An Artificial Neural Network Model Combined with Dietary Retinol Intake from Different Sources to Predict the Risk of Nonalcoholic Fatty Liver Disease

Objective This study aimed to develop an artificial neural network(ANN) model combined with dietary retinol intake from different sources to predict the risk of non-alcoholic fatty liver disease(NAFLD) in American adults.Methods Data from the 2007 to 2014 National Health and Nutrition Examination Survey(NHANES)2007–2014 were analyzed. Eligible subjects(n = 6,613) were randomly divided into a training set(n1 =4,609) and a validation set(n2 = 2,004) at a ratio of 7:3. The training set was used to identify predictors of NAFLD risk using logistic regression analysis. An ANN was established to predict the NAFLD risk using a training set. Receiver operating characteristic(ROC) curve analysis was performed to evaluate the accuracy of the model using the training and validation sets.Results Our study found that the odds ratios(ORs) and 95% confidence intervals(CIs) of NAFLD for the highest quartile of plant-derived dietary retinol intake(i.e., provitamin A carotenoids, such as β-carotene)(OR = 0.75, 95% CI: 0.57 to 0.99) were inversely associated with NAFLD risk, compared to the lowest quartile of intake, after adjusting for potential confounders. The areas under the ROC curves were 0.874 and 0.883 for the training and validation sets, respectively. NAFLD occurs when its incidence probability is greater than 0.388.Conclusion The ANN model combined with plant-derived dietary retinol intake showed a significant effect on NAFLD. This could be applied to predict NAFLD risk in the American adult population when government departments formulate future health plans.

Efficacy of surgical resection and ultra-reduced tension suture combined with superficial radiation in keloid treatment

BACKGROUND There are many available treatment options for keloid;however,single treatments are usually less effective.Therefore,more scientifically rational and effective com-bined treatment methods should be sought to solve the pain associated with keloids.AIM To explore the efficacy and safety of surgical resection and ultra-reduced tension suture combined with superficial radiation as keloid treatment.METHODS Fifteen keloid patients admitted to Qingdao Eighth People's Hospital from June 2020 to January 2022 were enrolled in this retrospective analysis.All patients underwent a comprehensive treatment approach comprising surgical resection,ultra-reduced tension suture incision,and superficial radiation therapy within 24 h postoperatively.The modified Vancouver Scar Scale(mVSS)and Patient and Observer Scar Assessment Scale(POSAS)were used to evaluate the treatment effect,whereas the efficacy,adverse effects,and recurrence rate were observed according to the 12-mo follow-up after treatment.RESULTS The mVSS and POSAS scores at 1 and 6 mo after combination treatment decreased compared to before treatment(P<0.001),and the overall response rate was 93.3%.Only one case recurred,yielding a 6.7%recurrence rate.The incidence of local chromour sedimentation rate in 1–3 mo after radiotherapy was 33.3%(5 patients),all subsiding after 6–9 mo,without complications,such as delayed wound healing or dermatitis.CONCLUSION Surgical resection,super subtraction sutures,and superficial radiotherapy are treatment methods with short courses,low recurrence rates,and good safety profiles.

Circulating Exosomal Lnc RNAs as Novel Diagnostic Predictors of Severity and Sites of White Matter Hyperintensities

Objective Exosomal long noncoding RNAs(lnc RNAs) are the key to diagnosing and treating various diseases. This study aimed to investigate the diagnostic value of plasma exosomal lnc RNAs in white matter hyperintensities(WMH).Methods We used high-throughput sequencing to determine the differential expression(DE) profiles of lnc RNAs in plasma exosomes from WMH patients and controls. The sequencing results were verified in a validation cohort using q RT-PCR. The diagnostic potential of candidate exosomal lnc RNAs was proven by binary logistic analysis and receiver operating characteristic(ROC) curves. The diagnostic value of DE exo-lnc RNAs was determined by the area under the curve(AUC). The WMH group was then divided into subgroups according to the Fazekas scale and white matter lesion site, and the correlation of DE exo-lnc RNAs in the subgroup was evaluated.Results In our results, four DE exo-lnc RNAs were identified, and ROC curve analysis revealed that exolnc_011797 and exo-lnc_004326 exhibited diagnostic efficacy for WMH. Furthermore, WMH subgroup analysis showed exo-lnc_011797 expression was significantly increased in Fazekas 3 patients and was significantly elevated in patients with paraventricular matter hyperintensities.Conclusion Plasma exosomal lnc RNAs have potential diagnostic value in WMH. Moreover, exolnc_011797 is considered to be a predictor of the severity and location of WMH.

Analysis of the intestinal flora in patientswith primary liver cancer

Objective To investigate the differences in intestinal flora of patients with primary liver cancer and ofhealthy individuals and to investigate the effect of the differential flora on the development of liver cancer.Methods Overall, 67 patients with primary liver cancer who received systematic and complete treatmentbetween January 2019 and December 2020 at the Sixth People’s Hospital of Qingdao and had completeclinical data were enrolled in this study, and 26 individuals who were healthy on physical examination inthe same period were used as healthy controls. Macro genome and 16s ribosome Deoxyribo Nucleic Acid(rDNA) high-throughput sequencing were performed on the stool flora of the enrolled patients and controls,and the differences in the intestinal flora were analyzed using the LEfSe bioinformatics software.Results Compared with the control samples, all the tested patient samples showed statistically significantdifferences in the number of colonies of 5 bacterial phyla, 5 orders, 8 families, 11 genera, and 14 species(P < 0.05).Conclusion Compared with healthy people, patients with primary liver cancer have significant differencesin the intestinal flora composition. The alteration of the intestinal flora may be correlated with the occurrenceof primary liver cancer, and the intestinal flora may become a novel target for the prevention and treatmentof primary liver cancer.

Primary resistance to crizotinib treatment in a non-small cell lung cancer patient with an EML4-ALK rearrangement:a case report

Crizotinib,a small molecular tyrosine kinase inhibitor,manifests dramatic responses in patients with non-small cell lung cancer with echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase(EML4-ALK)rearrangements.ALK gene point mutation is the primary mechanism of acquired crizotinib resistance;however,the intrinsic mechanism is not fully understood.Here,we report a patient with a low mutant allele fraction(MAF)of EML4-ALK rearrangement,who experienced primary resistance to crizotinib treatment.The patient was a 66-year-old Chinese man,who had a history of metastatic lung cancer and was treated with first-and third-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR TKIs).After 14 months of osimertinib treatment,his disease progressed,and next-generation sequencing was performed from a liquid biopsy of the patient’s blood.An EML4-ALK rearrangement was found and crizotinib was administered.The patient’s lung lesions continued to progress after one month of crizotinib treatment,and pemetrexed-bevacizumab was initiated.After two cycles of chemotherapy,the metastatic cancers shrunk,and the patient maintained stable disease at his last follow-up.EML4-ALK rearrangements can happen in patients with EGFR-positive NSCLC,after acquired resistance to EGFR TKI treatment.The EGFR T790M and C797G mutations occur in cis is a critical mechanism of resistance to osimertinib therapy.The MAF of EML4-ALK rearrangements in cancer cells might be a predictive factor for crizotinib treatment.

Clinical Observation of Bevacizumab Combined with S-1 in the Treatment of Pretreated Advanced Esophageal Carcinoma

Objective To investigate the clinical effects and safety of bevacizumab combined with S-1 as the second-line treatment of recurrent and/or metastatic esophageal cancer after chemoradiation. Methods Patients with recurrent or metastatic esophageal cancer after chemoradiation were treated with bevacizumab and S-1. Bevacizumab was used by intravenous infusion, 7.5mg/kg body weight on day 1; S-1 was used by oral at 80mg/m^2·d on day 1-14, 21 days as a cycle of treatment and repeated until either progressive disease or intolerable toxicity occurred. Chest CT were performed and RECIST 1.1 was used for response evaluation. Kaplan-Meier method was used for survival analysis. Side effects were recorded and analyzed. Results Totally 78 patients were enrolled in the study, including 67 squamous cell carcinoma and 11 adenocarcinoma histologically. The overall response(CR+PR) rate was 22.4%(17/76) and disease control(CR+PR+SD) rate was 61.8%(47/76) respectively. The median follow-up time was 20 months(range from 9 to 44 months). The median progression-free survival(PFS) was 4.9 months(95% CI 4.4-5.5) and the median overall survival(OS) was 8.1 months(95% CI 7.6-9.2). The median PFS and OS of patients with metastasis diseases were 6.2 months(95% CI 3.3 to 6.3) and 8.5 months(95% CI 5.8 to 11.2), where PFS was longer than that of patients with local regional recurrence(median 5.0 months, 95% CI 3.0 to 5.5, P=0.017) and OS was longer than that of patients with regional disease and metastasis(median 8.0 months, 95% CI 4.6 to 9.5, P=0.010). The common adverse effects were mild to moderate neutropenia(84.2%), grade Ⅰ -Ⅱ hand and foot syndrome(51.3%), grade Ⅰ -Ⅱ nausea(48.7%), mild epistaxis(30.1%) and mild vomiting(14.5%). Esophageal bleeding occurred in 7.9% of patients. One patient(1.3%) died from massive bleeding which was caused by esophageal perforation. Conclusion Bevacizumab combined with S-1 was effective and safe for esophageal cancer patients who had recurrent or metastatic diseases after chemoradiation.

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in early focal cerebral infarction following urokinase thrombolysis in rats

Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion,and is associated with cerebral microvascular permeability,blood-brain barrier destruction,inflammatory cell infiltration and brain edema.Matrix metalloproteinase-9 also likely participates in thrombolysis.A rat model of middle cerebral artery infarction was established by injecting autologous blood clots into the internal carotid artery.At 3 hours following model induction,urokinase was injected into the caudal vein.Decreased neurological severity score,reduced infarct volume,and increased expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were observed in the cerebral cortex 24 hours after urokinase thrombolysis.These results suggest that urokinase can suppress damage in the acute-early stage of cerebral infarction.

Sorafenib in Liver Function Impaired Advanced Hepatocellular Carcinoma

Objective To explore the efficacy and safty of sorafenib in Child-Pugh class B to class C hepatocellular carcinoma(HCC).Methods In this three-center open-label study from November 2011 to May 2013,we randomly assigned 189 patients with advanced Child-Pugh class B or C HCC patients into two groups,one group with 95 patient to receive sorafenib(400 mg a time,twice a day) and the other group with 94 patients to receive best supportive care.The primary end points were progression-free survival and overall survival.Results The median progression-free survival was 2.2 months and 1.9 months in the sorafenib group and best supportive care group respectively(Hazard ratio in the sorafenib group,0.55;95% confidence interval,0.40-0.75;P=0.002).The median overall survival was 4.0 months and 3.5 months in the sorafenib group and best supportive care group respectively(Hazard ratio in the sorafenib group,0.48;95% confidence interval,0.35-0.68;P<0.001).The main adverse effect of sorafenib was rash and acne of the skin(in 51.7% patients).The incidences of severe rash,diarrhea,and dry skin were 5.6%,5.6%,and 2.2% in the sorafenib group.One patient reached partial response in the sorafenib group.Conclusions Sorafenib is safe in patients with liver function impaired advanced HCC.It is effective in terms of progression-free survival and overall survival compared with best supportive care.Liver functions are the important predictive factors.

Treatment of Skin Reaction Induced by Nivolumab Combined with Radiotherapy in Non-small Cell Lung Cancer:A Case Report

Skin reaction or dermatological toxicities induced by immunotherapy is common.It usually manifests skin rash or erythema and can be cured by skin lotion or steroid.Nivolumab,a human IgG4 programmed cell death protein 1(PD-1)inhibitor,blocks T cells activation preventing signal and allows the immune system to clear cancer cells.Nivolumab was approved in the second-line therapy in squamous cell lung cancer by FDA,with less than 10%unusual skin reaction,like sensory neuropathy,peeling skin,erythema multiforme,vitiligo,and psoriasis.Radiotherapy could aggravate this skin reaction through inflammatory response and promotion of immunity.The combined treatment of anti-PD-1 and radiotherapy represented a new promising therapeutic approach in many studies,but the risk of side effects may be high.We reported a patient with advanced squamous cell lung cancer who suffered from serious skin immune-related adverse events when he was treated with nivolumab and radiotherapy.The immune overreaction of the treatment of anti-PD-1 treatment and radiotherapy might cause these serious skin adverse events.Our report warranted careful workup to reduce the risk of side effects by combinative therapy with anti-PD-1 and radiotherapy.

Combination chemotherapy with paclitaxel,cisplatin and fluorouracil for patients with advanced and metastatic gastric or esophagogastric junction adenocarcinoma:a multicenter prospective study

Objective:To evaluate the efficacy and toxicity of the combination regimen of paclitaxel,cisplatin and 5-FU(PCF) as first-line or second-line therapy in patients with advanced gastric and esophagogastric junction(EGJ) adenocarcinoma in China.Methods:The patients were treated with paclitaxel 150mg/m2 on d1;fractionated cisplatin 15mg/m 2 and continuous infusion 5-FU 600mg/(m2·d) intravenously on d1-d5 of a 21-d cycle until disease progression or unacceptable toxicities.Results:Seventy-five patients have been enrolled,among which,41 received PCF regimen as the first-line therapy(group A) and 34 received the regimen as the second-line therapy(group B) with the median age of 59 years old and Karnofsky performance status(KPS) score ≥80.Toxicities were analyzed in all 75 patients.Seventy-one patients were evaluable for efficacy.The median overall survival(mOS) was 12.0 months(95% CI:7.9-16.2 months) in group A and 7.3 months(95% CI:4.3-10.3 months) in group B,respectively.The median progression-free survival(mPFS) was 5.7 months(95% CI:4.1-7.2 months) and 5.0 months(95% CI:3.1-6.9 months),respectively.The response rate(CR+PR) was 40%(16/40;95% CI:24.9-56.7%) in group A and 22.6%(7/31;95% CI:9.6-41.1%) in group B.Major grade 3 or 4 adverse events include neutropenia(41.3%),febrile neutropenia(9.3%),nausea/anorexia(10.7%),and vomiting(5.3%).There was no treatment-related death.Conclusions:The combination chemotherapy with PCF is active and tolerable as first-line and secondline therapy in Chinese patients with advanced gastric and EGJ adenocarcinoma.The response and survival of PCF are same as those of DCF,but the tolerance is much better.

Bridging therapy and direct mechanical thrombectomy in the treatment of cardiogenic cerebral infarction with anterior circulation macrovascular occlusion

BACKGROUND Intravenous thrombolysis is an important treatment for cerebral infarction.However,it is difficult to achieve good results if the patient is complicated with anterior circulation macrovascular occlusion.In addition,the vascular recanalization rate is low,so mechanical thrombectomy,that is,bridging therapy,is needed AIM To investigate the efficacy and safety of bridging therapy and direct mechanical thrombectomy in the treatment of cardiogenic cerebral infarction with anterior circulation macrovascular occlusion.METHODS Ninety-six patients in our hospital with cardiogenic cerebral infarction with anterior circulation macrovascular occlusion from January 2017 to July 2020 were divided into a direct thrombectomy group(n=48)and a bridging group(n=48).Direct mechanical thrombectomy was performed in the direct thrombectomy group,and bridging therapy was used in the bridging treatment group.Comparisons were performed for the treatment data of the two groups(from admission to imaging examination,from admission to arterial puncture,from arterial puncture to vascular recanalization,and from admission to vascular recanalization),vascular recanalization rate,National Institutes of Health Stroke Scale(NIHSS)and Glasgow Coma Scale(GCS)scores before and after treatment,prognosis and incidence of adverse events.RESULTS In the direct thrombectomy group,the time from admission to imaging examination was 24.32±8.61 min,from admission to arterial puncture was 95.56±37.55 min,from arterial puncture to vascular recanalization was 54.29±21.38 min,and from admission to revascularization was 156.88±45.51 min,and the corresponding times in the bridging treatment group were 25.38±9.33 min,100.45±39.30 min,58.14±25.56 min,and 161.23±51.15 min;there were no significant differences between groups(P=0.564,0.535,0.426,and 0.661,respectively).There was no significant difference in the recanalization rate between the direct thrombectomy group(79.17%)and the bridging group(75.00%)(P=0.627).There were no significant differences between the direct thrombectomy group(16.69±4.91 and 12.12±2.07)and the bridging group(7.13±1.23) and(14.40±0.59)in preoperative NIHSS score and GCS score(P=0.200 and 0.203,respectively).After the operation,the NIHSS scores in both groups were lower than those before the operation,and the GCS scores were higher than those before the operation.There was no significant difference in NIHSS and GCS scores between the direct thrombectomy group(6.91±1.10 and 14.19±0.65)and the bridging group(7.13±1.23 and 14.40±0.59)(P=0.358 and 0.101,respectively).There was no significant difference in the proportion of patients who achieved a good prognosis between the direct thrombectomy group(52.08%)and the bridging group(50.008%)(P=0.838).There was no significant difference in the incidence of adverse events between the direct thrombectomy group(6.25%)and the bridging group(8.33%)(P=0.913).CONCLUSION Bridging therapy and direct mechanical thrombectomy can safely treat cardiogenic cerebral infarction with anterior circulation macrovascular occlusion,achieve good vascular recanalization effects and prognoses,and improve the neurological function of patients.

Rapamycin liposome gutta inhibiting fungal keratitis of rats

AIM: To study the therapeutic effect of rapamycin liposome eyedrops on fungal keratitis(FK) and its effect on the expression of monocyte chemotactic protein-1(MCP-1).METHODS: This study adopted the thin film dispersion method to prepare rapamycin liposomes eyedrops, as well as used the orthogonal design to analyze and study main influencing factors that affected the quality of liposomes. Totally 96 healthy Wistar rats were randomly divided into four groups: normal control group(A), FK blank control group(B), FK blank liposomes control group(C), and 30 FK rapamycin liposome treatment group(D). Groups B, C, and D were first prepared as FK animal models. The corneal response was recorded in details on day 1, 3, 5, 7, and 14 after modeling. Six rats were obtained and immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) were used to detect the expression of MCP-1 protein and mRNA, respectively.RESULTS: The severity of corneal lesions in the rapamycin treatment group was reduced, and the clinical score of the slit lamp examination was lower than that of Groups B and C(P<0.01). The expression of MCP-1 in rapamycin treatment group was significantly inhibited, comparing to that of groups B and C(P<0.01).CONCLUSION: Liposome is a good drug carrier for rapamycin. Rapamycin has a good therapeutic effect on FK. It can reduce FK fungal burden and significantly inhibit the expression of MCP-1 protein and mRNA.

Milk fat globule epithelial growth factorⅧ(MFG-E8)sustains survival of cancer cells by prompting tumor angiogenesis and suppressing host immunities

Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progression and survival. MFG-E8 contains a signal sequence for secretion, two epidermal growth factor(EGF)-like domains at the NH2 terminus and two discoidin domains with blood-clotting factor V/factor Ⅷ(C1 and C2) at the COOH terminus. The second EGF domain contains an arginine-glycine-aspartic(RGD) integrin-binding motif that engages α_vβ_5 integrins to facilitate cell adhesion and induce integrinmediated signal transduction. Integrin α_vβ_3 associates with VEGF receptor 2, engagement of integrins can promote angiogenesis, which plays key roles in growth, proliferation, and survival of cancer cells. VEGF stimulates the expression of α_vβ_3 and α_vβ_5 integrins on angiogenic vasculature, thereby potentiating effects of VEGF receptor engagement. Mice expressing a mutant form of α_vβ_3 integrin are unable to undergo tyrosine phosphorylation, confirming the important role that this integrin plays in pathological angiogenesis and providing important mechanistic insights. The C-terminus discoidin-like domains promote binding to membrane phospholipids, functioning close to VEGF like angiogenesis. MFG-E8 is an opsonin for apoptotic cells, and it acts as a bridging protein between apoptotic cells and phagocytes. It also influences cell immunities by altering CD4^+ and/or CD8^+ cells. Antibody or small peptide works with MFG-E8 at different functional sites or interacts with EGF-like domains and/or discoidin-like domains may play an important role in anti-angiogenesis or immune restoration. Altering the structures and/or functions of MFG-E8 and/or its domains is promising for development of novel anti-cancer strategies.

Modified Approach for Establishing Filament-induced Permanent Middle Cerebral Artery Occlusion Rats and Mice Models

BRAIN ischemia stroke is a devastating disease,with more than 10％ stroke patients either severely disabled or dead.Although rodent filament middle cerebral artery occlusion (MCAO)model can mimic human brain ischemic stroke well,its wide use was restricted by difficulty in surgery,especially in ligating pterygopalatineartery (PPA).Twenty-seven male Sprague-Dawley rats were randomly divided into A,B,C groups (n=9).All the rats were performed MCAO surgery with sutures of difference sizes.Group A used 4-0 blocking suture plus ipsilateral PPA block,group B used 3-0 blocking suture plus ipsilateral common carotid artery (CCA) block,and group C used 3-0 suture plus ipsilateral PPA block.Twenty-seven male C57BL/6 wild type mice were also randomly divided into a,b,c groups.Group a used 5-0blocking suture plus ipsilateral PPA block,group b used 6-0blocking suture plus ipsilateral CCA block,group c use 6-0suture plus ipsilateral PPA block.

Acute myocarditis presenting as accelerated junctional rhythm in Graves’disease:A case report

BACKGROUND Acute myocarditis is an acute myocardium injury that manifests as arrhythmia,dyspnea,and elevated cardiac enzymes.Acute myocarditis is usually caused by a viral infection but can sometimes be caused by autoimmunity.Graves’disease is an autoimmune disease that is a rare etiology of acute myocarditis.Accelerated junctional rhythm is also a rare manifestation of acute myocarditis in adults.CASE SUMMARY A rare case of new-onset Graves’disease combined with acute myocarditis and thyrotoxic periodic paralysis is reported.The patient was a 25-year-old young man who suddenly became paralyzed and felt palpitations and dyspnea.He was then sent to our emergency department(ED).Upon arrival,electrocardiography revealed an accelerated junctional rhythm and ST-segment depression in all leads,and laboratory findings showed extreme hypokalemia and elevated troponin I,with the troponin I level being 0.32 ng/mL(reference range,0-0.06 ng/mL).Coronary computer tomography angiography was performed,and there were no abnormal findings in the coronary arteries.Subsequently,the patient was admitted to the ED ward,where further testing revealed Graves’disease,along with continued elevated cardiac enzyme levels and B-type natriuretic peptide(BNP)levels.The troponin I level was 0.24 ng/mL after admission.All of the echocardiography results were normal:Left atrium 35 mm,left ventricle 48 mm,end-diastolic volume 102 mL,right atrium 39 mm×47 mm,right ventricle 25 mm,and ejection fraction 60%.Cardiac magnetic resonance was performed on the fifth day of admission,revealing myocardial edema in the lateral wall and intramyocardial and subepicardial late gadolinium enhancement in the lateral apex,anterior lateral,and inferior lateral segments of the ventricle.The patient refused to undergo an endomyocardial biopsy.After 6 d,the patient’s cardiac enzymes,BNP,potassium,and electrocardiography returned to normal.After the patient’s symptoms were relieved,he was discharged from the hospital.During a 6-mo follow-up,the patient was asymptomatic and subjected to thyroid function,liver function,kidney function,troponin I,and electrocardiograph routine tests for medicine adjustments.The hyperthyroid state was controlled.CONCLUSION Acute myocarditis is a rare manifestation of Graves’disease.Accelerated junctional rhythm is also a rare manifestation of acute myocarditis in adults.When the reason for hypokalemia and elevated cardiac enzymes in patients is unknown,cardiologists should consider Graves’disease and also pay attention to accelerated junctional rhythm.

Chronic colchicine poisoning with neuromyopathy,gastric ulcers and myelosuppression in a gout patient:A case report

Colchicine has been widely used as an anti-gout medication over the past decades.However,it is less commonly used due to its narrow therapeutic range,meaning that its lethal dose is close to its therapeutic dose.The lethal dose of colchicine is considered to be 0.8 mg/kg.As chronic colchicine poisoning has multiple manifestations,it poses a challenge in the clinician’s differential diagnosis.Historically,the drug was important in treating gout;however,clinical studies are currently underway regarding the use of colchicine in patients with coronavirus disease 2019 as well as its use in coronary artery disease,making this drug more important in clinical practice.CASE SUMMARY A 61-year-old male with a history of gout and chronic colchicine intake was admitted to our Emergency Department due to numbness and weakness of the lower limbs.The patient reported a history of colchicine intake for 23 years.After thorough examination,he was diagnosed with colchicine poisoning,manifesting as neuromyopathy,multiple gastric ulcers and myelosuppression.We advised him to stop taking colchicine and drinking alcohol.We also provided a prescription of lansoprazole and mecobalamin,and then asked him to return to the clinic for re-examination.The patient was followed up for 3-mo during which time his gout symptoms were controlled to the point where he was asymptomatic.CONCLUSION Colchicine overdose can mimic the clinical manifestations of several conditions.Physicians easily pay attention to the disease while ignoring the cause of the disease.Thus,the patient’s medication history should never be ignored.

^(125)I粒子组织间植入对小鼠LEWIS肺癌Egr-1及Caspase-3表达影响的实验研究(英文)

Objective:The aim of our study was to explore the influence of interstitial brachytherapy with 125I seeds on Caspase-3 and Egr-1 expressions of Lewis lung carcinoma in C57BL mice.Methods:Model mice of C57BL were planted with Lewis lung cells (LLC) and divided into the treatment group (n=18) and the control group (n=17).In each mouse of the treatment group,two BT-125-1 Model 125I seeds with apparent activity of 9.25 MBq were implanted into the tumor;whereas in each mouse of the control group two dummy seeds were implanted.The mice survival rates of both groups were recorded after 21 days.The tumor weights and dimensions of survived mice were measured,and the tumor volume inhibition rate was calculated.T-test was performed to compare differences of tumor weights and volumes between these two groups.Routine pathological slides of tumor tissue were observed under light microscope.The expression of Caspase-3 was detected by immunohistochemical method and the expression of Egr-1 was detected by RT-PCR method.Results:The survival rates were 88.88% in the treatment group and 70.59% in the control group,the difference had no statistical significance (P > 0.05).The tumor volume inhibition rate was 71.12%.Pathological examination showed degeneration and necrosis of cancer cells at the site nearby the seed in the treated group,but the tumor cells alive were still presented nearby the seed in the control group.The expressions of Caspase-3 and Egr-1 in the treated group were higher than those in the control group (t=12.825,P < 0.01;t=7.039,P < 0.01;respectively).Conclusion:The interstitial brachytherapy with 125I seeds could significantly inhibit the growth of Lewis lung carcinoma of mice.The possible mechanism may be that 125I interstitial brachytherapy can enhance the expressions of Egr-1 and Caspase-3,which could induce tumor cellular apoptosis.

Correlation analysis of breast fibroadenoma and the intestinal flora based on 16S rRNA sequencing

Objective To analyze the characteristics of the intestinal microflora in patients with breast fibroadenoma using 16S ribosomal RNA(rRNA)high-throughput sequencing.Methods Fecal samples from 20 patients with breast fibroadenoma and 36 healthy subjects were randomly collected and analyzed using high-throughput sequencing technology for 16S rRNA V4 region sequencing,and the alpha diversity(Chao index,Shannon index)was calculated using Mothur(v.1.39.5)software.Beta diversity was analyzed using QIIME(v1.80).SPSS software(version 23.0)and the t-test of two independent samples were used to analyze differences in the abundance of bacteria between the two groups.Results Compared with that in the healthy control group,theαdiversity of the intestinal microflora in breast fibroadenoma patients increased,but the difference was not statistically significant(P>0.05).At the phylum level,significant differences were observed between the two groups.The abundance of Firmicutes was higher in the breast fibroadenoma group(P<0.05),whereas the abundance of Synergistetes was higher in the healthy control group(P<0.005).A total of five bacterial genera showed significant differences between the two groups:the breast fibroadenoma group showed higher levels of Bautia(P<0.005),Coprococcus(P<0.005),Roseburia(P<0.05),and Ruminococcus(P<0.005),whereas Sutterella was more abundant in the healthy control group than in the breast fibroadenoma group(P<0.05).Conclusion The diversity and abundance of the intestinal flora in patients with breast fibroadenoma are significantly different from those in healthy subjects,suggesting that an imbalance in the intestinal flora is correlated with the occurrence of breast fibroadenoma.

Multidisciplinary Treatment for Severe Secondary Raynaud’s Phenomenon:A Case Report

Raynaud’s phenomenon is a symptom complex manifested as intermittent fingertip ischemia caused by cold or other sympathetic drivers.Secondary Raynaud’s phenomenon is often more severe and could even lead to finger ulceration,making it particularly complicated to treat.We describe a case of severe Raynaud’s phenomenon secondary to subclinical hypothyroidism lasting for more than 6 hours in a 65-year-old woman.The patient was also diagnosed with hypothyroidism,epilepsy,and secondary soft tissue infection of the right middle and ring fingers.After careful multidisciplinary consultation and discussion,the patient received vasodilation,anticoagulation,thyroxine supplementation,stellate ganglion block,hyperbaric oxygen therapy and debridement.The patient responded well to the medication,avoiding amputation or obviously dysfunction.Multidisciplinary team gathering the doctors from different departments proposes appropriate strategies for patients with severe Raynaud’s phenomenon and could improve the prognosis and satisfaction of patient effectively.

Mechanism of miR-214-mediated HIF1 α and KIM1 signaling pathway in rats with ischemic acute kidney injury

Objective:To investigate the mechanism of mir-214-mediated HIF1 alpha and KIM1 signaling pathways in rats with ischemic acute kidney injury. Methods:Rats were divided into three groups according to the difference of the preparation model, 16 in each group, sham operation group, IAKI group and miR-214 group.The rats in the latter two groups were established with ischemic acute kidney injury. After 48 hours, three groups of rats were treated with orbital venous blood. Urine was collected, biochemical parameters and KIM1 expression were detected. After using Masson's Trichrome, TUNEL, immunoblotting and PCR, renal histopathology, apoptosis of glomerular epithelial cells and expression of HIF1α, KIM1 protein and mRNA in renal tissues were detected. Results:The biochemical parameters of rats in the IAKI group included Scr, BUN and 24hUTP, which were higher than the previous group (P<0.05). The MIR-214 group was higher than the IAKI group. The sham operation group had intact renal tissue structure and good renal tubular and glomeruli. The IAKIgroup had increased glomerular interstitial, renal interstitial widening and inflammation. Severe infiltration, severe tubular atrophy, miR-214 group and IAKIgroup, renal interstitial inflammation increased, hardness increased, tubular atrophy more serious;black yellow is apoptotic cells, IAKIgroup rat renal tubular epithelial cell apoptosis The most serious, the degree of apoptosis was significantly higher than the sham operation group;the degree of apoptosis of renal tubular epithelial cells was increased in the miR-214 group compared with the IAKIgroup, and high levels of miR-214 could accelerate the apoptosis of epithelial cellsThe HIF1α and KIM1 proteins in the IAKI group were higher than those in the Previous group(P<0.05). The above indexes in the mir-214 group were better than those in the IAKI group(P<0.05). The HIF1α and KIM1 mRNA in the IAKI group were higher than in the sham operation group, and the above indicators in the mir-214 group(P<0.05). Better than the IAKI group(P<0.05);Conclusions:The increase of miR-214 accelerates the apoptosis of glomerular epithelial cells, impaired renal tissue damage, and mediates the elevation of HIF1α and KIM1, further aggravating the condition of IAKI rats.