Flavonoids in safflower extract reduce cisplatin-induced damage to human follicle dermal papilla cells by inhibiting DNA damage and Rad17/Chk1/Cdc25C signaling

Background:Cisplatin is a chemotherapeutic agent commonly used clinically for the treatment of various human cancers.Patients often reduce the use of cisplatin due to its side effects,which in turn affects its treatment.This study explored the mechanism of action of safflower extract as an adjuvant traditional Chinese medicine for chemotherapy.Methods:Primary human follicle dermal papilla cells(HFDPCs)were used as target cells for cisplatininduced damage to hair cells.Western blotting was used to investigate the molecular targets of cisplatin and safflower extract in causing HFDPCs damage.Cell survival and cell cycle were analyzed by mitochondrial staining reagent WST-1 and propidium iodide.Results:Cisplatin could reduce the viability of HFDPCs without causing cell death.Cisplatin increased the level of phospho-Rad17 in HFDPCs and activated the Chk1/Cdc25C signaling to reduce the expression of Cdc2 protein,thereby arresting the cells in the G2/M phase.The combination of safflower extract and the flavonoids could effectively inhibit the signal transduction of Rad17/Chk1/Cdc25 in cisplatin-treated cells and reduce the cell population in the G2/M phase.Finally,we also confirmed that safflower extract could effectively inhibit the damage to HFDPCs caused by cisplatin,mainly at the level of reducing the DNA damage caused by cisplatin.Conclusions:Safflower extract can be used as an adjuvant Chinese medicine for chemotherapy to reduce the damage caused by chemotherapy to normal hair follicle cells.

Impact of gut–brain interaction in emerging neurological disorders

The central nervous system(CNS)is a reservoir of immune privilege.Specialized immune glial cells are responsible for maintenance and defense against foreign invaders.The blood–brain barrier(BBB)prevents detrimental pathogens and potentially overreactive immune cells from entering the periphery.When the double-edged neuroinflammatory response is overloaded,it no longer has the protective function of promoting neuroregeneration.Notably,microbiota and its derivatives may emerge as pathogen-associated molecular patterns of brain pathology,causing microbiome–gut–brain axis dysregulation from the bottom-up.When dysbiosis of the gastrointestinal flora leads to subsequent alterations in BBB permeability,peripheral immune cells are recruited to the brain.This results in amplification of neuroinflammatory circuits in the brain,which eventually leads to specific neurological disorders.Aggressive treatment strategies for gastrointestinal disorders may protect against specific immune responses to gastrointestinal disorders,which can lead to potential protective effects in the CNS.Accordingly,this study investigated the mutual effects of microbiota and the gut–brain axis,which may provide targeting strategies for future disease treatment.

Role of peripheral eosinophilia in acute exacerbation of chronic obstructive pulmonary disease

BACKGROUND Eosinophil counts are a promising guide to systemic steroid administration for chronic obstructive pulmonary disease(COPD).AIM To study the role of peripheral eosinophilia in hospitalized patients with acute exacerbation of COPD(AECOPD).METHODS From January 2014 to May 2017,patients with AECOPD hospitalized in Taipei Tzu Chi Hospital were retrospectively stratified into two groups according to their peripheral eosinophil count:The EOS group(eosinophil count≥2%)and the non-EOS group(eosinophil count<2%).Demographics,comorbidities,laboratory data,steroid use,length of hospital stay,and COPD-related readmissions were compared between the groups.RESULTS A total of 625 patients were recruited,with 176 patients(28.2%)in the EOS group.The EOS group showed a lower prevalence of infection,lower cumulative doses of prednisolone equivalents,shorter length of hospital stay,and higher number of COPD-related readmissions than the non-EOS group.There were significantly linear correlations between eosinophil percentage and number of readmissions and between eosinophil percentage and length of hospital stay P<0.001,and a lower percent-predicted value of forced expiratory volume in one second(FEV1)were associated with shorter time to first COPD-related readmission[adjusted hazard ratio(adj.HR)=1.488,P<0.001;adj.HR=0.985,P<0.001,respectively].CONCLUSION The study findings suggest that the EOS group had the features of a shorter length of hospital stay,and lower doses of systemic steroids,but more frequent readmissions.The EOS group and lower percent-predicted FEV1 values were risk factors for shorter time to first COPD-related readmission.

Noninferiority clinical trial comparing the bowel cleansing efficacy of sodium phosphate tablets(Quiklean®)with a polyethylene glycol/bisacodyl kit

BACKGROUND Efficient bowel cleansing is essential for a successful colonoscopy,but the ideal cleansing agent,volume,and pharmaceutical dosage form have yet to be determined.Small-volume cleansers enhance patient compliance.AIM To compare the bowel cleansing efficacy of 32-tablet sodium phosphate(Quiklean®)with 2-L polyethylene glycol(PEG)/bisacodyl(Klean-Prep/Dulcolax®)under identical dietary recommendations.METHODS This multicenter,randomized,parallel-group,noninferiority clinical trial enrolled 472 outpatients,randomized 456 subjects,and scheduled 442 subjects to undergo colonoscopy(Quiklean®=222 and Klean-Prep/Dulcolax®=220).After bowel preparation,a colonoscopist performed the colonoscopy with video recorded for rating.The primary efficacy endpoint was the bowel cleansing quality using the Aronchick Scale.The secondary endpoints were the bowel cleansing efficacy of three colon segments,tolerability and acceptability,safety using the Ottawa bowel preparation scale,questionnaires by subjects,and monitoring of adverse events.RESULTS Success rates(Excellent+Good)of the bowel cleansing quality by Aronchick Scale were 98.6%(n=205)and 97.6%(n=204)in the Quiklean®and Klean-Prep/Dulcolax®groups,respectively.Quiklean®demonstrated noninferiority over Klean-Prep/Dulcolax®in colon cleansing efficacy.Quicken showed better tolerability and acceptability in the overall experience(was rated as excellent;24.0%vs 17.2%;P=0.0016)and the taste of the study preparation(was rated as excellent,23.1%vs 13.4%;P<0.0001)than Klean-Prep/Dulcolax®.Safety profiles did not differ between the two groups.Our data indicate that Quiklean®is an adequate,well-tolerated bowel cleansing preparation compared with the standard comparator Klean-Prep/Dulcolax®.CONCLUSION Quiklean®is sodium phosphate tablets available on Taiwan’s market for bowel preparation;it potentially offers patients an alternative to standard large-volume bowel preparation regimens and may,therefore,increase positive attitudes toward colonoscopies and participation rates.

Prognostic factors of short-term outcomes of intravitreal ranibizumab in diabetic macular edema

AIM：To evaluate the prognostic factors for short-term visual and anatomical improvement of intravitreal ranibizumab（IVR） for diabetic macular edema（DME）.METHODS：Fifty-one eyes from 35 patients that received three consecutive monthly IVR for DME with moderate visual loss were retrospectively recruited; all cases had their baseline best-corrected visual acuity（BCVA） between 20/400 and 20/40. BCVA and central subfield thickness（CST） at baseline and month 3 were collected. Linear mixed models were used to evaluate the prognostic factors for visual and anatomical improvement at month 3.RESULTS：Younger age, poorer baseline BCVA and proliferative diabetic retinopathy（PDR） were correlated with better visual improvement at month 3（P=0.002, 0.0001 and 0.007, respectively）. Thicker CST and the presence of subretinal fluid at baseline were correlated with a greater reduction in CST（P〈0.0001 and P=0.018, respectively）. The presence of epiretinal membrane or previous posterior subtenon injection of triamcinolone acetonide（PSTA） were associated with a smaller reduction in CST（P=0.029 and 0.018, respectively）, but had no significant effects in visual improvement at month 3（P〉0.05 for both）.CONCLUSION：For eyes with DME and moderate visual loss, those with younger age, poorer baseline BCVA or PDR tend to have better visual improvement after three consecutive monthly IVR. Epiretinal membrane or previous PSTA result in less resolution of CST, but do not significantly affect visual improvement.

Enhancement of matrix metalloproteinases 2 and 9 accompanied with neurogenesis following collagen glycosaminoglycan matrix implantation after surgical brain injury

Surgical brain injury may result in irreversible neurological deficits. Our previous report showed that partial regeneration of a traumatic brain lesion is achieved by implantation of collagen glycosaminoglycan（CGM）. Matrix metalloproteinases（MMPs） may play an important role in neurogenesis but there is currently a lack of studies displaying the relationship between the stimulation of MMPs and neurogenesis after collagen glycosaminoglycan implantation following surgical brain trauma. The present study was carried out to further examine the expression of MMP2 and MMP9 after implantation of collagen glycosaminoglycan（CGM） following surgical brain trauma. Using the animal model of surgically induced brain lesion, we implanted CGM into the surgical trauma. Rats were thus divided into three groups：（1） sham operation group： craniotomy only;（2） lesion（L） group： craniotomy ＋ surgical trauma lesion;（3） lesion ＋ CGM（L ＋ CGM） group： CGM implanted following craniotomy and surgical trauma lesion. Cells positive for SOX2（marker of proliferating neural progenitor cells） and matrix metalloproteinases（MMP2 and MMP9） in the lesion boundary zone were assayed and analyzed by immunofluorescence and ELISA commercial kits, respectively. Our results demonstrated that following implantation of CGM after surgical brain trauma, significant increases in MMP2^＋/SOX2^＋ cells and MMP9^＋/SOX2^＋ cells were seen within the lesion boundary zone in the L ＋ CGM group. Tissue protein concentrations of MMP2 and MMP9 also increased after CGM scaffold implantation. These findings suggest that implantation of a CGM scaffold alone after surgical brain trauma can enhance the expression of MMP2 and MMP9 accompanied by neurogenesis.

Review of epidermal growth factor receptor-tyrosine kinase inhibitors administration to non-small-cell lung cancer patients undergoing hemodialysis

Non-small-cell lung cancer(NSCLC)causes significant mortality worldwide.Patients with chronic renal failure have an increased risk of developing lungcancer.NSCLC Patients with chronic renal failure undergoing hemodialysis(HD)often exhibit poor performance,and chemotherapy is generally contraindicated.Oral epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)are effective treatment agents for NSCLC patients.However,the benefits andadverse effects of EGFR-TKIs in NSCLC undergoing HD are known.There are noclinical studies on the effects of EGFR-TKIs on NSCLC patients undergoing HD.We reviewed all previous case reports about EGFR-TKIs in NSCLC patientsundergoing HD.It is difficult to design studies about the effects of EGFR-TKIs inpatients undergoing HD,and this review is quite important.EGFR-TKIs are welltolerated in patients undergoing HD.The main routes of elimination of EGFRTKIsare metabolism via the liver,and renal elimination is minor.Therecommended doses and pharmacokinetics of these EGFR-TKIs for patientsundergoing HD are similar to those for patients with normal renal function.Theplasma protein binding of EGFR-TKIs is very high,and it is not necessary toadjust the dose after HD.In conclusion,EGFR-TKIs are effective and welltolerated in patients undergoing HD.

Ocular hypertension and severe intraocular pressure elevation after posterior subtenon injection of triamcinolone acetonide for various diseases

AIM:To evaluate and compare the incidences of ocular hyper tension and severe intraocular pressure(IOP)elevation after posterior subtenon injection of triamcinolone acetonide(PSTA)for various diseases.METHODS:Totally 179 eyes that had received PSTA for diabetic macular edema(n=108),pseudophakic cystoid macular edema(n=20),branch retinal vein occlusion(n=16),central retinal vein occlusion(CRVO,n=14),choroidal neovascularization(n=14)or noninfectious uveitis(n=7)were retrospectively enrolled.The primary outcomes included ocular hypertension defined as an IOP>21 mm Hg,and severe IOP elevation defined as a rise of 10 mm Hg or more in IOP compared with baseline.Cox regression models were used to analyze the hazard ratios(HRs)among different diseases.RESULTS:After PSTA,the mean IOPs from month 1 to month 6 all significantly increased(P<0.05).Ocular hypertension occurred in 30.7%of eyes(median time:8 wk),and severe IOP elevation occurred in 16.2%of eyes(median time:9 wk).Patients receiving PSTA for CRVO or uveitis had a significantly higher risk for ocular hypertension(HR=3.049,P=0.004 for CRVO;HR=5.464,P=0.019 for uveitis)and severe IOP elevation(HR=2.913,P=0.034 for CRVO;HR=7.650,P=0.009 for uveitis).CONCLUSION:IOP significantly increases within 6 mo after PSTA,with the onset of ocular hypertension happening mostly at 2 to 3 mo.Patients of CRVO or noninfectious uveitis have a higher risk of ocular hypertension or severe IOP elevation after PSTA and should be monitored for IOP more carefully.

Endoscopic surgery for inverted papilloma with carcinoma change of lacrimal drainage apparatus and nasal cavity

Dear Sir,Iam Dr.Yin-Hung Chang from the Department of Otolaryngology,Taipei Tzu Chi Hospital,the Buddhist Tzu Chi Medical Foundation.I would like to present a case of inverted papilloma with carcinoma change of lacrimal drainage apparatus and nasal cavity that had been successfully treated by endoscopic surgery.Lacrimal drainage apparatus tumors are rare but important

Uncommon cause of voiding dysfunction in a female patient-vaginal abscess: A case report

BACKGROUND Vaginal abscess is a treatable disease and should be considered in female patients with voiding difficulties and perineal tenderness. There are no reported cases of vaginal abscess causing voiding dysfunction in the absence of a previous surgery. Early diagnosis and drainage of vaginal abscesses may lead to excellent outcomes.CASE SUMMARY We presented a case of vaginal abscess that caused voiding dysfunction without surgery history. A 64-yearold woman had a past history of type 2 diabetes mellitus. She came to our clinic following urinary difficulty with perineal tenderness. Bladder ultrasonography revealed a pelvic cystic lesion with a mass effect on the bladder. The presence of a vaginal abscess was suspected following pelvic examination and transvaginal ultrasound.After transvaginal drainage of the vaginal abscess and a full course of antibiotic treatment, she recovered well without any urination symptoms. CONCLUSION Voiding dysfunction caused by vaginal abscess is rare but should be considered in female patients with perineal tenderness.

Snapping wrist due to bony prominence and tenosynovitis of the first extensor compartment:A case report

BACKGROUND A snapping wrist is a rare symptom that results from the sudden impingement of one anatomic structure against another,subsequently causing a sudden movement only during wrist movement.CASE SUMMARY A 30-year-old woman with a history of right wrist contusion reported right wrist snapping after overuse.The snapping became symptomatic after moving heavy objects.The pain persisted even when she received 1 mo of conservative treatment.Physical examination showed painful wrist snapping during wrist radioulnar motion and thumb abduction-adduction.Radiography demonstrated bone overgrowth over the radial styloid process.Sonography disclosed a tendon jumping over a bony prominence in the first compartment during wrist motion.Magnetic resonance imaging revealed no anomalous tendon nor tumorlike lesion.Under the wide-awake local anesthesia no tourniquet(WALANT)technique,the lesion was identified in the first extensor compartment.The patient received stepwise extensor retinaculum release,synovectomy,and bone spur removal.By 6th week,the patient was completely free of pain and unable to snap her wrist.She started working 7 wk after the surgery.One year after the surgery,the wrist snap was not recurrent.CONCLUSION Careful physical examination and dynamic sonography may confirm the diagnosis of a snapping wrist.With the WALANT technique,the lesion could be identified under direct vision,and we could take stepwise interventions according to intraoperative presentations.

Synchronous but separate neuroendocrine tumor and high-grade dysplasia/adenoma of the gall bladder:A case report

BACKGROUND Gall bladder neuroendocrine tumors(GB-NETs)are rare,accounting for less than 0.5%of all NETs.They usually lack specific symptoms and are difficult to diagnose preoperatively.In most cases,GB-NETs are incidentally found after cholecystectomy for large polyps or cholelithiasis,causing acute or chronic cholecystitis.The coexistence of GB-NET and GB adenocarcinoma is very rare.CASE SUMMARY We report a case of synchronous but separate GB-NET and adenoma with high-grade dysplasia in a patient who had undergone surgery for a progressively growing GB polypoid lesion.To the best of our knowledge,simultaneous separation of NETs and cancer in the GB has not been reported.CONCLUSION Coexistent GB carcinoid tumor and adenocarcinoma is rare.A surveillance program is needed for these large GB polyps.

Newborn Hip Screenings at 4 to 8 Weeks Are Optimal in Predicting Referral and Treatment Outcomes: A Retrospective Review

Optimal DDH screening timing and whether adding risk profiles could aid in detecting treatment outcome were investigated. Risk factors were employed to supplement ultrasound findings in flagging cases for follow-up. Initial screening results and harness treatment outcomes concordance were compared at different screening ages and screening protocols. Using clinical decision to supplement ultrasound screening allowed to accurately flag all 12 DDH treated cases upon initial visit. Clinical decision correctly identified cases that would have otherwise been missed (n = 2). However, doing so increased the rate of false positive cases at all time points of initial screening. Initial screens were more accurate for predicting treatment outcomes when using ultrasound only if done after 28 days [≤28 days (88.1%) vs. 29 - 56 days (98.5%), OR = 7.16, p < 0.001] or ultrasound with clinical decision [≤28 days (86.4%) vs. 29 - 56 days (95.7%), OR = 3.00, p < 0.001]. In contrast, screening after 56 days failed to marginally improve accuracy compared to screens done between 29 - 56 days, regardless of the screening protocol employed. Two important trade-offs emerged. First, when choosing timing of initial screening, optimal accuracy and harness treatment schedule should both be considered. Second, when considering whether to use a more conservative risk profile to supplement ultrasound findings, treatment accuracy and the ability to efficiently detect cases requiring harness treatment should both be considered. We provide evidence for performing an initial DDH ultrasound screen between 4 and 8 weeks (29 - 56 days), while employing clinical decision to aid in determining cases that require further follow-up evaluation.

Organophosphate pesticides and new-onset diabetes mellitus:From molecular mechanisms to a possible therapeutic perspective

Organophosphate is a commonly used pesticide in the agricultural sector.The main action of organophosphate focuses on acetylcholinesterase inhibition,and it therefore contributes to acute cholinergic crisis,intermediate syndrome and delayed neurotoxicity.From sporadic case series to epidemiologic studies,organophosphate has been linked to hyperglycemia and the occurrence of newonset diabetes mellitus.Organophosphate-mediated direct damage to pancreatic beta cells,insulin resistance related to systemic inflammation and excessive hepatic gluconeogenesis and polymorphisms of the enzyme governing organophosphate elimination are all possible contributors to the development of newonset diabetes mellitus.To date,a preventive strategy for organophosphatemediated new-onset diabetes mellitus is still lacking.However,lowering reactive oxygen species levels may be a practical method to reduce the risk of developing hyperglycemia.

The role of tazarotene-induced gene 1 in carcinogenesis:is it a tumor suppressor gene or an oncogene?

Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet in many cancer tissues,it is not expressed because of the methylation of its promoter.Additionally,the expression of TIG1 in cancer cells inhibits their growth and invasion,suggesting that TIG1 acts as a tumor suppressor gene.However,in some cancers,poor prognosis is associated with TIG1 expression,indicating its protumor growth characteristics,especially in promoting the invasion of inflammatory breast cancer cells.This review comprehensively summarizes the roles of the TIG1 gene in cancer development and details the mechanisms through which TIG1 regulates cancer development,with the aim of understanding its various roles in cancer development.

Tendency to Avoid Physical Activity and Sport:Associations with Weight Stigma,and Psychological Distress in a Two-Wave Longitudinal Study

Background:Physical inactivity is a major public health problem worldwide that results in physical and mental health problems.One major issue for physical inactivity is weight stigma(WS),especially perceived WS,which could lead to a tendency to avoid physical activity(PA).To better understand the association between perceived WS and PA,knowledge of the likely mediators in this association such as weight bias internalization(WBI)and psychological distress were investigated in the present study.Methods:Using a two-wave longitudinal study and convenient sampling,388 Taiwan residents participants(55%females;mean age=29.7 years[SD±6.3])completed two surveys six months apart.Body mass index(BMI),Perceived Weight Stigma Scale(PWSS),Weight Bias Internalization Scale(WBIS),Depression,Anxiety,Stress Scale(DASS-21),and Tendency to Avoid Physical Activity and Sport Scale(TAPAS)were assessed.Results:A mediation model controlling for age,gender,and BMI with 5000 bootstrapping resamples was performed.Perceived WS exerted significant direct effects on WBI(β=0.25;p<0.001),psychological distress(β=0.15;p=0.003),and tendency to avoid PA(β=0.10;p=0.027);WBI exerted a significant direct effect on tendency to avoid PA(β=0.47;p<0.001).Standardized indirect effects of WBI and psychological distress on the association between perceived WS and tendency to avoid PA were 0.12 and 0.01,respectively.Conclusion:Given the direct association of perceived WS on the tendency to avoid PA and the mediating role of WBI in this association,interventions addressing perceived WS and WBI may contribute to promoting PA.Therefore,health interventionists(both when planning and executing PA programs)need to consider weight stigmawhen encouraging physical activity.