BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth fac...BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth factors-binding proteins 2(IGFBP2),secreted phosphoprotein 1(SPP1),thrombospondin 1 protein(TSP1)and D-dimer levels in addition to currently used biomarkers[cancer antigen 125(CA125)and human epididymis protein 4(HE4)]in the diagnosis of epithelial OC(EOC).METHODS This is a case-control study that included fifty females diagnosed with EOC,10 females with benign ovarian masses recruited from the Egyptian National Cancer Institute,and 30 healthy females as a control group.All subjects were assessed for serum HE4,CA125,IGFBP2,TSP1 and SPP1 measurement by enzyme-linkedimmunosorbent assay.RESULTS There was a statistically significant difference in serum levels between EOC,benign ovarian masses,and healthy control groups regarding CA125 and SPP1(P<0.001 for both markers),while HE4 and IGFBP2 increased significantly in EOC compared to healthy control groups(P<0.001 for all markers)with no significant difference between EOC and benign ovarian masses groups.However,there was no statistically significant difference among EOC,benign ovarian masses,and healthy control groups regarding the TSP1 serum levels(P=0.051).Receiver operating characteristic analysis revealed that combined assessment of SPP1 with CA125 or TSP1 increased the diagnosis of EOC patients to a sensitivity,specificity,and area under curve of(93.3%,100%,0.968;respectively,P<0.001).CONCLUSION SPP1 may be a potential marker for the differentiation between benign and malignant ovarian masses,while IGFBP2 can differentiate between healthy females and females with ovarian masses.Combining SPP1 with CA125 or TSP1 provides high sensitivity and specificity for the detection of EOC patients.展开更多
Objective： The purpose of this study was to study the clinical, imaging characters and pathological characteristics of esophageal sarcomatoid carcinoma. Methods： We reviewed 23 cases of esophageal sarcomatoid carcin...Objective： The purpose of this study was to study the clinical, imaging characters and pathological characteristics of esophageal sarcomatoid carcinoma. Methods： We reviewed 23 cases of esophageal sarcomatoid carcinoma from Janu ary 2006 to December 2013 in four hospitals. The data of patients who were esophageal sarcomatoid carcinoma operated were retrospectively analyzed. All cases had completed upper gastrointestinal barium images materials and 14 of these cases had completed CT images materials. Upper gastrointestinal barium images and CT imaging features include tumor location, size, shape, and strengthen, etc. The biological parameters of lesions including the express of cytokeratin AE1/AE3, 34E12,, Vimentin, desmin, Actin, S100 and Ki67 detected by immunhistochemical UltraSensitiveTM SP method （n = 23）, and the patients＇ data of contrastographic picture （n = 23）, imaging characters of CT scan （n = 14）, and their relationship were studied. Results： Upper gastrointestinal barium images, CT imaging and gastrointestinal fiberscopy revealed Iobulated intraluminal filling defect 0.4 cm to 5.7 cm x 3.5 cmx 1.3 cm （mean = 3. 7 cm） in the mid （n = 14）, lower （n = 7） and upper （n = 2） intrathoracic esophagus. Among 23 cases of esophageal sarcomatoid carcinoma, 19 patients were of mushroom type, 2 patients was of ulcer type, and 2 patients were of medulla type; 19 patients were pedunculated, and 4 patients were no pedunculated （2 patients was of ulcer type）. The tumor surface was relatively smooth and esophageal compliance was maintained. The pathological changes of esophagus such as lightly locked, rigid wall nomanifest partly, esophageal lumens expand partly, major filling sublobe defect could be shown through contrast medium. Normal esophagus was no unpack obviously over pathological changes. Enhanced computed tomography showed tumors in the intrathoracic esophagus and 8 lymph nodes metastases in 3 cases. Histologically, carcinomatous and sarcomatous components coexist. Microscopically, the tumor comprised poorly differentiated squamous cell carcinoma and spindleshaped cells resembling leiomyosarcoma. Immu nohistochemically, spindleshaped sarcomatous cells displayed weekly positive reaction to cytokeratin AE1/AE3. Transitional zone was seen between sarcomatous and carcinomatous elements in 5 cases. The 17 lymph nodes metastases in 5 cases （53 lymph nodes） among 23 cases esophageal sarcomatoid carcinoma （187 lymph nodes） were observed. Conclusion： The clinical and radiologic features of esophageal sarcomatoid carcinoma overlap with those of other esophageal neoplasms. There are the radiologic imaging changes such as a large, intraluminal, polypoid mass, major filling sublobe defect and pedicle skin flap tumor in esophageal lumen, esophageal lumen extension partly, dissepiment rigidity wall no obviously, etc. Histologically, carcinomatous and sarcomatous components coexist and the biphasic pattern is the key diagnostic feature. However, esophageal sarcomatoid carcinoma has a more favorable prognosis than other malignant esophageal neoplasms. Immunohistochemical staining seems necessary to distinguish these lesions from other esophageal neoplasms.展开更多
Objective:To describe the prevalence of antiphospholipid antibodies in coronavirus disease-19(COVID-19)and to find potential associations between antiphospholipid antibody positivity and clinical outcomes.Methods:From...Objective:To describe the prevalence of antiphospholipid antibodies in coronavirus disease-19(COVID-19)and to find potential associations between antiphospholipid antibody positivity and clinical outcomes.Methods:From September to November 2020,clinical and laboratory data were collected from 50 COVID-19 patients hospitalized at Saiful Anwar General Hospital in Malang,Indonesia.Antiphospholipid antibodies were measured by finding Ig M anti-β2 glycoprotein,lupus anticoagulant,and Ig M/Ig G anticardiolipin.Clinical characteristics,thrombotic events,ICU admission,and mortality during hospitalization were recorded.Disease severity was defined by the Guidelines for the Prevention and Control of COVID-19,Indonesia.Results:Among 50 patients,5 patients(10.0%)were positive for antiphospholipid antibodies:4 patients(80.0%)had Ig M anti-β2 glycoprotein and 1 patient had Ig G anti-cardiolipin(20.0%)and Ig M anti-cardiolipin(20.0%),none of lupus anticoagulant was detected.Antiphospholipid antibodies were associated with anosmia(OR 8.1;95%CI 1.1-57.9;P=0.018),nausea and vomiting(OR 12.4;95%CI 1.2-122.6;P=0.010),diarrhea(OR 9.8;95%CI 1.3-70.9;P=0.010),cardiovascular disease(OR 1.4;95%CI 1.0-1.9;P=0.001),chronic kidney disease(OR 12.0;95%CI 1.6-90.1;P=0.05),acute coronary syndrome(OR 29.3;95%CI 2.0-423.7;P=0.001),moderate(OR 0.11;95%CI 0.01-1.10;P=0.031)and severe(OR 18.5;95%CI 1.8-188.4;P=0.002)disease severity,and in-hospital mortality(OR 8.1;95%CI 1.1-57.9;P=0.018).However,there is no correlation between the presence of antiphospholipid antibody and ICU admission.Conclusions:In summary,the prevalence of antiphospholipid antibodies in COVID-19 patients is low,mainly against Ig M anticardiolipin,and is associated with an acute coronary syndrome,gastrointestinal manifestations,moderate and severe disease severity,and increased risk of mortality.展开更多
AIM： To re-evaluate the diagnostic criteria of insulin resistance hepatic iron overload based on clinical, biochemical and histopathological findings. METHODS： We studied 81 patients with hepatic iron overload not e...AIM： To re-evaluate the diagnostic criteria of insulin resistance hepatic iron overload based on clinical, biochemical and histopathological findings. METHODS： We studied 81 patients with hepatic iron overload not explained by known genetic and acquired causes. The metabolic syndrome （MS） was defined according to ATPⅢ criteria. Iron overload was assessed by liver biopsy. Liver histology was evaluated by Ishak＇s score and iron accumulation by Deugnier＇s score; steatosis was diagnosed when present in ≥ 5% of hepatooltes. RESULTS： According to transferrin saturation levels, we observed significant differences in the amount of hepatic iron overload and iron distribution, as well as the number of metabolic abnormalities. Using Receiving Operating Curve analysis, we found that the presence of two components of the MS differentiated two groups with a statistically significant different hepatic iron overload （P 〈 0.0001）. Patients with ≥2 metabolic alterations and steatosis had lower amount of hepatic iron, lower transferrin saturation and higher sinusoidal iron than patients with 〈 2 MS components and absence of steatosis. CONCLUSION： In our patients, the presence of ≥ 2 alterations of the MS and hepatic steatosis was associated with a moderate form of iron overload with a prevalent sinusoidal distribution and a normal transferrin saturation, suggesting the existence of a peculiar pathogenetic mechanism of iron accumulation. These patients may have the typical dysmetabolic iron overload syndrome. By contrast, patients with transferrin saturation ≥ 60% had more severe iron overload, few or no metabolic abnormalities and a hemochromatosis-like pattern of iron overload.展开更多
Objectives: Serous ovarian carcinoma (SOC) is the commonest ovarian carcinoma type with poor prognosis due to early metastasis and first presentation with advanced stage. In this work, we investigated serum level of G...Objectives: Serous ovarian carcinoma (SOC) is the commonest ovarian carcinoma type with poor prognosis due to early metastasis and first presentation with advanced stage. In this work, we investigated serum level of Galactin-1 (Gal-1) and its tissue immunohistochemical expression in SOC patients at different stages trying to find out its significance as a diagnostic and prognostic marker. Patients and methods: The study included 95 females I-Control group: Twenty five healthy females;II-Patients group: Seventy females diagnosed as SOC at different stages;Stage I: 8 cases, Stage II: 12 cases, Stage III: 32 cases and Stage VI:18 cases. Serum Galectin-1 and CA-125 were measured by ELIZA and tissue Galectin-1 was assessed by immunohistochemistry. All patients were followed for up to 3 years after surgery. Results: Serum Gal-1 and CA-125 levels were significantly higehr in SOC patients compared to controls (p 0.001). We found a direct positive statistically significant correlation between serum Gal-1 and CA125 levels (p 0.001). Serum Gal-1 at cut off value > 135 ng/ml was superior to CA-125 a cut off value > 49 u/ml with sensitivity, specificity of 100%, vs 88.57, 96% for CA-125. Serum Gal-1 was significantly associated with tumor stage (p 0.001). Immunohistochemistry showed that patients with strong Gal-1 expression had higher serum level (p = 0.002). Stromal and tumor Gal-1 expression were significantly correlated with tumor grade (p 0.001) and stage (p = 0.001). Serum Gal-1, CA-125 and IHC Gal-1 expression were associated with poor survival (p 0.001, p = 0.009 and p = 0.002) respectively. Conclusion: Serum Gal-1 and its tissue IHC expression are useful diagnostic and prognostic markers for SOC patients.展开更多
BACKGROUND Colorectal cancer is the third most common malignancy and the fourth leading cause of cancer-related deaths worldwide.Several studies have shown an association between gut microbiota and colorectal cancer.G...BACKGROUND Colorectal cancer is the third most common malignancy and the fourth leading cause of cancer-related deaths worldwide.Several studies have shown an association between gut microbiota and colorectal cancer.Gut microbiota is unique and can be influenced by geographic factors and habits.This study aimed to determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer.AIM To determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer in Indonesia.METHODS This case-control study included 59 subjects(35 colorectal cancer patients and 24 non-colorectal cancer patients indicated for colonoscopy at Dr.Cipto Mangunkusumo Gastrointestinal Endoscopy Center and Fatmawati Hospital.Microbiota examination was performed using 16S rRNA sequencing.Bioinformatics analysis was performed using the wf-metagenomics pipeline from EPI2Me-Labs(Oxford Nanopore Technologies platform).RESULTS Patients with colorectal cancer had a higher median index value on the Shannon index(3.28 vs 2.82,P>0.05)and a lower value on the Simpson index(0.050 vs 0.060,P>0.05).Significant differences in beta diversity were observed at the genus(P=0.002)and species levels(P=0.001).Firmicutes,Proteobacteria,Bacteroidetes,and Fusobacteria were the dominant phyla.The genera Bacteroides,Campylobacter,Peptostreptococcus,and Parvimonas were found more frequently in colorectal cancer,while Faecalibacterium,Haemophilus,and Phocaeicola were more frequently found in non-colorectal cancer.The relative abundance of Fusobacterium nucleatum,Bacteroides fragilis,Enterococcus faecalis,Campylobacter hominis,and Enterococcus faecalis species was significantly elevated in patients with colorectal cancer.Meanwhile,Faecalibacterium prausnitzii,Faecalibacterium duncaniae,and Prevotella copri were more commonly found in non-colorectal cancer.CONCLUSION Patients with colorectal cancer exhibit distinct differences in the composition and diversity of their colonic mucosal microbiota compared to those with non-colorectal cancer.This study was reviewed and approved by the Ethics Committee of Faculty of Medicine,Universitas Indonesia(No.KET-1517/UN2.F1/ETIK/PPM.00.02/2023).展开更多
The arterial pulse tapping artifact,known as Aslanger’s sign,is an electrocardiographic artifact resulting from the transmission of arterial pulsation onto the limb electrodes of the standard 12-lead electrocardiogra...The arterial pulse tapping artifact,known as Aslanger’s sign,is an electrocardiographic artifact resulting from the transmission of arterial pulsation onto the limb electrodes of the standard 12-lead electrocardiograph(ECG)which are placed near the radial or posterior tibial arteries.[1-16]This electromechanical artifact is of cardiac origin and is synchronous with the cardiac cycle.[17]Nearly all reported cases of Aslanger’s sign exhibit an unusual waveform morphology in all 12 leads except one limb lead.[1-14,16]However,we previously reported a case of Aslanger’s sign that showed distorted waveforms from the ST to TP segments observed only in five limb leads among 12 leads.展开更多
BACKGROUND Acute myeloid leukemia(AML)is a complicated disease with uncontrolled hematopoietic precursor proliferation induced by various genetic alterations.Runt-related transcription factor-1(RUNX1)is commonly disru...BACKGROUND Acute myeloid leukemia(AML)is a complicated disease with uncontrolled hematopoietic precursor proliferation induced by various genetic alterations.Runt-related transcription factor-1(RUNX1)is commonly disrupted by chromosomal translocations in hematological malignancies.AIM To characterize RUNX1 gene rearrangements and copy number variations in newly diagnosed adult AML patients,with an emphasis on the impact of clinical and laboratory features on the outcome.METHODS Fluorescence in situ hybridization was used to test RUNX1 gene alterations in 77 newly diagnosed adult AML cases.NPM1,FLT3/ITD,FLT3/TKD,and KIT mutations were tested by PCR.Prognostic clinical and laboratory findings were studied in relation to RUNX1 alterations.RESULTS RUNX1 abnormalities were detected by fluorescence in situ hybridization in 41.6%of patients:20.8%had translocations,22.1%had amplification,and 5.2%had deletion.Translocations prevailed in AML-M2(P=0.019)with a positive expression of myeloperoxidase(P=0.031),whereas deletions dominated in M4 and M5 subtypes(P=0.008)with a positive association with CD64 expression(P=0.05).The modal chromosomal number was higher in cases having amplifications(P=0.007)and lower in those with deletions(P=0.008).RUNX1 abnormalities were associated with complex karyotypes(P<0.001)and were mutually exclusive of NPM1 mutations.After 44 months of follow-up,RUNX1 abnormalities affected neither patients’response to treatment nor overall survival.CONCLUSION RUNX1 abnormalities were mutually exclusive of NPM1 mutations.RUNX1 abnormalities affected neither patients’response to treatment nor overall survival.展开更多
Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significant...Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.展开更多
Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women.Lycium barbarum polysaccharide(LBP)is an extract from the fruits of the traditional Chinese herb,L.barbarum.LBP...Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women.Lycium barbarum polysaccharide(LBP)is an extract from the fruits of the traditional Chinese herb,L.barbarum.LBP is a promising anticancer drug,due to its high activity and low toxicity.Although it has anticancer properties,its mechanisms of action have not been fully established.Ferroptosis,which is a novel anticancer strategy,is a cell death mechanism that relies on iron-dependent lipid reactive oxygen species(ROS)accumulation.In this study,human breast cancer cells(Michigan Cancer Foundation-7(MCF-7)and MD Anderson-Metastatic Breast-231(MDA-MB-231))were treated with LBP.LBP inhibited their viability and proliferation in association with high levels of ferroptosis.Therefore,we aimed to ascertain whether LBP reduced cell viability through ferroptosis.We found that the structure and function of mitochondria,lipid peroxidation,and expression of solute carrier family 7 member 11(SLC7 A11,also known as x CT,the light-chain subunit of cystine/glutamate antiporter system X_(c)^(-))and glutathione peroxidase 4(GPX4)were altered by LBP.Moreover,the ferroptosis inhibitor,Ferrostatin-1(Fer-1),rescued LBP-induced ferroptosis-associated events including reduced cell viability and glutathione(GSH)production,accumulation of intracellular free divalent iron ions and malondialdehyde(MDA),and down-regulation of the expression of x CT and GPX4.Erastin(x CT inhibitor)and RSL3(GPX4 inhibitor)inhibited the expression of x CT and GPX4,respectively,which was lower after the co-treatment of LBP with Erastin and RSL3.These results suggest that LBP effectively prevents breast cancer cell proliferation and promotes ferroptosis via the x CT/GPX4 pathway.Therefore,LBP exhibits novel anticancer properties by triggering ferroptosis,and may be a potential therapeutic option for breast cancer.展开更多
AIM:To evaluate effective alternative antibiotics in treatment of cefotaxime-resistant spontaneous bacterial peritonitis.METHODS:One hundred cirrhotic patients with spontaneous bacterial peritonitis [ascitic fluid pol...AIM:To evaluate effective alternative antibiotics in treatment of cefotaxime-resistant spontaneous bacterial peritonitis.METHODS:One hundred cirrhotic patients with spontaneous bacterial peritonitis [ascitic fluid polymorphonuclear cell count(PMNLs) ≥ 250 cells/mm 3 at admission] were empirically treated with cefotaxime sodium 2 g/12 h and volume expansion by intravenous human albumin.All patients were subjected to history taking,complete examination,laboratory tests(including a complete blood cell count,prothrombin time,biochemical tests of liver and kidney function,and fresh urine sediment),chest X-ray,a diagnostic abdominal paracentesis,and the sample subjected to total and differential cell count,chemical examination,aerobic and anaerobic cultures.Patients were divided after 2 d by a second ascitic PMNL count into group Ⅰ;patients sensitive to cefotaxime(n = 81),group Ⅱ(n = 19);cases resistant to cefotaxime(less than 25% decrease in ascitic PMNL count).Patients of group Ⅱ were randomly assigned into meropenem(n = 11) or levofloxacin(n = 8) subgroups.All patients performed an end of treatment ascitic PMNL count.Patients were considered improved when:PMNLs decreased to < 250 cells/mm 3,no growth in previously positive culture cases,and improved clinical manifestations with at least 5 d of antibiotic therapy.RESULTS:Age,sex,and Child classes showed no significant difference between group Ⅰ and group Ⅱ.Fever and abdominal pain were the most frequent manifestations and were reported in 82.7% and 80.2% of patients in group Ⅰ and in 94.7% and 84.2% of patients in group Ⅱ,respectively.Patients in group Ⅱ had a more severe ascitic inflammatory response than group Ⅰ and this was demonstrated by more ascitic lactate dehydrogenase(LDH) [median:540 IU/L(range:150-1200 IU/L) vs median:240 IU/L(range:180-500 IU/L),P = 0.000] and PMNL [median:15 000 cell/mm 3(range:957-23 822 cell/mm 3) vs 3400 cell/mm 3(range:695-26 400 cell/mm 3),P = 0.000] counts.Ascitic fluid culture was positive in 32% of cases.Cefotaxime failed in 19% of patients;of these patients,11(100%) responded to meropenem and 6(75%) responded to levofloxacin.Two patients with failed levofloxacin therapy were treated according to the in vitro culture and sensitivity(one case was treated with vancomycin and one case was treated with ampicillin/sulbactam).In group Ⅱ the meropenem subgroup had higher LDH(range:108-860 IU/L vs 120-491 IU/L,P = 0.042) and PMNL counts(range:957-23 822 cell/mm 3 vs 957-15 222 cell/mm 3,P = 0.000) at initiation of the alternative antibiotic therapy;there was no significant difference in the studied parameters between patients responsive to meropenem and patients responsive to levofloxacin at the end of therapy(mean ± SD:316.01 ± 104.03PMNLs/mm 3 vs 265.63 ± 69.61 PMNLs/mm 3,P = 0.307).The isolated organisms found in group Ⅱ were;enterococci,acinetobacter,expanded-spectrum β-lactamase producing Escherichia coli,β-lactamase producing Enterobacter and Staphylococcus aureus.CONCLUSION:Empirical treatment with cefotaxime is effective in 81% of cases;meropenem is effective in cefotaxime-resistant cases.展开更多
The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that...The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s disease.In this review,we summarize the possible pathogenic mechanisms of Alzheimer’s disease,focusing on neuroinflammation.We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s disease.Finally,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.展开更多
BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important r...BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important roles in the regulation of biological processes such as cell proliferation and hepatic fibrosis.AIM To assess diffusion-weighted magnetic resonance imaging and miRs in diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.METHODS This prospective study included 208 patients and 82 age-and sex-matched controls who underwent diffusion-weighted magnetic resonance imaging of the abdomen, miR profiling, and liver biopsy. Pathological scoring was classified according to the METAVIR scoring system. The apparent diffusion coefficient (ADC) and miR were calculated and correlated with pathological scoring.RESULTS The ADC value decreased significantly with the progression of fibrosis, from controls(F0) to patients with early fibrosis(F1 and F2) to those with late fibrosis(F3 and F4)(median 1.92, 1.53, and 1.25 × 10^(-3) mm^2/s, respectively)(P = 0.001).The cut-off ADC value used to differentiate patients from controls was 1.83 × 10^(-3) mm^2/s with an area under the curve(AUC) of 0.992. Combining ADC and miR-200 b revealed the highest AUC(0.995) for differentiating patients from controls with an accuracy of 96.9%. The cut-off ADC used to differentiate early fibrosis from late fibrosis was 1.54 × 10^(-3) mm^2/s with an AUC of 0.866. The combination of ADC and miR-200 b revealed the best AUC(0.925) for differentiating early fibrosis from late fibrosis with an accuracy of 80.2%. The ADC correlated with miR-200 b(r =-0.61, P = 0.001), miR-21(r =-0.62, P = 0.001), and miR-29(r = 0.52,P = 0.001).CONCLUSION Combining ADC and miRs offers an alternative surrogate non-invasive diagnostic tool for diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.展开更多
OBJECTIVE： Ulcerative colitis is a chronically recurrent inflammatory bowel disease of unknown origin. In the present study, the effect of ginger （rhizome of Zingiber officinale Roscoe） volatile oil on a rat model ...OBJECTIVE： Ulcerative colitis is a chronically recurrent inflammatory bowel disease of unknown origin. In the present study, the effect of ginger （rhizome of Zingiber officinale Roscoe） volatile oil on a rat model of colitis was evaluated. METHODS： Volatile oil of ginger with doses of 100, 200, and 400 mg/kg, prednisolone （4 mg/kg）, or vehicle were administered orally to groups of male Wistar rats （n = 6） for 5 d. Animals were randomly divided into 6 groups, each group consisting of 6 rats. Colitis was induced by intracolonic instillation of 2 mL of 4% （v/v） acetic acid solution. All rats were sacrificed 24 h later and the tissue injuries were assessed macroscopically and histopathologically. RESULTS： Ginger volatile oil with all doses reduced colon weight/length ratio （P 〈 0.01） and the effects were similar to the reference drugs. Higher oral doses of volatile oil （200 and 400 mg/kg） reduced ulcer severity （P 〈 0.05 and P 〈 0.01）, ulcer area （P 〈 0.01） and ulcer index （P 〈 0.01）. On the other hand, evaluation of microscopic scores showed that the dose of 400 mg/kg of volatile oil was effective to reduce inflammation severity （P 〈 0.01） and inflammation extent （P 〈 0.05） compared to the control group. CONCLUSION： It is concluded that ginger volatile oil could effectively reduce symptoms of experimental colitis in a dose-dependent manner.展开更多
AIM:Smoking may affect adversely the response rate to interferon-α.Our objective was to verify this issue among chronic hepatitis C patients. METHODS:Over the year 1998,138 chronic hepatitis C male Egyptian patients ...AIM:Smoking may affect adversely the response rate to interferon-α.Our objective was to verify this issue among chronic hepatitis C patients. METHODS:Over the year 1998,138 chronic hepatitis C male Egyptian patients presenting to Cairo Liver Center, were divided on the basis of smoking habit into:group I which comprised 38 smoker patients(>30 cigarettes/d) and group Ⅱ which included 84 non-smoker patients. Irregular and mild smokers(16 patients)were excluded. Non eligible patients for interferon-α therapy were excluded from the study and comprised 3/38(normal ALT)in group I and 22/84 in group Ⅱ(normal ALT,advanced cirrhosis and thrombocytopenia).Group I was randomly allocated into 2 sub-groups:group Ia comprised 18 patients who were subjected to therapeutic phlebotomy while sub-group Ib consisted of 17 patients who had no phlebotomy.In sub-group la,3 patients with normal ALT after repeated phlebotomies were excluded from the study.Interferon-α 2b 3 MU/TIW was given for 6 mo to 15 patients in group Ia,17 patients in group Ib and 62 patients in group Ⅱ. Biochemical,virological end-of-treatment and sustained responses were evaluated. RESULTS:At the end of interferon-α treatment,ALT was normalized in 3/15 patients(20%)in group Ia and 2/17 patients(11.8%)in group Ib compared to17/62 patients (27.4%)in group Ⅱ(P=0.1).Whereas 2/15 patients(13.3%) in group Ia.and 2/17 patients(11.8%)in group Ib lost viraemia compared to 13/62 patients(26%)in group Ⅱ (P=0.3).Six months later,ALT was persistently normal in 2/15 patients(13.3%)in group 1a and 1/17 patients (5.9%)in group Ib compared to 9/62 patients(14.5%)in group Ⅱ(P=0.47).Viraemia was eliminated in 1/15 patients (6.7%)in group Ia and 1/17 patients(5.9%)in group Ib compared to 7/62 patients(11.3%) in group Ⅱ,but the results did not mount to statistical significance(P=0.4). CONCLUSION:Smokers suffering from chronic hepatitis C tend to have a lower response rate to interferon-α compared to non-smokers.Therapeutic phlebotomy improves the response rate to interferon-α therapy among this group.展开更多
A 10-year-old Chinese boy who had a history of congenital thrombocytopathy presented with severe iron deficiency anemia secondary to chronic gastric inflammation and duodenal ulcerations. Subtle oculocutaneous albinis...A 10-year-old Chinese boy who had a history of congenital thrombocytopathy presented with severe iron deficiency anemia secondary to chronic gastric inflammation and duodenal ulcerations. Subtle oculocutaneous albinism led to the finding of diminished dense bodies in the platelets under electron microscopy, hence the diagnosis of Hermansky-Pudlak syndrome (HPS). Biopsies from the stomach and duodenum revealed a lymphocytic infiltration in the submucosa, but H pylori infection was absent. The gastroduodenitis responded to the treatment with omeprazole while iron deficiency anemia was corrected by oral iron therapy. HPS is a rare cause of congenital bleeding disorder with multisystemic manifestations. Upper gastrointestinal involvement is rare and should be distinguished from a mere manifestation of the bleeding diathesis.展开更多
Consuming a high-fructose diet induces metabolic syndrome （MS）-Iike features, including endothelial dysfunction. Erectile dysfunction is an early manifestation of endothelial dysfunction and systemic vascular diseas...Consuming a high-fructose diet induces metabolic syndrome （MS）-Iike features, including endothelial dysfunction. Erectile dysfunction is an early manifestation of endothelial dysfunction and systemic vascular disease. Because mineral deficiency intensifies the deleterious effects of fructose consumption and mineral ingestion is protective against MS, we aimed to characterize the effects of 8weeks of natural mineral-rich water consumption on the structural organization and expression of vascular growth factors and receptors on the corpus cavernosum （CC） in 10% fructose-fed Sprague-Dawley rats （FRUCT）. Differences were not observed in the organization of the CC either on the expression of vascular endothelial growth factor （VEGF） or the components of the angiopoietins/Tie2 system. However, opposing expression patterns were observed for VEGF receptors （an increase and a decrease for VEGFR1 and VEGFR2, respectively） in FRUCT animals, with these patterns being strengthened by mineral-rich water ingestion. Mineral-rich water ingestion （FRUCTMIN） increased the proportion of smooth muscle cells compared with FRUCT rats and induced an upregulatory tendency of sirtuin I expression compared with the control and FRUCT groups. Western blot results were consistent with the dual immunofluorescence evaluation. Plasma oxidized low-density lipoprotein and plasma testosterone levels were similar among the experimental groups, although a tendency for an increase in the former was observed in the FRUCTMIN group. The mineral-rich water-treated rats presented changes similar to those observed in rats treated with MS-protective polyphenol-rich beverages or subjected to energy restriction, which led us to hypothesize that the effects of mineral-rich water consumption may be more vast than those directly observed in this study.展开更多
AIM: To estimate the prevalence of inherited and acquired thrombophilic risk factors in patients with abdominal venous thrombosis and to compare the risk factor profiles between Budd-Chiari syndromes (BCS) and splanch...AIM: To estimate the prevalence of inherited and acquired thrombophilic risk factors in patients with abdominal venous thrombosis and to compare the risk factor profiles between Budd-Chiari syndromes (BCS) and splanchnic vein thrombosis (SVT). METHODS: In this retrospective study, 36 patients with abdominal venous thrombosis were studied. The patients were divided into Budd-Chiari group (hepatic vein, IVC thrombosis) and splanchnic venous thrombosis group (portal, splenic, superior mesenteric veins) based on the veins involved. Hereditary and acquired thrombophilic risk factors were evaluated in all patients. RESULTS: Twenty patients had SVT, 14 had BCS, and 2 had mixed venous thrombosis. Ten patients (28%) had hereditary and 10 patients (28%) acquired thrombophilic risk factors. The acquired risk factors were significantly more common in the SVT group (SVT vs BCS: 45% vs 7%, χ2 = 5.7, P = 0.02) while hereditary risk factors did not show significant differences between the two groups (SVT vs BCS: 25% vs 36%, χ2 = 0.46, P = 0.7). Multiple risk factors were present in one (7%) patient with BCS and in 3 patients (15%) with SVT. No risk factors were identified in 57% of patients with BCS and in 45% of patients with SVT. CONCLUSION: Hereditary and acquired risk factors play an important role in the etiopathogenesis of abdominal venous thrombosis. Acquired risk factorsare significantly more common in SVT patients while hereditary factors are similar in both groups.展开更多
This report describes serial observations of the growth process of a small invasive ductal carcinoma (IDC) of the pancreas from imaging studies. Histopathological studies showed IDC with macroscopic retention cysts pr...This report describes serial observations of the growth process of a small invasive ductal carcinoma (IDC) of the pancreas from imaging studies. Histopathological studies showed IDC with macroscopic retention cysts proximal to an intraductal papillary-mucinous adenoma with mild atypia of the branch duct type in the pancreatic body, with no relation between the two lesions. IDC was demonstrated as an extremely low-echoic mass resembling a cyst with an unclear margin on the initial endoscopic ultrasonography. We misinterpreted the low-echoic mass as a benign intraductal mucinous-papillary neoplasm (IPMN) based on findings of other imaging studies, and the patient was followed-up. The mass increased from 7 mm to 13 mm in diameter over 22 mo, and remained smaller than 10 mm in diameter for about 420 d. The tumor volume doubling time was 252 d. The Ki67 labeling index was 15.9%, similar to that described in previous reports. Hence, IDC may grow slowly while remaining small.展开更多
Spindle cell carcinoma of the breast is a rare tumor. This tumor can proliferate rapidly and cause cystic changes because of internal tissue necrosis. We evaluated a 54-year-old woman with right breast lump. Mammograp...Spindle cell carcinoma of the breast is a rare tumor. This tumor can proliferate rapidly and cause cystic changes because of internal tissue necrosis. We evaluated a 54-year-old woman with right breast lump. Mammography showed a category four mass with a diameter of 2.5 cm. Ultrasonography(US) revealed a complex cystic lesion, and fine-needle aspiration(FNA) cytology demonstrated bloody fluid and malignant cells. Partial breast resection and sentinel lymph node biopsy were performed. Immunohistology revealed spindle cells with positive results for cytokeratin(AE1/AE3) and vimentin, partially positive results for s-100, and negative results for desmin and α-actin. The pathological stage was IIA, and biochemical characterization showed that the tumor was triple negative. Six courses of FEC-100 chemotherapy(5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2) were administered. Radiotherapy was performed. This case is discussed with reference to the literature.展开更多
文摘BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth factors-binding proteins 2(IGFBP2),secreted phosphoprotein 1(SPP1),thrombospondin 1 protein(TSP1)and D-dimer levels in addition to currently used biomarkers[cancer antigen 125(CA125)and human epididymis protein 4(HE4)]in the diagnosis of epithelial OC(EOC).METHODS This is a case-control study that included fifty females diagnosed with EOC,10 females with benign ovarian masses recruited from the Egyptian National Cancer Institute,and 30 healthy females as a control group.All subjects were assessed for serum HE4,CA125,IGFBP2,TSP1 and SPP1 measurement by enzyme-linkedimmunosorbent assay.RESULTS There was a statistically significant difference in serum levels between EOC,benign ovarian masses,and healthy control groups regarding CA125 and SPP1(P<0.001 for both markers),while HE4 and IGFBP2 increased significantly in EOC compared to healthy control groups(P<0.001 for all markers)with no significant difference between EOC and benign ovarian masses groups.However,there was no statistically significant difference among EOC,benign ovarian masses,and healthy control groups regarding the TSP1 serum levels(P=0.051).Receiver operating characteristic analysis revealed that combined assessment of SPP1 with CA125 or TSP1 increased the diagnosis of EOC patients to a sensitivity,specificity,and area under curve of(93.3%,100%,0.968;respectively,P<0.001).CONCLUSION SPP1 may be a potential marker for the differentiation between benign and malignant ovarian masses,while IGFBP2 can differentiate between healthy females and females with ovarian masses.Combining SPP1 with CA125 or TSP1 provides high sensitivity and specificity for the detection of EOC patients.
文摘Objective： The purpose of this study was to study the clinical, imaging characters and pathological characteristics of esophageal sarcomatoid carcinoma. Methods： We reviewed 23 cases of esophageal sarcomatoid carcinoma from Janu ary 2006 to December 2013 in four hospitals. The data of patients who were esophageal sarcomatoid carcinoma operated were retrospectively analyzed. All cases had completed upper gastrointestinal barium images materials and 14 of these cases had completed CT images materials. Upper gastrointestinal barium images and CT imaging features include tumor location, size, shape, and strengthen, etc. The biological parameters of lesions including the express of cytokeratin AE1/AE3, 34E12,, Vimentin, desmin, Actin, S100 and Ki67 detected by immunhistochemical UltraSensitiveTM SP method （n = 23）, and the patients＇ data of contrastographic picture （n = 23）, imaging characters of CT scan （n = 14）, and their relationship were studied. Results： Upper gastrointestinal barium images, CT imaging and gastrointestinal fiberscopy revealed Iobulated intraluminal filling defect 0.4 cm to 5.7 cm x 3.5 cmx 1.3 cm （mean = 3. 7 cm） in the mid （n = 14）, lower （n = 7） and upper （n = 2） intrathoracic esophagus. Among 23 cases of esophageal sarcomatoid carcinoma, 19 patients were of mushroom type, 2 patients was of ulcer type, and 2 patients were of medulla type; 19 patients were pedunculated, and 4 patients were no pedunculated （2 patients was of ulcer type）. The tumor surface was relatively smooth and esophageal compliance was maintained. The pathological changes of esophagus such as lightly locked, rigid wall nomanifest partly, esophageal lumens expand partly, major filling sublobe defect could be shown through contrast medium. Normal esophagus was no unpack obviously over pathological changes. Enhanced computed tomography showed tumors in the intrathoracic esophagus and 8 lymph nodes metastases in 3 cases. Histologically, carcinomatous and sarcomatous components coexist. Microscopically, the tumor comprised poorly differentiated squamous cell carcinoma and spindleshaped cells resembling leiomyosarcoma. Immu nohistochemically, spindleshaped sarcomatous cells displayed weekly positive reaction to cytokeratin AE1/AE3. Transitional zone was seen between sarcomatous and carcinomatous elements in 5 cases. The 17 lymph nodes metastases in 5 cases （53 lymph nodes） among 23 cases esophageal sarcomatoid carcinoma （187 lymph nodes） were observed. Conclusion： The clinical and radiologic features of esophageal sarcomatoid carcinoma overlap with those of other esophageal neoplasms. There are the radiologic imaging changes such as a large, intraluminal, polypoid mass, major filling sublobe defect and pedicle skin flap tumor in esophageal lumen, esophageal lumen extension partly, dissepiment rigidity wall no obviously, etc. Histologically, carcinomatous and sarcomatous components coexist and the biphasic pattern is the key diagnostic feature. However, esophageal sarcomatoid carcinoma has a more favorable prognosis than other malignant esophageal neoplasms. Immunohistochemical staining seems necessary to distinguish these lesions from other esophageal neoplasms.
文摘Objective:To describe the prevalence of antiphospholipid antibodies in coronavirus disease-19(COVID-19)and to find potential associations between antiphospholipid antibody positivity and clinical outcomes.Methods:From September to November 2020,clinical and laboratory data were collected from 50 COVID-19 patients hospitalized at Saiful Anwar General Hospital in Malang,Indonesia.Antiphospholipid antibodies were measured by finding Ig M anti-β2 glycoprotein,lupus anticoagulant,and Ig M/Ig G anticardiolipin.Clinical characteristics,thrombotic events,ICU admission,and mortality during hospitalization were recorded.Disease severity was defined by the Guidelines for the Prevention and Control of COVID-19,Indonesia.Results:Among 50 patients,5 patients(10.0%)were positive for antiphospholipid antibodies:4 patients(80.0%)had Ig M anti-β2 glycoprotein and 1 patient had Ig G anti-cardiolipin(20.0%)and Ig M anti-cardiolipin(20.0%),none of lupus anticoagulant was detected.Antiphospholipid antibodies were associated with anosmia(OR 8.1;95%CI 1.1-57.9;P=0.018),nausea and vomiting(OR 12.4;95%CI 1.2-122.6;P=0.010),diarrhea(OR 9.8;95%CI 1.3-70.9;P=0.010),cardiovascular disease(OR 1.4;95%CI 1.0-1.9;P=0.001),chronic kidney disease(OR 12.0;95%CI 1.6-90.1;P=0.05),acute coronary syndrome(OR 29.3;95%CI 2.0-423.7;P=0.001),moderate(OR 0.11;95%CI 0.01-1.10;P=0.031)and severe(OR 18.5;95%CI 1.8-188.4;P=0.002)disease severity,and in-hospital mortality(OR 8.1;95%CI 1.1-57.9;P=0.018).However,there is no correlation between the presence of antiphospholipid antibody and ICU admission.Conclusions:In summary,the prevalence of antiphospholipid antibodies in COVID-19 patients is low,mainly against Ig M anticardiolipin,and is associated with an acute coronary syndrome,gastrointestinal manifestations,moderate and severe disease severity,and increased risk of mortality.
基金Grant from the Association for the Study of Hemochromatosis and Iron Overload Disorders-ONLUS (P.T.), Monza
文摘AIM： To re-evaluate the diagnostic criteria of insulin resistance hepatic iron overload based on clinical, biochemical and histopathological findings. METHODS： We studied 81 patients with hepatic iron overload not explained by known genetic and acquired causes. The metabolic syndrome （MS） was defined according to ATPⅢ criteria. Iron overload was assessed by liver biopsy. Liver histology was evaluated by Ishak＇s score and iron accumulation by Deugnier＇s score; steatosis was diagnosed when present in ≥ 5% of hepatooltes. RESULTS： According to transferrin saturation levels, we observed significant differences in the amount of hepatic iron overload and iron distribution, as well as the number of metabolic abnormalities. Using Receiving Operating Curve analysis, we found that the presence of two components of the MS differentiated two groups with a statistically significant different hepatic iron overload （P 〈 0.0001）. Patients with ≥2 metabolic alterations and steatosis had lower amount of hepatic iron, lower transferrin saturation and higher sinusoidal iron than patients with 〈 2 MS components and absence of steatosis. CONCLUSION： In our patients, the presence of ≥ 2 alterations of the MS and hepatic steatosis was associated with a moderate form of iron overload with a prevalent sinusoidal distribution and a normal transferrin saturation, suggesting the existence of a peculiar pathogenetic mechanism of iron accumulation. These patients may have the typical dysmetabolic iron overload syndrome. By contrast, patients with transferrin saturation ≥ 60% had more severe iron overload, few or no metabolic abnormalities and a hemochromatosis-like pattern of iron overload.
文摘Objectives: Serous ovarian carcinoma (SOC) is the commonest ovarian carcinoma type with poor prognosis due to early metastasis and first presentation with advanced stage. In this work, we investigated serum level of Galactin-1 (Gal-1) and its tissue immunohistochemical expression in SOC patients at different stages trying to find out its significance as a diagnostic and prognostic marker. Patients and methods: The study included 95 females I-Control group: Twenty five healthy females;II-Patients group: Seventy females diagnosed as SOC at different stages;Stage I: 8 cases, Stage II: 12 cases, Stage III: 32 cases and Stage VI:18 cases. Serum Galectin-1 and CA-125 were measured by ELIZA and tissue Galectin-1 was assessed by immunohistochemistry. All patients were followed for up to 3 years after surgery. Results: Serum Gal-1 and CA-125 levels were significantly higehr in SOC patients compared to controls (p 0.001). We found a direct positive statistically significant correlation between serum Gal-1 and CA125 levels (p 0.001). Serum Gal-1 at cut off value > 135 ng/ml was superior to CA-125 a cut off value > 49 u/ml with sensitivity, specificity of 100%, vs 88.57, 96% for CA-125. Serum Gal-1 was significantly associated with tumor stage (p 0.001). Immunohistochemistry showed that patients with strong Gal-1 expression had higher serum level (p = 0.002). Stromal and tumor Gal-1 expression were significantly correlated with tumor grade (p 0.001) and stage (p = 0.001). Serum Gal-1, CA-125 and IHC Gal-1 expression were associated with poor survival (p 0.001, p = 0.009 and p = 0.002) respectively. Conclusion: Serum Gal-1 and its tissue IHC expression are useful diagnostic and prognostic markers for SOC patients.
文摘BACKGROUND Colorectal cancer is the third most common malignancy and the fourth leading cause of cancer-related deaths worldwide.Several studies have shown an association between gut microbiota and colorectal cancer.Gut microbiota is unique and can be influenced by geographic factors and habits.This study aimed to determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer.AIM To determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer in Indonesia.METHODS This case-control study included 59 subjects(35 colorectal cancer patients and 24 non-colorectal cancer patients indicated for colonoscopy at Dr.Cipto Mangunkusumo Gastrointestinal Endoscopy Center and Fatmawati Hospital.Microbiota examination was performed using 16S rRNA sequencing.Bioinformatics analysis was performed using the wf-metagenomics pipeline from EPI2Me-Labs(Oxford Nanopore Technologies platform).RESULTS Patients with colorectal cancer had a higher median index value on the Shannon index(3.28 vs 2.82,P>0.05)and a lower value on the Simpson index(0.050 vs 0.060,P>0.05).Significant differences in beta diversity were observed at the genus(P=0.002)and species levels(P=0.001).Firmicutes,Proteobacteria,Bacteroidetes,and Fusobacteria were the dominant phyla.The genera Bacteroides,Campylobacter,Peptostreptococcus,and Parvimonas were found more frequently in colorectal cancer,while Faecalibacterium,Haemophilus,and Phocaeicola were more frequently found in non-colorectal cancer.The relative abundance of Fusobacterium nucleatum,Bacteroides fragilis,Enterococcus faecalis,Campylobacter hominis,and Enterococcus faecalis species was significantly elevated in patients with colorectal cancer.Meanwhile,Faecalibacterium prausnitzii,Faecalibacterium duncaniae,and Prevotella copri were more commonly found in non-colorectal cancer.CONCLUSION Patients with colorectal cancer exhibit distinct differences in the composition and diversity of their colonic mucosal microbiota compared to those with non-colorectal cancer.This study was reviewed and approved by the Ethics Committee of Faculty of Medicine,Universitas Indonesia(No.KET-1517/UN2.F1/ETIK/PPM.00.02/2023).
文摘The arterial pulse tapping artifact,known as Aslanger’s sign,is an electrocardiographic artifact resulting from the transmission of arterial pulsation onto the limb electrodes of the standard 12-lead electrocardiograph(ECG)which are placed near the radial or posterior tibial arteries.[1-16]This electromechanical artifact is of cardiac origin and is synchronous with the cardiac cycle.[17]Nearly all reported cases of Aslanger’s sign exhibit an unusual waveform morphology in all 12 leads except one limb lead.[1-14,16]However,we previously reported a case of Aslanger’s sign that showed distorted waveforms from the ST to TP segments observed only in five limb leads among 12 leads.
文摘BACKGROUND Acute myeloid leukemia(AML)is a complicated disease with uncontrolled hematopoietic precursor proliferation induced by various genetic alterations.Runt-related transcription factor-1(RUNX1)is commonly disrupted by chromosomal translocations in hematological malignancies.AIM To characterize RUNX1 gene rearrangements and copy number variations in newly diagnosed adult AML patients,with an emphasis on the impact of clinical and laboratory features on the outcome.METHODS Fluorescence in situ hybridization was used to test RUNX1 gene alterations in 77 newly diagnosed adult AML cases.NPM1,FLT3/ITD,FLT3/TKD,and KIT mutations were tested by PCR.Prognostic clinical and laboratory findings were studied in relation to RUNX1 alterations.RESULTS RUNX1 abnormalities were detected by fluorescence in situ hybridization in 41.6%of patients:20.8%had translocations,22.1%had amplification,and 5.2%had deletion.Translocations prevailed in AML-M2(P=0.019)with a positive expression of myeloperoxidase(P=0.031),whereas deletions dominated in M4 and M5 subtypes(P=0.008)with a positive association with CD64 expression(P=0.05).The modal chromosomal number was higher in cases having amplifications(P=0.007)and lower in those with deletions(P=0.008).RUNX1 abnormalities were associated with complex karyotypes(P<0.001)and were mutually exclusive of NPM1 mutations.After 44 months of follow-up,RUNX1 abnormalities affected neither patients’response to treatment nor overall survival.CONCLUSION RUNX1 abnormalities were mutually exclusive of NPM1 mutations.RUNX1 abnormalities affected neither patients’response to treatment nor overall survival.
文摘Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.
基金supported by the National Natural Science Foundation of China(No.81960480)the Key Research and Development Program of Ningxia,China(No.2018BEB04008)。
文摘Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women.Lycium barbarum polysaccharide(LBP)is an extract from the fruits of the traditional Chinese herb,L.barbarum.LBP is a promising anticancer drug,due to its high activity and low toxicity.Although it has anticancer properties,its mechanisms of action have not been fully established.Ferroptosis,which is a novel anticancer strategy,is a cell death mechanism that relies on iron-dependent lipid reactive oxygen species(ROS)accumulation.In this study,human breast cancer cells(Michigan Cancer Foundation-7(MCF-7)and MD Anderson-Metastatic Breast-231(MDA-MB-231))were treated with LBP.LBP inhibited their viability and proliferation in association with high levels of ferroptosis.Therefore,we aimed to ascertain whether LBP reduced cell viability through ferroptosis.We found that the structure and function of mitochondria,lipid peroxidation,and expression of solute carrier family 7 member 11(SLC7 A11,also known as x CT,the light-chain subunit of cystine/glutamate antiporter system X_(c)^(-))and glutathione peroxidase 4(GPX4)were altered by LBP.Moreover,the ferroptosis inhibitor,Ferrostatin-1(Fer-1),rescued LBP-induced ferroptosis-associated events including reduced cell viability and glutathione(GSH)production,accumulation of intracellular free divalent iron ions and malondialdehyde(MDA),and down-regulation of the expression of x CT and GPX4.Erastin(x CT inhibitor)and RSL3(GPX4 inhibitor)inhibited the expression of x CT and GPX4,respectively,which was lower after the co-treatment of LBP with Erastin and RSL3.These results suggest that LBP effectively prevents breast cancer cell proliferation and promotes ferroptosis via the x CT/GPX4 pathway.Therefore,LBP exhibits novel anticancer properties by triggering ferroptosis,and may be a potential therapeutic option for breast cancer.
文摘AIM:To evaluate effective alternative antibiotics in treatment of cefotaxime-resistant spontaneous bacterial peritonitis.METHODS:One hundred cirrhotic patients with spontaneous bacterial peritonitis [ascitic fluid polymorphonuclear cell count(PMNLs) ≥ 250 cells/mm 3 at admission] were empirically treated with cefotaxime sodium 2 g/12 h and volume expansion by intravenous human albumin.All patients were subjected to history taking,complete examination,laboratory tests(including a complete blood cell count,prothrombin time,biochemical tests of liver and kidney function,and fresh urine sediment),chest X-ray,a diagnostic abdominal paracentesis,and the sample subjected to total and differential cell count,chemical examination,aerobic and anaerobic cultures.Patients were divided after 2 d by a second ascitic PMNL count into group Ⅰ;patients sensitive to cefotaxime(n = 81),group Ⅱ(n = 19);cases resistant to cefotaxime(less than 25% decrease in ascitic PMNL count).Patients of group Ⅱ were randomly assigned into meropenem(n = 11) or levofloxacin(n = 8) subgroups.All patients performed an end of treatment ascitic PMNL count.Patients were considered improved when:PMNLs decreased to < 250 cells/mm 3,no growth in previously positive culture cases,and improved clinical manifestations with at least 5 d of antibiotic therapy.RESULTS:Age,sex,and Child classes showed no significant difference between group Ⅰ and group Ⅱ.Fever and abdominal pain were the most frequent manifestations and were reported in 82.7% and 80.2% of patients in group Ⅰ and in 94.7% and 84.2% of patients in group Ⅱ,respectively.Patients in group Ⅱ had a more severe ascitic inflammatory response than group Ⅰ and this was demonstrated by more ascitic lactate dehydrogenase(LDH) [median:540 IU/L(range:150-1200 IU/L) vs median:240 IU/L(range:180-500 IU/L),P = 0.000] and PMNL [median:15 000 cell/mm 3(range:957-23 822 cell/mm 3) vs 3400 cell/mm 3(range:695-26 400 cell/mm 3),P = 0.000] counts.Ascitic fluid culture was positive in 32% of cases.Cefotaxime failed in 19% of patients;of these patients,11(100%) responded to meropenem and 6(75%) responded to levofloxacin.Two patients with failed levofloxacin therapy were treated according to the in vitro culture and sensitivity(one case was treated with vancomycin and one case was treated with ampicillin/sulbactam).In group Ⅱ the meropenem subgroup had higher LDH(range:108-860 IU/L vs 120-491 IU/L,P = 0.042) and PMNL counts(range:957-23 822 cell/mm 3 vs 957-15 222 cell/mm 3,P = 0.000) at initiation of the alternative antibiotic therapy;there was no significant difference in the studied parameters between patients responsive to meropenem and patients responsive to levofloxacin at the end of therapy(mean ± SD:316.01 ± 104.03PMNLs/mm 3 vs 265.63 ± 69.61 PMNLs/mm 3,P = 0.307).The isolated organisms found in group Ⅱ were;enterococci,acinetobacter,expanded-spectrum β-lactamase producing Escherichia coli,β-lactamase producing Enterobacter and Staphylococcus aureus.CONCLUSION:Empirical treatment with cefotaxime is effective in 81% of cases;meropenem is effective in cefotaxime-resistant cases.
基金supported by the Natural Science Foundation of Zhejiang Province of China,Nos.LQ22H090003(to JJ),LTGY23C090001(to XZ),LY23H020008(to BH)Sci-Tech Planning Project of Jiaxing,Nos.2021AY30001(to XZ)and 2022AY30020(to JJ).
文摘The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s disease.In this review,we summarize the possible pathogenic mechanisms of Alzheimer’s disease,focusing on neuroinflammation.We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s disease.Finally,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.
基金Science and Technology Development Foundation(STDF),Project NO.3457(TC/4/Health/2010/hep-1.6)
文摘BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important roles in the regulation of biological processes such as cell proliferation and hepatic fibrosis.AIM To assess diffusion-weighted magnetic resonance imaging and miRs in diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.METHODS This prospective study included 208 patients and 82 age-and sex-matched controls who underwent diffusion-weighted magnetic resonance imaging of the abdomen, miR profiling, and liver biopsy. Pathological scoring was classified according to the METAVIR scoring system. The apparent diffusion coefficient (ADC) and miR were calculated and correlated with pathological scoring.RESULTS The ADC value decreased significantly with the progression of fibrosis, from controls(F0) to patients with early fibrosis(F1 and F2) to those with late fibrosis(F3 and F4)(median 1.92, 1.53, and 1.25 × 10^(-3) mm^2/s, respectively)(P = 0.001).The cut-off ADC value used to differentiate patients from controls was 1.83 × 10^(-3) mm^2/s with an area under the curve(AUC) of 0.992. Combining ADC and miR-200 b revealed the highest AUC(0.995) for differentiating patients from controls with an accuracy of 96.9%. The cut-off ADC used to differentiate early fibrosis from late fibrosis was 1.54 × 10^(-3) mm^2/s with an AUC of 0.866. The combination of ADC and miR-200 b revealed the best AUC(0.925) for differentiating early fibrosis from late fibrosis with an accuracy of 80.2%. The ADC correlated with miR-200 b(r =-0.61, P = 0.001), miR-21(r =-0.62, P = 0.001), and miR-29(r = 0.52,P = 0.001).CONCLUSION Combining ADC and miRs offers an alternative surrogate non-invasive diagnostic tool for diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.
文摘OBJECTIVE： Ulcerative colitis is a chronically recurrent inflammatory bowel disease of unknown origin. In the present study, the effect of ginger （rhizome of Zingiber officinale Roscoe） volatile oil on a rat model of colitis was evaluated. METHODS： Volatile oil of ginger with doses of 100, 200, and 400 mg/kg, prednisolone （4 mg/kg）, or vehicle were administered orally to groups of male Wistar rats （n = 6） for 5 d. Animals were randomly divided into 6 groups, each group consisting of 6 rats. Colitis was induced by intracolonic instillation of 2 mL of 4% （v/v） acetic acid solution. All rats were sacrificed 24 h later and the tissue injuries were assessed macroscopically and histopathologically. RESULTS： Ginger volatile oil with all doses reduced colon weight/length ratio （P 〈 0.01） and the effects were similar to the reference drugs. Higher oral doses of volatile oil （200 and 400 mg/kg） reduced ulcer severity （P 〈 0.05 and P 〈 0.01）, ulcer area （P 〈 0.01） and ulcer index （P 〈 0.01）. On the other hand, evaluation of microscopic scores showed that the dose of 400 mg/kg of volatile oil was effective to reduce inflammation severity （P 〈 0.01） and inflammation extent （P 〈 0.05） compared to the control group. CONCLUSION： It is concluded that ginger volatile oil could effectively reduce symptoms of experimental colitis in a dose-dependent manner.
文摘AIM:Smoking may affect adversely the response rate to interferon-α.Our objective was to verify this issue among chronic hepatitis C patients. METHODS:Over the year 1998,138 chronic hepatitis C male Egyptian patients presenting to Cairo Liver Center, were divided on the basis of smoking habit into:group I which comprised 38 smoker patients(>30 cigarettes/d) and group Ⅱ which included 84 non-smoker patients. Irregular and mild smokers(16 patients)were excluded. Non eligible patients for interferon-α therapy were excluded from the study and comprised 3/38(normal ALT)in group I and 22/84 in group Ⅱ(normal ALT,advanced cirrhosis and thrombocytopenia).Group I was randomly allocated into 2 sub-groups:group Ia comprised 18 patients who were subjected to therapeutic phlebotomy while sub-group Ib consisted of 17 patients who had no phlebotomy.In sub-group la,3 patients with normal ALT after repeated phlebotomies were excluded from the study.Interferon-α 2b 3 MU/TIW was given for 6 mo to 15 patients in group Ia,17 patients in group Ib and 62 patients in group Ⅱ. Biochemical,virological end-of-treatment and sustained responses were evaluated. RESULTS:At the end of interferon-α treatment,ALT was normalized in 3/15 patients(20%)in group Ia and 2/17 patients(11.8%)in group Ib compared to17/62 patients (27.4%)in group Ⅱ(P=0.1).Whereas 2/15 patients(13.3%) in group Ia.and 2/17 patients(11.8%)in group Ib lost viraemia compared to 13/62 patients(26%)in group Ⅱ (P=0.3).Six months later,ALT was persistently normal in 2/15 patients(13.3%)in group 1a and 1/17 patients (5.9%)in group Ib compared to 9/62 patients(14.5%)in group Ⅱ(P=0.47).Viraemia was eliminated in 1/15 patients (6.7%)in group Ia and 1/17 patients(5.9%)in group Ib compared to 7/62 patients(11.3%) in group Ⅱ,but the results did not mount to statistical significance(P=0.4). CONCLUSION:Smokers suffering from chronic hepatitis C tend to have a lower response rate to interferon-α compared to non-smokers.Therapeutic phlebotomy improves the response rate to interferon-α therapy among this group.
文摘A 10-year-old Chinese boy who had a history of congenital thrombocytopathy presented with severe iron deficiency anemia secondary to chronic gastric inflammation and duodenal ulcerations. Subtle oculocutaneous albinism led to the finding of diminished dense bodies in the platelets under electron microscopy, hence the diagnosis of Hermansky-Pudlak syndrome (HPS). Biopsies from the stomach and duodenum revealed a lymphocytic infiltration in the submucosa, but H pylori infection was absent. The gastroduodenitis responded to the treatment with omeprazole while iron deficiency anemia was corrected by oral iron therapy. HPS is a rare cause of congenital bleeding disorder with multisystemic manifestations. Upper gastrointestinal involvement is rare and should be distinguished from a mere manifestation of the bleeding diathesis.
文摘Consuming a high-fructose diet induces metabolic syndrome （MS）-Iike features, including endothelial dysfunction. Erectile dysfunction is an early manifestation of endothelial dysfunction and systemic vascular disease. Because mineral deficiency intensifies the deleterious effects of fructose consumption and mineral ingestion is protective against MS, we aimed to characterize the effects of 8weeks of natural mineral-rich water consumption on the structural organization and expression of vascular growth factors and receptors on the corpus cavernosum （CC） in 10% fructose-fed Sprague-Dawley rats （FRUCT）. Differences were not observed in the organization of the CC either on the expression of vascular endothelial growth factor （VEGF） or the components of the angiopoietins/Tie2 system. However, opposing expression patterns were observed for VEGF receptors （an increase and a decrease for VEGFR1 and VEGFR2, respectively） in FRUCT animals, with these patterns being strengthened by mineral-rich water ingestion. Mineral-rich water ingestion （FRUCTMIN） increased the proportion of smooth muscle cells compared with FRUCT rats and induced an upregulatory tendency of sirtuin I expression compared with the control and FRUCT groups. Western blot results were consistent with the dual immunofluorescence evaluation. Plasma oxidized low-density lipoprotein and plasma testosterone levels were similar among the experimental groups, although a tendency for an increase in the former was observed in the FRUCTMIN group. The mineral-rich water-treated rats presented changes similar to those observed in rats treated with MS-protective polyphenol-rich beverages or subjected to energy restriction, which led us to hypothesize that the effects of mineral-rich water consumption may be more vast than those directly observed in this study.
文摘AIM: To estimate the prevalence of inherited and acquired thrombophilic risk factors in patients with abdominal venous thrombosis and to compare the risk factor profiles between Budd-Chiari syndromes (BCS) and splanchnic vein thrombosis (SVT). METHODS: In this retrospective study, 36 patients with abdominal venous thrombosis were studied. The patients were divided into Budd-Chiari group (hepatic vein, IVC thrombosis) and splanchnic venous thrombosis group (portal, splenic, superior mesenteric veins) based on the veins involved. Hereditary and acquired thrombophilic risk factors were evaluated in all patients. RESULTS: Twenty patients had SVT, 14 had BCS, and 2 had mixed venous thrombosis. Ten patients (28%) had hereditary and 10 patients (28%) acquired thrombophilic risk factors. The acquired risk factors were significantly more common in the SVT group (SVT vs BCS: 45% vs 7%, χ2 = 5.7, P = 0.02) while hereditary risk factors did not show significant differences between the two groups (SVT vs BCS: 25% vs 36%, χ2 = 0.46, P = 0.7). Multiple risk factors were present in one (7%) patient with BCS and in 3 patients (15%) with SVT. No risk factors were identified in 57% of patients with BCS and in 45% of patients with SVT. CONCLUSION: Hereditary and acquired risk factors play an important role in the etiopathogenesis of abdominal venous thrombosis. Acquired risk factorsare significantly more common in SVT patients while hereditary factors are similar in both groups.
文摘This report describes serial observations of the growth process of a small invasive ductal carcinoma (IDC) of the pancreas from imaging studies. Histopathological studies showed IDC with macroscopic retention cysts proximal to an intraductal papillary-mucinous adenoma with mild atypia of the branch duct type in the pancreatic body, with no relation between the two lesions. IDC was demonstrated as an extremely low-echoic mass resembling a cyst with an unclear margin on the initial endoscopic ultrasonography. We misinterpreted the low-echoic mass as a benign intraductal mucinous-papillary neoplasm (IPMN) based on findings of other imaging studies, and the patient was followed-up. The mass increased from 7 mm to 13 mm in diameter over 22 mo, and remained smaller than 10 mm in diameter for about 420 d. The tumor volume doubling time was 252 d. The Ki67 labeling index was 15.9%, similar to that described in previous reports. Hence, IDC may grow slowly while remaining small.
文摘Spindle cell carcinoma of the breast is a rare tumor. This tumor can proliferate rapidly and cause cystic changes because of internal tissue necrosis. We evaluated a 54-year-old woman with right breast lump. Mammography showed a category four mass with a diameter of 2.5 cm. Ultrasonography(US) revealed a complex cystic lesion, and fine-needle aspiration(FNA) cytology demonstrated bloody fluid and malignant cells. Partial breast resection and sentinel lymph node biopsy were performed. Immunohistology revealed spindle cells with positive results for cytokeratin(AE1/AE3) and vimentin, partially positive results for s-100, and negative results for desmin and α-actin. The pathological stage was IIA, and biochemical characterization showed that the tumor was triple negative. Six courses of FEC-100 chemotherapy(5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2) were administered. Radiotherapy was performed. This case is discussed with reference to the literature.
