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OBJECTIVE To explore the way to re-use epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKI） in patients with EGFR-TKI-induced interstitial pneumonia （IP）， using osimertinib as an example. METHODS The IP treatment regimen and re-use of EGFR-TKI regimen in a patient who developed IP after the use of osimertinib were analyzed. And a literature review was made by combining the characteristics of the cases which reported in the literature and the characteristics of this case. RESULTS The patient’s IP symptoms due to treatment with osimertinib had resolved after treatment. The patient’s IP symptoms also did not worsen after using almonertinib in combination with hormones as re-use of EGFR-TKI regimen. However， almonertinib was discontinued as the patient experienced disease progression. The adverse reactions of IP needed to be dealt with in time， the EGFR-TKI should be discontinued and symptomatic treatment should be given. CONCLUSIONS EGFR-TKI targeted therapy could be re-selected by replacing EGFR-TKI， adjusting the dose of EGFR-TKI， and using hormones in combination. EGFR-TKI-induced adverse drug reactions of IP are rare， but need to be observed closely. If other EGFR-TKI is used， close monitoring of adverse reactions and curative effects are also required in order to adjust the patient’s treatment plan in time.
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OBJECTIVE To systematically evaluate the safety of paroxetine in the treatment of pregnant patients with depression in the second and third trimesters of pregnancy， and provide reference for rational clinical use of it. METHODS Retrieved from Cochrane Library， PubMed， Embase， VIP， CNKI， Wanfang database and SinoMed database， by manual search， randomized controlled studies or observational studies were collected on depression patients who were given paroxetine vs. selective serotonin reuptake inhibitor （SSRI） in the second and third trimesters of pregnancy during the inception to Aug. 2022. Methodological qualities of the included studies were assessed by Cochrane Handbook 5.1.0 or Newcastle-Ottawa Scale （NOS）. Meta-analysis was performed with RevMan 5.4.1 software. RESULTS Finally， 9 observational studies were included， and all included studies were of high quality in NOS scale. Meta-analysis was performed on 8 cohort studies. Meta-analysis showed that the total incidence of adverse pregnancy outcomes of mothers and infants [RR＝0.99， 95%CI（0.89，1.10），P＝0.87]， total incidence of maternal adverse pregnancy outcomes [RR＝0.98， 95%CI （0.87，1.10）， P＝0.69] and premature birth [RR＝0.89， 95%CI （0.43， 1.83）， P＝0.75] in the second and third trimesters of pregnancy were lower than that with other SSRI， without statistical significance. The incidence of neonatal complications with paroxetine in the second and third trimesters of pregnancy was higher than that with other SSRI， but the difference was not statistically significant [RR＝1.02， 95%CI （0.82，1.29）， P＝0.84]. One study reported that the incidence of neonatal pulmonary hypertension in paroxetine group was higher than that in other SSRI group （0.4% vs. 0.3%）. CONCLUSIONS The safety of peroxetine in the second and third trimesters of pregnancy is comparable with that of other SSRI， but it is necessary to be alert to the occurrence of neonatal pulmonary hypertension.
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Metabolic syndrome is a clustering of metabolic disorder with unclear molecular mechanism. Increasing studies have found that the pathogenesis and progression of metabolic syndrome are closely related to inflammation. Here, we report celastrol, a traditional Chinese medicine, can improve high fat diet-induced metabolic syndrome through suppressing resistin-induced inflammation. Mechanistically, celastrol binds to adenylyl cyclase associated protein 1 (CAP1) and inhibits the interaction between CAP1 and resistin, which restrains the cyclic adenylate monophosphate (cAMP)-protein kinase A (PKA)-nuclear factor kappa-B (NF-
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The aims of this study were to determine the prognostic value of primary tumor surgery and identify optimal candidates for such surgery among patients with seminoma and distant metastasis at diagnosis. We identified 521 patients with seminoma and distant metastasis at diagnosis between 2004 and 2014 from the Surveillance, Epidemiology, and End Results database. Among these patients, 434 had undergone surgery, whereas 87 had not. The prognostic value of primary tumor surgery was assessed by Kaplan-Meier methods, log-rank analyses, and multivariate Cox's proportional hazards model. Survival curves and forest plots were also plotted. Survival analysis indicated that patients who underwent surgery had a better 5-year overall survival and cancer-specific survival than those who did not. Multivariate analyses demonstrated that primary tumor surgery is an independent prognostic factor for overall survival and cancer-specific survival, along with age at diagnosis, M stage, and marital status. In addition, primary tumor surgery still had considerable prognostic value in the subgroup of patients with lymph node metastasis. Further, forest plots demonstrated that patients with M1a stage, N1 or N2-3 stage, and a younger age at diagnosis (<60 years) may benefit from primary tumor surgery. In conclusion, our findings indicate that primary tumor surgery is correlated with improved survival in patients with seminoma and distant metastasis. Furthermore, primary tumor surgery is an independent prognostic indicator for patients with seminoma and distant metastasis.
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Accumulating evidence suggested that long noncoding RNAs (lncRNAs) possess a potential role in prostate cancer (PCa) diagnosis and prognosis. Rapid biochemical recurrence (BCR) is considered as a sign for clinical recurrence metastasis and PCa-specific mortality. Hence, the aim of the present study was to identify a lncRNA signature that can predict BCR of PCa accurately. Bioinformatics analysis, Kaplan-Meier analyses, Cox regression analyses, and Gene Set Enrichment Analysis (GSEA) were performed in a publicly available database with 499 PCa tissues and 52 matched normal tissues. A signature was identified. All these lncRNAs were differentially expressed between tumor and normal tissues and differentially expressed between high Gleason score and low Gleason score tissues. Furthermore, we developed a seven lncRNAs signature that can predict PCa BCR. Patients classified into low-risk group showed better BCR survival significantly than the patients in the high-risk group (hazard ratio = 0.32, 95% CI: 0.20-0.52, concordance index = 0.63). The area under the curve was 0.68 for BCR. The signature also had good discrimination for BCR in men with Gleason 7 PCa. In conclusion, our results suggest that the seven lncRNAs signature is a new biomarker of BCR and high risk in PCa. In addition, the individual lncRNA warrants further study to uncover the associated mechanisms of PCa progression and the signature could be used to design direct clinical trials for adjuvant therapy.
Subject(s)
Humans , Male , Middle Aged , Biomarkers, Tumor/genetics , Genetic Predisposition to Disease/genetics , Kaplan-Meier Estimate , Neoplasm Grading , Neoplasm Recurrence, Local/genetics , Prognosis , Proportional Hazards Models , Prostatic Neoplasms/genetics , RNA, Long Noncoding/genetics , Risk AssessmentABSTRACT
<p><b>OBJECTIVE</b>To investigate the prevalence of allergic diseases in children aged 0-24 months in the Wuhu urban area of Anhui Province and risk factors for allergic diseases.</p><p><b>METHODS</b>Cluster random sampling was performed to select 600 children aged 0-24 months and their mothers from the Wuhu urban area, and a questionnaire survey was conducted to collect the data of disease history, family history, mothers' conditions during pregnancy, and child-rearing situation. Univariate analysis and multivariate logistic regression analysis were performed for such data.</p><p><b>RESULTS</b>Among the 597 children included in the analysis, 56 (9.4%) were diagnosed with allergic diseases in the past. The univariate analysis showed that the age, use of antipyretic and analgesic drugs, a history of allergy in the father or grandparents, and the consumption of fish, shrimps, crabs, and shellfish during pregnancy were significantly associated with past allergic diseases (P<0.05). The multivariate logistic regression analysis showed that the age and a history of allergy in the father or grandparents were positively associated with past allergic diseases (OR=4.0-4.9, 2.7, and 2.4 respectively; P<0.05), while frequent consumption of fish, shrimps, crabs, and shellfish during pregnancy was negatively associated with past allergic diseases (OR=0.3; P<0.05).</p><p><b>CONCLUSIONS</b>A family history of allergy is an independent risk factor for allergic diseases in children aged 0-24 months in the Wuhu urban area of Anhui Province, while frequent consumption of fish, shrimps, crabs, and shellfish during pregnancy is a protective factor.</p>
Subject(s)
Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Hypersensitivity , Logistic Models , Risk FactorsABSTRACT
AIM:To observe the antiulcer effect of butyric acid and hydrogen , the main metabolites of Clos-tridium butyricum (C.butyricum), and to explore the underlying mechanism .METHODS: The mouse model of acute gastric mucosal lesion was prepared by gavage with ethanol .The mice were randomly divided into 4 groups:normal group , model group , butyric acid group and hydrogen group .The mice in butyric acid group and hydrogen group were given buty-rate and hydrogen prior to model establishment , respectively .Macroscopic observation of the pathological changes in gastric tissues was performed to evaluate the effect of the 2 metabolites of C.butyricum.Meanwhile, the mRNA expression levels of inflammatory factors, such as IL-12, RAN1 and MCP-1, were determined by RT-qPCR.The expression levels of apopto-sis-related proteins Bcl-2 and Bax were detected by immunohistochemical staining .RESULTS:The macroscopic observa-tion found that butyrate , not hydrogen , protected gastric mucosa .HE staining also showed that butyrate significantly attenu-ated the pathological damage of the gastric mucosa induced by ethanol .Compared with model group , the mRNA levels of inflammatory factors IL-12, RAN1 and MCP-1 in butyrate group significantly decreased (P<0.01).In butyrate group, the protein level of Bax was obviously decreased compared with model group (P<0.01), while the protein level of Bcl-2 was significantly increased ( P<0.01 ) .CONCLUSION: The gastric mucosa protective metabolite of C.butyricum may be butyric acid , not hydrogen .Butyric acid protects the gastric mucosa against ethanol-induced lesion by inhibiting the inflam- mation and reducing the expression ratio of Bax/Bcl-2.
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AIM:To observe the antiulcer effect of butyric acid and hydrogen , the main metabolites of Clos-tridium butyricum (C.butyricum), and to explore the underlying mechanism .METHODS: The mouse model of acute gastric mucosal lesion was prepared by gavage with ethanol .The mice were randomly divided into 4 groups:normal group , model group , butyric acid group and hydrogen group .The mice in butyric acid group and hydrogen group were given buty-rate and hydrogen prior to model establishment , respectively .Macroscopic observation of the pathological changes in gastric tissues was performed to evaluate the effect of the 2 metabolites of C.butyricum.Meanwhile, the mRNA expression levels of inflammatory factors, such as IL-12, RAN1 and MCP-1, were determined by RT-qPCR.The expression levels of apopto-sis-related proteins Bcl-2 and Bax were detected by immunohistochemical staining .RESULTS:The macroscopic observa-tion found that butyrate , not hydrogen , protected gastric mucosa .HE staining also showed that butyrate significantly attenu-ated the pathological damage of the gastric mucosa induced by ethanol .Compared with model group , the mRNA levels of inflammatory factors IL-12, RAN1 and MCP-1 in butyrate group significantly decreased (P<0.01).In butyrate group, the protein level of Bax was obviously decreased compared with model group (P<0.01), while the protein level of Bcl-2 was significantly increased ( P<0.01 ) .CONCLUSION: The gastric mucosa protective metabolite of C.butyricum may be butyric acid , not hydrogen .Butyric acid protects the gastric mucosa against ethanol-induced lesion by inhibiting the inflam- mation and reducing the expression ratio of Bax/Bcl-2.
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<p><b>OBJECTIVE</b>To investigate the influence of anthropometric measures of obesity, including body mass index (BMI), abdominal subcutaneous adipose tissue and visceral adipose tissue, on pathological characteristics in patients with clinically localized prostate cancer.</p><p><b>METHODS</b>From January 2006 to March 2013, the 413 patients of prostate cancer who received radical prostatectomy (RP) and their clinical and pathological data had been collected. The median age for the entire cohort was 68 years, which ranged from 48 to 78 years. All patients were diagnosed with prostate cancer before surgery and the Gleason score ranged from 4 to 10 (median 7). Anthropometric measures of abdominal adiposity including anterior abdominal fat, posterior abdominal fat and anteroposterior diameter were measured from the T2 weighted sagittal localization images of MRI scans and subcutaneous adipose tissue and the percentage of visceral adipose tissue were calculated. The patients' clinical and pathologic characteristics across BMI groups were compared used Student's t test for continuous variables or chi-squared test for categorical variables. Moreover, univariable and multivariable logistic regression models were used to address the influence of anthropometric measures of obesity on pathological outcomes.</p><p><b>RESULTS</b>The BMI ranged from 14.2 to 34.0 kg/m(2) and the median value was 23.8 kg/m(2). The abdominal subcutaneous adipose tissue ranged from 12.6 to 60.3 mm and the median value was 31.4 mm. The percentage of visceral adipose tissue ranged from 71.1% to 92.1% and the median value was 83.8%. In RP specimens, Gleason score ≥ 8 was observed in 141 patients (34.1%), pathological tumor stage was T3a in 69 patients (16.7%) and pathological tumor stage was T3b in 78 patients (18.9%). Positive surgical margin and lymph node involvement were observed in 71(17.2%) and 38(9.2%) patients, respectively. Although univariate analysis showed that BMI ≥ 25 kg/m(2) was associated with pathological Gleason score ≥ 8 (OR = 1.413, P = 0.035), this positive correlation disappeared in multivariate analysis(P = 0.095). In multivariate analysis, the percentage of visceral adipose tissue was significantly associated with pathological Gleason score (OR = 9.618, P = 0.000), extracapsular extension (OR = 6.750, P = 0.002) and seminal vesicle invasion (OR = 4.419, P = 0.007) after adjusting for patient age, PSA level, clinical stage and biopsy Gleason score.</p><p><b>CONCLUSIONS</b>Anthropometric measures of abdominal adiposity was more sophisticated than simple BMI to evaluate the risk of obesity with regard to the aggressiveness of prostate cancer. The percentage of visceral adipose tissue was an independent factor for pathological Gleason score, extracapsular extension and seminal vesicle invasion in RP specimens.</p>
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Aged , Humans , Male , Middle Aged , Adiposity , Anthropometry , Body Mass Index , Intra-Abdominal Fat , Logistic Models , Obesity , Prostate , Pathology , Prostatectomy , Prostatic Neoplasms , Pathology , Risk FactorsABSTRACT
<p><b>OBJECTIVE</b>To evaluate the incidence and severity of perioperative complications in elderly patients with radical prostatectomy (RP).</p><p><b>METHODS</b>A total of 242 patents underwent RP for prostate cancer were retrospectively assessed, whose clinicopathologic factors and perioperative complications were retrieved from the medical records. The mean age in the elderly group (n = 163) and control group (n = 79) were (73.2 ± 2.4) and (63.2 ± 4.8) years, respectively. The clinicopathologic factors including Charlson comorbidity index and preoperative prostate specific antigen were statistically significant different. The difference of clinicopathologic factors and perioperative complications between the elderly group (≥ 70 years old) and control group were statistically analyzed using the SPSS 17.0.</p><p><b>RESULTS</b>The incidence of perioperative complications was 23.5% in the elderly group and 22.7% in the control group. Except for gross hematuria (there were 12 cases in elderly group and 1 case in control group, respectively, χ(2) = 3.89, P < 0.05) and perioperative transfusion (there were 36 cases in elderly group and 7 cases in control group, respectively, χ(2) = 6.37, P < 0.05), there was no significant difference in each kind or total of perioperative complications.</p><p><b>CONCLUSION</b>The elderly patients underwent RP in experienced center are not associated with higher or more serious perioperative complications.</p>
Subject(s)
Aged , Humans , Male , Middle Aged , Incidence , Intraoperative Complications , Epidemiology , Postoperative Complications , Epidemiology , Prostatectomy , Prostatic Neoplasms , General Surgery , Retrospective StudiesABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of vascular endothelial growth factor (VEGF) on bone marrow-derived mesenchymal stem cell (MSC) proliferation and explore the signaling mechanism involved.</p><p><b>METHODS</b>MSC culture was performed following the classical whole bone marrow adhering method. The characteristics of MSC were identified by induction of multi-lineage differentiation and flow cytometry for surface marker analysis (CD34, CD45, CD29, and CD90). Following the addition of 50 nmol/L wortmannin, 50 µmol/L PD98059, 30 µmol/L SB203580, 10 µmol/L H89, 20 µmol/L Y27632, 1 µmol/L rapamycin, 10 µmol/L straurosporine, 6 nmol/L Go6976, or 50 µmol/L Pseudo Z inhibitors in the cell culture, the MSC were treated with 20 ng/ml VEGF and the changes of the cell proliferation rate was measured with MTT assay.</p><p><b>RESULTS</b>Cultured MSC were capable of multi-linage differentiation and did not express VEGF-R, CD29 or CD90. Treatment with 20 ng/ml VEGF obviously promoted MSC proliferation, and this effect was inhibited partially by p38 mitogen-activated protein kinase (MAPK) inhibitor rapamycin, PD98059, SB203580, Go6976, and straurosporine.</p><p><b>CONCLUSIONS</b>VEGF promotes MSC proliferation in close relation to the AKT-PKC pathway, in which PKC signal pathway may play the central role.</p>