Suppressive effects of exercise-conditioned serum on cancer cells:A narrative review of the influence of exercise mode,volume,and intensity

Cancer is a major cause of morbidity and mortality worldwide,and the incidence is increasing,highlighting the need for effective strategies to treat this disease.Exercise has emerged as fundamental therapeutic medicine in the management of cancer,associated with a lower risk of recur-rence and increased survival.Several avenues of research demonstrate reduction in growth,proliferation,and increased apoptosis of cancer cells,including breast,prostate,colorectal,and lung cancer,when cultured by serum collected after exercise in vitro(i.e.,the cultivation of cancer cell lines in an experimental setting,which simplifies the biological system and provides mechanistic insight into cell responses).The underlying mechanisms of exercise-induced cancer suppressive effects may be attributed to the alteration in circulating factors,such as skeletal muscle-induced cytokines(i.e.,myokines)and hormones.However,exercise-induced tumor suppressive effects and detailed information about training interventions are not well investigated,constraining more precise application of exercise medicine within clinical oncology.To date,it remains unclear what role different training modes(i.e.,resistance and aerobic training)as well as volume and intensity have on exercise-condi-tioned serum and its effects on cancer cells.Nevertheless,the available evidence is that a single bout of aerobic training at moderate to vigorous intensity has cancer suppressive effects,while for chronic training interventions,exercise volume appears to be an influential candidate driving cancer inhibitory effects regardless of training mode.Insights for future research investigating training modes,volume and intensity are provided to further our understanding of the effects of exercise-conditioned serum on cancer cells.

Exercise training mode effects on myokine expression in healthy adults:A systematic review with meta-analysis

Background:The benefits of exercise are well known;however,many of the underlying molecular mechanisms are not fully understood.Skeletal muscle secretes myokines,which mediate muscleorgan crosstalk.Myokines regulate satellite-cell proliferation and migration,inflammatory cascade,insulin secretion,angiogenesis,fatty oxidation,and cancer suppression.To date,the effects of different exercise modes(namely,aerobic and resistance exercise)on myokine response remain to be elucidated.This is crucial considering the clinical implementation of exercise to enhance general health and wellbeing and as a medical treatment.Methods:A systematic search was undertaken in PubMed,MEDLINE,CINAHL,Embase,SPORTDiscus,andWeb of Science in April 2023.Eligible studies examining the effects of a single bout of exercise on interleukin15(IL-15),irisin,secreted protein acidic and rich in cysteine(SPARC),oncostatinM(OSM),and decorin were included.A random-effects meta-analysis was also undertaken to quantify the magnitude of change.Results:Sixty-two studies were included(n=1193).Overall,exercise appeared to induce small to large increases in myokine expression,with effects observed immediately after to 60 min post-exercise,although these were mostly not statistically significant.Both aerobic and resistance exercise resulted in changes in myokine levels,without any significant difference between training modes,and with the magnitude of change differing across myokines.Myokine levels returned to baseline levels within 180 min to 24 h post-exercise.However,owing to potential sources of heterogeneity,most changes were not statistically significant,indicating that precise conclusions cannot be drawn.Conclusion:Knowledge is limited but expanding with respect to the impact of overall and specific effects of exercise on myokine expression at different time points in the systemic circulation.Further research is required to investigate the effects of different exercise modes at multiple time points on myokine response.

Endoscopic band ligation and endoscopic hemoclip placement for patients with Mallory-Weiss syndrome and active bleeding

AIM: To compare the hemostatic efficacy and safety of two mechanical endoscopic methods: endoscopic band ligation (EBL) and endoscopic hemoclip placement (EHP) in patients with actively bleeding Mallory-Weiss syndrome (MWS). METHODS: A prospective randomized study to compare the efficacy and safety of EHP with EBL was performed from January 2002 to August 2005. Forty-one patients with active bleeding from MWS were treated with EHP (n = 21) or EBL (n = 20). RESULTS: There were no significant differences between groups with respect to clinical and endoscopic characteristics. The mean number of hemoclips applied was 3.2 ± 1.5 and the mean number of bands applied was 1.2 ± 0.4. Primary hemostasis was achieved in all patients. Recurrent bleeding was observed in one patient from the EHP group and two from the EBL group. Patients with recurrent bleeding were treated by the same modality as at randomization and secondary hemostasis was achieved in all. There were no significant differences between the two groups in total transfusion amount or duration of hospital stay. No complications or bleeding-related death resulted. CONCLUSION: EHP and EBL are equally effective and safe for the management of active bleeding in patients with Mallory-Weiss syndrome, even in those with shock or comorbid diseases.

Thalidomide effect in endothelial cell of acute radiation proctitis

AIM: To determine whether thalidomide prevents microvascular injury in acute radiation proctitis in white rats. METHODS: Fourteen female Wistar rats were used: six in the radiation group, six in the thalidomide group, and two in normal controls. The radiation and thalidomide groups were irradiated at the pelvic area using a single 30 Gy exposure. The thalidomide (150 mg/kg) was injected into the peritoneum for 7 d from the day of irradiation. All animals were sacrificed and the rectums were removed on day 8 after irradiation. The microvessels of resected specimens were immunohistochemically stained with thrombomodulin (TM), von Willebrand Factor (vWF), and vascular endothelial growth factor (VEGF). RESULTS: The microscopic scores did not differ significantly between the radiation and thalidomide groups, but both were higher than in the control group. Expression of TM was significantly lower inthe endothelial cells (EC) of the radiation group than in the control and thalidomide groups (P < 0.001). The number of capillaries expressing vWF in the EC was higher in the radiation group (15.3 ± 6.8) than in the control group (3.7 ± 1.7), and the number of capillaries expressing vWF was attenuated by thalidomide (10.8 ± 3.5, P < 0.001). The intensity of VEGF expression in capillaries was greater in the radiation group than in the control group and was also attenuated by thalidomide (P = 0.003). CONCLUSION: The mechanisms of acute radiation- induced proctitis in the rats are related to endothelial cell injury of microvessel, which may be attenuated with thalidomide.

Efficacy and safety of controlled-release oxycodone/naloxone versus controlled-release oxycodone in Korean patients with cancer-related pain: a randomized controlled trial

Background: Controlled-release oxycodone/naloxone(OXN-CR) maintains the effect of opioid-induced analgesia through oxycodone while reducing the occurrence rate of opioid-induced constipation through naloxone. The present study was designed to assess the non-inferiority of OXN-CR to controlled-release oxycodone(OX-CR) for the control of cancer-related pain in Korean patients.Methods: In this randomized, open-labeled, parallel-group, phase IV study, we enrolled patients aged 20 years or older with moderate to severe cancer-related pain [numeric rating scale(NRS) pain score ≥4] from seven Korean oncology/hematology centers. Patients in the intention-to-treat(ITT) population were randomized(1:1) to OXNCR or OX-CR groups. OXN-CR was administered starting at 20 mg/10 mg per day and up-titrated to a maximum of80 mg/40 mg per day for 4 weeks, and OX-CR was administered starting at 20 mg/day and up-titrated to a maximum of 80 mg/day for 4 weeks.The primary efficacy endpoint was the change in NRS pain score from baseline to week4, with non-inferiority margin of-1.5. Secondary endpoints included analgesic rescue medication intake, patientreported change in bowel habits, laxative intake, quality of life(QoL), and safety assessments.Results: Of the ITT population comprising 128 patients, 7 with missing primary efficacy data and 4 who violated the eligibility criteria were excluded from the efficacy analysis. At week 4, the mean change in NRS pain scores was not significantly different between the OXN-CR group(n = 58) and the OX-CR group(n = 59)(-1.586 vs.-1.559,P = 0.948). The lower limit of the one-sided 95% confidence interval(-0.776 to 0.830) for the difference exceeded the non-inferiority margin(P < 0.001). The OXN-CR and OX-CR groups did not differ significantly in terms of analgesic rescue medication intake, change in bowel habits, laxative intake, QoL, and safety assessments.Conclusions: OXN-CR was non-inferior to OX-CR in terms of pain reduction after 4 weeks of treatment and had a similar safety profile. Studies in larger populations of Korean patients with cancer-related pain are needed to further investigate the effectiveness of OXN-CR for long-term pain control and constipation alleviation.Trial registration ClinicalTrials.gov NCT01313780, registered March 8。

羟考酮/纳洛酮控释片与羟考酮控释片治疗韩国癌性疼痛患者的疗效及安全性的随机对照研究

背景与目的羟考酮/纳洛酮控释片(controlled?release oxycodone/naloxone,OXN?CR)通过羟考酮发挥阿片类药物诱导的镇痛效果,同时纳洛酮可降低阿片类药物引起的便秘的发生率。本研究旨在评价与羟考酮控释片(controlled?release oxycodone,OX?CR)相比,OXN?CR在控制韩国患者癌性疼痛中的非劣效性。方法本项随机、开放标签、平行分组、IV期研究中,我们从韩国的7个肿瘤学/血液学中心招募了年龄20岁及以上、具有中重度癌性疼痛的患者[疼痛数字评价量表(numeric rating scale,NRS)疼痛评分≥4分]。意向治疗人群(intention天20 mg/10 mg,每天最大?to用?treat,ITT)随机(1:1)分为OXN?CR和OX?CR组。OXN?CR组:起始用药量为每药量80 mg/40 mg,用药4周。OX?CR组:起始用药量为20 mg/d,最大用药量为80 mg/d,用药4周。本研究的主要疗效终点为NRS疼痛评分从基线到第4周的变化,其非劣效性界值为-1.5。次要终点包括应急镇痛药摄入量、患者报告的排便习惯改变、缓泻药摄入量、生活质量(quality of life,QoL)及安全性评价。结果 128例患者组成的ITT人群中,7例因缺失主要疗效数据、4例因不符合资格标准被排除疗效分析。在第4周时,OXN?CR组(n=58)和OX?CR组(n=59)患者NRS疼痛评分的平均变化无显著性差异(-1.586 vs.-1.559,P=0.948)。组间差异的单侧95%置信区间(-0.776-0.830)的下限超过非劣效性边界(P <0.001)。OXN?CR和OX?CR两组患者在应急镇痛药摄入量、排便习惯改变、缓泻药摄入量、QoL和安全性评价方面均无显著差异。结论就治疗4周后减轻患者疼痛的效果而言,OXN?CR的疗效非劣于OX?CR,两者具有相似的安全性。对于OXN?CR在长期疼痛控制和缓解便秘方面的疗效,则需在更多韩国癌性疼痛患者人群中开展进一步的研究。

Is percutaneous endoscopic gastrostomy tube placement safe in patients with ventriculoperitoneal shunts?

AIM:To investigate whether percutaneous endoscopic gastrostomy (PEG) tube placement is safe in patients with ventriculoperitoneal (VP) shunts.METHODS: This was a retrospective study of all patients undergoing PEG insertion at our institution between June 1999 and June 2006. Post-PEG complications were compared between two groups according to the presence or absence of VP shunts. VP shunt infection rates, the interval between PEG placement and VP shunt catheter insertion, and long-term follow-up were also investigated.RESULTS: Fifty-five patients qualified for the study. Seven patients (12.7%) had pre-existing VP shunts. All patients received prophylactic antibiotics. The complication rate did not differ between VP shunt patients undergoing PEG (PEG/VP group) and non-VP shunt patients undergoing PEG (control group) [1 (14.3%) vs 6 (12.5%), P=1.000]. All patients in the PEG/VP group had undergone VP shunt insertion prior to PEG placement. The mean interval between VP shunt insertion and PEG placement was 308.7 d (range, 65-831 d). The mean follow-up duration in the PEG/VP group was 6.4 mo (range, 1-15 mo). There were no VP shunt infections, although one patient in the PEG/VP group developed a minor peristomal infection during follow-up.CONCLUSION: Complications following PEG placement in patients with VP shunts were infrequent in this study.

A squamous metaplasia in a gastric ulcer scar of the antrum

An 81-year-old man presented with epigastric pain and weight loss for one month. He had a past history of pulmonary tuberculosis, 10 years ago. We performed a gastroscopy, which showed a linear depressed whitish gastric ulcer scar (0.8 cm in length) in the posterior wall of the prepyloric antrum. The result of biopsy was reported as squamous epithelium. Immunohistochemical staining using an antibody to high molecular weight cytokeratin (HMC) revealed positive staining in the squamous epithelium. Two years later, the lesion was followed up. The lesion remained at same site endoscopically, but no squamous epithelium could be seen microscopically.

Prolapse gastropathy syndrome may be a predictor of pathologic acid reflux

AIM： To assess the occurrence of gastric acid reflux into the esophagus in endoscopically confirmed prolapse gastropathy syndrome （PGS）. METHODS： Using ambulatory esophageal pH measurement （BRAVOTM wireless esophageal pH monitoring system）, twenty-six patients with PGS were compared with twenty-one patients with erosive esophagitis （EE） as controls. We assessed several reflux parameters, including the percentage of total time at pH 〈 4, and the DeMeester score. RESULTS： There were no statistical differences between the PGS group and the EE group as to mean age, sex ratio and pH recording time. The EE group showed more severe reflux than the PGS group, as evaluated in terms of the longest duration of reflux, the number of reflux episodes, the number of reflux episodes lasting 〉 5 min, the total time with pH 〈 4 during acid reflux episodes, and the DeMeester score, but none of these parameters showed statistically significant difference. Although 53.8% （14/26） of the PGS group and 76.2% （16/22） of the EE group demonstrated pathologic acid reflux （DeMeester score 〉 14.72）, there was no statistically significant difference between the two groups in the incidence of pathologic acid reflux （P = 0.11）. CONCLUSION： There was no statistically significant difference in pathologic acid reflux between the PGS and EE group. These data suggest that endoscopically diagnosed PGS might be a predictor of pathologic acid reflux.

Comparison of two Nd:YAG laser posterior capsulotomy: cruciate pattern vs circular pattern with vitreous strand cutting

AIM： To investigate the effects and safety of neodymium： yttrium-aluminium-garnet（Nd：YAG） laser posterior capsulotomy with vitreous strand cuttingMETHODS： A total of 40 eyes of 37 patients with symptomatic posterior capsular opacity（PCO） were included in this prospective randomized study and were randomly subjected to either cruciate pattern or round pattern Nd：YAG posterior capsulotomy with vitreous strand cutting（modified round pattern）. The best corrected visual acuity（BCVA）, intraocular pressure（IOP）, refractive error, endothelial cell count（ECC）, anterior segment parameters, including anterior chamber depth（ACD） and anterior chamber angle（ACA） were measured before and 1 mo after the laser posterior capsulotomy. RESULTS： In both groups, the BCVA improved significantly（P〈0.001 for the modified round pattern group, P=0.001 for the cruciate pattern group）; the IOP and ECC did not significantly change. The ACD significantly decreased（P〈0.001 for both） and the ACA significantly increased（P=0.001 for the modified round pattern group and P=0.034 for the cruciate group）. The extent of changes in these parameters was not significantly different between the groups.CONCLUSION： Modified round pattern Nd：YAG laser posterior capsulotomy is an effective and safe method for the treatment of PCO. This method significantly changes the ACD and ACA, but the change in refraction is not significant. Modified round pattern Nd：YAG laser posterior capsulotomy can be considered a good alternative procedure in patients with symptomatic PCO.

Extraction and clipping repair of a chicken bone penetrating the gastric wall

We report a case of gastric penetration caused by accidental ingestion of a chicken bone in a 42-year old woman with a partially wearing denture. Three days ago, she accidentally swallowed several lumps of poorly-chewed chicken. Physical examination disclosed mild tenderness in the periumbilical area. Abdominal Computed tomography (CT) showed a suspicious penetration or perforation of the stomach wall measuring about 3 cm, by a linear radiopaque material at the lesser curvature of the antrum. The end of a chicken bone was very close to but did not penetrate the liver. Endoscopic examination revealed a chicken bone that penetrated into the prepyloric antrum. The penetrating chicken bone was removed with grasping forceps. Five endoscopic clips were applied immediately at the removal site and the periumbilical pain resolved promptly. After removal of the chicken bone, the patient was treated with conservative care for three days, after which she was completely asymptomatic and discharged without complication. To treat gastric penetration by a foreign body, endoclipping can be a useful method in patients with no signs or symptoms of peritoneal irritation.

Effects of Wind Fences on the Wind Environment around Jang Bogo Antarctic Research Station

This study investigated the flow characteristics altered by Jang Bogo Antarctic Research Station using computational fluid dynamics(CFD) modeling. The topography and buildings around Jang Bogo Station were constructed with computeraided-design data in the CFD model domain. We simulated 16 cases with different inflow directions, and compared the flow characteristics with and without Jang Bogo Station for each inflow direction. The wind data recorded by the site’s automatic weather station(AWS) were used for comparison. Wind rose analysis showed that the wind speed and direction after the construction of Jang Bogo Station were quite different from those before construction. We also investigated how virtual wind fences would modify the flow patterns, changing the distance of the fence from the station as well as the porosity of the fence. For westerly inflows, when the AWS was downwind of Jang Bogo Station, the decrease in wind speed was maximized(-81% for west-northwesterly). The wind speed reduction was also greater as the distance of the fence was closer to Jang Bogo Station. With the same distance, the fence with medium porosity(25%–33%) maximized the wind speed reduction.These results suggest that the location and material of the wind fence should be selected carefully, or AWS data should be interpreted cautiously, for particular prevailing wind directions.

三种选育高乙醇耐受性工业酿酒酵母方法的比较

由于乙醇耐性受多基因控制，因此需要从全基因组水平进行改造以期得到高乙醇耐受的突变体。文中分别使用紫外诱变、等离子体诱变及人工转录因子3种方法对工业酿酒酵母Sc4126进行改造，获得了乙醇耐性提高的突变体，并比较了3种方法的正突变率。人工转录因子文库转化的方法获得了最多数量的乙醇耐性突变体，高出紫外诱变和等离子体诱变方法1～2个数量级，且遗传稳定。研究结果表明，人工转录因子技术可以用于对工业酿酒酵母快速进行基因组工程改造。

A simple, flexible and high-throughput cloning system for plant genome editing via CRISPR-Cas system

CRISPR-Cas9 system is now widely used to edit a target genome in animals and plants. Cas9 protein derived from Streptococcus pyogenes（Sp Cas9） cleaves double-stranded DNA targeted by a chimeric single-guide RNA（sg RNA）. For plant genome editing, Agrobacterium-mediated T-DNA transformation has been broadly used to express Cas9 proteins and sg RNAs under the control of Ca MV 35 S and U6/U3 promoter, respectively. We here developed a simple and high-throughput binary vector system to clone a 19 20 bp of sg RNA, which binds to the reverse complement of a target locus, in a large T-DNA binary vector containing an Sp Cas9 expressing cassette. Twostep cloning procedures：（1） annealing two target-specific oligonucleotides with overhangs specific to the Aar I restriction enzyme site of the binary vector; and（2） ligating the annealed oligonucleotides into the two Aar I sites of the vector, facilitate the high-throughput production of the positive clones. In addition, Cas9-coding sequence and U6/U3 promoter can be easily exchanged via the GatewayTMsystem and unique Eco RI/Xho I sites on the vector, respectively. We examined the mutation ratio and patterns when we transformed these constructs into Arabidopsis thaliana and a wild tobacco, Nicotiana attenuata. Our vector system will be useful to generate targeted large-scale knock-out lines of model as well as non-model plant.