Ellagic acid inhibits gastric cancer cells by modulating oxidative stress and inducing apoptosis

Objective:To evaluate the anticancer effect of ellagic acid on gastric cancer cells.Methods:MTT assay was used to evaluate the effect of ellagic acid at different concentrations(0.5-100μg/mL)on gastric cancer AGS cells.RT-qPCR and Western blot analyses were applied to assess apoptosis(BCL-2,CASP-3,and BAX)and autophagy(LC3,ATG5,and BECN1)in AGS cells treated with ellagic acid.The expression of invasion-related markers including TP53,CDKN2A,and PTEN was determined.In addition,cell cycle markers including cyclin A,B,D,and E were measured by ELISA.Oxidative stress markers were evaluated using spectrophotometry.Results:Ellagic acid inhibited the proliferation of AGS cells in a concentration-and time-dependent manner.The expression of BCL-2 was significantly decreased(P<0.05)and CASP-3 and BAX were markedly increased(P<0.01)in AGS cells treated with ellagic acid.However,this compound induced no significant changes in the expression levels of LC3,ATG5,and BECN1(P>0.05).Moreover,the oxidative stress markers including SOD,TAC,and MDA were increased by ellagic acid(P<0.01).Conclusions:Ellagic acid can inhibit cell proliferation,induce apoptosis,and modulate oxidative stress in AGS cells.However,further in vivo and molecular studies are needed to verify its anticancer efficacy.

Flexible bronchoscopy for foreign body aspiration in children:A single-centre experience

BACKGROUND The technological evolution of bronchoscopy has led to the widespread adoption of flexible techniques and their use for both diagnostic and therapeutic purposes.Currently,there is an active debate regarding the comparative efficacy and safety of rigid vs flexible bronchoscopy in the treatment of foreign body aspiration.AIM To evaluate our experience with tracheobronchial foreign body extraction using flexible bronchoscopy and provide a literature overview.METHODS This was a single-centre retrospective study.Twenty-four patients were enrolled between January 2017 and January 2023.Medical records of patients aged below 18 years who were admitted to authors’affiliated institution with a suspected diagnosis of foreign body aspiration were collected from hospital’s database to Microsoft Excel 2019.Data were analysed using MedCalc Statistical Software.RESULTS Patient ages varied from 9 months to 11 years.The median age was 23.5 months,95%confidence interval(CI)19.49-44.77.We observed age clustering in children with foreign body aspiration at our institution with three age subgroups:(1)0-25 months;(2)40-60 months;and(3)120-140 months.We expectancy of an organic tracheobronchial foreign body was significantly higher in 0-25 months subgroup than that in older ones when subgroups 40-60 and 120-140 months were combined together(odds ratio=10.0,95%CI:1.44-29.26,P=0.0197).Successful foreign body extraction was performed in all cases.Conversion to a rigid bronchoscope was not required in any of the cases.No major complications(massive bleeding,tracheobronchial tree perforation,or asphyxia)were observed.CONCLUSION Flexible bronchoscopy is an effective and safe method for tracheobronchial foreign body extraction in children.

Pancreatic neuroendocrine tumor and solid-pseudopapillary neoplasm: Key immunohistochemical profiles for differential diagnosis

AIM To reveal better diagnostic markers for differentiating neuroendocrine tumor(NET) from solid-pseudopapillary neoplasm(SPN), focusing primarily on immunohistochemical analysis.METHODS We reviewed 30 pancreatic surgical specimens of NET(24 cases) and SPN(6 cases). We carried out comprehensive immunohistochemical profiling using 9 markers: Synaptophysin, chromogranin A, pancytokeratin, E-cadherin, progesterone receptor,vimentin, α-1-antitrypsin, CD10, and β-catenin.RESULTS E-cadherin staining in NETs, and nuclear labeling of β-catenin in SPNs were the most sensitive and specific markers. Dot-like staining of chromogranin A might indicate the possibility of SPNs rather than NETs. The other six markers were not useful because their expression overlapped widely between NETs and SPNs. Moreover, two cases that had been initially diagnosed as NETs on the basis of their morphological features, demonstrated SPN-like immunohistochemical profiles. Careful diagnosis is crucial as we actually found two confusing cases showing disagreement between the tumor morphology and immunohistochemical profiles.CONCLUSION E-cadherin, chromogranin A, and β-catenin were the most useful markers which should be employed for differentiating between NET and SPN.

Endoscopic treatment of blue rubber bleb nevus syndrome in a 4-year-old girl with long-term follow-up:A case report

BACKGROUND Blue rubber bleb nevus syndrome(BRBNS)is a rare vascular disease,difficult to diagnose and choose a treatment method,especially in young children.There are several limiting factors to the use of enteroscopy for diagnostics and treatment in pediatric patients,in general.The literature on BRBNS cases is limited and presents various therapeutic approaches.CASE SUMMARY We present here a case of BRBNS involving a 4-year-old female,whose intestinal venous lesions were successfully treated by endoscopic sclerotherapy and aethoxysklerol foam.Skin lesions,typical for BRBNS,appeared on the 8th d of the child’s life and their number increased over the next several months.The child also experienced episodes of critical decrease in hemoglobin level(by as much as 52 g/L)for several years,requiring iron supplementation and several blood transfusions.Video capsule endoscopy revealed numerous vascular formations in the small bowel.The combined findings of gastrointestinal venous formations and skin lesions prompted BRBNS diagnosis.Single-balloon enteroscopy was used to perform sclerotherapy,with aethoxysklerol foam.A positive effect was observed within 19 mo of follow-up.We continue to monitor the patient’s hemoglobin level,every 2 wk,and it has remained satisfactory(>120 g/L).CONCLUSION Endoscopic sclerotherapy can be effective in the clinical management of gastrointestinal manifestations of BRBNS in young children.

β-Arrestin 1(ARRB1) serves as a molecular marker of the peripheral circadian rhythm

The control of the circadian rhythm is important for health because it regulates physiological functions and is associated with health hazards.We aimed to identify a circadian biomarker of health status in human saliva,since collecting saliva is non-invasive,straightforward,and cost-effective.Among 500 genes potentially controlled by the salivary clock identified using chromatin immunoprecipitation(ChIP)assays,22 of them showed reasonable transcriptional responses according to a DNA array in a salivary model system.Among these 22 genes,ARRB1,which is expressed in human salivary glands,was also expressed in model HSG cells at the transcriptional and translational levels.The profile of ARRB1 expression in human saliva was circadian,suggesting that ARRB1 could serve as a candidate circadian biomarker in saliva.We compared ARRB1 with other biomarkers in salivary samples from jetlagged individuals.The circadian profile of ARRB1 reflected the time lag more than the profile of melatonin,whereas the profiles of cortisol andα-amylase did not reflect the time lag.Overall,these findings suggest that salivary ARRB1 could serve as a candidate biomarker that could be used to monitor the internal body clock.

Liver atrophy after percutaneous transhepatic portal embolization occurs in two histological phases: Hepatocellular atrophy followed by apoptosis

AIM To clarify the histological changes associated with liver atrophy after percutaneous transhepatic portalembolization(PTPE) in pigs and humans. METHODS As a preliminary study, we performed pathological examinations of liver specimens from five pigs that had undergone PTPE in a time-dependent model of liver atrophy. In specimens from embolized lobes(EMB) and nonembolized lobes(controls), we measured the portal vein to central vein distance(PV-CV), the area and number of hepatocytes per lobule, and apoptotic activity using the terminal deoxynucleotidyl transferase dU TP nickend labeling assay. Immunohistochemical reactivities were evaluated for light chain 3(LC3) and lysosomal-associated membrane protein 2(LAMP2) as autophagy markers and for glutamine synthetase and cytochrome P450 2 E1(CYP2 E1) as metabolic zonation markers. Samples from ten human livers taken 20-36 d after PTPE were similarly examined. RESULTS PV-CVs and lobule areas did not differ between EMB and controls at day 0, but were lower in EMB than in controls at weeks 2, 4, and 6(P ≤ 0.001). Hepatocyte numbers were not significantly reduced in EMB at day 0 and week 2 but were reduced at weeks 4 and 6(P ≤ 0.05). Apoptotic activity was higher in EMB than in controls at day 0 and week 4. LC3 and LAMP2 staining peaked in EMB at week 2, with no significant difference between EMB and controls at weeks 4 and 6. Glutamine synthetase and CYP2 E1 zonation in EMB at weeks 2, 4, and 6 were narrower than those in controls. Human results were consistent with those of porcine specimens. CONCLUSION The mechanism of liver atrophy after PTPE has two histological phases: Hepatocellular atrophy is likely caused by autophagy in the first 2 wk and apoptosis thereafter.

Gastroesophageal reflux disease in pediatric esophageal atresia:Assessment of clinical symptoms and pH-impedance data

BACKGROUND Esophageal atresia(EA)is the most common congenital anomaly of the gastrointestinal tract.Gastroesophageal reflux disease(GERD)is a frequent and lifelong problem in these patients.GERD can be asymptomatic and the incidence of esophageal gastric and intestinal metaplasia(Barrett’s esophagus)is increased in adults with EA compared with the general population.Timely and accurate diagnosis of GERD is important to reduce long-term problems and this may be achieved by pH-impedance testing.AIM To assess symptoms and pH-impedance data in children after EA,in order to identify their specific features of GERD.METHODS This study was conducted from November 2017 to February 2020 and involved 37 children who had undergone EA via open surgical repair(51.35%boys,48.65%girls;age range:1-14 years,median:4.99 years).GERD diagnosis was made based on multichannel intraluminal impedance/pH study and two groups were established:EA without GERD,n=17;EA with GERD,n=20.A control group was established with 66 children with proven GERD(68.18%boys,31.82%girls;median age:7.21 years),composed of a nonerosive reflux disease(referred to as NERD)group(n=41)and a reflux esophagitis group(n=25).Upper gastrointestinal endoscopy with a mucosal esophageal biopsy was performed on all patients.RESULTS The most frequently observed symptom in EA patients with GERD and without GERD was cough(70%and 76.5%respectively).The number of patients with positive symptom association probability in the EA groups was significantly larger in the EA without GERD group(P=0.03).In the control reflux esophagitis group,prevalence of gastrointestinal symptoms was significantly higher than in the NERD group(P=0.017).For both EA groups,there was strong correlation with index of proximal events(IPE)and total proximal events(EA with GERD:0.96,P<0.001;EA without GERD:0.97,P<0.001)but level of IPE was significantly lower than in GERD patients without any surgical treatment(P<0.001).Data on distal mean nocturnal baseline impedance were significantly different between the EA with GERD group(P<0.001)and the two control groups but not between EA without GERD and the two control groups.CONCLUSION Mean nocturnal baseline impedance may have diagnostic value for GERD in EA children after open surgical repair.IPE might be an additional parameter of pHimpedance monitoring.

Cytogenetic abnormalities in 200 male infertile cases in the southern region of India

Chromosomal abnormalities are one of the major causes of male infertility. But the exact mechanism by which chromosomal anomalies induces infertility is still not clear. Many studies have documented the chromosomal abnormalities ranging from 2.2% to 15.7% in infertile men. The present study has been carried out to document and find out the genetic cause of male infertility in the Southern region of India. The cytogenetic analysis of 200 male infertile cases, referred due to primary infertility from 2009 to 2012, were analyzed by GTG banding and evaluated retrospectively. The semen analysis was also performed. A total of 15 cases (7.5%) showed chromosomal aberrations. Four (2%) were 47, XXY and mosaic 47,XXY;Two (1%) were structural autosomal abnormalities;Two (1%) were inversion Y;Seven (3.5%) cases were Y heterochromatin variants and 185 cases (92.5%) showed normal 46,XY karyotype. The chromosomal abnormalities in our study is also in agreement with the data from the literature. Also abnormal spermatogenesis is observed in these cases. Apart from chromosomal analysis further in depth molecular analysis and genetic counseling is suggestive in such cases, especially those interested in IVF technologies.

应用脂质体凝集反应板快速检测活动性结核病患者抗原

背景:共有1360例临床确诊的肺内结核、肺外结核患者标本及其他非结核标本。目的:建立一种快速、敏感、特异的检测不同临床标本中结核分枝杆菌糖脂抗原的方法。研究设计:在1-乙基-3-3-二甲基氨丙基碳化二亚胺氢氯化物和N-羟基丁二酰胺溶液中将亲和纯化的兔抗糖脂抗体(IgG)结合在脂质体颗粒(0.2～0.4 um)上,制备TB/M检测板的反应试剂。结果:当检测样本中存在糖脂抗原时,连接抗体的脂质体在4 min内会出现1个深蓝色的凝集点。而正常健康人或其他疾病患者的样本未见凝集点。结果显示该方法检测活动性肺结核患者临床样本中的结核分枝杆菌糖脂抗原的敏感性可低至1 ng/ml,临床灵敏度为97.4%,特异性为96.9%。结论:TB/M检测试验比较经济(一次检测只需4个印度卢比或0.09美元)、快速(4 min),似乎有助于结核病流行国家大规模检测结核性脑膜炎、肺结核和其他肺外结核患者多种生物学标本(脑脊液、胸液、关节液、血清和组织活检标本)。

Genetic Analysis of 17 Children with Hunter Syndrome:Identification and Functional Characterization of Four Novel Mutations in the Iduronate-2-Sulfatase Gene

Mucopolysaccharidosis type II （MPS II） is a rare X-linked disorder caused by alterations in the iduronate-2-sulfatase （IDS） gene. In this study, IDS activity in peripheral mononuclear blood monocytes （PMBCs） was measured with a fluorimetric enzyme assay. Urinary glycosaminoglycans （GAGs） were quantified using a colorimetric assay. All IDS exons and intronic flanks were bidirectionally sequenced. A total of 15 mutations （all exonic region） were found in 17 MPS II patients. In this cohort of MPS II patients, all alterations in the IDS gene were caused by point nucleotide substitutions or small deletions. Mutations p.Arg88His and p.Arg172＊ occurred twice. All mu- tations were inherited except for p.Gly489Alafs＊7, a germline mutation. We found four new mutations （p.Ser142Phe, p.Arg233Gly, p.Glu430＊, and p.Ile360Tyrfs＊31）. In Epstein-Barr virus （EBV）-immortalized PMBCs derived from the MPS II patients, no IDS protein was detected in case of the p.Ser142Phe and p.Ile360Tyrfs＊31 mutants. For p.Arg233Gly and p.Glu430＊, we observed a residual expression of IDS. The p.Arg233Gly and p.Glu430＊ mutants had a residuary enzymatic activity that was lowered by 14.3 and 76-fold, respectively, compared with healthy controls. This observation may help explain the mild disease phenotype in MPS II patients who had these two mutations whereas the p.Ser142Phe and p.Ile360Tyrfs＊31 mutations caused the severe disease manifestation.

Model-based Tracking for Agent-based Control Systems in the Case of Sensor Failures

The study on artificial intelligence(AI) methods for tuning of particle accelerators has been reported in many literatures.This paper presents tuning method for agent-based control systems of transport lines in the case of sensor/actuator failures.The method uses model-based tracking concept to relax the demand on sensor data.The condition for successful operation of the stated scheme is derived,and the concept is demonstrated through simulation by applying it to the model of microtron,transport line-1 and booster of indus accelerator.The results show that this approach is very effective in transport line control during sensor/actuator failures.

Current and future opportunities for liquid biopsy of circulating biomarkers to aid in early cancer detection

Early diagnosis of cancer can significantly improve treatment and survival outcomes.Imaging and tissue biopsy are the gold standard diagnostic approaches but are costly,invasive,and often unable to detect early-stage tumors.The past decade has marked an acceleration in the discovery and development of liquid biopsy tests for aiding in the detection of various types of tumor markers in non-tissue samples,such as blood.Liquid biopsy markers include circulating tumor cells,as well as tumor cell fragments,nucleic acids,and proteins.Liquid biopsy may be useful in screening patients considered to be at high risk of developing cancer,for refining diagnosis when combined with other test results,and for early detection of recurrence.Advances in big data analytics,informatics,and artificial intelligence will make it possible to combine patient history,clinical data,and liquid biopsy marker profiles to achieve more accurate and earlier diagnosis.In this review,we summarize the current use of liquid biopsy in cancer care,including the development of multi-analyte panels to improve diagnostic accuracy and detect several cancer types in a single assay.We highlight recent advances for potential future applications of liquid biopsy to aid in the diagnosis of early-stage lung cancer.We also discuss the opportunities and challenges of integrating liquid biopsy into current algorithms for cancer screening and diagnosis.

Identification of slot discharges in rotating machine insulation system using variable frequency PD measurement

Slot discharge studies are very important from the insulation diagnosis perspective.Further in practice,testing of rotating machines with power frequency requires sources which are quite bulky and costly.Instead if the diagnosis is carried out at lower frequencies(<50 Hz),the size and cost of the test source can be reduced significantly.Therefore,it is important to know whether the study at low frequencies can be considered equivalent to study at power frequency.Hence,in this study,a slot discharge phenomenon occurring in a rotating machine insulation system was investigated experimentally at different frequencies(50,10,1 and 0.1 Hz).Slot discharges are known to have a distinct phase resolved partial discharge pattern for power frequency(50/60 Hz)excitation.These distinct patterns are useful in identifying the presence of slot discharge activity in rotating machines.Slot discharges were created on a 6.6 kV mica-epoxy stator coil and the slot discharge characteristics measured at different frequencies are compared.Slot discharge measurements were repeated by varying the air gap between the insulation surface and grounded steel plate.The changes in slot discharge characteristics due to the increase in air gap were found similar at all frequencies.The comparison suggests that the identification of slot discharge is also possible from the partial discharge(PD)measurement at low frequencies.

Treatment of isolated and recurrent tracheoesophageal fistula in children: a case series and literature review

Background Despite improvements in the treatment of esophageal atresia with tracheoesophageal fistula(TEF)in recent decades,complications still exist.The rate of fistula recanalization after surgical repair is~5%in large cohorts.However,there is controversy regarding the gold standard of treatment.This research aimed to evaluate the efficacy of treatment of pediatric patients with isolated(H-type)and recurrent TEF in our clinic.Methods We retrospectively analyzed 12 patients(7 boys,5 girls)aged 35 days-14.6 years.The median age of our patients was 632 days[95%CI(confident interval)120.1 to 2118.7];the mean birth weight was 2713 g(95%CI 2258 to 3169;median:2763 g);and the mean gestational age was 37.1 weeks(95%CI 35.4 to 38.8;median:37 weeks).All patients were managed for isolated or recurrent TEF between January 1,2015 and December 31,2020 using endoscopy(laser de-epithelialization).Results Laser de-epithelialization alone was effective in 8 of 12 patients(66.67%),with a mean number of de-epithelializations of 2.25(range:1-4).After one attempt at de-epithelialization,success was achieved in only two patients(n=16.67%).The mortality rate was 0%.The median follow-up for patients who received endoscopic treatment exclusively(n=8)was 3.7 years(95%CI 1.38 to 4.87)after the last stage of de-epithelialization.Conclusion Flexible endoscopy is an alternative treatment to open surgical repair of isolated and recurrent TEF in children.The effectiveness of endoscopic laser de-epithelialization alone with subsequent fistula obliteration was 66.7%,with a median follow-up of 3.7 years.