kip1, increased Cyclin E protein expression whereas the levels of Skp1, Skp2, and CDK2 were not affected. Upon inhibition of Cacy BP/SIP nuclear translocation, there were no changes in protein levels of p27Kip1 and Cyclin E, while p27Kip1 decrease could be prevented by the proteasome inhibitor MG132. Moreover, Cacy BP/SIP was found to bind to Skp1 by immunoprecipitation, an event that was abolished by mutant Cacy BP/SIP, which also failed to stimulate p27Kip1 degradation, even though the mutant could still translocate into the nucleus.CONCLUSION: Cacy BP/SIP nuclear translocation contributes to the proliferation of GC cells, and Cacy BP/SIP exerts this effect, at least in part, by stimulating ubiquitin-mediated degradation of p27Kip1.

MIIP inhibits clear cell renal cell carcinoma proliferation and angiogenesis via negative modulation of the HIF-2α-CYR61 axis

Objective:In various cancers,migration and invasion inhibitory protein(MIIP)is expressed at low level and is involved in cancer pathogenesis.Herein,we sought to explore the function of MIIP in clear cell renal cell carcinoma(ccRCC).Methods:CCK-8,colony formation,cell cycle,and endothelial cell tube formation assays were performed to evaluate the roles of MIIP in ccRCC proliferation and angiogenesis.To explore the underlyi ng mechanism,we con ducted RNA-sequencing,GSEA,qRT-PCR,Western blot,ELISA,cell transfection,coimmunoprecipitation,and ubiquitination assays in ccRCC cell lines.Furthermore,xenograft tumor growth in nude mice,and Ki-67 and CD31 staining in xenograft tissues were examined.Finally,the association of MIIP expression with clinical pathology and the expression status of HIF-2a and cysteine-rich 61(CYR61)were further analyzed in human RCC tissues through Western blot and immunohistochemistry.Results:Both in vitro and in vivo functional experiments indicated that forced expression of MIIP inhibited ccRCC proliferation and angiogenesis,whereas silencing MIIP either in normal HK-2 cells or in ccRCC cells had the opposite effect(P<0.05).Mechanistically,CYR61 was identified as a gene significantly downregulated by MIIP overexpression,and was required for the suppressive role of MIIP in ccRCC.MIIP was found to promote HSP90 acetylation and thus impair its chaperone function toward HIF-2a.Consequently,RACK1 binds HIF-2a and causes its ubiquitination and proteasomal degradation,thus decreasing the transcription of its target,CYR61.Finally,analyses of clinical samples demonstrated that MIIP is significantly downregulated in cancer vs.normal tissues in RCC cases,and its expression is negatively associated with histological grade,metastasis,the prognosis of patients with RCC,and the expression of HIF-2a and CYR61(P<0.05).Conclusions:MIIP is a novel tumor suppressor in ccRCC via negative regulation of HIF-2a-CYR61 axis.

Genomic Diversity and Evolution of Bacillus subtilis

Bacillus subtilis is the focus of both academic and industrial research.Previous studies have reported a number of sequence variations in different B.subtilis strains.To uncover the genetic variation and evolutionary pressure in B.subtilis strains,we performed whole genome sequencing of two B.subtilis isolates,KM and CGMCC63528.Comparative genomic analyses of these two strains with other B.subtilis strains identified high